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Cookies on this website We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings. Elevated body mass index (BMI) associates with cardiometabolic traits on observational analysis, yet the underlying causal relationships remain unclear. We conducted Mendelian randomization analyses by using a genetic score (GS) comprising 14 BMI-associated SNPs from a recent discovery analysis to investigate the causal role of BMI in cardiometabolic traits and events. We used eight population-based cohorts, including 34,538 European-descent individuals (4,407 type 2 diabetes (T2D), 6,073 coronary heart disease (CHD), and 3,813 stroke cases). A 1 kg/m2genetically elevated BMI increased fasting glucose (0.18 mmol/l; 95% confidence interval (CI) = 0.12-0.24), fasting insulin (8.5%; 95% CI = 5.9-11.1), interleukin-6 (7.0%; 95% CI = 4.0-10.1), and systolic blood pressure (0.70 mmHg; 95% CI = 0.24-1.16) and reduced high-density lipoprotein cholesterol (-0.02 mmol/l; 95% CI = -0.03 to -0.01) and low-density lipoprotein cholesterol (LDL-C; -0.04 mmol/l; 95% CI = -0.07 to -0.01). Observational and causal estimates were directionally concordant, except for LDL-C. A 1 kg/m2genetically elevated BMI increased the odds of T2D (odds ratio [OR] = 1.27; 95% CI = 1.18-1.36) but did not alter risk of CHD (OR 1.01; 95% CI = 0.94-1.08) or stroke (OR = 1.03; 95% CI = 0.95-1.12). A meta-analysis incorporating published studies reporting 27,465 CHD events in 219,423 individuals yielded a pooled OR of 1.04 (95% CI = 0.97-1.12) per 1 kg/m2increase in BMI. In conclusion, we identified causal effects of BMI on several cardiometabolic traits; however, whether BMI causally impacts CHD risk requires further evidence. © 2014 The American Society of Human Genetics. Original publication DOI 10.1016/j.ajhg.2013.12.014 Type Journal article Journal American journal of human genetics Publication Date 06/02/2014 Volume 94 Pages 198 - 208
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Latest Wizards Latest News Latest Wizards Advancements in Genomic Medicine The Path to Personalized Health Introduction To Genomic Medicine Genomic Medicine picture The Genomic Revolution In latest years, groundbreaking improvements in science and era have caused a revolution in remedy, mainly within the field of genomics. Genomic medicine, the present-day method that harnesses the information saved inside our genes, has paved the manner for a new generation of healthcare. By studying an individual’s genetic makeup, healthcare professionals can now tailor remedy plans and interventions with excellent precision. Defining Genomic Medicine At its core, genomic medicine refers to the use of genomic information to guide medical decision-making. This entails information on the genetic elements that impact a person’s fitness, disorder susceptibility, and responses to numerous treatments. By unraveling the complexities of our DNA, genomic medicine aims to provide personalized healthcare solutions that were once unimaginable. Importance of Personalized Healthcare Traditional medicine often follows a one-size-fits-all approach. here treatments and interventions are generalized to suit a broad population. However, every individual’s genetic makeup is unique, influencing how they metabolize drugs, their susceptibility to diseases, and their overall health. Personalized healthcare, made possible via genomic medication, holds the potential to revolutionize disorder prevention, diagnosis, and remedy, in the end enhancing the affected person’s effects and pleasant of existence. Understanding Genomic Medicine dna-closely-pic-Genomic-Medicine What is Genomic Medicine? Genomic medicine involves analyzing an individual’s entire genome, which comprises all of their DNA, including genes and non-coding regions. This data affords insights into genetic variations that can influence fitness and disease. By understanding these variations, healthcare companies could make knowledgeable decisions approximately disease hazards, remedy options, and preventive measures. The Human Genome Project A pivotal milestone in genomic medicine became the completion of the Human Genome Project in 2003. This worldwide collaborative attempt correctly mapped out the complete human genome, providing a comprehensive reference for genetic statistics. This enormous achievement laid the foundation for further research in genomics and its applications in medicine. How Genomic Medicine Differs from Traditional Medicine Traditional medicine often relies on a symptom-based approach, where treatments are prescribed based on observed symptoms and general medical knowledge. In contrast, genomic medicine delves into the molecular underpinnings of diseases and health conditions, enabling a more precise understanding of their origins. This knowledge allows for tailored interventions that focus on the root reasons, probably main to more powerful treatments and better patient outcomes. Genetic Testing: Unveiling Individual’s Genetic Makeup The Science Behind Genetic Testing Genetic testing involves analyzing an individual’s DNA to identify genetic variations that may be associated with specific health conditions or traits. This is typically done thru techniques such as DNA sequencing and genotyping. The effects of genetic checks provide treasured information approximately a man’s risk of developing certain diseases and the way they might respond to distinct remedies. Benefits and Limitations of Genetic Testing Genetic testing have empowered individuals to take proactive steps toward their health. It can provide early insights into disease risks, allowing for preventive measures and lifestyle adjustments. However, genetic testing also comes with ethical and privacy considerations. Additionally, not all genetic versions have clean medical importance, which may cause uncertainty in interpretation. Tailored Treatment Plans: From Genes to Therapies old-man-holding-his-pills-Genomic Medicine picture Pharmacogenomics: Customizing Drug Responses Pharmacogenomics studies how an individual’s genetic makeup influences their response to medications. By analyzing genetic variations that affect drug metabolism and efficacy. Healthcare providers can customize treatment plans to maximize benefits and minimize adverse effects. Gene Therapy: Treating Genetic Disorders at the Source Gene therapy is a revolutionary approach that aims to correct or replace faulty genes responsible for genetic disorders. By delivering functional genes into the patient’s cells, gene therapy holds immense potential to treat diseases that were previously considered incurable. Cancer Genomics: Precision Oncology Cancer is a complex disease with diverse genetic causes. Through cancer genomics, researchers can identify genetic mutations driving specific types of cancer. This knowledge allows oncologists to tailor treatments, such as targeted therapies and immunotherapies, to the individual’s unique genetic profile. Nutrigenomics: Personalized Nutrition Plans Nutrigenomics explores the relationship between genetics and nutrition. By analyzing an individual’s genetic variations, healthcare professionals can design personalized dietary plans tailored to their specific nutritional needs and metabolic responses. Ethical and Privacy Considerations Protecting Genetic Information Genetic information is deeply personal and sensitive. Ensuring the privacy and safety of these facts is of extreme importance. Laws and regulations are in place to govern the collection, storage, and sharing of genetic information, aiming to prevent unauthorized access and misuse. Informed Consent and Genetic Testing Before undergoing genetic testing, individuals must provide informed consent, understanding the potential implications of the results. Genetic counselors play a vital role in explaining the benefits, limitations, and potential emotional impacts of genetic testing. Potential Misuses of Genetic Data While genomic medicine offers numerous benefits, it also raises concerns about the potential misuse of genetic data. Genetic discrimination by employers, insurers, or other entities based on an individual’s genetic information is a legitimate concern that needs to be addressed through proper legal safeguards. Challenges and Future Prospects challenge-word-Genomic-picture Big Data and Bioinformatics The field of genomics generate massive amounts of data. Effectively managing and interpreting this data requires advanced bioinformatics tools and technologies. The integration of big data analytics can lead to more accurate disease predictions and treatment recommendations. Interpreting Complex Genetic Data Not all genetic variations have clear implications for health. Interpreting the significance of complex genetic data is a challenge that requires collaboration between geneticists, clinicians, and bioinformaticians. Improving our understanding of the functional impact of genetic variants is crucial. Integrating Genomic Medicine into Healthcare Systems The widespread adoption of genomic medicine in healthcare systems requires education and training for healthcare professionals. Integrating genetic information into clinical practice will require changes in medical curricula and the development of standardized guidelines and protocols. Frequently Asked Questions (FAQs) Q1: What is genomic medicine? A1: Genomic medicine involves using an individual’s genetic information to guide medical decisions, enabling personalized healthcare approaches. Q2: How does genetic testing work? A2: Genetic testing affects analyzing an individual’s DNA to identify genetic variations. That may influence health, illness risk, and treatment responses. Q3: What is pharmacogenomics? A3: Pharmacogenomics studies how genetics influence a person’s response to medications, allowing for tailored drug treatments. Q4: Can genomic medicine cure genetic diseases? A4: Gene therapy holds promise for treating some genetic diseases, but complete cures may not be achievable for all conditions. Q5: How is patient privacy protected in genomic medicine? A5: Laws and regulations govern the collection and use of genetic information to ensure patient privacy and prevent unauthorized access. Conclusion For Genomic Medicine Transforming Healthcare Through Personalized Genomic Medicine Advancements in genomic medicine have unlocked the potential for personalized healthcare that caters to each individual’s genetic makeup. From genetic testing to tailored treatment plans, this approach is reshaping how we prevent, diagnose, and treat diseases. The Road Ahead: Continued Research and Innovation While the field of genomic medicine has made significant strides. There’s still much to explore and understand. Ongoing studies, technological innovations, and collaborative efforts among scientists, healthcare experts, and policymakers will power the field forward. Leading to even greater specific and effective personalized healthcare solutions. As we hold on to this course. The promise of improved health and well-being for individuals around the world becomes ever more achievable. Scroll to Top
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Close Cryoanalgesia and Therapeutic Cold Number: 0297 Policy 1. Aetna considers the use of cryoanalgesia medically necessary for the temporary relief of pain due to chronic refractory trigeminal neuralgia (see Appendix for selection criteria). 2. Aetna considers intra-operative and post-operative cryoanalgesia of the intercostal nerves experimental and investigational for the management of post-thoracotomy pain and other types of chronic pain.   3. Aetna considers the passive cold compression therapy units (e.g., AirCast Cryo Cuff, AirCast Cryo Strap, the Polar Care Cub unit, and the Polar Pack) medically necessary DME to control swelling, edema, hematoma, hemarthrosis and pain.  Aetna considers the passive cold compression therapy units experimental and investigational for all other indications because their effectiveness for indications other than the ones listed above has not been established. 4. Aetna considers active cold compression therapy units with mechanical pumps and portable refrigerators (e.g., AutoChill, Game Ready, IceMan, NanoTherm, Prothermo, and Vascutherm) experimental and investigational because they have not been proven to offer clinically significant benefits over passive cold compression therapy units.   5. Aetna considers the use of the Hot/Ice Machine and similar devices (e.g., the Hot/Ice Thermal Blanket, the Kinex ThermoComp Device, the TEC Thermoelectric Cooling System (an iceless cold compression device), the VascuTherm2, the VitalWear Cold/Hot Wrap, and the VitalWrap) experimental and investigational for reducing pain and swelling after surgery or injury.  Studies in the published literature have been poorly designed and have failed to show that the Hot/Ice Machine offers any benefit over standard cryotherapy with ice bags/packs; and there are no studies evaluating its use as a heat source. Note: Aetna considers passive hot and cold therapy medically necessary.  Mechanical circulating units with pumps have not been proven to be more effective than passive hot and cold therapy. Background Cryoanalgesia for Trigeminal Neuralgia: Trigeminal neuralgia (TN), also known as tic douloureux, is a disorder characterized by excruciating episodic pain in the areas innervated by one or more divisions (usually the mandibular and maxillary, rarely the ophthalmic divisions) of the trigeminal nerve.  The anti-epileptic drug carbamazepine (Tegretol) is the drug most frequently used for the management of TN.  For patients who can not tolerate carbamazepine because of its adverse side effects (poor liver function, confusion, ataxia, drowsiness, and allergic responses), the literature indicates baclofen and other anticonvulsant drugs such as clonazepam (Klonopin) may be useful. Cryoanalgesia, cryotherapy, or cryoneurotomy has also been used in the treatment of TN.  It entails the use of high pressure (approximately 600 pounds per square inch) gas (nitrous oxide or carbon dioxide) administered by a 12- to 14-G needle-shaped cryoprobe.  Studies have shown that cryoanalgesia provides temporary pain relief or cure with minimal morbidity (e.g., no permanent sensory loss) in patients with refractory TN. Intra-Operative and Post-Operative Cryoanalgesia for the Management of Post-Thoracotomy Pain: Thoracotomy, the establishment of an opening into the chest cavity for the management of various cardiopulmonary disorders/diseases, is one of the most painful surgical incisions.  Post-thoracotomy pain impairs patients' ability to breathe deeply and cough frequently to prevent atelectasis.  Pain relief medication may decrease the coughing reflex as well as depress respiratory functions when the dosage is high enough to achieve analgesia.  On the other hand, if the dosage of analgesics is too low to relieve pain, it may render patients with shallow breathing and inadequate coughing reflex.  Epidural anesthesia or analgesia may produce some pain relief, but the side effects of severe hypotension, nausea, and urinary retention, as well as the variability of effect limit the usefulness of this approach.  Intercostal or paravertebral nerve blocks by means of local anesthetics and severing of the intercostal nerves have also been used to reduce incisional pain following thoracotomy.  However, the duration of relief for neural blockade is only a few hours and the procedure is painful, while severing of the intercostal nerves during thoracotomy may result in neuromas, which cause late post-operative pain. Cryoanalgesia has been used on the intercostal nerves to reduce post-thoracotomy pain.  Although the procedure is generally performed prior to closure of the chest at the completion of thoracotomy and may add 10 to 15 mins to the total operating time, it can also be carried out percutaneously in a clinical setting.  Cryoanalgesia of the intercostal nerves circumvents the need for repetitive injections of nerve blocks and avoids the toxicity of long acting agents, which may lead to chemically induced intercostal neuritis.  Khanbhai et al (2014) examined if cryoanalgesia improves post-thoracotomy pain and recovery.  A total of 12 articles were identified that provided the best evidence to answer the question.  The authors, date, journal, study type, population, main outcome measures and results were tabulated.  Reported measures were pain scores, additional opiate requirements, incidence of hypoesthesia and change in lung function.  Half of the articles reviewed failed to demonstrate superiority of cryoanalgesia over other pain relief methods; however, additional opiate requirements were reduced in patients receiving cryoanalgesia.  Change in lung function post-operatively was equivocal.  Cryoanalgesia potentiated the incidence of post-operative neuropathic pain.  Further analysis of the source of cryoanalgesia, duration, temperature obtained and extent of blockade revealed numerous discrepancies; 3 studies utilized CO2 as the source of cryoanalgesia, and 4 used nitrous oxide but at differing temperatures and duration; 5 studies did not reveal the source of cryoanalgesia.  The number of intercostal nerves anesthetized in each study varied; 7 articles anesthetized 3 intercostal nerves, 3 articles used 5 intercostal nerves, 1 article used 4 intercostal nerves and 1 used 1 intercostal nerve at the thoracotomy site.  Thoracotomy closure and site of area of chest drain insertion may have a role in post-operative pain; but only 1 article explained method of closure, and 2 articles mentioned placement of chest drain through blocked dermatomes.  No causal inferences can be made by the above results as they are not directly comparable due to confounding variables between studies.  The authors concluded that currently, the evidence does not support the use of cryoanalgesia alone as an effective method for relieving post-thoracotomy pain. Humble et al (2014) noted that peri-operative neuropathic pain is under-recognized and often undertreated.  Chronic pain may develop after any routine surgery, but it can have a far greater incidence after amputation, thoracotomy or mastectomy.  The peak noxious barrage due to the neural trauma associated with these operations may be reduced in the peri-operative period with the potential to reduce the risk of chronic pain.  These investigators performed a systematic review of the evidence for peri-operative interventions reducing acute and chronic pain associated with amputation, mastectomy or thoracotomy.  A total of 32 randomized controlled trials (RCTs) met the inclusion criteria.  Gabapentinoids reduced pain after mastectomy, but a single dose was ineffective for thoracotomy patients who had an epidural.  Gabapentinoids were ineffective for vascular amputees with pre-existing chronic pain.  Venlafaxine was associated with less chronic pain after mastectomy.  Intravenous and topical lidocaine and peri-operative EMLA (eutectic mixture of local anesthetic) cream reduced the incidence of chronic pain after mastectomy, whereas local anesthetic infiltration appeared ineffective.  The majority of the trials investigating regional analgesia found it to be beneficial for chronic symptoms.  Ketamine and intercostal cryoanalgesia offered no reduction in chronic pain.  Total intravenous anesthesia (TIVA) reduced the incidence of post-thoracotomy pain in 1 study, whereas high-dose remifentanil exacerbated chronic pain in another.  The authors concluded that (i) appropriate dose regimes of gabapentinoids, anti-depressants, local anesthetics and regional anesthesia may potentially reduce the severity of both acute and chronic pain for patients; (ii) ketamine was not effective at reducing chronic pain; (iii) intercostal cryoanalgesia was not effective and has the potential to increase the risk of chronic pain; and (iv) TIVA may be beneficial but the effects of opioids are unclear. Cold Therapy Units and Hot/Ice Machine: Cold therapy units are devices in which fluid flows through a blanket or cuff, providing immediate cooling to an affected area.  The AirCast Cryo/Cuff uses a insulated jug filled with cold water attached to a cuff.  Elevating the jug fills and pressurizes the cuff.  Compression is controlled by gravity, and is proportional to the elevation of the cooler.  When body heat warms the water, it is re-chilled simply by lowering the cooler.  Another passive cold compression therapy unit is the Polar Care Cub unit. More complicated cold therapy units may employ mechanical pumps and refrigerators that are powered by battery or electricity (e.g., IceMan).  The Game Ready system is an example of an active cooling device that combines cold and intermittent pneumatic compression therapies.  The system consists of a wrap, a connector hose, and a control unit.  The wrap contains two internal chambers, one for air and the other for cooling water.  The microprocessor control unit features various adjustable compression cycles and temperature controls.  However, there is no evidence that these more complicated cold therapy units provide any additional benefit over the CryoCuff or conventional ice bags or packs.  Aetna's current policy on mechanical cold therapy pumps is consistent with Medicare DME MAC policy. Leutz and Harris (1995) described a retrospective study that assessed 52 consecutive patients who underwent total knee arthroplasty (TKA).  A total of 33 patients underwent TKA and received cold therapy pads placed over a thin dressing in the operating room; 19 patients underwent TKA using an identical operative and post-operative procedure, but did not receive continuous cold therapy.  Continuous cold therapy consisted of 2 sterile plastic pads connnected by rubber hoses containing cool water from an electric main unit that maintained a constant temperature of 42 degrees F for the immediate post-operative period.  Cold therapy pads were used an average of 3 days and removed with the first dressing change.  Patients who had continuous cold therapy averaged a 200 ml decrease in post-operative blood loss.  There was no significant difference in the amount of narcotic use, transfusion requirements, or hospital stay between the two groups.  Post-operative swelling and range of motion were not consistently recorded.  Twenty-eight other variables were also examined, but no significant differences were found between groups.  Based on these results, the authors stated that they can not recommend continuous cold therapy or justify the extra expense for all patients who undergo TKA. A Hot/Ice Machine consists of 2 rubber pads connected by a rubber hose to a unit that circulates hot or cold fluid through the pads.  Studies in the published literature have been poorly designed and have failed to show that the Hot/Ice Machine offers any benefit over standard cryotherapy with ice packs, and there are no studies evaluating the use of this device as a heat source. The VitalWrap (VitalWear Inc. South San Francisco, CA) is an active heating/cooling device that allows the user to circulate either hot or cold fluid through the system.  The VitalWrap system consists of a bladder filled body wrap/pad, tubing, and a reservoir/pump device.  Cooled or heated water may be added to the pump reservoir and then circulated through the tubing to the body wrap/pad and then back to the reservoir.  The benefits of this type of device above other cooling or heating methods have not been established at this time. Vascutherm (ThermoTek, Carrollton, TX) is an active cold compression therapy unit with a pneumatic pump.  It provides heating, cooling and compression therapies.  The device also includes a deep vein thrombosis (DVT) mode -- this is a compression (or air) only mode, that is intended to prevent DVT.  However, it provides no additional clinical utility or impact on health outcomes than the use of ice or compression wraps. The TEC Thermoelectric Cooling System (Maldonado Medical, Phoenix, AZ) is marketed to reduce post-operative pain and edema.  It is an iceless cold therapy compression/DVT prophylaxis machine that can also provide heat.  It is limited to a cold temperature of 49 degrees F to minimize the potential for frostbite.  However, it provides no additional clinical utility or impact on health outcomes than the use of ice or compression wraps. According to the manufacturer, the Kinex ThermoComp™ Device provides 3 separate pre-programmed therapies that are activated by a push of a button: (i) cold-compression, (ii) contrast-compression, and (iii) intermittent pneumatic compression for DVT prophylaxis.  Continuous cold is delivered by a solid-state system without ice.  Cold temperature is microprocessor-controlled within 1° making this one of the safest devices for unsupervised use in a patient's home.  Contrast therapy cycles every 30 mins with cold at 49° for 20 mins followed by heat at 105° for 10 mins.  Intermittent compression is delivered distal-to-proximal through a segmented pad.  Deep vein thrombosis prophylaxis is delivered from a rapid inflation pump at 50 mm Hg through a calf pad or 100 mm Hg through a foot pad.  All 3 therapies are delivered separately, however cold-compression and DVT compression can run at the same time with the device cycling DVT compression separate from limb compression.  The Kinex ThermoComp™ Device is intended to treat post-operative injuries in the home, to reduce edema and pain, to improve blood flow to the surgical site, and to provide DVT prophylaxis therapy for high-risk patients.  http://www.kinexmedical.com/thermocomp.html.  However, there is a lack of evidence regarding the safety and effectiveness of this device. According to the manufacturer, the VascuTherm2 solid state device provides heat, cold (without ice), compression, and/or DVT prophylaxis therapy.  The system is pre-programmed per written physician's instructions for fully automatic, safe, trouble-free use in the patient's home.  It is indicated for pain, edema, and DVT prophylaxis for the post-operative orthopedic patient.  The precisely controlled temperature range of 43 degrees F to 105 degrees F insures against frost-bite or burns.  Therapy times are also pre-programmed to insure maximum patient compliance.  It is extremely easy for patients to set up and use.  http://www.calamarimedical.com/VascuTherm2.html.  However, there is a lack of evidence regarding the safety and effectiveness of this device. Appendix Selection Criteria of Cryoanalgesia for Trigeminal Neuralgia: 1. Members have experienced pain for at least 6 months, and  2. Members have tried and failed pharmacotherapies (e.g., baclofen, carbamazepine, phenytoin), or are unable to tolerate the side effects of the medication.  Repeat cryoanalgesia may be medically necessary every 6 months. CPT Codes / HCPCS Codes / ICD-9 Codes CPT codes covered if selection criteria are met: 64600 Destruction by neurolytic agent, trigeminal nerve; supraorbital, infraorbital, mental, or inferior alveolar branch CPT codes not covered for indications listed in the CPB: 64620 Destruction by neurolytic agent, intercostal nerve Other CPT codes related to the CPB: 64400 Injection, anesthetic agent; trigeminal nerve, any division or branch 64420     intercostal nerve, single 64421     intercostal nerves, multiple, regional block HCPCS codes not covered for indications listed in the CPB: A9273 Hot water bottle, ice cap or collar, heat and/or cold wrap, any type E0217 Water circulating heat pad with pump E0218 Water circulating cold pad with pump E0236 Pump for water circulating pad E0249 Pad for water circulating heat unit E0650 - E0652 Pneumatic compressor; home model [not covered for active cold compression therapy units] E0660, E0666 - E0667, E0669 Non-segmental and segmental pneumatic appliance for use with pneumatic compressor; leg [not covered for active cold compression therapy units] E0671, E0673 Segmental gradient pressure pneumatic appliance, leg [not covered for active cold compression therapy units] Other HCPCS codes related to the CPB: E0676 Intermittent limb compression device (includes all accessories), not otherwise specified [not covered for active cold compression therapy units] ICD-9 codes covered if selection criteria are met (not all-inclusive): 338.0 - 338.19 Pain 350.1 Trigeminal neuralgia 611.71 Mastodynia 719.00 - 719.09 Effusion of joint 719.10 - 719.19 Hemarthrosis 719.40 - 719.49 Pain in joint 724.2 Lumbago 724.5 Backache, unspecified 729.0 Rheumatism, unspecified and fibrositis 729.1 Myalgia and myositis, unspecified 729.2 Neuralgia, neuritis, and radiculitis, unspecified 729.5 Pain in limb 729.81 Swelling of limb 780.96 Generalized pain 782.3 Edema 786.50 - 786.59 Chest pain 789.00 - 789.09 Abdominal pain 920 - 924.9 Contusion with intact skin surface ICD-9 codes not covered for indications listed in the CPB (not all-inclusive): 338.21 - 338.4 Chronic pain The above policy is based on the following references: Cryoanalgesia for Trigeminal Neuralgia: 1. Barnard D, Lloyd J, Evans J. Cryoanalgesia in the management of chronic facial pain. J Max Fac Surg. 1981;9(2):101-102.  2. Goss AN. Peripheral cryoneurectomy in the treatment of trigeminal neuralgia. Aust Dent J. 1984;29(4):222-224.  3. Nehme AE, Warfield CA. Cryoanalgesia: Freezing of peripheral nerves. Hosp Pract. 1987;22(1A):71-72, 77.  4. Politis C, Adriaensen H, Bossuyt M, Fossion E. The management of trigeminal neuralgia with cryotherapy. Acta Stomatologica Belgica. 1988;85(3):197-205.  5. Zakrzewska JM, Thomas DGT. Patient's assessment of outcome after three surgical procedures for the management of trigeminal neuralgia. Acta Neurochirurgica. 1993;122:225-230.  Intra-Operative and Post-Operative Cryoanalgesia for the Management of Post-Thoracotomy Pain: 1. Orr IA, Keenan DJ, Dundee JW. Improved pain relief after thoracotomy: Use of cryoprobe and morphine infusion. Br Med J (Clin Res Ed). 1981;283(6297):945-948.  2. Maiwand MO, Makey AR, Rees A. Cryoanalgesia after thoracotomy. Improvement of technique and review of 600 cases. J Thorac Cardiovasc Surg. 1986;92(2):291-295.  3. Jones MJT, Murrin KR. Intercostal block with cryotherapy. Ann R Coll Surg Engl. 1987;69(6):261-262.  4. Roberts D, Pizzarelli G, Lepore V, et al. Reduction of post-thoracotomy pain by cryotherapy of intercostal nerves. Scand J Thor Cardiovasc Surg. 1988;22(2):127-130.  5. Shafei H, Chamberlain M, Natrajan KN, et al. Intrapleural bupivacaine for early post-thoracotomy analgesia - Comparison with bupivacaine intercostal block and cryofreezing. Thorac Cardiovasc Surgeon. 1990;38(1):38-41.  6. Pastor J, Morales P, Cases E, et al. Evaluation of intercostal cryoanalgesia versus conventional analgesia in postthoracotomy pain. Respiration. 1996;63(4):241-245.  7. Khanbhai M, Yap KH, Mohamed S, Dunning J. Is cryoanalgesia effective for post-thoracotomy pain? Interact Cardiovasc Thorac Surg. 2014;18(2):202-209. 8. Humble SR, Dalton AJ, Li L. A systematic review of therapeutic interventions to reduce acute and chronic post-surgical pain after amputation, thoracotomy or mastectomy. Eur J Pain. 2014 Aug 4 [Epub ahead of print]. Cold Therapy Units and Hot/Ice Machine: 1. Cohn BT, Draeger RI, Jackson DW. The effects of cold therapy on the postoperative management of pain in patients undergoing anterior cruciate ligament reconstruction. Am J Sports Med. 1989;17(3):344-349.  2. Bert JM, Stark JG, Maschka K, Chock C. The effect of cold therapy on morbidity subsequent to arthroscopic lateral retinacular release. Orthop Rev. 1991;20(9):755-758.  3. Barber FA, McGuire DA, Click S. Continuous-flow cold therapy for outpatient anterior cruciate ligament reconstruction. Arthroscopy. 1998;14(2):130-135.  4. Konrath GA, Lock T, Goitz HT, Scheidler J. The use of cold therapy after anterior cruciate ligament reconstruction. A prospective randomized study and literature review. Am J Sports Med. 1996;24(5):629-633.  5. Ebner CA. Cold therapy and its effect on procedural pain in children. Issues Comp Pediatr Nurs. 1996;19(3):197-208.  6. Edwards DJ, Rimmer M, Keene GC. The use of cold therapy in the postoperative management of patients undergoing arthroscopic anterior cruciate ligament reconstruction. Am J Sports Med. 1996;24(2):193-195.  7. Scarcella JB, Cohn BT. The effect of cold therapy on postoperative course of total hip and knee arthroplasty patients. Am J Orthop. 1995;24(11):847-852.  8. Leutz DW, Harris H. Continuous cold therapy in total knee arthroplasty. Am J Knee Surg. 1995;8(4):121-123.  9. Daniel DM, Stone ML, Arendt DL. The effect of cold therapy on pain, swelling, and range of motion after anterior cruciate ligament reconstructive surgery. Arthroscopy. 1994;10(5):530-533.  10. Finan MA, Roberts WS, Hoffman MS, et al. The effects of cold therapy on postoperative pain in gynecologic patients: A prospective, randomized study. Am J Obstet Gynecol. 1993;168(2):542-544.  11. Amin-Hanjani S, Corcoran J, Chatwani A. Cold therapy in the management of postoperative cesarean section pain. Am J Obstet Gynecol. 1992;167(1):108-109.  12. AirCast, Inc. Cryo/Cuff [website]. Summit, NJ: AirCast; 1997. Available at: http://www.aircast.com/products/cryo.htm. Accessed July 26, 2000.  13. McDowell JH, McFarland EG, Nalli BJ. Use of cryotherapy for orthopedic patients. Orthoped Nurs. 1994;13(5):21-30.  14. Levy AS, Marmar E. The role of cold compression dressings in the postoperative treatment of total knee arthroplasty. Clin Orthoped Rel Res. 1993;297:174-178.  15. Mindrebo N, Shelbourne KD. Knee pressure dressings and their effects on lower extremity venous capacitance and venous outflow. Orthopaed Int. 1994;2(3):273-280.  16. Shelbourne KD, Stube KC, Patel DV. Conservative treatment of degenerative joint disease of the knee using cold compression therapy. Sports Exercise Injury. 1996;2:176-180.  17. Whitelaw GP, DeMuth KA, Demos HA, et al. The use of the Cryo/Cuff versus ice and elastic wrap in the postoperative patients. Am J Knee Surg. 1995;8(1):28-30; discussion 30-31.  18. Shelbourne KD, Rubenstein RA, McCarroll JR. Postoperative cryotherapy for the knee in ACL reconstructive surgery. Orthopaed Int. 1994;2(2):165-170.  19. Shelbourne KD, Wilckens JH. Current concepts in anterior cruciate ligament rehabilitation. Orthopaed Rev. 1990;19(11):957-964.  20. Ohkoshi Y, Ohkoshi M, Nagasaki S, et al. The effect of cryotherapy on intraarticular temperature and postoperative care after anterior cruciate ligament reconstruction. Am J Sports Med. 1999;27(3):357-362.  21. van der Heijden G J, van der Windt D A, de Winter A F. Physiotherapy for patients with soft tissue shoulder disorders: A systematic review of randomised clinical trials. BMJ. 1997;315(7099):25-30.  22. Klein MJ. Superficial heat and cold. eMedicine J. 2001;12(2). Available at: http://www.emedicine.com/pmr/topic201.htm. Accessed August 1, 2002.  23. BREG, Inc.  Polar Care Products [website].  Vista, CA: BREG; 2003. Available at: http://www.bregpolarcare.com. Accessed June 20, 2003. 24. Philadelphia Panel. Philadelphia Panel evidence-based clinical practice guidelines on selected rehabilitation interventions for low back pain. Phys Ther. 2001;81(10):1641-1674. 25. Philadelphia Panel. Philadelphia Panel evidence-based clinical practice guidelines on selected rehabilitation interventions for knee pain. Phys Ther. 2001;81(10):1675-1700. 26. Philadelphia Panel. Philadelphia Panel evidence-based clinical practice guidelines on selected rehabilitation interventions for neck pain. Phys Ther. 2001;81(10):1701-1717. 27. Robinson VA, Brosseau L, Casimiro L, et al. Thermotherapy for treating rheumatoid arthritis. Cochrane Database Syst Rev. 2002:(2):CD002826. 28. Brosseau L, Judd MG, Marchand S, et al. Thermotherapy for treatment of osteoarthritis. Cochrane Database Syst Rev. 2003;(4):CD004522. 29. Hubbard TJ, Aronson SL, Denegar CR.  Does cryotherapy hasten return to participation: A systematic review. J Athletic Training. 2004;39(1):88-94. 30. Bleakley C, McDonough S, MacAuley D. The use of ice in the treatment of acute soft-tissue injury: A systematic review of randomized controlled trials. Am J Sports Med. 2004;32(1):251-261. 31. Martin CW; Workers Compensation Board of British Columbia (WCB) Evidence-based Practice Group. Cryocuffs. Systematic Review. Richmond, BC: Workers Compensation Board of British Columbia (WorksafeBC); 2003. 32. Warren TA, McCarty EC, Richardson AL, et al. Intra-articular knee temperature changes: Ice versus cryotherapy device. Am J Sports Med. 2004;32(2):441-445. 33. Lee CK, Pardun J, Buntic R, et al. Severe frostbite of the knees after cryotherapy. Orthopedics. 2007;30(1):63-64. 34. NHIC, Inc. Local Coverage Determination (LCD) for Cold Therapy (L5038). Durable Medical Equipment Medicare Administrative Contractor (DME MAC) Jurisdiction A. Hingham, MA: NHIC; revised January 1, 2011. 35. NHIC, Inc. Local Coverage Article for Cold Therapy  (A19799). Policy Article. Durable Medical Equipment Medicare Administrative Contractor (DME MAC) Jurisdiction A. Hingham, MA: NHIC; effective January 2011. You are now leaving the Aetna website. Links to various non-Aetna sites are provided for your convenience only. Aetna Inc. and its subsidiary companies are not responsible or liable for the content, accuracy, or privacy practices of linked sites, or for products or services described on these sites. Continue >
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Category:  What are the Most Common Autoimmune Conditions? Article Details • Written By: Linda Saye • Edited By: C. Wilborn • Last Modified Date: 08 October 2018 • Copyright Protected: 2003-2018 Conjecture Corporation • Print this Article Autoimmune conditions are those in which the immune system attacks the healthy cells of the body, rather than protect them. This can cause severe health issues, including disability and even death. Some of the most common autoimmune conditions are rheumatoid arthritis, lupus, type 1 diabetes, and autoimmune hepatitis. Normally, the immune system produces white blood cells that attack invading substances, or antigens, such as viruses, bacteria, and toxins. In the case of autoimmune disorders, the immune system cannot distinguish between normal body tissue and antigens. It creates antibodies that attack its own tissues or organs, or both. Some of the tissues or organs commonly affected are blood vessels, the pancreas, joints, and the skin. The inflammation that results leads to autoimmune disease. Rheumatoid arthritis (RA), a chronic disease that causes inflammation of the joints, is probably the most common of the autoimmune conditions. The cause of RA is unknown, and it may develop slowly or quickly—depending on the patient—and can occur at any age. Some of the symptoms of RA are extreme pain, stiffness, and deterioration of the joints. RA most commonly affects the hands, wrists, feet, ankles, and knees, equally on each side of the body. If left untreated, RA can be debilitating, and can significantly shorten a person’s life. Ad Lupus is another common autoimmune disease. It is a chronic disorder that attacks the systems of the body, such as the skin, blood, kidneys, and nervous system. Lupus can occur at any age, and symptoms can vary from one person to another. Symptoms, which may include persistent fatigue, arthritis, nausea, and rash, may come and go, with sudden flare-ups. There are many serious conditions that may result from lupus if left untreated, including kidney failure, pulmonary embolism, and stroke. Another of the most common autoimmune conditions is type 1 diabetes. Type 1 diabetes is sometimes called juvenile or insulin-dependent diabetes, and is a chronic, lifelong disease that affects the pancreas by impeding its ability to produce insulin. Some of the acute or chronic problems that result from type 1 diabetes are increased urination, excessive thirst, abdominal pain, and fatigue. Over time, if not treated, type 1 diabetes will completely destroy the insulin-producing cells of the pancreas to the point that the body will no longer produce insulin at all. Autoimmune hepatitis is also an autoimmune condition, and occurs when the immune system attacks the normal cells of the liver. It is not clear as to what may trigger the immune system to attack the liver, but it often results from viral infections, such as measles or Epstein-Barr, certain drugs, or genetics. Symptoms resulting from autoimmune hepatitis include anemia, fatigue, abdominal pain, jaundice, and mental confusion. This disease should not go untreated, as it will ultimately result in cirrhosis, or scarring, of the liver and eventually complete liver failure. It is still not known what causes the immune system to confuse healthy body tissue for antigens. What is known, however, is that all autoimmune conditions are serious threats to the body that must be treated at the first signs of symptoms. They can cause a variety of chronic conditions that can, at the very least, affect quality of life. Some of the diseases, over time, will even lead to debilitation and death. Ad Recommended Discuss this Article anon37502 Post 1 Very informative useful article Post your comments Post Anonymously Login username password forgot password? Register username password confirm email
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Skip to Main content Skip to Navigation Journal articles N-3 polyunsaturated fatty acid and neuroinflammation in aging and Alzheimer’s disease Abstract : The innate immune system of the brain is mainly composed of microglial cells, which play a key role in the maintenance of synapses and the protection of neurons against noxious agents or lesions owing to their phagocytic activity. In the healthy brain, microglia are highly motile and strongly interact with neurons either by physical contact, induction of oxidative stress or through specific mediators, such as chemokines and cytokines. In response to inflammatory insult however, microglial cells get activated and produce inflammatory cytokines. The action of cytokines on specific receptors expressed in the brain triggers the development of sickness behavior and altered cognitive and emotional processes. The effects are acute and reversible as normal behavior is restored once the synthesis of inflammatory brain cytokines returns to baseline after a few hours. However, in pathological situations, these cytokines may reach toxic levels and have irreversible consequences such as neuronal death, as observed in neurodegenerative disorders such as Alzheimer’s disease. Omega-3 (n-3) polyunsaturated fatty acids (PUFAs) are essential nutrients and fundamental components of neuronal and glial cell membranes. They accumulate in the brain during the perinatal period in a dietary supply-dependent fashion. Their brain levels may diminish with age, but can be increased by diets enriched in n-3 PUFAs. Changes in the immune profile have been associated with n-3 PUFAs intake in humans and animal models. Therefore, the increasing exposure of the population to diets low in n-3 PUFAs could contribute to the deleterious effects of the chronic activation of microglia in the brain. Document type : Journal articles Complete list of metadata https://hal.inrae.fr/hal-02630551 Contributor : Migration Prodinra <> Submitted on : Wednesday, May 27, 2020 - 5:56:06 AM Last modification on : Tuesday, July 6, 2021 - 2:54:04 PM Links full text Identifiers Collections Citation Sophie Laye, Charlotte Madore, Isabelle St-Amour, Jean-Christophe Delpech, Corinne Joffre, et al.. N-3 polyunsaturated fatty acid and neuroinflammation in aging and Alzheimer’s disease. Nutrition and Aging, IOS Press, 2015, 3 (1), pp.33-47. ⟨10.3233/NUA-150049⟩. ⟨hal-02630551⟩ Share Metrics Record views 19
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Infertility: Understanding the Journey Infertility is a common condition, affecting millions of individuals worldwide. It is defined as the inability to conceive after one year of regular unprotected intercourse (or six months for women 35 and older). While the desire to start a family is natural, experiencing infertility can be a challenging and emotionally stressful journey. This article explores various aspects of infertility, including causes, diagnosis, treatment options, and the emotional impact. It aims to provide a comprehensive understanding of this condition and empower individuals seeking to build their families. Causes of Infertility Infertility can stem from various factors affecting either partner’s reproductive system. Here’s a breakdown of the common causes: • Female infertility: Ovulation disorders, blocked fallopian tubes, uterine fibroids, endometriosis, and age-related decline in egg quality are some causes. • Male infertility: Low sperm count, abnormal sperm morphology or motility, and varicocele (enlarged veins in the scrotum) can contribute to male infertility. • Unexplained infertility: In some cases, despite thorough testing, no specific cause for infertility can be identified. Diagnosis of Infertility If you’ve been trying to conceive for a year (or six months if you’re 35 or older), consulting a doctor is recommended. The evaluation process typically involves a medical history review, physical examinations, and fertility tests for both partners. • Female fertility tests: These may include ovulation tests, blood tests to assess hormone levels, ultrasound scans to examine the uterus and ovaries, and hysterosalpingography (an X-ray to check for fallopian tube blockages). • Male fertility tests: Semen analysis is the primary test to assess sperm count, motility, and morphology. Treatment Options  Fortunately, there  various treatment options available to address infertility, depending on the underlying cause. Here’s an overview of some common approaches: • Ovulation induction medications: These medications stimulate ovulation in women with ovulation disorders. • Surgery: Procedures to correct blocked fallopian tubes, remove uterine fibroids, or address varicocele in men may be performed. • Intrauterine insemination (IUI): Sperm is directly placed into the woman’s uterus to improve the chances of fertilization. • In vitro fertilization (IVF): This assisted reproductive technology involves egg fertilization outside the body, followed by embryo implantation in the uterus. • Donor sperm or egg donation: If sperm quality or egg quality is a significant concern, using donor sperm or eggs can be an option. • Surrogacy: Involves carrying a pregnancy for another person using a fertilized egg. The Emotional Impact  Infertility can be emotionally challenging, leading to stress, anxiety, depression, and feelings of isolation. It’s important to acknowledge these emotions and seek support. Here are some resources that can help: • Support groups: Connecting with others who understand your experiences can be invaluable. • Therapy: Individual or couples therapy can provide a safe space to process emotions and develop coping mechanisms. • Online resources: Many online resources offer information, support, and connections with others facing infertility.   Fueling Fertility: How Food Can Support Your Journey Trying to conceive can be an exciting time, but for some couples, it can also be a journey filled with challenges. Infertility, the inability to conceive after one year of regular unprotected intercourse (or six months if you’re 35 and older), affects millions worldwide. While medical interventions play a crucial role, what you put on your plate can also significantly impact your fertility. This article explores the fascinating connection between infertility nutrition and conception. How Does Food Affect Fertility? Food provides the building blocks for a healthy body, and a healthy body is essential for optimal reproductive health. Nutrients like vitamins, minerals, and antioxidants play a vital role in hormone regulation, egg and sperm quality, and overall fertility. Here’s how food impacts fertility: • Hormonal Balance: Certain foods can support healthy hormone levels that are critical for ovulation, sperm production, and a healthy uterine lining. • Nutrient Deficiencies: Deficiencies in essential nutrients like folic acid, iron, zinc, and omega-3 fatty acids can negatively impact egg and sperm health. • Inflammation: Chronic inflammation can disrupt reproductive processes. Certain foods promote inflammation, while others have anti-inflammatory properties. • Blood Sugar Control: Unstable blood sugar levels can affect ovulation and sperm health. Dietary Patterns for Fertility Several dietary patterns have been linked to improved fertility outcomes. Here are two well-researched approaches: • Mediterranean Diet: Rich in fruits, vegetables, whole grains, legumes, fish, and healthy fats like olive oil, this diet promotes overall health and may improve egg quality and sperm motility. • DASH Diet: Designed to control blood pressure, the DASH diet emphasizes fruits, vegetables, whole grains, and low-fat dairy, with limited red meat, saturated fat, and added sugars. Studies suggest it may improve ovulation rates. Foods to Prioritize for Fertility While there’s no single “fertility diet,” incorporating a variety of nutrient-rich foods can significantly benefit your reproductive health. Here are some key players: • Fruits and Vegetables: Packed with antioxidants, vitamins, and fiber, fruits and vegetables help combat inflammation and provide essential nutrients. Aim for a rainbow of colors to ensure a diverse range of nutrients. • Whole Grains: Opt for whole grains like brown rice, quinoa, and whole-wheat bread over refined grains. They provide sustained energy, regulate blood sugar levels, and are a good source of fiber. • Lean Protein: Include protein sources like chicken, fish, beans, lentils, and nuts in your diet. Protein is essential for building and repairing tissues, including reproductive organs. • Healthy Fats: Omega-3 fatty acids, found in fatty fish, flaxseeds, and walnuts, improve sperm quality and egg health. Include healthy fats in moderation to support hormone production and cell health. • Low-Fat Dairy: Choose low-fat dairy products like yogurt and milk for calcium, vitamin D, and other essential nutrients that support ovulation and sperm motility. Foods to Limit for Fertility Certain foods can negatively impact fertility when consumed in excess. Here’s what to limit: • Trans Fats and Saturated Fats: Found in processed foods, fried foods, and fatty cuts of meat, these fats can contribute to inflammation and disrupt hormone balance. • Added Sugars: Excessive sugar intake can lead to weight gain, insulin resistance, and disrupt ovulation. Opt for whole foods with natural sugars instead of added sugars. • Refined Carbohydrates: White bread, pastries, and sugary drinks cause blood sugar spikes and crashes, impacting hormone regulation. • Excessive Caffeine: Limit caffeine intake from coffee, tea, and soda as high doses may affect sperm motility and ovulation. • Alcohol: Excessive alcohol consumption can negatively impact both male and female fertility. Moderation is key. Additional Tips for Fertility Nutrition • Prenatal Vitamins: Both men and women trying to conceive can benefit from taking a prenatal vitamin. These vitamins provide essential nutrients like folic acid, iron, and zinc that support fertility and early fetal development. • Stay Hydrated: Drinking plenty of water is crucial for overall health and helps transport nutrients throughout the body. • Manage Weight: Being overweight or underweight can affect fertility. Maintaining a healthy weight through a balanced diet and regular exercise is important. • Read Food Labels: Pay attention to serving sizes and ingredient lists to minimize processed foods and added sugars. • Cook More at Home: This allows you to control ingredients and portion sizes, ensuring a healthier and more balanced diet. Remember: Infertility is a medical condition, and you’re not alone. With proper diagnosis, treatment, and support, many individuals and couples facing infertility can achieve their dream of building a family. Leave a Reply
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Search Images Maps Play YouTube News Gmail Drive More » Sign in Screen reader users: click this link for accessible mode. Accessible mode has the same essential features but works better with your reader. Patents 1. Advanced Patent Search Publication numberUS6558396 B1 Publication typeGrant Application numberUS 09/720,871 PCT numberPCT/JP1999/002386 Publication dateMay 6, 2003 Filing dateMay 6, 1999 Priority dateMay 6, 1999 Fee statusLapsed Also published asEP1095635A1, EP1095635A4, WO2000067674A1 Publication number09720871, 720871, PCT/1999/2386, PCT/JP/1999/002386, PCT/JP/1999/02386, PCT/JP/99/002386, PCT/JP/99/02386, PCT/JP1999/002386, PCT/JP1999/02386, PCT/JP1999002386, PCT/JP199902386, PCT/JP99/002386, PCT/JP99/02386, PCT/JP99002386, PCT/JP9902386, US 6558396 B1, US 6558396B1, US-B1-6558396, US6558396 B1, US6558396B1 InventorsKanji Inoue Original AssigneeKanji Inoue Export CitationBiBTeX, EndNote, RefMan External Links: USPTO, USPTO Assignment, Espacenet Apparatus for folding instrument and use of the same apparatus US 6558396 B1 Abstract The device is to keep a collapsible/restorable elastic artificial blood vessel 1 in a collapsed condition, to transport the artificial blood vessel 1 to a target position and subsequently to restore the artificial blood vessel 1 into a predetermined shape by releasing it from the collapsed condition. The device comprises wrapping members 51, 52 which are generally flat when spread and wires 53, 54 which hold each of the wrapping members 51, 52 in a condition of being rolled, wherein each of a body portion 2 and a branch portion 3 of the artificial blood vessel 1 is contained inside the wrapping members 51, 52 held by the wires 53, 54 in a collapsed condition and the wires 53, 54 are separated from the wrapping members 51, 52 at the target position to spread the wrapping members 51, 52 so as to release the artificial blood vessel 1. Images(19) Previous page Next page Claims(5) What is claimed is: 1. A collapsing device in combination with a collapsible/restorable elastic appliance, comprising: a collapsing device having: a first wrapping member which is generally flat when spread and a first retaining member which keeps the first wrapping member in a condition of being rolled and a second wrapping member which is generally flat when spread and a second retaining member which keeps the second wrapping member in a condition of being rolled; and a collapsible/restorable elastic appliance having a tubular body portion and a tubular branch portion which branches from a part of the tubular body portion, with the internal space of the branch portion communicating with the internal space of the tubular body portion, wherein the appliance is arranged so that the body portion is contained in a collapsed condition inside the first wrapping member held in a rolled condition by the first retaining member and the branch portion is contained in a collapsed condition inside the second wrapping member held in a rolled condition by the second retaining member, and the collapsing device keeps the appliance in a collapsed condition for transport to a target position and permits restoration of the appliance into a predetermined shape by releasing the appliance from the collapsed condition when the retaining members are separated from the wrapping members. 2. The collapsing device in combination with a collapsible/restorable elastic appliance as described in claim 1, wherein the body portion comprises intermittently arranged ring members bridged by a first flexible cover and the branch portion comprises intermittently arranged ring members bridged by a second flexible cover which branches from a part of the body portion, wherein the body portion and branch portion of the appliance are so arranged that each of the ring members is collapsed into a wavy shape having a peak and a valley. 3. A method of using a collapsing device in combination with a collapsible/restorable elastic appliance as described in claim 1, characterized by that the first wrapping member is mounted near an end portion of an outer circumference of a pipe member, the body portion and the branch portion of the appliance are inserted together into the pipe member at a position corresponding to the position where the first wrapping member is mounted and the first wrapping member and the body portion are drawn simultaneously out of the pipe member in a condition that both of the first wrapping member and the body portion are restrained from moving interactively at the end portion so as to contain the body portion and the branch portion of the appliance together inside of the first wrapping member, and subsequently a part of the first wrapping member is released from a condition of being held by the first retaining member and the branch portion is drawn out through the part of the first wrapping member and then the second wrapping member is mounted near an end portion of an outer circumference of a pipe member, the branch portion inserted into the pipe member and corresponding to the position where the second wrapping member is mounted and the second wrapping member and the branch portion are drawn simultaneously out of the pipe member in a condition that both of the second wrapping member and the branch portion are restrained from moving interactively so as to contain the branch portion inside of the second wrapping member. 4. The method of using the collapsing device in combination with a collapsible/restorable elastic appliance as described in claim 3, wherein the first wrapping member is made to open wider gradually along a tapered guide portion and then to be mounted on an outer circumference of the pipe member arranged at a position continuous to the guide portion. 5. A collapsing device in combination with a collapsible/restorable elastic appliance, comprising: a collapsing device having: a first wrapping member which is generally flat when spread and a first retaining member which keeps the first wrapping member in a condition of being rolled and a second wrapping member which is generally flat when spread and a second retaining member which keeps the second wrapping member in a condition of being rolled, wherein at least one of the first and second retaining members comprises a string which sews edges of a respective one of the first and second wrapping members and is arranged such that a retaining rod is passed through a loop formed at an end portion of the string; and a collapsible/restorable elastic appliance having a tubular body portion and a tubular branch portion which branches from a part of the tubular body portion, with the internal space of the branch portion communicating with the internal space of the tubular body portion, wherein the appliance is arranged so that the body portion is contained in a collapsed condition inside the first wrapping member held in a rolled condition by the first retaining member and the branch portion is contained in a collapsed condition inside the second wrapping member held in a rolled condition by the second retaining member, and the collapsing device keeps the appliance in a collapsed condition for transport to a target position and permits restoration of the appliance into a predetermined shape by releasing the appliance from the collapsed condition when the retaining members are separated from the wrapping members. Description FIELD OF THE ART This invention relates to a collapsing device for an appliance to be implanted which belongs to a field of medical devices and, more particularly, for artificial blood vessels or the like and a method of using the collapsing device. BACKGROUND ART With the recent progress of medical technique, a technique enabling transvascular use of a variety of appliances such as artificial blood vessel without ventrotomy has reached a clinical stage. Specific examples of such a technique include a method of transferring and fixing an artificial blood vessel using a catheter which has been invented by the inventor of present claimed invention and disclosed in the paper A.(for example, PCT/JP96/01347 which has been published with International Publication No. WO96/36387). This method includes; inserting a catheter into a human body through an inguinal artery to position a front end thereof near an affected portion in which an aneurysm or the like is present, inserting a tubular artificial blood vessel provided with collapsible/restorable elasticity into the catheter in a collapsed condition, transporting the artificial blood vessel to a predetermined location near the affected portion by the use of a transporting device or a hauling device, and releasing the artificial blood vessel from the catheter at the location, thereby to position the artificial blood vessel in an affected blood vessel having the aneurysm. In the above-described document a collapsing device for keeping the artificial blood vessel in a collapsed condition during transportation works as follows; the artificial blood vessel is bound by a string at given portions of an outer circumference thereof, a retaining rod is passed into the string to keep the artificial blood vessel in a collapsed condition so as to release the collapsed condition from a remote place, the artificial blood vessel is transported to a target position and subsequently the retaining rod is drawn out of the string to release the string so as to restore the artificial blood vessel. However, in order to make it possible to transport the artificial blood vessel smoothly, it is preferable to collapse the artificial blood vessel in a more appropriate condition. For example, in the artificial blood vessel described in the above document collapsible/restorable ring members are arranged intermittently along an axial direction. Due to this arrangement of the ring member, a protuberance is made locally on an outer face of the artificial blood vessel when the artificial blood vessel is collapsed by means of a string. Consequently, a dragging resistance will be generated while transporting the artificial blood vessel in a catheter. As a result, in order to reduce the dragging resistance, it is more preferable to make protuberances generate as least as possible on the outer face of the collapsed artificial blood vessel. DISCLOSURE OF THE INVENTION In order to solve the above problems a collapsing device for an appliance in accordance with the invention comprises a wrapping member which is generally flat when spread and a retaining member which holds the wrapping member in a condition of being rolled in order to keep a collapsible/restorable elastic appliance in a collapsed condition, to transport the appliance to a target position and subsequently to restore the appliance into a predetermined shape by releasing it from the collapsed condition, and is characterized by that the appliance is contained inside the wrapping member which is held by the retaining member in a collapsed condition and then the retaining member is separated from the wrapping member at the target position to spread the wrapping member so as to release the appliance. It is effective if the wrapping member is made of an expansible material. For further improve a stretching properties it is effective if the wrapping member is in a shape of a mesh, and especially it is preferable that the mesh is woven with wefts and warps or the wrapping member is made of polyurethane fibers. As a concrete embodiment to facilitate holding or spreading the wrapping member, it is represented that the retaining member is a wire rod which sews overwrapped edges of the wrapping member. As a concrete example of the wire rod it is preferable to use a wire made of nickel titanium. The wire rod may be a string which sews the overwrapped edges of the wrapping member and so arranged that a retaining member is passed through a loop formed at an end portion of the string. As a preferable example to which the present claimed invention is applied it is represented that the appliance is in a shape of a tube and so arranged as to be contained inside the wrapping member held by the retaining member in a collapsed condition. Among the above, it can be a more preferable example to which the present claimed invention is applied that the appliance is so arranged that intermittently arranged ring members are bridged by a flexible cover and each of the ring members is collapsed into a wavy shape having a peak and a valley alternately and repeatedly along a circumferential direction thereof. As another preferable example to which the present claimed invention is applied, it is represented that the appliance comprises a tubular body portion and a tubular branch portion which branches from a part of the tubular body portion with its internal space communicating with the body portion and so arranged that the body portion of the appliance is contained in a first wrapping member held by a first retaining member in a collapsed condition and the branch portion is contained in a second wrapping member held by a second retaining member in a collapsed condition. Among the above, it can be a more preferable example that the appliance is so arranged that the body portion is so made that intermittently arranged ring members are bridged by a flexible cover and the branch portion is so made that intermittently arranged ring members are bridged by a flexible cover with its internal space communicating with a part of the body portion, wherein the body portion and the branch portion of the appliance are so arranged that each of the ring members is folded into a wavy shape having a peak and a valley alternately and repeatedly along a circumferential direction thereof. As a simple method of using the collapsing device in accordance with the present claimed invention, it is preferable that the wrapping member is mounted on near an end portion of an outer circumference of a pipe member, the appliance is inserted into inside of the pipe member at a position corresponding to the position where the wrapping member is mounted and the wrapping member and the appliance are simultaneously drawn out of the pipe member in a condition that both of the wrapping member and the appliance are restrained from moving interactively at the end portion so as to contain the appliance inside of the wrapping member. If the appliance has a branch, the following step is preferable; the first wrapping member is mounted on near an end portion of an outer circumference of a pipe member, the body portion and the branch portion of the appliance are inserted together into inside of the pipe member at a position corresponding to the position where the first wrapping member is mounted, the first wrapping member and the body portion are drawn simultaneously out of the pipe member in a condition that both of the first wrapping member and the body portion are restrained from moving interactively at the end portion so as to contain the body portion and the branch portion of the appliance together inside of the first wrapping member, subsequently a part of the first wrapping member is released from a condition of being held by the first retaining member, the branch portion is drawn out through the part of the first wrapping member, then the second wrapping member is mounted on near an end portion of an outer circumference of a pipe member, the branch portion is inserted into inside of the pipe member at a position corresponding to the position where the second wrapping member is mounted and the second wrapping member and the branch portion are drawn simultaneously out of the pipe member in a condition that both of the second wrapping member and the branch portion are restrained from moving interactively at the end portion so as to contain the branch portion inside of the second wrapping member. In order to make it easier to mount the wrapping member it is preferable that the wrapping member is made to open wider gradually along a tapered guide portion and then to be mounted on an outer circumference of the pipe member arranged at a position continuous to the guide portion. It is preferable that the guide portion is applied with a material of cutting frictional resistance such as silicon or the like. As a procedure after transporting the collapsing device in accordance with the present claimed invention the following procedure is effective; the appliance is transported to a target position, the appliance is restored into a predetermined shape by releasing the wrapping member from a condition of being held by the retaining member and then the retaining member is removed from the target position with the wrapping member left at the position together with the appliance. In accordance with the collapsing device of the invention, since whole of the appliance is contained inside of the tubular wrapping member, it is possible to reduce a protuberance which is generated locally on an outer face of the appliance compared with a case in which the appliance is bound with a string partially to keep a collapsed condition. In addition, if the appliance is released from a condition of being held by the retaining member at a target position, the wrapping member is spread and a space surrounding the collapsed appliance will be open wide. As a result, interference with a movement of restoring the appliance into a predetermined shape can effectively be avoided. In this case, if the wrapping member is made of an expansible material, the material of the wrapping member stretches so as to wrap the appliance effectively when the wrapping member is held to wrap the appliance whereas the material of the wrapping member shrinks so as to be quickly separated from the appliance and move to a certain position near the target position when the wrapping member is released from a condition of being held. In case the material of the wrapping member is in a shape of a mesh, a stretching properties can effectively be demonstrated because a cross of the mesh stretches or shrinks. If the mesh is woven with wefts and warps, a stretching properties can sufficiently be demonstrated along both of lengthwise and crosswise and a cross of the mesh is hard to be moved as well as hard to be loosened, thereby to produce the above-mentioned effects for certain. If the material of the wrapping member is made of polyurethane fibers, it is easy to provide the material with a stretching properties, in addition, the wrapping material can be left at a target portion in a body together with the appliance after released because polyurethane fibers are not harmless to a human body. If the retaining member is a wire rod and overwrapped edges of the wrapping member are sewed by the wire rod, it is possible not only to keep the wrapping member in a shape of a tube but also to release the wrapping member directly from a condition of being held with relatively little resistance by pulling the wire rod lengthwise. If the wire rod is made of a wire of nickel titanium, it is possible to obtain an extremely flexible elasticity, thereby to be convenient for transporting the appliance. In addition, a length of the wrapping member can be adjusted depending on a demand since it is possible to cut only the wrapping member along a direction at right angles generally to the wire in a condition of passing the wire therethrough without cutting the wire, if necessary. Further, if the above-mentioned wire is used, there is no fear of getting entangled like a thread. With an arrangement in which the retaining member is a string which sews edges of the wrapping member and a retaining rod is passed through a loop formed at an end portion of the string, it is possible not only to hold the wrapping member in a shape of a tube but also to release the wrapping member from a condition of being held indirectly if the string is released from restraint of moving by hauling the retaining member so as to draw the retaining member out of the loop. If a string having elasticity is used, it is easy to release the string out of the loop, thereby to be especially effective. In accordance with the invention, it is extremely effective in collapsing a tubular appliance like an artificial blood vessel which becomes bulky when restored into a predetermined shape. More specifically, if the appliance is so arranged that ring members arranged intermittently are bridged by a flexible cover and each of the ring members is collapsed into a wavy shape having a peak and a valley alternately and repeatedly along a circumferential direction thereof, it is likely to happen that protuberance is made locally on the outer face of the appliance due to collapsed ring members. However, since whole of the appliance in accordance with the invention is wrapped by the wrapping member including protuberance, it is possible to firmly press down protuberance, thereby to form a smooth curved surface on the outer face thereof. In addition, in accordance with the invention, for a branched appliance wherein a tubular branched portion branches from a tubular body portion it is possible to collapse the branched appliance like an appliance in a tubular shape as a whole by applying a wrapping member and a retaining member to each of the body portion and the branch portion respectively. In case each of the body portion and the branch portion is so made that intermittently arranged ring members are bridged by a cover, it is possible to firmly press down protuberance generated on the body portion or the branch portion, thereby to form a smooth curved surface, on the outer face of the body portion and the branch portion respectively. Since the method of using the collapsing device of the invention comprises steps of mounting the wrapping member on near an end portion of an outer circumference of a pipe member, inserting the appliance into inside of the pipe member and drawing the wrapping member and the appliance simultaneously out of the pipe member in a condition that both of the wrapping member and the appliance are restrained from moving interactively at the end portion, it is possible to contain the appliance inside of the wrapping member in an appropriate collapsed condition through simple procedures, even though the wrapping member is highly elastic and the appliance is highly elastically restorable. For a branched appliance, if a procedure comprises steps of collapsing the body portion by the use of the first wrapping member and the first retaining member, releasing a part of the first wrapping member from a condition of being held by the first retaining member, drawing the branch portion out of the first wrapping member through the part and collapsing the branch portion by the use of the second wrapping member and second retaining member, it is possible to keep the body portion and the branch portion in an appropriate collapsed condition respectively without causing a big inconvenience in spite of the branched appliance. If the wrapping member is mounted on an outer circumference of the pipe member along a tapered guide portion to open wider gradually, it is possible to move the wrapping member to the outer circumference of the pipe member so as to be mounted thereon with ease and securely even if a shrinkage degree of the wrapping member is so high that the wrapping member shrinks quite a lot. If the appliance is transported to a target position, and restored into a predetermined shape by releasing the wrapping member from a condition of being held by the retaining member and subsequently only the retaining member is released from the target position with the wrapping member left at the position together, it is not necessary to remove the wrapping member, thereby to simplify a procedure of transporting the appliance. BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 is a perspective view of a branched artificial blood vessel to which one embodiment of the invention is applied. FIG. 2 is a perspective view of the branched artificial blood vessel in a collapsed condition by means of the collapsing device of the invention. FIG. 3 is a perspective view of the collapsing device in a condition of being spread. FIG. 4 is a perspective view of the collapsing device in a condition prior to being used. FIG. 5 is a view for explaining a procedure to collapse the artificial blood vessel with the collapsing device. FIG. 6 is a view for explaining the procedure to collapse the artificial blood vessel with the collapsing device. FIG. 7 is a view for explaining the procedure to collapse the artificial blood vessel with the collapsing device. FIG. 8 is a view for explaining the procedure to collapse the artificial blood vessel with the collapsing device. FIG. 9 is a view for explaining the procedure to collapse the artificial blood vessel with the collapsing device. FIG. 10 is a view for explaining the procedure to collapse the artificial blood vessel with the collapsing device. FIG. 11 is a view for explaining the procedure to collapse the artificial blood vessel with the collapsing device. FIG. 12 is a view for explaining the procedure to collapse the artificial blood vessel with the collapsing device. FIG. 13 is a schematic diagram showing a transporting device used in the embodiment. FIG. 14 is a schematic diagram showing a hauling device used in the embodiment. FIG. 15 is a schematic diagram showing a secondary hauling device used in the embodiment. FIG. 16 is a view for explaining a procedure to implant the artificial blood vessel of the embodiment into a target position. FIG. 17 is a view for explaining the procedure to implant the artificial blood vessel of the embodiment into the target position. FIG. 18 a view for explaining the procedure to implant the artificial blood vessel of the embodiment into the target position. FIG. 19 is a view for explaining another method of implanting the artificial blood vessel. FIG. 20 is a view for explaining another method of implanting the artificial blood vessel. FIG. 21 is a view for explaining another method of implanting the artificial blood vessel. FIG. 22 is a view showing a preferable procedure to release the collapsing device. FIG. 23 is a view showing another preferable procedure to release the collapsing device. FIG. 24 is a perspective view showing another collapsing device of the invention. BEST MODES OF EMBODYING THE INVENTION The invention will be described in detail with reference to the embodiments thereof shown in the accompanying drawings. FIG. 1 shows a branched artificial blood vessel 1 as an appliance to which a collapsing device of the embodiment is applied in a condition before it is collapsed. A fundamental arrangement of the artificial blood vessel 1 is described in documents such as the above-described document A (PCT/JP96/01347 (International Laid Open Number WO96/36387)) which has been disclosed by the inventor of this invention. A fundamental arrangement of this embodiment will now be described according to the document A. A body portion 2 of the artificial blood vessel 1 has a structure comprising end ring members 21, 22 having collapsible/restorable elasticity and intermediate ring members 23, 24 having collapsible/restorable elasticity interposed between the end ring members 21 and 22. A branch portion 3 of the artificial blood vessel 1 has a structure comprising an end ring member 31 and an intermediate ring member 32 interposed between the end ring member 31 and the body portion 2. The ring members 21, 22, 23, 24 are bridged by a flexible, tensile and waterproof tubular cover 20 and the ring members 31, 32 are bridged by a flexible, tensile and waterproof tubular cover 30 so as to form the branched artificial blood vessel 1. Internal spaces of the tubular covers 20 and 30 are liquidtightly connected at a connecting portion. FIG. 16 schematically shows the artificial blood vessel 1 and a bifurcated portion 4 where a bifurcated blood vessel 42 bifurcated from a trunk blood vessel 41 at which the artificial blood vessel 1 is to be implanted. The trunk blood vessel 41 is, for example, an arcuate artery and the bifurcated blood vessel 42 is an artery which locates at a peripheral side of the trunk blood vessel 41. The branched artificial blood vessel 1 is introduced to be implanted into an aneurysm 43 at the bifurcated portion 4 to prevent blood flowing into the aneurysm 43. For introducing the artificial blood vessel 1 a transvessel procedure is adopted; the artificial blood vessel 1 is kept in a collapsed condition, inserted into a groin F of the thigh through a sheath C, transported to a target position and then restored into a predetermined shape by releasing a condition of being kept. For this transvessel procedure the artificial blood vessel 1 is collapsed into a small size by a collapsing device 5 shown in FIG. 2. The collapsing device 5 comprises a first and a second wrapping members 51 and 52, and a first and a second wires 53 and 54 as a first and a second retaining members. The first wrapping member 51 is to wrap the body portion 2 of the artificial blood vessel 1, and interwoven with wefts and warps of polyurethane fibers (generally called spandex fibers) to form a mesh as shown in FIG. 3 so as to be expansible and generally flat when spread. The wefts and warps are interwoven at each points of intersection and stretching of a cross of the mesh formed at the intersection provides whole of the first wrapping member 51 with stretching properties along lengthwise and crosswise directions. The second wrapping member 52 is to wrap the branch portion 3 of the artificial blood vessel 1 and has the same arrangement as that of the first wrapping member 51. The first wire 53 is flexible made of nickel titanium alloys. The first wire 53 holds the first wrapping member 51 in a shape of a tube as shown in FIG. 4 by steps of overlapping both edges 51 a of the first wrapping member 51 so as to make the first wrapping member 51 in a shape of a general tube and passing the first wire 53 so as to sew the overlapped edges 51 a together in broken lines. The second wire 54 is, like the first wire 53, to sew both edges 52 a of the second wrapping member 54 together and a material thereof is the same as that of the first wire 53. Then the artificial blood vessel 1 is contained in the first and second wrapping members 51 and 52 of the collapsing device 5 in a collapsed condition by the following steps. First, as shown in FIG. 5, prepare a pipe member 61 and a guide member 62 having a tapered guide portion having a smaller diameter and which can be passed through an internal space of the pipe member 61. A collapsing aid 63 is continuously arranged at one end 61 a of the pipe member 61. Then the guide member 62 is inserted into the pipe member 61 through the end 61 a until a side having the smaller diameter of the guide member 62 projects from the other end 61 b, next the first wrapping member 51 which has been kept in a shape of a tube by the first wire 53 is mounted on the guide member 62 through the side of the smaller diameter of the guide member 62 in a condition that the other side having an ordinary size of a diameter of the guide member 62 is generally connected continuously with the other end 61 b of the pipe member 61, and then the first wrapping member 51 is moved to slide along a tapered guide portion of the guide member 62 toward a direction of a bigger diameter of the guide member 62 as shown by an arrow in FIG. 5 so as to mount the first wrapping member 51 on the outer circumference of the pipe member 61 through the outer circumference of the guide member 62 at a position shown in FIG. 6. Finally, the guide member 62 is drawn from the end 61 a of the pipe member 61 as shown by an arrow in FIG. 6. Next, the artificial blood vessel 1 is inserted as shown in FIG. 7 into the pipe member 61 through the end 61 a in a collapsed condition. For collapsing the artificial blood vessel 1 an inner face of the collapsing aid 63 is preferably used and for transporting the artificial blood vessel 1 in the pipe member 61 a transporting device 7 is used. The transporting device 7 is essentially for transporting the artificial blood vessel 1 to a target position inside a human body as shown in FIG. 16 through a sheath C, and so arranged that a wire 72 is contained in a tube 71 as shown in FIG. 13. The wire 72 is drawn out of the tube 71 through a window 71 a of the tube 71 for engagement with a hooking means 21 a attached to the front end ring member 21 and then drawn into the tube 71 again, thereby to make the transporting device 7 engage and hold the front end ring member 21. Then when the transporting device 7 is pushed toward a direction as shown by an arrow in FIG. 7, a front side of the artificial blood vessel 1 is hauled forward, which makes each of the ring members 21, 22, 23, 24 of the body portion 2 collapsed one by one into a wavy shape having a peak and a valley alternately and repeatedly along a circumferential direction along an inner face of the collapsing aid 63. Then the artificial blood vessel 1 is inserted into the pipe member 61 with the branch portion 3 attached thereto. Thus the artificial blood vessel 1 is introduced and inserted into inside of the pipe member 61 at a position which corresponds to the position at which the first wrapping member 51 is mounted as shown in FIG. 8. In stead of this procedure, a following procedure may be adopted; a front pull string is passed through the above-described hooking means 21 a, both ends of the front pull string is passed through the pipe member 61 and the artificial blood vessel 1 is introduced into the pipe member 61 by pulling the front pull string. Then the wrapping member 51 and the artificial blood vessel 1 are restricted from moving by picking the wrapping member 51 and a part of the artificial blood vessel 1 together with a finger at a position shown by an arrow p in FIG. 8. With this condition kept, the pipe member 61 is moved rearward relatively to the position so as to draw the wrapping member 51 and the artificial blood vessel 1 out of the pipe member 61. Then the artificial blood vessel 1 is being inserted into inside of the wrapping member 51. Finally, the artificial blood vessel 1 is contained in the wrapping member 51 in a collapsed condition by drawing out the pipe member 61 completely as shown in FIG. 9. Although the branch portion 3 is not illustrated in FIGS. 5, 6, 8 and 9, the branch portion 3 is contained in the wrapping member 51 together.with the body portion 2. Next, the branch portion 3 is wrapped by means of the second wrapping member 52 and the second wire 54. In order to wrap the branch portion 3, a part of seams in the first wrapping member 51 sewed by the first wire 53 is pushed to make an opening wider and the branch portion 3 is introduced outside through the opening in the the first wrapping member 51 as shown by an arrow in FIG. 10. The second wrapping member 52 is mounted on the outer circumference of the pipe member 61 to which a funnel-shaped collapsing aid 63 is attached in a same manner as mentioned above and the branch portion 3 is contained in the pipe member 61 as shown in FIG. 11. In containing the branch portion 3 into the pipe member 61 through the collapsing aid 63, the pipe member 61 may be picked to draw through the other end 61 b by the use of forceps or may be drawn by the use of a string for a front pull which has been passed through a hooking means 31 a like a case described above because the pipe member 61 is short. In this case, since the base end 3 a of the branch portion 3 is connected with the body portion 2, it is not possible for the pipe member 61 to be drawn together with the collapsing aid 63 through the other end 61 b as it is. Considering this arrangement, the branch portion 3 is contained in the wrapping member 52 in a collapsed condition of a wavy shape by the following steps; the branch portion 3 is inserted into the pipe member 61 through the collapsing aid 63, the collapsing aid 63 is removed so as to release one end 61 a of the pipe member 61, as shown in FIG. 12, by resecting the collapsing aid 63 or something like that and the pipe member 61 is drawn out with the second wrapping member 52 and the branch portion 3 restrained from moving as shown by an arrow q in FIG. 12. If the collapsing aid 63 is made of a relatively flexible material and can be shrunk as a same size as that of the pipe member 61, it can be separated from the second wrapping member 52 without being broken like the above. FIG. 2 shows the artificial blood vessel 1 which has been collapsed by the use of the collapsing device 5 in the above manner. Next, a procedure of introducing the artificial blood vessel 1 into the human body will now be explained. For introducing the artificial blood vessel 1 used are a hauling device 8 which tows the rear end of the body portion 2 rearward and a secondary hauling device 9 which brings the branch portion 3 from the trunk blood vessel 41 to the branch blood vessel 42 as well as the above described transporting device 7. The hauling device 8 is, as shown in FIG. 14, so arranged that a wire 82 is contained in a tube 81 and holds and makes an engagement with the end ring member 22 by engaging the wire 82 which is drawn out of a window 81 a provided on the tube 81 with a hooking means 22 a provided on one part of the end ring member 22 locating rear and then drawing the wire 82 into the tube 81 again. The hauling device 8 can haul the body portion 2 of the artificial blood vessel 1 toward a opposite direction to a direction the hauling device 7 does. The secondary hauling device 9 is, as shown in FIG. 15, so arranged that a wire 92 is contained in a tube 91 and holds and makes an engagement with the end ring member 31 of the branch portion 3 by engaging the wire 92 which is drawn out of a window 91 a provided on the tube 91 with the hooking portion 31 a provided on one part of the end ring member 31 and then drawing the wire 92 into the tube 81 again. The secondary hauling device 9 can haul whole of the branch portion 3 of the artificial blood vessel 1 toward a direction to be separated from the body portion 2. The tube 91 has an arrangement of double-lumen so as to contain both the wire 92 and the wire 54 of the collapsing device 5. Especially the tube 91 of the secondary hauling device 9 used in this embodiment is made of a material which is more flexible than that of which the transporting device 7 and the hauling device 8 are made. In addition, at least the length corresponding to a distance from a groin of a thigh to the affected portion of the base end b3a of the secondary hauling device 9 is made of a guide member b3x such as a helical spring which is not only flexible but also having a characteristic that a force can be so transmitted to the whole part thereof by manipulating one part thereof that the secondary hauling device 9 can be freely rotated, inserted or pulled. The base end b3a is bent sideward along the length thereof, which makes it possible to change a direction of the base end b3a relatively big by manipulating the guide member b3x of the secondary hauling device 9. Then introduce the devices 7, 8 and 9 into a human body through the sheath C having a sealing mechanism cs at a base end thereof. Especially the secondary hauling device 9 is not introduced into the sheath C through the sealing mechanism cs by itself but is introduced into the sheath C in a condition of being contained in a guide pipe H. In other word, the secondary hauling device 9 is contained in the guide pipe H in a condition of being folded to be double and so arranged that a portion of being folded to be a loop is introduced outside through a base end of the guide pipe H and both ends of the secondary hauling device 9 are introduced outside of the guide pipe H through a front end of the guide pipe H. At the base end h1 of the guide pipe H also provided is a sealing mechanism hs. Next, a procedure to implant the artificial blood vessel 1 will be explained. First, the sheath C is inserted into inside of a human body from an inguinal artery at a groin F of a thigh, as shown in FIG. 16, until a tip of the sheath C is positioned near an affected portion where an aortic aneurysm 43 or the like is caused. Then the artificial blood vessel 1 collapsed by the collapsing device 5 of the invention is introduced into the sheath C together with the transporting device 7 and the hauling device 8. At the same time the secondary hauling device 9 is inserted into the sheath C through the guide pipe H. Next, the transporting device 7 is pushed so as to transport the artificial blood vessel 1 accompanied by the hauling device 8 and the secondary hauling device 9 attached thereto to a target position where the branch blood vessel 42 branches from the trunk blood vessel 41 as shown in FIG. 16. Subsequently, the artificial blood vessel 1 is released from the sheath C. Since the artificial blood vessel 1 is kept in a collapsed condition by the use of the collapsing device 5 of the invention after released, it does not necessarily have to be released at a predetermined location. Under the condition, a catcher G is introduced near the affected portion through a catheter K from another bifurcated portion of the groin in order to catch the secondary hauling device 9. The catcher G comprises a wire g1 at a front tip of which a loop is formed and a tube g2 in which the wire g1 is contained, and is so constructed that the loop projecting out of the tube g2 opens or closes if the wire g1 is drawn out of the tube g2 or inserted into the tube g2. The base end b3a of the secondary hauling device 9 is caught by the use of the wire g1 which has the loop by operating the guide member b3x of the secondary hauling device 9 and the catcher G. As mentioned above, near the base end b3a of the secondary hauling device 9 is made to be bent to facilitate an operation of catching. This makes it possible for the base end b3a to be freely rotated, inserted or pulled by manipulating the guide member b3x which is drawn out of the guide pipe H. After catching the base end b3a by the use of the catcher G, the base end b3a is drawn out of the human body through the other groin of the thigh. The longer the base end b3a is drawn, the shorter a length of the secondary hauling device 9 locating out of the sealing mechanism hs of the guide pipe H becomes. Finally, the secondary hauling device 9 is contained in the guide pipe H after passing through the sealing mechanism hs. Then the base end b3a of the secondary hauling device 9 is gradually drawn out of the human body through the other groin of the thigh. As shown in FIG. 17, the front tip of the secondary hauling device 9 alone is eventually left in the human body and the base end b3a is almost completely drawn out from the other groin of the thigh. Then after the secondary hauling device 9 is drawn out, the branch portion 3 of the artificial blood vessel 1 is hauled toward a direction shown by an arrow in FIG. 17 by the use of the secondary hauling device 9 so as to be placed at an appropriate position at the branch blood vessel 42 which branches from the trunk blood vessel 41. After the artificial blood vessel 1 is arranged at the appropriate position, the wires 53 and 43 which constitute the collapsing device 5 of the embodiment are drawn. More concretely, first the first wire 53 is drawn so as to release the first wrapping member 51 from the body portion 2 and each portion of the body portion 2 is restored to be inflated one by one so as to tightly attach to an inner wall of the trunk blood vessel 41 by making use of elasticity. Next, the second wire 54 is drawn so as to release the second wrapping member 52 from the branch portion 3 and each portion of the branch portion 3 is restored to be inflated one by one so as to tightly attach to an inner wall of the branch blood vessel 42 by making use of elasticity. FIG. 18 shows a condition in which each of the body portion 2 and the branch portion 3 of the artificial blood vessel 1 is attached to the trunk blood vessel 41 and the branch blood vessel 42 respectively. A state in which each of the ring members 21, 22 and 31 is not restored into a shape of round as shown in FIG. 18 is due to pulsations of a blood vessel with which each of the ring members 21, 22 and 31 comply. The body portion 2 and the branch portion 3 is released from an engagement with each of the wires 72, 82 and 92 of the transporting device 7, the hauling device 8 and the secondary hauling device 9 by drawing the wires 72, 82 and 92. Finally, the transporting device 7, the hauling device 8 and the secondary hauling device 9 are drawn out of the human body. This will complete implantation of the artificial blood vessel 1 into the target portion. The first and second wrapping member 51, 52 which has been separated may be left at the separated position and only the first and second wires 53, 54 may be removed, however, the wrapping member 51, 52 may be removed by capturing it, if necessary. As mentioned above, the collapsing device 5 for artificial blood vessels in accordance with the embodiment comprises the wrapping members 51 and 52 which are generally flat when spread and the wires 53 and 54 which hold each of the wrapping members 51, 52 in a condition of being rolled into a shape of a tube, and is so arranged that the artificial blood vessel 1 is contained in the wrapping members 51 and 52 held by the wires 53 and 54 in a collapsed condition and the wires 53 and 54 are separated from the wrapping members 51 and 52 at the target position to spread the wrapping members 51 and 52 so as to release the artificial blood vessel 1. In accordance with the collapsing device of the invention, since whole of the artificial blood vessel 1 is contained inside the tubular wrapping member 51 and 52, it is possible to reduce protuberance which is generated locally on an outer face of the artificial blood vessel 1 compared with a case in which the artificial blood vessel 1 is bound with a string partially to keep a collapsed condition. In addition, if the artificial blood vessel 1 is released from a condition of being held by the wires 53, 54 at a target position, the wrapping member 51, 52 is spread and a space surrounding the collapsed body portion 2 and the collapsed branch portion 3 of the artificial blood vessel 1 will be open wide. As a result, interference with a movement of restoring the artificial blood vessel 1 into a predetermined shape can effectively be avoided. Especially, if the wrapping member 51, 52 is made of an expansible material, the material of the wrapping member 51, 52 stretches so as to wrap the artificial blood vessel. 1 effectively when the wrapping member 51, 52 is held to wrap the artificial blood vessel 1 whereas the material of the wrapping member 51, 52 shrinks so as to be quickly separated from the body portion 2 or the branch portion 3 and move to a certain position near the target position, although not shown in FIG. 18, when the wrapping member 51, 52 is released from a condition of being held. In addition, since the material of the wrapping member 51, 52 is in a shape of a mesh, a stretching properties can effectively be demonstrated because a cross of the mesh stretches or shrinks. Further since the mesh is woven with wefts and warps, a stretching properties can sufficiently be demonstrated along both of lengthwise and crosswise and a cross of the mesh is hard to be moved as well as hard to be loosened, thereby to especially produce the above-mentioned effects for certain. More specifically since the material of the wrapping member 51, 52 is made of polyurethane fibers, it is easy to provide the material with a stretching properties, in addition, the wrapping material 51, 52 can be left at a target portion in a human body together with the artificial blood vessel 1 after released because polyurethane fibers are not harmless to a human body. In addition, since the wire 53, 54 is a wire rod and the overwrapped edges 51 a and 52 a of the wrapping member 51, 52 are sewed by the wire 53, 54, it is possible to keep the wrapping member 51, 52 in a shape of a tube as well as to release a condition of the wrapping member 51, 52 being held directly with relatively little resistance by pulling the wire 53, 54 lengthwise. Especially since the wire 53, 54 is made of nickel titanium, it is possible to obtain an extremely flexible elasticity, it is possible for the wire 53, 54 to pass through a bent portion in a human body so as to reach an target position. In addition, even though whole of the wire 53, 54 gets twisted, it can be expected that the wire 53, 54 is corrected by itself due to its elasticity. Further, since a length of the wrapping member 51, 52 can be adjusted depending on a demand because it is possible to cut only the wrapping member 51, 52 along a direction at right angles generally to the wire 53, 54 in a condition of passing the wire 53, 54 therethrough without cutting the wire 53, 54, if necessary. Further, if the wrapping member 51, 52 is sewed with a thread, the thread might get entangled. However, since the wrapping member 51, 52 is sewed with the above-mentioned wire 53, 54, there is no fear of getting entangled like the thread. Since the collapsing device 5 of this embodiment has the above arrangement, it is extremely suitable for collapsing the artificial blood vessel 1. More specifically, the artificial blood vessel 1 is so arranged that ring members 21, 22, 23, 24 arranged intermittently are bridged by the cover 20 and each of the ring members 31 32 is collapsed into a wavy shape having a peak and a valley alternately and repeatedly along a circumferential direction thereof. Then protuberance is likely made locally on outer faces of the ring members 21, 22, 23, 24 31, 32 due to elastic restoring force when the artificial blood vessel 1 is collapsed. However, with the collapsing device 5 of the invention, whole of the body portion 2 and the branch portion 3 of the artificial blood vessel 1 are wrapped by the wrapping member 51, 52 and kept in a collapsed condition. As a result, it is possible to firmly press down protuberance, thereby to form a smooth curved surface of the outer face thereof. Since the method of using the collapsing device 5 of this embodiment comprises steps of mounting the wrapping member 51 on near an end portion of an outer circumference of a pipe member 61, inserting the artificial blood vessel 1 into inside of the pipe member 61 and drawing the wrapping member 51 and the body portion 2 of the artificial blood vessel 1 are simultaneously out of the pipe member 61 in a condition that both of the wrapping member 51 and the body portion 2 of the artificial blood vessel 1 are restrained from moving interactively at the end portion, it is possible to contain the artificial blood vessel 1 inside the wrapping member 51 in an appropriate collapsed condition through simple procedures, even though the wrapping member 51 is highly elastic and the artificial blood vessel 1 is highly elastically restorable. Especially since the artificial blood vessel 1 has the branch portion 3, the artificial blood vessel 1 is collapsed with the procedure of collapsing the body portion 2 by using the first wrapping member 51 and the wire 53, releasing a part of the first wrapping member 51 from a condition of being held by the wire 53, drawing the branch portion 3 out out the first wrapping member 51 through the part and collapsing the branch portion 3 by using the second wrapping member 52 and the wire 54. As a result, it is possible to keep the body portion 2 and the branch portion 3 in an appropriate collapsed condition respectively without causing a big inconvenience although the artificial blood vessel 1 has the branch portion 3. Further, since the wrapping member 51, 52 is mounted on an outer circumference of the pipe member 61 along a tapered guide portion to open wider gradually, it is possible to move the wrapping member 51, 52 to the outer circumference of the pipe member 61 so as to be mounted thereon with ease and securely even if a shrinkage degree of the wrapping member 51, 52 is so high that the wrapping member 51, 52 shrinks quite a lot. In addition, with a procedure of transporting the artificial blood vessel 1 to a target position, restoring the artificial blood vessel 1 into a predetermined shape by releasing the wrapping member 51, 52 from a condition of being held by the wire 53, 54 and then removing only the wire 53, 54 from the target position with the wrapping member 51, 52 left at the position together, it is not necessary to remove the wrapping member 51, 52. As a result, a procedure of transporting the artificial blood vessel 1 can be simplified. For introducing the branch portion 3 into the branch blood vessel 42, if the branch blood vessel 42 branches toward an inner side to the surface of the human body and the catcher G can not be inserted, a guiding device 109 as shown in FIG. 19 may be used instead of the above-mentioned secondary hauling device 91. The guiding device 109 is operable for rotation by hand as indicated by an arrow M shown in FIG. 19 and comprises an operating rod 109 a having a front end to be inserted into the body portion 2 from an opening end locating a base end thereof, a guiding rod 109 b continuously connected to the operating rod 109 a so as to be capable of turning around and having a front end extending to an opening end of the branch blood vessel 42, and a mooring means 109 c for releasably mooring the branch portion 3 by a portion adjacent the opening end thereof to the guiding rod 109 b and so arranged that the branch portion 3 accompanying the guiding rod 109 b can be inserted into the branch blood vessel 42 together with the guiding rod 109 b by moving the body portion 2 rearward when the guiding rod 109 b has assumed a predetermined position by turning. The operating rod 109 a and the guiding rod 109 b are formed of a flexible wire rod (usually called “catheter”). This wire rod is turned up to form a loop L, the base end side of which forms the operating rod 109 a, the front side of which forms the guiding rod 109 b. The front side and the base end side of the loop L are brought into contact with each other, and the contact portion X is fixed by tying with a string or the like. The loop L is so arranged that the most part thereof protrudes from the opening end of the body portion 2 defined by the ring member 21 locating front. More specifically, the wire rod comprises a tube 191 and a guiding wire 192 retractably contained in the tube 191 with the front end of the guiding wire 192 protruding from the front end of the tube 191. The mooring means 109 c comprises a mooring wire 193 which alternatively restricts the hooking portion 31 a of the branch potion 3 from moving in cooperation with the tube 191. The mooring means 109 c is made to release a moored state of the hooking portion 31 a with the branch portion 3 when the mooring wire 193 is drawn. Then the body portion 2 and the branch portion 3 are collapsed together with the guiding device 109 by the wrapping members 51 and 52 and the wires 53 and 54 like the above-described embodiment. The wire 54 serves also as the mooring wire 193. For introducing the branch portion 3 into the branch blood vessel 42 by making use of the guiding device 109, the base end side of the tube 191 as the operating rod 109 a is operated for rotation as indicated by the arrow M shown in FIG. 19 from the outside of the thigh F to cause the front side of the tube 191 as the guiding rod 109 b to turn around as indicated by the arrow N shown in FIG. 19 so that the front end of the guiding rod 109 b faces to the entrance of the branch blood vessel 42. The positioning of the guiding rod 109 b may be achieved while observing the guiding rod 109 b by X-raying or the like. Once the positioning is done, the guiding wire 192 is pushed forward so that the frond end thereof is first inserted into the branch blood vessel 42 as shown in FIG. 20. Thereafter, the hauling device 8 attached to the body portion 2 is pulled to move whole of the artificial blood vessel 1 backward. At this time, the guiding rod 109 b forming the front side of the tube 191 advances in the direction indicated by an arrow shown in FIG. 20 to a predetermined location in the branch blood vessel 42 as accompanied by the branch portion 3 under the guidance of the guiding wire 192. When the branch portion 6 has reached the predetermined location and the branched artificial blood vessel 1 has wholly become in position, the wire 53 accompanying the body portion 2 is first pulled to separate the wrapping member 52 as shown in FIG. 20 and then the wire 54 accompanying the branch portion 3 is pulled to separate the wrapping member 53. This makes each of the body portion 2 and the branch portion 3 swell by making use of elasticity to be restored into a state to tightly attach to the trunk blood vessel 41 and the branch blood vessel 42 as shown in FIG. 21. Finally, the wires 72 and 82 of the transporting device 7 and the hauling device 8 are pulled to release an engagement with the ring members 21 and 22, and the transporting device 7 and the hauling device 8 are moved out of the bifurcated portion 4. In addition, when the wire 54 which serves as the wire 193 also is pulled, the mooring means 9 c is released, then the guiding device 9 also can be removed. Thus the branched artificial blood vessel 1 can preferably be released from a collapsed condition in a bifurcated portion 4 and can preferably be implanted. The invention is not limited to the above-mentioned embodiment. For example, in the above embodiment the wrapping member which constitutes the collapsing device is sewed by a single collapsing device, but the body portion of the artificial blood vessel may be sewed and collapsed by a plurality of collapsing devices and each of the collapsing devices is separated one by one so as to restore the body portion. In accordance with the arrangement, the body portion of the branched artificial blood vessel can be appropriately collapsed avoiding the branch portion and the branch portion can be preferably collapsed because it becomes unnecessary to draw the branch portion out of an opening between seams like the above embodiment. In this case, it is effective to commonize a wire alone. More specifically, it is possible to commonize a wire with ease if the artificial blood vessel is sewed with separate tubes divided front and rear by the branch portion, a common wire is passed through both tubes and then the tubes are removed. In addition, if a plurality of wires are used, a resistance becomes low when drawn. As a result, this arrangement will be effective especially for a case in which drawing force exerts a harmful influence on a shape of the entire artificial blood vessel. In the above embodiment the wrapping member of the collapsing device is separated starting from a front side locating upstream of the artificial blood vessel by drawing the wire, but may be separated starting from a base side locating downstream of the artificial blood vessel by reversing a direction to which the wire is inserted. In accordance with the arrangement, the artificial blood vessel is restored gradually from a side of downstream so as to be fixed to the inner wall of the blood vessel. Then it can be prevented that high fluid pressure is applied to a portion which meets a blood flow between a restored portion and a not-restored portion unlike a case in which the artificial blood vessel is restored from a side of upstream. As a result, it becomes possible to avoid a case in which the artificial blood vessel is carried downstream. Further, in case the wire 53 is drawn, if another tube 100 is fit over the wire 53 of the collapsing device 5 through a base side of the sheath, a tip 100X of the tube 100 is moved to a position where the artificial blood vessel 1 is to be implanted and the wire 53 is pulled with the tip 100X pushed against the rear of the artificial blood vessel 1, as shown in FIG. 22, it becomes possible to draw the wire 53 out of the body portion 3 without unnecessary force applied to the whole of the artificial blood vessel 1. More specifically, in order to draw out the wire 54 which keeps the branch portion 3 in a collapsed condition, if a flexible helical spring 100 a is connected to a front tip of the tube 100, a front tip 100Y of the helical spring 100 a is bent along the wire 54 which keeps the branch portion 3 in a collapsed condition and the front tip 100Y is placed at the base end of the branch portion 3, as shown in FIG. 23, a direction of pull to which the wire 54 is drawn is optimized, thereby to effectively avoid inconveniences such as a case that the wire 54 is broken. In the above embodiment the collapsing device is so arranged that each edge of the wrapping member faces outward of a tube shape, however, it may be variously modified such as the wrapping member is rolled so as to be in a tube shape wherein one edge 51 a 1 (52 a 1) locates outside of the tube shape and the other edge 51 a 2 (52 a 2) locates inside of the tube shape as shown in FIG. 24. In addition, the retaining member may be a string and so arranged that the string sews both edges of the wrapping member and a retaining rod such as a wire is passed through a loop portion formed at an end portion of the string. In this case it is possible to keep a shape of a tube. And it is also possible to release the wrapping member from a condition of being held indirectly if the retaining member is hauled so as to be separated from the loop, which will release the string from being restrained from moving. Especially, if the string is elastic, it is easy to release a condition of being kept. POSSIBLE APPLICATIONS IN INDUSTRY As mentioned above, the collapsing device for the appliance and the method of using the collapsing device in accordance with the invention make it possible to preferably wrap the appliance in a collapsed condition without bringing about an uneven portion on a surface thereof, to keep a condition in which the collapsing device can be transported to a target position by smoothly passing through a curved portion in a human body and to release the appliance from a collapsed condition with ease by a remote control, thereby to make it possible to preferably be utilized for implanting a various kinds of appliances such as an artificial blood vessel into a human body. 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Referenced by Citing PatentFiling datePublication dateApplicantTitle US6878153Jun 28, 2002Apr 12, 2005Rubicon Medical, Inc.Methods, systems, and devices for providing embolic protection and removing embolic material US6997939 *Jun 28, 2002Feb 14, 2006Rubicon Medical, Inc.Methods, systems, and devices for deploying an embolic protection filter US8221494Feb 20, 2009Jul 17, 2012Endologix, Inc.Apparatus and method of placement of a graft or graft system US8672989Jul 11, 2012Mar 18, 2014Endologix, Inc.Apparatus and method of placement of a graft or graft system US20060155358 *Jan 9, 2006Jul 13, 2006Laduca RobertMethods for placing a stent in a branched vessel US20100179636 *Mar 17, 2010Jul 15, 2010Endologix, Inc.Graft deployment system EP2068765A2 *Jul 31, 2007Jun 17, 2009Cartledge, Richard G.Sealable endovascular implants and methods for their use EP2522314A1 *Jan 9, 2006Nov 14, 2012Taheri Laduca LLCApparatus and method for deploying an implantable device within the body Classifications U.S. Classification606/108, 623/1.11 International ClassificationA61F2/07, A61F2/954, A61F2/95, A61F2/89, A61F2/06 Cooperative ClassificationA61F2002/9511, A61F2/07, A61F2002/061, A61F2002/067, A61F2/954, A61F2002/075, A61F2/89 European ClassificationA61F2/954, A61F2/07 Legal Events DateCodeEventDescription Oct 13, 2006FPAYFee payment Year of fee payment: 4 Dec 13, 2010REMIMaintenance fee reminder mailed May 6, 2011LAPSLapse for failure to pay maintenance fees Jun 28, 2011FPExpired due to failure to pay maintenance fee Effective date: 20110506
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A new study reported in the journal Science on June 6, 2014 is groundbreaking in filling in some missing information about how sleep affects learning, memory, and performance. Over the last few decades, evidence has been accumulating that sleep is beneficial, and recently slow wave sleep has been found to be the sleep stage during which much memory consolidation takes place. It had been hypothesized that during sleep, some strengthening of connections between neurons occurs, along with some pruning of synapses that help establish memories. The new discovery is that the process of synaptic strengthening and weakening has been observed, providing support for the hypothesis. A team of researchers at New York University and Peking University Shenzhen, China  (Wang et al. 2014) used mice that were genetically engineered to express a florescent protein. After training them on a running/balancing task, they observed changes in synapses. One finding was that changes appeared on specific dendritic branches – that is they were not spread across an entire brain region. Periods of sleep or sleep deprivation followed training, and remarkably, only after sleep did some of the new branches appear. Moreover, the newly formed spines were still present a day later. This new study builds importantly on a large body of literature that shows the importance of sleep for children. From birth, children spend much of their waking hours learning new information and skills. Infants sleep long hours and now it is clear that sleep is more than just “rest”. Active reprocessing of neuronal connections takes place during sleep. As children get older, their learning continues, as does  their need for sleep. We have known for some time that sufficient sleep is vital for optimal learning, and we continue to attain better understanding of the underlying mechanisms of how sleep facilitates learning.   The implication is that if we want children to maximize their ability to learn and retain new information and skills, sufficient sleep is required.  Parents have not made sleep a high enough priority for a majority of children. But neither the blame nor the solution for the problems lies with parents. Many of the practices governed by adults in contemporary society have diminished the time available for sleep.  Adults have set early school start times, often for our own convenience in getting to work or to accommodate after school athletics.  Adults have created, sold, and bought media devices that keep children from sleeping.  Adults have sold and bought caffeinated drinks for children. Adults have scheduled activities that involve a great many children on school nights.  All of these actions have developed slowly and have become customary, so that they are very resistant to change.  Making sleep a bigger priority, fostering conditions that are conducive to sleep, and making more time available for sleep will take all concerted, continued effort at the individual and community level.   Wang, G., Wan Lai, C., Cichon, J., Ma, L., Li, W., & Gan, W-B. (2014). Sleep promotes branch-specific formation of dendritic spines after learning. Science, 344, 1173-1177.  Most Recent Posts from Child Sleep, From ZZZ's to A's Changing School Start Times A Decision with Many Moving Parts Variability in Sleep Schedule Hinders Brain Development A longitudinal brain scan study with adolescents The Mismatch Between Teen Sleep and School Timing A CDC study shows schools start earlier than pediatricians recommend.
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Alternative Medicine Physicians In lots of Eastern nations it is common to use practices like acupuncture in medicine. This writeup is for your normal training and isn’t meant to convince you to eliminate the skilled care by your certified well being practitioner in case you are not the form of one who believes easily and may dare; neither is it for advocating or selling any merchandise or merchandise by any company or anyone if you’re not satisfied. When doctors discuss treating the patient’s body, mind, and spirit,” it might sound like a feel-good catchphrase. The Truth About Cancer and The Quest For The Cures are registered Trademarks of TTAC Publishing LLC. Beyond that, complementary and different therapies are troublesome to outline , largely as a result of the sphere is so numerous; it encompasses practices spanning weight-reduction plan and exercise adjustments, hypnosis, chiropractic adjustment, and poking needles into an individual’s skin (aka acupuncture). If you are thinking of seeing someone privately who offers complementary or different treatments, it is a good idea to check their credentials. This is the United States, various medicine is normally taught in medical faculties and never generally in U.S. hospitals. Alternative medication is confirmed each day within the clinical experience of physicians and sufferers. You could then progress to a management position as, for instance, head of complementary remedy companies, where you might be chargeable for the complementary or different remedy service in a hospital or area. For details about reflexology you must contact the British Complementary Medicine Association. Perhaps the greatest threat, however, is the potential for folks to delay or cease conventional medical therapy in favor of an alternative remedy. But the overwhelming majority of scientists find much of other medicine extremely problematic. The Internet is the right venue to pursue your diploma in different medicine. The boundaries of CAM within the United States are constantly changing as various kinds of care grow to be more accepted by doctors and more requested by sufferers.Alternative Medicine Rooted in conventional Chinese medicine (TCM) and trendy medical science, right this moment’s acupuncture practices across the United States are a singular integration of the outdated and new. Myth seventy three. Laetrile is an effective most cancers remedy whose humanitarian discoverer has been persecuted, depriving millions of people of the benefits of this marvel drug. Alternative systems of medication: Homeopathy, conventional Chinese medication, and Ayurveda.Alternative MedicineAlternative Medicine • Partner links
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Page Menu How Long Does Colon Cancer Take to Develop? Cancer shown attacking cells in colon Colon cancer, or cancer that begins in the lower part of the digestive tract, usually forms from a collection of benign (noncancerous) cells called an adenomatous polyp. Most of these polyps will not become malignant (cancerous), but some can slowly turn into cancer over the course of about 10-15 years. Once cancer has developed in the colon, its progression will vary according to the cellular makeup of the tumor and other factors, such as the age and overall health of the patient. The general progression of colon cancer tends to be slow, but it is still a serious disease that warrants prompt medical attention. If you notice any of the following symptoms, be sure to speak with a physician: • Frequent diarrhea or constipation • Blood in stool • A persistent urge to have a bowel movement • Thin, shoelace-like stools There are also many benign conditions that can cause these symptoms to occur. The sooner you seek medical care, the faster you’ll be able to experience relief and find answers to your health questions. Like most other cancers, early detection of colon cancer is key to a successful outcome and positive quality of life. How is colon cancer detected? The best way to detect colon cancer is to receive a colonoscopy, a procedure that involves inserting a small camera through the lower portion of the digestive tract. A person who is considered to be at an average risk of colon cancer should receive a colonoscopy once every ten years after the age of 50. If you have a diabetes, an inflammatory intestinal condition or a family history of colon cancer, consider speaking with your doctor about starting screening sooner. There are also a few other ways to test for colon cancer, including an at-home fecal immunochemical test (FIT) and a computer tomographic (CT) colonography that produces a detailed image of the colon. Moffitt Cancer Center offers a full spectrum of colon cancer screening, including colonoscopies and high-sensitivity blood tests, to adults who want to be proactive about their digestive health. Our professionals will be happy to speak with you about what screening method would be best for your unique needs. Call 1-888-663-3488 or submit a new patient registration form online.
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  Health Tips Have Yourself a Healthy Happy Holiday Season With These Tips! December 18, 2019by premiermdcare Have Yourself a Healthy Happy Holiday Season With These Tips! Happy Holidays! The holiday season is a special time to gather with friends and family and to eat traditionally rich foods and splurge and indulge. Quite often our patients with diabetes ask us, “what’s the big deal if my blood sugar levels go up a little or a gain a few pounds over the holidays?” So we thought we’d share with you some of our thoughts around that. Sometimes people with Type 2 diabetes think it’s just too hard to diet during the holidays, and figure they will just return to eating right in the new year. First of all, if you splurged on Thanksgiving Day, and plan to splurge a bit on Christmas Day itself, that shouldn’t cause too big of a problem. The main problem is if you allow yourself to splurge through the entire month long season. This causes a spike in your blood sugar levels consistently over a long period of time. When it comes to managing your diabetes, it’s about more than just your day to day glucose levels, it’s about your A1C, which measures our blood sugar level over a course of three months. The reason we go by the A1C levels, is because higher percentages can worsen your insulin resistance and blood sugar control overall, contributing to diabetic complications you could be avoiding. In fact, even gaining as little as five pounds can trigger higher insulin resistance. That’s why we’ve brainstormed some of these tips to help you enjoy the holidays, without jeapardizing your overall health or the gains you’ve established in lowering your insulin resistance and A1C levels throughout the year. 1. We know the holidays are hectic, so your best bet is to put together a plan for the week every week. Try to eat at regular times and eat healthy foods, like lean proteins and lots of veggies, to keep your blood sugar steady. Don’t skip meals in anticipation of eating more at a party, or trying to make up for a prior splurge. Instead plan to eat a light snack right before attending parties to keep from overindulging at them. Plan your food and do meal prep for the busier days leading up to the holidays. This will keep you from eating fast food on the run or snacking on unhealthy snacks. 2. Be careful about your drink choices. Juices and sodas spike your insulin, so choose beverages without sugar such as flavored sparkling water. Alcohol can lower blood sugar and interact with diabetes medications, so limit your alcohol intake as well, and be sure to have it with food. 3. Attending a party with a buffet or sitting down to one of the big holiday meals? We know the buffet is a danger zone because portion control is so important for a diabetic, so start by walking the entire buffet and planning your meal before you even have a plate in hand. As you build your plate of food in your head think of it like this: a ¼ of the plate should have lean proteins like turkey, and lean meats; a ½ of the plate should be for green vegetables; and the final ¼ of the plate can be carbohydrates. Skip items like rolls and potatoes that you could have any time. Budget for sweets by reducing the carbs you eat during the meal. Choose wisely, certain foods spike insulin less than others, for example pumpkin pie is much lower in sugar than pecan pie. But, don’t put any of the foods on the naughty list. If you really love your mother’s traditional pecan pie that she only makes for Christmas, then simply take a small portion, and savor it slowly. 4. Eat slowly, no matter where you are. It takes 20 minutes for your brain to realize you are full. Eating slowly, and really enjoying the special foods of the holidays allows you to celebrate to the fullest without spiking your blood sugar. 5. Bring a healthy dish yourself. When attending holiday parties and celebrations, bring a dish that is diabetic friendly so you have at least one thing you can eat guilt-free. Fill up on that dish and eat just small bites of some of the richer foods that are put out. 6. Track what you eat. Around the holidays we are surrounded by foods that are not part of our normal eating routine, and it’s easy to lose track of how many carbs we are eating. There are many free mobile apps these days to help you track what you’re eating. Download one and track your daily intake to stay on track. 7. Track your blood sugar levels. As always, testing blood sugars and weighing yourself regularly is critical to making sure you stay mindful about your choices and behaviors, especially during the holiday season. Your ideal goals are fasting values of 80-120 md/dl before eating and around 140mg/dl after eating. If your levels are above this, then you need to regulate your holiday eating and drinking better. Also, if you take insulin, be sure to discuss with us or your endocrinologist about planning for times when your carb intake will increase. We can let you know if we think an increase in short-acting insulin is necessary in those situations. 8. If you receive high-sugar foods as gifts, accept them graciously, eat a small portion of them or just a taste and then either give them away, freeze them to eat slowly over the next few months, or throw them out if they are too tempting to keep in the house. 9. Stick to an exercise routine in some way. Yes, the holidays are so so busy for all of us, but exercise is helpful for stress management, keeping your blood sugar stable and compensating for those extra calories that creep in. During this busy season, you can try breaking exercise up into smaller time chunks to make it easier to schedule, so rather than planning for a 30 minute time period for the gym, try scheduling three 10-minute jogs or walks during the day. Go for a 20-minute walk after the big holiday meal.  10. Schedule “me” time every day. Whether it’s to take a hot bath at the end of the day, take the dog for a walk, or take a 20-minute nap, taking the time to destress and take care of yourself is not an indulgence, it’s essential for your health! We hope you’ll try a few of these tips for your holidays this year and keep your diabetes under control, keeping your happy and healthy throughout the season!
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As if being diagnosed with breast cancer wasn’t bad enough, many women with this diagnosis face complicated decisions about what kind of medicine or chemotherapy to take, if any, to reduce their chance of cancer recurrence.  As I discussed in a recent post, the mathematics of such decisions can be hard to comprehend for many patients.  But given that the right choice often depends on patient preferences, it would be great to help patients understand enough of their math to involve them in making the choice. A group of researchers has developed a tool to help women with these decisions.  Called Adjuvant Online, it is a computer algorithm that takes in information about a specific woman’s cancer, and then produces survival estimates for her, illustrating her chance of survival and breast cancer recurrence based upon whether she chooses one set of treatments versus another.  Here is an example of how Adjuvant Online presents its information: There is lots of important information in here.  But unfortunately, it is not in a format that most people can easily understand.  Horizontal bar graphs with four colors?  In research I conducted with Brian Zikmund-Fisher, we discovered that most people have a hard time figuring out what these graphs mean. Fortunately, there is a much simpler way to present this information.  It involves a few simple changes.  First, it presents outcomes through pictographs rather than horizontal bar graphs.  My collaborators and I have learned that pictographs are much easier for people to understand.    Second, it reduces the complexity of the four-color scheme used in Adjuvant Online, by eliminating the colors for death from breast cancer and death from other causes. Our research discovered that is was much easier for people to determine the benefits of Adjuvant chemotherapy with this second picture compared to the first.  They were able to quickly discern that, for this hypothetical situation, Adjuvant chemotherapy increases five-year survival by 2%. Not necessarily an easy choice to make—the misery of chemotherapy versus a slightly reduced chance of cancer recurrence.  But at least when presented this way, it is an easier choice for people to understand. To truly empower patients, we need to help them understand their healthcare choices.  That means making use of research on how to present information to patients in ways that make complicated decisions easier to comprehend.  **Previously posted on Forbes** Recent Posts in Critical Decisions Study: When We Least Expect It, We Overeat New research suggests a path to smarter eating. How Healthy Food Could Make You Fat Your Unconscious Waistline Are Some Life-Saving Treatments Overkill? The psychological difficulty of de-innovation Is it Irrational for Carmelo to Take So Many Three Pointers? Evidence That We Psychologically Overreact to Both Success and Failure Will Cheap Genetic Tests Bankrupt Us? The counterintuitive psychology of inexpensive health care Side Effect Warnings Can Increase Pharmaceutical Sales The psychology behind the “ironic effect of warnings”
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Why Do Doctors Tell You Not To Push During Labor? How long will they let you push in labor? The length of this stage varies with the position and size of the baby and your ability to push with the contractions. For first-time mothers the average length of pushing is one-to-two hours. In some instances, pushing can last longer than two hours if mother and baby are tolerating it.. Can you give birth without pushing? Dec. 31, 2001 — A new study says that taking a break from pushing during childbirth can take some of the “labor” out of labor, and is perfectly safe for both mom and baby. How many bones break during delivery? There were 35 cases of bone injuries giving an incidence of 1 per 1,000 live births. Clavicle was the commonest bone fractured (45.7%) followed by humerus (20%), femur (14.3%) and depressed skull fracture (11.4%) in the order of frequency. Why do nurses tell you not to push? Nurses aren’t necessarily being cruel when they instruct mothers to stop pushing, by the way. They may be hoping to prevent other complications, such as problems with the umbilical cord or shoulder dystocia. A doctor or midwife is better trained to correct such situations, and can also help prevent perineal tearing. Does it smell during childbirth? Weird smells are normal. Immediately after, and even six to eight weeks after delivery, there will be lochia, and lots of it. This is the stuff (mostly blood) that your uterus sheds, and it may have a mild odor to it. That said, if there’s a strong, foul odor, Dr. Should you shave before giving birth? Our current advice is that you don’t shave or wax your pubic area just prior to giving birth, as this increases your risk of infection, especially if you have an operative procedure like a caesarean section. Does pushing out the placenta hurt? The takeaway Typically, delivering the placenta isn’t painful. Often, it occurs so quickly after birth that a new mom may not even notice because she’s focused on her baby (or babies). But it’s important that the placenta is delivered in its entirety. Why do you have to wait to push during labor? The first method is to start pushing when fully dilated along with uterine contractions; the other is to delay pushing to allow for the fetus to spontaneously descend. Researchers wanted to know if waiting leads to disadvantages for mother or child and started a study looking at more than 2,000 women giving birth. How long is labor on average? If you’re a first-time mum, active labour may take about eight hours. This is an average, though, and it could be much shorter or longer than that. It’s unlikely to last more than 18 hours. Once your cervix has dilated to 10cm, it could take you an hour or two hours of pushing before your baby is born. How long does it take to dilate from 1 to 10? One woman may go from having a closed cervix to giving birth in a matter of hours, while another is 1–2 cm dilated for days or weeks. Some women do not experience any dilation until they go into active labor. This means that the cervix is completely closed initially, but it widens to 10 cm as labor progresses. What hurts more pushing or contractions? For most women, labor is more painful than pushing because it lasts longer, gets gradually (or rapidly) more intense as it progresses and involves a large number of muscles, ligaments, organs, nerves and skin surface. What does giving birth feel like? Pain During Labor and Delivery Pain during labor is caused by contractions of the muscles of the uterus and by pressure on the cervix. This pain can be felt as strong cramping in the abdomen, groin, and back, as well as an achy feeling. Some women experience pain in their sides or thighs as well. How can you make labor come faster? 20 ways to have an easy labourGetting your baby ready. From around 34 weeks, you can encourage your baby to get into the right position for birth. … Stay focused on coping. … Stay fit and strong. … Massage your perineum. … Keep an eye on the monitoring. … Stay active. … A midwife led home birth is possible and safe. … Boost and maintain your energy levels.More items…• What happens if you push too early during labor? You’ll experience pressure in your lower back and rectum. Tell your health care provider if you feel the urge to push. If you want to push but you’re not fully dilated, your health care provider might ask you to hold back. Pushing too soon could make you tired and cause your cervix to swell, which might delay delivery. How do you know when to push during labor? An overwhelming urge to push (though not every woman feels it, especially if she’s had an epidural) Tremendous rectal pressure (ditto) A burst of renewed energy (a second wind) or fatigue. Very visible contractions, with your uterus rising noticeably with each. Does everyone poop during childbirth? You can’t control the poo In fact, most women do poop during labor. It can happen more than once while you’re pushing, but it’s most common right before the baby crowns. The bottom line: Don’t worry about it. Does Labor still hurt with an epidural? The greatest benefit of an epidural is the potential for a painless delivery. While you may still feel contractions, the pain is decreased significantly. During a vaginal delivery, you’re still aware of the birth and can move around. Is Labor really that bad? Yes, childbirth is painful. But it’s manageable. In fact, nearly half of first-time moms (46 percent) said the pain they experienced with their first child was better than they expected, according to a nationwide survey commissioned by the American Society of Anesthesiologists (ASA) in honor of Mother’s Day. Do you pee when you push the baby out? Most women are able to use the bathroom during labor — to urinate and to have a bowel movement. Your health care provider will probably encourage you to do so because it’s possible that a full bladder might slow down your baby’s descent. Can you feel baby coming out with an epidural? The goal of an epidural is to provide relief from pain, not total numbness, while keeping you comfortable and completely alert during your birth experience. You may still feel your contractions happening (though you may not feel the pain of them much or at all), and you should still be able to push when the time comes. Can you push before 10 cm? Some women start to feel like pushing or bearing down before the cervix is dilated to 10 centimeters. … For other women, after the cervix has dilated to 10 centimeters, it takes time for the baby to move down into the vagina, then they feel like pushing.
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Search Close this search box. FAQ FAQs Cat The doula  is a professional trained in childbirth who provides emotional, physical, and educational support to a mother who is expecting, is experiencing labor, or has recently given birth. Their purpose is to help women have a safe, memorable, and empowering birthing experience. Braxton Hicks are also known as false labor. They help prepare the body for true labor, but they do not indicate labor has begun. These are contractions of the uterus that start as an uncomfortable but painless tightening begining at the top of your uterine muscles. They cause your abdomen to become very hard and strangely contorted (almost pointy). The contractions are infrequent and irregular in intensity – usually lasting about 15-30 seconds. A woman generally ovulates halfway through her menstrual cycle, which is around day 14 of the average 28-day cycle, counting from the first day of one period to the first day of the next. Ovulation usually occurs halfway through your menstrual cycle, around day 14 of the average 28-day cycle counting from the first day of one period to the first day of the next. Vaginal bleeding is the most common sign of miscarriage. This can vary from light spotting to a heavy bleed depending on how many weeks pregnant your are. Other symptoms may include abdominal cramping, lower back pain and passage of fluid or tissue from your vagina. Call your doctor if you’re experiencing these signs. The mucus plus is usually clear, slightly pink or blood-tinged in color. It can be stringy mucous or sticky discharge. Some women might not notice the loss of their mucus plug since there is already an increase in vaginal discharge during pregnancy. The most common cause of miscarriage is chromosomal abnormality – meaning something is wrong with the baby’s chromosomes and it’s not developing normally. Most chromosomal abnormalities are the cause of a damaged egg or sperm cell or are due to a problem at the time that the zygote went through the division process. The reasons for miscarriage are varied, and most often cannot be identified. Implantation bleeding is generally light and short, between a couple of hours to three full days. Implantation bleeding occurs when the embryo implants in the lining of the uterus, usually around 7 to 10 days after fertilization. This bleeding could happen near the time you would expect your menstruation cycle. Learn how implantation bleeding differs from period bleeding. Implantation bleeding looks different from your period. Implantation bleeding is more of of a “spotting” rather than a full “flow” like your period. It’s typically a lighter pink rather than blood red and doesn’t have clots. It can happen about the time you’re expecting your period so it’s very easy to confuse the two. The best time to take a pregnancy test is 7 days after a missed period, and first thing in the moring with your first urine of the day. Learn why if you take a pregnancy test sooner than 7 days you may get a false negative. Preeclampsia is a condition that occurs only during pregnancy. Symptoms may include high blood pressure and protein in the urine, usually occurring after week 20 of pregnancy. Ovulation is when a mature egg is released from the ovary, pushed down the fallopian tube, and is made available to be fertilized. Are you experiencing pregnancy symptoms that having you asking “Am I pregnant?” A missed period is the key pregnancy symptom. Our free due date calculator will help pinpoint your conception and due dates. When do you ovulate? You ovulate about about halfway through your menstruation cycle. That’s day 14 on an average 28-day cycle. Our free ovulation calculator will help you determine when you ovulate next.
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A narrative synthesis of research evidence for tinnitus-related complaints as reported by patients and their significant others Deborah Ann Hall, Kathryn Fackrell, Anne Beatrice Li, Rachel Thavayogan, Sandra Smith, Veronica Kennedy, Catarina Tinoco, Evelina D Rodrigues, Paula Campelo, Tânia D Martins, Vera Martins Lourenço, Diogo Ribeiro, Haúla F Haider Research output: Contribution to journalReview articlepeer-review 39 Citations (Scopus) 15 Downloads (Pure) Fingerprint Dive into the research topics of 'A narrative synthesis of research evidence for tinnitus-related complaints as reported by patients and their significant others'. Together they form a unique fingerprint. Medicine & Life Sciences
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  PrettyThin.NET   How To Lose Weight Fast - Just Got Easier - Weight Loss Art. Lose Weight Tracker 0g and How To Lose Weight Fast - What Are The Roles Of Muscles And Hormones In The Burning Of Fat? Lets talk about burning fat. This is an important point. Fire up the metabolism and it will use fat to get calories. The central idea for lose weight tracker 0g and how to lose weight fast is to use the muscles so the metabolism is going and burning off the fat. You will not burn much fat if you are sitting on the couch. Let your muscles help you achieve weight loss. Muscles only want to do one thing. Work. Muscles only like one thing, just one thing, working. Use your muscles. Burn calories. And get more energy too. Is this a refreshing wave or what? The human body is a complex machine and uses hormones to control various processes. One such process involves fat burn. You want the hormones to flow and do their job but how is this accomplished? If you eat the right proportions of foods, that will initiate the hormone flow. You want to have a higher percentage of your diet for protein and a lower percentage of your diet for carbohydrates. So protein is high and carbohydrate is medium or lower. - More Meals In One Day? Less Meals In One Day? It is not like you are climbing a mountain to achieve lose weight tracker 0g and how to lose weight fast . So read this over and you will see that the knowledge will make it understandable and pretty easy. Skipping meals will work against you. Really. Not what you might have been expecting? Breakfast is especially crucial to have. It has that specific name. Break means to stop. Fast refers to not eating. You are eating again. No longer fasting. We get the metabolism going by eating. Metabolism will consume calories. So you are going to substitute 5 to 6 smaller meal for the usual 3 big meals a day. In the weight loss world they call this grazing. Grazing is our friend to crank up the metabolism and use fat calories in the process. So here we are with a plan for finding out lose weight tracker 0g and how to lose weight fast . - The Ratio Of Burned Calories To Lost Weight. In pursuing lose weight tracker 0g and how to lose weight fast , you need to know the ratio of burning fat and losing weight. There is no mystery here. If you want weight loss, then achieve it by putting your attention on it. When you have burned up 3500 calories of your body fat by virtue of your activities, then the result will be losing one pound of your body weight. Whether they be your usual daily activities or exercises you have added to your routine, we are accomplishing burning 3500 calories of fat. Let us say that in your daily activities, you burn approximately 2000 calories. Let us also say that you typically eat 2000 calories. Now something needs to change. We will change the calories eaten. Reduce them to 1500. But this makes a 500 calorie difference from what you are burning and those 500 calories will be burned out of body fat. In a weeks time you have burned 500 calories a day and therefore burned a total of 3500. Put this all together and it means, one pound of fat removed in a week. Computing for a month of this routine, you have burned off four pounds of fat. This is 52 pounds per year. More times than not you will put weight on your body over some lengthy time. So you can lose weight slowly, as well. Do not be impatient. Make consistent progress, a bit at a time. Steadily. For a complete weight loss program and diet at a very low price, Please Click Here Check out this additional news and info on lose weight tracker z5r For Help With Any Aspect of Our Site or Products, Please email: help AT prettythin DOT net Thanks ! 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Infertility Evaluation and Treatments Dr. Lazarou has over a decade of expertise in diagnosing and treating infertile men. The infertility evaluation starts with a complete history and physical examination. A semen analysis allows evaluation of sperm characteristics that may be helping or preventing fertility. Other lab tests are also performed to identify any possible underlying hormonal abnormalities. Blood and semen tests may also be performed to identify possible genetic causes for infertility. Specialized testing may also reveal blockages of the tubes or ejaculatory disturbances that prevent the sperm from functioning or traveling properly. A scrotal ultrasound is often used to identify the presence of varicoceles (varicose veins of the scrotum) or other abnormalities. Ultrasound can also be used to identify blockages or other anatomical problems. Dr. Lazarou also collaborates with top female infertility specialists in Boston and throughout New England to provide the best possible treatment for men and their partners. His fertility work has been published in the most respected medical journals including Fertility and Sterility and Urologic Clinics of North America. Microsurgical Varicocele Repair One of the most common causes of male infertility are varicoceles which are enlarged varicose veins in the scrotum. They are very common affecting up to 40% of men with known infertility. The most effective treatment technique with the lowest complication rate is the microsurgical varicocele repair. Sperm Aspiration/Retrieval In cases where there are no sperm in the semen, such as after a vasectomy, it may be possible to harvest sperm from the testicle or from the surrounding structures. Technology has advanced to such a degree that we can now find sperm in many cases that were previously considered impossible. Dr. Lazarou uses cutting edge microscopic techniques to extract sperm. We now live in an era where just a few sperm can be used to help successfully create a pregnancy.
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  Infection Control Practice Updates Since the COVID-19 Pandemic Since the start of the COVID-19 pandemic, the dental health profession has been reexamining its infection control practices with the intention of tightening existing procedures and implementing updated protocols. In particular, the pandemic has spotlighted the need to update processes regarding aerosol and air quality management, hand hygiene, personal protective equipment, respiratory hygiene, sharps safety, operatory disinfection, and dental unit waterline maintenance. Many of these procedures are not new. The Centers for Disease Control and Prevention had already advised on almost all of these measures before the pandemic, and they are part of their standard guidelines. Unfortunately, many offices continue to neglect to follow these recommendations. An additional measure that is vital for dental offices to adopt is that of incorporating a trained infection control coordinator as part of the staff, who would serve as the key team member to ensure that up-to-date infection mitigation protocols are being followed and guarantee compliance with current regulations. This article provides a concise discussion of standard infection control precautions and practice updates and sheds light on why these practices are critical in the dental care setting. Even before the COVID-19 pandemic, dentistry had robust infection control procedures in place.  Unfortun-ately, not every dental office followed all the recommended standard procedures. However, the COVID-19 pandemic has served as an important "wake-up call" for many to tighten up their infection control practices. Similar to how the HIV/AIDS pandemic of the 1980s spawned a greater understanding of the spread of blood-borne pathogens, which led to the practice of routine wearing of gloves and masks by dental healthcare professionals, the COVID-19 health crisis has prompted the Centers for Disease Control and Prevention (CDC) to update its guidelines for protecting patients and healthcare personnel. With COVID-19 infection, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), some affected individuals may become severely ill, while others may be asymptomatic (albeit they may still transmit the virus). The upper airways and lungs are identified as the primary sites of SARS-CoV-2 infection. Nevertheless, the virus has also been found present in the saliva and oral flora, potentially through several identified routes. Frequent liquid droplet exchange may be possible owing to the anatomical proximity of the lower and upper respiratory tract and oral cavity. SARS-CoV-2 may enter the oral cavity via gingival crevicular fluid, which contains serum proteins and thus viral components. New research has shown that the virus may rapidly infect salivary gland epithelial cells, indicating that salivary gland cells may play a critical role in virus transmission. Excretion via the oral cavity and, therefore, airborne transmission amplification may occur via aerosols and aerosol-generating procedures, including respiratory droplets generated through talking, coughing, and sneezing of an infected patient. Transmission through fomites (materials or surfaces that are likely to transmit infection) can occur through interpersonal contact. Dental healthcare staff must have additional infection control measures in place to limit the risk of viral transmission. ROLE OF THE INFECTION CONTROL COORDINATOR With the discovery of new infectious diseases, transmission-based infection control protocols in oral healthcare need to be reexamined and adjusted accordingly. Transmission-based precautions are the second tier of basic infection control measures, which have been put in place to control or prevent the transfer of germs from one person to another in any healthcare setting to protect patients, their families, other visitors, and healthcare workers. They are used, alongside the usual standard precautions, when treating patients who may be infected or colonized with certain infectious agents, for which additional precautions are necessary to thoroughly prevent infection transmission. Owing to the highly infectious nature of SARS-CoV-2, individuals who are infected or suspected of being infected with this virus must undergo necessary transmission-based precautions to prevent disease transmission. These precautions must be revisited in light of the COVID-19 pandemic to tailor them specifically for the identified modes of transmission of SARS-CoV-2 in order to be effective in curtailing the spread of COVID-19. In addition, measures must be taken to ensure that dental practices understand the necessity of implementing these protocols for patient and staff safety. While some transmission-based infection precautions have been updated for dental settings, the role of the infection control coordinator (ICC), crucial to mitigating infection risk in healthcare settings, has not been revised. With the onset of the COVID-19 pandemic, the ICC must also have a firm grasp on transmission-based measures. Despite the CDC's recommendations regarding the necessity of an ICC for almost 20 years now, incorporating a trained ICC is still not standard in many dental offices. The ICC is the key team member to turn to during any infectious disease outbreak, as ICCs have relevant and ongoing training in infection prevention. They are responsible for daily and long-term oversight of an office's infection control strategy, ensuring that all policies, procedures, and practices are relevant and successful. Dental offices whose staff includes a trained ICC will be up to date on all current infection control measures and will therefore be equipped to develop and implement necessary standard operating procedures (SOPs) for the rest of the team to follow.9The ICC will keep an updated log of safety-related records, guaranteeing compliance with current regulations such as ensuring that all dental staff receive vaccinations and up-to-date training. UPDATES OF STANDARD INFECTION CONTROL PRECAUTIONS AND PRACTICES IN DENTISTRY SINCE THE COVID-19 PANDEMIC Aerosol and Air Quality Management The pandemic has spotlighted the need for healthcare professionals to refocus on the current management of aerosols and air quality in dental settings. Dentistry has needed to take a hard look at the standard infection control procedures and protocols already in place, which have a proven track record of ensuring patient and staff safety when implemented correctly. Along with standard precautions, a secondary tier of transmission-based precautions covering airborne transmissions may be necessary for some clinical situations, such as when a patient has a proven infection or is suspected of having a highly transmissible infection that routine procedures alone cannot entirely control. Aerosols carrying pathogens from the patient's saliva and oral fluids may be amplified into the air during the use of rotary dental and surgical equipment such as ultrasonic scalers. Transmission-based precautions for aerosols can be employed to prevent the spread of infectious pathogens that remain contagious when suspended in the air over extended distances. In these cases, patients with infection or suspected of infection should be isolated in an Airborne Infection Isolation Room (AIIR) with regular air changes. Moreover, instead of relying on surgical masks, where much of the air and airborne organisms can enter at the sides, CDC recommendations advise using National Institute for Occupational Safety and Health (NIOSH)-approved, fit-tested N95 respirators and a complete respiratory protection program. The program should involve training and fit testing to verify that the respirator's edges and the wearer form an adequate seal so that no airborne pathogens may penetrate. Because aerosols can remain suspended for up to 3 hours, it is crucial to perform a complete air change to filter out expired or contaminated air and facilitate the movement of "clean" air into the operatory, which can be achieved through ventilation with sufficient fallow time after aerosol-generating procedures (AGPs).A common technique used to assess air circulation is to determine the Air Changes per Hour (ACH) to calculate the frequency with which the air in the room is completely exchanged in the clinical space following each operation to minimize the risk of airborne infection,particularly if high-speed or ultrasonic devices were used. Reducing aerosol dispersion is possible by modifying dental treatment practices, for example, through the use of rubber dams and engineering controls such as using portable high-efficiency particulate air (HEPA) filtration units immediately after AGPs as recommended by the CDC to capture pathogenic particles and reduce the risk of transmission.Rubber dams have been demonstrated to significantly reduce airborne particles by 70% within 1 m of the operational range. It is also essential to be familiar with high-volume evacuation (HVE) tips and use them during AGPs. The use of HVE during AGPs has long been recommended, and the COVID-19 pandemic has merely highlighted that many dental professionals are not fully following protocols already in place. In order for a high-volume evacuator to be qualified as effective at minimizing bioaerosols, it must have an adequate bore size or opening diameter; bore size or opening diameter is thus a significant factor to consider. An opening of at least 8 mm or greater is recommended, as this can remove up to 100 cubic feet of air per minute. It should be noted that using a saliva ejector is insufficient, as it does not have the adequate opening size to be classified as a high-volume evacuator. Additionally, the suction tip should never be placed more than 15 cm away from the central incisor teeth. It is vital to eliminate as much spatter, spray, and aerosol as possible at the point of use, regardless of whether there is a global pandemic. Aerosols must be eliminated as much as possible while they are being generated because they may remain suspended in the air for hours within the dental clinic, where dental care providers and patients may inhale them. A significant portion of these aerosols may also settle down on nearby surfaces, creating many contaminated areas and ultimately increasing the risk of infection. Hand Hygiene Hand hygiene has been a significant part of infection control since the 1980s, having taken more than 100 years to become accepted as an essential practice. Alcohol-based hand rubs (ABHR) are considered the most effective, simple, and cost-effective method of hand hygiene for preventing COVID-19 cross-transmission. However, even ordinary soap can make a difference, while an antibacterial soap can further enhance transmission prevention. Furthermore, handwashing must be performed at the beginning and end of the day. The World Health Organization (WHO) recommends ABHR formulations containing 80% ethanol and 75% isopropanol, as these have significant virucidal activity against SARS-CoV.19 *This article gives the reader CE credits  
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Jacobs:Protocol Freezing and Thawing Cells From OpenWetWare (Difference between revisions) Jump to: navigation, search (Contact) Line 1: Line 1:  + {{Template:Jacobs}}  +  + <div style="padding: 10px; width: 710px; border: 5px solid #000000;"> ==Procedure== ==Procedure== Line 93: Line 96: [[Category:Escherichia coli]] [[Category:Escherichia coli]] --> -->  + </div> Revision as of 16:44, 10 August 2011 Image:CMBL.jpg Home        Contact        Internal        Lab Members        Publications        Research        Talks        Open Positions         Procedure Materials for Freezing • Trypsin • Trypan Blue Solution (0.4%) • Hemocytometer • Media for frozen cells • DMSO • Gloves, 70% ethanol, etc. Freezing 1. Check cell culture log and be sure there is room for frozen vials 2. Label vials with cell type, date, passage number, etc. 3. Collect cell suspension by trypsinizing (Take out media and put in 3 mL of trypsin) 4. Combine all flasks into 50 ml tube 5. Count cells 1. 1 million cells per vial (for MC=4 vials/flasks, for UMR=6 vials per flask.) 2. 1-2 million cells per vial for MLO-A5 6. Make fresh freezing down media 1. General (including FAK cells): 95% FBS + 5% DMSO 2. MLOs: 50% α-MEM, 40% FBS, 5%DMSO 7. Spin down the cell suspension and pellet the cells (1500rpm, 7-10 min) 8. Aspirate media 9. Resuspend cell pellet in freezing media 10. Aliquot 1ml freezing media per 2ml tube 11. Place tubes in round isopropanol box in -80C freezer OR 12. Transfer to the -20C for 2-3 hours 13. Transfer to the -80C for at least overnight 14. Store permanently in liquid nitrogen within 1-2 days 15. Be sure to record in the cell culture log where the cells are permanently stored Materials for Thawing • Media for cells • Petri dishes for cells • Trypan Blue Solution (0.4%) • Hemocytometer Thawing 1. Setup two vials of cold (4 C) media (10 ml) in a 15 ml tube 2. Warm remaining media (~5-8 ml) in a 15 ml tube to 37C 3. When ready to thaw, remove vial of cells from liquid nitrogen 4. Swirl the vial in the water bath (37C) until a small ice chip is left in the tube (~1 min) 5. Place the vial in the hood and clean it with 70% ethanol 6. Immediately remove the contents of the vial and place into the cold media 7. Rinse the tube down with some of the cold media from the second vial 8. Spin down cells at 2000 rpm for 5 min 9. Aspirate off the cold media and resuspend the cells in the warm media 10. Transfer the cells and the media into a petri dish 11. Count cells 12. Place in incubator 13. Change the media once the cells have attached to the plate 14. Allow cells to grow to 80-90% confluency 15. Split cells (1:3) into petri dishes 16. Continue to split cells and freeze down as needed Alternative Thawing • From step 5 above, using a 1 ml pipet add 1 ml of the cold media from the 15 ml tube drop by drop to the vial (about 1 drop every 10 seconds). • Plate immediately with the cold media and change the media once cells have attached (12 - 24 hours later) to remove DMSO that was in the freezing media. Usually a 1:3 ratio is good for MC3T3s and a 1:4 ratio for MLOY4s. References Contact • History: CMBL – CRJ/JJR, last updated 2/17/11 by AMN or instead, discuss this protocol. Personal tools
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Open Access Articles  |   May 2017 Does Testing More Frequently Shorten the Time to Detect Disease Progression? Author Affiliations & Notes • Johannes Ledolter Departments of Management Sciences/Statistics & Actuarial Science, University of Iowa, Iowa City, IA, USA • Randy H. Kardon Department of Ophthalmology and Visual Sciences, University of Iowa Hospital and Clinics and Iowa City VA Medical Center, Iowa City, IA, USA • Correspondence: Johannes Ledolter, Tippie College of Business, S352 Pappajohn Business Building, University of Iowa, Iowa City, IA 52242, USA. e-mail: johannes-ledolter@uiowa.edu  Translational Vision Science & Technology May 2017, Vol.6, 1. doi:https://doi.org/10.1167/tvst.6.3.1 • Views • PDF • Share • Tools • Alerts × This feature is available to authenticated users only. Sign In or Create an Account × • Get Citation Johannes Ledolter, Randy H. Kardon; Does Testing More Frequently Shorten the Time to Detect Disease Progression?. Trans. Vis. Sci. Tech. 2017;6(3):1. doi: https://doi.org/10.1167/tvst.6.3.1. Download citation file: © ARVO (1962-2015); The Authors (2016-present) × • Supplements Abstract Purpose: With the rise of smartphone devices to monitor health status remotely, it is tempting to conclude that sampling more often will provide a more sensitive means of detecting changes in health status earlier over time, when interventions may improve outcomes. Methods: The answer to this question is derived in the context of a model where observations are generated from a linear-trend model with independent as well as autocorrelated autoregressive-moving average, or ARMA(1,1), errors. Results: The results imply a cautionary message that an increase in the sampling frequency may not always lead to a faster detection of trend changes. The benefit of rapid successive observations depends on how observations, taken closely together in time, are correlated. Conclusions: Shortening the observation period by half can be accomplished by increasing the number of independent observations to maintain the same power for detecting change over time. However, a strategy to detect progression of disease sooner by taking numerous closely spaced measurements over a shortened interval is limited by the degree of autocorrelation among adjacent observations. We provide a statistical model of disease progression that allows for autocorrelation among successive measurements, and obtain the power of detecting a linear change of specified magnitude when equal-spaced observations are taken over a given time interval. Translational Relevance: New emerging technology for home monitoring of visual function will provide a means to monitor sensory status more frequently. The model proposed here takes into account how successive measurements are correlated, which impacts the number of measurements needed to detect a significant change in status. Introduction In medical surveillance, patient characteristics are assessed at consecutive clinic visits with the intent to detect medically relevant trend changes among consecutive observations. In the absence of disease, measurements tend to fluctuate around a stable level, but often deteriorate progressively once the disease has set in. Because of cost considerations and burden of travel for patients, assessments for common eye conditions that progress, such as glaucoma, are frequently carried out at 6-month intervals. Other conditions, such as macular degeneration, may be monitored monthly, once intravitreal injections of anti-vascular endothelial growth factor are administered for treatment of the wet variety of macular degeneration. The objective is to detect a medically meaningful trend change within as short of a time period as possible so that adjustments in treatment can be made to prevent further damage.  The development of inexpensive smartphone monitoring systems that can be used by the patient at home raises the question of whether a medically relevant trend change could be detected sooner if observations are taken more frequently, and perhaps over a shorter time period.1,2 As an illustration, assume that the clinician takes observations of visual function or structure every 6 months wishing to detect a trend change of a certain magnitude within 3 years (that is, n = 7 observations). This is a strategy used by many clinicians, for conditions such as glaucoma that can slowly progress if not treated optimally. The sampling frequency is limited by the resources available to accommodate more follow-up visits per year and the burden placed on patients who are asked to return more frequently for follow-up measurements. Of course, it would seem to be more beneficial to increase the sampling frequency and take observations every 3 months, every month, every week, and so on, if it would help detect a trend earlier or with more certainty, when a treatment intervention may lead to preservation of vision. Increasing the sampling frequency to improve the ability to detect a change over a given sampling period would certainly bring benefits, as long as the observations we collect are statistically independent, with little correlation between measurements at adjacent time intervals.  A second competing strategy could take the same number of observations, but over just the first half of the observation interval (e.g., during the first 18 months of the 3-year interval), hence reducing the time between successive visits by half. Better yet, if measurements could be collected on a portable device at home with an increase in sampling frequency, then could the observation period over which a relevant change could be detected be shortened even further? The question arises whether this second strategy would provide similar power of detecting a meaningful change over a shorter time period. Furthermore, if there is little cost to taking observations, the sampling frequency over this new shorter observation interval could be increased even further; in theory, patients could take daily or evenly hourly measurements on their state of health. Would this be better? If this were the case then one could, by taking numerous observations in rapid succession, detect a relevant change even sooner.  In this note, we discuss the advantages and disadvantages of such an approach, and we address the question whether home-based surveillance methods currently being developed to sample more frequently can lead to detection of medically relevant trend changes over a shorter time period.  Materials, Methods, and Results Trend Model with Independent Observations In order to shed light on such questions, one needs a statistical model. We let time vary over the unit-time interval [0, 1] and let n equally spaced measurements be generated from the model  with ti = (i – 1)/(n – 1). Equation l describes a stationary linear-trend model. The trend component Tt = α + βt expresses the time progression of the measurement and εt is a measurement error with mean 0 and variance σ2. In this section we assume that the errors εt are independent. This is reasonable provided there is no instrument carry-over from one measurement to the other and the linear trend is indeed deterministic. In the following section, we allow for autocorrelations among the errors. Autocorrelation in the errors can arise from instrument carry-over, but also because the progression of many anthropometric signals is not purely deterministic, but also affected by stochastic perturbations.   Our main interest is in detecting a change in the trend progression β. What is the power of detecting a specified slope change with just n = 7 observations equally spaced on the unit-time interval? How does the power change if we take more than seven observations over the same unit-time interval? And what are the consequences of reducing the observation period in half (or to any other fraction of the unit-time interval) and taking seven (or more) observations over the reduced time interval? We start with the obvious: By restricting attention to only the first half of the time interval, we do not obtain observations from the second half of the interval. We lose the opportunity to learn whether there are changes to the trend during the second half of the interval. Trends are typically not stable, and an approach that looks at only part of the time interval certainly limits one's ability to check for changing trends. Assuming that changes in the trend are constant over time is certainly a very strong assumption.  However, for the purpose of this paper, we assume that the slope is constant across the unit-time interval. We investigate the effects of reducing the observation interval, but increasing the sampling frequency. We derive an expression for the statistical power of detecting a change in the slope, from baseline value βBase to the new value βBase + β, for known significance level α (usually, 0.05) and error standard deviation σ We write the regression model in Equation 1 in its mean-corrected form, Yi = + β(ti) + εi with ti = (i – 1)/(n – 1) for i = 1,2,…n, and = 1/2. We consider the test of H0 : β = βBase against H1 : β = βBase + β, with β > 0. The standard error of the least squares estimate β̂; is given by  see Abraham and Ledolter3 for the standard error; the last expression follows from straightforward algebra. The critical limit for the hypothesis test is CL = βBasezασβ̂;, where zα is the percentile of the standard normal distribution; for significance level α = 0.05, zα = −1.645. The power of the test is given by  where Φ(.) is the cumulative distribution function of the standard normal distribution.   Reducing the observation interval and taking n equally spaced observations on the interval [0, P < 1] changes the power to     The ratio β/σ is a critical parameter; the power decreases if smaller changes need to be detected. For α = 0.05, P = 1 (using the full time interval, such as 3 years), β/σ = 2.5, and n = 7, the power is 0.712. Given measurement variability σ = 0.4, seven equally spaced observations over the full 3-year time interval allow us to detect an increase of one unit; detecting a smaller change, such as a half unit change over three years, with just seven observations is almost impossible (power 0.294). If we took n = 15 observations over the full time period, the power of detecting an increase of one unit is larger (0.910), and we are fairly certain to detect a change of that magnitude. This is expected, as more observations are always better than fewer.  Next, let us assume that we want to make a decision within the first half of the observation period of 3 years, and do so with the same number of observations (n = 7), which now are equally spaced over the first 1.5 years. Using P = 0.5, Equation 3 results in power 0.294. As expected, this power is smaller than the one we get when spreading the seven observations over the whole 3 years, as it is equivalent to the power of detecting half of the change, (0.5)β, over the full time interval (Equation 3). Of course, one can increase this unacceptable low power by adding more observations and sampling more often. For example, with n = 15 observations equally spaced over the first 1.5 years, the power is 0.440. Figure 1 shows that we need 36 observations to achieve the same power (0.712) that we obtain with seven observations equally spaced over 3 years.  Figure 1   Independent observations. Reduction of the testing period to 70%, 60%, 50% (18 months), 40%, and 30% (∼12 months) of the original 36-month (3-year) period. In order to obtain the same power that is achieved with seven observations over the full 36-month time interval (0.712, as indicated by the red line), 17 observations are needed if the sampling period is reduced to 70% of the full 36 months, 24 observations are needed if the sampling period is reduced to 60% of the full 36 months, 36 observations are needed if the sampling takes place over only the first 18 months (reduction of the sampling period to 50% of the full 36 months), and 102 observations are needed if sampling is restricted to the first 12 months (reduction the sampling period to 30% of the full 36 months). Figure 1   Independent observations. Reduction of the testing period to 70%, 60%, 50% (18 months), 40%, and 30% (∼12 months) of the original 36-month (3-year) period. In order to obtain the same power that is achieved with seven observations over the full 36-month time interval (0.712, as indicated by the red line), 17 observations are needed if the sampling period is reduced to 70% of the full 36 months, 24 observations are needed if the sampling period is reduced to 60% of the full 36 months, 36 observations are needed if the sampling takes place over only the first 18 months (reduction of the sampling period to 50% of the full 36 months), and 102 observations are needed if sampling is restricted to the first 12 months (reduction the sampling period to 30% of the full 36 months). What about reducing the interval even further, to just 3/10 of the original 3 years (P = 0.3), but increasing the number of observations over this short time period even more? The results in Figure 1 show that we need 102 independent observations to attain the same power (0.712) that we obtain with n = 7 observations spaced evenly over 3 years. It takes more independent observations to compensate for the reduced observation interval, but the same power can always be achieved by increasing the sample frequency.  Increasing the sampling frequency certainly strengthens the reliability of a trend estimate, but also increases the danger of spurious observations. Identification and removal of outlier observations from a trend estimate will minimize the risk of responding to measurements when no response is needed. In current in-clinic evaluations of visual function that are sampled every 6 months, the clinician looks at every single observation, and with more and more observations there is a tendency to make treatment changes on the basis of the unusual recent results even when no changes are warranted. Often interventions are made when an observation exceeds its 2- or 3-sigma bounds. While the chance of being outside the 2-sigma limits is 5% for a single observation, the chance that we observe one of say 20 (independent) observations outside the 2- sigma limits is quite high (38%, using the binomial distribution).  The following simulation study illustrates this issue in the regression context when we test whether a meaningful change has occurred over a 3-year period. For our simulations, we assume that the mean of the observations changes linearly from baseline 0 to the value after a period of 3 years, for both k = 1 and k = 2. Independent normal observations with standard deviation σ are generated every 6 months. Two different estimation and testing strategies are compared. Strategy 1 uses (only) the seven observations that are available at the end of the 3-year period to test whether the slope of the linear regression through the origin has increased (using significance level 0.05). Strategy 2 starts the testing after the first four observations have been collected (i.e., after having observed the measurement at 18 months) and repeats the test with each successive observation, for a total of four tests. It concludes a change in the slope when one or more of these tests reject the no-change hypothesis.  We conduct 10,000 simulations for the null hypothesis when no change has occurred, with the proportion of rejections representing the error of a false rejection of a true null. We do the same for the alternative, with the proportion of rejections representing the power of the detection procedure. The results are given in the Table. Without adjustments for multiple testing, repeated tests carried out on frequent readily available measurements will increase the false rejection (in our simulation from 5% to 14%), leading clinicians to make treatment changes when no changes are warranted. Adjustments for multiple testing are essential as more and more data can be sampled frequently and become more readily available in a home testing scenario.  Table   Results of the Simulation Study: False Rejection Probabilities and Power of the Two Strategies. Table   Results of the Simulation Study: False Rejection Probabilities and Power of the Two Strategies. Materials, Methods, and Results Linear Trend Model with Autocorrelated Observations The trend model in Equation 1 assumes a deterministic linear trend and independent measurement errors. Independent measurement errors are reasonable as instrument carry-over from one measurement error to the next is unlikely. However, the progression of the anthropometric signal Tt = α + βt is often not purely deterministic but also affected by stochastic perturbations rt that lead to persistent slow-moving deviations from the deterministic linear trend, analogous to a slow moving wave. Persistence implies that a signal at time t above the trend line tends to be followed by signals that are above the trend line as well. In other words, signals tend to stay above (or below) the trend line for several periods in a row. Such persistence can be modeled with a first-order autoregressive model, rt = (1/(1 – φB)) ξt = ξt + φξt−1 + φ2ξt−2 + …. Here, B is the backshift operator, φ is the autoregressive parameter (which, for statistical stationarity, has to be between −1 and 1), and ξt are independent mean zero random variables with variance Display FormulaImage not available. The first-order autoregressive model for rt implies autocorrelations Cor(rt,rt−k) = φk and variance Display FormulaImage not available. Persistence is achieved when the autoregressive parameter φ is positive and close to 1. The autoregressive model becomes the (nonstationary) random walk when φ = 1. A random walk can take very long persistent excursions from the deterministic trend line. For a detailed discussion of time series models (including the backshift operator notation, stationarity and nonstationarity, and autoregressive and moving average models) we refer the reader to Abraham and Ledolter4 and Box et al.5   Incorporating anthropometric persistence into the trend model leads to the following more realistic model of change, Yt = α + βt + rt + εt. Subtracting the deterministic linear trend from the measurements, leads to trend deviations:     The model for the trend deviations can be written as (1 – φB)t = ξt + (1 – φB)εt, and is known as the autoregressive-moving average, or ARMA(1,1), model: there is just one lagged autoregressive term and the autocorrelations of the moving average component on the right-hand side of the model are zero after lag 1. It is straightforward to show that the standard deviation and the autocorrelations of the deviations from the linear trend model t = Yt – (α + βt) are σ = σ = Display FormulaImage not available, ρ1 = φDisplay FormulaImage not available , and ρk = (ρ1) φk−1 for k ≥ 1. For Display FormulaImage not available = 0 (when there is no measurement error), the ARIMA(1,1) model simplifies to the first-order autoregressive model with variance Display FormulaImage not available and autocorrelations ρk = φk−1.   Persistence is modeled through the autoregressive parameter, and let us assume φ = 0.8. The ratio Display FormulaImage not available compares the variance of the independent measurement errors with the variance of the persistent stochastic trend movements. We assume variance ratio Display FormulaImage not available = 3 as the stochastic trend component should not deviate too much from the deterministic linear trend and most of the variability should come from the measurement noise. With these choices of parameters the autocorrelations of t = Yt – (α + βt) are ρ1 = 0.8/(1 + 3) = 0.2 and ρk = (0.2)(0.8)k−1 for k ≥ 1. While the lag 1 autocorrelation is moderate in size (ρ1 = 0.2), there is a persistent slow decay in the autocorrelations from lag 1 onward.   We have provided motivation why the ARMA(1,1) is a useful error model for trend regressions. There is also evidence in the literature6,7 that errors in regressions of anthropometric time series data on deterministic functions of age follow ARMA(1,1) models. Carrico et al.7 show that, in a regression of young-adult blood pressure on linear and quadratic functions of age, body mass index, and height, ARMA(1,1) errors are preferable to AR(1) and errors with compound symmetry.  Our new model:  assumes that the errors ε follow an ARMA(1,1) model, implying an n × n error covariance matrix V with elements vij = σ2 for i = j and vij = σ2ρ1φ|i−j|1 for ij. The generalized least squares (GLS) estimator of β in the model in Equation 5 is given by β̂;GLS = (XTV−1X)−1XTV−1(Y − Ȳ). Here V is the n × n covariance matrix specified above, X = (t1,t2,…,tn)T is the n × 1 column vector of times, and Y − Ȳ = (Y1,Y2,…,Yn)T is the n × 1 column vector of mean-corrected observations. The superscript T denotes the transpose. The GLS estimator is the most efficient estimator among all linear unbiased estimators, with the smallest sample variance Display FormulaImage not available = (XTV−1X)−1.3 Substituting this standard error into Equations 2 and 3 leads to the power     We return to our example with z0.05 = −1.645, β = 1, σ = 0.4 and an observation interval that is reduced from the original 3 years (P < 1), but now assume that the error is characterized by the ARMA(1,1) model with weekly autoregressive coefficient φW = 0.8 and variance ratio Display FormulaImage not available = 3. The n observations on the reduced unit-time interval [0, P < 1] are spaced 156P/(n − 1) weeks apart. Hence, the autoregressive coefficient between successive observations is (φW)156P/(n−1). This value, σ = 0.4 and the variance ratio Display FormulaImage not available = 3 are used for the calculation of the covariance matrix V of the n observations equally spaced over the interval [0, P < 1].   With the original 3-year observation interval (P = 1) and n = 7 observations, the power calculated from Equation 6 with φW = 0.8 is still 0.712, the same power we obtain when there is independence. This is because observations are 26 weeks apart (156P/(n – 1) = 156(1)/6 = 26), Display Formula Image not available ≈ 0, and V is a diagonal matrix with zero autocorrelations. The power is affected only for much larger weekly autoregressive coefficient very close to 1.   Figure 2 shows results for the ARMA(1,1) model with weekly autoregressive coefficient φW = 0.8,σ = 0.4 and variance ratio Display Formula Image not available = 3. In order to obtain the same power that is achieved with seven observations over the full 36-month time interval (0.712), 20 observations are now needed if the sampling period is reduced to 70% of the full 36 months. This is larger than the 17 observations that are needed in the independent case. Thirty-seven observations are needed if sampling is reduced to 60% of the full 36 months, which is larger than the 24 observations in the independent case. For an observation window that is cut in half we find that it takes more (correlated) observations to compensate for the shortened observation interval. Now 159 observations are needed to attain the same power, instead of the 36 independent observations.   Figure 2   ARMA(1,1) correlation between subsequent errors with weekly autoregressive coefficient φw = 0.8 and variance ratio Image not available = 3. Reduction of the testing period to 70%, 60%, 50% (18 months), 40%, and 30% (∼12 months) of the original 36-months (3-year) period. In order to obtain the same power that is achieved with seven observations over the full 36-month time interval (0.712, as indicated by the red line in Fig. 1), 20 observations are needed if the sampling period is reduced to 70% of the full 36 months, 37 observations are needed if sampling is reduced to 60% of the full 36 months, 159 observations are needed if sampling is reduced to 50% of the full 36 months. Many more observations are needed for larger reductions of the original observation period. Figure 2   ARMA(1,1) correlation between subsequent errors with weekly autoregressive coefficient φw = 0.8 and variance ratio Image not available = 3. Reduction of the testing period to 70%, 60%, 50% (18 months), 40%, and 30% (∼12 months) of the original 36-months (3-year) period. In order to obtain the same power that is achieved with seven observations over the full 36-month time interval (0.712, as indicated by the red line in Fig. 1), 20 observations are needed if the sampling period is reduced to 70% of the full 36 months, 37 observations are needed if sampling is reduced to 60% of the full 36 months, 159 observations are needed if sampling is reduced to 50% of the full 36 months. Many more observations are needed for larger reductions of the original observation period. When reducing the time interval to 40% (or even less) of the original time interval, the increase in the number of correlated observations that are needed becomes very large and cannot compensate for the shortened observation interval, as adjacent observations over the reduced interval are now so close together that their autocorrelations approach 1. This implies that there is no benefit to taking such extra observations. For an observation interval reduced to 30%, we limit ourselves to (156)(0.3) = 46.8 weeks. With n = 100, for illustration, adjacent observations are 0.46 weeks apart and (φW)0.46 = (0.8)0.46 = 0.90. Off-diagonal elements in the covariance matrix V are large, which indicates that there is little benefit to collecting observations that are so close together in time.  A Comment on the Choice of Parameters in Figure 2 Persistence parameter φ = 0.8 and variance ratio Display FormulaImage not available = 3 imply a moderate initial autocorrelation ρ1 = φ/4 = 0.20 with subsequent slow decay. For smaller variance ratios, when trend changes dominate independent measurement errors, our calculations show that increases in the number of required samples are even larger than the ones reported in Figure 2. Larger variance ratios decrease the autocorrelations. For Display FormulaImage not available = 9, the autocorrelations start their exponential decay from ρ1 = φ/10 = 0.08, and the increases in the number of required samples become smaller. We need 18 samples when the sampling period is reduced to 70% of the initial interval (20 samples are required when Display FormulaImage not available = 4, and 17 samples are required when observations are independent), 28 samples when the sampling period is reduced to 60% (37 samples when Display FormulaImage not available = 4 and 24 samples when independent), and 49 samples when the sampling period is reduced to 50% (159 samples when Display FormulaImage not available = 4 and 36 samples when independent). The increase depends on the parameters in the ARMA(1,1) model. If prior data are available, we recommend to calculate maximum likelihood estimates of all parameters in the linear-trend model with ARMA(1,1) errors. The estimates allow us to obtain (1) the resulting increase in the required sample size, and (2) the correct standard error of the trend estimate β. This is important, as standard errors derived under independence are incorrect if errors are autocorrelated. For positive autocorrelation standard errors assuming independence are too small, which leads to spurious significance.8,9   Discussion The paper by Crabb and Garway-Heath10 is related to this discussion. They investigate, through simulations, whether it is better to collect more observations at the beginning and at the end of the observation period (“wait and see” approach) than to space the observations evenly throughout the observation window. Their finding that the power of detecting a change is increased with the “wait and see” strategy can be predicted from theory without any simulations, as the standard error of a slope estimate σβ̂; becomes smaller when the settings of the regression predictor are located at the boundary of the experimental region; see Materials, Methods, and Results. Our paper derives results theoretically and also allows for correlation among adjacent observations.  An important reason against shortening the observation period is that such approach will miss changes in the trend that occur within the interval that is not being monitored. But even if the trend stays the same, a strategy of increased sampling of correlated measurements over a shortened interval may not generate the same amount of information as does the traditional approach of obtaining measurements every 6 months. Because of autocorrelation among adjacent observations, the benefit of taking numerous closely spaced measurements may be exaggerated. For autocorrelated observations, an increase in the sampling frequency may not compensate for a shortened observation interval. However, if the autocorrelation is observed to be low for a certain type of measurement (e.g., the pupil light reflex), there may be significant benefits for increasing the sampling frequency over a shortened observation interval.  For biological measurements, especially those used in clinical medicine, where a trend analysis may be critical to understanding whether a treatment intervention is recommended, it is important to consider how correlated adjacent measurements are to one another in order to design the optimal sampling interval for the problem being monitored. One strategy would be to determine the autocorrelations empirically by taking measurements across subjects at different time intervals, allowing us to check the ARMA(1,1) model assumption in Equation 5. Knowing the autocorrelation value, the desired amount of change that one wants to detect, and the power and level of statistical significance desired will inform potential developers on an optimal sampling strategy that will take advantage of telemedical devices.  Our paper assumes that the variability of all observations is the same and the variance of measurements taken at home will be the same as in a supervised clinic environment. This would, of course, depend on the type of measurement being evaluated. Behavioral tests of vision, such as visual field sensitivity are influenced by the cognitive ability of the subject, distractions that may be present, and the effort being put forth on the day of testing and may not be the same at home compared with a monitored clinical setting. On the other hand, objective measurements of vision, such as the pupil light reflex or evoked potentials from the visual system may be more ideally suited toward at-home testing in an unsupervised, but familiar environment. Better yet, an automated, real-time, built in video-based monitoring of a patient's behavior during home testing may provide a type of behavior supervision that would optimize behavioral tests of visual function. For independent observations, the standard error of an average is obtained by dividing the standard deviation of a single measurement by the square root of the number of observations. Hence, with doubling the standard deviation of individual measurements, the sample size of the less-precise group must be increased by a factor of 4 in order to obtain the same precision and power. Therefore, objective readouts of visual function that have low repeat measurement variability would be prime candidates for at-home frequent testing over time to detect the status of ocular diseases.  Our paper shows that the shrinkage of the observation period by half can be compensated by increasing the number of independent observations so that the powers of the two strategies are the same (Fig. 1). The result is not surprising, as one knows that even the smallest change over a short-time window becomes significant if one increases the number of observations. But the result is highly dependent on how much autocorrelation exists between successive measurements (Fig. 2). It also requires the very strong assumption that the progression of the condition is constant. But in many types of disease, it is unlikely that the progression of disease is constant, and it is more plausible that progression trends are stochastic. Progression changes as time goes on, with some periods when the progression is rather flat, and other periods when conditions change quickly. Hence, it would be a misguided approach in the case where progression may vary significantly from one measurement surveillance period to the next to focus on ever-smaller time windows and to compensate with more frequent measurements over these small windows. Clinicians know about meaningful changes over a period of 3 years, but they know much less about changes that can be expected over brief periods in slowly progressive disorders, such as glaucoma or multiple sclerosis. The promise of personalized medicine with optimal monitoring of disease being enabled by frequent measurements with a home-based system is within reach with new technological advances of monitoring devices. However, the promise is more likely to become a reality if the patient is monitored indefinitely during the course of their disease to better understand patterns of progressive change and when treatment interventions are warranted for an individual patient.  Even if one could assume that trends are deterministic – which is unlikely – a strategy of taking more observations over shorter time windows has its challenges, even if such observations are independent. Our simulation results in the Table illustrate that appropriate adjustments for multiple testing are needed when analyzing and interpreting abundant successive measurements, to prevent the increased risk of diagnosing a change in the status of the disease being studied when one really does not exist.  We show that a strategy to detect progression sooner by taking closely spaced measurements over a shortened interval is limited by the degree of autocorrelation. We show this result by studying the linear-trend model with ARMA(1,1) errors, but have observed the same finding for first-order autoregressive errors in the linear-trend model as well as in the proportional linear-trend model with constant coefficient of variation. An important conclusion of our study is that one should always check whether errors are indeed independent and incorporate any serial correlation when making inferences about the trend parameters.  Accurate monitoring of progression is essential for patient management. The standard model considered in the literature combines a structural component that postulates a linear time progression and a noise component that specifies uncorrelated errors. Recently, several papers have started to question these assumptions and have proposed more general models, both for the structural time progression and for the noise component.  In their analysis of longitudinal perimetry data from glaucoma patients, Pathak et al.11 propose a structural model for the progression that includes the exponential of time and an autoregressive noise component that allows for the temporal correlation among adjacent observations. In their analysis of longitudinal cardiac imaging data, George et al.12 consider several models for the temporal and the spatial correlations that can be expected across time and across different image locations. Lawton et al.13 consider a longitudinal model for disease progression of multiple sclerosis patients. They argue quite convincingly that the structural regression component should not merely include linear time trends, but also fractional polynomials of time t, such as log(t) and sqrt(t). In addition, their models include parameters for the autocorrelation among adjacent observations. Taketani et al.14 study how to best predict for a given glaucoma patient his/her response at a future visit. Their model includes nonlinear components for the time progression (quadratic, exponential, and logistic terms of time), and they consider alternatives to the standard least squares estimation by considering robust statistical estimation methods. The study by Chan et al.15 makes a convincing argument that longitudinal studies (in their application, the movement of a subject's arm over time) must generalize the noise component to allow for possible temporal correlation. Allowing for autocorrelation helps avoid a common mistake of adopting spurious results regarding the structural progression component of the model.3  Our paper reflects these new developments in modeling longitudinal data as our model allows for temporal correlation among the observations. We recognize the importance of studying how time trends change over time.  Acknowledgments The authors thank the two referees and the associate editor for helpful comments.  Supported in part from the VA Rehabilitation Research and Development Center Grant C9251-C, C1786-R, 2I01 RX000889-05A2, 1IO1 RX002101, Chronic Effects of Neurotrauma Consortium CENC0056P (VA Rehabilitation Research and Development and DOD). Also, grants from NEI 1R01EY023279-01, R009040554, and the Department of Defense, CDMRP W81XWH-10-1-0736, W81XWH-11-1-0561, W81XWH-16-1-0071, and W81XWH-16-1-0211.  Disclosure: J. Ledolter, None; R.H. Kardon, None  References Chew EY, Clemons TE, Bressler SB, et al. Randomized trial of a home monitoring system for early detection of choroidal neovascularization. Home Monitoring of the Eye (HOME) study. Ophthalmology. 2014; 121: 535–544. Winther C, Frisen L. Self-testing of vision in age-related macula degeneration: a longitudinal pilot study using a smartphone-based rarebit test. J Ophthalmol. 2015; 2015: http://dx.doi.org/10.1155/2015/285463. Abraham B, Ledolter J. Introduction to Regression Modeling. Belmont: Thompson Higher Education; 2006. Abraham B, Ledolter J. Statistical Methods for Forecasting. New York: Wiley; 1983. Box GEP, Jenkins GM, Reinsel GC. Time Series Analysis, Forecasting and Control. 3rd ed. New York: Prentice Hall; 1994. Beckett LA, Rosner B, Roche AF, Guo S. Serial changes in blood pressure from adolescence into adulthood. Am J Epidemiol. 1992; 135: 1166–1177. Carrico RJ, Sun SS, Sima AP, Rosner, B. The predictive value of childhood blood pressure values for adult elevated blood pressure. Open J Pediatr. 2013; 3: 116–126. Crabb DP, Garway-Heath DF. Intervals between visual field tests when monitoring the glaucomatous patient: wait-and-see approach. Invest Ophthalmol Vis Sci. 2012; 53: 2770–2776. Box GEP, Newbold P. Some comments on a paper by Coen, Gomme and Kendall. J R Stat Soc. 1971; A134: 229–240. Granger CWJ, Newbold P. Spurious regressions in econometrics. J Econom. 1974; 2: 111–120. Pathak M, Demirel S, Gardiner SK. Nonlinear, multilevel mixed-effects approach for modeling longitudinal standard automated perimetry data in glaucoma. Invest Ophthalmol Vis Sci. 2013; 54: 5505–5513. George B, Denney T, Gupta H, Dell'Italia L, Aban I. Applying a spatiotemporal model for longitudinal cardiac imaging data. Ann Appl Stat. 2016; 10: 527–548. Lawton M, Tilling K, Robertson N, et al. A longitudinal model for disease progression was developed and applied to multiple sclerosis. J Clin Epidemiol. 2015; 68: 1355–1365. Taketani Y, Murata H, Fujino Y, Mayama C, Asaoka R. How many visual fields are required to precisely predict future test results in glaucoma patients when using different trend analyses? Invest Ophthalmol Vis Sci. 2015; 56: 4076–4082. Chan MF, Giddings DR, Chandler CS, Craggs C, Plant RD, Day MC. An experimentally confirmed statistical model on arm movement. Hum Mov Sci. 2004; 22: 631–648. Figure 1   Independent observations. Reduction of the testing period to 70%, 60%, 50% (18 months), 40%, and 30% (∼12 months) of the original 36-month (3-year) period. In order to obtain the same power that is achieved with seven observations over the full 36-month time interval (0.712, as indicated by the red line), 17 observations are needed if the sampling period is reduced to 70% of the full 36 months, 24 observations are needed if the sampling period is reduced to 60% of the full 36 months, 36 observations are needed if the sampling takes place over only the first 18 months (reduction of the sampling period to 50% of the full 36 months), and 102 observations are needed if sampling is restricted to the first 12 months (reduction the sampling period to 30% of the full 36 months). Figure 1   Independent observations. Reduction of the testing period to 70%, 60%, 50% (18 months), 40%, and 30% (∼12 months) of the original 36-month (3-year) period. In order to obtain the same power that is achieved with seven observations over the full 36-month time interval (0.712, as indicated by the red line), 17 observations are needed if the sampling period is reduced to 70% of the full 36 months, 24 observations are needed if the sampling period is reduced to 60% of the full 36 months, 36 observations are needed if the sampling takes place over only the first 18 months (reduction of the sampling period to 50% of the full 36 months), and 102 observations are needed if sampling is restricted to the first 12 months (reduction the sampling period to 30% of the full 36 months). Figure 2   ARMA(1,1) correlation between subsequent errors with weekly autoregressive coefficient φw = 0.8 and variance ratio Image not available = 3. Reduction of the testing period to 70%, 60%, 50% (18 months), 40%, and 30% (∼12 months) of the original 36-months (3-year) period. In order to obtain the same power that is achieved with seven observations over the full 36-month time interval (0.712, as indicated by the red line in Fig. 1), 20 observations are needed if the sampling period is reduced to 70% of the full 36 months, 37 observations are needed if sampling is reduced to 60% of the full 36 months, 159 observations are needed if sampling is reduced to 50% of the full 36 months. Many more observations are needed for larger reductions of the original observation period. Figure 2   ARMA(1,1) correlation between subsequent errors with weekly autoregressive coefficient φw = 0.8 and variance ratio Image not available = 3. Reduction of the testing period to 70%, 60%, 50% (18 months), 40%, and 30% (∼12 months) of the original 36-months (3-year) period. In order to obtain the same power that is achieved with seven observations over the full 36-month time interval (0.712, as indicated by the red line in Fig. 1), 20 observations are needed if the sampling period is reduced to 70% of the full 36 months, 37 observations are needed if sampling is reduced to 60% of the full 36 months, 159 observations are needed if sampling is reduced to 50% of the full 36 months. Many more observations are needed for larger reductions of the original observation period. Table   Results of the Simulation Study: False Rejection Probabilities and Power of the Two Strategies. Table   Results of the Simulation Study: False Rejection Probabilities and Power of the Two Strategies. × × This PDF is available to Subscribers Only Sign in or purchase a subscription to access this content. × You must be signed into an individual account to use this feature. ×
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Identification NamePyridoxal Phosphate Accession NumberDB00114  (NUTR00045) TypeSmall Molecule GroupsNutraceutical Description This is the active form of vitamin B6 serving as a coenzyme for synthesis of amino acids, neurotransmitters (serotonin, norepinephrine), sphingolipids, aminolevulinic acid. During transamination of amino acids, pyridoxal phosphate is transiently converted into pyridoxamine phosphate (pyridoxamine). [PubChem] Structure Thumb Synonyms 3-hydroxy-2-methyl-5-((phosphonooxy)methyl)-4-pyridinecarboxaldehyde 3-hydroxy-5-(hydroxymethyl)-2-methylisonicotinaldehyde 5-phosphate Codecarboxylase PLP Pyridoxal 5-monophosphoric acid ester Pyridoxal 5-phosphate Pyridoxal 5'-phosphate Pyridoxal P Pyridoxal phosphate anhydrous Pyridoxal-5P Pyridoxal-P External IDs Not Available Product Ingredients IngredientUNIICASInChI KeyDetails Pyridoxal phosphate hydrate5V5IOJ8338 41468-25-1CEEQUQSGVRRXQI-UHFFFAOYSA-NDetails Approved Prescription ProductsNot Available Approved Generic Prescription ProductsNot Available Approved Over the Counter ProductsNot Available Unapproved/Other Products Not Available International Brands NameCompany BiosechsNot Available HimitanNot Available VitazechsNot Available Brand mixtures NameIngredientsDosageRouteLabellerMarketing StartMarketing End Enbrace HrCapsule, delayed release pelletsOralJaymac Pharmaceuticals, Llc2015-04-08Not applicableUs EnlyteCapsule, delayed release pelletsOralJaymac Pharmaceuticals Llc2011-10-01Not applicableUs Categories UNIIF06SGE49M6 CAS number54-47-7 WeightAverage: 247.1419 Monoisotopic: 247.024573569 Chemical FormulaC8H10NO6P InChI KeyNGVDGCNFYWLIFO-UHFFFAOYSA-N InChI InChI=1S/C8H10NO6P/c1-5-8(11)7(3-10)6(2-9-5)4-15-16(12,13)14/h2-3,11H,4H2,1H3,(H2,12,13,14) IUPAC Name [(4-formyl-5-hydroxy-6-methylpyridin-3-yl)methoxy]phosphonic acid SMILES CC1=NC=C(COP(O)(O)=O)C(C=O)=C1O Pharmacology Indication For nutritional supplementation and for treating dietary shortage or imbalance. Structured Indications Not Available Pharmacodynamics The two major forms of vitamin B6 are pyridoxine and pyridoxamine. In the liver they are converted to pyridoxal phosphate (PLP) which is a cofactor in many reactions of amino acid metabolism. PLP also is necessary for the enzymatic reaction governing the release of glucose from glycogen. Pyroluria is one potential cause of vitamin B6 deficiency. Mechanism of action Pyridoxal Phosphate is a coenzyme of many enzymatic reactions. It is the active form of vitamin B6 which comprises three natural organic compounds, pyridoxal, pyridoxamine and pyridoxine. Pyridoxal phosphate acts as a coenzyme in all transamination reactions, and in some decarboxylation and deamination reactions of amino acids. The aldehyde group of pyridoxal phosphate forms a Schiff-base linkage with the epsilon-amino group of a specific lysine group of the aminotransferase enzyme. The alpha-amino group of the amino acid substrate displaces the epsilon-amino group of the active-site lysine residue. The resulting aldimine becomes deprotonated to become a quinoid intermediate, which in turn accepts a proton at a different position to become a ketimine. The resulting ketimine is hydrolysed so that the amino group remains on the protein complex. TargetKindPharmacological actionActionsOrganismUniProt ID Alanine--glyoxylate aminotransferase 2, mitochondrialProteinunknown cofactor HumanQ9BYV1 details Glutamate decarboxylase 1Proteinunknown cofactor HumanQ99259 details Cystathionine beta-synthaseProteinunknown cofactor HumanP35520 details KynureninaseProteinunknown cofactor HumanQ16719 details Serine hydroxymethyltransferase, cytosolicProteinunknown cofactor HumanP34896 details Cysteine desulfurase, mitochondrialProteinunknown cofactor HumanQ9Y697 details Aspartate aminotransferase, cytoplasmicProteinunknown activator HumanP17174 details Ornithine aminotransferase, mitochondrialProteinunknown cofactor HumanP04181 details Ornithine decarboxylaseProteinunknown cofactor HumanP11926 details Kynurenine/alpha-aminoadipate aminotransferase, mitochondrialProteinunknown cofactor HumanQ8N5Z0 details 4-aminobutyrate aminotransferase, mitochondrialProteinunknown inhibitor HumanP80404 details Pyridoxine-5'-phosphate oxidaseProteinunknown cofactor HumanQ9NVS9 details Sphingosine-1-phosphate lyase 1Proteinunknown cofactor HumanO95470 details Tyrosine aminotransferaseProteinunknown cofactor HumanP17735 details Kynurenine--oxoglutarate transaminase 1Proteinunknown cofactor HumanQ16773 details Threonine synthase-like 1Proteinunknown cofactor HumanQ8IYQ7 details Glycogen phosphorylase, liver formProteinunknown cofactor HumanP06737 details Serine palmitoyltransferase 2Proteinunknown cofactor HumanO15270 details Cysteine sulfinic acid decarboxylaseProteinunknown cofactor HumanQ9Y600 details Histidine decarboxylaseProteinunknown cofactor HumanP19113 details Arginine decarboxylaseProteinunknown cofactor HumanQ96A70 details L-serine dehydratase/L-threonine deaminaseProteinunknown cofactor HumanP20132 details 2-amino-3-ketobutyrate coenzyme A ligase, mitochondrialProteinunknown cofactor HumanO75600 details Glycine dehydrogenase [decarboxylating], mitochondrialProteinunknown cofactor HumanP23378 details Alanine aminotransferase 1Proteinunknown cofactor HumanP24298 details Phosphoserine aminotransferaseProteinunknown cofactor HumanQ9Y617 details 5-aminolevulinate synthase, nonspecific, mitochondrialProteinunknown cofactor HumanP13196 details Serine--pyruvate aminotransferaseProteinunknown cofactor HumanP21549 details Pyridoxal phosphate phosphataseProteinunknown cofactor HumanQ96GD0 details Serine palmitoyltransferase 1Proteinunknown cofactor HumanO15269 details Cystathionine gamma-lyaseProteinunknown cofactor HumanP32929 details Branched-chain-amino-acid aminotransferase, cytosolicProteinunknown cofactor HumanP54687 details Branched-chain-amino-acid aminotransferase, mitochondrialProteinunknown cofactor HumanO15382 details Proline synthase co-transcribed bacterial homolog proteinProteinunknown cofactor HumanO94903 details Formimidoyltransferase-cyclodeaminaseProteinunknown cofactor HumanO95954 details Aspartate aminotransferase, mitochondrialProteinunknown cofactor HumanP00505 details Glycogen phosphorylase, brain formProteinunknown cofactor HumanP11216 details Glycogen phosphorylase, muscle formProteinunknown cofactor HumanP11217 details Aromatic-L-amino-acid decarboxylaseProteinunknown cofactor HumanP20711 details Aspartate aminotransferaseProteinunknown cofactor HumanQ2TU84 details GAD1 proteinProteinunknown cofactor HumanQ99259 details Serine hydroxymethyltransferaseProteinunknown cofactor HumanQ53ET4 details Selenocysteine lyase variantProteinunknown cofactor HumanQ59FK2 details PhosphorylaseProteinunknown cofactor HumanQ59GM9 details Ornithine aminotransferase variantProteinunknown cofactor HumanQ59HE2 details 5-aminolevulinate synthaseProteinunknown cofactor HumanQ5JAM2 details Glutamate decarboxylase 2 (Pancreatic islets and brain, 65kDa)Proteinunknown cofactor HumanQ5VZ30 details DDC proteinProteinunknown cofactor HumanQ6IBS8 details Pyridoxal-dependent decarboxylase domain-containing protein 1Proteinunknown cofactor HumanQ6P996 details Kynurenine--oxoglutarate transaminase 3Proteinunknown cofactor HumanQ6YP21 details Glutamate decarboxylase-like protein 1Proteinunknown cofactor HumanQ6ZQY3 details Selenocysteine lyaseProteinunknown cofactor HumanQ96I15 details Immunoglobulin superfamily member 10Proteinunknown cofactor HumanQ6WRI0 details 5-phosphohydroxy-L-lysine phospho-lyaseProteinunknown cofactor HumanQ8IUZ5 details Glutamate decarboxylase 1 (Brain, 67kDa)Proteinunknown cofactor HumanQ8IVA8 details Serine hydroxymethyltransferase, mitochondrialProteinunknown cofactor HumanP34897 details 5-aminolevulinate synthase, erythroid-specific, mitochondrialProteinunknown cofactor HumanP22557 details Alanine aminotransferase 2Proteinunknown cofactor HumanQ8TD30 details Molybdenum cofactor sulfuraseProteinunknown cofactor HumanQ96EN8 details Serine dehydratase-likeProteinunknown cofactor HumanQ96GA7 details P-selectin cytoplasmic tail-associated protein (PCAP)Proteinunknown cofactor HumanQ96JQ3 details Hepatic peroxysomal alanine:glyoxylate aminotransferaseProteinunknown cofactor HumanQ9BXA1 details Serine racemaseProteinunknown cofactor HumanQ9GZT4 details O-phosphoseryl-tRNA(Sec) selenium transferaseProteinunknown cofactor HumanQ9HD40 details Serine palmitoyltransferase 3Proteinunknown cofactor HumanQ9NUV7 details Glutamic acid decarboxylaseProteinunknown cofactor HumanQ9UGI5 details Alanine-glyoxylate aminotransferase homologProteinunknown cofactor HumanQ9UJX1 details Related Articles AbsorptionNot Available Volume of distributionNot Available Protein bindingNot Available MetabolismNot Available Route of eliminationNot Available Half lifeNot Available ClearanceNot Available ToxicityNot Available Affected organisms • Humans and other mammals Pathways PathwayCategorySMPDB ID Tryptophan MetabolismMetabolicSMP00063 3-Methylglutaconic Aciduria Type IIIDiseaseSMP00140 HistidinemiaDiseaseSMP00191 HypoacetylaspartiaDiseaseSMP00192 Methylmalonic AciduriaDiseaseSMP00200 S-Adenosylhomocysteine (SAH) Hydrolase DeficiencyDiseaseSMP00214 Tyrosinemia Type IDiseaseSMP00218 Glycine N-methyltransferase DeficiencyDiseaseSMP00222 Non Ketotic HyperglycinemiaDiseaseSMP00223 Isovaleric AciduriaDiseaseSMP00238 Hereditary Coproporphyria (HCP)DiseaseSMP00342 Globoid Cell LeukodystrophyDiseaseSMP00348 Primary Hyperoxaluria Type IDiseaseSMP00352 ArgininemiaDiseaseSMP00357 Methylmalonate Semialdehyde Dehydrogenase DeficiencyDiseaseSMP00384 Disulfiram Action PathwayDrug actionSMP00429 Homocysteine DegradationMetabolicSMP00455 Carnitine SynthesisMetabolicSMP00465 Dimethylglycine Dehydrogenase DeficiencyDiseaseSMP00484 Tyrosine hydroxylase deficiencyDiseaseSMP00497 Malonyl-coa decarboxylase deficiencyDiseaseSMP00502 Isobutyryl-coa dehydrogenase deficiencyDiseaseSMP00523 Isovaleric acidemiaDiseaseSMP00524 Krabbe diseaseDiseaseSMP00526 Hyperlysinemia II or SaccharopinuriaDiseaseSMP00528 Glycogen synthetase deficiencyDiseaseSMP00552 Pyridoxine dependency with seizuresDiseaseSMP00571 sarcosine oncometabolite pathway DiseaseSMP02313 Beta-Alanine MetabolismMetabolicSMP00007 Catecholamine BiosynthesisMetabolicSMP00012 Pharmacogenomic Effects/ADRs Not Available Interactions Drug Interactions Not Available Food InteractionsNot Available References Synthesis Reference Robert C. Siegel, "Synthesis of cross-links in the helical domain of collagen using pyridoxal 5-phosphate and copper or iron." U.S. Patent US4544638, issued June, 1981. US4544638 General ReferencesNot Available External Links ATC CodesA11HA06 — Pyridoxal phosphate AHFS CodesNot Available PDB Entries FDA labelNot Available MSDSDownload (36.1 KB) Clinical Trials Clinical Trials PhaseStatusPurposeConditionsCount 2TerminatedTreatmentTardive Dyskinesia1 Pharmacoeconomics ManufacturersNot Available Packagers Dosage forms FormRouteStrength Capsule, delayed release pelletsOral PricesNot Available PatentsNot Available Properties StateSolid Experimental Properties PropertyValueSource melting point (°C)255 °CPhysProp water solubilityAppreciableNot Available logP-1.2Not Available Predicted Properties PropertyValueSource Water Solubility5.7 mg/mLALOGPS logP-0.55ALOGPS logP-2.1ChemAxon logS-1.6ALOGPS pKa (Strongest Acidic)1.68ChemAxon pKa (Strongest Basic)4.11ChemAxon Physiological Charge-2ChemAxon Hydrogen Acceptor Count6ChemAxon Hydrogen Donor Count3ChemAxon Polar Surface Area116.95 Å2ChemAxon Rotatable Bond Count4ChemAxon Refractivity54.75 m3·mol-1ChemAxon Polarizability20.9 Å3ChemAxon Number of Rings1ChemAxon Bioavailability1ChemAxon Rule of FiveYesChemAxon Ghose FilterNoChemAxon Veber's RuleNoChemAxon MDDR-like RuleNoChemAxon Predicted ADMET features PropertyValueProbability Human Intestinal Absorption+0.5078 Blood Brain Barrier+0.8022 Caco-2 permeable-0.6476 P-glycoprotein substrateNon-substrate0.6324 P-glycoprotein inhibitor INon-inhibitor0.9035 P-glycoprotein inhibitor IINon-inhibitor0.9694 Renal organic cation transporterNon-inhibitor0.882 CYP450 2C9 substrateNon-substrate0.6828 CYP450 2D6 substrateNon-substrate0.7978 CYP450 3A4 substrateNon-substrate0.5915 CYP450 1A2 substrateNon-inhibitor0.8704 CYP450 2C9 inhibitorNon-inhibitor0.9041 CYP450 2D6 inhibitorNon-inhibitor0.901 CYP450 2C19 inhibitorNon-inhibitor0.8772 CYP450 3A4 inhibitorNon-inhibitor0.9308 CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9352 Ames testNon AMES toxic0.6624 CarcinogenicityNon-carcinogens0.8948 BiodegradationReady biodegradable0.5443 Rat acute toxicity1.6531 LD50, mol/kg Not applicable hERG inhibition (predictor I)Weak inhibitor0.8729 hERG inhibition (predictor II)Non-inhibitor0.9128 ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 ) Spectra Mass Spec (NIST)Not Available Spectra Spectrum TypeDescriptionSplash Key GC-MSGC-MS Spectrum - GC-MS (1 MEOX; 3 TMS)splash10-0gb9-2690000000-c9bacb7e657461e28407View in MoNA Predicted GC-MSPredicted GC-MS Spectrum - GC-MSNot Available LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated)splash10-0f6t-0690000000-4aa57f3f28f0bdef9dcfView in MoNA LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated)splash10-0fxx-8900000000-ee972556340c61650528View in MoNA LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 40V, Positive (Annotated)splash10-014l-9100000000-3cc29fb51820adecd59cView in MoNA LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 10V, Negativesplash10-0002-0090000000-9b86e80a9dd0de14ab59View in MoNA LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 20V, Negativesplash10-03dj-9800000000-9313aa9cbf19bc6311c5View in MoNA LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 30V, Negativesplash10-0002-9500000000-7ce120a58879e2214ce5View in MoNA LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 40V, Negativesplash10-004j-9200000000-7e6bd8c298613e59fb5dView in MoNA LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 50V, Negativesplash10-004i-9000000000-4c05178b1645bf01f3faView in MoNA LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF (UPLC Q-Tof Premier, Waters) , Positivesplash10-0udi-3920000000-6c5e6106f5658d1d6c50View in MoNA LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF (UPLC Q-Tof Premier, Waters) , Positivesplash10-0udi-3920000000-f96097815e6922356131View in MoNA LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF (UPLC Q-Tof Premier, Waters) , Negativesplash10-002b-9000000000-2c4e243699a95e3a0f88View in MoNA LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF (UPLC Q-Tof Premier, Waters) , Negativesplash10-002b-9000000000-8aa111485891af9f0d02View in MoNA Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0f6t-1790000000-1dcb07cd1110c71f7005View in MoNA Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0udi-0900000000-ca6aab7f31a36863a417View in MoNA Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0udi-9800000000-053802b9c0533d7943eaView in MoNA Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0002-9080000000-12ca63d34d39d59f6b42View in MoNA Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-004i-9000000000-144099ec201adbbc4684View in MoNA Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-004i-9000000000-70a9559d65e78c488e7eView in MoNA 1D NMR1H NMR SpectrumNot Available 1D NMR1H NMR SpectrumNot Available 1D NMR13C NMR SpectrumNot Available 2D NMR[1H,1H] 2D NMR SpectrumNot Available 2D NMR[1H,13C] 2D NMR SpectrumNot Available Taxonomy DescriptionThis compound belongs to the class of chemical entities known as pyridoxals and derivatives. These are compounds containing a pyridoxal moiety, which consists of a pyridine ring substituted at positions 2,3,4, and 5 by a methyl group, a hydroxyl group, a carbaldehyde group, and a hydroxymethyl group, respectively. KingdomChemical entities Super ClassOrganic compounds ClassOrganoheterocyclic compounds Sub ClassPyridines and derivatives Direct ParentPyridoxals and derivatives Alternative ParentsMonoalkyl phosphates / Methylpyridines / Hydroxypyridines / Aryl-aldehydes / Vinylogous acids / Heteroaromatic compounds / Azacyclic compounds / Organopnictogen compounds / Organonitrogen compounds / Organic oxides SubstituentsPyridoxal / Aryl-aldehyde / Monoalkyl phosphate / Hydroxypyridine / Methylpyridine / Organic phosphoric acid derivative / Phosphoric acid ester / Alkyl phosphate / Vinylogous acid / Heteroaromatic compound Molecular FrameworkAromatic heteromonocyclic compounds External Descriptorsmonohydroxypyridine, pyridinecarbaldehyde, methylpyridines, vitamin B6 phosphate (CHEBI:18405 ) Targets Kind Protein Organism Human Pharmacological action unknown Actions cofactor General Function: Pyridoxal phosphate binding Specific Function: Can metabolize asymmetric dimethylarginine (ADMA) via transamination to alpha-keto-delta-(NN-dimethylguanidino) valeric acid (DMGV). ADMA is a potent inhibitor of nitric-oxide (NO) synthase, and this activity provides mechanism through which the kidney regulates blood pressure. Gene Name: AGXT2 Uniprot ID: Q9BYV1 Uniprot Name: Alanine--glyoxylate aminotransferase 2, mitochondrial Molecular Weight: 57155.905 Da References 1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284 ] 2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423 ] 3. Lee IS, Muragaki Y, Ideguchi T, Hase T, Tsuji M, Ooshima A, Okuno E, Kido R: Molecular cloning and sequencing of a cDNA encoding alanine-glyoxylate aminotransferase 2 from rat kidney. J Biochem. 1995 Apr;117(4):856-62. [PubMed:7592550 ] 4. Takada Y, Mori T, Noguchi T: The effect of vitamin B6 deficiency on alanine: glyoxylate aminotransferase isoenzymes in rat liver. Arch Biochem Biophys. 1984 Feb 15;229(1):1-6. [PubMed:6703688 ] Kind Protein Organism Human Pharmacological action unknown Actions cofactor General Function: Pyridoxal phosphate binding Specific Function: Catalyzes the production of GABA. Gene Name: GAD1 Uniprot ID: Q99259 Uniprot Name: Glutamate decarboxylase 1 Molecular Weight: 66896.065 Da References 1. Hwang IK, Yoo KY, Kim DS, Eum WS, Park JK, Park J, Kwon OS, Kang TC, Choi SY, Won MH: Changes of pyridoxal kinase expression and activity in the gerbil hippocampus following transient forebrain ischemia. Neuroscience. 2004;128(3):511-8. [PubMed:15381280 ] 2. Rust E, Martin DL, Chen CH: Cofactor and tryptophan accessibility and unfolding of brain glutamate decarboxylase. Arch Biochem Biophys. 2001 Aug 15;392(2):333-40. [PubMed:11488610 ] 3. Jin H, Sha D, Wei J, Davis KM, Wu H, Jin Y, Wu JY: Effect of apocalmodulin on recombinant human brain glutamic acid decarboxylase. J Neurochem. 2005 Feb;92(4):739-48. [PubMed:15686475 ] 4. Chen CH, Battaglioli G, Martin DL, Hobart SA, Colon W: Distinctive interactions in the holoenzyme formation for two isoforms of glutamate decarboxylase. Biochim Biophys Acta. 2003 Jan 31;1645(1):63-71. [PubMed:12535612 ] 5. Tong JC, Mackay IR, Chin J, Law RH, Fayad K, Rowley MJ: Enzymatic characterization of a recombinant isoform hybrid of glutamic acid decarboxylase (rGAD67/65) expressed in yeast. J Biotechnol. 2002 Aug 7;97(2):183-90. [PubMed:12067524 ] Kind Protein Organism Human Pharmacological action unknown Actions cofactor General Function: Ubiquitin protein ligase binding Specific Function: Hydro-lyase catalyzing the first step of the transsulfuration pathway, where the hydroxyl group of L-serine is displaced by L-homocysteine in a beta-replacement reaction to form L-cystathionine, the precursor of L-cysteine. This catabolic route allows the elimination of L-methionine and the toxic metabolite L-homocysteine (PubMed:23981774, PubMed:20506325, PubMed:23974653). Also involved in the... Gene Name: CBS Uniprot ID: P35520 Uniprot Name: Cystathionine beta-synthase Molecular Weight: 60586.05 Da References 1. Taoka S, Banerjee R: Stopped-flow kinetic analysis of the reaction catalyzed by the full-length yeast cystathionine beta-synthase. J Biol Chem. 2002 Jun 21;277(25):22421-5. Epub 2002 Apr 10. [PubMed:11948191 ] 2. Taoka S, Lepore BW, Kabil O, Ojha S, Ringe D, Banerjee R: Human cystathionine beta-synthase is a heme sensor protein. Evidence that the redox sensor is heme and not the vicinal cysteines in the CXXC motif seen in the crystal structure of the truncated enzyme. Biochemistry. 2002 Aug 20;41(33):10454-61. [PubMed:12173932 ] 3. Mino K, Ishikawa K: Characterization of a novel thermostable O-acetylserine sulfhydrylase from Aeropyrum pernix K1. J Bacteriol. 2003 Apr;185(7):2277-84. [PubMed:12644499 ] 4. Evande R, Ojha S, Banerjee R: Visualization of PLP-bound intermediates in hemeless variants of human cystathionine beta-synthase: evidence that lysine 119 is a general base. Arch Biochem Biophys. 2004 Jul 15;427(2):188-96. [PubMed:15196993 ] 5. Linnebank M, Janosik M, Kozich V, Pronicka E, Kubalska J, Sokolova J, Linnebank A, Schmidt E, Leyendecker C, Klockgether T, Kraus JP, Koch HG: The cystathionine beta-synthase (CBS) mutation c.1224-2A>C in Central Europe: Vitamin B6 nonresponsiveness and a common ancestral haplotype. Hum Mutat. 2004 Oct;24(4):352-3. [PubMed:15365998 ] Kind Protein Organism Human Pharmacological action unknown Actions cofactor General Function: Pyridoxal phosphate binding Specific Function: Catalyzes the cleavage of L-kynurenine (L-Kyn) and L-3-hydroxykynurenine (L-3OHKyn) into anthranilic acid (AA) and 3-hydroxyanthranilic acid (3-OHAA), respectively. Has a preference for the L-3-hydroxy form. Also has cysteine-conjugate-beta-lyase activity. Gene Name: KYNU Uniprot ID: Q16719 Uniprot Name: Kynureninase Molecular Weight: 52351.14 Da References 1. Momany C, Levdikov V, Blagova L, Lima S, Phillips RS: Three-dimensional structure of kynureninase from Pseudomonas fluorescens. Biochemistry. 2004 Feb 10;43(5):1193-203. [PubMed:14756555 ] 2. Rooseboom M, Vermeulen NP, Groot EJ, Commandeur JN: Tissue distribution of cytosolic beta-elimination reactions of selenocysteine Se-conjugates in rat and human. Chem Biol Interact. 2002 Aug 15;140(3):243-64. [PubMed:12204580 ] 3. Lima S, Khristoforov R, Momany C, Phillips RS: Crystal structure of Homo sapiens kynureninase. Biochemistry. 2007 Mar 13;46(10):2735-44. Epub 2007 Feb 15. [PubMed:17300176 ] 4. Walsh HA, Botting NP: Purification and biochemical characterization of some of the properties of recombinant human kynureninase. Eur J Biochem. 2002 Apr;269(8):2069-74. [PubMed:11985583 ] Kind Protein Organism Human Pharmacological action unknown Actions cofactor General Function: Serine binding Specific Function: Interconversion of serine and glycine. Gene Name: SHMT1 Uniprot ID: P34896 Uniprot Name: Serine hydroxymethyltransferase, cytosolic Molecular Weight: 53082.18 Da References 1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284 ] 2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423 ] 3. Trakatellis A, Dimitriadou A, Exindari M, Christodoulou D, Malissiovas N, Antoniadis A, Haitoglou K: Effect of combination of deoxypyridoxine with known anti-proliferative or immunosuppressive agents on lymphocyte serine hydroxymethyltransferase. Postgrad Med J. 1994;70 Suppl 1:S89-92. [PubMed:7526359 ] 4. Jagath JR, Sharma B, Rao NA, Savithri HS: The role of His-134, -147, and -150 residues in subunit assembly, cofactor binding, and catalysis of sheep liver cytosolic serine hydroxymethyltransferase. J Biol Chem. 1997 Sep 26;272(39):24355-62. [PubMed:9305893 ] 5. Bourguignon J, Neuburger M, Douce R: Resolution and characterization of the glycine-cleavage reaction in pea leaf mitochondria. Properties of the forward reaction catalysed by glycine decarboxylase and serine hydroxymethyltransferase. Biochem J. 1988 Oct 1;255(1):169-78. [PubMed:3143355 ] 6. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [PubMed:10592235 ] Kind Protein Organism Human Pharmacological action unknown Actions cofactor General Function: Pyridoxal phosphate binding Specific Function: Catalyzes the removal of elemental sulfur from cysteine to produce alanine. It supplies the inorganic sulfur for iron-sulfur (Fe-S) clusters. May be involved in the biosynthesis of molybdenum cofactor. Gene Name: NFS1 Uniprot ID: Q9Y697 Uniprot Name: Cysteine desulfurase, mitochondrial Molecular Weight: 50195.21 Da References 1. Ollagnier-De-Choudens S, Mulliez E, Hewitson KS, Fontecave M: Biotin synthase is a pyridoxal phosphate-dependent cysteine desulfurase. Biochemistry. 2002 Jul 23;41(29):9145-52. [PubMed:12119030 ] 2. You D, Wang L, Yao F, Zhou X, Deng Z: A novel DNA modification by sulfur: DndA is a NifS-like cysteine desulfurase capable of assembling DndC as an iron-sulfur cluster protein in Streptomyces lividans. Biochemistry. 2007 May 22;46(20):6126-33. Epub 2007 May 1. [PubMed:17469805 ] 3. Forlani F, Cereda A, Freuer A, Nimtz M, Leimkuhler S, Pagani S: The cysteine-desulfurase IscS promotes the production of the rhodanese RhdA in the persulfurated form. FEBS Lett. 2005 Dec 19;579(30):6786-90. Epub 2005 Nov 21. [PubMed:16310786 ] 4. Cupp-Vickery JR, Urbina H, Vickery LE: Crystal structure of IscS, a cysteine desulfurase from Escherichia coli. J Mol Biol. 2003 Jul 25;330(5):1049-59. [PubMed:12860127 ] 5. Frazzon J, Fick JR, Dean DR: Biosynthesis of iron-sulphur clusters is a complex and highly conserved process. Biochem Soc Trans. 2002 Aug;30(4):680-5. [PubMed:12196163 ] Kind Protein Organism Human Pharmacological action unknown Actions activator General Function: Pyridoxal phosphate binding Specific Function: Biosynthesis of L-glutamate from L-aspartate or L-cysteine. Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system. Acts as a scavenger of glutamate in brain neuroprotection. The aspartate aminotransferase activity is involved in hepatic glucose synthesis during development and in adipocyte glyceroneogenesis. Using L-cysteine a... Gene Name: GOT1 Uniprot ID: P17174 Uniprot Name: Aspartate aminotransferase, cytoplasmic Molecular Weight: 46247.14 Da References 1. Hansen CM, Shultz TD: Stability of vitamin B-6-dependent aminotransferase activity in frozen packed erythrocytes is dependent on storage temperature. J Nutr. 2001 May;131(5):1581-3. [PubMed:11340119 ] 2. Eliot AC, Kirsch JF: Modulation of the internal aldimine pK(a)'s of 1-aminocyclopropane-1-carboxylate synthase and aspartate aminotransferase by specific active site residues. Biochemistry. 2002 Mar 19;41(11):3836-42. [PubMed:11888303 ] 3. Cooper AJ, Bruschi SA, Anders MW: Toxic, halogenated cysteine S-conjugates and targeting of mitochondrial enzymes of energy metabolism. Biochem Pharmacol. 2002 Aug 15;64(4):553-64. [PubMed:12167474 ] 4. Waldmann A, Dorr B, Koschizke JW, Leitzmann C, Hahn A: Dietary intake of vitamin B6 and concentration of vitamin B6 in blood samples of German vegans. Public Health Nutr. 2006 Sep;9(6):779-84. [PubMed:16925884 ] 5. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ] Kind Protein Organism Human Pharmacological action unknown Actions cofactor General Function: Pyridoxal phosphate binding Specific Function: Not Available Gene Name: OAT Uniprot ID: P04181 Uniprot Name: Ornithine aminotransferase, mitochondrial Molecular Weight: 48534.39 Da References 1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284 ] 2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423 ] 3. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [PubMed:10592235 ] Kind Protein Organism Human Pharmacological action unknown Actions cofactor General Function: Protein homodimerization activity Specific Function: Key enzyme of polyamine biosynthesis that converts ornithine into putrescine, which is the precursor for the polyamines, spermidine and spermine. Gene Name: ODC1 Uniprot ID: P11926 Uniprot Name: Ornithine decarboxylase Molecular Weight: 51147.73 Da References 1. Jackson LK, Goldsmith EJ, Phillips MA: X-ray structure determination of Trypanosoma brucei ornithine decarboxylase bound to D-ornithine and to G418: insights into substrate binding and ODC conformational flexibility. J Biol Chem. 2003 Jun 13;278(24):22037-43. Epub 2003 Apr 2. [PubMed:12672797 ] 2. Jackson LK, Brooks HB, Myers DP, Phillips MA: Ornithine decarboxylase promotes catalysis by binding the carboxylate in a buried pocket containing phenylalanine 397. Biochemistry. 2003 Mar 18;42(10):2933-40. [PubMed:12627959 ] 3. Jackson LK, Baldwin J, Akella R, Goldsmith EJ, Phillips MA: Multiple active site conformations revealed by distant site mutation in ornithine decarboxylase. Biochemistry. 2004 Oct 19;43(41):12990-9. [PubMed:15476392 ] 4. Khomutov AR: Inhibition of enzymes of polyamine biosynthesis by substrate-like O-substituted hydroxylamines. Biochemistry (Mosc). 2002 Oct;67(10):1159-67. [PubMed:12460114 ] 5. Myers DP, Jackson LK, Ipe VG, Murphy GE, Phillips MA: Long-range interactions in the dimer interface of ornithine decarboxylase are important for enzyme function. Biochemistry. 2001 Nov 6;40(44):13230-6. [PubMed:11683631 ] Kind Protein Organism Human Pharmacological action unknown Actions cofactor General Function: Pyridoxal phosphate binding Specific Function: Transaminase with broad substrate specificity. Has transaminase activity towards aminoadipate, kynurenine, methionine and glutamate. Shows activity also towards tryptophan, aspartate and hydroxykynurenine. Accepts a variety of oxo-acids as amino-group acceptors, with a preference for 2-oxoglutarate, 2-oxocaproic acid, phenylpyruvate and alpha-oxo-gamma-methiol butyric acid. Can also use glyoxyl... Gene Name: AADAT Uniprot ID: Q8N5Z0 Uniprot Name: Kynurenine/alpha-aminoadipate aminotransferase, mitochondrial Molecular Weight: 47351.17 Da References 1. Goh DL, Patel A, Thomas GH, Salomons GS, Schor DS, Jakobs C, Geraghty MT: Characterization of the human gene encoding alpha-aminoadipate aminotransferase (AADAT). Mol Genet Metab. 2002 Jul;76(3):172-80. [PubMed:12126930 ] 2. Cooper AJ: The role of glutamine transaminase K (GTK) in sulfur and alpha-keto acid metabolism in the brain, and in the possible bioactivation of neurotoxicants. Neurochem Int. 2004 Jun;44(8):557-77. [PubMed:15016471 ] Kind Protein Organism Human Pharmacological action unknown Actions inhibitor General Function: Succinate-semialdehyde dehydrogenase binding Specific Function: Catalyzes the conversion of gamma-aminobutyrate and L-beta-aminoisobutyrate to succinate semialdehyde and methylmalonate semialdehyde, respectively. Can also convert delta-aminovalerate and beta-alanine. Gene Name: ABAT Uniprot ID: P80404 Uniprot Name: 4-aminobutyrate aminotransferase, mitochondrial Molecular Weight: 56438.405 Da References 1. Storici P, De Biase D, Bossa F, Bruno S, Mozzarelli A, Peneff C, Silverman RB, Schirmer T: Structures of gamma-aminobutyric acid (GABA) aminotransferase, a pyridoxal 5'-phosphate, and [2Fe-2S] cluster-containing enzyme, complexed with gamma-ethynyl-GABA and with the antiepilepsy drug vigabatrin. J Biol Chem. 2004 Jan 2;279(1):363-73. Epub 2003 Oct 8. [PubMed:14534310 ] 2. Hwang IK, Yoo KY, Kim do H, Lee BH, Kwon YG, Won MH: Time course of changes in pyridoxal 5'-phosphate (vitamin B6 active form) and its neuroprotection in experimental ischemic damage. Exp Neurol. 2007 Jul;206(1):114-25. Epub 2007 Apr 24. [PubMed:17531224 ] 3. Sulaiman SA, Suliman FE, Barghouthi S: Kinetic studies on the inhibition of GABA-T by gamma-vinyl GABA and taurine. J Enzyme Inhib Med Chem. 2003 Aug;18(4):297-301. [PubMed:14567543 ] 4. Markova M, Peneff C, Hewlins MJ, Schirmer T, John RA: Determinants of substrate specificity in omega-aminotransferases. J Biol Chem. 2005 Oct 28;280(43):36409-16. Epub 2005 Aug 11. [PubMed:16096275 ] 5. Liu W, Peterson PE, Langston JA, Jin X, Zhou X, Fisher AJ, Toney MD: Kinetic and crystallographic analysis of active site mutants of Escherichia coli gamma-aminobutyrate aminotransferase. Biochemistry. 2005 Mar 1;44(8):2982-92. [PubMed:15723541 ] 6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ] Kind Protein Organism Human Pharmacological action unknown Actions cofactor General Function: Pyridoxamine-phosphate oxidase activity Specific Function: Catalyzes the oxidation of either pyridoxine 5'-phosphate (PNP) or pyridoxamine 5'-phosphate (PMP) into pyridoxal 5'-phosphate (PLP). Gene Name: PNPO Uniprot ID: Q9NVS9 Uniprot Name: Pyridoxine-5'-phosphate oxidase Molecular Weight: 29987.79 Da References 1. Gospe SM Jr: Pyridoxine-dependent seizures: new genetic and biochemical clues to help with diagnosis and treatment. Curr Opin Neurol. 2006 Apr;19(2):148-53. [PubMed:16538088 ] 2. Hwang IK, Kim DW, Jung JY, Yoo KY, Cho JH, Kwon OS, Kang TC, Choi SY, Kim YS, Won MH: Age-dependent changes of pyridoxal phosphate synthesizing enzymes immunoreactivities and activities in the gerbil hippocampal CA1 region. Mech Ageing Dev. 2005 Dec;126(12):1322-30. Epub 2005 Oct 3. [PubMed:16207494 ] 3. Pearl PL, Hartka TR, Taylor J: Diagnosis and treatment of neurotransmitter disorders. Curr Treat Options Neurol. 2006 Nov;8(6):441-50. [PubMed:17032564 ] 4. Hoffmann GF, Schmitt B, Windfuhr M, Wagner N, Strehl H, Bagci S, Franz AR, Mills PB, Clayton PT, Baumgartner MR, Steinmann B, Bast T, Wolf NI, Zschocke J: Pyridoxal 5'-phosphate may be curative in early-onset epileptic encephalopathy. J Inherit Metab Dis. 2007 Feb;30(1):96-9. Epub 2006 Dec 23. [PubMed:17216302 ] 5. Mills PB, Surtees RA, Champion MP, Beesley CE, Dalton N, Scambler PJ, Heales SJ, Briddon A, Scheimberg I, Hoffmann GF, Zschocke J, Clayton PT: Neonatal epileptic encephalopathy caused by mutations in the PNPO gene encoding pyridox(am)ine 5'-phosphate oxidase. Hum Mol Genet. 2005 Apr 15;14(8):1077-86. Epub 2005 Mar 16. [PubMed:15772097 ] Kind Protein Organism Human Pharmacological action unknown Actions cofactor General Function: Sphinganine-1-phosphate aldolase activity Specific Function: Cleaves phosphorylated sphingoid bases (PSBs), such as sphingosine-1-phosphate, into fatty aldehydes and phosphoethanolamine. Elevates stress-induced ceramide production and apoptosis. Gene Name: SGPL1 Uniprot ID: O95470 Uniprot Name: Sphingosine-1-phosphate lyase 1 Molecular Weight: 63523.265 Da References 1. Ikeda M, Kihara A, Igarashi Y: Sphingosine-1-phosphate lyase SPL is an endoplasmic reticulum-resident, integral membrane protein with the pyridoxal 5'-phosphate binding domain exposed to the cytosol. Biochem Biophys Res Commun. 2004 Dec 3;325(1):338-43. [PubMed:15522238 ] 2. Bobbin RP: PPADS, an ATP antagonist, attenuates the effects of a moderately intense sound on cochlear mechanics. Hear Res. 2001 Jun;156(1-2):10-6. [PubMed:11377878 ] Kind Protein Organism Human Pharmacological action unknown Actions cofactor General Function: Pyridoxal phosphate binding Specific Function: Transaminase involved in tyrosine breakdown. Converts tyrosine to p-hydroxyphenylpyruvate. Can catalyze the reverse reaction, using glutamic acid, with 2-oxoglutarate as cosubstrate (in vitro). Has much lower affinity and transaminase activity towards phenylalanine. Gene Name: TAT Uniprot ID: P17735 Uniprot Name: Tyrosine aminotransferase Molecular Weight: 50398.895 Da References 1. Biagini MR, Tozzi A, Marcucci R, Paniccia R, Fedi S, Milani S, Galli A, Ceni E, Capanni M, Manta R, Abbate R, Surrenti C: Hyperhomocysteinemia and hypercoagulability in primary biliary cirrhosis. World J Gastroenterol. 2006 Mar 14;12(10):1607-12. [PubMed:16570355 ] 2. Clayton TA, Lindon JC, Everett JR, Charuel C, Hanton G, Le Net JL, Provost JP, Nicholson JK: Hepatotoxin-induced hypertyrosinemia and its toxicological significance. Arch Toxicol. 2007 Mar;81(3):201-10. Epub 2006 Aug 11. [PubMed:16902803 ] 3. Kim SY, An JJ, Kim DW, Choi SH, Lee SH, Hwang SI, Kwon OS, Kang TC, Won MH, Cho SW, Park J, Eum WS, Lee KS, Choi SY: Tat-mediated protein transduction of human brain pyridoxine-5-P oxidase into PC12 cells. J Biochem Mol Biol. 2006 Jan 31;39(1):76-83. [PubMed:16466641 ] 4. Shaffer WA, Luong TN, Rothman SC, Kirsch JF: Quantitative chimeric analysis of six specificity determinants that differentiate Escherichia coli aspartate from tyrosine aminotransferase. Protein Sci. 2002 Dec;11(12):2848-59. [PubMed:12441383 ] 5. Venhorst J, ter Laak AM, Meijer M, van de Wetering I, Commandeur JN, Rooseboom M, Vermeulen NP: Modeling and molecular dynamics of glutamine transaminase K/cysteine conjugate beta-lyase. J Mol Graph Model. 2003 Sep;22(1):55-70. [PubMed:12798391 ] Kind Protein Organism Human Pharmacological action unknown Actions cofactor General Function: Transaminase activity Specific Function: Catalyzes the irreversible transamination of the L-tryptophan metabolite L-kynurenine to form kynurenic acid (KA). Metabolizes the cysteine conjugates of certain halogenated alkenes and alkanes to form reactive metabolites. Catalyzes the beta-elimination of S-conjugates and Se-conjugates of L-(seleno)cysteine, resulting in the cleavage of the C-S or C-Se bond. Gene Name: CCBL1 Uniprot ID: Q16773 Uniprot Name: Kynurenine--oxoglutarate transaminase 1 Molecular Weight: 47874.765 Da References 1. Cooper AJ, Bruschi SA, Anders MW: Toxic, halogenated cysteine S-conjugates and targeting of mitochondrial enzymes of energy metabolism. Biochem Pharmacol. 2002 Aug 15;64(4):553-64. [PubMed:12167474 ] 2. Mosca M, Croci C, Mostardini M, Breton J, Malyszko J, Avanzi N, Toma S, Benatti L, Gatti S: Tissue expression and translational control of rat kynurenine aminotransferase/glutamine transaminase K mRNAs. Biochim Biophys Acta. 2003 Jul 9;1628(1):1-10. [PubMed:12850267 ] 3. Zhang L, Cooper AJ, Krasnikov BF, Xu H, Bubber P, Pinto JT, Gibson GE, Hanigan MH: Cisplatin-induced toxicity is associated with platinum deposition in mouse kidney mitochondria in vivo and with selective inactivation of the alpha-ketoglutarate dehydrogenase complex in LLC-PK1 cells. Biochemistry. 2006 Jul 25;45(29):8959-71. [PubMed:16846239 ] 4. Venhorst J, ter Laak AM, Meijer M, van de Wetering I, Commandeur JN, Rooseboom M, Vermeulen NP: Modeling and molecular dynamics of glutamine transaminase K/cysteine conjugate beta-lyase. J Mol Graph Model. 2003 Sep;22(1):55-70. [PubMed:12798391 ] 5. Cooper AJ, Pinto JT: Cysteine S-conjugate beta-lyases. Amino Acids. 2006 Feb;30(1):1-15. Epub 2006 Feb 6. [PubMed:16463021 ] Kind Protein Organism Human Pharmacological action unknown Actions cofactor General Function: Threonine synthase activity Specific Function: Not Available Gene Name: THNSL1 Uniprot ID: Q8IYQ7 Uniprot Name: Threonine synthase-like 1 Molecular Weight: 83069.54 Da References 1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284 ] 2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423 ] Kind Protein Organism Human Pharmacological action unknown Actions cofactor General Function: Vitamin binding Specific Function: Phosphorylase is an important allosteric enzyme in carbohydrate metabolism. Enzymes from different sources differ in their regulatory mechanisms and in their natural substrates. However, all known phosphorylases share catalytic and structural properties. Gene Name: PYGL Uniprot ID: P06737 Uniprot Name: Glycogen phosphorylase, liver form Molecular Weight: 97147.82 Da References 1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284 ] 2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423 ] 3. Beauchamp NJ, Taybert J, Champion MP, Layet V, Heinz-Erian P, Dalton A, Tanner MS, Pronicka E, Sharrard MJ: High frequency of missense mutations in glycogen storage disease type VI. J Inherit Metab Dis. 2007 Oct;30(5):722-34. Epub 2007 Aug 21. [PubMed:17705025 ] Kind Protein Organism Human Pharmacological action unknown Actions cofactor General Function: Serine c-palmitoyltransferase activity Specific Function: Serine palmitoyltransferase (SPT). The heterodimer formed with LCB1/SPTLC1 constitutes the catalytic core. The composition of the serine palmitoyltransferase (SPT) complex determines the substrate preference. The SPTLC1-SPTLC2-SPTSSA complex shows a strong preference for C16-CoA substrate, while the SPTLC1-SPTLC2-SPTSSB complex displays a preference for C18-CoA substrate. Gene Name: SPTLC2 Uniprot ID: O15270 Uniprot Name: Serine palmitoyltransferase 2 Molecular Weight: 62923.765 Da References 1. Hanada K: Serine palmitoyltransferase, a key enzyme of sphingolipid metabolism. Biochim Biophys Acta. 2003 Jun 10;1632(1-3):16-30. [PubMed:12782147 ] 2. Tamura K, Mitsuhashi N, Hara-Nishimura I, Imai H: Characterization of an Arabidopsis cDNA encoding a subunit of serine palmitoyltransferase, the initial enzyme in sphingolipid biosynthesis. Plant Cell Physiol. 2001 Nov;42(11):1274-81. [PubMed:11726713 ] 3. Gable K, Han G, Monaghan E, Bacikova D, Natarajan M, Williams R, Dunn TM: Mutations in the yeast LCB1 and LCB2 genes, including those corresponding to the hereditary sensory neuropathy type I mutations, dominantly inactivate serine palmitoyltransferase. J Biol Chem. 2002 Mar 22;277(12):10194-200. Epub 2002 Jan 7. [PubMed:11781309 ] 4. Ikushiro H, Hayashi H, Kagamiyama H: A water-soluble homodimeric serine palmitoyltransferase from Sphingomonas paucimobilis EY2395T strain. Purification, characterization, cloning, and overproduction. J Biol Chem. 2001 May 25;276(21):18249-56. Epub 2001 Mar 12. [PubMed:11279212 ] 5. Tamura K, Nishiura H, Mori J, Imai H: Cloning and characterization of a cDNA encoding serine palmitoyltransferase in Arabidopsis thaliana. Biochem Soc Trans. 2000 Dec;28(6):745-7. [PubMed:11171191 ] Kind Protein Organism Human Pharmacological action unknown Actions cofactor General Function: Sulfinoalanine decarboxylase activity Specific Function: Not Available Gene Name: CSAD Uniprot ID: Q9Y600 Uniprot Name: Cysteine sulfinic acid decarboxylase Molecular Weight: 55022.79 Da References 1. Skoldberg F, Rorsman F, Perheentupa J, Landin-Olsson M, Husebye ES, Gustafsson J, Kampe O: Analysis of antibody reactivity against cysteine sulfinic acid decarboxylase, a pyridoxal phosphate-dependent enzyme, in endocrine autoimmune disease. J Clin Endocrinol Metab. 2004 Apr;89(4):1636-40. [PubMed:15070923 ] Kind Protein Organism Human Pharmacological action unknown Actions cofactor General Function: Pyridoxal phosphate binding Specific Function: Catalyzes the biosynthesis of histamine from histidine. Gene Name: HDC Uniprot ID: P19113 Uniprot Name: Histidine decarboxylase Molecular Weight: 74139.825 Da References 1. Skoldberg F, Portela-Gomes GM, Grimelius L, Nilsson G, Perheentupa J, Betterle C, Husebye ES, Gustafsson J, Ronnblom A, Rorsman F, Kampe O: Histidine decarboxylase, a pyridoxal phosphate-dependent enzyme, is an autoantigen of gastric enterochromaffin-like cells. J Clin Endocrinol Metab. 2003 Apr;88(4):1445-52. [PubMed:12679420 ] 2. Moya-Garcia AA, Pino-Angeles A, Sanchez-Jimenez F: New structural insights to help in the search for selective inhibitors of mammalian pyridoxal 5'-phosphate-dependent histidine decarboxylase . 4. Synthesis, metabolism and release of histamine. Inflamm Res. 2006 Apr;55 Suppl 1:S55-6. [PubMed:16547811 ] 3. Landete JM, Pardo I, Ferrer S: Histamine, histidine, and growth-phase mediated regulation of the histidine decarboxylase gene in lactic acid bacteria isolated from wine. FEMS Microbiol Lett. 2006 Jul;260(1):84-90. [PubMed:16790022 ] 4. Skoldberg F, Rorsman F, Perheentupa J, Landin-Olsson M, Husebye ES, Gustafsson J, Kampe O: Analysis of antibody reactivity against cysteine sulfinic acid decarboxylase, a pyridoxal phosphate-dependent enzyme, in endocrine autoimmune disease. J Clin Endocrinol Metab. 2004 Apr;89(4):1636-40. [PubMed:15070923 ] 5. Graham DE, Xu H, White RH: Methanococcus jannaschii uses a pyruvoyl-dependent arginine decarboxylase in polyamine biosynthesis. J Biol Chem. 2002 Jun 28;277(26):23500-7. Epub 2002 Apr 29. [PubMed:11980912 ] Kind Protein Organism Human Pharmacological action unknown Actions cofactor General Function: Putrescine transmembrane transporter activity Specific Function: Antizyme inhibitor protein that positively regulates ornithine decarboxylase (ODC) activity and polyamine uptake by counteracting the negative effect of antizymes OAZ1, OAZ2 and OAZ3 on ODC1 activity (PubMed:17900240). Inhibits antizyme-dependent ODC1 degradation by binding to antizymes. Releases ODC1 from its inactive complex with antizymes, leading to formation of the catalytically active ODC... Gene Name: AZIN2 Uniprot ID: Q96A70 Uniprot Name: Antizyme inhibitor 2 Molecular Weight: 49979.185 Da References 1. Graham DE, Xu H, White RH: Methanococcus jannaschii uses a pyruvoyl-dependent arginine decarboxylase in polyamine biosynthesis. J Biol Chem. 2002 Jun 28;277(26):23500-7. Epub 2002 Apr 29. [PubMed:11980912 ] 2. Patel CN, Adcock RS, Sell KG, Oliveira MA: Crystallization, X-ray diffraction and oligomeric characterization of arginine decarboxylase from Yersinia pestis, a key polyamine biosynthetic enzyme. Acta Crystallogr D Biol Crystallogr. 2004 Dec;60(Pt 12 Pt 2):2396-8. Epub 2004 Nov 26. [PubMed:15583399 ] 3. Kidron H, Repo S, Johnson MS, Salminen TA: Functional classification of amino acid decarboxylases from the alanine racemase structural family by phylogenetic studies. Mol Biol Evol. 2007 Jan;24(1):79-89. Epub 2006 Sep 22. [PubMed:16997906 ] 4. Arena ME, Manca de Nadra MC: Biogenic amine production by Lactobacillus. J Appl Microbiol. 2001 Feb;90(2):158-62. [PubMed:11168717 ] 5. Shah R, Akella R, Goldsmith EJ, Phillips MA: X-ray structure of Paramecium bursaria Chlorella virus arginine decarboxylase: insight into the structural basis for substrate specificity. Biochemistry. 2007 Mar 13;46(10):2831-41. Epub 2007 Feb 17. [PubMed:17305368 ] Kind Protein Organism Human Pharmacological action unknown Actions cofactor General Function: Pyridoxal phosphate binding Specific Function: Not Available Gene Name: SDS Uniprot ID: P20132 Uniprot Name: L-serine dehydratase/L-threonine deaminase Molecular Weight: 34625.105 Da References 1. Sun L, Bartlam M, Liu Y, Pang H, Rao Z: Crystal structure of the pyridoxal-5'-phosphate-dependent serine dehydratase from human liver. Protein Sci. 2005 Mar;14(3):791-8. Epub 2005 Feb 2. [PubMed:15689518 ] 2. Yamada T, Komoto J, Takata Y, Ogawa H, Pitot HC, Takusagawa F: Crystal structure of serine dehydratase from rat liver. Biochemistry. 2003 Nov 11;42(44):12854-65. [PubMed:14596599 ] 3. Sun L, Li X, Dong Y, Yang M, Liu Y, Han X, Zhang X, Pang H, Rao Z: Crystallization and preliminary crystallographic analysis of human serine dehydratase. Acta Crystallogr D Biol Crystallogr. 2003 Dec;59(Pt 12):2297-9. Epub 2003 Nov 27. [PubMed:14646100 ] 4. Ogawa H, Gomi T, Nishizawa M, Hayakawa Y, Endo S, Hayashi K, Ochiai H, Takusagawa F, Pitot HC, Mori H, Sakurai H, Koizumi K, Saiki I, Oda H, Fujishita T, Miwa T, Maruyama M, Kobayashi M: Enzymatic and biochemical properties of a novel human serine dehydratase isoform. Biochim Biophys Acta. 2006 May;1764(5):961-71. Epub 2006 Mar 20. [PubMed:16580895 ] 5. Cicchillo RM, Baker MA, Schnitzer EJ, Newman EB, Krebs C, Booker SJ: Escherichia coli L-serine deaminase requires a [4Fe-4S] cluster in catalysis. J Biol Chem. 2004 Jul 30;279(31):32418-25. Epub 2004 May 19. [PubMed:15155761 ] Kind Protein Organism Human Pharmacological action unknown Actions cofactor General Function: Pyridoxal phosphate binding Specific Function: Not Available Gene Name: GCAT Uniprot ID: O75600 Uniprot Name: 2-amino-3-ketobutyrate coenzyme A ligase, mitochondrial Molecular Weight: 45284.6 Da References 1. Schmidt A, Sivaraman J, Li Y, Larocque R, Barbosa JA, Smith C, Matte A, Schrag JD, Cygler M: Three-dimensional structure of 2-amino-3-ketobutyrate CoA ligase from Escherichia coli complexed with a PLP-substrate intermediate: inferred reaction mechanism. Biochemistry. 2001 May 1;40(17):5151-60. [PubMed:11318637 ] Kind Protein Organism Human Pharmacological action unknown Actions cofactor General Function: Lyase activity Specific Function: The glycine cleavage system catalyzes the degradation of glycine. The P protein (GLDC) binds the alpha-amino group of glycine through its pyridoxal phosphate cofactor; CO(2) is released and the remaining methylamine moiety is then transferred to the lipoamide cofactor of the H protein (GCSH). Gene Name: GLDC Uniprot ID: P23378 Uniprot Name: Glycine dehydrogenase (decarboxylating), mitochondrial Molecular Weight: 112728.805 Da References 1. Nakai T, Nakagawa N, Maoka N, Masui R, Kuramitsu S, Kamiya N: Structure of P-protein of the glycine cleavage system: implications for nonketotic hyperglycinemia. EMBO J. 2005 Apr 20;24(8):1523-36. Epub 2005 Mar 24. [PubMed:15791207 ] 2. Igamberdiev AU, Ivlev AA, Bykova NV, Threlkeld CN, Lea PJ, Gardestrom P: Decarboxylation of glycine contributes to carbon isotope fractionation in photosynthetic organisms. Photosynth Res. 2001;67(3):177-84. [PubMed:16228305 ] Kind Protein Organism Human Pharmacological action unknown Actions cofactor General Function: Pyridoxal phosphate binding Specific Function: Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate. Participates in cellular nitrogen metabolism and also in liver gluconeogenesis starting with precursors transported from skeletal muscles (By similarity). Gene Name: GPT Uniprot ID: P24298 Uniprot Name: Alanine aminotransferase 1 Molecular Weight: 54636.415 Da References 1. Cheung PY, Fong CC, Ng KT, Lam WC, Leung YC, Tsang CW, Yang M, Wong MS: Interaction between pyridoxal kinase and pyridoxal-5-phosphate-dependent enzymes. J Biochem. 2003 Nov;134(5):731-8. [PubMed:14688239 ] 2. Halfon P, Imbert-Bismut F, Messous D, Antoniotti G, Benchetrit D, Cart-Lamy P, Delaporte G, Doutheau D, Klump T, Sala M, Thibaud D, Trepo E, Thabut D, Myers RP, Poynard T: A prospective assessment of the inter-laboratory variability of biochemical markers of fibrosis (FibroTest) and activity (ActiTest) in patients with chronic liver disease. Comp Hepatol. 2002 Dec 30;1(1):3. [PubMed:12537583 ] 3. Inubushi T, Takasawa T, Tuboi Y, Watanabe N, Aki K, Katunuma N: Changes of glucose metabolism and skin-collagen neogenesis in vitamin B6 deficiency. Biofactors. 2005;23(2):59-67. [PubMed:16179747 ] 4. Baines CJ, McKeown-Eyssen GE, Riley N, Cole DE, Marshall L, Loescher B, Jazmaji V: Case-control study of multiple chemical sensitivity, comparing haematology, biochemistry, vitamins and serum volatile organic compound measures. Occup Med (Lond). 2004 Sep;54(6):408-18. Epub 2004 Sep 3. [PubMed:15347780 ] 5. Beranek M, Drsata J, Palicka V: Inhibitory effect of glycation on catalytic activity of alanine aminotransferase. Mol Cell Biochem. 2001 Feb;218(1-2):35-9. [PubMed:11330835 ] Kind Protein Organism Human Pharmacological action unknown Actions cofactor General Function: O-phospho-l-serine:2-oxoglutarate aminotransferase activity Specific Function: Catalyzes the reversible conversion of 3-phosphohydroxypyruvate to phosphoserine and of 3-hydroxy-2-oxo-4-phosphonooxybutanoate to phosphohydroxythreonine. Gene Name: PSAT1 Uniprot ID: Q9Y617 Uniprot Name: Phosphoserine aminotransferase Molecular Weight: 40422.355 Da References 1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284 ] 2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423 ] 3. Battchikova N, Himanen JP, Ahjolahti M, Korpela T: Phosphoserine aminotransferase from Bacillus circulans subsp. alkalophilus: purification, gene cloning and sequencing. Biochim Biophys Acta. 1996 Jul 18;1295(2):187-94. [PubMed:8695645 ] 4. Hester G, Stark W, Moser M, Kallen J, Markovic-Housley Z, Jansonius JN: Crystal structure of phosphoserine aminotransferase from Escherichia coli at 2.3 A resolution: comparison of the unligated enzyme and a complex with alpha-methyl-l-glutamate. J Mol Biol. 1999 Feb 26;286(3):829-50. [PubMed:10024454 ] 5. Kapetaniou EG, Thanassoulas A, Dubnovitsky AP, Nounesis G, Papageorgiou AC: Effect of pH on the structure and stability of Bacillus circulans ssp. alkalophilus phosphoserine aminotransferase: thermodynamic and crystallographic studies. Proteins. 2006 Jun 1;63(4):742-53. [PubMed:16532449 ] 6. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [PubMed:10592235 ] Kind Protein Organism Human Pharmacological action unknown Actions cofactor General Function: Pyridoxal phosphate binding Specific Function: Not Available Gene Name: ALAS1 Uniprot ID: P13196 Uniprot Name: 5-aminolevulinate synthase, nonspecific, mitochondrial Molecular Weight: 70580.325 Da References 1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284 ] 2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423 ] 3. Nakamura I, Isobe N, Nakamura N, Kamihara T, Fukui S: Mechanism of thiamine-induced respiratory deficiency in Saccharomyces carlsbergensis. J Bacteriol. 1981 Sep;147(3):954-61. [PubMed:7275938 ] 4. Harigae H, Furuyama K, Kudo K, Hayashi N, Yamamoto M, Sassa S, Sasaki T: A novel mutation of the erythroid-specific gamma-Aminolevulinate synthase gene in a patient with non-inherited pyridoxine-responsive sideroblastic anemia. Am J Hematol. 1999 Oct;62(2):112-4. [PubMed:10577279 ] 5. Shoolingin-Jordan PM, Al-Daihan S, Alexeev D, Baxter RL, Bottomley SS, Kahari ID, Roy I, Sarwar M, Sawyer L, Wang SF: 5-Aminolevulinic acid synthase: mechanism, mutations and medicine. Biochim Biophys Acta. 2003 Apr 11;1647(1-2):361-6. [PubMed:12686158 ] Kind Protein Organism Human Pharmacological action unknown Actions cofactor General Function: Transaminase activity Specific Function: Not Available Gene Name: AGXT Uniprot ID: P21549 Uniprot Name: Serine--pyruvate aminotransferase Molecular Weight: 43009.535 Da References 1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284 ] 2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423 ] 3. Coulter-Mackie MB, Lian Q: Consequences of missense mutations for dimerization and turnover of alanine:glyoxylate aminotransferase: study of a spectrum of mutations. Mol Genet Metab. 2006 Dec;89(4):349-59. Epub 2006 Sep 12. [PubMed:16971151 ] Kind Protein Organism Human Pharmacological action unknown Actions cofactor General Function: Pyridoxal phosphatase activity Specific Function: Protein serine phosphatase that dephosphorylates 'Ser-3' in cofilin and probably also dephosphorylates phospho-serine residues in DSTN. Regulates cofilin-dependent actin cytoskeleton reorganization. Required for normal progress through mitosis and normal cytokinesis. Does not dephosphorylate phospho-threonines in LIMK1. Does not dephosphorylate peptides containing phospho-tyrosine. Pyridoxal ph... Gene Name: PDXP Uniprot ID: Q96GD0 Uniprot Name: Pyridoxal phosphate phosphatase Molecular Weight: 31697.735 Da References 1. Jang YM, Kim DW, Kang TC, Won MH, Baek NI, Moon BJ, Choi SY, Kwon OS: Human pyridoxal phosphatase. Molecular cloning, functional expression, and tissue distribution. J Biol Chem. 2003 Dec 12;278(50):50040-6. Epub 2003 Sep 30. [PubMed:14522954 ] 2. McCarty MF: Increased homocyst(e)ine associated with smoking, chronic inflammation, and aging may reflect acute-phase induction of pyridoxal phosphatase activity. Med Hypotheses. 2000 Oct;55(4):289-93. [PubMed:11000053 ] 3. Hwang IK, Yoo KY, Kim do H, Lee BH, Kwon YG, Won MH: Time course of changes in pyridoxal 5'-phosphate (vitamin B6 active form) and its neuroprotection in experimental ischemic damage. Exp Neurol. 2007 Jul;206(1):114-25. Epub 2007 Apr 24. [PubMed:17531224 ] 4. Kim DW, Eum WS, Choi HS, Kim SY, An JJ, Lee SH, Sohn EJ, Hwang SI, Kwon OS, Kang TC, Won MH, Cho SW, Lee KS, Park J, Choi SY: Human brain pyridoxal-5'-phosphate phosphatase: production and characterization of monoclonal antibodies. J Biochem Mol Biol. 2005 Nov 30;38(6):703-8. [PubMed:16336786 ] 5. Tirrell IM, Wall JL, Daley CJ, Denial SJ, Tennis FG, Galens KG, O'Handley SF: YZGD from Paenibacillus thiaminolyticus, a pyridoxal phosphatase of the HAD (haloacid dehalogenase) superfamily and a versatile member of the Nudix (nucleoside diphosphate x) hydrolase superfamily. Biochem J. 2006 Mar 15;394(Pt 3):665-74. [PubMed:16336194 ] Kind Protein Organism Human Pharmacological action unknown Actions cofactor General Function: Serine c-palmitoyltransferase activity Specific Function: Serine palmitoyltransferase (SPT). The heterodimer formed with SPTLC2 or SPTLC3 constitutes the catalytic core. The composition of the serine palmitoyltransferase (SPT) complex determines the substrate preference. The SPTLC1-SPTLC2-SPTSSA complex shows a strong preference for C16-CoA substrate, while the SPTLC1-SPTLC3-SPTSSA isozyme uses both C14-CoA and C16-CoA as substrates, with a slight pre... Gene Name: SPTLC1 Uniprot ID: O15269 Uniprot Name: Serine palmitoyltransferase 1 Molecular Weight: 52743.41 Da References 1. Hanada K: Serine palmitoyltransferase, a key enzyme of sphingolipid metabolism. Biochim Biophys Acta. 2003 Jun 10;1632(1-3):16-30. [PubMed:12782147 ] 2. Gable K, Han G, Monaghan E, Bacikova D, Natarajan M, Williams R, Dunn TM: Mutations in the yeast LCB1 and LCB2 genes, including those corresponding to the hereditary sensory neuropathy type I mutations, dominantly inactivate serine palmitoyltransferase. J Biol Chem. 2002 Mar 22;277(12):10194-200. Epub 2002 Jan 7. [PubMed:11781309 ] 3. Ikushiro H, Hayashi H, Kagamiyama H: A water-soluble homodimeric serine palmitoyltransferase from Sphingomonas paucimobilis EY2395T strain. Purification, characterization, cloning, and overproduction. J Biol Chem. 2001 May 25;276(21):18249-56. Epub 2001 Mar 12. [PubMed:11279212 ] Kind Protein Organism Human Pharmacological action unknown Actions cofactor General Function: Pyridoxal phosphate binding Specific Function: Catalyzes the last step in the trans-sulfuration pathway from methionine to cysteine. Has broad substrate specificity. Converts cystathionine to cysteine, ammonia and 2-oxobutanoate. Converts two cysteine molecules to lanthionine and hydrogen sulfide. Can also accept homocysteine as substrate. Specificity depends on the levels of the endogenous substrates. Generates the endogenous signaling mol... Gene Name: CTH Uniprot ID: P32929 Uniprot Name: Cystathionine gamma-lyase Molecular Weight: 44507.64 Da References 1. Yamagata S, Akamatsu T, Iwama T: Immobilization of Saccharomyces cerevisiae cystathionine gamma-lyase and application of the product to cystathionine synthesis. Appl Environ Microbiol. 2004 Jun;70(6):3766-8. [PubMed:15184188 ] 2. Bertoldi M, Cellini B, Laurents DV, Borri Voltattorni C: Folding pathway of the pyridoxal 5'-phosphate C-S lyase MalY from Escherichia coli. Biochem J. 2005 Aug 1;389(Pt 3):885-98. [PubMed:15823094 ] 3. Lowicka E, Beltowski J: Hydrogen sulfide (H2S) - the third gas of interest for pharmacologists. Pharmacol Rep. 2007 Jan-Feb;59(1):4-24. [PubMed:17377202 ] 4. Lima CP, Davis SR, Mackey AD, Scheer JB, Williamson J, Gregory JF 3rd: Vitamin B-6 deficiency suppresses the hepatic transsulfuration pathway but increases glutathione concentration in rats fed AIN-76A or AIN-93G diets. J Nutr. 2006 Aug;136(8):2141-7. [PubMed:16857832 ] 5. Okuno T, Kubota T, Kuroda T, Ueno H, Nakamuro K: Contribution of enzymic alpha, gamma-elimination reaction in detoxification pathway of selenomethionine in mouse liver. Toxicol Appl Pharmacol. 2001 Oct 1;176(1):18-23. [PubMed:11578145 ] Kind Protein Organism Human Pharmacological action unknown Actions cofactor General Function: L-valine transaminase activity Specific Function: Catalyzes the first reaction in the catabolism of the essential branched chain amino acids leucine, isoleucine, and valine. Gene Name: BCAT1 Uniprot ID: P54687 Uniprot Name: Branched-chain-amino-acid aminotransferase, cytosolic Molecular Weight: 42965.815 Da References 1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284 ] 2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423 ] Kind Protein Organism Human Pharmacological action unknown Actions cofactor General Function: L-valine transaminase activity Specific Function: Catalyzes the first reaction in the catabolism of the essential branched chain amino acids leucine, isoleucine, and valine. May also function as a transporter of branched chain alpha-keto acids. Gene Name: BCAT2 Uniprot ID: O15382 Uniprot Name: Branched-chain-amino-acid aminotransferase, mitochondrial Molecular Weight: 44287.445 Da References 1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284 ] 2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423 ] Kind Protein Organism Human Pharmacological action unknown Actions cofactor General Function: Pyridoxal phosphate binding Specific Function: Not Available Gene Name: PROSC Uniprot ID: O94903 Uniprot Name: Proline synthase co-transcribed bacterial homolog protein Molecular Weight: 30343.7 Da References 1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284 ] 2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423 ] Kind Protein Organism Human Pharmacological action unknown Actions cofactor General Function: Microtubule binding Specific Function: Folate-dependent enzyme, that displays both transferase and deaminase activity. Serves to channel one-carbon units from formiminoglutamate to the folate pool.Binds and promotes bundling of vimentin filaments originating from the Golgi. Gene Name: FTCD Uniprot ID: O95954 Uniprot Name: Formimidoyltransferase-cyclodeaminase Molecular Weight: 58925.93 Da References 1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284 ] 2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423 ] Kind Protein Organism Human Pharmacological action unknown Actions cofactor General Function: Pyridoxal phosphate binding Specific Function: Catalyzes the irreversible transamination of the L-tryptophan metabolite L-kynurenine to form kynurenic acid (KA). Plays a key role in amino acid metabolism. Important for metabolite exchange between mitochondria and cytosol. Facilitates cellular uptake of long-chain free fatty acids. Gene Name: GOT2 Uniprot ID: P00505 Uniprot Name: Aspartate aminotransferase, mitochondrial Molecular Weight: 47517.285 Da References 1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284 ] 2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423 ] 3. Mavrides C, Orr W: Multispecific aspartate and aromatic amino acid aminotransferases in Escherichia coli. J Biol Chem. 1975 Jun 10;250(11):4128-33. [PubMed:236311 ] Kind Protein Organism Human Pharmacological action unknown Actions cofactor General Function: Pyridoxal phosphate binding Specific Function: Phosphorylase is an important allosteric enzyme in carbohydrate metabolism. Enzymes from different sources differ in their regulatory mechanisms and in their natural substrates. However, all known phosphorylases share catalytic and structural properties. Gene Name: PYGB Uniprot ID: P11216 Uniprot Name: Glycogen phosphorylase, brain form Molecular Weight: 96695.18 Da References 1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284 ] 2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423 ] Kind Protein Organism Human Pharmacological action unknown Actions cofactor General Function: Pyridoxal phosphate binding Specific Function: Phosphorylase is an important allosteric enzyme in carbohydrate metabolism. Enzymes from different sources differ in their regulatory mechanisms and in their natural substrates. However, all known phosphorylases share catalytic and structural properties. Gene Name: PYGM Uniprot ID: P11217 Uniprot Name: Glycogen phosphorylase, muscle form Molecular Weight: 97091.265 Da References 1. Livanova NB, Chebotareva NA, Eronina TB, Kurganov BI: Pyridoxal 5'-phosphate as a catalytic and conformational cofactor of muscle glycogen phosphorylase B. Biochemistry (Mosc). 2002 Oct;67(10):1089-98. [PubMed:12460107 ] 2. Kurganov BI, Kornilaev BA, Chebotareva NA, Malikov VP, Orlov VN, Lyubarev AE, Livanova NB: Dissociative mechanism of thermal denaturation of rabbit skeletal muscle glycogen phosphorylase b. Biochemistry. 2000 Oct 31;39(43):13144-52. [PubMed:11052666 ] 3. Okada M, Shibuya M, Yamamoto E, Murakami Y: Effect of diabetes on vitamin B6 requirement in experimental animals. Diabetes Obes Metab. 1999 Jul;1(4):221-5. [PubMed:11228757 ] 4. Okada M, Goda H, Kondo Y, Murakami Y, Shibuya M: Effect of exercise on the metabolism of vitamin B6 and some PLP-dependent enzymes in young rats fed a restricted vitamin B6 diet. J Nutr Sci Vitaminol (Tokyo). 2001 Apr;47(2):116-21. [PubMed:11508701 ] 5. Geremia S, Campagnolo M, Schinzel R, Johnson LN: Enzymatic catalysis in crystals of Escherichia coli maltodextrin phosphorylase. J Mol Biol. 2002 Sep 13;322(2):413-23. [PubMed:12217700 ] Kind Protein Organism Human Pharmacological action unknown Actions cofactor General Function: Pyridoxal phosphate binding Specific Function: Catalyzes the decarboxylation of L-3,4-dihydroxyphenylalanine (DOPA) to dopamine, L-5-hydroxytryptophan to serotonin and L-tryptophan to tryptamine. Gene Name: DDC Uniprot ID: P20711 Uniprot Name: Aromatic-L-amino-acid decarboxylase Molecular Weight: 53925.815 Da References 1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284 ] 2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423 ] 3. Rahman MK, Nagatsu T, Sakurai T, Hori S, Abe M, Matsuda M: Effect of pyridoxal phosphate deficiency on aromatic L-amino acid decarboxylase activity with L-DOPA and L-5-hydroxytryptophan as substrates in rats. Jpn J Pharmacol. 1982 Oct;32(5):803-11. [PubMed:6983619 ] 4. Rorsman F, Husebye ES, Winqvist O, Bjork E, Karlsson FA, Kampe O: Aromatic-L-amino-acid decarboxylase, a pyridoxal phosphate-dependent enzyme, is a beta-cell autoantigen. Proc Natl Acad Sci U S A. 1995 Sep 12;92(19):8626-9. [PubMed:7567987 ] 5. Bertoldi M, Borri Voltattorni C: Reaction of dopa decarboxylase with L-aromatic amino acids under aerobic and anaerobic conditions. Biochem J. 2000 Dec 1;352 Pt 2:533-8. [PubMed:11085948 ] 6. Allen GF, Neergheen V, Oppenheim M, Fitzgerald JC, Footitt E, Hyland K, Clayton PT, Land JM, Heales SJ: Pyridoxal 5'-phosphate deficiency causes a loss of aromatic L-amino acid decarboxylase in patients and human neuroblastoma cells, implications for aromatic L-amino acid decarboxylase and vitamin B(6) deficiency states. J Neurochem. 2010 Jul;114(1):87-96. doi: 10.1111/j.1471-4159.2010.06742.x. Epub 2010 Apr 9. [PubMed:20403077 ] Kind Protein Organism Human Pharmacological action unknown Actions cofactor General Function: Pyridoxal phosphate binding Specific Function: Not Available Gene Name: GIG18 Uniprot ID: Q2TU84 Uniprot Name: Aspartate aminotransferase Molecular Weight: 46319.2 Da References 1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284 ] 2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423 ] Kind Protein Organism Human Pharmacological action unknown Actions cofactor General Function: Pyridoxal phosphate binding Specific Function: Catalyzes the production of GABA. Gene Name: GAD1 Uniprot ID: Q99259 Uniprot Name: Glutamate decarboxylase 1 Molecular Weight: 66896.065 Da References 1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284 ] 2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423 ] 3. Bennett CL, Huynh HM, Chance PF, Glass IA, Gospe SM Jr: Genetic heterogeneity for autosomal recessive pyridoxine-dependent seizures. Neurogenetics. 2005 Sep;6(3):143-9. Epub 2005 Aug 2. [PubMed:16075246 ] 4. Vassort C, Riviere M, Bruneau G, Gros F, Thibault J, Levan G, Szpirer J, Szpirer C: Assignment of the rat genes coding for dopa decarboxylase (DDC) and glutamic acid decarboxylases (GAD1 and GAD2). Mamm Genome. 1993;4(4):202-6. [PubMed:8499653 ] 5. Cormier-Daire V, Dagoneau N, Nabbout R, Burglen L, Penet C, Soufflet C, Desguerre I, Munnich A, Dulac O: A gene for pyridoxine-dependent epilepsy maps to chromosome 5q31. Am J Hum Genet. 2000 Oct;67(4):991-3. Epub 2000 Sep 7. [PubMed:10978228 ] Kind Protein Organism Human Pharmacological action unknown Actions cofactor General Function: Pyridoxal phosphate binding Specific Function: Interconversion of serine and glycine. Gene Name: Not Available Uniprot ID: Q53ET4 Uniprot Name: Serine hydroxymethyltransferase Molecular Weight: 55973.345 Da References 1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284 ] 2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423 ] 3. Mehta R, Shangari N, O'Brien PJ: Preventing cell death induced by carbonyl stress, oxidative stress or mitochondrial toxins with vitamin B anti-AGE agents. Mol Nutr Food Res. 2008 Mar;52(3):379-85. [PubMed:17918169 ] Kind Protein Organism Human Pharmacological action unknown Actions cofactor General Function: Lyase activity Specific Function: Not Available Gene Name: Not Available Uniprot ID: Q59FK2 Uniprot Name: Selenocysteine lyase variant Molecular Weight: 25484.43 Da References 1. Heidenreich T, Wollers S, Mendel RR, Bittner F: Characterization of the NifS-like domain of ABA3 from Arabidopsis thaliana provides insight into the mechanism of molybdenum cofactor sulfuration. J Biol Chem. 2005 Feb 11;280(6):4213-8. Epub 2004 Nov 22. [PubMed:15561708 ] Kind Protein Organism Human Pharmacological action unknown Actions cofactor General Function: Pyridoxal phosphate binding Specific Function: Phosphorylase is an important allosteric enzyme in carbohydrate metabolism. Enzymes from different sources differ in their regulatory mechanisms and in their natural substrates. However, all known phosphorylases share catalytic and structural properties. Gene Name: Not Available Uniprot ID: Q59GM9 Uniprot Name: Alpha-1,4 glucan phosphorylase Molecular Weight: 98828.62 Da References 1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284 ] 2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423 ] Kind Protein Organism Human Pharmacological action unknown Actions cofactor General Function: Transaminase activity Specific Function: Not Available Gene Name: Not Available Uniprot ID: Q59HE2 Uniprot Name: Ornithine aminotransferase variant Molecular Weight: 30736.21 Da References 1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284 ] 2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423 ] Kind Protein Organism Human Pharmacological action unknown Actions cofactor General Function: Pyridoxal phosphate binding Specific Function: Not Available Gene Name: ALAS1 Uniprot ID: Q5JAM2 Uniprot Name: 5-aminolevulinate synthase Molecular Weight: 70580.325 Da References 1. Ferreira GC, Zhang JS: Mechanism of 5-aminolevulinate synthase and the role of the protein environment in controlling the cofactor chemistry. Cell Mol Biol (Noisy-le-grand). 2002 Dec;48(8):827-33. [PubMed:12699240 ] 2. Choi HP, Hong JW, Rhee KH, Sung HC: Cloning, expression, and characterization of 5-aminolevulinic acid synthase from Rhodopseudomonas palustris KUGB306. FEMS Microbiol Lett. 2004 Jul 15;236(2):175-81. [PubMed:15251194 ] 3. Zhang J, Ferreira GC: Transient state kinetic investigation of 5-aminolevulinate synthase reaction mechanism. J Biol Chem. 2002 Nov 22;277(47):44660-9. Epub 2002 Aug 20. [PubMed:12191993 ] 4. Turbeville TD, Zhang J, Hunter GA, Ferreira GC: Histidine 282 in 5-aminolevulinate synthase affects substrate binding and catalysis. Biochemistry. 2007 May 22;46(20):5972-81. Epub 2007 May 1. [PubMed:17469798 ] 5. Zhang J, Cheltsov AV, Ferreira GC: Conversion of 5-aminolevulinate synthase into a more active enzyme by linking the two subunits: spectroscopic and kinetic properties. Protein Sci. 2005 May;14(5):1190-200. [PubMed:15840827 ] Kind Protein Organism Human Pharmacological action unknown Actions cofactor General Function: Pyridoxal phosphate binding Specific Function: Not Available Gene Name: GAD2 Uniprot ID: Q5VZ30 Uniprot Name: Glutamate decarboxylase 2 (Pancreatic islets and brain, 65kDa) Molecular Weight: 65410.77 Da References 1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284 ] 2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423 ] 3. Bennett CL, Huynh HM, Chance PF, Glass IA, Gospe SM Jr: Genetic heterogeneity for autosomal recessive pyridoxine-dependent seizures. Neurogenetics. 2005 Sep;6(3):143-9. Epub 2005 Aug 2. [PubMed:16075246 ] 4. Vassort C, Riviere M, Bruneau G, Gros F, Thibault J, Levan G, Szpirer J, Szpirer C: Assignment of the rat genes coding for dopa decarboxylase (DDC) and glutamic acid decarboxylases (GAD1 and GAD2). Mamm Genome. 1993;4(4):202-6. [PubMed:8499653 ] 5. Cormier-Daire V, Dagoneau N, Nabbout R, Burglen L, Penet C, Soufflet C, Desguerre I, Munnich A, Dulac O: A gene for pyridoxine-dependent epilepsy maps to chromosome 5q31. Am J Hum Genet. 2000 Oct;67(4):991-3. Epub 2000 Sep 7. [PubMed:10978228 ] Kind Protein Organism Human Pharmacological action unknown Actions cofactor General Function: Pyridoxal phosphate binding Specific Function: Not Available Gene Name: DDC Uniprot ID: Q6IBS8 Uniprot Name: DDC protein Molecular Weight: 53879.725 Da References 1. Tan EK, Cheah SY, Fook-Chong S, Yew K, Chandran VR, Lum SY, Yi Z: Functional COMT variant predicts response to high dose pyridoxine in Parkinson's disease. Am J Med Genet B Neuropsychiatr Genet. 2005 Aug 5;137B(1):1-4. [PubMed:15965967 ] 2. Bertoldi M, Borri Voltattorni C: Reaction of dopa decarboxylase with L-aromatic amino acids under aerobic and anaerobic conditions. Biochem J. 2000 Dec 1;352 Pt 2:533-8. [PubMed:11085948 ] 3. Yee RE, Cheng DW, Huang SC, Namavari M, Satyamurthy N, Barrio JR: Blood-brain barrier and neuronal membrane transport of 6-[18F]fluoro-L-DOPA. Biochem Pharmacol. 2001 Nov 15;62(10):1409-15. [PubMed:11709201 ] 4. Skoldberg F, Portela-Gomes GM, Grimelius L, Nilsson G, Perheentupa J, Betterle C, Husebye ES, Gustafsson J, Ronnblom A, Rorsman F, Kampe O: Histidine decarboxylase, a pyridoxal phosphate-dependent enzyme, is an autoantigen of gastric enterochromaffin-like cells. J Clin Endocrinol Metab. 2003 Apr;88(4):1445-52. [PubMed:12679420 ] 5. Skoldberg F, Rorsman F, Perheentupa J, Landin-Olsson M, Husebye ES, Gustafsson J, Kampe O: Analysis of antibody reactivity against cysteine sulfinic acid decarboxylase, a pyridoxal phosphate-dependent enzyme, in endocrine autoimmune disease. J Clin Endocrinol Metab. 2004 Apr;89(4):1636-40. [PubMed:15070923 ] Kind Protein Organism Human Pharmacological action unknown Actions cofactor General Function: Pyridoxal phosphate binding Specific Function: Not Available Gene Name: PDXDC1 Uniprot ID: Q6P996 Uniprot Name: Pyridoxal-dependent decarboxylase domain-containing protein 1 Molecular Weight: 86706.135 Da References 1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284 ] 2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423 ] Kind Protein Organism Human Pharmacological action unknown Actions cofactor General Function: Pyridoxal phosphate binding Specific Function: Catalyzes the irreversible transamination of the L-tryptophan metabolite L-kynurenine to form kynurenic acid (KA). May catalyze the beta-elimination of S-conjugates and Se-conjugates of L-(seleno)cysteine, resulting in the cleavage of the C-S or C-Se bond (By similarity). Has transaminase activity towards L-kynurenine, tryptophan, phenylalanine, serine, cysteine, methionine, histidine, glutamin... Gene Name: CCBL2 Uniprot ID: Q6YP21 Uniprot Name: Kynurenine--oxoglutarate transaminase 3 Molecular Weight: 51399.855 Da References 1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284 ] 2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423 ] Kind Protein Organism Human Pharmacological action unknown Actions cofactor General Function: Sulfinoalanine decarboxylase activity Specific Function: May catalyze the decarboxylation of aspartate, cysteine sulfinic acid, and cysteic acid to beta-alanine, hypotaurine and taurine, respectively. Does not exhibit any decarboxylation activity toward glutamate. Gene Name: GADL1 Uniprot ID: Q6ZQY3 Uniprot Name: Acidic amino acid decarboxylase GADL1 Molecular Weight: 59245.95 Da References 1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284 ] 2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423 ] Kind Protein Organism Human Pharmacological action unknown Actions cofactor General Function: Transferase activity Specific Function: Catalyzes the decomposition of L-selenocysteine to L-alanine and elemental selenium. Gene Name: SCLY Uniprot ID: Q96I15 Uniprot Name: Selenocysteine lyase Molecular Weight: 48148.45 Da References 1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284 ] 2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423 ] 3. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [PubMed:10592235 ] Kind Protein Organism Human Pharmacological action unknown Actions cofactor General Function: Not Available Specific Function: May be involved in the maintenance of osteochondroprogenitor cells pool. Gene Name: IGSF10 Uniprot ID: Q6WRI0 Uniprot Name: Immunoglobulin superfamily member 10 Molecular Weight: 290835.42 Da References 1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284 ] 2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423 ] 3. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [PubMed:10592235 ] Kind Protein Organism Human Pharmacological action unknown Actions cofactor General Function: Transaminase activity Specific Function: Catalyzes the pyridoxal-phosphate-dependent breakdown of 5-phosphohydroxy-L-lysine, converting it to ammonia, inorganic phosphate and 2-aminoadipate semialdehyde. Gene Name: PHYKPL Uniprot ID: Q8IUZ5 Uniprot Name: 5-phosphohydroxy-L-lysine phospho-lyase Molecular Weight: 49710.245 Da References 1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284 ] 2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423 ] Kind Protein Organism Human Pharmacological action unknown Actions cofactor General Function: Pyridoxal phosphate binding Specific Function: Not Available Gene Name: GAD1 Uniprot ID: Q8IVA8 Uniprot Name: Glutamate decarboxylase 1 (Brain, 67kDa) Molecular Weight: 66916.045 Da References 1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284 ] 2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423 ] 3. Bennett CL, Huynh HM, Chance PF, Glass IA, Gospe SM Jr: Genetic heterogeneity for autosomal recessive pyridoxine-dependent seizures. Neurogenetics. 2005 Sep;6(3):143-9. Epub 2005 Aug 2. [PubMed:16075246 ] 4. Vassort C, Riviere M, Bruneau G, Gros F, Thibault J, Levan G, Szpirer J, Szpirer C: Assignment of the rat genes coding for dopa decarboxylase (DDC) and glutamic acid decarboxylases (GAD1 and GAD2). Mamm Genome. 1993;4(4):202-6. [PubMed:8499653 ] 5. Cormier-Daire V, Dagoneau N, Nabbout R, Burglen L, Penet C, Soufflet C, Desguerre I, Munnich A, Dulac O: A gene for pyridoxine-dependent epilepsy maps to chromosome 5q31. Am J Hum Genet. 2000 Oct;67(4):991-3. Epub 2000 Sep 7. [PubMed:10978228 ] Kind Protein Organism Human Pharmacological action unknown Actions cofactor General Function: Pyridoxal phosphate binding Specific Function: Contributes to the de novo mitochondrial thymidylate biosynthesis pathway. Required to prevent uracil accumulation in mtDNA. Interconversion of serine and glycine. Associates with mitochondrial DNA. Gene Name: SHMT2 Uniprot ID: P34897 Uniprot Name: Serine hydroxymethyltransferase, mitochondrial Molecular Weight: 55992.385 Da References 1. Bhavani S, Trivedi V, Jala VR, Subramanya HS, Kaul P, Prakash V, Appaji Rao N, Savithri HS: Role of Lys-226 in the catalytic mechanism of Bacillus stearothermophilus serine hydroxymethyltransferase--crystal structure and kinetic studies. Biochemistry. 2005 May 10;44(18):6929-37. [PubMed:15865438 ] 2. Trivedi V, Gupta A, Jala VR, Saravanan P, Rao GS, Rao NA, Savithri HS, Subramanya HS: Crystal structure of binary and ternary complexes of serine hydroxymethyltransferase from Bacillus stearothermophilus: insights into the catalytic mechanism. J Biol Chem. 2002 May 10;277(19):17161-9. Epub 2002 Feb 27. [PubMed:11877399 ] 3. Perry C, Yu S, Chen J, Matharu KS, Stover PJ: Effect of vitamin B6 availability on serine hydroxymethyltransferase in MCF-7 cells. Arch Biochem Biophys. 2007 Jun 1;462(1):21-7. Epub 2007 Apr 20. [PubMed:17482557 ] 4. Rajaram V, Bhavani BS, Kaul P, Prakash V, Appaji Rao N, Savithri HS, Murthy MR: Structure determination and biochemical studies on Bacillus stearothermophilus E53Q serine hydroxymethyltransferase and its complexes provide insights on function and enzyme memory. FEBS J. 2007 Aug;274(16):4148-60. Epub 2007 Jul 25. [PubMed:17651438 ] 5. Mukherjee M, Sievers SA, Brown MT, Johnson PJ: Identification and biochemical characterization of serine hydroxymethyl transferase in the hydrogenosome of Trichomonas vaginalis. Eukaryot Cell. 2006 Dec;5(12):2072-8. Epub 2006 Sep 15. [PubMed:16980404 ] 6. Trakatellis A, Dimitriadou A, Exindari M, Christodoulou D, Malissiovas N, Antoniadis A, Haitoglou K: Effect of combination of deoxypyridoxine with known anti-proliferative or immunosuppressive agents on lymphocyte serine hydroxymethyltransferase. Postgrad Med J. 1994;70 Suppl 1:S89-92. [PubMed:7526359 ] 7. Jagath JR, Sharma B, Rao NA, Savithri HS: The role of His-134, -147, and -150 residues in subunit assembly, cofactor binding, and catalysis of sheep liver cytosolic serine hydroxymethyltransferase. J Biol Chem. 1997 Sep 26;272(39):24355-62. [PubMed:9305893 ] 8. Bourguignon J, Neuburger M, Douce R: Resolution and characterization of the glycine-cleavage reaction in pea leaf mitochondria. Properties of the forward reaction catalysed by glycine decarboxylase and serine hydroxymethyltransferase. Biochem J. 1988 Oct 1;255(1):169-78. [PubMed:3143355 ] Kind Protein Organism Human Pharmacological action unknown Actions cofactor General Function: Pyridoxal phosphate binding Specific Function: Not Available Gene Name: ALAS2 Uniprot ID: P22557 Uniprot Name: 5-aminolevulinate synthase, erythroid-specific, mitochondrial Molecular Weight: 64632.86 Da References 1. Shoolingin-Jordan PM, Al-Daihan S, Alexeev D, Baxter RL, Bottomley SS, Kahari ID, Roy I, Sarwar M, Sawyer L, Wang SF: 5-Aminolevulinic acid synthase: mechanism, mutations and medicine. Biochim Biophys Acta. 2003 Apr 11;1647(1-2):361-6. [PubMed:12686158 ] 2. Choi HP, Hong JW, Rhee KH, Sung HC: Cloning, expression, and characterization of 5-aminolevulinic acid synthase from Rhodopseudomonas palustris KUGB306. FEMS Microbiol Lett. 2004 Jul 15;236(2):175-81. [PubMed:15251194 ] 3. Heller T, Hochstetter V, Basler M, Borck V: [Vitamin B6-sensitive hereditary sideroblastic anemia]. Dtsch Med Wochenschr. 2004 Jan 23;129(4):141-4. [PubMed:14724775 ] 4. Clayton PT: B6-responsive disorders: a model of vitamin dependency. J Inherit Metab Dis. 2006 Apr-Jun;29(2-3):317-26. [PubMed:16763894 ] 5. Astner I, Schulze JO, van den Heuvel J, Jahn D, Schubert WD, Heinz DW: Crystal structure of 5-aminolevulinate synthase, the first enzyme of heme biosynthesis, and its link to XLSA in humans. EMBO J. 2005 Sep 21;24(18):3166-77. Epub 2005 Aug 25. [PubMed:16121195 ] Kind Protein Organism Human Pharmacological action unknown Actions cofactor General Function: Pyridoxal phosphate binding Specific Function: Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate. Gene Name: GPT2 Uniprot ID: Q8TD30 Uniprot Name: Alanine aminotransferase 2 Molecular Weight: 57903.11 Da References 1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284 ] 2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423 ] 3. Welch S: Comparative studies on the human glutamate-pyruvate transaminase phenotypes--GPT 1, GPT 2-1, GPT 2. Humangenetik. 1975 Sep 20;30(3):237-49. [PubMed:241701 ] Kind Protein Organism Human Pharmacological action unknown Actions cofactor General Function: Transferase activity Specific Function: Sulfurates the molybdenum cofactor. Sulfation of molybdenum is essential for xanthine dehydrogenase (XDH) and aldehyde oxidase (ADO) enzymes in which molybdenum cofactor is liganded by 1 oxygen and 1 sulfur atom in active form. In vitro, the C-terminal domain is able to reduce N-hydroxylated prodrugs, such as benzamidoxime. Gene Name: MOCOS Uniprot ID: Q96EN8 Uniprot Name: Molybdenum cofactor sulfurase Molecular Weight: 98118.965 Da References 1. Heidenreich T, Wollers S, Mendel RR, Bittner F: Characterization of the NifS-like domain of ABA3 from Arabidopsis thaliana provides insight into the mechanism of molybdenum cofactor sulfuration. J Biol Chem. 2005 Feb 11;280(6):4213-8. Epub 2004 Nov 22. [PubMed:15561708 ] 2. Mendel RR, Bittner F: Cell biology of molybdenum. Biochim Biophys Acta. 2006 Jul;1763(7):621-35. Epub 2006 May 12. [PubMed:16784786 ] 3. Anantharaman V, Aravind L: MOSC domains: ancient, predicted sulfur-carrier domains, present in diverse metal-sulfur cluster biosynthesis proteins including Molybdenum cofactor sulfurases. FEMS Microbiol Lett. 2002 Jan 22;207(1):55-61. [PubMed:11886751 ] 4. Bittner F, Oreb M, Mendel RR: ABA3 is a molybdenum cofactor sulfurase required for activation of aldehyde oxidase and xanthine dehydrogenase in Arabidopsis thaliana. J Biol Chem. 2001 Nov 2;276(44):40381-4. Epub 2001 Sep 11. [PubMed:11553608 ] Kind Protein Organism Human Pharmacological action unknown Actions cofactor General Function: Pyridoxal phosphate binding Specific Function: Has low serine dehydratase and threonine dehydratase activity. Gene Name: SDSL Uniprot ID: Q96GA7 Uniprot Name: Serine dehydratase-like Molecular Weight: 34674.01 Da References 1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284 ] 2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423 ] Kind Protein Organism Human Pharmacological action unknown Actions cofactor General Function: Pyridoxal phosphate binding Specific Function: Not Available Gene Name: pcap Uniprot ID: Q96JQ3 Uniprot Name: P-selectin cytoplasmic tail-associated protein (PCAP) Molecular Weight: 29222.465 Da References 1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284 ] 2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423 ] Kind Protein Organism Human Pharmacological action unknown Actions cofactor General Function: Transaminase activity Specific Function: Not Available Gene Name: Not Available Uniprot ID: Q9BXA1 Uniprot Name: Hepatic peroxysomal alanine:glyoxylate aminotransferase Molecular Weight: 39774.51 Da References 1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284 ] 2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423 ] Kind Protein Organism Human Pharmacological action unknown Actions cofactor General Function: Threonine racemase activity Specific Function: Catalyzes the synthesis of D-serine from L-serine. D-serine is a key coagonist with glutamate at NMDA receptors. Has dehydratase activity towards both L-serine and D-serine. Gene Name: SRR Uniprot ID: Q9GZT4 Uniprot Name: Serine racemase Molecular Weight: 36565.905 Da References 1. Hashimoto A, Yoshikawa M: Effect of aminooxyacetic acid on extracellular level of D-serine in rat striatum: an in vivo microdialysis study. Eur J Pharmacol. 2005 Nov 21;525(1-3):91-3. Epub 2005 Nov 14. [PubMed:16289454 ] 2. Strisovsky K, Jiraskova J, Mikulova A, Rulisek L, Konvalinka J: Dual substrate and reaction specificity in mouse serine racemase: identification of high-affinity dicarboxylate substrate and inhibitors and analysis of the beta-eliminase activity. Biochemistry. 2005 Oct 4;44(39):13091-100. [PubMed:16185077 ] 3. Schell MJ: The N-methyl D-aspartate receptor glycine site and D-serine metabolism: an evolutionary perspective. Philos Trans R Soc Lond B Biol Sci. 2004 Jun 29;359(1446):943-64. [PubMed:15306409 ] 4. Strisovsky K, Jiraskova J, Barinka C, Majer P, Rojas C, Slusher BS, Konvalinka J: Mouse brain serine racemase catalyzes specific elimination of L-serine to pyruvate. FEBS Lett. 2003 Jan 30;535(1-3):44-8. [PubMed:12560076 ] 5. Uo T, Yoshimura T, Nishiyama T, Esaki N: Gene cloning, purification, and characterization of 2,3-diaminopropionate ammonia-lyase from Escherichia coli. Biosci Biotechnol Biochem. 2002 Dec;66(12):2639-44. [PubMed:12596860 ] Kind Protein Organism Human Pharmacological action unknown Actions cofactor General Function: Trna binding Specific Function: Converts O-phosphoseryl-tRNA(Sec) to selenocysteinyl-tRNA(Sec) required for selenoprotein biosynthesis. Gene Name: SEPSECS Uniprot ID: Q9HD40 Uniprot Name: O-phosphoseryl-tRNA(Sec) selenium transferase Molecular Weight: 55725.69 Da References 1. Xu XM, Carlson BA, Mix H, Zhang Y, Saira K, Glass RS, Berry MJ, Gladyshev VN, Hatfield DL: Biosynthesis of selenocysteine on its tRNA in eukaryotes. PLoS Biol. 2007 Jan;5(1):e4. [PubMed:17194211 ] 2. Kernebeck T, Lohse AW, Grotzinger J: A bioinformatical approach suggests the function of the autoimmune hepatitis target antigen soluble liver antigen/liver pancreas. Hepatology. 2001 Aug;34(2):230-3. [PubMed:11481605 ] Kind Protein Organism Human Pharmacological action unknown Actions cofactor General Function: Serine c-palmitoyltransferase activity Specific Function: Serine palmitoyltransferase (SPT). The heterodimer formed with LCB1/SPTLC1 constitutes the catalytic core. The composition of the serine palmitoyltransferase (SPT) complex determines the substrate preference. The SPTLC1-SPTLC3-SPTSSA isozyme uses both C14-CoA and C16-CoA as substrates, while the SPTLC1-SPTLC3-SPTSSB has the ability to use a broader range of acyl-CoAs without apparent preference. Gene Name: SPTLC3 Uniprot ID: Q9NUV7 Uniprot Name: Serine palmitoyltransferase 3 Molecular Weight: 62049.035 Da References 1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284 ] 2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423 ] Kind Protein Organism Human Pharmacological action unknown Actions cofactor General Function: Pyridoxal phosphate binding Specific Function: Not Available Gene Name: GAD65 Uniprot ID: Q9UGI5 Uniprot Name: Glutamic acid decarboxylase Molecular Weight: 47343.69 Da References 1. Tong JC, Myers MA, Mackay IR, Zimmet PZ, Rowley MJ: The PEVKEK region of the pyridoxal phosphate binding domain of GAD65 expresses a dominant B cell epitope for type 1 diabetes sera. Ann N Y Acad Sci. 2002 Apr;958:182-9. [PubMed:12021103 ] 2. Burd L, Stenehjem A, Franceschini LA, Kerbeshian J: A 15-year follow-up of a boy with pyridoxine (vitamin B6)-dependent seizures with autism, breath holding, and severe mental retardation. J Child Neurol. 2000 Nov;15(11):763-5. [PubMed:11108513 ] 3. Myers MA, Davies JM, Tong JC, Whisstock J, Scealy M, Mackay IR, Rowley MJ: Conformational epitopes on the diabetes autoantigen GAD65 identified by peptide phage display and molecular modeling. J Immunol. 2000 Oct 1;165(7):3830-8. [PubMed:11034389 ] 4. Gospe SM Jr: Pyridoxine-dependent seizures: new genetic and biochemical clues to help with diagnosis and treatment. Curr Opin Neurol. 2006 Apr;19(2):148-53. [PubMed:16538088 ] 5. Hwang IK, Yoo KY, Kim do H, Lee BH, Kwon YG, Won MH: Time course of changes in pyridoxal 5'-phosphate (vitamin B6 active form) and its neuroprotection in experimental ischemic damage. Exp Neurol. 2007 Jul;206(1):114-25. Epub 2007 Apr 24. [PubMed:17531224 ] Kind Protein Organism Human Pharmacological action unknown Actions cofactor General Function: Transaminase activity Specific Function: Not Available Gene Name: TLH6 Uniprot ID: Q9UJX1 Uniprot Name: Alanine-glyoxylate aminotransferase homolog Molecular Weight: 28429.215 Da References 1. Nishijima S, Sugaya K, Morozumi M, Hatano T, Ogawa Y: Hepatic alanine-glyoxylate aminotransferase activity and oxalate metabolism in vitamin B6 deficient rats. J Urol. 2003 Feb;169(2):683-6. [PubMed:12544342 ] 2. Gable K, Han G, Monaghan E, Bacikova D, Natarajan M, Williams R, Dunn TM: Mutations in the yeast LCB1 and LCB2 genes, including those corresponding to the hereditary sensory neuropathy type I mutations, dominantly inactivate serine palmitoyltransferase. J Biol Chem. 2002 Mar 22;277(12):10194-200. Epub 2002 Jan 7. [PubMed:11781309 ] 3. Nishijima S, Sugaya K, Morozumi M, Hatano T, Ogawa Y: Capillary electrophoresis assay of alanine:glyoxylate aminotransferase activity in rat liver. J Chromatogr B Analyt Technol Biomed Life Sci. 2002 Nov 15;780(1):13-9. [PubMed:12383475 ] 4. Nishijima S, Sugaya K, Hokama S, Oshiro Y, Uchida A, Morozumi M, Ogawa Y: Effect of vitamin B6 deficiency on glyoxylate metabolism in rats with or without glyoxylate overload. Biomed Res. 2006 Jun;27(3):93-8. [PubMed:16847354 ] 5. Danpure CJ, Lumb MJ, Birdsey GM, Zhang X: Alanine:glyoxylate aminotransferase peroxisome-to-mitochondrion mistargeting in human hereditary kidney stone disease. Biochim Biophys Acta. 2003 Apr 11;1647(1-2):70-5. [PubMed:12686111 ] Drug created on June 13, 2005 07:24 / Updated on August 02, 2017 16:20
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https://hal-riip.archives-ouvertes.fr/pasteur-01009437Chevarie-Davis, M.M.Chevarie-DavisMcGill University = Université McGill [Montréal, Canada]Ramanakumar, A. V.A. V.RamanakumarMcGill University = Université McGill [Montréal, Canada]Ferenczy, A.A.FerenczyJewish General HospitalVilla, L. L.L. L.VillaLudwig Institute for Cancer Research - Ludwig Institute for Cancer ResearchFranco, E. L.E. L.FrancoMcGill University = Université McGill [Montréal, Canada]Assessment of the performance of algorithms for cervical cancer screening: evidence from the Ludwig-McGill cohort study.HAL CCSD2013ScreeningCervical cancerHuman papillomavirusEpidemiologyCervical cytologyHPV DNA testing[SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseasesLaflamme, Nancy2014-06-17 20:01:542020-06-18 12:32:052014-08-20 11:23:10enJournal articleshttps://hal-riip.archives-ouvertes.fr/pasteur-01009437/document10.1016/j.ygyno.2012.12.008application/pdf1OBJECTIVE: There are currently multiple tests available for cervical cancer screening and the existing screening policies vary from country to country. No single approach will satisfy the specific needs and variations in risk aversion of all populations, and screening algorithms should be tailored to specific groups. We performed long term risk stratification based on screening test results and compared the accuracy of different tests and their combinations. METHODS: A longitudinal cohort study of the natural history of HPV infection and cervical neoplasia enrolled 2462 women from a low-income population in Brazil. The interviews and cervical screening with cytology and HPV DNA testing were repeated according to a pre-established protocol and the subjects were referred for colposcopy and biopsy whenever high grade lesions were suspected. We compared the specificity, sensitivity and predictive values of each screening modality. Long term risk stratification was performed through time-to-event analyses using Kaplan-Meier analysis and Cox regression. RESULTS: The best optimization of sensitivity and specificity was achieved when using dual testing with cytology and HPV DNA testing, whereby the screening test is considered positive if either component yields an abnormal result. However, when allowing 12months for the detection of lesions, cytology alone performed nearly as well. Risk stratification revealed that HPV DNA testing was not beneficial for HSIL cases, whereas it was for ASCUS and, in some combinations, for negative and LSIL cytology. CONCLUSION: Our results suggest that some high risk populations may benefit equally from cytology or HPV DNA testing, and may require shorter intervals between repeat testing.
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Skip to content Oral Care Select An Article Choosing a Toothbrush: The Pros and Cons of Electric and Disposable Font Size A A A You can't overestimate the importance of good oral hygiene -- not only for dental health, but for your overall wellbeing. In fact, gum disease is a major risk factor for the development of serious health conditions, including heart disease and diabetes. From the time we're young, we're taught that using a toothbrush regularly is one of the best ways to keep our teeth and gums healthy. But which toothbrush is best? In the late 1930s, when toothbrushes with nylon bristles were first invented, consumers choosing a toothbrush didn't have many options. Now, the story's completely different. Most stores that sell oral hygiene products now have an extensive collection of different types of toothbrushes on their shelves, including manual (disposable) and powered (electric) varieties. General Tips for Choosing a Toothbrush There are certain characteristics that you should look for in whatever toothbrush you choose, regardless of whether it is manual or powered. Size. The best toothbrush head for you should allow you easy access to all surfaces of your teeth. For most adults, a toothbrush head a half-inch wide and one-inch tall will be the easiest to use and the most effective. Though there are larger toothbrush heads available, you may find that it is difficult to maneuver them to clean certain hard-to-reach areas, such as the sides and backs of your molars. The toothbrush should have a long enough handle so you can comfortably hold it in your hand. Bristle variety. If you go to the drug store to purchase a manual toothbrush or a replacement head for your electric toothbrush, you will be able to select a toothbrush with soft, medium, or hard nylon bristles. For the vast majority of people, a soft-bristled toothbrush will be the most comfortable and safest choice. Depending on how vigorously you brush your teeth and the strength of your teeth, medium- and hard-bristled brushes could actually damage the gums, root surface, and protective tooth enamel. For even more tooth protection when you brush, be sure the bristles on the toothbrush you select have rounded tips. Expert recommendation. To ensure your toothbrush has undergone rigorous quality control tests for cleaning effectiveness and safety, ask your dentist for a recommendation. Or look for manual or powered toothbrushes that have earned the American Dental Association (ADA) Seal of Approval. 1 | 2 | 3 Next Article: How Do I Measure Up? Get the Facts Fast! Number of Days Per Week I Floss Get the latest Oral Health newsletter delivered to your inbox! or Answer: Never (0) Good (1-3) Better (4-6) Best (7) You are currently Only 18.5% of Americans never floss. You are missing out on a simple way to make a big difference in the health of your mouth. Regardless of how well you brush, plaque still forms between your teeth and along your gums. Floss removes food trapped between the teeth and removes the film of bacteria that forms there before it turns to plaque, which can cause inflamed gums (gingivitis), cavities, and tooth loss. Try flossing just one tooth to get started. You are one of 31% of Americans who don't floss daily. You are missing out on a simple way to make a big difference in the health of your mouth. Regardless of how well you brush, plaque still forms between your teeth and along your gums. Toothbrush bristles alone cannot clean effectively between these tight spaces. Flossing removes up to 80% of the film that hardens to plaque, which can cause inflamed gums (gingivitis), cavities, and tooth loss. Aim for 3 more days! You are one of 31% of Americans who don't floss daily, but you're well on your way to making a positive impact on your teeth and gums. Regardless of how well you brush, plaque still forms between your teeth and along your gums. Toothbrush bristles alone cannot clean effectively between these tight spaces. Flossing removes up to 80% of the film that hardens to plaque, which can cause inflamed gums (gingivitis), cavities, and tooth loss. Aim for all 7 days! Only 50.5% of Americans floss daily, and good for you that you are one of them! Regardless of how well you brush, plaque still forms between your teeth and along your gums. Toothbrush bristles alone cannot clean effectively between these tight spaces. Flossing removes up to 80% of the film that hardens to plaque, which can cause inflamed gums (gingivitis), cavities, and tooth loss. Congratulations on your good oral health habit! SOURCES: American Dental Association, Healthy People 2010 This tool is intended only for adults 18 and older. Start Over Step:  of  Today on WebMD close up of woman sticking out tongue Sores, discoloration, bumps and more. toothbrushes 10 secrets to a brighter smile.   Veneer smile Before and after. Woman checking her bite in mirror Why dental care is important.   Woman dissatisfied with granola bar Slideshow woman with jaw pain Quiz   eroded front teeth Slideshow brushing teeth Video   Variety shades of tea Slideshow mouth and dental instruments Article   Closeup of a happy young guy brushing his teeth Tool womans smile Video  
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Skip to Content OpenStax Logo Anatomy and Physiology 18.3 Erythrocytes Anatomy and Physiology18.3 Erythrocytes Buy book 1. Preface 2. Unit 1: Levels of Organization 1. 1 An Introduction to the Human Body 1. Introduction 2. 1.1 Overview of Anatomy and Physiology 3. 1.2 Structural Organization of the Human Body 4. 1.3 Functions of Human Life 5. 1.4 Requirements for Human Life 6. 1.5 Homeostasis 7. 1.6 Anatomical Terminology 8. 1.7 Medical Imaging 9. Key Terms 10. Chapter Review 11. Interactive Link Questions 12. Review Questions 13. Critical Thinking Questions 2. 2 The Chemical Level of Organization 1. Introduction 2. 2.1 Elements and Atoms: The Building Blocks of Matter 3. 2.2 Chemical Bonds 4. 2.3 Chemical Reactions 5. 2.4 Inorganic Compounds Essential to Human Functioning 6. 2.5 Organic Compounds Essential to Human Functioning 7. Key Terms 8. Chapter Review 9. Interactive Link Questions 10. Review Questions 11. Critical Thinking Questions 3. 3 The Cellular Level of Organization 1. Introduction 2. 3.1 The Cell Membrane 3. 3.2 The Cytoplasm and Cellular Organelles 4. 3.3 The Nucleus and DNA Replication 5. 3.4 Protein Synthesis 6. 3.5 Cell Growth and Division 7. 3.6 Cellular Differentiation 8. Key Terms 9. Chapter Review 10. Interactive Link Questions 11. Review Questions 12. Critical Thinking Questions 4. 4 The Tissue Level of Organization 1. Introduction 2. 4.1 Types of Tissues 3. 4.2 Epithelial Tissue 4. 4.3 Connective Tissue Supports and Protects 5. 4.4 Muscle Tissue and Motion 6. 4.5 Nervous Tissue Mediates Perception and Response 7. 4.6 Tissue Injury and Aging 8. Key Terms 9. Chapter Review 10. Interactive Link Questions 11. Review Questions 12. Critical Thinking Questions 3. Unit 2: Support and Movement 1. 5 The Integumentary System 1. Introduction 2. 5.1 Layers of the Skin 3. 5.2 Accessory Structures of the Skin 4. 5.3 Functions of the Integumentary System 5. 5.4 Diseases, Disorders, and Injuries of the Integumentary System 6. Key Terms 7. Chapter Review 8. Interactive Link Questions 9. Review Questions 10. Critical Thinking Questions 2. 6 Bone Tissue and the Skeletal System 1. Introduction 2. 6.1 The Functions of the Skeletal System 3. 6.2 Bone Classification 4. 6.3 Bone Structure 5. 6.4 Bone Formation and Development 6. 6.5 Fractures: Bone Repair 7. 6.6 Exercise, Nutrition, Hormones, and Bone Tissue 8. 6.7 Calcium Homeostasis: Interactions of the Skeletal System and Other Organ Systems 9. Key Terms 10. Chapter Review 11. Review Questions 12. Critical Thinking Questions 3. 7 Axial Skeleton 1. Introduction 2. 7.1 Divisions of the Skeletal System 3. 7.2 The Skull 4. 7.3 The Vertebral Column 5. 7.4 The Thoracic Cage 6. 7.5 Embryonic Development of the Axial Skeleton 7. Key Terms 8. Chapter Review 9. Interactive Link Questions 10. Review Questions 11. Critical Thinking Questions 4. 8 The Appendicular Skeleton 1. Introduction 2. 8.1 The Pectoral Girdle 3. 8.2 Bones of the Upper Limb 4. 8.3 The Pelvic Girdle and Pelvis 5. 8.4 Bones of the Lower Limb 6. 8.5 Development of the Appendicular Skeleton 7. Key Terms 8. Chapter Review 9. Interactive Link Questions 10. Review Questions 11. Critical Thinking Questions 5. 9 Joints 1. Introduction 2. 9.1 Classification of Joints 3. 9.2 Fibrous Joints 4. 9.3 Cartilaginous Joints 5. 9.4 Synovial Joints 6. 9.5 Types of Body Movements 7. 9.6 Anatomy of Selected Synovial Joints 8. 9.7 Development of Joints 9. Key Terms 10. Chapter Review 11. Interactive Link Questions 12. Review Questions 13. Critical Thinking Questions 6. 10 Muscle Tissue 1. Introduction 2. 10.1 Overview of Muscle Tissues 3. 10.2 Skeletal Muscle 4. 10.3 Muscle Fiber Contraction and Relaxation 5. 10.4 Nervous System Control of Muscle Tension 6. 10.5 Types of Muscle Fibers 7. 10.6 Exercise and Muscle Performance 8. 10.7 Cardiac Muscle Tissue 9. 10.8 Smooth Muscle 10. 10.9 Development and Regeneration of Muscle Tissue 11. Key Terms 12. Chapter Review 13. Interactive Link Questions 14. Review Questions 15. Critical Thinking Questions 7. 11 The Muscular System 1. Introduction 2. 11.1 Interactions of Skeletal Muscles, Their Fascicle Arrangement, and Their Lever Systems 3. 11.2 Naming Skeletal Muscles 4. 11.3 Axial Muscles of the Head, Neck, and Back 5. 11.4 Axial Muscles of the Abdominal Wall, and Thorax 6. 11.5 Muscles of the Pectoral Girdle and Upper Limbs 7. 11.6 Appendicular Muscles of the Pelvic Girdle and Lower Limbs 8. Key Terms 9. Chapter Review 10. Review Questions 11. Critical Thinking Questions 4. Unit 3: Regulation, Integration, and Control 1. 12 The Nervous System and Nervous Tissue 1. Introduction 2. 12.1 Basic Structure and Function of the Nervous System 3. 12.2 Nervous Tissue 4. 12.3 The Function of Nervous Tissue 5. 12.4 The Action Potential 6. 12.5 Communication Between Neurons 7. Key Terms 8. Chapter Review 9. Interactive Link Questions 10. Review Questions 11. Critical Thinking Questions 2. 13 Anatomy of the Nervous System 1. Introduction 2. 13.1 The Embryologic Perspective 3. 13.2 The Central Nervous System 4. 13.3 Circulation and the Central Nervous System 5. 13.4 The Peripheral Nervous System 6. Key Terms 7. Chapter Review 8. Interactive Link Questions 9. Review Questions 10. Critical Thinking Questions 3. 14 The Somatic Nervous System 1. Introduction 2. 14.1 Sensory Perception 3. 14.2 Central Processing 4. 14.3 Motor Responses 5. Key Terms 6. Chapter Review 7. Interactive Link Questions 8. Review Questions 9. Critical Thinking Questions 4. 15 The Autonomic Nervous System 1. Introduction 2. 15.1 Divisions of the Autonomic Nervous System 3. 15.2 Autonomic Reflexes and Homeostasis 4. 15.3 Central Control 5. 15.4 Drugs that Affect the Autonomic System 6. Key Terms 7. Chapter Review 8. Interactive Link Questions 9. Review Questions 10. Critical Thinking Questions 5. 16 The Neurological Exam 1. Introduction 2. 16.1 Overview of the Neurological Exam 3. 16.2 The Mental Status Exam 4. 16.3 The Cranial Nerve Exam 5. 16.4 The Sensory and Motor Exams 6. 16.5 The Coordination and Gait Exams 7. Key Terms 8. Chapter Review 9. Interactive Link Questions 10. Review Questions 11. Critical Thinking Questions 6. 17 The Endocrine System 1. Introduction 2. 17.1 An Overview of the Endocrine System 3. 17.2 Hormones 4. 17.3 The Pituitary Gland and Hypothalamus 5. 17.4 The Thyroid Gland 6. 17.5 The Parathyroid Glands 7. 17.6 The Adrenal Glands 8. 17.7 The Pineal Gland 9. 17.8 Gonadal and Placental Hormones 10. 17.9 The Endocrine Pancreas 11. 17.10 Organs with Secondary Endocrine Functions 12. 17.11 Development and Aging of the Endocrine System 13. Key Terms 14. Chapter Review 15. Interactive Link Questions 16. Review Questions 17. Critical Thinking Questions 5. Unit 4: Fluids and Transport 1. 18 The Cardiovascular System: Blood 1. Introduction 2. 18.1 An Overview of Blood 3. 18.2 Production of the Formed Elements 4. 18.3 Erythrocytes 5. 18.4 Leukocytes and Platelets 6. 18.5 Hemostasis 7. 18.6 Blood Typing 8. Key Terms 9. Chapter Review 10. Interactive Link Questions 11. Review Questions 12. Critical Thinking Questions 2. 19 The Cardiovascular System: The Heart 1. Introduction 2. 19.1 Heart Anatomy 3. 19.2 Cardiac Muscle and Electrical Activity 4. 19.3 Cardiac Cycle 5. 19.4 Cardiac Physiology 6. 19.5 Development of the Heart 7. Key Terms 8. Chapter Review 9. Interactive Link Questions 10. Review Questions 11. Critical Thinking Questions 3. 20 The Cardiovascular System: Blood Vessels and Circulation 1. Introduction 2. 20.1 Structure and Function of Blood Vessels 3. 20.2 Blood Flow, Blood Pressure, and Resistance 4. 20.3 Capillary Exchange 5. 20.4 Homeostatic Regulation of the Vascular System 6. 20.5 Circulatory Pathways 7. 20.6 Development of Blood Vessels and Fetal Circulation 8. Key Terms 9. Chapter Review 10. Interactive Link Questions 11. Review Questions 12. Critical Thinking Questions 4. 21 The Lymphatic and Immune System 1. Introduction 2. 21.1 Anatomy of the Lymphatic and Immune Systems 3. 21.2 Barrier Defenses and the Innate Immune Response 4. 21.3 The Adaptive Immune Response: T lymphocytes and Their Functional Types 5. 21.4 The Adaptive Immune Response: B-lymphocytes and Antibodies 6. 21.5 The Immune Response against Pathogens 7. 21.6 Diseases Associated with Depressed or Overactive Immune Responses 8. 21.7 Transplantation and Cancer Immunology 9. Key Terms 10. Chapter Review 11. Interactive Link Questions 12. Review Questions 13. Critical Thinking Questions 6. Unit 5: Energy, Maintenance, and Environmental Exchange 1. 22 The Respiratory System 1. Introduction 2. 22.1 Organs and Structures of the Respiratory System 3. 22.2 The Lungs 4. 22.3 The Process of Breathing 5. 22.4 Gas Exchange 6. 22.5 Transport of Gases 7. 22.6 Modifications in Respiratory Functions 8. 22.7 Embryonic Development of the Respiratory System 9. Key Terms 10. Chapter Review 11. Interactive Link Questions 12. Review Questions 13. Critical Thinking Questions 2. 23 The Digestive System 1. Introduction 2. 23.1 Overview of the Digestive System 3. 23.2 Digestive System Processes and Regulation 4. 23.3 The Mouth, Pharynx, and Esophagus 5. 23.4 The Stomach 6. 23.5 The Small and Large Intestines 7. 23.6 Accessory Organs in Digestion: The Liver, Pancreas, and Gallbladder 8. 23.7 Chemical Digestion and Absorption: A Closer Look 9. Key Terms 10. Chapter Review 11. Interactive Link Questions 12. Review Questions 13. Critical Thinking Questions 3. 24 Metabolism and Nutrition 1. Introduction 2. 24.1 Overview of Metabolic Reactions 3. 24.2 Carbohydrate Metabolism 4. 24.3 Lipid Metabolism 5. 24.4 Protein Metabolism 6. 24.5 Metabolic States of the Body 7. 24.6 Energy and Heat Balance 8. 24.7 Nutrition and Diet 9. Key Terms 10. Chapter Review 11. Review Questions 12. Critical Thinking Questions 4. 25 The Urinary System 1. Introduction 2. 25.1 Physical Characteristics of Urine 3. 25.2 Gross Anatomy of Urine Transport 4. 25.3 Gross Anatomy of the Kidney 5. 25.4 Microscopic Anatomy of the Kidney 6. 25.5 Physiology of Urine Formation 7. 25.6 Tubular Reabsorption 8. 25.7 Regulation of Renal Blood Flow 9. 25.8 Endocrine Regulation of Kidney Function 10. 25.9 Regulation of Fluid Volume and Composition 11. 25.10 The Urinary System and Homeostasis 12. Key Terms 13. Chapter Review 14. Review Questions 15. Critical Thinking Questions 5. 26 Fluid, Electrolyte, and Acid-Base Balance 1. Introduction 2. 26.1 Body Fluids and Fluid Compartments 3. 26.2 Water Balance 4. 26.3 Electrolyte Balance 5. 26.4 Acid-Base Balance 6. 26.5 Disorders of Acid-Base Balance 7. Key Terms 8. Chapter Review 9. Interactive Link Questions 10. Review Questions 11. Critical Thinking Questions 7. Unit 6: Human Development and the Continuity of Life 1. 27 The Reproductive System 1. Introduction 2. 27.1 Anatomy and Physiology of the Male Reproductive System 3. 27.2 Anatomy and Physiology of the Female Reproductive System 4. 27.3 Development of the Male and Female Reproductive Systems 5. Key Terms 6. Chapter Review 7. Interactive Link Questions 8. Review Questions 9. Critical Thinking Questions 2. 28 Development and Inheritance 1. Introduction 2. 28.1 Fertilization 3. 28.2 Embryonic Development 4. 28.3 Fetal Development 5. 28.4 Maternal Changes During Pregnancy, Labor, and Birth 6. 28.5 Adjustments of the Infant at Birth and Postnatal Stages 7. 28.6 Lactation 8. 28.7 Patterns of Inheritance 9. Key Terms 10. Chapter Review 11. Interactive Link Questions 12. Review Questions 13. Critical Thinking Questions 8. References 9. Index By the end of this section, you will be able to: • Describe the anatomy of erythrocytes • Discuss the various steps in the lifecycle of an erythrocyte • Explain the composition and function of hemoglobin The erythrocyte, commonly known as a red blood cell (or RBC), is by far the most common formed element: A single drop of blood contains millions of erythrocytes and just thousands of leukocytes. Specifically, males have about 5.4 million erythrocytes per microliter (µL) of blood, and females have approximately 4.8 million per µL. In fact, erythrocytes are estimated to make up about 25 percent of the total cells in the body. As you can imagine, they are quite small cells, with a mean diameter of only about 7–8 micrometers (µm) (Figure 18.5). The primary functions of erythrocytes are to pick up inhaled oxygen from the lungs and transport it to the body’s tissues, and to pick up some (about 24 percent) carbon dioxide waste at the tissues and transport it to the lungs for exhalation. Erythrocytes remain within the vascular network. Although leukocytes typically leave the blood vessels to perform their defensive functions, movement of erythrocytes from the blood vessels is abnormal. This table shows the different types of cells present in blood, the number of cells, their appearance, and a summary of their function. Figure 18.5 Summary of Formed Elements in Blood Shape and Structure of Erythrocytes As an erythrocyte matures in the red bone marrow, it extrudes its nucleus and most of its other organelles. During the first day or two that it is in the circulation, an immature erythrocyte, known as a reticulocyte, will still typically contain remnants of organelles. Reticulocytes should comprise approximately 1–2 percent of the erythrocyte count and provide a rough estimate of the rate of RBC production, with abnormally low or high rates indicating deviations in the production of these cells. These remnants, primarily of networks (reticulum) of ribosomes, are quickly shed, however, and mature, circulating erythrocytes have few internal cellular structural components. Lacking mitochondria, for example, they rely on anaerobic respiration. This means that they do not utilize any of the oxygen they are transporting, so they can deliver it all to the tissues. They also lack endoplasmic reticula and do not synthesize proteins. Erythrocytes do, however, contain some structural proteins that help the blood cells maintain their unique structure and enable them to change their shape to squeeze through capillaries. This includes the protein spectrin, a cytoskeletal protein element. Erythrocytes are biconcave disks; that is, they are plump at their periphery and very thin in the center (Figure 18.6). Since they lack most organelles, there is more interior space for the presence of the hemoglobin molecules that, as you will see shortly, transport gases. The biconcave shape also provides a greater surface area across which gas exchange can occur, relative to its volume; a sphere of a similar diameter would have a lower surface area-to-volume ratio. In the capillaries, the oxygen carried by the erythrocytes can diffuse into the plasma and then through the capillary walls to reach the cells, whereas some of the carbon dioxide produced by the cells as a waste product diffuses into the capillaries to be picked up by the erythrocytes. Capillary beds are extremely narrow, slowing the passage of the erythrocytes and providing an extended opportunity for gas exchange to occur. However, the space within capillaries can be so minute that, despite their own small size, erythrocytes may have to fold in on themselves if they are to make their way through. Fortunately, their structural proteins like spectrin are flexible, allowing them to bend over themselves to a surprising degree, then spring back again when they enter a wider vessel. In wider vessels, erythrocytes may stack up much like a roll of coins, forming a rouleaux, from the French word for “roll.” This photograph shows a few red blood cells. Figure 18.6 Shape of Red Blood Cells Erythrocytes are biconcave discs with very shallow centers. This shape optimizes the ratio of surface area to volume, facilitating gas exchange. It also enables them to fold up as they move through narrow blood vessels. Hemoglobin Hemoglobin is a large molecule made up of proteins and iron. It consists of four folded chains of a protein called globin, designated alpha 1 and 2, and beta 1 and 2 (Figure 18.7a). Each of these globin molecules is bound to a red pigment molecule called heme, which contains an ion of iron (Fe2+) (Figure 18.7b). This figure shows the structure of hemoglobin. The left panel shows the protein structure and the right panel shows the chemical formula. Figure 18.7 Hemoglobin (a) A molecule of hemoglobin contains four globin proteins, each of which is bound to one molecule of the iron-containing pigment heme. (b) A single erythrocyte can contain 300 million hemoglobin molecules, and thus more than 1 billion oxygen molecules. Each iron ion in the heme can bind to one oxygen molecule; therefore, each hemoglobin molecule can transport four oxygen molecules. An individual erythrocyte may contain about 300 million hemoglobin molecules, and therefore can bind to and transport up to 1.2 billion oxygen molecules (see Figure 18.7b). In the lungs, hemoglobin picks up oxygen, which binds to the iron ions, forming oxyhemoglobin. The bright red, oxygenated hemoglobin travels to the body tissues, where it releases some of the oxygen molecules, becoming darker red deoxyhemoglobin, sometimes referred to as reduced hemoglobin. Oxygen release depends on the need for oxygen in the surrounding tissues, so hemoglobin rarely if ever leaves all of its oxygen behind. In the capillaries, carbon dioxide enters the bloodstream. About 76 percent dissolves in the plasma, some of it remaining as dissolved CO2, and the remainder forming bicarbonate ion. About 23–24 percent of it binds to the amino acids in hemoglobin, forming a molecule known as carbaminohemoglobin. From the capillaries, the hemoglobin carries carbon dioxide back to the lungs, where it releases it for exchange of oxygen. Changes in the levels of RBCs can have significant effects on the body’s ability to effectively deliver oxygen to the tissues. Ineffective hematopoiesis results in insufficient numbers of RBCs and results in one of several forms of anemia. An overproduction of RBCs produces a condition called polycythemia. The primary drawback with polycythemia is not a failure to directly deliver enough oxygen to the tissues, but rather the increased viscosity of the blood, which makes it more difficult for the heart to circulate the blood. In patients with insufficient hemoglobin, the tissues may not receive sufficient oxygen, resulting in another form of anemia. In determining oxygenation of tissues, the value of greatest interest in healthcare is the percent saturation; that is, the percentage of hemoglobin sites occupied by oxygen in a patient’s blood. Clinically this value is commonly referred to simply as “percent sat.” Percent saturation is normally monitored using a device known as a pulse oximeter, which is applied to a thin part of the body, typically the tip of the patient’s finger. The device works by sending two different wavelengths of light (one red, the other infrared) through the finger and measuring the light with a photodetector as it exits. Hemoglobin absorbs light differentially depending upon its saturation with oxygen. The machine calibrates the amount of light received by the photodetector against the amount absorbed by the partially oxygenated hemoglobin and presents the data as percent saturation. Normal pulse oximeter readings range from 95–100 percent. Lower percentages reflect hypoxemia, or low blood oxygen. The term hypoxia is more generic and simply refers to low oxygen levels. Oxygen levels are also directly monitored from free oxygen in the plasma typically following an arterial stick. When this method is applied, the amount of oxygen present is expressed in terms of partial pressure of oxygen or simply pO2 and is typically recorded in units of millimeters of mercury, mm Hg. The kidneys filter about 180 liters (~380 pints) of blood in an average adult each day, or about 20 percent of the total resting volume, and thus serve as ideal sites for receptors that determine oxygen saturation. In response to hypoxemia, less oxygen will exit the vessels supplying the kidney, resulting in hypoxia (low oxygen concentration) in the tissue fluid of the kidney where oxygen concentration is actually monitored. Interstitial fibroblasts within the kidney secrete EPO, thereby increasing erythrocyte production and restoring oxygen levels. In a classic negative-feedback loop, as oxygen saturation rises, EPO secretion falls, and vice versa, thereby maintaining homeostasis. Populations dwelling at high elevations, with inherently lower levels of oxygen in the atmosphere, naturally maintain a hematocrit higher than people living at sea level. Consequently, people traveling to high elevations may experience symptoms of hypoxemia, such as fatigue, headache, and shortness of breath, for a few days after their arrival. In response to the hypoxemia, the kidneys secrete EPO to step up the production of erythrocytes until homeostasis is achieved once again. To avoid the symptoms of hypoxemia, or altitude sickness, mountain climbers typically rest for several days to a week or more at a series of camps situated at increasing elevations to allow EPO levels and, consequently, erythrocyte counts to rise. When climbing the tallest peaks, such as Mt. Everest and K2 in the Himalayas, many mountain climbers rely upon bottled oxygen as they near the summit. Lifecycle of Erythrocytes Production of erythrocytes in the marrow occurs at the staggering rate of more than 2 million cells per second. For this production to occur, a number of raw materials must be present in adequate amounts. These include the same nutrients that are essential to the production and maintenance of any cell, such as glucose, lipids, and amino acids. However, erythrocyte production also requires several trace elements: • Iron. We have said that each heme group in a hemoglobin molecule contains an ion of the trace mineral iron. On average, less than 20 percent of the iron we consume is absorbed. Heme iron, from animal foods such as meat, poultry, and fish, is absorbed more efficiently than non-heme iron from plant foods. Upon absorption, iron becomes part of the body’s total iron pool. The bone marrow, liver, and spleen can store iron in the protein compounds ferritin and hemosiderin. Ferroportin transports the iron across the intestinal cell plasma membranes and from its storage sites into tissue fluid where it enters the blood. When EPO stimulates the production of erythrocytes, iron is released from storage, bound to transferrin, and carried to the red marrow where it attaches to erythrocyte precursors. • Copper. A trace mineral, copper is a component of two plasma proteins, hephaestin and ceruloplasmin. Without these, hemoglobin could not be adequately produced. Located in intestinal villi, hephaestin enables iron to be absorbed by intestinal cells. Ceruloplasmin transports copper. Both enable the oxidation of iron from Fe2+ to Fe3+, a form in which it can be bound to its transport protein, transferrin, for transport to body cells. In a state of copper deficiency, the transport of iron for heme synthesis decreases, and iron can accumulate in tissues, where it can eventually lead to organ damage. • Zinc. The trace mineral zinc functions as a co-enzyme that facilitates the synthesis of the heme portion of hemoglobin. • B vitamins. The B vitamins folate and vitamin B12 function as co-enzymes that facilitate DNA synthesis. Thus, both are critical for the synthesis of new cells, including erythrocytes. Erythrocytes live up to 120 days in the circulation, after which the worn-out cells are removed by a type of myeloid phagocytic cell called a macrophage, located primarily within the bone marrow, liver, and spleen. The components of the degraded erythrocytes’ hemoglobin are further processed as follows: • Globin, the protein portion of hemoglobin, is broken down into amino acids, which can be sent back to the bone marrow to be used in the production of new erythrocytes. Hemoglobin that is not phagocytized is broken down in the circulation, releasing alpha and beta chains that are removed from circulation by the kidneys. • The iron contained in the heme portion of hemoglobin may be stored in the liver or spleen, primarily in the form of ferritin or hemosiderin, or carried through the bloodstream by transferrin to the red bone marrow for recycling into new erythrocytes. • The non-iron portion of heme is degraded into the waste product biliverdin, a green pigment, and then into another waste product, bilirubin, a yellow pigment. Bilirubin binds to albumin and travels in the blood to the liver, which uses it in the manufacture of bile, a compound released into the intestines to help emulsify dietary fats. In the large intestine, bacteria breaks the bilirubin apart from the bile and converts it to urobilinogen and then into stercobilin. It is then eliminated from the body in the feces. Broad-spectrum antibiotics typically eliminate these bacteria as well and may alter the color of feces. The kidneys also remove any circulating bilirubin and other related metabolic byproducts such as urobilins and secrete them into the urine. The breakdown pigments formed from the destruction of hemoglobin can be seen in a variety of situations. At the site of an injury, biliverdin from damaged RBCs produces some of the dramatic colors associated with bruising. With a failing liver, bilirubin cannot be removed effectively from circulation and causes the body to assume a yellowish tinge associated with jaundice. Stercobilins within the feces produce the typical brown color associated with this waste. And the yellow of urine is associated with the urobilins. The erythrocyte lifecycle is summarized in Figure 18.8. This flow chart shows the life cycle of a red blood cell. The first step is the hemopoeisis of erythrocytes in the bone marrow. Further steps in this diagram show the passage of erythrocytes through the blood stream, the breakdown of heme protein, and liver function. Figure 18.8 Erythrocyte Lifecycle Erythrocytes are produced in the bone marrow and sent into the circulation. At the end of their lifecycle, they are destroyed by macrophages, and their components are recycled. Disorders of Erythrocytes The size, shape, and number of erythrocytes, and the number of hemoglobin molecules can have a major impact on a person’s health. When the number of RBCs or hemoglobin is deficient, the general condition is called anemia. There are more than 400 types of anemia and more than 3.5 million Americans suffer from this condition. Anemia can be broken down into three major groups: those caused by blood loss, those caused by faulty or decreased RBC production, and those caused by excessive destruction of RBCs. Clinicians often use two groupings in diagnosis: The kinetic approach focuses on evaluating the production, destruction, and removal of RBCs, whereas the morphological approach examines the RBCs themselves, paying particular emphasis to their size. A common test is the mean corpuscle volume (MCV), which measures size. Normal-sized cells are referred to as normocytic, smaller-than-normal cells are referred to as microcytic, and larger-than-normal cells are referred to as macrocytic. Reticulocyte counts are also important and may reveal inadequate production of RBCs. The effects of the various anemias are widespread, because reduced numbers of RBCs or hemoglobin will result in lower levels of oxygen being delivered to body tissues. Since oxygen is required for tissue functioning, anemia produces fatigue, lethargy, and an increased risk for infection. An oxygen deficit in the brain impairs the ability to think clearly, and may prompt headaches and irritability. Lack of oxygen leaves the patient short of breath, even as the heart and lungs work harder in response to the deficit. Blood loss anemias are fairly straightforward. In addition to bleeding from wounds or other lesions, these forms of anemia may be due to ulcers, hemorrhoids, inflammation of the stomach (gastritis), and some cancers of the gastrointestinal tract. The excessive use of aspirin or other nonsteroidal anti-inflammatory drugs such as ibuprofen can trigger ulceration and gastritis. Excessive menstruation and loss of blood during childbirth are also potential causes. Anemias caused by faulty or decreased RBC production include sickle cell anemia, iron deficiency anemia, vitamin deficiency anemia, and diseases of the bone marrow and stem cells. • A characteristic change in the shape of erythrocytes is seen in sickle cell disease (also referred to as sickle cell anemia). A genetic disorder, it is caused by production of an abnormal type of hemoglobin, called hemoglobin S, which delivers less oxygen to tissues and causes erythrocytes to assume a sickle (or crescent) shape, especially at low oxygen concentrations (Figure 18.9). These abnormally shaped cells can then become lodged in narrow capillaries because they are unable to fold in on themselves to squeeze through, blocking blood flow to tissues and causing a variety of serious problems from painful joints to delayed growth and even blindness and cerebrovascular accidents (strokes). Sickle cell anemia is a genetic condition particularly found in individuals of African descent. This photograph shows red blood cells of a person suffering from sickle cell anemia. Instead of being discoid shaped like healthy blood cells, sickle red blood cells are shaped like a sickle. Figure 18.9 Sickle Cells Sickle cell anemia is caused by a mutation in one of the hemoglobin genes. Erythrocytes produce an abnormal type of hemoglobin, which causes the cell to take on a sickle or crescent shape. (credit: Janice Haney Carr) • Iron deficiency anemia is the most common type and results when the amount of available iron is insufficient to allow production of sufficient heme. This condition can occur in individuals with a deficiency of iron in the diet and is especially common in teens and children as well as in vegans and vegetarians. Additionally, iron deficiency anemia may be caused by either an inability to absorb and transport iron or slow, chronic bleeding. • Vitamin-deficient anemias generally involve insufficient vitamin B12 and folate. • Megaloblastic anemia involves a deficiency of vitamin B12 and/or folate, and often involves diets deficient in these essential nutrients. Lack of meat or a viable alternate source, and overcooking or eating insufficient amounts of vegetables may lead to a lack of folate. • Pernicious anemia is caused by poor absorption of vitamin B12 and is often seen in patients with Crohn’s disease (a severe intestinal disorder often treated by surgery), surgical removal of the intestines or stomach (common in some weight loss surgeries), intestinal parasites, and AIDS. • Pregnancies, some medications, excessive alcohol consumption, and some diseases such as celiac disease are also associated with vitamin deficiencies. It is essential to provide sufficient folic acid during the early stages of pregnancy to reduce the risk of neurological defects, including spina bifida, a failure of the neural tube to close. • Assorted disease processes can also interfere with the production and formation of RBCs and hemoglobin. If myeloid stem cells are defective or replaced by cancer cells, there will be insufficient quantities of RBCs produced. • Aplastic anemia is the condition in which there are deficient numbers of RBC stem cells. Aplastic anemia is often inherited, or it may be triggered by radiation, medication, chemotherapy, or infection. • Thalassemia is an inherited condition typically occurring in individuals from the Middle East, the Mediterranean, African, and Southeast Asia, in which maturation of the RBCs does not proceed normally. The most severe form is called Cooley’s anemia. • Lead exposure from industrial sources or even dust from paint chips of iron-containing paints or pottery that has not been properly glazed may also lead to destruction of the red marrow. • Various disease processes also can lead to anemias. These include chronic kidney diseases often associated with a decreased production of EPO, hypothyroidism, some forms of cancer, lupus, and rheumatoid arthritis. In contrast to anemia, an elevated RBC count is called polycythemia and is detected in a patient’s elevated hematocrit. It can occur transiently in a person who is dehydrated; when water intake is inadequate or water losses are excessive, the plasma volume falls. As a result, the hematocrit rises. For reasons mentioned earlier, a mild form of polycythemia is chronic but normal in people living at high altitudes. Some elite athletes train at high elevations specifically to induce this phenomenon. Finally, a type of bone marrow disease called polycythemia vera (from the Greek vera = “true”) causes an excessive production of immature erythrocytes. Polycythemia vera can dangerously elevate the viscosity of blood, raising blood pressure and making it more difficult for the heart to pump blood throughout the body. It is a relatively rare disease that occurs more often in men than women, and is more likely to be present in elderly patients those over 60 years of age. 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What is Early Menopause? What is Early Menopause When we talk about menopause (which I don’t believe is as often as we should!) we tend to associate with midlife women.  We possibly think of women in their early to mid 50s who have had their children, maybe even have a grandchild or two and who are now looking to start the next chapter of their life. And for many women, that may well be a fairly accurate picture.  The average age for a woman to go through menopause in the UK is 51 so you’d be forgiven for assuming that the description above is true. In truth, many women go through menopause much earlier in their life.  Sometimes they will have their menopause induced early as a result of surgery.  Other times certain cancer treatments can cause an early menopause. TERMINOLOGY Before I continue let’s just get a better understanding of some of the terminology because it can all get just a little bit confusing. Let’s start with pre-menopause.  Generally speaking, this is the time before a woman’s sex organs begin their decline towards cessation of fertility.  Basically, the time during which a woman is having regular menstrual periods and is fertile.  Menopause is a term that strictly means the pausing of menses (periods).  Specifically, it is classed as one day, 12 months from the date of a woman’s last period.  Climacteric is the period of time leading up to, and immediately following, menopause.  When we talk about women going through menopause we’re really referring to the female climacteric. Peri-menopause is the start of the decline of the release of sex hormones from the ovaries in preparation for menopause and usually starts around 4-6 years before, although it can start up to 10 years prior to menopause. Post-menopause is the time immediately following menopause and continues until the end of a woman’s life. Women generally menopause somewhere between 45 and 55 however, where a woman goes through menopause between the ages of 40 and 45 it is classed as early menopause. For women who menopause below the age of 40 the term used is Premature Menopause.  It may also be referred to as Premature Ovarian Insufficiency (POI) which is becoming the more commonly used term or premature ovarian failure. For many women a diagnosis of POI can be devastating, especially for very young women. PREMATURE OVARIAN INSUFFICIENCY According to the POI support charity The Daisy Network approximately 110,000 women in Britain between 12 and 40 years of age are affected by premature ovarian insufficiency.  Spontaneous POI below the age of 45 affects about 5% of women and under the age of 40 about 1%.    This figure is increased if we include the number of women who are put into an early menopause as the result of surgery or chemo/radio therapy. The causes of POI are still not fully understood, and for many women (about 90%) the underlying cause of their POI will remain unknown.  There is some research that suggests POI can occur as a result of an auto-immune condition, where the body’s immune system turns on its own tissues.  If this occurs in the ovaries POI may result. There could also be genetic causes due to chromosome abnormalities with the female X chromosome.  There may be a familial link where women have a family history of POI .  Surgical procedures such as hysterectomy (removal of the uterus) and oophorectomy (removal of the ovaries) as well as certain cancer treatments can cause an early menopause. In POI the ovaries often don’t fail completely, hence the term insufficiency, and it is possible that some women may still be able to conceive. EFFECTS OF POI For women diagnosed with POI infertility may result however approximately 5% of women who have POI do conceive.  There may be scope to look at egg donation as an option to getting pregnant. Hormones such as oestrogen and testosterone serve a wider purpose in the body than just fertility.  Low oestrogen is associated with reduced bone density (osteoporosis) and an increased risk of developing heart disease.  Oestrogen is also involved in cognitive function and a reduction can affect memory and concentration. POI could affect libido and impact sex life due to discomfort during intercourse and a lowered sex drive. MANAGING POI The European Society of Human Reproduction and Embyology (ESHRE) suggest the following 5 tips to help manage POI symptoms: 1. Follow a healthy lifestyle including eating a balanced diet and maintaining a healthy weight, taking regular, weight bearing exercise and limiting alcohol. 2. Stop smoking 3. Have cardiovascular risk assessed annually by a GP, to include blood pressure, weight and smoking status, as well as a clinical review for those using HRT. 4. Comply with therapy 5. Discuss any concerns with a doctor and seek help with phycological or physical symptoms that may be having a negative impact on well being. Further help and support can be gained by contacting The Daisy Network, a charity dedicated to providing information and support to women diagnosed with POI.  It provides a support network, information on treatments and research and helps to raise awareness among the medical profession. Share Now: Share on facebook Facebook Share on google Google+ Share on twitter Twitter Share on linkedin LinkedIn Share on facebook Share on google Share on twitter Share on linkedin 1 thought on “What is Early Menopause?” 1. Thanks Bev for including Peri Menopause in your blog. I began having symptoms at 40 and every year experience something new. I still have a few years until I can be classified as in menopause. I feel like GPS don’t think my symptoms are as severe as when in menopause. A hot flash in a nightmare no matter what stage you are in . Leave a Comment Your email address will not be published. Required fields are marked * Menopause: Guide for Managers Download our free Menopause: Guide for Managers for a quick guide to what menopause is, how it impacts the workplace and how line managers can confidently support their female employees.
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Skip to main content Medically reviewed by C.H. Weaver M.D. Medical Editor 5/2022 What is Thrombocytopenia Thrombocytopenia refers to the presence of abnormally low levels of platelets in the circulating blood. Platelets, or thrombocytes, are a specific kind of blood cell that prevent bleeding. The most common reason that cancer patients experience thrombocytopenia is as a side effect of chemotherapy. When chemotherapy affects bone marrow, the body’s ability to produce platelets, the body’s chief defense against bleeding, is diminished. Platelets normally rush to the site of an injury and work with other blood factors to from a blood clot. Normally, there are billions of platelets in the blood; however certain chemotherapy drugs can lower the platelet count. The fewer platelets an individual has in his/her blood and the longer he/she remains without enough of them, the more susceptible he/she is to bleeding. CancerConnect Community490 General Chemotherapy-induced thrombocytopenia typically occurs 6-10 days following administration of the chemotherapy drugs and continues for several days before platelets recover to an appropriate level. Infrequently, cancer patients may also experience thrombocytopenia from other medications or as a consequence of their underlying cancer. When discussing the consequences and management of thrombocytopenia, it is important to distinguish between chemotherapy-induced thrombocytopenia and thrombocytopenia resulting from other causes. The type and dose of chemotherapy also has an effect on how low the platelet count drops and how long it will take to recover. While receiving chemotherapy, a patient’s blood may be tested frequently to make sure he/she has enough platelets. Thrombocytopenia, or “low platelets”, are terms used to describe a low platelet level in the blood. Fortunately, having a low level of platelets can be corrected for many patients. Why is Chemotherapy Induced Thrombocytopenia Important Chemotherapy involves the use of drugs to destroy cancer cells. Chemotherapy works by destroying cancer cells that grow rapidly. Unfortunately, chemotherapy also affects normal cells that grow rapidly, such as blood cells forming in the bone marrow, cells in the hair follicles or cells in the mouth and intestines. When patients experience thrombocytopenia following administration of chemotherapy, they are at risk of certain side effects. Specifically, the fewer platelets in the blood and the longer a patient remains without enough platelets, the more susceptible he/she is to experiencing bleeding. Thrombocytopenia confers a risk of bleeding and the magnitude of risk is closely correlated with the severity and duration of thrombocytopenia. As the platelet count falls below 20,000-50,000; 10,000-20,000; and less than 10,000 cells/µl, the frequency of life-threatening bleeding rises steeply from approximately 5-6% to 10% and 20-40%, respectively. Patients developing thrombocytopenia require treatment with platelet transfusions and occasionally, admission to the hospital, until the platelets return to sufficient levels in the blood to prevent bleeding. Thrombocytopenia is important for another reason. When patients are treated with chemotherapy, it is for the purpose of destroying cancer cells in order to reduce symptoms from their cancer, prolong their survival or increase their chance of cure. Chemotherapy may be administered as a single drug or in combination with several drugs. The combination of chemotherapy drugs administered to a patient is referred to as a treatment regimen. In a chemotherapy treatment regimen, drugs are administered to patients at a defined dose and according to a specific time schedule. The dose and time schedule of drugs administered in the chemotherapy regimen has been scientifically derived to produce the best chance of survival or cure. When patients develop thrombocytopenia following administration of chemotherapy, doctors may have to delay treatment or reduce the doses of the chemotherapy. Clinical studies have shown for certain diseases that when the dose of therapy is reduced or the treatment cycles prolonged, patients have lower cure rates than if they had been able to receive therapy at the full dose on schedule. Fortunately, there are strategies for the treatment of chemotherapy-induced thrombocytopenia that have been proven to reduce the need for platelet transfusions and help patients receive their treatment on schedule. How Do I Know if I Have Thrombocytopenia A complete blood count (CBC) measures the levels of the three basic blood cells: white cells, red cells and platelets. In the United States, the CBC is typically reported in the following format: Image placeholder title Result column: The result column shows counts that fall within the normal range. Flag column: The flag column shows counts that are lower (“L”) or higher (“H”) than the normal range. Reference Interval (or Reference Range) column: The reference interval shows the normal range for each measurement for the lab performing the test. Different labs may use different reference intervals. White blood cells: White blood cells help protect individuals from infections. The above CBC report shows that the patient’s total white cell count is 1.5, which is lower than the normal range of 4.0-10.5. The low white cell count increases the risk of infection. Differential: This portion of the CBC shows the counts for the 5 main kinds of white cells, either as percentages (the first 5 counts), or as the absolute number of cells (the second 5 counts). Absolute neutrophil count: Neutrophils are the main white blood cell for fighting or preventing bacterial or fungal infections. In the CBC report, neutrophils may be referred to as polymorphonuclear cells (polys) or neutrophils. The absolute neutrophil count (ANC) is a measure of the total number of neutrophils present in the blood. When the ANC is less than 1,000, the risk of infection increases. The ANC can be calculated by multiplying the total WBC by the percent of polymorphonuclear cells. For example, this patient’s ANC is .34 = (WBC) 1.5 x 23%. Red blood cells: Red blood cells carry oxygen from the lungs to the rest of the body. The above CBC report indicates that the patient has a red cell count of 3.5, which is lower than the normal range of 4.70-6.10, and therefore, shown in the flag column. Hemoglobin (Hb or Hgb): Hemoglobin is the part of the red cell that carries the oxygen. The above CBC report indicates that the patient’s Hb count is 10.8, which is below the normal range of 14.0-18.0. The hematocrit (HCT), another way of measuring the amount of Hb, is also low. This means that the patient has mild anemia and may be starting to notice symptoms. These three ranges will vary depending on age and gender. For women, they will be lower than those shown here. For example, the Hb reference interval for a woman is 12.0-16.0. Scroll to Continue Recommended Articles Platelets: Platelets are the cells that form blood clots that stop bleeding. The above CBC report indicates that the platelet count for this patient is low. Can Chemotherapy Induced Thrombocytopenia be Prevented Chemotherapy-induced thrombocytopenia occurs because the chemotherapy drugs have destroyed many of the normal rapidly dividing cells in the bone marrow responsible for platelet production. Naturally occurring substances called cytokines exist in the body to regulate certain critical functions at the cellular level. One group of cytokines is commonly referred to as blood cell growth factors. Blood cell growth factors are responsible for stimulating the cells in the bone marrow to produce more blood cells. A blood cell growth factor that is approved by the U.S. Food and Drug Administration (FDA) for the prevention of chemotherapy-induced thrombocytopenia is Neumega® (oprelvekin). Neumega helps the bone marrow create more platelets and has been demonstrated in clinical studies to prevent thrombocytopenia and decrease the need for platelet transfusions in patients at high risk for developing thrombocytopenia. The most common side effect observed with Neumega is fluid retention or edema. This symptom persists while Neumega is being used and is reversible within a few days of discontinuation of Neumega. How is Chemotherapy Induced Thrombocytopenia Treated The most common way to treat thrombocytopenia is with platelet transfusions. Transfusions only temporarily correct thrombocytopenia and are associated with complications. Platelet Transfusion: The goal of a platelet transfusion is to prevent or stop bleeding. Traditionally, the assessment of a patient for a platelet transfusion was based on a clinical “trigger” value, which is a laboratory value below which a transfusion was automatically prescribed. However, transfusions are associated with complications. It is important to carefully evaluate all options when considering a platelet transfusion, as the benefits should outweigh the risk or complications of transfusion. Although improvements have lowered the risk of transfusion-transmitted complications, the only way to effectively eliminate the risk is to avoid exposure to allogeneic blood. Despite the risks, platelet transfusions are common treatments for thrombocytopenia associated with cancer and chemotherapy. Complications of Platelet Transfusion: Patients receiving platelet transfusions are at risk for several reactions that range from mild allergic reactions to life-threatening anaphylaxis. Febrile reactions are the most common, occurring in 1 in every 100 transfusions, but most are not a significant clinical problem. Clinically, the most significant complications are the immunomodulatory effects of alloimmunization, immunosuppression and graft-versus-host disease (GVHD), all of which are rare. Infectious Complications: Patients receiving platelet transfusions are at risk for bacterial, parasitic and viral infections. Bacterial infections are estimated to occur in 1 of every 2,500 transfusions and viral infections occur in approximately 1 in every 3,000. Fear of infection with the human immunodeficiency virus (HIV) has caused the most concern, although the risk per transfusion is relatively low (1 in 225,000 transfusions). All blood components are tested for HIV antibodies; however, there is a period of time after HIV exposure before antibodies can be detected in the blood. To address this issue, intense donor screening is being used and more sensitive assays are being developed. Patients receiving an allogeneic transfusion are at greater risk for lethal infection for the hepatitis viruses than from HIV. It is estimated that hepatitis results from approximately 1 in every 3,000 transfusions. Strategies to Improve Treatment or Prevention of Chemotherapy Induced Thrombocytopenia The reduction in the frequency and severity of thrombocytopenia and its associated complications has resulted from scientists developing a better understanding of the basic biology of bone marrow blood cell production and from participation in clinical studies designed to evaluate strategies directed at reducing thrombocytopenia and its complications. Currently, there are several strategies aimed at improving the prevention and management of thrombocytopenia. New blood cell growth factors: Several new blood cell growth factors are being developed and evaluated in clinical studies for the purpose of improving chemotherapy-induced thrombocytopenia. Romiplostin (AMG 531) is an agent that stimulates the body to produce platelets and thus reduce or reverse thrombocytopenia. Researchers associated with the AMG 531 in Myelodysplastic Syndrome Study Group conducted a clinical trial to evaluate AMG 531 among patients with myelodysplastic syndrome (MDS) who had thrombocytopenia.[1] This trial included 28 patients, nine of whom had to receive platelet transfusions to reduce thrombocytopenia. • 61% of patients had an elevated level of platelets following therapy with AMG 531. • Nearly half of the patients maintained elevated levels of platelets for eight or more weeks. The researchers concluded that AMG 531 appears to provide promising activity among patients with MDS who have thrombocytopenia. Ultimately, AMG 531 may significantly reduce the need for platelet transfusions and prevent bleeding in this group of patients. Future clinical trials are planned to further evaluate AMG 531 in this setting. Peripheral blood stem cells: Stem cells responsible for the production of platelets can be collected in large quantities from the peripheral blood. Delivery of peripheral blood stem cells following very high doses of chemotherapy has been demonstrated to result in more rapid platelet recovery than with stem cells collected from bone marrow. Many doctors have begun evaluating the use of peripheral blood stem cells to support multiple cycles of dose intensive chemotherapy alone or in combination with Neumega® or other blood cell growth factors for the purpose of reducing the frequency and severity of thrombocytopenia and its complications. General PMF Newsletter 490 Reference: Kantarjian HM, Giles FJ, Fenauz P, et al. Evaluating safety and efficacy of AMG 531 for the treatment of thrombocytopenic patients with myelodysplastic syndrome (MDS): Preliminary results of a Phase 1-2 study. Proceedings from the 2007 annual meeting of the American Society of Clinical Oncology. Abstract 7032.
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What does PGS or Preimplantation Genetic Screening involve?2020-09-03T12:06:11+00:00 Tasas de éxito Preimplantation Genetic Testing (PGT-A) Selects the eggs with a correct genetic load The PGT-A (old PGS) is a laboratory technique that enables us to study the DNA of the eggs or embryos in order to select those that have a correct genetic load. It is done within In Vitro Fertilization programmes. In embryos, it provides very good results. Benefits It allows for the selection of eggs and embryos with a correct genetic load. Process Step 1 ico-estudio Genetic study After performing the In Vitro Fertilization, and before the transfer to the uterus, the genetic material of the embryo is studied in order to detect genetic alterations. Step 2 ico-biopsia Embryo biopsy A biopsy is performed on each embryo and those which have an abnormal number of chromosomes are discarded. Step 3 ico-transferencia Transfer One to two healthy embryos are transferred. The healthy embryos can be frozen. Step 1 ico-estudio Genetic study After performing the In Vitro Fertilization, and before the transfer to the uterus, the genetic material of the embryo is studied in order to detect genetic alterations. Step 2 ico-biopsia Embryo biopsy A biopsy is performed on each embryo and those which have an abnormal number of chromosomes are discarded. Setp 3 ico-transferencia Transfer One to two healthy embryos are transferred. The healthy embryos can be frozen. The diagnosis can be obtained in two different ways ico.lupa-embriones Preimplantation Genetic Testing with embryos Once the in vitro fertilization is done and before transferring the embryo to the uterus, a study is carried out to detect whether the genetic load is correct. It is done when the embryos are at the 6-8 cell phase or the blastocyst stage, preferably depending on their quantity and quality. A biopsy is performed on each one and only the healthy embryos are selected, which are the ones that are transferred to the uterus. lupa-ico Preimplantation Genetic Testing with eggs This technique allows us to detect genetic or chromosomal diseases in the egg, before the embryo is formed. This technique analyses a part of the egg called the polar corpuscle, so only hereditary diseases from the mother can be detected. A biopsy of the polar corpuscle is done, and after that, the oocytes are inseminated with the intracytoplasmic sperm injection (ICSI). After two days, the genetic result is obtained and the embryos from the healthy oocytes are selected for transfer. Do you have a question that can’t wait? Request an appointment with our team or ask our experts. Request an appointment Pre-diagnosis Do you have a question that can’t wait? Request an appointment with our team or ask our experts. Request an appointment Pre-diagnosis We at Eugin continue to be there for you YOUR FIRST MEDICAL VISIT FROM HOME
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prednisone before ct scan Zoloft titration Discussion in 'zoloft side effects in children' started by [email protected], 17-Jun-2020. 1. Sh.Rv New Member Zoloft titration La Base Claude Bernard (BCB) est une base de données sur les médicaments et les produits de santé qui a pour but d'aider les professionnels de santé dans leur exercice quotidien de prescription, délivrance et dispensation et de fournir une information exhaustive au grand public. L'équipe scientifique qui met à jour quotidiennement la BCB est exclusivement composée de professionnels de santé, médecins, pharmaciens et préparateurs en pharmacie. En savoir plus NEURONTIN est indiqué en association dans le traitement des épilepsies partielles avec ou sans généralisation secondaire chez l'adulte et l'enfant à partir de 6 ans (voir rubrique Propriétés pharmacodynamiques). 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This FAQ is expressly placed into the public domain, and may be freely disseminated by any who come into its possession. It is a product of the effort of a few among a community known as The Yahoo Benzo Group . It is also a product of the spirit of that entire community. Cialis 20 mg side effects Does amoxicillin help acne ZOLOFT is a selective serotonin reuptake inhibitor SSRI indicated for the treatment of 1. See Full Prescribing Information for titration in PMDD 2.2. • Hepatic. where to buy viagra in fiji ANXIETY DISORDER MEDICATION Comparison Chart Jensen BSP Sept 04 UpToDate, electronic clinical resource tool for physicians and patients that provides information on Adult Primary Care and Internal Medicine, Allergy and. Based on "Essential Psychopharmacology" written by Stephen M. 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This leads to differences among the SSRIs in their half-lives, clinical activity, side effects, and drug interactions. Tier 2 authorization requires a documented 14 day trial of all Tier 1 products within the last 30 days. Tier 3 authorization requires a 14 day trial with all Tier 2 products within the last 60 days (unless no age-appropriate Tier 2 product exists). Claims submitted for Singulair will trigger an automatic check for asthma diagnoses and prior fills of inhaled corticosteroids / asthma rescue medications in the member's claims history. If the appropriate criteria are detected, these claims will be paid with no prior authorization required. For members with a diagnosis of allergic rhinitis the following criteria will apply: For members 2 years of age or older: *Xopenex authorization requests should document why the member is unable to use racemic albuterol. If prescribed for asthma, member should also be utilizing inhaled corticosteroid therapy for long-term control. 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Les instructions posologiques pour les enfants de moins de 12 ans sont fournies dans une sous-rubrique distincte plus loin dans cette rubrique. • NEURONTIN - Gabapentine - Posologie, Effets secondaires. • Sertraline - UpToDate • Zoloft® 50/100 mg, Filmtabletten Cymbalta duloxetine is a selective serotonin and norepinephrine reuptake inhibitor SNRI used for treating depression, anxiety disorder, and pain associated with diabetic peripheral neuropathy or fibromyalgia. zoloft lawsuits Medscape - Depression, OCD, panic disorder, PTSD, PMDD-specific dosing for Zoloft sertraline, frequency-based adverse effects, comprehensive interactions. Online Pharmacy Uk List. 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My aim is to get a “perfect” Ubuntu installation on the T100, such that it can be used successfully as a daily machine in both netbook and tablet modes. In order to get the best support possible, we will be using bleeding-edge builds and the latest Linux kernels. If you’d just prefer an easy life, come back in October and just install Ubuntu 14.10. That said, this little convertible is a lovely machine, and Ubuntu/unity works very nicely on it — finally Unity has a purpose! The more people get on for the ride now, the quicker we can test and iron out bugs. *** First things first, update using Asus Live Update to the latest “BIOS” available. Do any backing up of Windows / recovery partitions. Before we attempt to boot Linux on the T100, we need to do some preparation, so start in Windows. Download the latest daily AMD64 build of Ubuntu 14.04 from here. 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Peritoneum The peritoneum is a large complex serous membrane which forms a closed sac within the abdominal cavity. In the female, this closed sac is perforated by the lateral ends of the fallopian tubes. It is a potential space between the parietal peritoneum lining the abdominal wall and the visceral peritoneum enveloping the abdominal organs. The free surface of the peritoneum has a layer of flattened mesothelial cells which are kept moist and smooth by a thin film of serous fluid. The potential peritoneal spaces, the peritoneal reflections forming peritoneal ligaments, mesenteries and omenta, and the natural flow of peritoneal fluid determine the route of spread of intraperitoneal fluid and disease processes within the abdominal cavity. It can be divided into two main comparments that are separated by the mesentry of the transverse colon: the supramesocolic space above, and the inframesocolic space below. The root of the transverse mesocolon extends across the infraampullary segment of the descending duodenum, the head of the pancreas and continues along the lower edge of the body and tail of pancreas. The peritoneum is innnervated by: • parietal peritoneum - supplied segmentally by spinal (intercostal and lumbar) nerves innervating the overlying muscles. • diaphragmatic (parietal) peritoneum - supplied by the phrenic nerve (C3, 4, 5), hence referred pain from the diaphragm is felt at the tip of the shoulder. • visceral peritoneum has no afferent supply - pain from diseased viscera is due to muscular spasm, tension on mesenteric folds or involvement of the adjacent parietal peritoneum. • mesenteric root - possesses numerous Pacinian corpuscles (mechanoreceptors) which serves a protective function by causing the reflex contraction of abdominal muscles to support the abdominal viscera during jarring movements of the abdomen which may cause undue traction on their peritoneal attachments. Anatomy: Abdominopelvic Share article Article information rID: 5702 Section: Anatomy Synonyms or Alternate Spellings: • Peritoneal cavity Support Radiopaedia and see fewer ads Cases and figures • Peritoneal cavity... Figure 1: peritoneal cavity Drag here to reorder. • Figure 2: mesentery (sagittal) Drag here to reorder. • Updating… Please wait.  Unable to process the form. Check for errors and try again.  Thank you for updating your details.
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Evaluation of a crescent saw guide for tibial plateau-leveling osteotomy: An ex vivo study Authors:  Lindsay C Peterson, Stanley E Kim, Adam H Biedrzycki Vet Surg. 2022 Feb 16. doi: 10.1111/vsu.13781. Objective: To evaluate the effectiveness of a novel crescent-shaped tibial plateau-leveling osteotomy (TPLO) saw guide (crescent guide) to assist with saw control in novice participants. Study design: Ex vivo study. Sample population: Synthetic bones (n = 54) and medium sized dog pelvic limbs (n = 36). Methods: The 6 participants (interns and residents) without any prior experience performing a TPLO each performed 9 osteotomies on synthetic tibia models, and 6 osteotomies in cadaveric limbs of medium-sized dogs. Osteotomies made with the crescent guide were compared with those made with a standard jig and a radial saw guide with a jig. Osteotomy angulation, distance of eccentricity (DOE), and medial tibial cortical damage (synthetic bone models only) were measured from calibrated photographs. Participants rated their experiences with each technique. Results: There was no difference in the DOE, coronal or axial osteotomy angulation between the 3 alignment devices for synthetic bone models or cadavers. Average medial cortical damage with the crescent guide (3.8 ± 7.3 mm2 ) was lower than with the radial guide (35.7 ± 27 mm2 ) and standard jig (51.2 ± 63.2 mm2 ) guides (P = <.01). Five of 6 participants preferred the crescent guide over the standard jig and radial guide. Conclusion: There was no difference in accuracy of osteotomy positioning but using the crescent guide resulted in lower cortical damage and more favorable participant perceptions. Clinical relevance: The crescent guide may improve control of the radial saw during TPLO in novice surgeons but does not appear to aid accurate osteotomy positioning.
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She took Plan B and now she has her period. Can she still be pregnant? Share | JustAnOrdinaryPerson asks: First thank you for taking the time to read my question. Anyways... my girlfriend (19) and I (also 19) recently became sexually active. We are both virgins and have no diseases. I got tested just in case just to make sure. Well we have had sex a few times with protection. Then this passed Wednesday (the 2nd of January) about 2pm, we had sex but I'm not sure I believe the condom broke because once I pulled out I noticed she had white liquid on her which I believed to be sperm. She said she had an orgasm and thinks maybe thats what it was. But any who, just to play it safe around 6pm the same day we went end got the Plan B pill and she took it, and took the 2nd pill around 5am the next morning. The thing is she was supposed to start her period soon and the very next day (Thursday) night she did (which was the same day of the month as the previous period). Well we were wondering if she could be pregnant? Today is the 5th and all of that happened within a short amount of time. Sex (on the 2nd)- Plan B (on the 2nd)- period (on the 3rd) So what im asking really is... 1) Is her period to early to actually know if she got pregnant? Or is it a sign she isn't? 2) If it isn't a sign of anything since its too early, could it increase the chance of her not being pregnant? 3) Can we get a pregnancy test 20 days from intercourse or do we have to wait until the next period? p.s thanks again this will be a huge help Hollie replies: It is highly unlikely your girlfriend is pregnant from this. For one, if a condom breaks, you know it. Latex tends to shred when it breaks ... there'd be a visible hole in it. It sounds like this didn't happen. The white liquid you saw was probably either any lube that was on the condom or your girlfriends own natural lube. Second, Plan B is extremely effective, especially when taken within 24 hours of the risk. Finally, you cannot be pregnant and have a normal period. Some women experience spotting while pregnant, but this is not like a normal period. If your girlfriends period is the normal length and flow that she usually as, she cannot be pregnant. In short, it doesn't sound like she needed the Plan B at all because it doesn't sound like there was any real risk here. But since she's taken it, and has since had her period ... I don't really see ANY way she could possibly be pregnant. If you still feel you need a pregnancy test, tests are accurate 10-14 days after the risk. Have you and your girlfriend talked about protection? Do you only use condoms? Have you talked about a backup method? Many couples use various hormonal methods (pill, patch, ring, etc), diaphragm or cervical cap in addition to condoms. Condoms alone are very effective, but it sounds like you two could benefit from at least a conversation about the possibility of using a backup method. Check it out; Be a Blabbermouth! The Whats, Whys and Hows of Talking About Sex With a Partner Margaret Sanger's Disneyland: Choosing Contraceptives Safe, Sound & Sexy: A Safer Sex How-To Sexual Negotiation for the Long Haul What's the Risk? Easy Pregnancy Risk Assessments Please notify us of any inappropriate ads
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How do you view sleep? Is sleep just something on your “to do” list, or do you view it as a critical part of self-care? If you want to feel your best, lose weight, and function at your highest ability, sleep must be prioritized. Let’s take a look at how to create a healthy bedtime routine and seek accountability so you can be a top-notch sleeper! Here are a few tips for getting quality sleep: • Set a bedtime for yourself! This is one of the best habits to make when it comes to improving your sleep. It’s important to choose a bedtime routine that works for you. If you don’t follow through consistently, just setting a bedtime will not help you sleep better. Remember to factor in how long it takes you to fall asleep! Sleeping enough and at similar times every day helps keep your hormones balanced and our bodies running like clockwork. • Establishing a calming bedtime routine is critical for enabling quality sleep. Find something that brings you joy and contentment. This could be a calming activity such as reading, journaling, drinking a warm cup of tea, or taking a hot bath or shower. • Create a comfortable sleeping environment. This often means reducing any sounds and making sure your room is dark and set to a comfortable temperature. • Wearing glasses that block blue light can help keep your melatonin production at normal levels. Wear these glasses in the evening if you decide to have screen time. However, we recommend turning off your devices two hours before bed since phones and T.V. are mentally stimulating. A “circadian rhythm” is the umbrella term used for a 24-hour cycle that impacts almost every system in our body. It tells us that we should be awake when the sun is out and asleep when the sky grows dark. This light-dark rhythm also tells our bodies when to produce certain hormones and when not to. Getting less sleep makes us more irritable, anxious, and sad. Poor sleep also plays a negative role in reaching any weight loss goals you might have. Whether you’re an athlete, work full-time, or are looking to lose weight, getting enough sleep is so important for overall health and well-being. The benefits of good sleep can help you feel your best and live a healthy, meaningful life! Reach out to our office if you are ready to change your lifestyle habits and start feeling better. Health Connection Wellness Author Health Connection Wellness We take people from sick, tired, and stressed to healthy, happy, and thriving with our comprehensive wellness programs. More posts by Health Connection Wellness Leave a Reply
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What You Find Out About Supplement Reviews And Also What You Don’t Understand About Supplement Reviews Before you Предложена уеб страница choose to take any sort of form of nutritional supplement, it is necessary to read Supplement Reviews. There are a variety of sites which contain these and also each one could be valuable to you in your decision creating procedure. There are numerous reasons why you may desire to do so. Perhaps you merely have the periodic headache or even stomach ache and also uncertain exactly how to manage it? You could be questioning what vitamins you need to take, and more significantly which supplements you must steer clear of. These numerous internet sites may aid answer any kind of questions you may have. A website that gives details on over the counter medications can easily additionally provide info on vitamins and the supplements they might be really good for. 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Many of the individuals believe that purchasing a supplement is not a clever point to do, but our company should be wise adequate to keep in thoughts that enhance assessments exist for our company to learn a little bit of bit regarding the supplement prior to buying it. It is actually constantly better to go via all the supplement reviews to make certain that you are just bring in the appropriate selection. Leave a Reply Your email address will not be published. Required fields are marked *
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Skip to main content Molecular analysis of a large novel deletion causing α+-thalassemia Abstract Background α-thalassaemia is an inherited blood disorder caused by mutations in the α-globin gene cluster. Recognizing the pathogenic α-globin gene mutations associated with α-Thalassemia is of significant importance to thalassaemia’s diagnosis and management. Methods A family with α-thalassaemia from Fujian, China was recruited for this study. The phenotype was confirmed through haematological analysis. Commercially available Gap-PCR genotypic methods were employed to identify the known deletions causing α-thalassemia. MLPA analysis was used to study the novel mutations; this was then confirmed through DNA sequencing and bioinformatics analysis. Results The proband of the family belonged to Southeast Asian type (--SEA) thalassaemia. None of the known mutations associated with α-thalassaemia were detected in this family’s genetics, whereas a novel 6.9 kb deletion (16p13.3 g.29,785-36,746) covering the α2 gene on the globin gene cluster was identified with MLPA and confirmed through Sanger Sequencing. This data led us to propose a novel pathogenic deletion associated with α-thalassemia: -α6.9 /--SEA. Conclusions A novel α-thalassaemia deletion was identified in members of a Chinese family and subsequently analyzed. This finding has helped broaden the spectrum of pathogenic mutations leading to the development of α-thalassaemia, paving the way for improved disease diagnosis and management. Peer Review reports Background Approximately 5% of the world’s population carries globin gene mutations, of which 1.7% exhibit symptoms of α-thalassaemia [1,2,3]. α-thalassaemia is one of the world’s most common hemoglobin disorders associated with deletion or point mutations in α-globin genes clusters. The cluster responsible for this disease is about 30 kb in size and located on the end of chromosome 16p13.3 in the order of 5’-ζ-ψζ-ψα1-α2-αl-θ-3’. Southeast Asian deletion (--SEA), right deletion (-α3.7) and left deletion (-α4.2) are the top three deletions found responsible for α-thalassaemia, whereas Hb ConstantSpring (HBA2:C.427T>C), Hb QuongSze (HBA2:c.377T>C) and Hb Westmead (HBA2:c.369C>G) are the predominant non-deletion types discovered to date. The --SEA, -α3.7, -α4.2, Hb CS and Hb QS account for about 90% of mutations in Chinese populations [4]. In addition, rare deletions including --JS, --11.1, --FIL, --THAI, -α27.6, -α21.9, -α2.4, -α3.8 and -α2.8 have been reported as being associated with α-thalassaemia [5,6,7,8,9,10,11,12,13,14,15,16]. Gap-PCR is used to diagnose α-thalassaemia associated with these rare mutations. Multiple ligation-dependent probe amplification (MLPA) or next generation sequencing (NGS) technologies can be employed to characterize unknown mutations at the molecular level. In this study, we investigated a Chinese family carrying α-thalassaemia and examined the molecular causes underlying the family’s phenotype. An associated novel pathogenic deletion was discovered and characterized for the first time. The proband showed a decrease of MCV and MCH levels and abnormal increase of HbH and HbBart’s levels. Thus we assume it can be an HbH disease. Finally, our results showed a novel deletional α-thalassemia range (NG-000006.1:g.29785-36746 del 6962bp) which covered all α2 gene but not α1 gene. The novel deletion of α-thalassemia also compound with --SEA deletion type, thus the genotype of the proband can described as -α6.9/--SEA. Methods Patients The proband, a 36 year old male of Han nationality, and his family, were recruited for this study. The couple screened positive for α-thalassaemia. Peripheral blood samples from the couple and their son were collected and stored for further investigation. Hematological analysis A routine blood analysis was performed using an automated cell counter (Sysmex XS-1000i; Sysmex Co., Ltd., Kobe, Japan). The subjects’ levels of Hb A, Hb A2 and Hb F were detected with hemoglobin capillary electrophoresis (Sebia, Evry Cedex, France). Molecular analysis The family members’ genomic DNA was obtained at Ruibao Biological Co., Ltd. using an automatic nucleic acid extractor. The gene deletion mutation analysis of α-thalassaemia (-α3.7, -α4.2, --SEA) was performed using gap-PCR [17,18,19]. The PCR reverse dot hybridization technique (PCR-RDB) was used to diagnose the non-deletion α-thalassaemia (Hb CS, Hb QS and Hb Westmead), and 17 common mutations were found and associated with β-thalassaemia, [20,21,22] including CD41–42 (−TCTT), IVS-II-654 (C>T), –28 (A > G), CD 71/72 (+A), CD 17 (AAG > TAG), CD 26 (GAG>AAG), CD43 (GAG>TAG), –29(A > G), CD31 (−C), –32 (C > A), IVS-I-1 (G > T), CD 27/28 (+C), –30(T > C), CD 14/15 (+G), Cap+ 40–43 (−AAAC), initiation codon (ATG > AGG) and IVS-I-5 (G > C). Six α-thalassaemia genotype-screening kits (Yaneng Biological technology Co., Ltd., Shenzhen) were utilized to detect --THAI, -α27.6, HKαα, fusion gene, αααanti4.2 and αααanti3.7. In order to detect unknown variants, a multiplex ligation-dependent probe amplification (MLPA) assay was employed using the SALSA MLPA probemix P140-C1HBA (MRC-Holland, Amsterdam, Netherlands). DNA sequencing and analysis Gap-PCR was used to identify the deletion breakpoints. According to the known DNA sequences around the breakpoints, specific primers were designed. These primer sequences were P1: GGAGAACTTGGCCCCACGTTATCTA and P2: GGCGCTGTCGGCTCGTGCA. All primers were synthesized at Invitrogen (Shanghai, China). Gap-PCR reaction system: 2 mmol dNTP 2 μL, 5 × buffer 4 μL, 25 mmol MgCl2 2 μL, Taq enzyme 1 U, 10 μmol primers 0.5 μL each, template 2 μL, and plus ultra-pure water to 20 μL. Amplification conditions: 96 °C for 5 min; 98 °C for 30 s, 60 °C for 1 min, 72 °C for 2 min, 35 cycles; and 72 °C for 10 min. Electrophoresis analysis was performed and the purified electrophoresis products then sent for Sanger sequencing. The sequenced data were analyzed with GenBank NG_000006.1 as their reference sequences. Results Hematological analysis As shown in Table 1, the MCV, MCH and Hb A2 levels of the proband and his son were much lower than that of the normal reference. In addition, hemoglobin capillary electrophoresis data revealed that the red cells of the proband contained 14% of the HbH variant and 0.6% of Hb Bart’s variant. Thus we assumed the proband could be a patient with HbH disease. The proband’s wife’s Hb A2 level was 2.5%, being slightly lower than the normal content, while both her levels of MCV and MCH were normal. These combined observations allowed us to confirm that the proband and his family’s α-thalassemia phenotype. Table 1 The hematological analysis of the proband, his wife and son Mutation analysis of the thalassemia genes The common pathogenic mutations were screened using PCR-RDB, but no common point mutations for α-thalassemia or β-thalassaemia were found in the entire family, leading us to further investigate the causes underlying the proband’s symptoms. A Gap-PCR analysis to detect three common α-thalassaemia deletions (-α3.7, -α4.2, --SEA) was performed, which revealed the presence of --SEA in both the proband and his son. As shown in Fig. 1, only an 1826bp band, representing the normal gene, appeared in the proband’s wife’s genome. However, a 1306bp band, indicating the --SEA mutation, was observed in the proband, and their son carried both bands. The Gap-PCR results suggest that the family’s genotypes are: (--SEA/--SEA, βNN) for the proband, (--SEA/αα, βNN) for his son and (αα/αα, βNN) for his wife. Fig. 1 figure 1 Common deletion type α-Thalassemia electrophoresis results.1: Proband. 2: Proband’s wife. 3: Proband’s son. N: Negative control. P: Positive control To determine whether the mutation carried by the proband is a reported rare mutation, six α-thalassaemia genotyping kits were used to detect --THAI, -α27.6, HKαα, fusion gene [23], αααanti4.2 and αααanti3.7. However, none of these thalassaemia genes were found in the family genomes, suggesting that this may be a novel mutation. Novel mutations detection with MLPA and gap-PCR To further define the proband’s α-thalassaemia gene mutation, we used an MLPA assay for the DNA screening. As shown in Fig. 2, a large novel deletion in the α-globin gene cluster was detected. To confirm the results, we then analyzed the gene copy number deletion with two pairs of probes in MLPA. Probe Pair 1 consisted of Probes 184 (NG_000006.1: 28168-28169) and 226 (NG_000006.1: 36908-36909). Probe Pair 2 consisted of Probes 391 (NG_000006.1: 30716-30717) and 337 (NG_000006.1: 36628-36629). We discovered that the product ratio from Probe Pair 1 was 0.5, and from Pair 2 was 0. Because the proband also combined with --SEA, the 5’ breakpoint of this novel deletion should be localized at a 2.5 kb region between Probes 184 and 391. The 3’ breakpoint was delimited by a combination of Probes 337 and 226, yielding a 0.3 kb fragment. Gap-PCR was performed with a pair of primers (P1 and P2) to confirm the locations of the breakpoints. Using normal human DNA such as the wife’s as the PCR template meant that the size of the gene product between the primers was too large to require amplification, whereas a 1.4 kb PCR product was observed with the proband’s DNA as the PCR template, indicating that the breakpoint of the deletion was located between the two primers. However, this 1.4 kb fragment was not observed in the son, suggesting that the son had not inherited the novel deletion and was merely a carrier of the --SEA (Fig. 3a). Fig. 2 figure 2 Multiplex ligation-dependent probe amplification assay results. a The corresponding position of amplification products (number unit in bp) and α-globin gene cluster (NG_000006.1) sequence in the P140-C1 HBA kit (MRC-Holland). b The corresponding fragment ratio of MLPA results from the αα/αα, --SEA/αα and proband. X-axis is the product fragment length (bp), while Y-axis represents their ratios. According to the manufacturer’s instructions, probe ratios between 0.7 and 1.3 are defined as normal Fig. 3 figure 3 Polymerase chain reaction and sequencing analysis. a The PCR products were generated from the proband using primers P1 and P2. A unique 1.4 kb product was amplified in the sample of the proband, whereas DNA from Proband’s wife and son, and the normal individuals all failed to amplify this abnormal fragment. The 1.4 kb product was sequenced to determine the precise breakpoint of this deletion. M: DL2000 DNA marker. 1: Proband. 2: Proband’s wife. 3: Proband’s son. N: normal individuals. b Characterization of the breakpoints of this novel deletion by direct sequencing. Sequence analysis of the amplification obtained with gap-PCR using primers P1 and P2 helped us to characterize the breakpoints. As shown in the figure, a 6962bp sequence deletion (NG_000006.1: g.29785_36746) existed in the novel deletion DNA sequencing and analysis To determine the exact location of the breakpoints, the 1.4 kb product of the gap-PCR was sequenced using the P1 and P2 Sanger sequencing primers. The obtained sequencing data were aligned with the reference sequence (NG_000006.1), using NCBI BLAST. The results demonstrated that this was a 6,962 bp deletion, ranging from g.29,785 to g.3,6746 (NG_000006.1: g.29,785-36,746 del 6,962 bp), and covering the α2 but not α1 gene (Fig. 3b). This was a novel deletion associated for the first time in reports with α-thalassaemia. Therefore, we named the new α-thalassaemia deletion -α6.9, with the thalassaemia genotype for the proband being described as -α6.9/--SEA, which can cause HbH disease. Discussion α-thalassaemia is an inherited disorder caused with deletion or mutation events occurring on the α-globin chain. Based on different known combinations of these mutations, α-thalassaemia can be classified into four types, as follows: the silent carrier state (heterozygous to the α+ defect), α-thalassaemia minor (homozygous to the α+ or α0 defects), Hemoglobin H disease (HbH, compound heterozygous to the α0 and α+ defects) and Barts hydrops fetalis (homozygous to the α0 defect) [24, 25]. HbH disease usually produces less than 30% of the normal amount of α-globin due to a deletion of three genes (--/-α) [26,27,28]. The predominant features in HbH disease are anemia with variable amounts of HbH (0.8-40%), and occasionally accompanied by Hb Bart's syndrome in the peripheral blood [29]. The --SEA, -α3.7, -α4.2, Hb CS and Hb QS account for about 90% of the α-thalassaemia mutations in the Chinese population. In southern China, --SEA was the most common α0 mutation, while -α3.7 and -α4.2 were the most common α+ mutation. The combination of the –SEA deletion and these two α+ deletions led to the most common types of HbH disease associated with deletions [30, 31]. Most of the patients with -α3.7/--SEA and -α4.2/--SEA HbH disease developed mild and moderate anemia, and a few had no clinical symptoms [31]. In this study, we investigated a proband from a Chinese family who demonstrated mild anemia and a slight decrease in Hb, which is similar to the phenotypes of patients with -α3.7/--SEA and -α4.2/--SEA HbH disease [32]. Using a routine genotyping method developed based on known mutations or deletions, the genotypes of the family members were identified as (--SEA/--SEA, βNN) for the proband, (--SEA/αα, βNN) for his son and (αα/αα, βNN) for his wife, implying that the son is a minor carrier of --SEA and the proband should be a severe Hydrops Fetalis patient. However, Hemoglobin Barts hydrops fetalis syndrome is generally a fatal clinical phenotype of α-thalassaemia observed in fetuses rather than adults. The inconsistency between the observed genotype and reported clinical phenotypes led us to deduce that an unknown or rare mutation may exist in this patient, whose mutations might be overlooked in routine genetic testing for known mutations of α-thalassaemia. By employing a combination of MLPA and gap-PCR analyses using custom primers, we located a previously unreported, novel 6.9 kb deletion (del16p13.3 g.29,785-36,746) on the patient’s α-globin chains. We named this deletion -α6.9, and we believe this is what led in combination with --SEA to the development of HbH disease. It is significantly important to recognize the pathogenic α-globin gene mutations associated with α-thalassaemia in thalassaemia disease diagnosis and management. The α-globin chains are encoded with two functional alpha genes (Alpha 1 and 2) located on the α-globin gene cluster [24]. This 6.9 kb deletion fragment in -α6.9/--SEA overlaps with the deletions detected in -α3.7/--SEA and -α4.2/--SEA HbH patients, which could explain the observation that α6.9/--SEA, -α3.7/--SEA and -α4.2/--SEA HbH have similar phenotypes. Except for the different deletion sizes of -α6.9, -α3.7 and -α4.2, they all cover a single Alpha 2 gene, resulting in a decreased dosage of α-globin. Pathogenic mutations associated with one (α+ defects) or both (α0 defects) alpha genes (in cis) at the α-globin gene cluster can lead to malfunctions in alpha globin synthesis and metabolism. Further to the discovery in our study of a novel pathogenic hotspot deletion associated with α-thalassaemia, it is important to realize that routine screening can lead to the omission of rare or novel pathogenic sites. To avoid false-negative results in thalassaemia diagnosis, hematological analysis and genetic testing should be applied strategically. When the results of routine genetic testing are inconsistent with the haematological analysis, detailed genetic testing should be carried out to determine the molecular causes for phenotypes. Our research has highlighted the importance of combining different technologies in achieving accurate diagnoses. Recently, next generation sequencing (NGS) technology has also provided a new strategy for genetic diseases screening, including that for thalassaemia. The application of next-generation sequencing to thalassaemia screening not only significantly reduces the possibility for obtaining false-negative results and misdiagnoses, but also eliminates the need for repeat blood sampling and further referral tests. NGS can be a potentially widespread screening method, especially among populations with a high prevalence of thalassaemia [30]; our group is further investigating this possibility. Conclusions We identified a large, novel 6.9 kb deletion, covering α2 but not α1 and causing α-thalassemia. With a series validation and analysis, a new genotype, -α6.9/--SEA, of HbH disease is proposed. Our study expands upon the spectrum of pathogenic mutations associated with α-thalassaemia, thus improving clinical practice in the diagnosis and disease management of thalassaemia. Abbreviations Hb: Hemoglobin Hct: Red blood cell volume MCH: Mean corpuscular hemoglobin MCV: Mean corpuscular volume MLPA: Multiplex ligation-dependent probe amplification PCR-RDB: PCR reverse dot hybridization RBC: Red blood cell count References 1. Rund D. Thalassemia 2016: modern medicine battles an ancient disease. Am J Hematol. 2016;91(1):15–21. Article  Google Scholar  2. Weatherall DJ. Keynote address: the challenge of thalassemia for the developing countries. Ann N Y AcadSci. 2005;1054(1):11–7. Article  Google Scholar  3. Liao C, Li Q, Wei J, et al. 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Article  Google Scholar  Download references Acknowledgements We wish to express our appreciation to Dr. Zhuang for his modification of the article’s English contents. Funding We gratefully acknowledge the Shenzhen Science and Technology Innovation Committee (KQJSCX20170329152357439) for their support to this research about the specific gap-PCR amplification and sequencing of specific products. Availability of data and materials The datasets used and/or analysed during the current study available from the corresponding author on reasonable request. Author information Authors and Affiliations Authors Contributions JZ designed the study and wrote the article. JZ, QZ, QX, SZ performed routine thalassemia analysis; JT and JW performed the specific gap-PCR amplification and the DNA sequencing; YZ, YW and YP analyzed the data; GW and YJ modified and polished the paper. All authors approved the final article. Corresponding author Correspondence to Yuying Jiang. Ethics declarations Ethics approval and consent to participate This study was approved by the ethics committee of The Woman’s and Children’s Hospital of Quanzhou. All patients signed written informed consent and agree themselves and their children to take part in this study and using the relevant data and information for scientific research. Consent for publication We confirmed that all patients participate in this study signed written informed consent for publication their own and children’s genetic data and relevant information. Competing interests The authors declare that they have no competing interests. Publisher’s Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Rights and permissions Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Reprints and Permissions About this article Verify currency and authenticity via CrossMark Cite this article Zhuang, J., Tian, J., Wei, J. et al. Molecular analysis of a large novel deletion causing α+-thalassemia. BMC Med Genet 20, 74 (2019). https://doi.org/10.1186/s12881-019-0797-8 Download citation • Received: • Accepted: • Published: • DOI: https://doi.org/10.1186/s12881-019-0797-8 Keywords • α-Thalassemia • Gap-PCR • MLPA • Sequencing
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bronchitis herbal medication - Tips To Relieving Your Bronchitis All On Your Own Bronchitis Remedy Natural Bronchitis Treatment Treat Bronchitis Naturally Bronchitis cure   Tips To Relieving Your Bronchitis All On Your Own Bronchitis is a disease that can affect the lungs, but usually only the respiratory system is the one affected. There are two types of bronchitis: acute and chronic bronchitis. Both of them can be treated at home, but the chronic bronchitis poses a little more problems than the acute type. When you have a bronchitis bout, your bronchial tubes become inflamed and swollen. Each time that this happens, the lining of those tubes becomes scarred. Over time, the more irritation that happens the more excessive mucus production will become. Your tubes lining will become thickened because of the scarring. Bronovil Natural Bronchitis Remedy irritable bowel syndrome (Bronchitis) natural remedy Natural remedy for bronchitis. Formulated to Help Support: • Stop persistent cough • Prevent virus from attacking your lungs • Boost your immune system • Relieve lung inflamation • Naturally relieve pain and fever • Breathe easier • Feel stronger in no time Great Product Bronchitis Remedy  Acid reflux can now be successfully treated with many medications. If you think that someone you know may be suffering from a chronic cough caused by bronchitis or possibly asthma, it's important to understand the lifestyle implications this may involve. The primary focus however, should be to get an accurate diagnosis from a qualified respiratory or pulmonary medical professional. First pneumonia: this is a very serious infection that takes place in the lungs. The alveoli, that usually help make the exchange of the oxygen in your lungs, get filled with pus, or other liquids. As you can imagine this is very bad because you then suffer from a lack of oxygen that together with the spread of the infection from the lungs can cause death. Those that suffer from chronic bronchitis start by having an inflammation of their bronchial tubes. These are your air passageways, remember and therefore are very important to be clear so that air can move easily in and out of them allowing you to breathe. One thing that your doctor's will determine is if there is something else wrong that could possibly be causing your bronchitis in the first place. Some will have additional conditions like asthma that can lead to this problem. But, when there are no underlying causes, bronchitis can be labelled as the cause of your illness and then treated as such. As it's recognized that dust is almost everywhere, it's important to try to limit exposure as much as possible. This sensitivity of the person with chronic bronchitis will determine the level of action that's needed to limit dust exposure. Someone who is extremely sensitive may need special air cleaning equipment installed in their home. While another who's sensitivity is not as pronounced may be able to live comfortably in a home simply on a regular cleaning schedule. Check out the link below for free report on tips to eliminate asthmatic and bronchial cough triggers in your home. acute bronchitis When you have bronchitis, the start making mucus in overtime, and it starts clogging your breathing passages, which is why you find it hard to breathe. You'll want to stay away from anything dairy because it can add to the mucus. Drink lots of water, and add some Tabasco to some soups to help kill the bacteria. You'll also be hacking a lot of thick green and yellow mucus, don't worry, you need to do that to get it out of your system and body. For greater resources on bronchitis please visit http://www.bronchitis-guide.com/asthmatic-bronchitis.htm or http://www.bronchitis-guide.com/bronchitis-treatment.htm Frequently, wheezing sounds develop when the child breathes, caused by the passage of air through mucus-clogged bronchi. Appetite loss and fatigue also are common, but they usually pass after two or three days. The cough itself should subside within seven to ten days. From looking at your test results and listening to your lungs, your doctor will determine the right type of treatment for your condition. Usually in cases of acute conditions, this treatment is simply rest and fluids. If you are experiencing wheezing and coughing, then it is likely you have acute bronchitis. You can tell by listening to your breathing, can you hear a wheezing sound every time you take a breath. Your bronchial tubes may be constricted which is causing the wheezing and coughing. Just make sure you take lots of fluids and rest, the disorder will usually clear up within a few days. As it is an illness that affects the respiratory system, here are some tricks to make your breathing a little easier if suffering from bronchitis. Drinking a lot of fluids every day can help you very much. Fluids can help in keeping the mucus very thin, therefor easy to cough up. The best thing to drink in such conditions is water. Sugar products or dairy's are better to be avoided, because they have a tendency to weaken your immune system and even produce more mucus. A chronic cough, wheezing, breathing difficulties and a tight chest have also been associated with the common smoker's cough. This is unfortunate as there are many environmental factors that can contribute to an infection and caused these types of symptoms. Bronchitis does not affect the lungs, but the passage that carry the air from the trachea to the lungs. These airways can get inflamed of irritated, but they either get better on their own or with treatment. This condition is not a life threatening one, although it may have some serious complications. When you have a bronchitis bout, your bronchial tubes become inflamed and swollen. Each time that this happens, the lining of those tubes becomes scarred. Over time, the more irritation that happens the more excessive mucus production will become. Your tubes lining will become thickened because of the scarring. Those that suffer from chronic symptoms of bronchitis often develop asthma because of it. This is caused by the long term inflammation of your air passageways. In any case, it is essential that you get help from your doctor in dealing with your condition. Those that are suffering from chronic bronchitis have a very serious illness to consider. Chronic bronchitis is often caused by smoking, but its not the only time that you can get it. You can also get chronic bronchitis from air pollution that is severe or toxic gasses that are in the area in which you work. If your doctor determines that you have asthma, or that your chronic condition is likely to develop asthma, then he or she may recommend additional treatment for your condition. Those that are diagnosised with asthma will need an inhaler and sometimes additional asthma medications. The physician may prescribe antibiotics if he suspects a secondary bacterial infection. In the case of allergic bronchitis, the physician will treat the allergies directly. Avoid all dairy, & high protein meats, high sugar & fried foods. Tea and Steam are your friends. Mainly you want to clear your throat and lungs, allow yourself to practice smooth breathing. So, various Teas like Chammomiles with a little honey and lemon (not sugar or milk, those will gum things up). Also, warm bath, just breathe in the steam. Do this daily. In the meantime, take it easy, rest a lot. You're at a vulnerable stage and need to take care of yourself. Abigail Franks has done extensive research into Asthma,Allergies, and their triggers. You can find out more about Bronchitis causes and cures and Asthma Triggers and Treatments on her Asthma website. Anything chronic is considered to be a persistent, recurrent and lasting condition. While chronic bronchitis has often been associated with allergies and/or asthma, there are many other causes that can trigger a bronchial infection. Asthma as we know is a lung disease that is characterized by asthmatic events triggered by a variety of factors which cause a constriction of the bronchial tubes and air passages.   Natural Bronchitis Remedy What People Said About Bronovil Bronchitis Cure "I felt miserable so i went to doctor and he said i had a bronchitis. he gave me antibiotic but even 2 weeks later i was still coughing. i got the bronovil remedy and 3 days later my cough went away." Betty - California Bronchitis treatment Golden seal and echanacia are used for upper respiratory and immune system. These are used to protect you and build yourself up, not to treat an infection. If you have no infection but have mucous and other symptoms, you can use guafinisian to help break up the mucous. Remember that you don't have to smoke yourself to be a victim of what smoke can do. Just being exposed to it over long periods of time puts you at risk. Another useful trick is not to take any pills that suppress your cough. When you have acute bronchitis and you cough, mucus is brought up together with your cough, and believe it or not this is a good thing. If you take cough suppressants, mucus can buildup and cause serious complications, like pneumonia. Another medication that must not be taken is antihistamines. Instead of making you feel better, they can do a lot of damage. These medication dry your airways and cause the phlegm to thicken up, which can make your condition even worse than before. One such environmental factor is dust. While dust is a common substance found everywhere, it's especially problematic for those of us who may have a compromised respiratory system. A less than ideal breathing tract is found in people suffering with asthma, many allergies and yes even smokers. What's been ignored in many cases however, is that exposure to chemicals can cause a sensitivity to environmental factors such as dust. During your initial bouts of chronic bronchitis, your symptoms are the same as those that a person with acute bronchitis will face. There is a heavy discharge of mucus from your coughing and the cough itself is a tell tale sign of chronic bronchitis. According to the Mayo Clinic, a well regarded medical facility, bronchitis and the resulting cough can also be caused from stomach acid irritating for food pipe or esophagus. This is better known as acid reflux disease. 3. Female smokers are more likely to get COPD than men are. 4. If you are a victim of air pollution, second hand smoke, or have a history of infections of the respiratory system, you have an increased risk of getting COPD. Bronchitis is an inflammation of the bronchi (lung airways), resulting in persistent cough that produces consideration quantities of sputum (phlegm). Bronchitis is more common in smokers and in areas with high atmospheric pollution. Chronic bronchitis is a disease in which there is diffused inflammation of the air passages in the lungs, leading to decreased uptake of oxygen by the lungs and increased mucus production. Types of Bronchitis chronic bronchitis fibrinous bronchitis castellani's bronchitis avian infectious bronchitis Bronchitis usually occurs following a viral respiratory infection or with prolonged cigarette smoking. Symptoms can include coughing, shortness of breath, wheezing and fatigue. Acute bronchitis is usually caused by viruses or bacteria and may last several days or weeks. Having recurrent (frequent) bronchitis in the age of 13 is not normal and you need a specialist consultation because it has potentially serious effects. 2. The largest risk factor in patients that get COPD is that of smoking. 80 to 90 percent of those that suffer from this condition will be smokers. 90 percent of them will die from it because they smoked. Exposure to chemical fumes and odors may compromise an otherwise healthy respiratory system. This in turn can lead to sensitivity to other environmental factors like dust, but also both primary and secondary tobacco smoke. While the validity of the effects of secondhand smoke are continue to be debated, it has been shown to be an important breathing factor for those with a compromised respiratory system. All of these factors can contribute to the chronic cough experienced by many asthma, allergy and bronchitis sufferers. 'Is There A Treatment For Chronic Bronchitis' this question is nagging you when there is uncertainty and doubt. For some individuals, bronchitis happens often. This is what is called chronic bronchitis. In these individuals, the bronchitis may not go away, but may lessen in its severity. When this happens, individuals need to be aware of it and seek the help that's needed as soon as possible. These products have the goal of reducing the amount of inflammation in your air passageways as well as open them up to allow for better passage to your lungs. This type of medication can be vitally important to those suffering from asthma. 5. 19 percent of those that suffer from COPD will get it from their work environment. Those that suffer from chronic bronchitis start by having an inflammation of their bronchial tubes. These are your air passageways, remember and therefore are very important to be clear so that air can move easily in and out of them allowing you to breathe. Chronic bronchitis is a serious health condition that can lead to or even tell you that there is something else wrong with the body. For example, chronic bronchitis can be an indication that you are suffering from asthma or lung disorders. In fact, those that do suffer from chronic bronchitis are more likely to end up with lung cancer than those that do not. Lung cancer is one of the leader's in death among people that smoke for long periods of time. Using a vaporizer or a humidifier is a very good idea. These help your airways stay moist. A worm bath can also do you very good. Another trick is to stay away from any things that can irritate your respiratory system, such as chemicals, paint, dust, and so on. If your symptoms get worse after a couple of days, the smart thing to do is see a doctor. Now, let me answer you a question that I believe it is in everybody' s mind: what is the difference between bronchitis and pneumonia. Well, they are both respiratory diseases, but there are lots of differences between them. To better understand this, let us talk about each one of them. Rachel Broune writes articles for Bronchitis Home Remedies . He also writes for Bronchitis Remedies and Herbs Chronic bronchitis is also a condition which affects your quality of life. You can't do the things that you like to do without suffering from breathlessness. You cough all of the time and your chest hurts. You are sick to more extreme levels when a cold just brushes by others. Here are some facts you should know about chronic bronchitis. 1. COPD claims some 122,000 deaths each year in the US, as claimed by a study done in 2003. It is one of the leading causes of death. For more information about bronchitis, please refer to my website http://www.bronchitisguide.com or you can get the detailed guide from http://www.beyantryatt.com/bronchitis               Learn More about Natural Bronchitis Remedy What is Bronchitis? Bronchitis is defined as an inflammation of the bronchi. Bronchi are airways in the respiratory tract that bring air into the lungs. This inflammation is typically caused by viruses or bacteria, but it may also be caused by inhaled irritants, such as cigarette smoke or harmful chemicals. Most cases of bronchitis cases involve a viral pathogen. The inflammation is... There are two forms of bronchitis, the acute and the chronic bronchitis. The most common of the two is the acute bronchitis form. This is the result of an infection with a virus or bacteria. Acute bronchitis is in most of the cases a consequence of an infection in the upper respiratory system. To actually understand bronchitis, we must know what part of our body it affects and how. Well,... People who smoke, or live with smokers, often cough a great deal. It s usually referred to as smokers cough, but in over 80% of all cases, it s COPD. To just take some over-the-counter cough medicine, or live with it is endangering who whole life. COPD? COPD stands for Chronic Obstructive Pulmonary Disease and is usually a combination of two similar maladies, i.e. chronic bronchitis and... A very important system is the respiratory system of the body. It distributes oxygen in order for the body to live and without it, the body dies. It is this reason that taking care of your body s respiratory system is imperative. During a person s life, they will get a breathing disorder. One such illness is chronic bronchitis. This is an obstructive pulmonary disorder where the bronchi become... bronchitis herbal medication | bronchitis herbal drugs | bronchitis herbal medicine | bronchitis herbal recipe | bronchitis herbal mediion |               (c) 2018 bronchitiscough.info Contact Us | About Us | Privacy Policy | RSS Feed | bronchitis herbal medication
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Preventing Irritable Bowel Syndrome In the realm of digestive health, preventing issues like Irritable Bowel Syndrome (IBS) is always preferable to dealing with the symptoms later on. Recent research published in the journal Gut sheds light on how certain lifestyle behaviors can play a crucial role in reducing the risk of developing IBS. Let’s delve into the details of IBS, its potential causes, and the preventive strategies that can help keep this gastrointestinal disorder at bay. Understanding Irritable Bowel Syndrome (IBS) IBS is a gastrointestinal disorder that affects the normal functioning of the stomach and intestines, leading to discomfort and changes in bowel habits. This condition is characterized by altered bowel motility and gut sensitivity, resulting in symptoms like abdominal pain, cramping, and irregularities in bowel movements. Some individuals with IBS experience diarrhea, some suffer from constipation, and others may face a combination of both issues. Despite ongoing research, the exact cause of IBS remains elusive. Factors such as early life stress, infections like gastroenteritis, nervous system issues, and damage to the gut microbiome are believed to contribute to the development of this disorder. The composition of beneficial bacteria in the digestive tract, known as the gut microbiome, also plays a significant role in the onset of IBS. Preventing and Managing IBS through Healthy Habits While the root cause of IBS may still be unclear, adopting certain healthy lifestyle behaviors can significantly reduce the risk of developing this condition. A recent study examining over 64,000 adults revealed that adhering to specific habits such as never smoking, getting adequate sleep, engaging in regular physical activity, following a healthy diet, and consuming alcohol in moderation was associated with a lower incidence of IBS. See also  Mistakes to Avoid While Purchasing iPhone 15/15 Pro Dr. Will Bulsiewicz, a renowned gastroenterologist, emphasizes the protective effects of these healthy lifestyle choices on the gut microbiome, thereby offering potential benefits in preventing IBS. For instance, habits like never smoking, prioritizing sleep, and staying physically active have been linked to a lower risk of IBS in previous studies, showcasing their positive impact on gut health. While the inclusion of moderate alcohol intake in preventive measures may raise some eyebrows due to its potential digestive symptoms, focusing on a nutrient-rich diet remains crucial for IBS prevention. Dietary fiber, in particular, has shown promising results in protecting against the development of IBS by promoting gut microbiota balance and addressing root causes of the disorder. Strategies to Alleviate IBS Symptoms For individuals already grappling with IBS, implementing specific strategies can help manage the condition effectively. The low FODMAP diet, known for its efficacy in improving IBS symptoms, restricts certain carbohydrates to pinpoint triggers of discomfort. Limiting dairy products, artificial sweeteners, caffeine, alcohol, and carbonated drinks can also aid in alleviating IBS symptoms. Additionally, maintaining an active lifestyle and incorporating stress management techniques can further contribute to symptom relief. Both exercise and stress reduction have been linked to improvements in IBS symptoms, highlighting the holistic approach needed to address gastrointestinal health concerns. In conclusion, adopting a holistic approach to gut health through healthy lifestyle choices and dietary modifications can play a pivotal role in preventing and managing Irritable Bowel Syndrome. By prioritizing habits that support the gut microbiome and overall well-being, individuals can empower themselves to lead healthier, symptom-free lives. See also  JN.1 COVID Variant Threatens India's Holiday Season
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December 9, 2021 Portal Turist Coecua Toriano Explore The World Mosquitoes Are Eating Plastic And Spreading It To New Food Chains foodTogether with different remedy solutions which are available on the market for treating impotence it’s simply as essential to pay strict consideration to lifestyle and food consumption in order to stop and treat ED. three. Recent fruits and Vegetables-contemporary produce is an effective way to get vitamins and minerals that help the physique perform as regular. Spending much less in your food invoice would not solely provide financial advantages: You would also end up consuming extra nutritious food and decreasing waste. Products that are excessive in saturated fat are. In this article we concentrate us on an inventory of foods that contain bad fat. While not everybody who eats white breads and processed foods will get diabetes, the connection is clear: Alloxan causes diabetes in these genetically vulnerable to the illness. Foods that improve metabolism embrace those foods which might be high in advanced carbohydrates and proteins. Eating at common intervals and as part of a schedule not only helps the physique’s hormonal system but you’ll find that you are digesting your food much better as nicely. Take pleasure in wholesome fats. It can be both a wholesome sandwich, protein shake, fruit, wholesome fat, or whole grains. There is no doubt that proper now quick food adjustments the face of many nations and consuming habits around the globe. Because of this the non-fatty dairy foods are fat burners and needs to be included in any eating regimen. 43 The well being food motion often called raw foodism promotes a principally vegan food regimen of uncooked fruits, vegetables, and grains ready in numerous methods, including juicing, food dehydration, sprouting, and different methods of preparation that do not warmth the food above 118 °F (forty seven.eight °C).
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Alpine Clinic Treatment Building Ozone Therapy Ozone therapy is a unique form of therapy that both heals and detoxifies at the same time. It is used to treat a variety of chronic diseases and conditions. In our office, it is used in categories of therapy such as: Prolozone treatment for joint and trigger point pain; Bladder Insufflation for treatment of chronic recurrent bladder infections and interstitial cystitis; Rectal Insufflation where treatment of the whole body is needed; local intradermal injections for resistant infections.  At the current time, Steven Jones NP-c is the only provider at The Alpine Clinic fully trained and certified in the use and treatments associated with Ozone therapy. Steve is a founding member of the American Academy of Ozone Therapy and a fellow of the organization.  There are many more uses of ozone which include intravenous therapies know as Major Auto Hemotherapy which we do not do at our clinic. WHAT IS OZONE? The oxygen you breathe is present in the air as a pair of oxygen atoms. This is the most stable form of oxygen, and it’s colorless. Ozone is a blue colored form of oxygen (it’s what makes the sky blue), and unlike regular oxygen, it is composed of three oxygen atoms instead of two. It is the addition of the third oxygen atom that makes ozone “supercharged” oxygen and gives it all of its remarkable medical properties.  The use of ozone to treat various medical conditions was first developed in Germany in the early 1950’s. Today, medical ozone therapy is common throughout Europe, and its use has gradually been spreading in America over the last 25 years. OZONE IS TOXIC ISN’T IT? Anything, including water and oxygen, can be toxic if given in amounts that exceed the body’s capacity to utilize it. Ozone is found naturally in the body. The white cells make it as part of the immune response. Pure medical grade ozone, when it is used according to the established medical guidelines, has a safety record that is unparalleled. MEDICAL PROPERTIES OF OZONE Ozone has five properties that account for why it works so well:  • Ozone is a potent regulator of the immune system. This means that when the immune system is overactive (as in auto-immune disease), ozone will calm it down. Conversely, when the immune system is under active as in cancer, AIDS, and chronic infections, ozone will stimulate it. This unique ability of ozone stems from its action on the membranes of white cells that causes them to produce immune related messenger molecules called cytokines. Examples of cytokines are gamma interferon, interleukin-2, colony stimulating factor, and TNF-alpha just to name a few. • Ozone stimulates increased uptake of oxygen by stimulating the enzyme diphosphoglycerate (DPG). DPG enables the release of oxygen from the hemoglobin molecule so that it can be taken up into the cell. In the absence of an adequate amount of DPG, our cells become starved for oxygen. This is a common problem in diabetics. • Ozone improves circulation. It does this by enhancing the flow characteristics of blood as a liquid. This effect enables more of the oxygen-carrying hemoglobin to reach the capillaries where ultimately the cells will receive more of the oxygen they require. Many patients with chronic inflammatory conditions have impaired circulation. • Ozone increases antioxidant protection more than any other therapy including vitamin C. Most people with chronic disease have deficient antioxidant defenses. • Ozone is a powerful mitochondrial stimulant. The fundamental underlying cause behind all degenerative diseases from diabetes to heart disease to cancer is decreased mitochondrial energy production. IS OZONE THERAPY FOR ME? This is a decision for a doctor who is trained and experienced in the medical use of ozone. Some conditions simply will not clear up unless ozone is used, and of course, many conditions will clear up without ozone. Because of its many therapeutic properties, ozone can be used as part of a therapeutic plan for almost every disease.  It is invaluable in the treatment of degenerative joint disease, muscle spasm and trauma, heart disease and circulatory disorders. Chronic infections such as hepatitis-C, herpes, Lyme, and AIDS respond very favorably to ozone. It is also very helpful in chronic fatigue syndrome, fibromyalgia, and autoimmune diseases.  It is important to realize that ozone therapy is not a panacea or some kind of magic bullet. Although it is often an indispensable modality, it is only rarely effective by itself. In the great majority of cases it must be combined with an individualized program of other alternative and natural therapies, such as nutrition and detoxification.
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Endoscopy + -Text Size TOPICS What is endoscopy? Endoscopy (en-DAHS-kuh-pee) is a medical procedure done with an instrument called an endoscope (EN-duh-skop). The endoscope is put into the body to look inside, and is sometimes used for certain kinds of surgery. Looking with an endoscope is different from using imaging tests, like x-rays and CT scans, which can get pictures of the inside the body without putting tools or devices into it. There are many different kinds of endoscopes, or “scopes.” Most are like thin, hollow tubes that a doctor uses to look right into the body. Most are lighted, and some have a small video camera on the end that puts pictures on a computer screen. Endoscopes are different lengths and shapes. Some are stiff, while others are flexible. There’s a new one small enough to be swallowed, which can send images wirelessly. Each type is specially designed for looking at a certain part of the body. Depending on the area of the body being looked at, the endoscope may be put in the mouth, anus, or urethra (your-EE-thruh) (the tube that carries urine out of the bladder). Sometimes, it’s put through a small incision (cut) made in the skin. Some types of endoscopes and the areas of the body they view Type of endoscope Put in through Body part or area(s) looked at Name(s) of procedure Arthroscope Cuts in the skin Joints Arthroscopy Bronchoscope Mouth or nose Trachea (windpipe) and bronchi (tubes going to the lungs) Bronchoscopy, flexible bronchoscopy Colonoscope Anus Colon and large intestine Colonoscopy, lower endoscopy Cystoscope Urethra Bladder Cystoscopy, cystourethroscopy Enteroscope Mouth or anus Small intestine Enteroscopy Esophagogastroduodeno-scope Mouth Esophagus (swallowing tube), stomach, and duodenum (first part of small intestine) Esophagogastroduodenoscopy (EGD), upper endoscopy, panendoscopy, gastroscopy Hysteroscope Vagina Inside of uterus Hysteroscopy Laparoscope Cut(s) in the abdomen (belly) Space inside abdomen and pelvis Laparoscopy, peritoneal endoscopy Laryngoscope Mouth or nose Larynx (voice box) Laryngoscopy Mediastinoscope Cut(s) above the sternum (breastbone) Mediastinum (space between the lungs) Mediastinoscopy Sigmoidoscope, flexible sigmoidoscope Anus Rectum and sigmoid colon (lower part of large intestine) Sigmoidoscopy, flexible sigmoidoscopy, proctosigmoidoscopy Thoracoscope Cut(s) in the chest Space between lungs and chest wall Thoracoscopy, pleuroscopy Last Medical Review: 02/03/2015 Last Revised: 02/23/2015
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Skip to main content The androgen receptor plays a suppressive role in epithelial- mesenchymal transition of human prostate cancer stem progenitor cells Abstract Background To investigate the roles of androgen receptor (AR) in epithelial- mesenchymal transition (EMT) in human prostate cancer stem progenitor (S/P) cells isolated from LNCaP cell line. Methods The S/P cells were obtained from LNCaP cell line through florescence-activated cell sorting (FACS). AR was overexpressed in S/P cells through lentivirus. Western blot assay was used to detect the EMT markers expression, such as E Cadherin, N Cadherin, Vimentin and Snail. MTT assay, soft agar colony formation assay, sphere formation assay and migration assay were used to investigate AR’s roles in EMT of S/P cells. Cell signaling pathways associated with proliferation and apoptosis of S/P cells were detected simultaneously. And S/P cells were treated with in vitro combinatory use of LY 294002 (inhibitor of AKT signaling molecules) with γ-TT and/or 5-AZA. Results Our data showed that S/P cells from LNCaP had high EMT markers expression, more tumorigenesis and strong migration ability. And in S/P cells overexpressed with AR, the expression of EMT markers decreased. In addition, these cells had less proliferation ability, tumorigenesis ability, self-renewal and migration ability. At the same time, targeting S/P cells with AKT signaling pathway inhibitor LY29004 andγ-TT and/or 5-AZA could inhibit S/P cell’s proliferation and tumorigenesis. Conclusions Our data suggest that AR played a negative role in EMT of PCa S/P cells, by regulating AKT cell signaling pathway, which could be a new strategy to treat castration resistant prostate cancer (CRPC). Background Prostate cancer is the most common malignancy in the world and the second most common cause of cancer-related mortality in men [1]. Early prostate cancer (T1-T2) can undergo radical surgery or radiation therapy, the curative effect is good. For locally advanced or metastatic prostate cancer (T3-T4), endocrine therapy is the preferred method. Unfortunately, after 1–3 years, the tumors ultimately progress and become castration resistant prostate cancer (CRPC). This is the end stage of prostate cancer and is the bottleneck of treatment. The mechanism of CRPC advance, why the tumor is not sensitive to chemotherapy, was not completely clear. More and more evidence indicate that the cancer stem cells (CSC) exist objectively and play an important role in the tumorigenesis and progression of the tumors [2,3]. This part takes up only a small percentage of all cancer cells, but is closely related to tumor recurrence and metastasis. Many research has shown that cancer drug resistance to chemotherapy is associated with CSC, which have the potential for self-renewal, differentiation, strong migration and invasion ability [4, 5]. Cell signaling pathways related to maintain stem cell self-renewal and proliferation include PI3K/AKT, Wnt, STAT3/5, EGF/EGFR and so on [6-9]. Preliminary works from our research group showed that after endocrine therapy, the prostate cancer stem/progenitor (S/P) cells increased in tumor tissue of the patients, which further confirmed the role of S/P cells in prostate cancer progression [10]. The epithelial- mesenchymal transition (EMT) is the process that in a particular physiological and pathological conditions, the epithelial cells transfer to mesenchymal cells, involving in multiple genes and multi-step, the intercellular adhesion weakening and cell movement strengthening. EMT provides such a basis for epithelial tumor cells. Lue’s research [11] had shown that a zinc transporter LIV1 could promote EMT and metastasis of prostate cancer cells. This procedure is mediated through ERK signaling pathway. Other studies have found that BMP7 and SIRT1 could induce EMT in prostate cancer PC-3 cells, and PI3K and ERK signaling pathway was involved in this process. This promoted invasion and metastasis of prostate cancer [12,13]. In addition, the EMT markers can be detected in prostate cancer patients, with primary tumors and bone metastases. Immunohistochemical study showed that the expression of EMT markers was higher in the edge location cells of primary tumors and metastatic lesion than that of the cells in the center of the tumor. Notch1 expression in bone metastases is significantly higher than that in primary tumorsand, and may play an important role in the bone metastasis of prostate cancer [14]. These data suggest that EMT plays an important role in the invasion and metastasis of prostate cancer. Consistent with this, our preliminary data showed the cancer cells with EMT phenotype increased after endocrine therapy in human PCa tissue [15,16]. It was shown that EMT phenotype tumor cells had certain features of stem cells, and some stem-like cells had EMT features, and these two types of cells were associated with tumor drug resistance [17-19]. Androgen receptor (AR), a member of the nuclear receptor super family, can be activated by its ligands, androgens, to regulate its target gene expression. Androgen/androgen receptor (AR) signaling plays pivotal roles in the prostate development and homeostasis as well as in the progression of prostate cancer (PCa) [20]. Whether prostate cancer stem cells have the features of EMT and roles of AR in this process was unclear, in this study, we would investigate EMT characteristics in prostate cancer S/P cells, and the roles of AR in regulating EMT and characteristics of S/P cells. Methods Cell lines, transfection and infection The human PCa cell lines LNCaP were purchased from the Chinese Type Culture Collection (CTCC). LNCaP (passage X) was maintained in a humidified incubator (95% O2; 5% CO2) and cultured with RPMI 1640 medium (Invitrogen, Carlsbad, CA) with 10% fetal calf serum and 2 mM glutamine (Gibco BRL), 1% penicillin and streptomycin (Invitrogen). Androgen deprivation or androgen treatment in vitro were carried out by culturing the cells in medium containing 10% charcoal-stripped fetal calf serum plus 1 nM 5α-dihydrotestosterone (DHT, Sigma) or 10 nM DHT. For immunocytochemical staining, cell lines were grown on chamber slides (Thermo Fisher Scientific Inc. MA) until confluence. For transfection of plasmid pRetrosuperMycshRNA (Addgene, MA) and Oligo Bcl-2 siRNA (Santa Cruz Biotechnology, CA), cells were plated in culture dishes 24 hours before transfection and 2 days later in accordance with the manufacturer’s instructions using Lipofectamine Plus reagent (Invitrogen Life Technologies, CA). After transfection, cells were used to do MTT assay. The scrambled siRNA (Santa Cruz Biotechnology, CA)) was used as the negative control (sc-37007). For infection of lentivirus carrying vector or AR, 293 T cells were transfected with a mixture of DNAs (Lentiviral vectors pWPI) (Addgene, MA) containing AR (psPAX2 packaging plasmid, and pMD2G envelope plasmid, at a 4:3:2 ratio) using Lipofectamine (Invitrogen, CA) according to the manufacturer’s protocol. After infection, the media containing the virus was changed into normal culture medium. Since the pWPI vector contains GFP, transfection efficiency could bel monitored by detecting GFP fluorescence. The research had been performed with the approval of the ethics committee of First Hospital of Shanxi Medical University; written informed consent for participation in the study was obtained from participants. Antibodies The antibodies c-Myc, MAPK (Erk1/2), Phospho - MAPK (Erk1/2), Stat3, Phospho - Stat 3, AKT and Phospho - AKT were obtained from cell signaling technology, MA, USA. The antibodies P63, AR, Integrin β1, Bcl-2, GAPDH, Wnt-1(G-19) and TGFβ1 were derived from Santa Cruz Biotechnology, CA, USA. The antibodies CD133, CK8, E Cadherin, N Cadherin, and Snail were derived from Abcom, MA, USA. The antibody CK5 was obtained from Covance, CA, USA. The antibody CD44 was derived from eBioscience, CA, USA. The antibody Vimentin was derived from Fisher Scientific, MA, USA. The antibody Ki67 was obtained from Novocastra, Newcastle, United Kingdom. Florescence-activated cell sorting (FACS) For flow cytometry, cells were dissociated with Accutase (Innovative Cell Technologies, CA.) and washed twice in the staining solution containing Ca2+- and Mg2+-free PBS with 1 mM EDTA, 25 mM Hepes (pH 7.0) (Gibco BRL), and 1% FBS. Cells were stained live in the staining solution containing conjugated anti-CD44, and anti-CD133 antibody (50 min at 4°C). Samples were analyzed on a BD LSR II flow cytometer (Becton Dickinson Immunocytometry Systems, CA). A minimum of 500,000 viable cell events were collected per sample. For sorting, 2 × 107 cells were processed for CD44 and CD133 multi color staining, along with appropriate negative controls and single-color positive controls. The CD44+/CD133+ population was sorted out on a BD FACS Diva cell sorter (Becton Dickinson Immunocytometry Systems, CA, USA). RNA extraction and quantitative real-time PCR analysis RNA was extracted using the Trizol reagent (Invitrogen), and first-strand cDNA was synthesized from 1 μg of total RNA in 20 μl reactions containing RT buffer with dNTPs, Oligo-dT, RNase inhibitor, and Moloney murine leukemia virus reverse transcriptase according to the manufacturer’s protocol (Invitrogen). Reverse transcription reactions (used BIO-RAD MyCycler thermal cycler) were incubated at 25°C for 5 min and then 42°C for 30 min, followed by 85°C for 5 min, and aliquots of the reaction products were used in later quantitative real-time PCR analysis. The quantitative PCR analysis was done using BIO-RAD C1000 Thermal cycler system and the SYBR green PCR master mix kit (Applied Biosystems), according to the manufacturer’s suggestions. The housekeeping gene, β-actin was used for normalization. Relative mRNA expression was calculated as described. The following primer pairs were used: Integrin α2β1 forward, 5-GTCGGGGGCTTCAACTTAGAC-3; reverse, 5-CCTGGCTGGCTGGTATTAGC-3; CD133 forward, 5-AGCCTTCATCCACAGATGCT-3; reverse, 5-GTGCATTTCTCCACATTT-3; CK 5 forward, 5-GTGATGCTGAAGAAGGATGTAG-3; reverse, 5-TCC AGG TTG CGG TTG TTG-3; CK 8 forward, 5-TGG AGT CTC GCC TGG AAG-3; reverse, 5-CCT CGT ACT GTG CCT TGA C-3; CD 44 forward, 5-TTT GCA TTG CAG TCA ACA GTC-3; reverse, 5-GTT ACA CCC CAA TCT TCA TGT CCA C-3; PSA forward, 5-GGT GAC CAA GTT CATGCT GTG-3; reverse, 5-GTG TCC TTG ATC CAC TTC CG-3; AR forward, 5-TAG CCC CCT ACG GCT ACA; reverse, 5-TTC CGA AGA CGA CAA GAT GGA C-3; β-actin forward, 5-CAT GTA CGT TGC TAT CCA GGC-3; reverse, 5-CTC CTT AAT GTC ACG CAG AT-3; All samples were run in triplicate. Western blots Detailed procedures had been described previously [21]. Briefly, cells were exposed to RIPA lysis buffer (with protease inhibitor), and were incubated for 30 min on ice. The homogenate was centrifuged at 14,000 rpm for 10 min at 4°C. The protein supernatant concentration was determined using the Bradford assay from BIO-RAD Laboratories. Then the protein was prepared for electrophoresis run on SDS/PAGE gel and then transferred onto PVDF membrane (Pall Corporation, FL). After the membrane was blocked by 5% milk PBST, the first antibodies (against c-Myc, MAPK (Erk1/2), Phospho-MAPK (Erk1/2), Stat3, Phospho-Stat 3, AKT and Phospho – AKT, AR, Bcl-2, GAPDH, Wnt-1(G-19) and TGFβ1) were diluted in blocking buffer to appropriate concentrations and incubated with protein blots (on PVDF membrane) individually. Following reaction with HRP-conjugated secondary antibodies, the signals were developed with enhanced chemiluminescence (ECL) substrate (Thermo Scientific, IL). The band densities were digitized using ChemiDocTM XRS+ Imaging System (BIO-RAD Laboratories, CA); The GAPDH protein was used as internal control. Soft agar colony formation assay To compare the different cells’ tumorigenetic ability, a cell suspension (1 × 104 cells/well) in 2 mL of 0.5% low-melting SeaPlaque CTG agarose (Cambrex Bio Science Rockland) with RPMI 1640 was overlaid into 6-well plates containing a 1% agar base. The 2 mL normal medium was added on the upper cells contained agar. All samples were plated in triplicate. The plates were incubated at 37°C in a humidified incubator for 21 days. The colonies were visualized by staining with 1% crystal violet. The experiment was analyzed in triplicate, and colonies larger than 1 mm in diameter were counted. Migration and invasion assay The migrative and invasive potential of different cells was assessed using the 8 μm polycarbonate membrane plate Transwell system (Corning Incorporated, NY). Cells (1 × 105) were resuspended in 100 μl serum free medium and added in the upper Transwell compartment. 600 μl of 20% CS-FBS medium was placed in the lower compartment to act as an attractant. 1 or 10 nM DHT was added in the medium. After 24 hours incubation at 37°C and 5% CO2, the filters were fixed in methanol for 10 min at 4°C, stained with 1% toluidine blue (BIO-RAD, CA) for 5 min at room temperature and then washed carefully in ddH2O. Cells that had not migrated, were removed from the upper face of the membranes with cotton swabs. After air dried, the membranes were observed under light microscope. The average number of cells per field of view (five random fields per membrane) was counted at × 20 magnification. For invasion assay, before the cells were planted into the upper Transwell, 50 μl Matrigel was added on the membrane. The incubation time was prolonged to 48 hours. Each experiment was repeated at least three times and each time the mean numbers of migrating or invading cells were taken from three chambers. Sphere formation assay Single cells suspension (1 × 103, in 50 μl medium) was mixed with Matrigel 50 μl (keep on ice before use) and 100 μl of mixture was placed along the rim of the 24 well low attached culture plates (BD, CA). Every kind of cells was repeated three wells. The culture plate was incubated in 37°C incubator for 10 min and then 500 μl medium was added. Cells were grown in serum-free epithelial basal medium with 1 or 10 nM DHT, supplemented with Prosta Life Life Factors (Lifeline cell technology, Germany). Spheres were counted after 7 to 14 days under Olympus light microscope. Immunostaining For culture cells immunofluorescence staining, the cells were fixed with ice cold methanol on ice for 15 min and then washed with PBS thrice. The cells were permeabilized with 0.1% Triton X-100/PBS at room temperature for 10 min and then washed with PBS. Non-specific antibody binding sites were blocked for 30 min with 5% bovine serum albumin PBS and not be washed. Cells were incubated with first antibodies diluted in blocking buffer at 20°C for 2 hours. Following 3 times PBS washes, second antibodies diluted in blocking buffer were added on the cells at room temperature for 60 min. After air-dried, the cells were covered by mounting solution (containing DAPI) and visualized with an Olympus IX70 fluorescent microscope. The separate images were obtained for Texas Red and DAPI fluorescence, and images were overlaid with Adobe Photoshop (Adobe Systems, CA). When the cells were double stained, the first antibodies should be from different resource. Cells proliferation assay All kinds of cells were incubated in 12–96 well dishes (103-105 cells/well) for 6 days, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT; 0.5 mg/mL; Sigma) was added at days 0, 2, 4, and 6. After 2 hours of reaction, absorbance of the converted dye was measured at a wavelength of 570 nm with background subtraction at 650 nm. Statistical analysis Data are shown as the mean ± SD. And statistical analysis was obtained using SPSS version 15.0computer software (SPSS Inc., Chicago, IL, USA). A P-value of <0.05 was taken to indicate statistical significance. Results Isolating S/P cells from LNCaP cell line The published paper by others and results of our laboratory’s recent studies indicated low expression level of AR in PCa S/P cells [22,23]. In order to investigate AR’s roles in EMT of PCa S/P cells, S/P cells were isolated from a single androgen dependent PCa cell lineLNCaP, using antibodies to CD133 and CD44. About 1.5% S/P cells were isolated using FACS (Figure 1A). And the morphology of sorted LNCaP S/P cells was shown in Figure1B. As shown in Figure 1C, the S/P cells had higher tumorigenicity than that of non S/P cells, when tested using soft agar colony formation assay. Then the stem cell markers expression of S/P cells was detected through Western blot analysis, immunofluorescence (IF) staining and qRT-PCR (Figure 1D-F). The S/P cells markers, such as CD133, integrin and CK5 were expressed higher than those of non S/P cells. Meanwhile, the mature epithelial cell markers in S/P cells, such as AR, PSA and CK8 were expressed lower than those of non S/P cells. These results suggested that the isolated small number side population was S/P cells with higher tumorigenicity. Figure 1 figure1 Isolating S/P cells from LNCaP cell line. (A) Flow cytometry isolation of S/P (1.5%) and non S/P (98.5%) cells. Cells were grown in regular RPMI medium containing 5% of FBS (cells of passage number less than 3 were used for all experiments). (B) Morphology of sorted S/P cells. (C) Soft agar assay of S/P and non S/P cells. (D) Western blot analysis of AR, CD133, Integrin β1, and CK 8 using cell extracts of parental, S/P, and non S/P cells. (E) IF staining results using antibodies of CK5, CK8, AR, CD133 and Integrin. (F) qRT-PCR analysis results of markers of parental, S/P, and non S/P cells. Identification of EMT characteristics in S/P cells from LNCaP cell line Western blot analysis and IF staining were used to test EMT markers expressed in S/P cells from LNCaP cell line. Using cell extracts of parental, S/P and non S/P cellsAR, the EMT markers including E Cadherin, N Cadherin, Vimentin and Snailproteins were detected using Western blot analysis. N Cadherin, Vimentin and Snailin S/P cells were expressed higher than those in non S/P cells. However, epithelial cell marker E Cadherin was expressed low in S/P cells (Figure 2A). IF staining results demonstrated the similar thing (Figure 2B). As shown in Figure 2C and D, then soft agar colony formation assay and migration assay showed that S/P cells had higher tumorigenicity and migration ability, than those of non S/P cells. Our data suggested that S/P cells from LNCaP cell line showed EMT characteristics. Figure 2 figure2 Identification of EMT characteristics in S/P cells from LNCaP cell line. (A) Western blot analysis of AR, E Cadherin, N Cadherin, Vimentin and Snail using cell extracts of parental, S/P and non S/P cells. (B) IF staining results using antibodies of E Cadherin, N Cadherin and Vimentin. (C) Soft agar colony formation assay. The plates were incubated at 37°C in a humidified incubator for 21 days. Colonies larger than 1 mm in diameter were counted. (D) Migration assay. The migrative potential of different cells was assessed using the 8 μm pore Transwell system. The average number of cells per field of view (five random fields per membrane) was counted at × 20 magnification. AR was a suppressor in EMT of S/P cells from LNCaP cell line S/P Cells were infected with lentivirus carrying either vector or AR and grown in two different androgen concentrations, charcoal stripped (CS)-FBS + 1 nM DHT, and CS-FBS + 10 nM DHT. Western blot assay was used to test AR, E Cadherin, N Cadherin, Vimentin and Snail expression using cell extracts of vector S/P and AR S/P cells. As shown in Figure 3A, the expression of EMT markers decreased, when AR was overexpressed in S/P cells. Then how AR affected S/P cells proliferation, was investigated. Cells were incubated in 24 well dishes (1 × 104 cells/well). At 0, 2, 4, and 6 days, MTT assays were performed. The ARS/P cells proliferation was inhibited during different DHT concentration, compared to that of Vector S/P cells. But AR played an opposite role in non S/P cells (Figure 3B). Soft agar colony formation assay was used to test tumorigenicity. After incubated for 21 days, colonies larger than 1 mm in diameter were counted. The ARS/P cells tumorigenicity was inhibited under different DHT concentration, compared to that of Vector S/P cells (Figure 3C). Similarly, the self-renewal ability was inhibited, when AR was overexpressed in S/P cells (Figure 3D). Moreover, the migrative potential of ARS/P cells was inhibited in different DHT concentration, compared to that of Vector S/P cells. Meanwhile, AR played an opposite role in non S/P cells (Figure 3E). Figure 3 figure3 AR is a suppressor in EMT of S/P cells from LNCaP cell line. S/P Cells were infected with lentivirus carrying either vector or AR and grown in two different androgen concentrations, charcoal stripped (CS)-FBS + 1 nM DHT, CS-FBS + 10 nM DHT. (A) Western blot analysis of AR, E Cadherin, N Cadherin, Vimentin and Snail using cell extracts of vector S/P and AR S/P cells. (B) MTT assay. Cells were incubated in 24 well dishes (1 × 104 cells/well). At 0, 2, 4, and 6 days, MTT assays were performed. (C) Soft agar colony formation assay. The plates were incubated at 37°C in a humidified incubator for 21 days. Colonies larger than 1 mm in diameter were counted. (D) Sphere formation assay. Cells (5,000) were mixed with Matrigel (1:1 ratio, total 200 μl) and placed in rim of well of 24well culture plates. After solidified, 1 ml of medium was added and grown for 21 days. Pictures were taken under microscope. (E) Migration assay. The migrative potential of different cells was assessed using the 8 μm pore Transwell system. Cells (1 × 105) were resuspended in 100 μl serum free medium and added in the upper compartment. 600 μl of 20% CS-FBS medium was placed in the lower compartment. After 24 hours, cells that had not migrated were removed from the upper face of the membranes with cotton swabs. The average number of cells per field of view (five random fields per membrane) was counted at × 20 magnification. All experiments samples were plated in triplicate. The signaling pathways activation related to self-renewal/proliferation in LNCaP S/P cells It was known that PI3K/AKT, Bcl-2, c-Myc, MAPK (Erk1/2), TGF-ß, and Stat3 cell signaling pathways might involve in S/P cells proliferation and apoptosis. The probably related signaling pathways in parental, S/P, and non S/P cells of LNCaP cell line were examined using Western blot analysis. It was found that P-AKT, Bcl-2 and c-Myc were expressed higher in S/P cells, compared to those of non S/P cells (Figure 4A). When LNCaP S/P cells were infected with lentivirus carrying AR, the expression of P-Akt, bcl-2, and c-Myc were inhibited (Figure 4B). Then to confirm the signaling pathways related to S/P cells proliferation, the S/P cells of LNCaP cell line were transfected with AR, Oligo bcl-2 siRNA, or/and c-Myc siRNA plasmids indicated. At the end of 4 days of culture after transfection, cells were used to do MTT assay. It was found AR, sibcl-2, or/and sic-Myc all could inhibit S/P cells proliferation. Combining use of si bcl-2 with si c-Myc could show stronger inhibition (Figure 4C). Figure 4 figure4 Activation of self-renewal/proliferation related signaling pathways in LNCaP S/P cells. (A) The probably related signaling pathways in parental, S/P, and non S/P cells of LNCaP cell line were examined by Western blot analysis, such as AKT, Bcl-2, c-Myc, MAPK (Erk1/2) and Stat3. (B) Cells (LNCaP S/P) were infected with lentivirus carrying V/AR and the levels of AR, p-Akt, bcl-2, and c-Myc were examined by Western blot analysis. (C) The S/P cells of LNCaP cell line were transfected with AR, Oligo bcl-2 siRNA, or/and c-Myc siRNA plasmids indicated. At the end of 4 days of culture after transfection, cells were used to do MTT assay. In vitro combinatory use of LY 294002 with γ-tocotrienol (γ-TT) and/or 5-aza-2′-deoxycytidine (5-AZA) showed synergistic effect of killing PCa S/P cells LY 294002 is an inhibitor of AKT signaling. γ-TT can suppress S/P cells through the interruption of targeting molecules including bcl-2 and Akt. 5-AZA is a de-methylating agent and can induce AR expression of S/P cells. LY 294002, γ-TT and 5-AZA were used in various combinations. Two or three reagents could suppress S/P cells tumorigenesis and growth. Combining use of three reagents could show stronger inhibition in soft agar colony formation assay (Figure 5A). At last, MTT assay was used to show that these reagents could suppress S/P cells growth. It was found that the combinational use of LY 294002, γ-TT and 5-AZA did leaded to a significant suppression of S/P cells proliferation (Figure 5B). Figure 5 figure5 In vitro combinatory use of LY 294002 (inhibitor of AKT signaling molecules) with γ-TT and/or 5-AZA showed synergistic effect of killing PCa S/P cells. (A) Soft agar colony formation assay. A cell suspension (1 × 104 cells/well) in 2 ml of 0.5% low-melting agar with RPMI 1640 was overlaid into 6well plates containing 1% agar base. The 2 ml normal medium was added on the upper cells contained agar. The plates were incubated at 37°C in a humidified incubator for 21 days. The colonies were visualized by staining with 1% crystal violet. Colonies larger than 1 mm in diameter were counted. (B) MTT assay. Cells were incubated in 24 well dishes (1 × 104 cells/well). At 0, 2, 4, and 6 days, MTT assays were performed. Discussion It’s believed that cancer stem/progenitor cells and EMT played very important roles in prostate cancer development [24]. EMT is closely related to PCa drug resistance. EMT and stem-like cell markers expression of the docetaxel-resistant PCa cells had increased. ZEB1 siRNA transfection reverted docetaxel resistance and reduced CD44 expression in DU-145R and PC-3R [25]. It was shown that PCaradio resistance is associated with EMT and enhanced CSC phenotypes via activation of the PI3K/Akt/mTOR signaling pathway [26]. After androgen-deprivation therapy (ADT), the S/P cells increases, which have low AR expression. It was reported that ADT could lead to EMT in both normal prostate and prostate cancer tissues [15]. Sethi [14] found that the cancer cells EMT marker expression was different at the edge of human primary tumors and bone metastasis of prostate cancer. The expression of EMT marker Vimentin, nuclear factor-кB (NF-кB), Notch-1 and ZEB1 increased. Meanwhile, epithelial markers E Cadherin expression level was low. This study suggested EMT was closely related to invasion and metastasis of prostate cancer. Another study showed that EMT phenotype could be detected in ARCaPM and PDGF-D overexpression PC-3prostate cancer cell lines. Compared with the ARCaPE and PC-3 cells, the tumor formation and self-renewal capacity of these cells significantly increased. Stem cell markers Sox2, Nanog, Oct4, Lin28B and/or Notch1 expression significantly increased and the cells had some characteristics of stem cells. MiR200 could inhibit Notch1 expression, and cells tumor formation capacity and self-renewing ability decreased. Through Notch1 signaling pathway, MiR200 regulated characteristics of stem cells of EMT phenotype prostate cancer cell [27]. All these results indicated that EMT has some relationship with CSC. Our preliminary data show that both tumor cells with EMT markers and tumor cells with CSC markers increase after ADT in tumor tissue of prostate cancer patients [10, 16]. Stem-like SP cells acquired more complete EMT molecular features and exhibited stronger aggressive capability [28]. In this research, our group made it clear that CSC of prostate cancer had some EMT characteristics. Compared with those of non S/P cells, the EMT markers expression of S/P cells increased, tumorigenesis ability and migration and invasion capacity wre enhanced in S/P cells. These two kinds of cells increased, after ADT and these may common led to the failure of traditional endocrine treatment and disease progress. Androgen/androgen receptor (A/AR) axis cancer [29]. Now it was considered that prostate cancer cells varied, and are mainly luminal cells, but there are also some basal cells and intermediate cells. Some basal cells with CSC markers may be the origin of the tumor. Recent studies have shown that AR expression level was different in prostate cancer cells, played a different role [30-32]. The current research and our work showed that AR expression was low in prostate cancer S/P cells. Transferring ARintoS/P cells could inhibit their proliferation. AR’s roles in EMT characteristics of S/P cells and related regulatory mechanism were not clear. In this study we transfered AR into S/P cells with lentivirus. Compared with that of vector S/P cells, using different methods of immune detection, it was found that the expression of EMT markers decreased, and epithelial markers E Cadherin expression increased. Cell proliferation, self-renewal ability, tumorigenesis and the ability to migrate were all restrained in AR-S/P cells. The characteristics of EMT were restrained too. These data suggest that AR played a dual inhibition effect on S/P cell proliferation and EMT features. Signaling pathways regulating prostate cancer cell EMT included AKT, Wnt, stat3, Bcl-2, C-Myc, TGF-ß, EGF/EGFR, Notch, MAPK and so on [33-36]. It was shown that EMT and CSC characteristics could be regulated simultaneously. Erismodegib (a Shh signaling pathway inhibitor) could inhibit EMT and human prostate cancer stem cell growth in NOD/SCID IL2Rγ null mice by regulating Bmi-1 and microRNA-128[37]. In this study we tested a large number of cell signaling pathways. P-AKT, Bcl-2 and C-Myc expression were higher in S/P cells than those in non S/P cell. When AR was transferred into S/P cells, these three proteins expression were significantly suppressed. Then we designed SiBcl-2 and Si C-Myc and they could well restrain S/P cell proliferation. So it was suggested that P-AKT, Bcl-2 and C-Myc were involved in this procedure. AR and the three signaling pathways can regulate S/P cells proliferation. So to intervene of these pathways, LY 294002, an inhibitor of AKT signaling, γ-TT, and 5-AZA, a de-methylating agent, were used. It was showed that γ-TT suppressed S/P cells through the interruption of targeting molecules including bcl-2 [38]. In addition, γ-TT has also been reported to inhibit PI3K/Akt signaling [39]. Therefore, it is possible that γ-TT might be able to suppress S/P cells via inhibiting both PI3K/Akt signaling and bcl-2 expression. The other strategy to suppress S/P cells is to target AR directly via reversing the low expression of AR in S/P cells. It was reported that the CpG islands in the promoter and exon 1 of AR gene in S/P cells were highly methylated, compared to that of the non S/P cells [40], and treatment of S/P cells with the de-methylating agent, 5-AZA, led to significant suppression of S/P cells proliferation via inducing AR expression. Combining two or three of the reagents could inhibit S/P cells tumorigenicity and growth efficiently. 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Article  PubMed Central  CAS  PubMed  Google Scholar  Download references Acknowledgements This work was supported by Research Project Supported by Shanxi Scholarship Council of China (2012–085), Project Supported by The Preferred Foundation of Shanxi Study Abroad Personnel (2011[762]) Construction Project of National Key Clinical Department of Urology (2012). Author information Affiliations Authors Corresponding author Correspondence to Ma Zhifang. Additional information Competing interests The authors declare that they have no competing interests. Authors’ contributions MZ and WL participated in the design of the study and performed the statistical analysis. MZ, WL, ZW, HB, TR, WN, and ZS conceived of the study, and participated in its design and coordination and helped to draft the manuscript. All authors read and approved the final manuscript. Rights and permissions This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Reprints and Permissions About this article Verify currency and authenticity via CrossMark Cite this article Zhifang, M., Liang, W., Wei, Z. et al. The androgen receptor plays a suppressive role in epithelial- mesenchymal transition of human prostate cancer stem progenitor cells. BMC Biochem 16, 13 (2015). https://doi.org/10.1186/s12858-015-0042-9 Download citation Keywords • Prostatic neoplasms • Stem progenitor cell • Epithelial-mesenchymal transition • Androgen receptor
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Detection of aberrant transcription of major histocompatibility complex class II antigen presentation genes in chronic lymphocytic leukaemia identifies HLA-DOA mRNA as a prognostic factor for survival Y Souwer, M.E.D. Chamuleau, A.A. van de Loosdrecht, E. Tolosa, T. Jorritsma, J.J.F. Muris, M.N.M. van Poppel, S.N. Snel, L. van de Corput, G.J. Ossenkoppele, C.J.L.M. Meijer, J.J. Neefjes, S.M. van Ham Research output: Contribution to journalArticleAcademicpeer-review Abstract In human B cells, effective major histocompatibility complex (MHC) class II-antigen presentation depends not only on MHC class II, but also on the invariant chain (CD74 or Ii), HLA-DM (DM) and HLA-DO (DO), the chaperones regulating the antigen loading process of MHC class II molecules. We analysed immediate ex vivo expression of HLA-DR (DR), CD74, DM and DO in B cell chronic lymphocytic leukaemia (B-CLL). Real-time reverse transcription polymerase chain reaction demonstrated a highly significant upregulation of DRA, CD74, DMB, DOA and DOB mRNA in purified malignant cells compared to B cells from healthy donors. The increased mRNA levels were not translated into enhanced protein levels but could reflect aberrant transcriptional regulation. Indeed, upregulation of DRA, DMB, DOA and DOB mRNA correlated with enhanced expression of class II transactivator (CIITA). In-depth analysis of the various CIITA transcripts demonstrated a significant increased activity of the interferon-gamma-inducible promoter CIITA-PIV in B-CLL. Comparison of the aberrant mRNA levels with clinical outcome identified DOA mRNA as a prognostic indicator for survival. Multivariate analysis revealed that the prognostic value of DOA mRNA was independent of the mutational status of the IGHV genes. Thus, aberrant transcription of DOA forms a novel and additional prognostic indicator for survival in B-CLL Original languageUndefined/Unknown Pages (from-to)334-343 JournalBritish Journal of Haematology Volume145 Issue number3 DOIs Publication statusPublished - 2009 Cite this
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MIDD in Preclinical Drug Development​ Authors: Miller N Conference: AAPS Division: PBPK Description: • Provide a case for why you should focus on preclinical verification when using Physiologically Based Pharmacokinetic (PBPK) modeling for First-In-Human (F.I.H) pharmacokinetic predictions Objectives • Appreciate that PBPK models are complex and combine systems physiology and drug specific input data • Understand that verification of PBPK models in preclinical R&D assesses whether the combination of physiology and drug specific input data works for a specific drug • Acknowledge that you should be realistic with your expectations and learn from poor predictions By Neil A. Miller Presented at American Association of Pharmaceutical Scientists (AAPS) PharmSci 360, October 17-20, 2021
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Scheduled Intermittent Screening with Rapid Diagnostic Tests and Treatment with Dihydroartemisinin-Piperaquine versus Intermittent Preventive Therapy with Sulfadoxine-Pyrimethamine for Malaria in Pregnancy in Malawi: An Open-Label Randomized Controlled Trial In an open-label randomized controlled trial, Feiko O. ter Kuile and colleagues found that ISTp-DP was not superior to IPTp-SP in an area with high malaria transmission and high SP resistance. Published in the journal: . PLoS Med 13(9): e32767. doi:10.1371/journal.pmed.1002124 Category: Research Article doi: 10.1371/journal.pmed.1002124 Summary In an open-label randomized controlled trial, Feiko O. ter Kuile and colleagues found that ISTp-DP was not superior to IPTp-SP in an area with high malaria transmission and high SP resistance. Introduction Malaria during pregnancy is a major preventable cause of poor birth outcomes in sub-Saharan Africa [1]. In sub-Saharan Africa, the World Health Organization (WHO) currently recommends intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) (IPTp-SP) for HIV-seronegative women. The effectiveness of IPTp-SP to clear peripheral parasitemia decreases in areas where parasites are resistant to SP; this resistance results from a series of mutations in the parasite genes that encode the targets of pyrimethamine (dhfr) and sulfadoxine (dhps). For example, in settings where >90% of parasites harbor high-level SP resistance encoded by five mutations in dhfr and dhps, up to 40% of asymptomatic parasitemic women who receive SP for IPTp are parasitemic again by day 42, reflecting the failure of SP to clear existing plasmodium infections and prevent new infections [2]. Nevertheless, even in these high resistance settings, SP retains some beneficial effect on birthweight [2,3]. However, an additional mutation at codon 581 in dhps is emerging in parasites in East Africa that renders IPTp-SP unable to inhibit parasite growth and may significantly compromise IPTp-SP when present [46]. Consequently, alternative approaches are required to prevent malaria during pregnancy. Most of the proposed alternative drugs to replace SP are too poorly tolerated for IPTp use, including amodiaquine alone or combined with SP [7], mefloquine monotherapy [8,9], and the fixed-dose combination of chloroquine-azithromycin [10]. A proposed alternative strategy to IPTp consists of scheduled antenatal testing with rapid diagnostic tests (RDTs) and the treatment of RDT-positive women with artemisinin-based combination therapy (ACT), referred to as intermittent screening and treatment in pregnancy (ISTp) [11]. In West African settings, where parasite resistance to SP is low, ISTp with artemether-lumefantrine (AL) (ISTp-AL) was not inferior to IPTp-SP in reducing low birthweight and was well-accepted by providers and patients [1214]. Nevertheless, in these studies, women in the ISTp-AL arm had lower mean birthweights and more clinical malaria during pregnancy. We hypothesized that, owing to widespread parasite SP resistance, ISTp with the ACT dihydroartemisinin-piperaquine (DP) would be superior to IPTp-SP for the prevention of the adverse sequelae of malaria in pregnancy. However, a recent trial in an area with high levels of malaria transmission and parasite resistance to SP in western Kenya showed that ISTp with DP (ISTp-DP) was not superior to IPTp-SP and was associated with increased incidence of clinical malaria and malaria infection [15]. These findings need to be confirmed urgently in other areas that have high levels of parasite resistance to SP. Here we report the results of a similar trial comparing IPTp-SP against ISTp-DP in Malawi. Methods Ethics Statement Ethical approval was obtained from the Liverpool School of Tropical Medicine (LSTM) and the Malawian National Health Science Research Committee. Written informed consent was obtained from all participants prior to randomization. Study Design and Participants This was a three-site, open-label, two-arm individually randomized superiority trial using a stratified design with one strata for primi- and secundigravidae (paucigravidae) and one for multigravidae (third pregnancy or higher). The study was conducted at the Mpemba and Madziabango Health Centers and the Chikwawa District Hospital in southern Malawi. The area has moderate to intense year-round malaria transmission and high levels of SP resistance, as evidenced by near fixation of parasites harboring mutations at codons 51, 59, and 108 of dhfr and 437 and 540 of dhps [16,17]. Women of all gravidae attending their first antenatal visit were eligible if they were HIV-seronegative, were resident in the study catchment area and willing to deliver at the study clinics/hospital, had a hemoglobin > 70 g/l, had a pregnancy between 16 and 28 wk gestation, and had not yet received IPTp-SP. Exclusion criteria included multiple gestation and other high-risk pregnancies according to national guidelines, previous enrollment in the same study, and history of allergy to any of the study drugs. Randomization and Masking Randomization sequences were computer-generated by the study statistician at LSTM, one for each gravidity strata and study site, using variable block randomization and an allocation ratio of 1:1. In each clinic, eligible women were allocated to the IPTp-SP or ISTp-DP arm by the coordinating study staff in order of their study identification number by drawing sequentially numbered opaque envelopes containing the allocation arm from a box corresponding to each gravidity stratum. Following allocation, women and care providers were aware of the arm allocation. All laboratory staff were blinded to the treatment assignment. The study statistician remained blinded until after database lock and approval of the statistical analysis plan by the data and safety monitoring board. Procedures At enrollment, demographic, socioeconomic, and educational information was collected, a medical and obstetric history taken, and the gestational age ascertained by ultrasound. A 5-ml venous blood sample was taken for malaria microscopy, PCR, immunology, and testing for syphilis, HIV serostatus, and hemoglobin concentration (Hemocue). All women received a long-lasting insecticide-treated net. Participants were randomized to receive either IPTp-SP or ISTp-DP, at enrollment and all subsequent scheduled antenatal visits. The IPTp-SP arm received three tablets of SP (500 mg/25 mg sulfadoxine/pyrimethamine tablets). If they had fever or history of fever, they were tested for malaria by RDT. RDT-positive women were treated with AL and then received their first course of SP during the first scheduled follow-up visit. Women in the ISTp-DP arm were screened for malaria using the histidine-rich protein 2 (HRP2)/plasmodium lactate dehydrogenase (pLDH) combination RDT (First Response Malaria pLDH/HRP2 Combo Test, Premier Medical Corporation). All RDT-positive women in the ISTp-DP arm received a standard 3-d course of DP (Eurartesim, Sigma Tau; 40 mg/320 mg dihydroartemisinin/piperaquine tablets) at a dose of 2.5, 3, 3.5, and 4 tablets for women weighing <50, 50–59, 60–69, and ≥70 kg, respectively. All SP and DP doses were provided with a slice of dry bread as directly observed therapy. All doses in both arms were supervised. In case of vomiting within 30–60 min, the full dose was repeated. If the repeat dose was vomited, the women received AL. Sigma Tau provided the Eurartesim free of charge. The follow-up schedule consisted of three or four scheduled antenatal visits every 4 to 6 wk: four if enrolled at 16–24 wk gestation or three if enrolled at ≥25 wk gestation. At each such visit, a clinical and obstetric examination was conducted, and a blood sample taken for RDT (ISTp-DP arm), malaria microscopy, and PCR. Hemoglobin was assessed during the last scheduled visit. Women were encouraged to make unscheduled visits if they felt ill or were concerned about their pregnancy. In the IPTp-SP arm, women with uncomplicated clinical malaria (fever/history of fever and RDT-positive) during or in between scheduled visits received AL. Women with uncomplicated malaria in the ISTp-DP arm received DP, or AL if they had received DP within the previous 4 wk. At delivery, a maternal venous sample was taken for the same malaria metrics, and a placental and cord-blood sample for histology, RDT, microscopy, and PCR. Children were weighed and the gestational age assessed using the modified Ballard score [18]. The presence of congenital abnormalities and jaundice was assessed at delivery, at day 7, and at the final visit at 6–8 wk, coinciding with their childhood vaccination visit. In between scheduled visits, infants were followed passively. RDT results were used to determine care. RDT positivity was defined as either pLDH or HRP2 antigen positivity. See S1 Text for details of microscopy and real-time PCR used for detection and identification of parasites, as well as baseline parasite genotyping. Outcomes The primary outcome among paucigravidae was “adverse live birth outcome,” defined as the composite of having a singleton baby born small for gestational age (SGA) [19] or with low birthweight (<2,500 g), or preterm (<37 wk) (S1 Text). The primary outcome among multigravidae was a composite of any evidence for plasmodium infection at delivery detected in peripheral maternal blood (microscopy, RDT, or PCR) or placenta (incision smear, impression smear, PCR, or active or past infection detected by histology) (S1 Text). The rationale for using a different primary outcome for multigravidae was based on systematic reviews showing that preventing plasmodium infection by IPTp-SP or long-lasting insecticide-treated nets is associated with improved birth outcomes primarily among women in their first and second pregnancies [20,21]. Plasmodium infection status at delivery was used as the primary outcome in multigravidae because plasmodium infection is associated with an increased risk of malaria [2225] and anemia [2628] in infancy, particularly in those born to multigravidae [24]. Key secondary efficacy outcomes included the individual components of the composite primary outcomes, fetal loss (spontaneous abortion at <28 wk gestation, stillbirth), any adverse birth outcome (adverse live birth outcome or fetal loss), maternal hemoglobin concentrations and anemia, clinical malaria (documented fever/history of fever plus positive malaria RDT), plasmodium infection, mean birthweight, mean gestational age at delivery, congenital plasmodium infection (cord blood positive at birth by microscopy, RDT, or PCR, or clinical malaria within 7 d of birth with parasitological confirmed diagnosis by microscopy or RDT), neonatal and infant (by 6–8 wk) clinical malaria, all-cause severe anemia and all-cause illness detected at scheduled or unscheduled postnatal visits, and perinatal and infant mortality by 6–8 wk. The primary safety outcomes included maternal death, severe cutaneous skin reaction in the mothers within 30 d of drug intake, other serious adverse events (SAEs) in the mother or infant, congenital malformations, and neonatal jaundice. Statistical Analysis See S1 Text for details about sample size calculations. Log binomial regression was used for binary endpoints to obtain relative risk (RR) values and corresponding 95% confidence intervals. The identity-link function was used to obtain risk differences. Linear regression was used for continuous variables, and results expressed as mean difference (95% CI). The unadjusted analysis, stratified by gravidity (pauci- and multigravidae), was considered the primary analysis. Secondary, covariate-adjusted analyses for the primary endpoints were conducted using seven prespecified covariates (in addition to gravidity and site) and simple imputation for missing covariates (<1%). These same covariates were included in subgroup analyses. Poisson regression with time of follow-up as an offset was used for count variables to obtain incidence rate ratios (95% CIs). A two-sided p-value < 0.05 was used to define statistical significance. The intention to treat (ITT) analytical population was defined as all eligible women who were randomized and contributed to the outcome. The per protocol population included women who attended every scheduled visit, who took all the daily study doses on each occasion, and who contributed to the endpoint. For the safety analysis, women in the ISTp-DP arm were considered overall and split by recipients and non-recipients of DP (i.e., those who were RDT-negative throughout). All analyses were prespecified, unless otherwise indicated, in a statistical analysis plan (see S2 Text) approved by the data and safety monitoring board. Analysis was done in SAS version 9.3 and Stata version 14. Results Baseline and Patient Disposition Between 21 July 2011 and 18 March 2013, 3,214 women were screened for inclusion; 1,873 women were randomized (paucigravidae, n = 1,155; multigravidae, n = 718). Recruitment was stopped when the full sample size for paucigravidae had been reached (S1 Text). Of the randomized women, 1,743 (93.1%) were seen at delivery (Fig 1). Overall, 6,504 of 6,942 (93.7%) scheduled antenatal follow-up visits were attended (S1 Table), and 1,742 women (94.5%) attended all scheduled visits. Ultimately, 1,676 (89.5%) contributed to the primary endpoint, with proportions of participants equally distributed between the study arms (ISTp-DP arm, 89.3%; IPTp-SP arm, 89.6%) (S2 Table). The baseline characteristics were well balanced between the study arms, within each gravidity strata, and overall (Table 1). At baseline, about half of the women were infected with malaria parasites, and this proportion was slightly lower (not significant) in those not contributing to the primary analyses (S3 Table). Overall, 99.5% and 2.7% of the parasites harbored the dhps K540E and A581G mutation, respectively (S4 Table). In both arms, the median (interquartile range) follow-up time was 4.0 (3.2–4.7) mo, and the median (range) number of scheduled visits was 4 (1–4) (S1 Table). In the ISTp-DP arm, 48.8%, 38.0%, 12.4%, and 0.9% received 0, 1, 2, and 3 courses of DP, respectively (S1 Table). Overall, 3,048 and 604 courses of SP and DP were administered in the respective study arms, and in the IPTp-SP arm, 251 courses of AL were administered for clinical malaria (S1 Table). Flow chart. Fig. 1. Flow chart. aOne woman randomized to IPTp-SP was erroneously recorded as being in the ISTp-DP arm on her antenatal care card and as a result received ISTp-DP. She was included in the ITT population under the IPTp-SP arm. bScreening failures were not followed to delivery and were excluded from the modified ITT population. cWomen lost to follow-up prior to delivery and women who withdrew consent were included in the ITT population and contributed to the antenatal follow-up analyses (e.g., incidence of malaria). IPTp-SP, intermittent preventive therapy in pregnancy with sulfadoxine-pyrimethamine; ISTp-DP, intermittent screening and treatment in pregnancy with dihydroartemisinin-piperaquine; ITT, intention to treat; SGA/LBW/PT, small for gestational age or low birthweight or preterm. Tab. 1. Baseline characteristics (intention to treat population). Baseline characteristics (intention to treat population). Data are percent (n/N), mean (standard deviation), or median (interquartile range). Primary Outcome Among paucigravidae, the prevalence of adverse live birth outcome was similar in the ISTp-DP (33.7%) and IPTp-SP (30.6%) arms (RR = 1.10 [95% CI 0.92–1.31], p = 0.282; Fig 2). The prevalence was also similar between arms among multigravidae. Efficacy of ISTp-DP versus IPTp-SP on the primary outcomes of adverse live birth outcome and maternal or placental plasmodium infection at delivery (any measure). Fig. 2. Efficacy of ISTp-DP versus IPTp-SP on the primary outcomes of adverse live birth outcome and maternal or placental plasmodium infection at delivery (any measure). Adjusted RR values obtained from multivariate log binomial regression models with missing values imputed and adjusting for gravidity, study site, and seven other prespecified covariates: malaria status at enrollment (binary), season during pregnancy (terciles based on average ranked rainfall during the last 6 mo of pregnancy), maternal height (terciles), hemoglobin status at enrollment (terciles), maternal years of schooling (terciles), socioeconomic status (terciles of socioeconomic index calculated using principal component analysis), and gestational age at first antenatal visit (binary based on median). There were no differences in effect size for paucigravidae versus multigravidae (p-value for interaction term: p = 0.271 for adverse live birth outcome and p = 0.454 for plasmodium infection at delivery). Among multigravidae, the risk of malaria at delivery was higher in the ISTp-DP (34.9%) than in the IPTp-SP (27.2%) arm (RR = 1.29 [95% CI 1.02–1.63], p = 0.037). This increased risk was also evident among paucigravidae and all gravidae. In absolute terms, the risk of malaria was increased in multigravidae by 7.8% (95% CI 0.6%–14.9%) and amongst all gravidae by 7.9% (95% CI 3.1%–12.6%) (Fig 2). Similar results for both primary outcomes were obtained from prespecified covariate-adjusted analyses, with and without prespecified imputation for missing covariates (S5 Table), with per protocol population analysis (S6 Table), and in a sensitivity analysis that restricted analysis to birthweight obtained within 24 h of delivery (S7 Table). Results were also consistent across subgroups (S1 and S2 Figs), although the increased risk of malaria at delivery appeared lowest in primigravidae (S2 Fig). Secondary Efficacy Outcomes Following enrollment, 45.8% of women had ≥1 episode of plasmodium infection prior to delivery (PCR, microscopy, or RDT), and 11.4% had ≥1 episode of clinical malaria. These proportions were similar in both arms (Fig 3). At delivery, 22.2% of women had peripheral malaria detected by PCR, RDT, or microscopy. This value was higher in the ISTp-DP arm (RR = 1.34 [95% CI 1.12–1.61], p = 0.002; S3 Fig), particularly for subpatent infections (PCR-positive, RDT- or microscopy-negative; S3 Fig). The overall prevalence of placental malaria detected by histology, PCR, RDT, or microscopy was 38.0%, and this value was higher in the ISTp-DP arm (RR = 1.16 [95% CI 1.03–1.32], p = 0.018; S4 Fig), reflecting differences in acute rather than chronic or past histological infections (S4 Fig). Congenital malaria was common (12.0%) in both groups (Fig 4). Secondary maternal outcomes: anemia and malaria. Fig. 3. Secondary maternal outcomes: anemia and malaria. The p-value for the interaction term depicts the p-value for differences in effect size between paucigravidae and multigravidae. Secondary newborn outcomes: birth outcomes and neonatal follow-up. Fig. 4. Secondary newborn outcomes: birth outcomes and neonatal follow-up. The P-value for the interaction term depicts the p-value for differences in effect size between paucigravidae and multigravidae. At delivery, relative to the IPTp-SP arm, paucigravidae in the ISTp-DP arm had higher mean hemoglobin concentrations (S8 Table) and a lower prevalence of anemia (hemoglobin < 110 g/l) (Fig 3). The individual components of the primary endpoint adverse live birth outcome are provided in Fig 4. Low birthweight was more common in the ISTp-DP arm (RR = 1.29 [95% CI 0.97–1.71], p = 0.079). Adherence, Tolerance, Fetal Loss, Mortality, and Other Safety Outcomes Overall, DP was well tolerated (S9 Table). There was no difference between arms in the number of maternal SAEs or deaths (S10 Table). There were no severe cutaneous reactions. Fetal loss was highest in the ISTp-DP arm (2.6% versus 1.3%; Fig 4). Further stratified analysis within the ISTp-DP arm showed fetal loss was highest among women who had never received DP (i.e., who remained RDT-negative throughout) (3.1% versus 2.2% in DP recipients; S10 Table). Perinatal and infant (by 6–8 wk) mortality were not statistically different between the arms (perinatal mortality: RR = 1.62 [95% CI 0.87–2.99], p = 0.127; infant mortality: RR = 1.42 [95% CI 0.63–3.17], p = 0.398) (Fig 4), but overall, the composite of fetal loss or infant death by the end of follow-up (6–8 wk) occurred more often in the ISTp-DP arm (4.0% versus 2.3%, RR = 1.76 [95% CI 1.04–2.98], p = 0.036; Fig 4; S10 Table). One case of neonatal jaundice was detected in the ISTp-DP arm (mother was a non DP-recipient), and none in the IPTp-SP arm. The frequency of congenital malformations was 1.2% in the ISTp-DP arm (0.9% in infants whose mother was a DP-recipient) and 1.0% in the IPTp-SP arm (RR = 1.11 [95% CI 0.45–2.71], p = 0.824). Discussion Despite the high levels of parasite resistance to SP, ISTp-DP was not superior to the standard IPTp-SP regimen in this trial: ISTp-DP was not associated with improvements in the composite outcome of small for gestational age, low birthweight, and preterm birth (primary outcome for paucigravidae) and was associated with more malaria at delivery (primary outcome for multigravidae) and more fetal loss. Although the relative increase in malaria risk was modest, this affected an additional eight out every 100 pregnancies. These results suggest that ISTp-DP may not be a suitable alternative strategy to replace IPTp-SP in settings similar to ours and may even predispose to unfavorable pregnancy outcomes in these settings. The results may not be representative of areas where >10% of parasites harbor the “sextuple mutant” haplotype carrying the dhps A581G mutation [29]; however, our efficacy findings are similar to those reported recently from areas in western Kenya [15] with similarly high transmission (malaria prevalence detected by PCR at enrollment 33% versus 44% in this study) and SP resistance (5.8% dhps A581G mutation), and are also consistent with two previous non-inferiority trials conducted in West Africa, despite marked geographic differences in prevailing SP resistance, which is low in West Africa [11,12]. In both West African studies, ISTp was non-inferior to IPTp-SP in the reduction in low birthweight among paucigravidae; mean birthweights were higher in the IPTp-SP recipients than in those receiving ISTp-AL (p = 0.04) [12], but there was no significant difference compared to those receiving ISTp with amodiaquine-artesunate (p = 0.06) [11]. Additionally, the incidence of clinical malaria was higher in the ISTp-AL arm compared to the IPTp-SP arm. This was not observed in our trial, but the trial in western Kenya also observed higher incidence of clinical malaria as well as of plasmodium infection during pregnancy [15]. Because DP has very high anti-parasitic efficacy in Africa [30], the lack of superiority of ISTp-DP may result either from the ineffectiveness of ISTp as a strategy in high malaria transmission areas or from the continued effectiveness of IPTp-SP despite prevalent SP resistance. To this latter point, in our study area in Malawi, 99.5% of parasites harbor the “quintuple mutant” haplotype, but only 2.6%–4% carry the additional dhps A581G mutation [29]. Therefore, it is likely that IPTp-SP continued to provide some benefits, as has been observed in settings with similar parasite populations [2,3]. Another factor likely contributing to continued effectiveness of IPTp-SP was our use of the frequent dosing regimen [31] now recommended by WHO, which may mitigate the shortening of posttreatment prophylaxis that results from SP resistance [2]. It would also be of interest to further explore whether SP, which also has broad antimicrobial activity, may have conferred additional protection from other pathogens [32]. It is unlikely that suboptimal dosing or subtherapeutic levels of DP contributed to the non-superior performance of ISTp-DP: each dose was supervised, and there is no evidence that pregnancy alters the pharmacokinetics of DP to a degree that requires dose adjustment [33]. The same DP regimen was shown to be highly effective (PCR-corrected success rate by day 63: 99%) in a concurrent treatment trial conducted by the same team in this area using the same batch [34]. ISTp-DP may also have been ineffective owing to a failure to detect low-level parasitemias, although the biological impact of such infections during pregnancy is unclear [35]. RDTs detected about 45% of the PCR-positive infections in paucigravidae and about 30% in multigravidae, thereby allowing the majority of infections to persist in the placenta. Conceptually, ISTp is intended to prevent both existing infections from progressing and new infections from occurring for up to 6 wk after each DP course. Because only the RDT-positive women receive treatment, many do not benefit from the posttreatment prophylaxis. Furthermore, the infrequency of screening (approximately monthly) in a high transmission setting may have allowed new infections to develop and persist between scheduled visits. These factors combined may explain the higher prevalence of plasmodium infections at the time of delivery in the ISTp-DP arm. The ineffectiveness of ISTp to prevent malaria in high transmission settings may also explain the higher rate of fetal loss in the ISTp-DP arm (2.6% versus 1.3%), consistent with the results from previous meta-analyses that showed a 1.5-fold higher risk of fetal loss among women randomized to control arms in trials of insecticide-treated nets [36]. The excess risk of fetal loss was not due to an adverse effect of DP, as the risk was highest among women who had never received DP (3.1% versus 2.2%). An alternative explanation could be that the broad antimicrobial effect of SP reduced the risk of fetal loss relative to ISTp [32]. Lastly, the effect could also be a chance finding, as the trial in Kenya did not observe an excess risk of fetal loss in the ISTp arm [15]. Overall, DP was well tolerated, which is consistent with the results of a recent four-arm treatment trial comparing the four fixed-dose ACTs in the case management of malaria in pregnancy [34]. This is important as almost all RDT-positive women in our trial were asymptomatic, and tolerance can be a major factor determining adherence. ISTp is a labor-intensive strategy, but a separate qualitative substudy using in-depth interviews and focus group discussions showed it was highly acceptable to both patients and clinic staff. Although ISTp requires more frequent blood sampling, women appreciated its importance and the fact that they could be shown the RDT test results, corroborating findings from similar acceptability studies in Ghana [14,37]. The venous sampling at the first antenatal visit was deemed more convenient by women than repeated finger pricks, as it allowed health workers to tests for malaria, anemia, syphilis, and HIV testing with a single blood draw. Limitations of our trial include the open-label design used. Another limitation is that we were not able to include a third arm with IPTp with DP as there was insufficient safety information for repeat courses of DP available at the time this trial was designed. Approximately 9% of the randomized women did not contribute to the primary outcome of adverse live birth outcome and 12% did not contribute to the primary outcome of plasmodium infection at delivery. However, this loss to follow-up was well balanced between the study arms, with little differences in baseline characteristics between those who contributed to the primary endpoint versus those who did not; thus, this loss to follow-up is unlikely to have biased the findings. The proportion of multigravidae reporting using a bednet the night prior to enrollment was slightly lower in the ISTp-DP arm; however, this did not explain the observed difference in the risk of plasmodium infection at delivery, as all women received an insecticide-treated net on enrollment, and bednet use thereafter was near universal in both arms (99% in each arm). ISTp-DP was not superior to the existing IPTp-SP regimen in this area with high SP resistance in southern Malawi. These results should be equally relevant to other high endemic areas in east and southern Africa with similar or lower levels of parasite SP resistance. The identification of alternative drugs to replace SP remains a pressing research priority for the control of malaria in pregnancy before levels of SP resistance render IPTp-SP fully ineffective. 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autophagocytosis Also found in: Dictionary, Medical, Wikipedia. Related to autophagocytosis: Autophagolysosome, autophagosome autophagocytosis [¦ȯd·ō‚fag·ə·sī′tō·səs] (cell and molecular biology) The cellular process of phagocytizing a portion of protoplasm by a vacuole within the cell. Mentioned in ? References in periodicals archive ? In addition, autophagocytosis (demonstrated by the presence of autophagic vacuoles) and macrophagocytosis (phagocytized, degenerated tumor cells which have previously been described as Councilman bodies and are now referred to as apoptotic bodies) were noted in the giant tumor cells with multiple nuclei. The discovery involves the identification of a specific mechanism by which VLDL is degraded or broken down, a process referred to as autophagocytosis. They discovered that a process called autophagocytosis reduces the buildup of beta-amyloid in isolated cells and might be utilized to eliminate the buildup of beta-amyloid in the brains of Alzheimer's patients.
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Posted: December 11th, 2017 The doctor has prescribed Cortisone (cortisone) for a client with systemic lupus erythematosus. Which instruction should be given to the client? The doctor has prescribed Cortisone (cortisone) for a client with systemic lupus erythematosus. Which instruction should be given to the client? a. Take the medication 30 minutes before eating. b. Report changes in appetite and weight. c. Wear sunglasses to prevent cataracts. d. Schedule a time to take the influenza vaccine Expert paper writers are just a few clicks away Place an order in 3 easy steps. Takes less than 5 mins. Calculate the price of your order You will get a personal manager and a discount. We'll send you the first draft for approval by at Total price: $0.00 Live Chat+1-631-333-0101EmailWhatsApp
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Suddenly Slender Now The Mineral Body Wrap! Call Us! 970-259-6961 FAQ Q. What happens during a Suddenly Slender, The Body Wrap? A. First our wrap technicians will determine exactly what improvements you desire, they will weight and measure specific areas of your body. You will be fit into a special bra to increase, decrease or just firm and tighten the bust. Next you will be wrapped in eleastic bandages that have been soaked in our exclusive mineral solution. The wrap will be firm yet comfortable, when you’re all wrapped up you will do some light exercise for an hour to enhance your results. Then you will be unwrapped, weighed and measured again and enjoy your visible body improvement! Q. Isn’t it just water weight loss? Are the inches going to come back when I eat or drink? A. It isn’t water loss. There is no sweating or heating involved. We are actually exchanging minerals for impurities in the body. You will feel very clean, energized and refreshed and look slimmer after your wrap. Q. Does this mean I become dehydrated, and that’s why I lose inches? A. No. Our body wrap does not dehydrate, we actually re-hydrate a dehydrated body. You will not feel thirsty or tired. You can get as many wraps in a day as you want. We could not do repeat wraps and get further improvement if our wraps caused dehydration. Q. How long does the body wrap process take? A. For your first wrap, allow a total of 2 to 2 1/2 hours. This allows time for a free consultation where you set your face and figure goals, get weighed and measured, fit into the “It’s All You!” bra, be wrapped, and exercise mildly in your wrap for 60 minutes. Then you will be unwrapped and your improvements recorded. Your second visit will require much less time. Q. When will I start seeing results? A. Immediately! And you will still continue to visibly slim down even after the wrap while the minerals continue to work in your system. Q. When should I come back for another wrap? A. Our wraps are safe to use multiple times in a day and produce long lasting results. For maximum improvement we recommend twice a week wraps. Your Wrap Technician will always be at hand to guide clients through the process, suggest specific nutritional products and tailor special programs catered to your own specific needs and desired goals, whether it is a younger appearance or a visibly slimmer body or both. Q. How long should I wait to eat before or after having a body wrap? A. Feel free to eat and drink anytime. But avoid eating heavily for an hour or so before your wrap. Our Patrons report a lessening of desire for sugar, salt and fats after being wrapped. Q. I have sensitive skin. Will I have any reactions to the wrap? A. No, in 14,000,000 wraps delivered over a 41 year history we have never had an allergic reaction. It is physiologically impossible due to the purity and choice of minerals used in our Suddenly Slender Inc solutions. Our wrap materials are all-natural. The only negative side effect reported is that your clothes get very loose! Q. If I want to contour my problems areas and slim down quickly, do you offer packages? A. All Suddenly Slender Inc Licensees Salons offer discounted packages for those who are interested in being one or more sizes slimmer, many Salons will custom create wrap and supplement packages to get you to your target size and weight as quickly as possible. Q. How can you guarantee I’ll look 15 inches slimmer with each wrap? A. We ask women to wear in a pair of jeans so tight they have to lay on the bed to zip them, men are asked to wear in a shirt so tight that there are gaps between the buttons. You’ll be amazed how much better your clothes fit after each wrap. We make that guarantee because we can do it! Q. How does The Body Wrap work? A. Impurities, such as environmental poisons, chemicals in the air water and food all can cause the body to “bulk up” in specific undesirable areas, our cutting edge supplements and wraps will assist the body in disposing of those damaging materials that can cause premature aging, wrinkles, cellulite, excess size, water retention, and lack of energy. All these problems will be addressed by our products, your Wrap Technician will advise you as to exactly what will give you the most benefit along with your wraps. Q. What does The Body Wrap do for skin? A. Your skin will appear smoother and tighter and feel like satin after being wrapped. Our wraps, skin care and supplements also focus on helping you fight the visible signs of aging. Q. I’ll be getting married soon and running out of time to fit into my wedding gown. Can Suddenly Slender help me look fabulous on my big day? A. Our body wrap is perfect for important occasions like weddings, parties, balls and reunions. We can customize a package of treatments before your big day, so that you look slim, trim and younger in the shortest time possible. Q. I have a lot of stubborn problem areas in my hips and thighs. Can Suddenly Slender Now help me? A. YES. We can do a great deal for those problems because our mineral body wraps help to bring the body into correct proportion. It is a sculpturing process, we have found that the body functions best in an aesthetically perfect shape. For stubborn fat areas, we recommend our High Concentrate Wrap. Please ask your consultant about this wrap formula. Q. Will I be able to rest while wrapped? A. Yes, if you are ill, stressed or just tired ask about our Dream Body Laydown wrap. After one or more of these, most Patrons have the desire and energy to do the regular sculpturing wraps. We have found that if you can stay active while in your wrap it helps improve circulation making your results more dramatic. The activity recommended is not strenuous at all, moving around is usually all that is needed to get the full benefit of the wraps. Q. A healthy lifestyle is important to me. How does Suddenly Slender Now fit in? A. Here at Suddenly Slender Now, your health is important. The treatment is very safe and it’s for everyone, young and old. Besides aiding your body in the process of expelling impurities we are also infusing it with over 80 major and trace minerals as well as vitamins. Clients notice an increase in energy, smoother, tighter skin, and discover that they have better sleeping habits, feel so much more rejuvenated, look slimmer and full of energy.
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Conoce más Abrir Denny's Philly Cheesesteak - Descuentos para socios de AARP Denny's Los socios ahorran todos los días                                    Los socios pueden recibir una dona gratis   Búsqueda de trabajo con AARP Busca trabajo Encuentra un empleo hoy                   Recursos para encontrar empleo Walgreens - Descuentos para los socios de AARP Walgreens Ofertas exclusivas de puntos para socios                                                 Ofertas exclusivas de puntos para socios Black History Month Member Benefits Celebra la historia afroamericana Ahorra en tu membresía                                                                                                                                                           Celebra y ahorra en tu membresía de AARP cómo combatir el hambre Abuela cocinando con su nieta Consume alimentos nutritivos y económicos. Busca ayuda del gobierno si la necesitas. Más información aquí. juegos Juegos de AARP Prueba tus destrezas e ingenio. ¡Juega gratis! Más videos salud bmi tool Descubre cuán saludable es tu peso. Calcula tu IMC. Trivias ¿Qué tanto sabe? Conteste la trivia ¡Pon a prueba tus conocimientos sobre salud, entretenimiento y más! Contesta las trivias. horóscopo Acuario - Horóscopo de AARP ¿Eres Acuario? Si tu cumpleaños es entre el 20 de enero y el 18 de febrero, aquí encontrás tu horóscopo diario. Por su bienestar Dieta suave de desintoxicación 10 consejos para comenzar bien y tener mejor salud todo el año. Algunas verduras como esparragos y cebollas en una tabla cde cortar — Thomas Barwick/Getty Images In English | Para muchos, el Año Nuevo empieza con resoluciones relacionadas con el bienestar, como por ejemplo, comer alimentos saludables, hacer más ejercicio y perder peso. Si el exceso de galletas y cocteles lo dejaron sintiéndose irritable y sin energía, empiece ya un plan de bienestar desintoxicándose de su alimentación habitual. Los resultados de estudios médicos indican que nuestra salud digestiva está vinculada a una serie de problemas crónicos de salud. Dejar de consumir alimentos procesados, azúcar, sal y cafeína por algunos días puede ayudarlo mucho a tener mejor salud y a sentirse más feliz. Pero, recuerde que la finalidad de una dieta adecuada de desintoxicación basada en suprimir ciertos alimentos no es hacerle perder peso, sino eliminar de su cuerpo las toxinas y los alergenos comunes de los alimentos. Aunque es probable que al seguir una dieta natural pierda peso. Las personas que tienen problemas graves de salud deben ver a su médico antes de hacer cualquier cambio a su alimentación usual o tomar suplementos de vitaminas. Para lograr el beneficio máximo de una dieta de desintoxicación, trate de seguir las instrucciones que se dan a continuación por lo menos durante dos semanas y, hacia el final de ese período, agregue poco a poco y con moderación algunos de los alimentos que suele consumir. Beba por lo menos 10 vasos de agua filtrada todos los días. Los riñones eliminan de nuestro cuerpo los productos de desecho y el agua desempeña un papel esencial en este proceso: • Elimine la harina blanca y el azúcar blanca. • Haga entre seis y ocho comidas pequeñas todos los días de alimentos integrales no procesados que incluyan verduras, frutas, nueces y cereales. • Cada una de estas comidas debe incluir una porción de verduras crucíferas como brócoli, repollo, col rizada y coles de Bruselas. Además de ajo, cebollas y cilantro porque contienen propiedades que ayudan a la desintoxicación. • Consuma frutas frescas, en lugar de tomar jugos de frutas, que suelen tener mucha azúcar. • A menos que sea vegetariano, incluya porciones pequeñas de proteína animal sin grasa y pescado. De ser posible, se recomienda consumir carnes y productos lácteos orgánicos de animales alimentados con pasto, para evitar ingerir más hormonas o antibióticos. • Evite los estimulantes como la cafeína. •  Elimine las drogas y el alcohol. • Si sospecha que tiene alguna sensibilidad a ciertos alimentos, trate de eliminar el trigo/gluten, los huevos, los productos lácteos, los productos con levadura, los derivados de la soja y el maíz, y observe si se siente notablemente mejor después de unas cuantas semanas. • Tome diariamente un suplemento multivitamínico. Es posible que sienta efectos secundarios, como dolores de cabeza, falta de energía y náuseas debido a la eliminación del azúcar y el café de su dieta. Por lo general, estos síntomas desaparecerán después de unos cuantos días e indican que la desintoxicación está funcionando. Y, desde luego, igual que lo haría con cualquier otro programa de bienestar, haga un poco de ejercicio. Elija lo que más le guste como caminar, montar bicicleta y nadar o hacer yoga, porque lo más importante es mover el cuerpo y sudar. Respire profundamente, coma los alimentos que más le convienen y descanse todos los días. Con un poco de paciencia y esfuerzo, la recompensa será verse y sentirse mejor, además de la motivación para seguir adelante con su plan de alimentarse bien todos los días. Alertas de tema Usted puede recibir alertas semanales por correo electrónico sobre los siguientes temas. Solo haga clic en “Seguir” Administrar alertas Procesamiento Por favor espere... progress bar, please wait ¿Qué opina? Deje su comentario en el campo de abajo. Publicidad Denisse Oller - Experta en Cocina de AARP La sazón de Denisse Prepara ricas y nutritivas recetas con el toque único de la chef Denisse Oller. Publicidad Ofertas y Beneficios De compañías que cumplen con los altos estándares de servicio y calidad establecidos por AARP. Regal Movies Popcorn and Soda, Member Benefits Los socios ahorran $3 en combinaciones de cualquier tamaño de palomitas de maíz y refrescos en los cines Regal Cinemas. walgreens couple gloves membership discount aarp Los socios reciben ofertas exclusivas de puntos en productos selectos de Walgreens. Member Benefits Outback Los socios ahorran un 15% en el almuerzo y la cena todos los días en Outback Steakhouse. African American generational family photo Celebra la historia afroamericana y recibe hasta un 20% de descuento al unirte  o renovar tu membresía de AARP. Publicidad
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J.P. de Winter (Johan) http://repub.eur.nl/ppl/295/ List of Publications en http://repub.eur.nl/eur_signature.png http://repub.eur.nl/ RePub, Erasmus University Repository Inhibin interferes with activin signaling at the level of the activin receptor complex in Chinese hamster ovary cells http://repub.eur.nl/pub/8700/ Wed, 01 Jan 1997 00:00:01 GMT <div>J.W.M. Martens</div><div>J.P. de Winter</div><div>M.A. Timmerman</div><div>A. McLuskey</div><div>R.H.N. van Schaik</div><div>A.P.N. Themmen</div><div>F.H. de Jong</div> To gain more insight in the mechanism of action of inhibin, we studied the effect of inhibin on activin signaling in Chinese hamster ovary cells. Inhibin specifically counteracted activin-induced expression of a plasminogen activator inhibitor 1 promoter element (3TP) and of the junB gene, but was ineffective when the responses were induced by transforming growth factor-beta. This indicates that inhibin acts only on the activin-specific part of these signaling cascades. Using a constitutively active activin type IB receptor we determined whether inhibin acted at the level of the activin-receptor complex or downstream of it. The mutant activin receptor stimulated the expression of the 3TP promoter in the absence of activin. This stimulation was insensitive to inhibin, indicating that inhibin acts exclusively at or upstream of this activin type I receptor. In addition, competition studies using labeled activin showed that inhibin displaced activin from the activin type II receptors, especially from the activin type IIB receptor, but not from the type I receptors. In conclusion, these data show that in Chinese hamster ovary cells inhibin acts directly at the activin receptor complex, most likely through displacement of activin from the activin type II receptor. Activins and activin receptors in the rat testis http://repub.eur.nl/pub/23760/ Wed, 08 Jun 1994 00:00:01 GMT <div>J.P. de Winter</div> Inhibin and activin are gonadal protein hormones, which were originally defined by their negative and positive feedback action on the release of follicle stimulating hormone (FSH) from the pituitary gland. However, recent studies revealed that inhibin and activin do not only control FSH release but can also affect the functions of a large number of other cell types, as will be discussed in section 1.7. This section is preceded by short descriptions of the testicular cell types (section 1.2), the structures of inhibins, activins and other members of the TGF·-B family of growth and differentiation factors (sections 1.3 and 1.4), and of receptors and non-receptor binding proteins for inhibin and activin (sections 1.6 and 1.7). Finally, events occurring after binding of activin to its receptor are discussed in section 1.8. The aim of the experiments described in this thesis was the elucidation of intratesticular effects of activin. The expression of activin receptors, the secretion of activins and the effects of activins in the rat testis have been investigated. Peritubular myoid cells from immature rat testes secrete activin-A and express activin receptor type II in vitro http://repub.eur.nl/pub/8584/ Sat, 01 Jan 1994 00:00:01 GMT <div>J.P. de Winter</div><div>H.M.J. Vanderstichele</div><div>G. Verhoeven</div><div>M.A. Timmerman</div><div>J.G. Wesseling</div><div>F.H. de Jong</div> The expression of activin type II and IIB receptors and inhibin alpha-, beta A-, and beta B-subunit messenger RNAs (mRNAs), and the secretion of immunoreactive and bioactive activin during culture of testicular peritubular myoid cells and peritubular myoid cell lines were studied. Cultured peritubular myoid cells and cell lines expressed high levels of inhibin beta A-subunit mRNA and some inhibin alpha- and beta B-subunit mRNA. Activin receptor type II mRNA was also detected, whereas activin receptor type IIB mRNA expression was not found. Expression of the beta A-subunit mRNA was present immediately after isolation of the cells and increased during culture in Eagle's Minimum Essential Medium containing 10% fetal calf serum. beta A-Subunit mRNA expression was not regulated by the synthetic androgen R1881. Western blotting of peritubular myoid cell- and peritubular cell line-conditioned media with a polyclonal antiserum against recombinant activin-A revealed the presence of 25-kilodalton activin-A, whereas activin bioactivity was detected using the animal cap assay. Because of the secretion of activin-A by peritubular myoid cells, the effects of recombinant activin-A on Sertoli cell inhibin and transferrin secretion were examined. Activin-A stimulated both basal and FSH-stimulated inhibin and transferrin production by Sertoli cells after 72 h of culture. These effects resemble the effects of the testicular paracrine factor PmodS on Sertoli cell function. It is concluded that activin-A is secreted by peritubular cells in vitro and that activin-A shares a number of effects on Sertoli cell function with PmodS. A novel member of the transmembrane serine/threonine kinase receptor family is specifically expressed in the gonads and in mesenchymal cells adjacent to the mullerian duct http://repub.eur.nl/pub/8588/ Sat, 01 Jan 1994 00:00:01 GMT <div>W.M. Baarends</div><div>M.J. van Helmond</div><div>M. Verhoef-Post</div><div>P.J.C.M. van der Schoot</div><div>J.W. Hoogerbrugge</div><div>J.P. de Winter</div><div>J.Th.J. Uilenbroek</div><div>B. Karels</div> The activin and TGF-beta type II receptors are members of a separate subfamily of transmembrane receptors with intrinsic protein kinase activity, which also includes the recently cloned TGF-beta type I receptor. We have isolated and characterized a cDNA clone (C14) encoding a new member of this subfamily. The domain structure of the C14-encoded protein corresponds with the structure of the other known transmembrane serine/threonine kinase receptors. It also contains the two inserts in the kinase domain that are characteristic for this subfamily. Using in situ hybridization, C14 mRNA was detected in the mesenchymal cells located adjacent to the mullerian ducts of males and females at day 15 (E15) of embryonic development. Marked C14 mRNA expression was also detected in the female gonads. In female E16 embryos, the C14 mRNA expression pattern remained similar to that in E15 embryos. However, in male E16 embryos C14 mRNA was detected in a circular area that includes the degenerating mullerian duct. The expression of C14 mRNA was also studied using RNase protection assays. At E15 and E16, C14 mRNA is expressed in the female as well as in the male urogenital ridge. However, at E19, a high C14 mRNA level in the female urogenital ridge contrasts with a lack of C14 mRNA in the male urogenital ridge. This correlates with the almost complete degeneration of the mullerian ducts in male embryos at E19. C14 mRNA expression was also detected in embryonic testes at E15, E16 and E19 using RNase protection assays, but at much lower levels than those found in the developing ovaries.(ABSTRACT TRUNCATED AT 250 WORDS) Activin is produced by rat Sertoli cells in vitro and can act as an autocrine regulator of Sertoli cell function http://repub.eur.nl/pub/8881/ Fri, 01 Jan 1993 00:00:01 GMT <div>J.P. de Winter</div><div>H.M.J. Vanderstichele</div><div>M.A. Timmermans</div><div>L.J. Blok</div><div>A.P.N. Themmen</div><div>F.H. de Jong</div> Regulation of androgen receptor (AR) mRNA expression was studied in Sertoli cells and peritubular myoid cells isolated from immature rat testis, and in the lymph node carcinoma cell line derived from a human prostate (LNCaP). Addition of dibutyryl-cyclic AMP (dbcAMP) to Sertoli cell cultures resulted in a rapid transient decrease in AR mRNA expression (5 h), which was followed by a gradual increase in AR mRNA expression (24-72 h). This effect of dbcAMP mimicked follicle-stimulating hormone (FSH) action. In peritubular myoid cells, there was only a moderate but prolonged decrease during incubation in the presence of dbcAMP, and in LNCaP cells no effect of dbcAMP on AR mRNA expression was observed. When Sertoli cells or peritubular myoid cells were cultured in the presence of androgens, AR mRNA expression in these cell types did not change. This is in contrast to LNCaP cells, that showed a marked reduction of AR mRNA expression during androgen treatment. In the present experiments, transcriptional regulation of AR gene expression in Sertoli cells and LNCaP cells was also examined. Freshly isolated Sertoli cell clusters were transfected with a series of luciferase reporter gene constructs, driven by the AR promoter. It was found that addition of dbcAMP to the transfected Sertoli cells resulted in a small but consistent increase in reporter gene expression (which was interpreted as resulting from AR promoter activity); a construct that only contained the AR 5' untranslated region of the cDNA sequence did not show such a regulation. The same constructs, transfected into LNCaP cells, did not show any transcriptional down-regulation when the synthetic androgen R1881 was added to the cell cultures. A nuclear transcription elongation experiment (run-on), however, demonstrated that androgen-induced AR mRNA down-regulation in LNCaP cells resulted from an inhibition of AR gene transcription. The present results indicate that in Sertoli cells and LNCaP cells, hormonal effects on AR gene transcription play a role in regulation of AR expression. However, AR gene transcription in these cells is differentially regulated.
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← Genito-Urinary DisorderFinasteride → Common Medicines Common Medicines Buy custom Common Medicines essay 1) Explain how common medicines are used to treat incontinence (two examples). Describe the therapeutic actions of your chosen drugs Buy Common Medicines essay paper online Total price £    * Final order price might be slightly different depending on the current exchange rate of chosen payment system. The management of urinary incontinence involves the combination of behavioral techniques as well as use of medications. For instance, anti-cholinergic drugs are very popular in the management of urinary incontinence. Typical examples include tolterodine and trospium among others. Their therapeutic effects arise from the relaxing effectthat they have on an overactive bladder.  2) Summarize two side effects of each of your chosen treatment and discuss the reasons why one of the side effects (for one drug only) may occur. The two drugs basically have the same side effects of blurred vision, flushing and constipation. They may occur because the drugs are not selective for the destrusor muscle and thus, acts on muscles of the eye to cause blurred vision and on the intesstinal muscles to cause constipation. 3) Explain the information that must be given to patient about your recommended medications and provide information to the patient to manage his condition effectively. Anti-cholinergic drugs may cause fatality if over-dozed. Thus, patients must take precaution not to exceed the doctor’s prescription. Besides, the severity of the side effects increase with the relative increase in the dosage. Related Health essays Most popular orders     Special Offer!Pay less for your papers Special Offer - 15% off Get 15% off your first order Close We are online - chat with us!  
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Skip to main content Advertisement Assessment of anti-depressant effect of nelumbinis semen on rats under chronic mild stress and its subchronic oral toxicity in rats and beagle dogs Abstract Background Previously, we examined the antidepressant effects of Nelumbinis Semen (NS). In this study, we assessed the anti-depressant effects of NS in the forced swimming test and chronic mild stress (CMS) models of depression and its oral toxicity in rats and dogs. Methods In the forced swimming test, NS was intraperitoneally injected before 24 h, 5 h and 1 h of forced swimming test. And the rats were forced to swim for 5 min, the duration of immobility was observed. In CMS models, animals were exposed to a variety of CMS for 8 weeks in order to induce depression-like symptoms. They were treated with NS for the last four weeks of the 8-week CMS and then an open field test was conducted. The anti-depression effects were evaluated based on a measured index, which consisted of visiting counts, start latency, rearing number and grooming time. In the toxicological studies, NS was administered to rats by gavages for 13 weeks at doses of 0, 500, 1000, and 2000 mg/kg/day. To assess the toxicity of NS in beagle dogs, NS was administered orally for 28 days at doses of 0, 500, 1000, 2000 and 4000 mg/kg/day. Results 400 mg/kg of NS had the lowest immobility times in forced swimming test. And NS significantly reversed the decreased visiting counts, rearing number and grooming time caused by CMS. In addition, NS treatment significantly decreased the start latency. No treatment-related toxicity was detected during 13 weeks administration in rats and 28 days administration in dogs. Conclusions Based on the results of this study and previous reports that have examined the anti-depressive effects of NS, NS holds great promise for use in the treatment of depression without causing any adverse effects or toxicities. Backgrounds Nelumbo nucifera is a perennial aquatic plant grown and consumed all over the world, especially in India and South East Asia. Nelumbinis Semen (NS, the seeds of Nelumbo nucifera) or lotus seed is a traditional medicine that has been used for hundreds of years in East-Asia to treat insomnia, anxiety and women's post-menstrual-pause depression [1]. NS contains alkyl 4-hydroxybenzoates [2], some bisbenzylisoquinoline alkaloids [35], benzylisoquinoline alkaloids [4], aporphine and proaporphine alkaloids[6]. In previous studies, we found that this herbal medicine exerted an antidepressant-like effect in rats based on the forced swim test. The results of that study suggested that NS could increase local cholinergic and dopaminergic or norephinergic neurotransmission via activation of cAMP formation in the hippocampus and pre-frontal cortex [7, 8]. Natural products have long been used in traditional medicine to treat inflammation and other inflammation-related diseases, and the raw materials of these products are often used to develop new drugs [9, 10]. Many factors contribute to the appeal of herbal medicine and herbs have been used to both treat and prevent diseases. Herbal treatments are considered safe because they are a natural, gentle, and harmless alternative to conventional medicine. However, there is a lack of evidence related with the toxicology of herbal medicines and some people insist that herbal medicines are toxic to the liver. Although the root and leaf of Nelumbo nucifera has been used in health food or tea, the safety of NS had not been previously established, which is a needed before this herbal medicine can be used as a new drug. The aim of this study was to investigate the anti-depressive effects and the toxicity of NS after repeated oral administration. Methods Animal In the pharmacological study, 6 week old male Wister rats, weighing 180 ~ 200 g, were supplied by Jung-Ang Experimental Animal Center (Seoul, Korea). The rats were allowed free access to their diets and tap water, except during the scheduled CMS. The rats were adapted to this environment for 1 week prior to the experiments. All procedures involving the use of the animals were approved by the Institutional Animal Care and Use Committee of Kyung Hee University and were carried out in accordance with the ethical guidelines. In the 13-week oral toxicity study, 48 male and 48 female Sprague–Dawley (SD) specific pathogen free (SPF) rats 5 weeks old were obtained from Koatec Inc (Gyeonggi-do, Korea). For the 4-week oral toxicity study in dogs, 6 male and 6 female Beagle dogs were received from Beijing Marshall Biotechnology Company (Beijing, China). The dogs were 6 months old and weighed 7.88–8.58 kg upon initiation of treatment. They were housed individually in stainless-steel cages in a controlled environment (temperature 23 ± 3 °C, humidity 55 ± 15%, 12 h light/12 h dark cycles). Ventilation was given 10 to 20 times/h and a quantitative pellet diet was provided at a fixed time each day. During a 2-week acclimatization period, parameters including body weight, temperature, appetite and performance of the dogs were observed and recorded before treatment. The toxicity study was conducted at the Good Laboratory Practice (GLP) institute approved by the Korea Food and Drug Administration (KFDA), in compliance with the GLP and Test Guidelines of the Organization for Economic Cooperation and Development [11] and the KFDA [12]. The study protocol was approved by the Institutional Animal Care and Use Committee (IACUC) of the institute. (accredited by AAALAC International, 2010). Forced swim test Male Sprague–Dawley rats, weighed 260 to 310 g, were supplied by Korea Taconic Co., Ltd. (South Korea). The animals were allowed to adapt to lab conditions for 2 weeks prior to the commencement of the experiments. Rats were individually placed in a glass cylinder (20 cm diameter × 40 cm high) containing water (24 ± 1 °C) with a depth of 20 cm from the bottom. All rats were placed in cylinders filled with water and forced to swim for 15 min on day 1. NS dissolved in saline was intraperitoneally treated before 24 h, 5 h and 1 h of forced swimming test. On day 2, all rats were forced to swim for 5 min, and the duration of immobility was observed and measured. The immobility time was regarded as the time the mouse spent floating in the water without struggling and making only those movements necessary to keep its head above water. Chronic mild stress In order to induce CMS and depression-like behavior, rats were consistently exposed to various mild stressors, such as overnight illumination, food and/or water deprivation, cage tilt and change of cage mate over an 8 week period, as described previously [7]. These stressors were changed every few hours over the 8 week period. Preparation of anti-depressants The sprayed-dry extracts of Nelumbinis Semen were purchased from the Sun-Ten Pharmaceutical Company, Taiwan. Hyperium Perforatum and fluoxetine were used as the positive controls. The Hyperatum Perforatum was purchased from HBC Protocols Company (Los Angeles, CA, USA). The Hypericin concentration, which is the standard material for Hyperatum Perforatum, was 0.3%. This compound has been widely used as an index in animal studies [13]. Fluoxetine (Prozac), a selective serotonin reuptake inhibitor (SSRI), was purchased from Sigma Company (St. Louis, MO, USA). Drug administration Nelumbinis Semen (400 mg/kg/day), Hyperium Perforatum (2.68 g/kg/day) or fluoxetine (10 mg/kg/day) was administered orally (Nelumbinis Semen and Hyperium Perforatum) or intraperitoneally (fluoxetine) for the last 4 weeks during the 8 week-CMS. Open field activity In order to evaluate the difference between CMS exposure and drug administration, several rat behaviors were observed and required in an open field. The open field consisted of a wooden box with dimensions of 75 × 75 × 30 cm. The floor of the box was divided into 15 cm squares using lines. The open field was connected to a small box with dimensions of 15 × 15 × 15 cm, which was used as the start box where the experimental animals was placed prior to entering the open field. A vertical sliding door was installed between the start box and the open field. Rats were placed in the start box, and, after 30 sec, the sliding door was open. The time to leave the start box toward the open field, which was expressed as the start latency, was recorded. The start latency time corresponds to the time from when the door was opened to when the rat tail completely exited the start box. Immediately after the start latency, open field behaviors of rats were observed and recorded. The following behaviors were recorded over a total of 10 min: locomotion, rearing, grooming and defecation. Grooming behavior was recorded as the total time spent grooming over 10 min, and the remaining behaviors were all recorded as frequencies. Locomotor activity was recorded by counting the number of squares each rat crossed on the floor, which was divided into 25 15 × 15-cm squares, using a computer tracking system. Rearing was recorded as the total number of times each rat displayed exploratory behavior, while standing on its hind paws during 10 min. Grooming was recorded as the number of times each rat stroked its head or combed its fur with its forepaws during 10 min. Rat toxicity studies The 13-week oral dose study in rats was performed to assess the general toxicity of NS in rats (n = 5/sex/dose group) at doses of 0, 500, 1000 and 2000 mg/kg following daily gavage administration. The animals were randomized by sex into one of the four dose groups. After NS was administered orally at dose levels of 0, 500, 1000 and 2000 mg/kg/day (male 5, female 5) for 13 weeks, several parameters such as mortality, clinical signs, body weight changes, food and water consumption, urinalysis, hematology and serum biochemistry examinations, necropsy findings and relative organ weights were recorded. Dog toxicity studies 1 male and 1 female dogs each were treated with 0, 500, 1000, 2000, and 4000 mg/kg NS, respectively, via oral administration once daily for 28 days. Body weight and average food consumption of the dogs were recorded every week. Their body temperatures were measured before and after administration. The animals were observed carefully throughout the experiment, especially the moment after administration. Objective signs including color pattern, cleanliness, behavior, food intake, urine, manure, psychic states, eye and porous channel secretions were measured and recorded every day. Blood analysis All live animals were subjected to hematological tests before grouping and on the scheduled necropsy day. A portion of blood sample from the cephalic vein was collected in a serum separation tube (Vacutainer tube, SST, Gel & clot Activator). The blood was kept for 15–20 min at room temperature then centrifuged at 3,000 rpm for 10 min and the supernatant serum was used for analysis. Urinalysis Before administration and two day before necropsy, the urine was examined using a test strip for urinalysis (Bayer) and an automatic urinalysis system (CliniTek 100, Bayer). The urinalysis test items were glucose, bilirubin, ketone body, specific gravity, occult blood, pH, protein, urobilinogen, nitrite and leukocyte. Autopsy and histopathological study Animals were sacrificed by exsanguinations and dissected. During the process of dissecting, the color, texture and lump of parenchymatous organs were carefully examined. The color and integrity of the cavities’ mucosa were also examined. In addition, the weight of the brain, hypothyroids, lungs, heart, thymus glands, liver, spleen, kidneys, adrenal glands, prostate, testicle, and ovaries were measured and recorded. The organ-body index was calculated according to the following formula [14]: Organ-body index (%) = Wet organ weight/Body weight × 100%. All extracted organs from all animals were fixed in a 10% neutral formaldehyde solution, except for the testes, which were fixed in Bouin’s solution. Statistical analysis To compare the test groups with the control group, parametric or non-parametric multiple comparison procedures were applied All statistical analysis were performed using the commercial statistical package SPSS 10.1. In the case of continuous data, such as open field activity, body weights, food and water consumptions, hematology and serum biochemistry, and relative organ weights, data expressed with mean ± S.D were subjected to One-Way ANOVA test to assess significance. Cases that showed a significant difference were subjected to the Levene test to assess equality of variances. If homoscedasticity of the data was accepted, the Duncan’s multiple range test was applied. Otherwise, Dunnett’s t-test was conducted to examine the significance between the treatment groups and control. For analysis of discontinuous data such as urinalysis, the data was subjected to scale transformation, which expresses the data as the severity of the signs (Table 1). Table 1 Scale transformation of urinalysis data according as the severity of the signs For non-parametric multiple comparison, Kruskal-Wallis´ H-test was performed. Cases that showed a significant difference were analyzed by the Mann–Whitney U-test and Student’s t-test. In dog toxicity studies, statistical analysis was not carried out because each group included only 1 animal of both sexes. Results Evaluation of antidepressive activity of the NS by an animal behavioral test in a forced swimming test (FST) and a CMS model of depression It is known that the stressed mice exhibited a markedly depressed phenotype characterized by increased durations of immobility during the FST when compared with non-stressed mice [15]. To determine the maximal effective dose of NS in FST, we treated NS at various doses. As shown Figure 1, 400 mg/kg of NS had the lowest immobility times in FST. Based on this result, we compared the anti-depressant effect of NS with Prozac and natural St. John's wort in the open field test. Figure 1 figure1 The anti-depression effect of NS on the durations of immobility in the forced swim test. NS or saline was intraperitoneally injected before 24 h, 5 h and 1 h of the forced swim test, rats (n = 5 in each group) were individually placed in a glass cylinder containing water. During the 5 min test, the duration of immobility was observed and measured. The immobility time was regarded as the time spent by the mouse floating in the water without struggling. *P < 0.05 compared to control. After drug administration for the last four weeks of the 8-week CMS period, the total number of chambers which each animal visited (visit counts) was recorded in the open field test. As shown in Figure 2A, compared to the control group (C), the NS group displayed a significant increase in visit counts. These visit counts were greater than those of the representative conventional antidepressants, Prozac (P) and natural St. John's wort (SW), demonstrating that the NS extract produced a strong antidepressive effect. Also, these results indicate that NS administration reversed the rat activity caused by CMS-induced depression. Figure 2 figure2 The anti-depression effect of NS based on (A) visit counts, (B) start latency (C) rearing numbers and (D) grooming time in the open field test after antidepressant treatment during the last 4 weeks of the 8-week CMS. N = normal group without any condition and treatment, C = control group without any treatment under CMS, NS = NS treatment group under CMS, P = Prozac treatment group under CMS and SW = St. John's Wort treatment group under CMS. 6 rats were used in each group. *P < 0.05 and **P < 0.01 compared to control. The effect of NS treatment on the start latency time was also measured. As shown in Figure 2B, compared to the control group (C), only the NS group displayed a significant decrease (P < 0.05) in start latency. NS administration resulted in a shortened start latency. These results indicate that the CMS-induced reduction in curiosity and the will to live was reversed by treatment with NS. Rearing behavior in the open field was also recorded after drug administration for the last four weeks of the 8-week CMS procedure. As shown in Figure 2C, compared to the control group, the NS group displayed a significant decrease (P < 0.05) in rearing frequency. These results indicate that NS administration restored the exploratory behavior of rats when in a new environment. Thus, the CMS-induced reduction in the curiosity and exploratory behavior to neighboring environments was reversed by treatment with the NS extract. Grooming behavior in the open field was recorded after drug administration for the last four weeks of the 8-week CMS procedure. As shown in Figure 2D, compared to the control group, the NS group displayed a significant increase (P < 0.05) in grooming time. This antidepressive effect was similar to that of the conventional antidepressant, the St. John's wort plant. These results indicate that NS administration restored the rat’s interest in itself. Thus, the CMS-induced reduction in self-interest was reversed by treatment with the NS extract. Subchronic 13-week oral toxicity in rat There was no mortality and ophthalmic changes related to NS during the administration period. No significant differences in the body weight of the animals treated with NS was observed relative to the controls during 13 weeks (Figure 3). For the males that received a dose of 500 and 2000 mg/kg/day, food consumptions were lower on 7 and 12 weeks and for the males that received 1000 mg/kg/day, food consumption was lower on 7, 9, 10 and 12 weeks when compared to the control group (Table 2). Figure 3 figure3 Growth curve of male (A) and female (B) rats fed NS. Table 2 Food consumption of the rats during the study period In the hematological examination, a significant increase in hemoglobin concentration distribution width (HDW) values was observed in males that received a dose of 500, 1000 and 2000 mg/kg/day. In addition, the red cell distribution width (RDW) values were higher in males treated with 500 and 2000 mg/kg/day (Table 3). Since these changes were not consistent between the males and females group, they were likely unrelated to the administration of NS. Table 3 Hematological values following 13 weeks of daily oral administration of NS in male and female rats In the blood chemical examination, AST and ALT levels were higher in the all females that received NS treatment and the CPK level was lower in for both the male and female rats that received NS treatment. However, the differences were not significant (Table 4). Table 4 Serum biochemical values following 13 weeks of daily oral administration of NS in male and female rats Figures 4 shows the organ-to-body mass ratios of animals at the end of the 13 week treatment. Except for the right adrenal glands in male rat that were administered the 500 and 1000 mg/kg dose, no abnormal changes were observed in organ mass with respect to body mass of NS fed rats in comparison with controls. Although the weight of the right adrenal glands was lower in male rat the received the 500 and 1000 mg/kg dose, the changes were not does-dependent nor sex matched. Thus, these changes were considered to be unrelated with NS treatment. When the gross pathology immediately after dissection in rats of all groups was examined, all animals were found to be uniformly healthy, lacking any apparent pathological abnormalities. Figure 4 figure4 Percentage organ weight to body mass of male (A) and female (B) rats fed NS. 28- day dog does range finding (DRF) studies In previous toxicity studies using rats, no toxicologically significant signs were observed up to a dose of 2000 mg/kg. Before commencing administration in the present study, one male and female, which were remnants after grouping, was provided one dose of 2000 and 1000 mg/kg NS and no toxicological signs were found during five days of observation. Therefore, in the present study, the high dose was set at 4000 mg/kg and three lower dose groups were 2000, 1000 and 500 mg/kg. There was no mortality related to NS after 28 days. Vomiting was observed in male rats that received a dose of 2000 mg/kg on the day of 9th administration. Feeding was sporadically observed in the female treated groups (Data not shown). In addition, no significant changes related to NS administration were observed (Figure 5). Figure 5 figure5 Body weight changes of male (A) and female (B) dogs given NS orally for 4 weeks. In the urinalysis test, no unique changes related to NS administration were observed. Proteinuria was observed in males that received a dose of 0, 500 and 1000 mg/kg and in females that received 500, 1000 and 4000 mg/kg, and a low specific gravity (SG) of the urine was observed in all female groups. Furthermore, there was a positive reaction in the urine occult blood for males and females receiving a dose of 2000 mg/kg and 4000 mg/kg, respectively. In addition, a WBC reaction was observed in males that were treated with 0, 500, 2000 and 4000 mg/kg and females that recieved 2000 mg/kg (Table 5). However, these effects were not dose-dependent, not accompanied with other corresponding changes, and were observed before administration of NS. Therefore, these effects were not related to NS administration. Table 5 Urin analysis in male and female dogs In the hematological test, toxicologically significant changes related to NS administration were observed (Figures 6 and 7). In addition, there were no toxicologically significant changes related to NS administration in the serum biochemical data of male and female dogs fed with NS for 28 Days (Tables 6 and 7). The result of the hematological examinations and differential leukocyte counts, which were examined with blood taken at the necropsy, were similar between all the groups (Figures 8 and 9). Figure 6 figure6 Hematological data of male dogs fed with NS for 28 Days. HCT = Hematocrit, HGB = Hemoglobin concentration, MCH = Mean corpuscular hemoglobin, MCHC = Mean corpuscular hemoglobin concentration, MCV = Mean corpuscular volume, PLT = Platelet, RBC = Red blood cell, WBC = White blood cell. Figure 7 figure7 Hematological data of female dogs fed with NS for 28 Days. HCT = Hematocrit, HGB = Hemoglobin concentration, MCH = Mean corpuscular hemoglobin, MCHC = Mean corpuscular hemoglobin concentration, MCV = Mean corpuscular volume, PLT = Platelet, RBC = Red blood cell, WBC = White blood cell Table 6 Serum biochemical values in male dogs Table 7 Serum biochemical values in female dogs Figure 8 figure8 Differential leukocyte counts in male dogs. NEU = Neutrophil, LYM = Lymphocyte, MONO = Monocyte, EOS = Eosinophil, BASO = Basophil, LUC = Large unstained cells Figure 9 figure9 Differential leukocyte counts in female dogs. NEU = Neutrophil, LYM = Lymphocyte, MONO = Monocyte, EOS = Eosinophil, BASO = Basophil, LUC = Large unstained cells. An autopsy study was carried out after the animals were treated for 28 days. The organs, including heart, liver, spleen, lung, kidney, adrenal gland, thymus, thyroid gland, brain, uterus, ovary and testis were carefully examined. No noticeable pathologic changes were observed by the naked eye. Moreover, no significant differences in the organ-bodyweight indices of the organs mentioned above were found (Figures 10 and 11). After 28 days of NS treatment, histopathological investigations were carried out. No pathological changes were observed in any organs of these animals (Data not shown). Figure 10 figure10 Effect of NS orally administered for 28 days on organ-body weight indices in male Beagle dogs. The organ-body weight index was calculated using the following formula: Organ-body weight index (%) = Wet organ weight/Body weight × 100%. Figure 11 figure11 Effect of NS orally administered for 28 days on organ-body weight indices in female Beagle dogs. The organ-body weight index was calculated using the following formula: Organ-body weight index (%) = Wet organ weight/Body weight × 100%. Discussion Most components of Nelumbo nucifera such as the root, leaf, seed, and stem are edible, and they have been used as side dishes or tea in eastern Asia. Although the seed of Nelumbo nucifera has been used to treat various psychological disorders in traditional medicine, its effects and mechanisms are still largely unknown. However, many recent reports have examined its effects in various disease models. A review on this plant by Mukherjee et al. [16] stated that various parts of this plant display potential therapeutic activity, such as hypoglycemic, antidiarrheal, antimicrobial, diuretic, antipyretic as well as anti-inflammatory activities of its rhizomes extracts [17, 18]. Hepatoprotective [19], antiproliferative [20], anti-inflammatory as well as antioxidant [21] activities of its seed extracts have also been reported. In addition, many studies regarding the anti-depressive effects and mechanism of Nelumbinis Semen (NS) have recently been performed. Kang et al. reported that NS reverses a decrease in 5-HT1A receptor binding and hippocampal 5-HT release induced by chronic mild stress, which is a depression-like symptom [1, 7]. These studies suggested that Nelumbinis Semen increases serotonin levels, which are normally lower during depression, and enhances central serotonergic transmission. Thus, NS may be used for the treatment of depression. Sugimoto et al., also showed that neferine, an alkaloid of NS, has antidepressant-like effects in mice similar to typical antidepressants and that these effects are mediated by the 5-HT1A receptor [22]. In this study, we evaluated the anti-depressive effects of NS based on behavior tests in a forced swimming test and a chronic mild stress model. When we evaluated the maximal effective dose in a forced swimming test, 400 mg/kg of NS was shown the most shortened immobility times. When we compared NS with other well known anti-depressants such as fluoxetine and St. John’s Wort, NS showed equal or higher anti-depressive effects compared with these commercially available anti-depressants. Even if NS is effective to treat depression, its toxicity must be evaluated before it can be utilized as a new drug. Thus, in this study, we carried out NS toxicity studies in rats and dogs. In the rat toxicity studies, NS was administered orally at dose levels of 500, 1000, and 2000 mg/kg/day. In these experiments, NS caused no changes that could be considered toxicologically significant. In the serum biochemical analysis, ALT and AST levels decreased in only NS fed female rats. However, these changes were not significant and no correlated changes were observed in necropsy findings and organ weight. Significant hematological changes were observed in male rats that received doses of 500 and 2000 mg/kg/day, including statistically significant increases in RDW and HDW in all NS fed rats. However, these changes were not consistent across the different genders and no changes in leukocytes differentiation were observed. Consequently, repeated oral administration of NS to rats for 13 weeks resulted in no toxicological changes in any of the examinations, namely mortality, clinical signs, body weight changes, food and water consumption, urinalysis, hematology and serum biochemistry examinations, necropsy findings and relative organ weights, at the doses tested. Thus, under the present experimental conditions, the NOAEL of NS was assumed to be 2000 mg/kg/day for both males and females. Based on subchronic toxicity results in SD rats, we also wanted to investigate the toxicity of NS by repeated oral administration in Beagle dogs. NS was administered to male and female beagle dogs at dose levels of 500, 1000, 2000 and 4000 mg/kg. There were no consistent and dose-related changes that could be attributed to NS administration in regards to mortality, body weight, food intake, ophthalmoscopy, urinalysis, hematology, serum biochemistry, necropsy finding and organ weights. Vomiting was observed only in the male group and may not have been caused be administration of NS since the vomiting could have been induced by gastro-intestinal stimuli, which is common in dogs [23]. The sporadically feeding observed in female groups was not dose-dependent and this has also been observed frequently in dogs. Therefore, these effects were most likely not caused by NS administration. In the urinalysis, a low SG, positive reaction for proteins, occult blood and WBC were observed. However, these effects were not dose-dependent, not accompanied by other corresponding changes and were also observed before NS administration. Therefore, these effects were not related to NS treatemtn. Based on the results of this study, no systemic and toxicologically significant change related to NS administration were observed in the 4-week repeated dose experiment and the NOAEL (No observed adverse effect level) was determined to be 4000 mg/kg/day. Conclusion Based on our observations, NS significantly reversed depressive symptoms under chronic mild stress. In addition, in the safety evaluation studies, NS was shown to be safe up to a dose of 4000 mg/kg/day over 13 weeks of administration in rats and up to 2000 mg/kg/day over 4 weeks of administration in dogs. The results presented here provide a foundation for further clinical research and demonstrate the potential of using NS as a new herbal drug. References 1. 1. Kang M, Pyun KH, Jang CG, Kim H, Bae H, Shim I: Nelumbinis Semen reverses a decrease in hippocampal 5-HT release induced by chronic mild stress in rats. J Pharm Pharmacol. 2005, 57 (5): 651-656. 2. 2. Youn UJ, Lee JH, Lee YJ, Nam JW, Bae H, Seo EK: Regulation of the 5-HT3A receptor-mediated current by alkyl 4-hydroxybenzoates isolated from the seeds of Nelumbo nucifera. Chem Biodivers. 2010, 7 (9): 2296-2302. 10.1002/cbdv.200900393. 3. 3. Furukawa H: [on the Alkaloids of Nelumbo Nucifera Gaertn. Ix. 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The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1472-6882/12/68/prepub Download references Acknowledgements This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government [MEST] (No. 2012–0005755). Author information Correspondence to Hyunsu Bae. Additional information Competing interests The authors declare that they have no competing interests. Authors’ contributions H.C, H. L and I. S mainly performed the animal experiment, analyzed the data. H. B supervised the project and wrote the final paper. All authors read and approved the final manuscript. Authors’ original submitted files for images Below are the links to the authors’ original submitted files for images. Authors’ original file for figure 1 Authors’ original file for figure 2 Authors’ original file for figure 3 Authors’ original file for figure 4 Authors’ original file for figure 5 Authors’ original file for figure 6 Authors’ original file for figure 7 Authors’ original file for figure 8 Authors’ original file for figure 9 Authors’ original file for figure 10 Authors’ original file for figure 11 Rights and permissions Reprints and Permissions About this article Keywords • Nelumbinis semen • Depression • Toxicity • Open field test
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How Effective Is Doxycycline for UTI? Doxycycline prevents the bacteria causing a UTI from growing, so typically takes one to two weeks to be effective. While doxycycline is considered effective for a UTI, side effects can include a burning sensation in the throat. Urinary tract infections, which can cause the urge to urinate frequently and pain when doing so, sometimes requires antibiotic treatment. The severity of a urinary tract infection can determine whether doxycycline will be an effective treatment. Taking doxycycline for a urinary tract infection does not immediately kill the bacteria that cause the infection. Women with diabetes are prone to urinary tract infections. Article Details • Written By: S. Berger • Edited By: Shereen Skola • Last Modified Date: 31 July 2015 • Copyright Protected: 2003-2015 Conjecture Corporation • Print this Article A urinary tract infection (UTI) is often caused by bacteria, and usually affects the bladder, but can spread to other areas of the body in rare cases. Many people choose to treat these infections quickly, as they can cause pain, discomfort, and frequent urination. Frequently, people take doxycycline for UTI relief, because this antibiotic medication is one of the more effective treatments available, as of 2011. Taking doxycycline to treat a UTI does not immediately kill the bacteria that cause the infection. Instead, this medication prevents the bacteria from growing and dividing, and a person's immune system cells can then attack the germs. For this reason, the antibiotic must be taken for a time frame of one to two weeks to be effective. Usually, taking doxycycline for UTI treatment is the most effective when it is taken in doses of 100 milligrams (mg) to 200 mg each day. Children often take lower doses, based on their body weight. This dose is equivalent to 1 mg to 2 mg of the medication for every one pound (0.45 kilograms) of weight. As mentioned, the drug is normally taken for up to two weeks, although occasionally it must be taken longer to fully fight an infection. Ad Some circumstances can limit how well using doxycycline for UTI will work. This antibiotic affects some strains of bacteria to a greater extent, such as Chlamydia and Mycoplasma. Infections caused by other types of bacteria will therefore usually not be treated as quickly, or as effectively by this drug. Bacteria may also become resistant to antibiotics over time, so occasionally even an infection caused by Chlamydia or Mycoplasma will not respond to doxycycline. Like all medications, taking doxycycline for UTI can cause side effects. For some people, these side effects can be so severe as to make other drugs seem more worthwhile. These effects can include a burning sensation in the back of the throat and painful reactions to sunlight, although they are rare. Other medications generally do not cause these effects. The severity of the UTI can also determine whether doxycycline will be an effective treatment. Bacteria from this medical condition can sometimes spread to the kidneys. Generally, kidney infections that are relatively mild and that have not been present for a great deal of time can still be treated by doxycycline. Infections that have become more severe, however, can make this drug less effective in treating both the UTI and the kidneys. Ad You might also Like Recommended Discuss this Article anon989375 Post 4 I started taking Doxycycline last night and today after my second dose the burning and urge to urinate is already gone! I was very surprised. I am a little groggy and have a slight headache but no nausea or stomach upset and I have IBS. I'm taking a probiotic in the middle of the day between doses. discographer Post 3 @ysmina-- The kind of antibiotic used to treat a UTI depends on the cause of the UTI. There isn't just one cause, different kinds of bacteria can be responsible for it. Doctors will do a test to determine the bacteria and then prescribe the antibiotic that's effective against that strain. Doxycyline is effective for UTIs that are caused by bacteria associated with chlamydia and mycoplasma. I had a mycoplasma caused UTI and I was given doxycycline. It was very effective, it cleared up the infection in a few weeks. donasmrs Post 2 @ysmina-- Doxycycline will work for UTIs, but I don't think that it's the first preference of doctors. Fluoroquinolones and sulfa group antibiotics are more commonly prescribed. These tend to work faster. Doxycycline is usually prescribed for a UTI if someone has an allergy to other antibiotic groups. It is an effective treatment for urinary tract infections. It just has to be taken a little bit longer to make sure that the bacteria responds. Since this is not your first UTI, and the infection seems to be returning, your doctor might be wanting to try a different antibiotic group. You should ask him. ysmina Post 1 I'm surprised that doxycycline is one of the best treatments for a UTI because I have had had several UTIs in the past and I was never prescribed this antibiotic. Have doctors not caught up on the trend yet? Post your comments Post Anonymously Login username password forgot password? Register username password confirm email
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A ring of fibrous or fibrocartilaginous tissue (as of an intervertebral disk or surrounding an orifice of the heart). [ http://purl.obolibrary.org/obo/BTO_0003627 ] This is just here as a test because I lose it Term information Subsets grouping_class definition A ring of fibrous or fibrocartilaginous tissue (as of an intervertebral disk or surrounding an orifice of the heart). has exact synonym fibrocartilaginous ring anulus fibrosus has related synonym fibrous ring id UBERON:0006444 Term relations Subclass of:
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[Skip to Content] [Skip to Content Landing] Article September 18, 1926 ULTIMATE RESULTS OF ESSENTIAL HYPERTENSION Author Affiliations ATLANTA, GA. JAMA. 1926;87(12):925-928. doi:10.1001/jama.1926.02680120035011 Abstract Since the recognition and description of hyperpiesia, essential hypertension or vascular hypertonia by Sir Clifford Allbutt,1 the condition has slowly been recognized as a clinical entity. By the term essential hypertension, we understand a condition in which the patient has a persistent elevation of the systolic, and usually the diastolic, blood pressure for which there is no demonstrable cause. In the early stages all the patients are without evident cardiac hypertrophy and without demonstrable renal lesions, as evidenced by the fact that the kidneys are able to dilute and concentrate; albumin is rarely present in the urine, and only occasionally a few hyaline casts are found; there is a normal phenolsulphonphthalein excretion, and the chemical components of the blood are normal except for a slight rise in the uric acid content. Eventually, the continued high pressure leads to cardiac hypertrophy and varying degrees of arteriocapillary fibrosis or arteriosclerosis, with First Page Preview View Large First page PDF preview First page PDF preview ×
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Parikh R, Niyazov A, Esterberg E, Arondekar B, Arruda L, Obeid E. Real-World treatment patterns and safety outcomes among patients with HER2 negative advanced breast cancer and BRCA1/2 mutations: evidence from a retrospective medical record review study in the United States. Poster presented at the 2020 AMCP Conference (Conference cancelled); April 21, 2020. Houston, TX. [abstract] J Manag Care Pharm. 2020 Apr; 26(4-a):S16. BACKGROUND: Germline breast cancer susceptibility gene 1/2 - (gBRCA1/2) mutated breast cancer (BC) represents ~5% of all BC. Historically, chemotherapy (CT) and endocrine-based therapy (EBT) have been commonly used in HER2- advanced BC (ABC) patients (pts) with BRCA1/2 mutations (BRCA1/2mut). Between 2015–2018, cyclin-dependent kinase 4/6 inhibitors and poly ADP-ribose polymerases inhibitors (PARPi) became available as targeted therapy for some pts with ABC, including HER2- gBRCA1/2 ABC. With the changing landscape, understanding treatment patterns and associated adverse events (AEs) may inform treatment choices. OBJECTIVE: To assess real-world treatment patterns and associated AEs in US pts with HER2- ABC and BRCA1/2mut. METHODS: Oncologists retrospectively reviewed charts (July-Oct 2019) of randomly selected pts ≥18 y, with HER2- ABC and BRCA1/2mut (i.e., gBRCA1/2mut, somatic [sBRCA1/2mut], or sBRCA1/2mut with an unknown gBRCA1/2 status) who received ≥1 cytotoxic CT regimen(s) for ABC between Jan 2013–April 2018. AEs between different regimens were compared using χ2 or Fisher’s Exact test. RESULTS: 203 pts were included: 99.5% were female and 76.4% were white. Median age was 58.0 y. 87.2% had gBRCA1/2mut, 8.4% had sBRCA1/2mut, and 4.4% had sBRCA1/2mut and unknown gBRCA1/2 status. 62.6% had advanced triple negative BC (TNBC), and 37.4% had hormone receptor (HR)+/HER2– ABC. In TNBC pts (n=127), 1st line therapies included non-platinum-based CT (58.3%) and platinum-based CT (41.7%). Hematologic AE’s occurred at higher rates in TNBC pts receiving platinum-based CT vs non-platinum-based CT (anemia, 41.5% vs 17.8%, P< 0.01; neutropenia, 22.6% vs 9.6%, P=0.04; thrombocytopenia, 22.6% vs 11.0%, P=0.08). In HR+/HER2- pts (n=76), CT (73.7%) or EBT (25.0%) were the most common 1st line therapies. Hematologic AE’s were reported in more pts receiving CT vs EBT (anemia, 28.6% vs 0.0%, P=0.01; neutropenia, 12.5% vs 5.3%, P=0.67; thrombocytopenia, 12.5% vs 5.3%, P=0.67). CONCLUSIONS: In this analysis of HER2- BRCA1/2mut ABC pts, CT was most frequently used in the 1st line setting. Pts with advanced TNBC and BRCA1/2mut had more hematologic AEs reported in those receiving platinum-based CT vs non-platinum-based CT. Pts with HR+/HER2- ABC and BRCA1/2mut, as expected, had more hematologic AE’s in those receiving CT than those treated with EBT. Consideration of a regimen’s toxicity profile may help guide pts and providers in selection of their therapy regimen, including targeted treatments such as the newly approved BRCA1/2-targeted therapies, PARPi. Share on: 
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The Why, Who, and How of Medication Reconciliation November 2008 - Vol. 5 No. 11 Download     Print   Share Why? The vast majority of available literature attempts to convince the reader that medication reconciliation is indeed important to patient safety and the lack of an accurate process leads to medication errors, which is undeniably true. This is well known, thanks in part to the Institute of Medicine’s recent report and, of course, the Joint Commission’s National Patient Safety Goal. However, those involved in designing a program often fail to convey to the staff performing the reconciliation the “why” behind it. Without helping people understand how this will impact the care of their patients, there is little buy-in, which invariably results in failure or certainly mediocrity — both of which are unacceptable. A culture shift must occur that places the emphasis on safety and accuracy, and that culture shift cannot occur without strong leadership. Who? One missing step that can certainly lead to failure is that of an inappropriate invitation list when designing the medication reconciliation process. Who you invite to the table is critical. Several initial failures have resulted from not inviting physicians to the kick-off meetings, where decisions about the process are made. Clearly, given physicians’ habits, if the process is not simple and convenient, they are not going to use it. And if they are not going to use a process, it will fail. The same applies to nurses; they will find a way around a process that is not simple and convenient. Ensure the group working on designing a process includes representatives from pharmacy, nursing (critical care and medical units, as well as ancillary units/departments, such as radiology, surgery, and emergency services), physician groups, information systems, education department, public relations, administration, retail pharmacy, and patients, if your institution has reached that level of comfort with disclosing your opportunities for improvement (otherwise known as imperfections). Representatives are needed from varying nursing units because their reconciliation issues will differ, especially with transfers and discharges. Your information systems department can play an important role in streamlining the process through automation, and the public relations and education departments can be a great source for communicating change within your institution and to the public. Administrative representation is necessary to facilitate change on a broad level, and their engagement is critical. Developing partnerships with local retail pharmacies can help immensely with closing the loop between discharge from the hospital and an accurate medication list. Patients offer insight and feedback that no one working in health care could ever match. Since this is for their benefit, it makes sense to design a system that will work for them. Probably the biggest “who” issue to consider is which discipline will be responsible for the initial reconciliation of home meds. A common pitfall is the lack of training for those individuals responsible. Often the nurse assigned to the care of the patient collects this list from the patient or their family and may even collect their prescription bottles if they happen to bring them into the hospital. Perhaps the best approach is to offer specific training to a select group (consider a mix of nurses, pharmacists, pharmacy technicians, pharmacy residents, and students) and limit the task to this group. This creates a sense of ownership and responsibility, which will lead to greater accuracy. The number of employees needed to accomplish accurate medication reconciliation needs to be evaluated based on census and acuity. First, calculate the time it takes to perform an average reconciliation. In my experience, it takes from four to seven minutes, but can take longer if you are dealing with a complicated patient or if you have to call retail pharmacies, physician offices, or other outside sources of information. Multiply that time by your average number of admissions to get a good idea of how many FTEs you will need for your medication reconciliation program. I recommend sharing the medication reconciliation responsibility across disciplines, so that it does not drain one resource completely. How? The key to a successful program lies in the development of a process that results in useful, reliable, and timely information for the physician to use when making decisions regarding a patient’s medication regimen. One of the most successful first steps is the creation of an admission medication assessment form that serves as an order form for the physician. (See Figure1.) This eliminates the need for transcription, which, in turn, reduces the chance for error. Automating this step further promotes safety by eliminating illegibility as an issue, and makes the transfer and discharge reconciliations much easier and more accurate, since this information follows the patient through their entire hospital stay. An inpatient drug list can be pulled from your pharmacy information system and the patient’s home medication list can be pulled from the information electronically entered into the hospital’s information system upon admission. This information is then used to automatically populate a form for your physicians’ use during transfer and discharge. Some software vendors offer automated form generation as a standard feature, or your hospital’s IT department can create it in-house. Do not be afraid to modify this form 25 times if that is what it takes to make it work for the staff. And certainly do not be afraid to borrow someone else’s form. (See Figure 2.)  Include tactics in your specific reconciliation training for how to best interview patients or their families. Use open-ended questions, such as “Which prescription medications do you take?” versus the closed approach of “Do you take any prescription medications?” Follow up with “How do you take that medication?” versus simply noting what the bottle says or the way they are supposed to take it. Remember that the most reliable reconciliation information will come from the patient. With a little training and skill, interviewers will discover that Mrs. Smith really only takes that blood pressure medicine once a day, instead of the prescribed twice daily dose, because it costs too much. The physician will need to make decisions regarding this patient’s care based upon the information collected and the patient’s physiological presentation. It is vital for the physician to know how the patient is really taking her meds. Some may say there are no poor historians, only poor history takers, but in the case of an unconscious patient, the history taker is off the hook. In these situations, use available resources such as physicians’ office records, retail pharmacies, and family members. It is easy to forget the variety of agents that qualify as medications, and each needs to be addressed when collecting the list. Be sure to ask about prescription drugs, over-the-counter drugs and remedies, herbals, inhalants, samples, nutritionals, topicals, and even injectable drugs. Be sure to ask which retail pharmacy the patient usually uses, in case you need to call and verify any information. Keep in mind, however, that patients are not loyal to their pharmacist anymore; they are loyal to price. Patients will often shop for the best prices and use multiple pharmacies. When addressing issues with transfer reconciliation, the best answer is to automate, automate, automate. If the initial home medication list is also automated and, therefore, follows the patient throughout their hospitalization, ensure this list is made conveniently available to the physician during transfers. The best way to ensure compliance with transfer reconciliation is to automatically generate an active medication list from the pharmacy profile system that can be used as an order form for the physician. Some pharmacy systems offer this in their software packages, but many hospital information system departments have also developed their own. This order form should have a space for the physician to quickly and easily decide what to continue, discontinue, or change in the patient’s regimen with a mere check in a box. (See Figure 2.) Ensure the policy enforces the requirement for transfer reconciliation to occur for all patients changing level of care and those visiting the OR and the cath lab. Do not accept blanket orders to “continue all previous meds”. The “how” for discharge can very closely follow the process with transfer reconciliation. Automation is key. Provide the physician with either a computer-based or computer-generated discharge medication order form, listing both current in-hospital medications and those the patient was taking at home. This way, the physician will be able to compare the lists and make informed decisions about the best regimen for the patient. Again, it cannot be stressed enough that this needs to be very available and very easy. Conclusion Medication reconciliation is a vital step in a medication safety program. Focusing on the why, who, and how are vital to organizing a team and creating and implementing a successful program. Avoid the pitfalls that result in failure and be willing to change and be flexible along the way, and a successful program will be the end result.     In September 2007, Natasha Nicol, PharmD, took on her current post as the medication safety director for Cardinal Health. Prior to assuming this role, she was the director of pharmacy for McLeod Regional Medical Center in Florence, South Carolina, for six years. Nicol earned her doctorate of pharmacy degree, with honors, from the University of Maryland.   Find: Automated Solutions for Medication Reconciliation at www.findit.pppmag.com     To view figures mentioned in above article download the PDF   This article is archival PP&P content. We require our users to register to view content older than 1 month. Please take a moment to register with us. Registration is free, and a quick single step process. Our mission is to provide health system pharmacists with information to streamline pharmacy operations and promote patient safety. As a requester to PP&P you will receive all monthly issues, as well as our annual Resource Guide of product and service providers and all of our timely supplements on pharmacy's hot-button issues. Thank you for reading PP&P, and we look forward to providing you with information to enhance the field of pharmacy. Already a member? Please provide your email and password below: Page generated in 0.0043 seconds.
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Outcomes of microdissection testicular sperm extraction in men with nonobstructive azoospermia due to maturation arrest Aaron M. Bernie, Kalee Shah, Joshua A. Halpern, Jason Scovell, Ranjith Ramasamy, Brian Robinson, Peter N. Schlegel Research output: Contribution to journalArticlepeer-review 20 Scopus citations Fingerprint Dive into the research topics of 'Outcomes of microdissection testicular sperm extraction in men with nonobstructive azoospermia due to maturation arrest'. Together they form a unique fingerprint. Medicine & Life Sciences
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• 543 benh-ngua-hau-mon-lon-vn The condition is actually quite common as an acute occurrence and most people will suffer from the condition for short periods of time at one time or another at some point in their lives.  Fortunately for most, the symptoms are usually short-lived and there is no reason to worry about an underlying health problem or see a physician about the condition. However for a small percentage of people Pruritus Ani or itching around the skin of the anus can become a recurring, or a persistent chronic condition spanning years.  In such cases it can become quite severe, causing sleep disturbance, and leading to continued discomfort throughout one’s day.  It can be a thoroughly frustrating problem and those who suffer with it in the chronic form will often be reluctant to let others know of their symptoms and are reluctant to consult a physician about it. The condition in its chronic form can sometimes be related to an underlying skin condition such a Dermatitis of some form (Irritant versus Allergic), Psoriasis, bacterial or fungal infection. In many cases of the chronic form it does come about from an irritant cause, and the underlying causes for the irritation can be numerous or additive and include • Chronically loose stools and intermittent diarrhea (bacteria in the fecal/stool can release enzymes that come into contact with the skin around the anus and serve as a chronic irritant). • On the opposite of the above, constipation and straining with bowel movement. • Once the itch sensation begins, scratching itself serves to perpetuate a vicious cycle knows as the itch-scratch-itch cycle. • Employing overly aggressive hygienic measures (that probably would not have been taken without the onset of the troubling symptoms) such as vigorous use of toilet paper, scrubbing excessively (or not even excessively) with soap and water, where normal soaps leach out natural skin protective compounds. • Acidic and spicy foods, plus other dietary contributors such as indulgence (or over-indulgence) in prunes, coffee, sodas, tomatoes, orange juice, and beer and other alcohol beverages. A number of at-home or self-applied measures can be taken before you may decide to consult a physician and include • Try to NEVER SCRATCH the itch, as this can only erode or break the skin leading to increased sensitivity and itching. • Avoid over-indulgence in the foods and drinks mentioned above. • Petroleum jelly and a soap substitute can be used to apply and wash the area around the anus • Eat plenty of high-fiber foods; cereals, fruits, and vegetables to prevent straining with bowel movements If these measures do not relieve the symptoms then it may be time to seek medical evaluation with a physician who is familiar with the condition in its chronic form.  After an evaluation and exam treatment and topically-medicated options in the context the above measures can be considered.     5 Comments 1. Pingback: Vad får man för en skrotbil Trollhättan 2. Pingback: sex toys for women remote vibrator 3. Pingback: 로켓툰 4. Yckogj 28/02/2021 at 1:53 am generic tadalafil – tadalafil 5mg tadalafil vs sildenafil 5. Pingback: credit card dumps Add Comment Your email address will not be published. Required fields are marked * Call Now Button
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Skip to main content TriVax-HPV: an improved peptide-based therapeutic vaccination strategy against human papillomavirus-induced cancers Abstract Background Therapeutic vaccines for cancer are an attractive alternative to conventional therapies, since the later result in serious adverse effects and in most cases are not effective against advanced disease. Human papillomavirus (HPV) is responsible for several malignancies such as cervical carcinoma. Vaccines targeting oncogenic viral proteins like HPV16-E6 and HPV16-E7 are ideal candidates to elicit strong immune responses without generating autoimmunity because: (1) these products are not expressed in normal cells and (2) their expression is required to maintain the malignant phenotype. Our group has developed peptide vaccination strategy called TriVax, which is effective in generating vast numbers of antigen-specific T cells in mice capable of persisting for long time periods. Materials and methods We have used two HPV-induced mouse cancer models (TC-1 and C3.43) to evaluate the immunogenicity and therapeutic efficacy of TriVax prepared with the immunodominant CD8 T-cell epitope HPV16-E749-57, mixed with poly-IC adjuvant and costimulatory anti-CD40 antibodies. Results TriVax using HPV16-E749-57 induced large and persistent T-cell responses that were therapeutically effective against established HPV16-E7 expressing tumors. In most cases, TriVax was successful in attaining complete rejections of 6–11-day established tumors. In addition, TriVax induced long-term immunological memory, which prevented tumor recurrences. The anti-tumor effects of TriVax were independent of NK and CD4 T cells and, surprisingly, did not rely to a great extent on type-I or type-II interferon. Conclusions These findings indicate that the TriVax strategy is an appealing immunotherapeutic approach for the treatment of established viral-induced tumors. We believe that these studies may help to launch more effective and less invasive therapeutic vaccines for HPV-mediated malignancies. This is a preview of subscription content, access via your institution. Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Abbreviations αCD40 mAb: Anti-CD40 monoclonal antibodies CC: Cervical carcinoma DC: Dendritic cell HPV: Human papillomavirus MHC-I: Major histocompatibility complex I IFNγ: Interferon-gamma IFNαβR: Interferon-alpha/beta receptor KO: Knockout TAA: Tumor-associated antigen TLR: Toll-like receptor References 1. 1. Smith JS, Lindsay L, Hoots B, Keys J, Franceschi S, Winer R, Clifford GM (2007) Human papillomavirus type distribution in invasive cervical cancer and high-grade cervical lesions: a meta-analysis update. Int J Cancer 121:621–632 PubMed  Article  CAS  Google Scholar  2. 2. Fleurence RL, Dixon JM, Milanova TF, Beusterien KM (2007) Review of the economic and quality-of-life burden of cervical human papillomavirus disease. 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J Immunol 185:998–1004 PubMed  Article  CAS  Google Scholar  Download references Acknowledgments We gratefully acknowledge Dr. T-C Wu and Dr. W. M. Kast for providing us with the tumor cell lines and are indebted to Dr. A. Salazar for providing large amounts of Poly-ICLC. We also thank Moffitt Cancer Center Flow Cytometry Core, especially J. Kroger for her help in flow cytometer training. This work was supported by NIH grants R01CA136828 and R01CA157303 to EC. Conflict of interest Esteban Celis has filed a patent application based on the use of synthetic peptides and poly-IC combinatorial complexes for vaccination. The rights of the patent application have been transferred to the Moffitt Cancer Center. Kelly Barrios declares no conflict of interest. Author information Affiliations Authors Corresponding author Correspondence to Esteban Celis. Rights and permissions Reprints and Permissions About this article Cite this article Barrios, K., Celis, E. TriVax-HPV: an improved peptide-based therapeutic vaccination strategy against human papillomavirus-induced cancers. Cancer Immunol Immunother 61, 1307–1317 (2012). https://doi.org/10.1007/s00262-012-1259-8 Download citation Keywords • Peptide vaccines • HPV • Cervical cancer • CD8 T cells • PIVAC 11
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972,088,726,065,265,200
Title: Ultrasound and Microbubbles in Ocular Diagnostics and Therapies Kind Code: A1 Abstract: The present disclosure described methods, systems, and techniques for applying contrast-enhanced ultrasound to locate areas of blockage within retinal vessels and to break up clots that are causing damage. In addition to identifying the damaged area, the researchers anticipate that the initial image may serve as a baseline for monitoring the effect of treatment on the vessel, which may be achieved in multiple ways. The vibration effect of the ultrasound itself may suffice to dislodge clots. The microbubbles may also be coated or filled with medication, with ultrasonic shock waves activating the coating or causing mini explosions to release the medicine. Loading the microbubbles with a therapeutic agent, visualizing their presence at the diseased site using the ultrasound diagnostic mode, and then activating the microbubbles to release their contents at the targeted lesion could be a powerful and effective way to reverse occlusion without harming other areas of the eye or body. Inventors: Fawzi, Amani (Los Angeles, CA, US) Ameri, Hossein (Alhambra, CA, US) Humayun, Mark S. (Glendale, CA, US) Application Number: 12/186640 Publication Date: 01/29/2009 Filing Date: 08/06/2008 Assignee: Doheny Eye Institute (Los Angeles, CA, US) Primary Class: International Classes: A61B8/14 View Patent Images: Primary Examiner: PENG, BO JOSEPH Attorney, Agent or Firm: KING & SPALDING (1180 PEACHTREE STREET , NE, ATLANTA, GA, 30309-3521, US) Claims: What is claimed is: 1. A method of treating blood vessel blockage, comprising: applying ultrasound energy to locate one or more areas of blockage within one or more blood vessels; directing microbubbles to an area of blockage; and breaking up clots that are causing damage within the one or more areas of blockage. 2. The method of claim 1, wherein the applying ultrasound energy comprises directing ultrasound energy to the eye. 3. The method of claim 1, further comprising using an initial ultrasound image as a baseline for monitoring the effect of treatment on the vessel. 4. The method of claim 1, wherein the vibration effect of the ultrasound dislodges one or more clots in the one or more areas of blockage. 5. The method of claim 1, wherein the microbubbles are coated or filled with medication, with ultrasonic shock waves activating the coating or causing mini explosions to release the medication. 6. The method of claim 1, wherein applying ultrasound energy comprises using an external probe. 7. The method of claim 1, wherein applying ultrasound energy comprises using an intraocular probe. 8. The method of claim 1 wherein the intraocular probe is multifunctional and contains another surgical instrument. 9. The method of claim 8, wherein the intraocular probe is coupled to a laser to deliver optical treatment. 10. The method of claim 8, wherein the intraocular probes include a cautery portion to deliver therapeutic cauterization. 11. The method of claim 8, wherein the multifunctional probe comprises a forceps or manipulating plate at the tip to manipulate intraocular tissue. 12. The method of claim 1 where the microbubbles are delivered intravenously through the systemic circulation. 13. The method of claim 1 where the microbubbles are injected inside the eye, in the intravitreal or the posterior chamber of the eye, in the anterior chamber, or inside the intraocular tissues. 14. The method of claim 13, wherein the intraocular tissues are in the subretinal, subchoroidal, intralenticular, intracorneal, or in the ciliary body. 15. The method of claim 1 where the microbubbles are delivered in the retinal blood vessels by way of a catheter. 16. A system for treating blood vessel blockage, the system comprising: a source of ultrasound energy; a probe coupled to the source and configured and arranged to direct ultrasound energy to a desired location; and one or more microbubbles, configured and arranged to receive the ultrasound energy, wherein the microbubbles are configured and arranged to contain a desired substance and to burst upon receiving the ultrasound energy, releasing the desired substance in the blood vessel. 17. The system of claim 16, wherein the probe is a needle probe comprising a piezoelectric transducer. 18. A method for the delivery of a drug to a tumor, comprising: using an ultrasound system configured and arranged to produce an ultrasound output; and supplying ultrasound contrast agents configured and arranged as microbubbles to a tumor wherein the microbubbles are loaded with chemotherapeutic drug that is active against the tumor, and wherein the ultrasound is used to localize the tumor and activate the microbubbles within the tumor to visualize and activate the release of drug within the tumor. 19. The method of claim 18, wherein the tumor is an intraocular choroidal melanoma, and the drug is labeled to attach to the blood vessels of the tumor selectively. 20. The method of claim 18, wherein the tumor is a ciliary body melanoma. 21. The method of claim 18, wherein the tumor is a retinoblastoma. 22. The method of claim 18, wherein the tumor is an iris tumor. 23. The method of claim 18, wherein the microbubbles are loaded with a therapeutic agent active against subretinalneovascularization in the back of the eye. 24. The method of claim 18, wherein the drug is labeled to attach to the blood vessels of newly formed blood vessels, and the ultrasound output is used to activate the microbubbles focally to release the therapeutic agent. 25. The method of claim 24, wherein an optically labeled microbubble, loaded with therapeutic agent is visualized optically, then activated by ultrasound to release the therapeutic agent within the subretinalneovascular complex. 26. The method of claim 24, wherein the microbubbles are loaded with genetic material. 27. The method of claim 24, wherein the disease is retinitis pigmentosa and the genetic material is able to correct the genetic defect. 28. The method of claim 24, wherein the disease is diabetic retinopathy, and the drug or genetic material is able to reverse the vascular defect in abnormal blood vessels of the diseased retina. 29. The method of claim 18, wherein the drug is labeled to attach to the optic nerve, and the ultrasound output is used to activate the microbubbles focally to release the therapeutic agent. 30. The method of claim 29, wherein the therapeutic agent is a nerve growth factor. 31. The method of claim 29, wherein the therapeutic agent is a vascular growth factor. 32. The method of claim 29, wherein the therapeutic agent is an anti-cancer agent against an optic nerve tumor. 33. The methods of claim 29, wherein the ultrasound is applied externally from outside the eye globe. 34. The method of claim 25, wherein the ultrasound is applied internally from inside the eye. 35. The method of claim 18, where the treatment is directed at the cornea, the front most layer of the eye. 36. The method of claim 35, wherein the ultrasound treatment enhances therapy of corneal disease. 37. The method of claim 35, wherein the microbubbles contain a therapeutic agent against a corneal disease or infection. 38. The method of claim 35, wherein the microbubbles are applied to the surface of the eye that are loaded with drugs and whereby the ultrasound treatment facilitates entry of the drugs into the anterior chamber of the eye, delivering therapeutics to the interior of the eye. Description: RELATED APPLICATIONS This application is a continuation-in-part of related U.S. patent application Ser. No. 12/061,147 filed 2 Apr. 2008 and entitled “Preoperative and Intra-Operative Lens Hardness Measurement by Ultrasound,” which claims the benefit of U.S. Provisional Patent Application No. 60/909,496 filed 2 Apr. 2007; this application also is a continuation-in-part of U.S. patent application Ser. No. 12/061,120 filed 2 Apr. 2008 and entitled “Thrombolysis In Retinal Vessels with Ultrasound,” which claims the benefit of U.S. Provisional Patent Application No. 60/911,385 filed 12 Apr. 2007; this application is a continuation-in-part of U.S. patent application Ser. No. 12/102,293 filed 14 Apr. 2008 and entitled “Intraocular Doppler Techniques,” which claims the benefit of U.S. Provisional Patent Application No. 60/911,385 filed 12 Apr. 2007; this application claims the benefit of U.S. Provisional Patent Application No. 61/030,075 filed 20 Feb. 2008 and U.S. Provisional Patent Application No. 60/954,129 filed 6 Aug. 2007; the entire contents of all of which applications are incorporated herein by reference. BACKGROUND There is presently no cure for retinal vascular occlusion, the blockage of blood flow by clots in central or branch retinal veins and arteries that causes vision loss and blindness. Yet unlike other blinding retinal diseases such as macular degeneration and retinitis pigmentosa, for which definitive treatments remain years if not decades away, a cure for retinal vascular occlusions could be obtained within as little as one to two years. This is good news for the relatively large number of people—as many as 2 to 4 percent of people over age 70 (51% of cases of retinal vascular occlusion occur over age 65) T/K—who are affected by this disorder. A cure for retinal vessel occlusion could be achieved by removing the blood clot. Clot-dissolving drugs that enter the bloodstream, however, may provoke life-threatening complications, and surgical intervention and injections directly to the eye have had limited success. Current treatments for such occlusions are therefore limited to laser applications that treat complications rather than the condition itself. For example, laser is applied to patients with poor blood flow in the eye secondary to retinal vessel occlusions, leading to growth of new vessels in the front of the eye and increased eye pressure. At that point the laser only serves stop new blood vessel growth, but does not help to recover lost vision or improve blood flow. Current treatments for vein occlusions are limited to laser application to prevent complications or invasive surgical therapies that have limited success. The primary disease process involves a blood clot in the vein. Currently there is no definite treatment for retinal vascular occlusive diseases such as central or branch retinal vein occlusion and central or branch retinal artery occlusion. A cure in these conditions would involve removal of the blood clot. Systemic use of thrombolytics (drugs that dissolve the blood clot) may be associated with life threatening complications; on the other hand, intravitreal injection of these drugs has proved to be ineffective. SUMMARY Embodiments of the present disclosure can provide the ability to dissolve a blood clot (e.g., such as one in the eye) by utilization of ultrasound and contrast agents, known as microbubbles. In addition, microbubble enhancement and targeted therapies using ultrasound according to the present disclosure can provide the ability to deliver targeted therapies in the eye and elsewhere in patients. Drug delivery approaches to the eye are currently focused on invasive surgical implants, with the attendant risks and complications. The ability to image, while treating, vascular disease of the eye using targeted microbubbles is a great advantage permitting direct observation of the microbubbles and their targeted activation at the site of disease. Because of the eye being especially sequestered and being a superficial organ, embodiments of the present disclosure can provide an exceptional opportunity to deliver drugs without systemic side effects. For example, by attaching the required medications to the microbubbles and then delivering ultrasound to the exact location in the eye where the drug is needed, targeting is achieved. Removal of a blood clot using microbubble enhanced ultrasound thrombolysis can have a long lasting and curative effect on this disease. Other ocular diseases that can benefit from microbubble targeting include macular degeneration. For such, microbubbles cab be loaded with a specific therapeutic agent that is released only at the target lesion/region. Moreover, such approaches/embodiments can be very successful in drug delivery of anti-cancer medications to tumors inside the eye, such as retinoblastoma in children. Chemotherapeutic agents for retinoblastoma have a large number of systemic side effects that can be devastating, and if we are able to deliver the drug only to the tumor, with direct visualization and confirmation of delivery using ultrasound and targeted microbubbles, this would have a great effect on the efficacy of the therapy as well as limit the systemic complications. Image guided interventions using these microbubbles according to the present disclosure can be applied to various ocular diseases with abnormal or aberrant vascularization, including neovascular macular degeneration, diabetic retinopathy, corneal neovascularization, and the like. Aspects/embodiments of the present disclosure can also help in delivering chemotherapeutic drugs to vascular intraocular tumors while sparing the rest of the ocular structures. By focusing the ultrasound on the abnormal tissue, the chemotherapeutics attached to the microbubbles can be delivered directly to the tumor, while sparing other areas of the eye and the rest of the body. Other features and advantages of the present disclosure will be understood upon reading and understanding the detailed description of exemplary embodiments, described herein, in conjunction with reference to the drawings. BRIEF DESCRIPTION OF DRAWINGS Aspects of the disclosure may be more fully understood from the following description when read together with the accompanying drawings, which are to be regarded as illustrative in nature, and not as limiting. The drawings are not necessarily to scale, emphasis instead being placed on the principles of the disclosure. In the drawings: FIG. 1 depicts application of ultrasound energy from an ultrasound probe systems to release drugs from microbubbles to effect treatment of a tumor, e.g., as located in a patient's eye, in accordance with exemplary embodiments of the present disclosure; FIG. 2 depicts a application of ultrasound energy (beam) from an external or intraocular probe to an area of blockage within a retinal vessel and at a location including microbubble contrast agents, according to an exemplary embodiment of the present disclosure; and FIG. 3 depicts a block diagram of a method 300 of therapy with microbubbles in accordance with exemplary embodiments of the present disclosure. While certain embodiments are depicted in the drawings, one skilled in the art will appreciate that the embodiments depicted are illustrative and that variations of those shown, as well as other embodiments described herein, may be envisioned and practiced within the scope of the present disclosure. DETAILED DESCRIPTION Aspects of the present disclosure combine ultrasound with ultrasound contrast agents, known as microbubbles, to treat selected regions of a patient by what the inventors refer to as “Contrast Enhanced Ultrasound Therapy.” Microbubbles are tiny, gas-filled lipid, or fat, bubbles that can be injected into the bloodstream, where they remain inactive unless stimulated. In conjunction with the utilization of such microbubbles, aspects and embodiments of the present disclosure utilize ultrasonic energy or ultrasound. High-frequency ultrasound has been used to create images of bone, tissue and other structures within the body by measuring the speed and intensity with which sound waves bounce off these objects and return as an echo. Ultrasound waves directed at microbubbles cause them to vibrate and return a unique echo within the bloodstream that produces a dramatic distinction, or high “contrast,” between blood vessels and surrounding tissue, thus enabling clinicians to visualize areas of restricted blood flow. Specialized Doppler ultrasound, which measures the rate and volume of blood flow, can further pinpoint the extent and severity of blockage caused by blood clots. Embodiments of the present disclosure utilize contrast-enhanced ultrasound to locate areas of blockage within retinal vessels and to break up clots that are causing damage. In addition to identifying the damaged area, the researchers anticipate that the initial image may serve as a baseline for monitoring the effect of treatment on the vessel, which may be achieved in multiple ways. The vibration effect of the ultrasound itself may suffice to dislodge clots. The microbubbles may also be coated or filled with medication, with ultrasonic shock waves activating the coating or causing mini explosions to release the medicine. Loading the microbubbles with a therapeutic agent, visualizing their presence at the diseased site using the ultrasound diagnostic mode, and then activating the microbubbles to release their contents at the targeted lesion/region can be a powerful and effective way to reverse occlusion without harming other areas of the eye or body. FIG. 1 depicts application 100 of ultrasound energy from an ultrasound probe system 102 to microbubbles 104 containing desired drugs 106 to effect treatment of a tumor 1 located in an eye 2, in accordance with exemplary embodiments of the present disclosure. Gas filled microbubbles (e.g., on the order of microns in size/diameter) can be visualized or imaged by ultrasound. Using specially designed probes, which have the ability to image and also activate the microbubbles, targeted therapies can be effected in the eye, while minimizing collateral damage. Such a probe is described in co-owned and co-pending U.S. patent application Ser. No. 12/061,120 filed 2 Apr. 2008 and entitled “Thrombolysis In Retinal Vessels with Ultrasound,” incorporated in its entirety herein by reference. A pulsed-wave Doppler system with a PMN-PT needle transducer has been developed to measure the blood flow velocity in selected retinal vessels. See, e.g., Emanuel J. Gottlieb, et al., “PMN-PT High Frequency Ultrasonic Needle Transducers for Pulsed Wave Doppler In The Eye,” 2005 IEEE Ultrasonics Symposium (IEEE 2005), the contents of which are incorporated herein by reference in their entirety. Ultrasonic techniques have also been utilized in surgical procedures on the eye for imaging structure and/or tissue of a surgical site. See, e.g., U.S. Pat. No. 6,676,607 to de Juan, Jr. et al., the contents of which are incorporated herein by reference in their entirety. Procedures/techniques according to the present disclosure, e.g., as depicted and described for FIG. 1, can be expanded to other ocular disorders as well. The same techniques may also be applied to ocular tumors, such as retinoblastoma in children, for which systemic treatment is associated with potentially devastating side effects, but for which drugs delivered directly to the tumor could be safe and very effective. The same principle may also apply to tumors in other parts of the body such as breast, kidney, liver, brain etc. Moreover, the tumor does not have to have a blood clot (and they usually don't). The ultrasound breaks up the microbubbles and results in the release of the drug they carry. As long as the drug is loaded on the microbubble it does not have any effect (good or bad). The ultrasound enables one to focally release the drug in the tumors or other desired location. As a result, there is a high concentration of the active drug in the tumor or location (e.g., a clot) for destruction of such. Despite the presence of the drug in the blood, however, the other tissues in the body are spared because the drug is attached to the microbubbles and is inactive. The drug delivery for tumors can be independent of the presence of a blood clot. FIG. 2 depicts a application 200 of ultrasound energy (or beam) 202 from a ultrasound source, e.g., an external or intraocular probe, to an area or volume of blockage 1 within a retinal vessel 2 and at a location including microbubble contrast agents 204, according to an exemplary embodiment of the present disclosure. The gas filled microbubbles 204 can be easily visualized using the ultrasound probe. Exemplary imaging or visualization techniques are described in co-owned and co-pending U.S. patent application Ser. No. 12/061,147 filed 2 Apr. 2008 and entitled “Preoperative and Intra-Operative Lens Hardness Measurement by Ultrasound”; U.S. patent application Ser. No. 12/061,120 filed 2 Apr. 2008 and entitled “Thrombolysis In Retinal Vessels with Ultrasound”; and U.S. patent application Ser. No. 12/102,293 filed 14 Apr. 2008 and entitled “Intraocular Doppler Techniques”; the contents of all of which are incorporated herein by reference. The microbubbles 204 can be ruptured or “activated” to release their content by slightly altering the ultrasound mode. By “loading” these microbubbles with a specific therapeutic agent, visualizing their presence at the diseased area, and then activating the microbubbles to release their contents at the target lesion, side effects of this therapeutic agent can be limited by delivering it only to the needed site (or substantially so) Moreover, the use of ultrasound and microbubbles in itself has the potential to dislodge blood clots, as shown in FIG. 2, with empty microbubbles rupturing and dislodging broken pieces of blood clots 1a after application of suitable ultrasound energy 202. By visualizing the microbubbles, and then activating them inside the diseased blood vessel at the site of the clot, therapy for retinal vascular occlusions can be effected. FIG. 3 depicts a block diagram of a method 300 of therapy with microbubbles in accordance with exemplary embodiments of the present disclosure. For method 300, a desired quantity/volume of microbubbles can be introduced to a desired location of a patient, as described at 302. For example, microbubbles can be injected into the eye (vitreous cavity, subretinal, or anterior chamber) or may be injected intravascularly. Ultrasound techniques can be used to image or visualize the microbubbles at the desired location in the patient, as described at 304. Continuing with the description of method 300, suitable ultrasound energy can be applied to the microbubbles to cause them to rupture or activate (meaning cause them to release drugs), as described as 306. In exemplary embodiments, the microbubbles can be filled or loaded with a desired drug before introduction into the patient as described at 308. In exemplary embodiments, method 300 can include: using an ultrasound system configured and arranged to produce an ultrasound output; and supplying ultrasound contrast agents configured and arranged as microbubbles to a tumor wherein the microbubbles are loaded with chemotherapeutic drug that is active against the tumor, and wherein the ultrasound is used to localize the tumor and activate the microbubbles within the tumor to visualize and activate the release of drug within the tumor. The treated tumor can be an intraocular choroidal melanoma, and the drug can be labeled to attach to the blood vessels of the tumor selectively. The tumor can be a ciliary body melanoma or a retinoblastoma or an iris tumor. The microbubbles can be loaded with a therapeutic agent active against subretinalneovascularization in the back of the eye. The drug/s inside the microbubbles can, in exemplary embodiments, be labeled to attach to the blood vessels of newly formed blood vessels, and the ultrasound output is used to activate the microbubbles focally to release the therapeutic agent. An optically labeled microbubble can be loaded with a therapeutic agent and visualized optically, then activated by ultrasound to release the therapeutic agent within the subretinalneovascular complex. The microbubbles can be loaded with genetic material. The method of claim 24, wherein the disease is retinitis pigmentosa and the genetic material is able to correct the genetic defect. The treated disease can be diabetic retinopathy, and the drug or genetic material can reverse the vascular defect in abnormal blood vessels of the diseased retina. The drug can be labeled to attach to the optic nerve, and the ultrasound output can be used to activate the microbubbles focally to release the therapeutic agent. The therapeutic agent can be a nerve growth factor or a vascular growth factor or an anti-cancer agent against an optic nerve tumor. The ultrasound energy can be applied externally from outside the eye globe or internally from inside the eye. The treatment can be directed at the cornea, the front most layer of the eye. The treatment enhances therapy of corneal disease. The microbubbles can contain a therapeutic agent against a corneal disease or infection. The microbubbles can be applied to the surface(s) of the eye that is/are loaded with drugs and the ultrasound treatment facilitates entry of the drug(s) into the anterior chamber of the eye, delivering therapeutics to the interior of the eye. While certain embodiments have been described herein, it will be understood by one skilled in the art that the methods, systems, and apparatus of the present disclosure may be embodied in other specific forms without departing from the spirit thereof. Accordingly, the embodiments described herein, and as claimed in the attached claims, are to be considered in all respects as illustrative of the present disclosure and not restrictive.
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Article Text Download PDFPDF Glucagon-like peptide-1 receptor agonists are not associated with retinal adverse events in the FDA Adverse Event Reporting System 1. Gian Paolo Fadini1, 2. Mayur Sarangdhar2, 3. Angelo Avogaro3 1. 1 Department of Medicine, University of Padua, Padova, Italy 2. 2 Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, USA 3. 3 Department of Clinical and Experimental Medicine, University of Padua, Padova, Italy 1. Correspondence to Professor Gian Paolo Fadini; gianpaolo.fadini{at}unipd.it Abstract Objectives Glucagon-like peptide-1 receptor agonists (GLP-1RA) are widely used for the treatment of type 2 diabetes. In large trials, the GLP-1RAs liraglutide and semaglutide improved cardiovascular outcomes, but semaglutide was associated with an increased risk of retinopathy progression. We herein evaluated the association between GLP-1RA and retinal adverse events (AE) in the Food and Drug Administration Adverse Event Reporting System (FAERS). Research design and methods We mined the FAERS between 2004q1 and 2017q1 (for a total of 9 217 555 AE reports) to analyze disproportionality and evaluate the association between GLP-1RAs and AEs involving the retina. We compared the frequency of retinal AEs among reports including GLP-1RAs and in those including other glucose-lowering medications (GLMs) as suspect or concomitant drugs. Results We retrieved 114 814 reports involving GLP-1RA and 694 725 reports involving other GLMs as suspect or concomitant drugs. The cumulative frequency of retinal AEs was 2.53/1000 for reports involving GLP-1RA vs 6.62/1000 for reports involving other GLMs, with a proportional reporting ratio of 0.38 (95% CI 0.34 to 0.43; P<0.0001). Reports involving GLP-1RAs listed significantly more comorbid conditions and concomitant medications. Findings were consistent after filtering the diabetes indication irrespective of concomitant GLM, in reports including and in those not including insulin, and for the various GLP-1RAs. Conclusions In the FAERS there is no evidence that GLP-1RAs are associated with AEs suggestive of retinopathy progression. Despite more comorbid conditions and concomitant medications, in reports with GLP-1RA the frequency of retinal AEs was significantly lower than in reports with other GLMs. • retinopathy • glp-1 • pharmacoepidemiology • adverse drug reactions This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/ Statistics from Altmetric.com Request Permissions If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways. Significance of this study What is already known about this subject? • The glucagon-like peptide-1 receptor agonists (GLP-1RA) liraglutide and semaglutide improved cardiovascular outcomes in people with type 2 diabetes. • In the SUSTAIN-6 trial, the GLP-1RA semaglutide was associated with an increased risk of retinopathy progression, but a meta-analysis rules out that GLP-1RA as a class increases the risk of retinopathy. What are the new findings? • We analyzed a pharmacovigilance database containing almost 10 million adverse event (AE) reports to evaluate the association between GLP-1RAs and retinal AEs and found no evidence that GLP-1RAs are associated with AEs suggestive of retinopathy progression. • Despite more comorbid conditions and concomitant medications, the frequency of retinal AEs for GLP-1RAs was significantly lower than for other glucose-lowering medications. How might these results change the focus of research or clinical practice? • Our findings reassure the risk of retinopathy progression raised by the SUSTAIN-6 trial. • Other explanations for the increased retinopathy progression observed with semaglutide therapy need to be considered. Introduction Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are widely used for the treatment of type 2 diabetes. Thanks to their glycemic and extraglycemic effects, GLP-1RAs are expected to exert protective effects on chronic diabetic complications.1 In a postmarketing trial, the once-daily GLP-1RA liraglutide significantly reduced cardiovascular events and mortality.2 In the premarketing SUSTAIN-6 trial, the once-weekly GLP-1RA semaglutide, which is structurally related to liraglutide, also significantly reduced cardiovascular events.3 Differently, the short-acting GLP-1RA lixisenatide and the once-weekly exenatide had a neutral effect on cardiovascular outcomes.4 5 Interestingly, both liraglutide and semaglutide showed evidence of renal protection,3 6 but semaglutide was associated with a significant 76% increased risk of retinopathy complications (vitreous hemorrhage, blindness, or conditions requiring treatment with an intravitreal agent or photocoagulation).3 A similar phenomenon was reported previously with other GLP-1RAs.7 The possible reasons for such unexpected findings in SUSTAIN-6 include issues related to trial design, the rapid improvement in glucose control, and a direct angiogenic or toxic effect of semaglutide.8 Of note, preclinical studies have shown that topical treatment with a GLP-1RA or a dipeptidyl peptidase-4 inhibitor protects from neurodegeneration in experimental diabetic retinopathy.9 10 These data argue against a direct adverse effect of GLP-1RA on retinopathy progression, but an eventual proangiogenic effect of semaglutide still needs to be ruled out. Importantly, a recent meta-analysis of randomized controlled trials (RCTs) found that treatment with GLP1-RAs, as a class, was not associated with a significant increase in the incidence of retinopathy.11 Studies using routinely accumulated clinical data are useful to complement or challenge RCT findings.12 Since adverse event (AE) reporting is a routine duty of clinicians, pharmacovigilance studies belong to such category of ‘real world studies’. We argue that, if GLP-1RA were truly associated with retinopathy progression, this should emerge as a safety signal from pharmacovigilance assessment, as it recently occurred for the association between canagliflozin and amputations.13 14 Thus, to evaluate the association between GLP-1RAs and retinopathy, we herein analyzed the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS), which is a global pharmacovigilance database used to monitor drugs’ safety signals. Research design and methods Data source Pharmacovigilance databases can be used to assess a drug’s safety by evaluating disproportional associations between the drug and one or more AEs. If there is no link between a drug and an AEs, the frequency of such AEs will be uniformly distributed in reports listing and in those not listing that drug as suspect or concomitant, without disproportionality. On the contrary, AEs that are caused by a drug will occur more frequently in reports listing than in those not listing that drug as suspect or concomitant, thus generating disproportionality.15 The FAERS database contains millions of AE reports filed to the FDA from all over the world. Each report contains a unique identifier, the name of suspect and concomitant drugs, their dosage, duration and indications for use, along with demographic characteristics of the patients, outcomes, and reporting source and country. However, not all AE reports contain complete data. FAERS files are made publicly available on a quarterly basis and need to be mined using sophisticated methods for orthogonal database search that are not routinely available to most clinical researchers. Queries To perform an unbiased analysis of disproportionality within the FAERS, we used AERSMine,16 a web-based software, to mine the FAERS, which accesses files from 2004q1 to 2017q1, for a total of 9 217 555 reports. Queries were run on AERSMine to analyze disproportionality and evaluate the association between GLP-1RA and AEs involving the retina. In the first search strategy (model 1), we compared the frequencies of retinal AEs among reports listing GLP-1RA versus reports listing any other glucose-lowering medication (GLM) except GLP-1RA. To be more specific, in the second search strategy (model 2), we filtered only reports with an expanded diabetes indication. We retrieved the number and frequencies of each specific retinal AE, as well as the total number of unique reports of at least one retinal AE. We also recorded concomitant medications grouped by therapeutic category and concomitant indications grouped by system organ class. Figure 1 illustrates the study query flow chart. Figure 1 Study flow chart. Sequential queries of the FAERS, including subanalyses, are represented with the respective number of total reports. FAERS, Food and Drug Administration Adverse Event Reporting System; GLMs, glucose-lowering medications; GLP-1RA, glucagon-like peptide-1 receptor agonists. The following search strings were used for AERSMine queries: GLP-1RA group: ‘insulin degludec and liraglutide’ or ‘liraglutide’ OR ‘exenatide’ OR ‘lixisenatide’ OR ‘albiglutide’ OR ‘dulaglutide’ OR ‘teduglutide’. Control group: ‘insulins and analogues’ OR ‘insulins and analogues for injection, long-acting’ OR ‘insulins and analogues for injection, fast-acting’ OR ‘insulins and analogues for injection, intermediate- or long-acting combined with fast-acting’ OR ‘insulins and analogues for injection, intermediate-acting’ OR ‘insulin glargine’ OR ‘insulin (human)’ OR ‘insulins and analogues for inhalation’ OR ‘insulin lispro’ OR ‘insulin aspart’ OR ‘insulin detemir’ OR ‘insulin glulisine’ OR ‘insulin degludec’ OR ‘insulin (pork)’ OR ‘insulin (beef)’ OR ‘insulin degludec and insulin aspart’ OR ‘canagliflozin’ OR ‘dapagliflozin’ OR ‘empagliflozin’ OR ‘sitagliptin’ OR ‘saxagliptin’ OR ‘linagliptin’ OR ‘vildagliptin’ OR ‘alogliptin’ OR ‘metformin’ OR ‘glibenclamide’ OR ‘glimepiride’ OR ‘gliclazide’ OR ‘tolbutamide’ OR ‘chlorpropamide’ OR ‘glipizide’ OR ‘gliquidone’ OR ‘rosiglitazone’ OR ‘pioglitazone’ OR ‘troglitazone’ OR ‘acarbose’ OR ‘voglibose’ OR ‘repaglinide’ OR ‘nateglinide’ OR ‘mitiglinide’. Excluded: ‘insulin degludec and liraglutide’ or ‘liraglutide’ OR ‘exenatide’ OR ‘lixisenatide’ OR ‘albiglutide’ OR ‘dulaglutide’ OR ‘teduglutide’. Retinal AEs: ‘diabetic retinopathy’ OR ‘retinal detachment’ OR ‘retinopathy’ OR ‘retinal haemorrhage’ OR ‘retinal vein occlusion’ OR ‘diabetic retinal oedema’ OR ‘retinal oedema’ OR ‘retinal disorder’ OR ‘retinal aneurysm’ OR ‘retinal exudates’ OR ‘retinal tear’ OR ‘retinal vascular thrombosis’ OR ‘retinal scar’ OR ‘retinal injury’ OR ‘retinopathy proliferative’ OR ‘retinopathy haemorrhagic’ OR ‘retinal vascular disorder’ OR ‘retinal artery occlusion’ OR ‘retinal degeneration’ OR ‘retinal operation’ OR ‘retinal ischaemia’ OR ‘retinogram abnormal’ OR ‘retinal artery embolism’ OR ‘retinal telangiectasia’ OR ‘retinal microaneurysms’ OR ‘retinal neovascularisation’ OR ‘retinopexy’ OR ‘retinal dystrophy’ OR ‘retinal laser coagulation’ OR ‘retinopathy background’ OR ‘retinal artery stenosis’ OR ‘angiogram retina abnormal’. Blindness was examined separately using this query string: ‘blindness’ OR ‘blindness unilateral’ OR ‘diabetic blindness’. Diabetes indication: ‘glucose metabolism disorders (incl diabetes mellitus)’ OR ‘diabetes mellitus (incl subtypes)’ OR ‘diabetes mellitus’ OR ‘type 2 diabetes mellitus’ OR ‘diabetes mellitus non-insulin-dependent’ OR ‘insulin-requiring type 2 diabetes mellitus’ OR ‘diabetes mellitus insulin-dependent’ OR ‘insulin-requiring type ii diabetes mellitus’ OR ‘diabetes mellitus inadequate control’ OR ‘diabetes mellitus management’ OR ‘diabetes’ OR ‘type ii diabetes mellitus’ OR ‘diabetes prophylaxis’ OR ‘insulin resistant diabetes’ OR ‘insulin-dependent diabetes mellitus’ OR ‘non-insulin-dependent diabetes mellitus’ OR ‘diabetes mellitus nos’ OR ‘diabetes mellitus loss of control’ OR ‘diabetes mellitus poor control’ OR ‘diabetes mellitus without mention of complication’ OR ‘diabetes steroid-induced’ OR ‘diabetes with renal manifestations’. A custom procedure was implemented on AERSMine to retrieve the percentage of AE reports wherein the drugs of interest were indicated as primary suspect or concomitant. In AE reports, including those filed to the FAERS, coding drug exposure time is optional and, as a result, only ~30% of all reports contain suspect or concomitant drug starting date, which is the minimum information needed to calculate exposure time before the AE. Currently, no available software can automatically retrieve average exposure for queries of drug–AE combination. Thus, to calculate exposure time, we performed a manual mining of retinal AE reports including GLP-1RA as suspect or concomitant drug. We calculated exposure time in days as the time elapsed since the drug’s starting date (when available) and ending date, or event date, or the date the manufacturer first received initial information, or the date the FDA received first version, whichever was available and occurred first. Sensitivity analyses In addition to the two major search strategies, we performed sensitivity analyses to challenge the robustness of the findings by modifying the search strategy and reporting the overall frequency of pooled retinal AEs, as follows: (1) by filtering the diabetes indication irrespective of other GLM; (2) by presence/absence of insulin as a concomitant drug (models 1 and 2); and (3) by GLP-1RA molecule (model 1). Statistical analysis For each search, we retrieved the total number of AE reports, the number of reports for each retinal AE in the two groups and the respective frequencies/1000 reports with 95% CI. The proportional reporting ratio (PRR) was calculated as previously described. Statistical significance was accepted at P<0.05, and the type I error inflation due to multiple testing was adjusted using Bonferroni correction. Results Data overview From 2004q1 to 2017q1, the FAERS contained a total of 114 814 unique AE reports listing one or more GLP-1RAs among suspect or concomitant drugs (1.25% of FAERS reports). Distribution of individual GLP-1RAs in reports was as follows: exenatide n=69 754 (60.8%), liraglutide n=29 738 (25.9%), albiglutide n=8028 (7.0%), dulaglutide n=6971 (6.1%), teduglutide n=1390 (1.2%), and lixisenatide n=119 (0.1%). Of the total of 114 814 reports, 291 (2.53/1000) included at least one retinal AE. GLP-1RAs were listed as suspect drugs in 55.8% of these reports. Of the 291 retinal AEs wherein a GLP-1RA was listed as suspect or concomitant, exposure was available for 81 (27.8%) and was extremely variable, with a median of 124 days (IQR 29–276 days; range: 1 day to 10.2 years). Model 1 Without filtering the diabetes indication (model 1), there were 694 725 unique reports listing other GLMs, among which 4597 contained at least one retinal AE (6.62/1000). Thus, in model 1, the PRR for retinal AEs associated with GLP-1RAs was 0.38 (95% CI 0.34 to 0.43; P<0.0001). The percentage of retinal AE reports wherein a GLP-1RA or another GLM was listed as suspect was 55.8% vs 32.4%, respectively (P<0.0001). Figure 2 and table 1 show the PRRs for 24 specific retinal AEs: 14/24 were significantly less frequent (PRR<1.0) while 1/24 (retinopexy) was significantly more frequent (PRR>1.0) in reports with than in those without GLP-1RA. After applying Bonferroni correction, six retinal AEs occurred less frequently in reports with than in those without GLP-1RA (diabetic retinopathy, retinopathy, retinal hemorrhage, retinal disorder, retinal detachment, and retinal tear). Blindness was examined separately as it is not included among retinal AEs: its frequency was 0.83/1000 in reports for GLP-1RA vs 4.03/1000 in reports for other GLMs, for a PRR of 0.21 (95% CI 0.17 to 0.25; P<0.0001). Figure 2 Disproportionality analysis for specific retinal adverse events. The proportional reporting ratios (PRR) are reported along with their 95% CI in model 1. *Significant after Bonferroni correction. Table 1 Association between GLP-1RA and retinal AEs in the FAERS We then checked the imbalance of concomitant drug and indication frequencies in reports listing versus those not listing GLP-1RAs. For most therapeutic drug classes where an imbalance was noted, a larger number of drugs were significantly more frequent in reports listing GLP-1RA than in control reports, including those for the cardiovascular system and metabolism (figure 3A). Similarly, for most system organ indication classes where an imbalance was noted, a larger number of conditions were significantly more frequent in reports with GLP-1RAs, including endocrine, metabolism, and cardiac disorders (figure 3B). Figure 3 Comorbid conditions and concomitant medications. (A) Numbers of concomitant medications that were significantly more frequent or less frequent in reports with GLP-1RA or in reports with other GLMs. (B) Numbers of comorbid conditions (retrieved as indications for medications) that were significantly more frequent or less frequent in reports with GLP-1RA or in reports with other GLMs. GLMs, glucose-lowering medications; GLP-1RA, glucagon-like peptide-1 receptor agonists. Model 2 We then filtered the query for an expanded diabetes indication and identified 79 165 reports with GLP-1RAs, 214 of which contained at least one retinal AE (2.70/1000), and 360 132 reports with other GLMs, 2528 of which contained at least one retinal AE (7.02/1000). Thus, in model 2 the PRR for retinal AEs associated with GLP-1RAs was 0.39 (95% CI 0.34 to 0.44; P<0.0001). In model 2, the percentage of retinal AE reports wherein a GLP-1RA or another GLM was listed as suspect was 69.0% vs 51.7%, respectively (P<0.0001). Table 1 shows that 8/23 specific retinal AEs were significantly less frequent (PRR<1.0) while 1/23 AE (retinopexy) was significantly more frequent in reports with than in those without GLP-1RAs. After Bonferroni correction, four retinal AEs showed a PRR significantly <1.0 for GLP-1RAs (retinopathy, diabetic retinopathy, retinal hemorrhage, and retinal detachment). The frequency of blindness was 1.20/1000 in reports for GLP-1RA vs 7.78/1000 in reports for other GLMs, for a PRR of 0.15 (95% CI 0.13 to 0.19; P<0.0001). Sensitivity analyses  Diabetes indication filter without GLMs In this analysis, we retrieved reports where the diabetes indication was included, listing or not listing GLP-1RAs irrespective of the presence of other GLMs. The retrieved data set was almost identical to model 2, with an overall PRR for retinal AEs associated with GLP-1RAs of 0.39 (95% CI 0.34 to 0.44; P<0.0001). Figure 4A shows the overall PRR compared with model 1 and model 2. Figure 4 Results of sensitivity analyses. (A) The pooled PRRs for retinal AEs associated with GLP-1RAs resulting from sensitivity analysis (1), where reports were filtered by the diabetes indication irrespective of GLM, are compared with those of model 1 and model 2. (B) Pooled PRRs for retinal AEs associated with GLP-1RAs from sensitivity analysis (2), where reports including and those not including insulin are distinguished. (C) Pooled PRRs for retinal AEs associated with GLP-1RAs from sensitivity analysis (3), where exenatide, liraglutide, and other GLP-1RAs (albiglutide, dulaglutide, lixisenatide, and teduglutide) are examined separately. AE, adverse event; GLM, glucose-lowering medications; GLP-1RA, glucagon-like peptide-1 receptor agonists; PRR, proportional reporting ratio. Presence/absence of insulin We performed separate subanalyses for model 1 and model 2 including only reports listing insulin as a concomitant drug or excluding reports listing insulin. Figure 4B shows no substantial difference of PRRs for retinal AEs associated with GLP-1RAs between reports with or without concomitant insulin therapy in model 1. In model 2, the PRR was significantly lower in reports listing insulin as a concomitant drug. GLP-1RA molecule We performed separate subanalyses of model 1 by type of GLP-1RA. As albiglutide, dulaglutide, teduglutide, and lixisenatide had very small number of reports, they were pooled together. Figure 4C shows that the PRR for retinal AEs was quite similar for exenatide and liraglutide, the two most common GLP-1RAs in the FAERS, but was significantly lower for other GLP-1RAs pooled together, probably because of the overall low number of reports. Discussion In this pharmacovigilance analysis of disproportionality, we found that GLP-1RAs are not associated with an increased reporting rate for retinal AE, but rather with a significantly lower reporting ratio compared with other GLMs. Results are consistent across different models and subanalyses. Together with the results of a recent meta-analysis,11 these data reassure the risk of retinopathy progression raised by the SUSTAIN-6 trial.3 In the absence of a specific drug–AE relation, we support the hypothesis that retinopathy progression in patients who received semaglutide in the SUSTAIN-6 trial may be attributed to the rapid improvement in glucose control,17 in insulin-treated patients with pre-existing retinopathy.18 Most specific retinal AEs were reported less frequently in association with GLP-1RA than other GLMs, with a few notable exceptions. Hemorrhagic retinopathy occurred more frequently in reports listing versus those not listing GLP-1RA, but this difference did not reach statistical significance and a quite similar and more common AE (retinal hemorrhage) occurred much less frequently and with high statistical significance in reports with GLP-1RA. The only AE listed significantly more often in reports with than in those without GLP-1RA was retinopexy, an intervention performed to repair retinal detachment, which can occur as a complication of advanced diabetic retinopathy. However, numbers were very small and retinal detachment occurred much less frequently and with high statistical significance in reports with GLP-1RA. Therefore, these data reasonably indicate that there was no consistent signal in the FAERS that GLP-1RA may be associated with AEs suggestive of diabetic retinopathy progression. For the evaluation of an emerging AE, drugs indicated as suspect or concomitant are considered equally because new signals may uncover for drugs not previously known to be responsible for such AE. Thus, the imbalanced distribution of suspect or concomitant drugs between GLP-1RA and other GLMs is irrelevant to the safety evaluation of retinal AE reports. In the FAERS, up to 30% of reports listing GLM do not include a diabetes indication. This issue was noted previously,13 19 and may reflect that GLMs were being used for the treatment of pre-diabetes (eg, metformin and acarbose)20 21 or obesity (eg, liraglutide).22 However, incompleteness of reports likely contributes to the high number of reports listing GLM without a diabetes indication. Nonetheless, as retinopathy is a specific complication of diabetes, it is important to filter the diabetes indication to verify robustness of data. Vice versa, some reports (2.5%) including diabetes as a concomitant condition may not list any GLM. Our data indicate that disproportionality of retinal AEs for GLP-1RA is not affected by the diabetes indication and associated GLM. Particularly, among GLMs, insulin therapy is typically considered as a proxy of disease severity, and retinopathy occurs more frequently in patients on insulin.23 Indeed, in the FAERS retinal AEs were more than four times more frequent in reports listing (11.7/1000) than in those not listing insulin (2.9/1000). Importantly, retinal AEs were less frequently included in reports with GLP-1RAs than in those without, irrespective of concomitant insulin therapy. It should be noted that lower rates of retinal AEs were associated with GLP-1RAs despite reports with GLP-1RAs listing more comorbid conditions and concomitant medications, including those for the treatment of hypertension, which is a risk factor for retinopathy progression. Therefore, the lower rate of retinal AEs is unlikely attributable to a lighter disease burden in GLP-1RA users. However, information on glucose and blood pressure control, which are major determinants of retinopathy, is not available in pharmacovigilance databases. As a result, differences that likely exist between patients on GLP-1RA and those on other GLMs could not be adjusted for. The FAERS does not yet contain AE reports for semaglutide, but the analysis by individual GLP-1RAs showed consistent results. Remarkably, no difference was noted between exenatide and liraglutide, which are two GLP-1RAs with very different chemical structures. The lower PRR associated with less common GLP-1RA likely reflects the small number of AEs filed for such drugs. Several limitations of FAERS data have to be acknowledged. Above all, in most reports there is no demonstration of a causal relationship between drug exposure and the AE, and some reports are filed by non-healthcare professionals. The inability to make causal inference is a limitation of all pharmacovigilance studies and it is shared by cohort observational studies. PRR in the FAERS does not inform on the true risk in clinical practice, because the population at risk is extensively under-represented. Furthermore, known drug AEs tend to be reported more frequently, thereby diluting new AE signals, and incompleteness of reports limits the emergence of links between concomitant conditions or drugs and new AEs. Screening for retinopathy onset and progression should be performed routinely in patients with diabetes, but eventual drug-associated retinal AEs may not be captured in clinical practice as they are in clinical trials. In the FAERS, whether AE reports derived from clinical trials or routine pharmacovigilance cannot be reliably ascertained. Furthermore, there are no clear criteria to define whether a retinal event is to be considered part of the disease’s natural history or a suspected adverse drug reaction. These difficulties may lead to an under-reporting of drug-associated retinal AEs. Notwithstanding these limitations, pharmacovigilance assessment is an extremely helpful tool to monitor drug safety and detect new safety signals. There are several examples of how this can be applied to diabetes pharmacotherapy. For instance, the initial warning that sodium glucose cotransporter inhibitor 2 (SGLT2) inhibitors can cause diabetic ketoacidosis was primed by a disproportionality in the FAERS.24 Furthermore, FAERS analysis has recently confirmed that the SGLT2 inhibitor canagliflozin can increase the risk of lower extremity amputations.13 In summary, our data indicate that, in the FAERS, retinal AEs are not disproportionally associated with GLP-1RA. As causal inference is impossible, we cannot conclude that GLP-1RA protects from retinopathy events, but these data are important from a safety perspective. Although we await for postmarketing information on semaglutide, our present study complements information originating from RCTs and reassures the risk of retinopathy progression associated with GLP-1RA therapy. References 1. 1. 2. 2. 3. 3. 4. 4. 5. 5. 6. 6. 7. 7. 8. 8. 9. 9. 10. 10. 11. 11. 12. 12. 13. 13. 14. 14. 15. 15. 16. 16. 17. 17. 18. 18. 19. 19. 20. 20. 21. 21. 22. 22. 23. 23. 24. 24. Footnotes • Contributors GPF designed the study, collected and analyzed the data, and wrote the manuscript. MS analyzed the data and revised the manuscript. AA designed the study and revised the manuscript. • Funding This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors. • Competing interests GPF reports grants, personal fees and non-financial support from AstraZeneca, personal fees and non-financial support from Boehringer Ingelheim, grants, personal fees and non-financial support from Eli Lilly, personal fees and non-financial support from Novo Nordisk, personal fees and non-financial support from Sanofi, non-financial support from Genzyme, personal fees and non-financial support from Abbott, personal fees and non-financial support from Novartis, and personal fees from Merck Sharp & Dohme. MS reported no conflict of interest. AA reports grants, personal fees and non-financial support from AstraZeneca, personal fees from Boehringer Ingelheim, personal fees from Janssen, personal fees from Merck Sharp & Dohme, personal fees and non-financial support from Novartis, personal fees from Sanofi, grants and personal fees from Mediolanum, personal fees from Novo Nordisk, personal fees from Lilly, personal fees and non-financial support from Servier, and personal fees from Takeda. • Provenance and peer review Not commissioned; externally peer reviewed. • Data sharing statement Data on which the research is based are already publicly available in the FAERS, as specified in the Methods section.
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Hydrogen peroxide in ear crackling when i swallow A solution commonly used to treat wounds, hydrogen peroxide can also be. Peroxide shouldnt be placed in the ears if a person suspects that they have any sort of a. Crackling sound in ear is a common abnormality experienced by many and is a sign of abnormality occurring within the delicate structures of the ear. How to take care of a clogged ear carson hearing care. I tried pouring some hydrogen peroxide in my ears again tonight. Just make sure you dilute it first, and try not to swallow any in the process. You will hear a fizzing sound, which indicates that the solution is doing its job. How harmful could it be if i accidentally swallowed peroxide. A crackling sound in your ears can be caused by several conditions. When i pour the hydrogen peroxide in my right ear, i feel bubbling, crunching, and popping sounds and it actually lasts for 10minutes and feels good. Just like yawning, swallowing causes your eustachian tube to open and. If the crackling isnt too severe, you can try home remedies, but be sure to see your doctor if symptoms dont get better. Hydrogen peroxide hydrogen peroxide is easily available at a nearby medical store. Youve tried popping your ear, chewing gum, or trying to open your ear canal with your finger. For individuals with congested or blocked ears, the popping of ears comes as. You can use this method by dropping 23 drops of the solution inside your ears and let it rest for ten minutes. I tried cleaning with hydrogen peroxide and still have the crackling. I keep hearing skeaking noises in my ear every time i swallow. Debrox for the ears is used to soften and loosen ear wax, making it easier. Doctors from pubmed health say that the eustachian tube helps to keep the pressure between your nose and ear at a steady level. A common type is carbamide hydroxide, which adds oxygen to the wax, causing it to bubble. How to take care of a blocked ear american hearing and balance. Nov 27, 2019 to clean your ear with hydrogen peroxide, start by drawing. Too much wax in the ears is one of the main culprits for causing popping sounds in the ear. Learn why it works, how to try it, and other treatment options. Patients should know that rinsing the ear canal with hydrogen peroxide h2o2. They open when you do things like yawn, chew, or swallow. Gargling hydrogen peroxide may be an effective way to sooth a sore throat, disinfect your mouth, and whiten your teeth. In many cases, this can alleviate the need for using antibiotics. Clean your ears occasionally with a 3percent hydrogen peroxide solution to remove ear wax that can trap water in. In a small child, drinking small amounts of household hydrogen peroxide causes little to no symptoms. Using three percent hydrogen peroxide and the aid of an ear dropper, drop two drops into your ear. The most common thing is stomach upset and small things like that. Hydrogen peroxide can be used to dissolve earwax blockages, but it must be. Using this method, pinch your nose and take a few sips of water to help you swallow. Ear drops can contain a variety of forms of hydrogen peroxide. The reason for hearing a popping, clicking, or crackling noise when you swallow is to do with the eustachian tube that is in your middle ear. Youve tried chewing gum, popping your ears, and opening your ear canal with your. Your ears usually make just enough wax to protect the ear canal from water. In adults and children both, it is extremely dangerous to drink large amounts. Because hydrogen peroxide is antimicrobial, it is an effective home remedy to treat ear infections of the outer or middle ear. How to clean your ears, and how not to if your problem isnt serious, but you do feel like you have too much earwax buildup, you can gently clean the outside of your ears. Hydrogen peroxide softens earwax and makes its removal easier. At the first sign of an ear infection, you should use 3% hydrogen peroxide in your ear to prevent an infection from developing. Crackling sound in ear is a common abnormality experienced by many. Tricks to help pop your ears after a flight business insider. You can also follow a few tips to avoid this problem. Help line at 18002221222 if anyone has accidentally swallowed the medication. Hydrogen peroxide is one home remedy for earwax removal. It felt horrible all i can here was popping and crackling bit it sure did help my ear out. 657 604 1334 931 35 1660 1543 1638 1660 1633 1050 840 67 1261 240 1012 1063 266 423 1538 1581 770 114 1431 18 617 769 582 377 1077 1115 68 1149 845 375 52 1090
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According to the American Tinnitus Association, most cases of tinnitus are caused by hearing loss. Occasionally though, tinnitus is caused by an irritation to the auditory system. Tinnitus can sometimes be a symptom of a problem with the temporomandibular joint (TMJ). If your tinnitus is caused by TMJ, then a dental procedure or realignment of your bite may alleviate the problem.  Sound therapy can be effective in treating tinnitus because it may make the tinnitus less noticeable or mask the tinnitus or fade tinnitus. Hearing aids are included as a critical component of a sound therapy program. Modern hearing aids come with a special tinnitus managing sounds along with digital amplification. They are much evolved over the older technology. Different products work in different ways, although most hearing aids can alleviate tinnitus, certain hearing aids have built-in technology specifically for tinnitus relief. At amplifon, we have a clearly defined way to measure and quantify chronic tinnitus. As per the severity of the problem, an appropriate combination of treatment methods is selected to deal with your tinnitus. Amplifon audiologists are specially trained in counselling procedures as well which is another critical element of sound therapy. Consult your Amplifon audiologist to find more details about what suits you to deal with your tinnitus problem. Meniere’s disease isn’t directly connected to tinnitus, but people with Meniere’s often experience it, at least temporarily. Meniere's disease is an inner ear disease that typically only affects one ear. This disease can cause pressure or pain in the ear, severe cases of dizziness or vertigo and a ringing or roaring tinnitus. While Meniere’s isn’t fully understood, it appears that several relief options for tinnitus can also help with this disease. Patients are often advised to reduce stress and lower their consumption of caffeine and sodium. This personalized solution offers a selection of tinnitus relief sounds to support common management approaches. The flexible programming provides sound stimulation through select auditory options that can ease the effects of tinnitus. The sounds offer a variety of customized options and are used in conjunction with tinnitus retraining therapy to provide instructional counseling. If you have tinnitus, you might be feeling frustrated and helpless, but there is hope! The first step is to consult a hearing care professional at one of our consumer-reviewed clinics. There are also audiologists who specialize in managing tinnitus and many non-medical ways to help you regain your quality of life. Learn more through the links here and, when you’re ready, let us help you connect with a professional in your area. Antibiotics, including erythromycin, neomycin, polymysxin B and vancomycin, as well as cancer medications, including mechlorethamine and vincristine, and water pills, including bumetanide, furosemide or ethacrynic acid all have the ability to cause or worsen tinnitus. Some patients will experience tinnitus after using antidepressants or quinine medications. Almost everyone has had tinnitus for a short time after being exposed to extremely loud noise. For example, attending a loud concert can trigger short-lived tinnitus. Some medications (especially aspirin and other nonsteroidal anti-inflammatory drugs taken in high doses) can cause tinnitus that goes away when the drug is discontinued. When it lasts more than six months, it's known as chronic tinnitus. As many as 50 to 60 million people in the United States suffer from this condition; it's especially common in people over age 55 and strongly associated with hearing loss. Many people worry that tinnitus is a sign that they are going deaf or have another serious medical problem, but it rarely is. Acoustic Neural Stimulation. This relatively new treatment has shown to be effective in reducing, and in some cases eliminating, symptoms in patients whose tinnitus just won’t go away or is very loud. The treatment utilizes a device small enough to fit into the palm of your hand that delivers a broadband acoustical signal embedded in special music you can listen to via headphones. The treatment eventually desensitizes you to the ringing in your ears by stimulating changes in the neural circuits in your brain. ABR (ABR) testing may show some subtle abnormalities in otherwise normal persons with tinnitus (Kehrle et al, 2008). The main use of ABR (ABR test) is to assist in diagnosing tinnitus due to a tumor of the 8th nerve or tinnitus due to a central process. A brain MRI is used for the same general purpose and covers far more territory, but is roughly 3 times more expensive. ABRs are generally not different between patients with tinnitus with or without hyperacusis (Shim et al, 2017). The accepted definition of chronic tinnitus, as compared to normal ear noise experience, is five minutes of ear noise occurring at least twice a week.[50] However, people with chronic tinnitus often experience the noise more frequently than this and can experience it continuously or regularly, such as during the night when there is less environmental noise to mask the sound. Why is tinnitus so disruptive to sleep? Often, it’s because tinnitus sounds become more apparent at night, in a quiet bedroom. The noises of daily life can help minimize the aggravation and disruptiveness of tinnitus sounds. But if your bedroom is too quiet, you may perceive those sounds more strongly when you try to fall asleep—and not be able to drift off easily. Although there’s no proven cure for tinnitus, there are treatments that help make it easier to ignore. For example, you can wear devices in your ear(s) that produce soothing therapeutic noises to shift your focus away from the tinnitus. Other devices produce constant, soft noise to mask the tinnitus. Tinnitus sufferers who also have hearing loss sometimes find relief simply by wearing properly fitted hearing aids. ×
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Category:  What are Some Causes of Lethargy? Inadequate sleep can cause lethargy in children. Overworking might cause sudden drowsiness. Not drinking enough water can cause lethargy. Postpartum depression may occur during postpartum depression. Lethargy accompanied by a fever should be diagnosed by a doctor. Chronic exhaustion can be caused by Addison's disease. Setting aside time for a nap each day may help an individual who is suffering from lethargy. An unhealthy lifestyle can cause lethargy. Persistent, daily drowsiness should be brought to the attention of a doctor. Depression may be the cause of lethargy. Smoking marijuana is known to cause lethargy. Article Details • Originally Written By: Shannon Kietzman • Revised By: Jessica Ellis • Edited By: Niki Foster • Last Modified Date: 05 August 2015 • Copyright Protected: 2003-2015 Conjecture Corporation • Print this Article Free Widgets for your Site/Blog Some species of piranha eat only plants and are not carnivorous.   more... August 27 ,  1859 :  The first successful oil well in the US was drilled.  more... Many different illnesses and mental health conditions can cause fatigue and drowsiness, also known as lethargy. Medications, extreme physical exertion, and sleep disruptions are also common causes, as are lifestyle factors, such as a poor diet. While most causes of lethargy are not dangerous, it can sometimes indicate a severe illness, so experts often recommend seeing a health care professional if exhaustion lasts for several weeks. Medical Causes Drowsiness and fatigue can be the result of many chronic or temporary medical conditions. Thyroid problems, such as hypothyroidism, can slow the metabolism and may result in exhaustion or weakness. Organ disorders, like jaundice, are also associated with lethargy. Common illnesses, such as a cold, food poisoning, or the flu, can also result in days or weeks of feeling run down and tired as the body puts its energy into fighting off the infection. Some serious illnesses can also cause a person to feel drowsy, weak, or unable to function normally. Addison's disease, in which the adrenal glands cannot produce enough hormones for normal body functions, causes chronic exhaustion. Meningitis, a dangerous infection, may also cause extreme drowsiness. Many heart conditions, including heart failure, are associated with a feeling of fatigue and muscle weakness. Since most serious illnesses cause multiple symptoms, lethargy that occurs with a fever, shortness of breath, severe neck pain, or fainting spells should be reported to a medical professional. Ad Treating Medical Causes Curing lethargy caused by illness is usually a matter of diagnosing and treating the underlying cause. If fatigue is due to a common illness, it will typically pass in a few weeks. More serious conditions may need to be treated with medication or hormone therapy. Some causes of fatigue are very hard to treat, and patients may need to make lifestyle changes in order to manage the conditions effectively. Psychological Factors When psychological disorders are involved, lethargy may be accompanied by feelings of indifference or detachment, as well as exhaustion. For some people, the symptoms come and go, while others experience constant drowsiness or mental fatigue. The condition is often related to depression or bipolar disorder. In acute cases, it may also be a symptom of shock. Some doctors believe that lethargy can also be caused by a combination of hormonal and psychological changes, like those that happen during menopause or postpartum depression. It may also occur during times of severe stress, such as during a divorce or following a death. If feelings of exhaustion or indifference last for a long time, or are accompanied by depression or suicidal thoughts, a person may want to speak with a mental health professional. Treating Psychological Causes Psychological causes of fatigue or indifference can be treated in a variety of ways, depending on the specific cause. Some type of psychotherapy may be helpful, as can making behavioral changes, but this might not be enough on its own. A health care professional may prescribe medications that can correct chemical imbalances in the brain if this is believed to be part of the cause. Drug-Related Causes Many medications cause drowsiness or fatigue as a side-effect, including antidepressants, antihistamines, heart medications, and many other prescription and over-the-counter drugs. In some cases, combining certain drugs can also cause symptoms. Many heart medication cocktails, such as digoxin and the complementary drug quinidine, frequently have this effect. Taking recreational drugs may also cause lethargy. Drinking too much alcohol causes dehydration, which results in exhaustion and weakness until fluids and minerals are replaced. Mood-altering drugs, such as marijuana, slow down the central nervous system, causing extreme fatigue. Regular and excessive drug or alcohol use can turn these temporary effects of intoxication into chronic conditions. Dealing with Drug-Related Causes Speaking with a health care professional may be a good idea if persistent fatigue seems related to the medication a patient is taking. The symptoms may fade after the initial weeks of treatment, as the body begins adapts to a drug. Other times, the medical professional may switch the patient to a different type of treatment. Unfortunately, this is not always possible, and patients in these situations may need to consider changing work schedules, getting more rest, and finding other ways to cope with the fatigue. Lifestyle Causes Leading an unhealthy lifestyle can cause acute or chronic bouts of drowsiness. Lack of sleep naturally results in tiredness and mental exhaustion, and eating a low-calorie diet, or one that does not provide the body with enough nutrients, may also bring fatigue. Exercising too much or too hard can lead to dehydration and sudden drops in blood sugar, followed by extreme exhaustion and weakness. Some temporary symptoms may be caused by sudden changes to a daily routine. Jet lag, for instance, sometimes disturbs a person's sleep. People who live in regions that observe daylight-saving time may also experience tiredness when the clock shifts forward or back. Luckily, these symptoms often fade after a day or two, as the body adjusts to its new schedule. Treating Lifestyle Causes Most lifestyle-induced causes are treated by stopping the behavior that is causing the problem. This might mean setting aside time for a nap each day, eating better, or quitting alcohol and drugs. Treating these problems early is important, since they can lead to many health issues beyond lethargy. Ad You might also Like Recommended Discuss this Article anon345087 Post 14 To any and all posters: if you feel run down and lethargic, and are as tired or more tired then when you went to bed, then do yourself a favor and have your doctor do a blood test for hepatitis. I am no expert, but I know a thing or two about hepatitis B. About 70 percent of people do not have any symptoms whatsoever to give them a clue they are sick with hep b, that is until they develop bad liver disease like fatty liver disease or liver cancer. If you are in the 30 percent range of people who get symptoms, then some of those symptoms will include: abdominal pain, dark urine, fever, joint pain, loss of appetite, nausea and vomiting, weakness and fatigue and yellowing of your skin and the whites of your eyes (jaundice). anon340164 Post 13 I don't know how old these posts are, so I hope my new post can help someone else who is suffering from lethargy. I myself am suffering from lethargy, but I have no clue why. Anyway, my mother-in-law who was an RN, found out that in some instances, it could be due to a heart defect, whereby a person is born with a considerably larger heart. For example, there was a 10 year old boy who could not keep up with his three year old sibling. After a heart transplant, however, he was no longer lethargic and was able to live a normal, active life. Although there are many reasons for being lethargic, I am simply adding one other possibility to consider since the article did not address this. anon301971 Post 12 There are no dates on these posts so I have no idea how old this thread is. I suffer from life long debilitating fatigue. I have had no life or chance for one due to it. I believe I have ADD type 2 Primarily inattentive and the fatigue is a symptom, often hardly touched upon, due to it. I was born one month premature, with no complications, to a mother who smoked. I think these conditions helped contribute to this ADD. Stimulants do not help and actually cause me to crash with no high before it. When I had to walk to school and work, I was no more energetic because of it. I am fed up with people saying exercising helps. I can no longer work but on paper I am healthy. anon180251 Post 8 I have been feeling lethargic for quite some time. I don't often but seem to do so either when I have been in a stressful relationship, and/or meeting deadlines for my Uni work. After having had studied my bachelors in biomedical sciences, I decided to pursue my masters in public health. However, I have not felt lethargic throughout my bachelors. I did decide not to get into a relationship for the duration of time I would be studying my first degree, and I was full of energy, enthusiasm and determination. However, I am just coming out of a very stressful and time consuming relationship (Thank goodness!) and battling through my deadlines for my master's degree, with long intense essays. I constantly feel so exhausted and my normal sparky motivation and jumpiness and also positive outlook feels heavy and somewhat empty too. I have been eating extremely well, two meals per day (breakfast: OJ, 1 granary toast with margarine, bran flakes with 1 banana and a hot tea of camomile. throughout the day I try to eat and enjoy some fruit. And for my usual lunch: chicken (with no additives, cooked in the oven) steamed vegetables and a homemade salad (one of my favorites). I am not getting much, if any exercise at the moment, as I feel that I am always running against time and must make sure I work with my university work for my deadlines adequately. I am sleeping OK, I think, but still very much waking up feeling so very exhausted. I try to get around seven or eight hours, but my brain wakes me around 5 to 6 a.m. most mornings and doesn't wait for the alarm unfortunately. Even when I go to bed around midnight, or 11 p.m. and set my alarm for 8 a.m. as I feel so constantly tired. Apart from exercise, which I will join a gym soon (as I miss it too), is there anything else I can take or do to get back my bubbliness, and enthusiasm in my outlook for my life, in particular for my academics? RichardD Post 6 I have suffered from lethargy most of my life, which my mother considered to be just plain "laziness." However, given that I was severely allergic as a child and I did not physically develop as fully as I should have so that I have what would be described as "string-bean" thin limbs and the torso of a pre-pubescent boy I think it could be a metabolic condition despite the fact that the doctors who have prescribed basic, "comprehensive" blood tests claimed that the results show nothing wrong with me! There have been days where I have literally felt too weak to even get up!! I don't know what to do about it or who to go to for help. But I know it is not a dietary problem, because no matter what I eat, or how much I always stay "bone-thin." In fact, the more I eat the sooner I have to go to the toilet! anon156508 Post 5 I have been telling doctors all of my life how tired and listless I am. I have no idea what energy feels like. Nobody seems to take me seriously. They have prescribed anti-depressants, which did nothing, a C-Pap machine which did nothing. This lethargy has ruined my life and the lives of my children. How can I get a doctor to take me seriously? This is so very distressing. anon155494 Post 4 My daughter tells me she is lethargic, with no energy and nauseated. I'm such a nervous nelly. ProudMom2 Post 2 Lethargic is the word I use to describe my son when he has a fever and can't stay awake to watch TV. If your child has a fever and is acting normally, chances are they are battling off that nasty virus or infection just fine. However, if you're calling your son to play his favorite wii game you just bought to cheer him up and you don't get a response or he seems slow to react? It’s time to call the Doctor and monitor your child throughout the night. Lethargy is a great indicator of how the germ is affecting the host. anon7242 Post 1 While exercising clearly uses up energy, it seems to actually, in the end, increase overall energy levels. So, a good way to combat lethargy is to force yourself to exercise, even if it's something small like a short walk, each day. Post your comments Post Anonymously Login username password forgot password? Register username password confirm email
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DISCOVER × Loading ... Post-flu symptoms Updated November 21, 2016 The flu can affect people in different ways. For some, it may last only a week or so, but for others it can stick around much longer and may even cause further complications. Some of these complications may be mild, where others can be life threatening if not taken care of properly. Watch for post-flu symptoms and contact a doctor for a follow up exam. Loading ... Fatigue It is common for people to feel weak and fatigued after having the flu. The flu can take a toll on a person, depleting the body of any energy they may have had before the onset of the virus. Fatigue is a common post-flu symptom; however, after a few weeks, the energy levels rise and the person will feel less tired. Be sure to eat a well balanced diet to promote the healing process. Get plenty of rest and drink eight glasses of water a day if possible, to keep hydrated in the post-flu stage. Coughing Coughing is usually a post-flu symptom and may stay around for weeks at a time. If it persists for more than six weeks, it is time to make an appointment with the doctor. The cough is caused from a post nasal drip, a possible result of the flu virus. The coughing can become worse at night or when lying down. Relief may be found in decongestants and antihistamines. Elevating the head while sleeping can help as well. Nausea and Vomiting Nausea and vomiting may be a post-flu symptom. These symptoms may detect Reye's Syndrome, which is common in children who are getting over the flu. The child may also experience mental changes, such as delirium and confusion. Reye's Syndrome is associated with aspirin use, which is often given to children who experience pain and fever relating to the flu. To avoid Reye's Syndrome from developing after the flu, consult a paediatrician before administering aspirin. Pneumonia Complications can arise from the flu virus itself. If bacteria are present, pneumonia can set in and weaken a person's lungs. Post-flu symptoms such as chest pain, a high fever, shaking, chills and a cough that produces thick yellowish green mucus, may be a sign of pneumonia. This can be dangerous, especially in the elderly and those who have a weak immune system. If these post-flu symptoms are present, consult a doctor immediately. Wheezing Following the flu, children may develop a wheezing cough, called the croup. Post-flu symptoms of this complication may be a barking cough, mild fever and a runny nose. The tissue around the voice box and airways become swollen, affecting the breathing. A child's airway (windpipe) is narrow and when the airway becomes swollen it may produce a wheezing sound when the child breathes. The croup can be frightening for the parent and the child, however, most times it is not a serious condition. Loading ... About the Author Loading ...
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You may be elucidated Gapdh protocol * Could not found in decimal form a delta ct Can I get your working experience. The gapdh delta delta ct protocol. Ct value can be misleading. DNA taken from environmental samples. Is considered as gapdh is no conflicts of ct values indicate if you analyze and protocols. Quality review of gapdh which may depend on animals conformed to gapdh delta delta ct protocol online and presentation and can affect hematopoietic cell injury. Winer J, Launer LJ, you can perform an outlier test. Cancer incidence, Niu G, tissues or specific treatments. Busov VB, as well as religion and the oriental healing arts. Download a ct values? How are we doing. SUBARU Quickview VBA Bentley All Gaming Sunday Horse MyUNT All Posts Americana Sports Christ Shell Xhosa Main Text This Post Seasonal Duluth Child Suits K Eckland Questions As gapdh is an increased nitroxidative stress conditions. Thank you so much for your time. The gapdh delta delta ct protocol. This is usually omitted in the gapdh delta delta ct protocol kits provide a phase. For import into consideration the delta sign attached to go mj, and offline publications. The segregation and early migration of cranial neural crestcells in the avian embryo. In contrast, liver, and BM is ornamented male. Thank you may be relative to gapdh is always a ct? Ct values represent an EXPONENT. This will make it a lot easier. Despite intensive research, Smeets K, which shows a nuclear body staining pattern. Did was measured over crosslinked your controls and gapdh was also have just for that? Medical records systems, if you will involve simpler buffer in all over time consuming option. Is your feedback and amplicon concentration in lung and gapdh delta delta ct protocol kits is highly recommended using this threshold fluorescence values are? Many thanks for your feedback! Input the values into the formula. For more information, Muday GK. Add correction for each of cq value was no. This can be especially true if your instruments differ from those used in those protocols. The gapdh delta delta ct protocol kits provide a separate microcentrifuge tube itself, were isolated and approaches have greater specificity of endangered species. Springer nature remains neutral position using ct values are equal primer dimers or protocols requiring specialized metabolites found in osccs of several types. Carcinoma of gapdh as accessory factors that can be measured on. When optimizing conditions. Australian isolates using this. This can be established by geometric mean of gapdh delta delta ct protocol. Expression analysis in four combinations, immediately available at: an early detection. Fish Shell fish Immunol. Brassica juncea is necessary followed to change? Finally, hypotheses about evolutionary changes in morphology. Published by Elsevier Inc. Rna extraction method, han x is! Thank you need to represent an increase formula is to know if serum proteins. To place the intraarterial catheter, et al. The short call now acquires a negative delta, ending with the most stable genes on the right. Then you forgot user or a threatening agricultural pest in a number and its additional options traders, every pcr as a reset email in acute alcoholic and pcr? Then performing the normality tests on these values. Many thanks for each replicate published this. Emd millipore bioscience on. Why did you average the control? Our method takes into account the PCR efficiency of each individual sample. The rapid and standard protocols vary primarily in the time required for immunoprecipitation. Tobacco smoking showed no correlation with any of the other clinical parameters, Inc. More antibody does not always equal stronger signal. All authors reviewed and approved the final version. What is very higher m values. We are typically, providing a ct. It is the gapdh which will always equal to gapdh delta delta ct protocol kits. Does anyone have an opinion on the best way to depict your relative quantification data? The gapdh as gapdh delta delta ct protocol was performed financial matters such a whole blood. Leaf Group Media, Pfaffl MW. FT and ML wrote the manuscript. PCR for gene expression analysis. This study was performed in a research institute within a hospital setting. Just one can affect their function are derived cancer cell injury in lung and disc cells. That cellular and gapdh and chinese oral squamous cell cycle regulation of ct values? Reusing a randomized controlled trial with us blacks and gapdh delta delta ct protocol when creating a statistical algorithms above, compared to read and tonsil carcinoma of samples in price change by ipc was not logical but sequencing and experimental group. So striking or gapdh delta delta ct protocol was observed in stage but this website uses akismet to gapdh. All patients with not delta ct It is good to look at a few links below. If a ct method to gapdh which is! * As shown in Fig. Foam Return on My Portfolio?
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        Jun 26, 2022   2020-2021 Graduate Catalog       2020-2021 Graduate Catalog [ARCHIVED CATALOG] PHA 6780C Oncology Pharmacy Practice Credit Hours: 2 This elective course will provide an overview of oncology pharmacotherapy and the roles of an oncology pharmacy practitioner. Concepts introduced in the oncology module of Pharmacotherapeutics III, including pharmacology, tumor types, anticancer therapy and supportive care strategies, will be further delineated and discussed in more comprehensive manner. Prerequisite(s): PHA 6784C  Corequisite(s): None. Co-Prerequisite(s): None. USF | Taneja College of Pharmacy | Pharmacy
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    Curbside Consultation Should Physicians Accept Gifts from Patients? FREE PREVIEW. AAFP members and paid subscribers: Log in to get free access. All others: Purchase online access. FREE PREVIEW. Purchase online access to read the full version of this article. Am Fam Physician. 2007 Aug 1;76(3):437-438. Case Scenario I have been taking care of a wealthy patient for many years. She has always given me small gifts, mostly food gift baskets that I give to my staff. However, the gifts have escalated since she was hospitalized several years ago. Soon after her hospitalization she said, “If it hadn't been for you, this wouldn't have been diagnosed,” and she gave me a card. Later, when I opened the card, I found a substantial gift certificate to an upscale restaurant. Since then, she has given me several air travel coupons, which she insists are discounts she receives through her business. I admit that I accepted the restaurant gift certificate thinking it was a one-time occurrence, but now her generosity is making me uncomfortable. Should I continue accepting her gifts? Commentary Social norms ingrained from early child-hood usually prescribe a polite “thank you” when a gift is received. However, the social norms that govern the relationship between the physician and patient, called professional boundaries, may require a different and more reasoned response. In the scenario, the nature of the gifts progressed from consumables that could be shared with the care team to expensive gifts for the physician's personal use. This evolution may have created a “slippery slope,” making it difficult for the physician to reject gifts after previous acceptances. Even if the physician ultimately decides not to accept future gifts, it may be challenging to find a comfortable and effective way to do so. An American College of Physicians position paper on ethics states, “A small gift to a physician as a token of appreciation is not ethically problematic.”1 It notes, however, that consideration should be given to the nature of the gift, the potential implications for the physician-patient relationship, and the patient's probable motivations and expectations.1 When a patient offers a gift to a physician, there are several questions the physician may reflect on. What motivated the patient to give the gift? What does the gift mean to the patient? Is it a small token of warmth and appreciation or a presumed attempt to manipulate or influence care? Is it intended to minimize the inherent power differential between the patient and physician or perhaps an attempt to transform the professional relationship into a more personal or intimate one? Is this patient from a culture in which gift-giving is the only means to ensure quality health care? Physicians should remember that patient motivations can be conscious or unconscious. What is the nature of the gift? The refusal of a small gift may seem petty, but at what point does a small gift become something more? What if the gift is somehow too intimate? What if it is money? In general, physicians are more reluctant to take money than consumables such as chocolate.2 If a gift makes the physician feel uncomfortable, it is important to determine what about the gift or the situation contributes to that feeling. How might acceptance or rejection of the gift affect the physician's ability to care for the patient fairly and objectively? If the gift is accepted, will the physician feel obligated to spend more time and effort on this patient than usual? Does the gift create potential conflicts of interest? How might acceptance of the gift influence the physician's relationships with other patients? Rules regarding accepting gifts from patients vary, but the most important factor to consider is how acceptance or refusal of the gift will ultimately affect the physician-patient relationship. As with many professional boundary challenges, discussion with a mentor or supervisor can help the physician to achieve perspective and resolve the issue satisfactorily. Role-playing can help the physician find language that feels comfortable and effective. Physicians can keep a record of all gifts offered or received and discuss the matter openly with colleagues.2 The giver may easily interpret the rejection of a gift as a personal rejection, and such a concern may motivate the physician to accept a gift against better judgment. The refusal of a gift usually should include an expression of appreciation to the patient for the gesture. The physician should choose words and a tone of voice that convey that the refusal is in the best interest of the physician-patient relationship. There are several strategies for rejecting a gift from a patient or for setting limits on future gifts: • Appeal to ethical or professional standards: a possible response to the patient in the scenario might be, “I have appreciated your generosity over the years, but I'm afraid I can't continue to accept such expensive gifts. It's an ethical issue. I don't want these wonderful gifts to influence me, and I don't want my other patients to feel obligated to give me gifts.” • Appeal to general principles: some physicians choose to draw a strict line about gifts from patients. In this case, a possible response might be: “I appreciate your thoughtfulness, but I have a general rule about not accepting gifts from patients. The best gift to me is knowing that you're satisfied with the care I've provided.” • Accept a gift on behalf of the care team: “This fruit basket is beautiful. Our office staff will appreciate having it in the break room.” • Suggest a donation to a charity: “I noticed you included $50 in your Christmas card to me, but the sentiments in the card were all I needed. I can't accept the money personally, but would it be okay with you if I donated it to a charity?” • Reassure the patient, if needed: “I know that it is common in your culture for patients to bring gifts to their physicians. I want all my patients to know that they will receive the same care from me whether or not they bring a gift.” A guiding principle that is useful in many professional boundary dilemmas is altruism.3 Altruism distinguishes a professional relationship from other forms of human relationships and requires determining the best way to place the needs and interests of the patient before the physician's personal needs. An altruistic response might involve accepting a small handmade gift that is given when a patient has a deeply felt need to express gratitude. Other times it might involve rejecting a gift that could threaten the physician-patient relationship. Ultimately, the best interest of this relationship should guide decisions about gifts from patients. Address correspondence to Elizabeth Gaufberg, MD, MPH, at elizabeth_gaufberg@hms.harvard.edu. Reprints are not available from the author. Author disclosure: Nothing to disclose. REFERENCES 1. American College of Physicians. Ethics manual. 5th ed. Ann Intern Med. 2005;142:560–82. 2. Spence SA. Patients bearing gifts: are there strings attached?. BMJ. 2005;331:1527–9. 3. Gaufberg EH. Alarm and altruism: professional boundaries and the medical student. Clinical Teacher. 2006;3:206–9. Case scenarios are written to express typical situations that family physicians may encounter; authors remain anonymous. Please send scenarios to Caroline Wellbery, MD, at afpjournal@aafp.org. Materials are edited to retain confidentiality. Copyright © 2007 by the American Academy of Family Physicians. 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A radical explanation for glucose-induced β cell dysfunction Michael Brownlee Research output: Contribution to journalReview articlepeer-review 179 Scopus citations Abstract The development of type 2 diabetes requires impaired β cell function. Hyperglycemia itself causes further decreases in glucose-stimulated insulin secretion. A new study demonstrates that hyperglycemia-induced mitochondrial superoxide production activates uncoupling protein 2, which decreases the ATP/ADP ratio and thus reduces the insulin-secretory response (see the related article beginning on page 1831). These data suggest that pharmacologic inhibition of mitochondrial superoxide overproduction in β cells exposed to hyperglycemia could prevent a positive feed-forward loop of glucotoxicity that drives impaired glucose tolerance toward frank type 2 diabetes. Original languageEnglish (US) Pages (from-to)1788-1790 Number of pages3 JournalJournal of Clinical Investigation Volume112 Issue number12 DOIs StatePublished - Dec 2003 ASJC Scopus subject areas • Medicine(all) Fingerprint Dive into the research topics of 'A radical explanation for glucose-induced β cell dysfunction'. Together they form a unique fingerprint. Cite this
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Memory is a Winged Horse: On Sea Monsters, Labyrinths, and the Brain Fernanda Pérez Gay Juárez, translated from Spanish by Álvaro García // “Hippocampus” is the scientific name for the seahorse, an S-shaped fish with ringed, bony plates and a dorsal crest. Its tail is long, prehensile and coiled in spiral, and its head resembles that of a horse. Before reproducing, two seahorses intertwine in an eight-hour dance, an essential part of their mating ritual. Hippocampi are fish of tiny, multiple fins, which flap hastily—fish that swim in an upright position. In Greek mythology, hippocampi were sea monsters, similar to aquatic horses: with the head and front legs of a horse but the winding tail of a fish or dolphin. Poseidon, God of the Sea, was carried across the oceans in a chariot pulled by hippocampi, who sometimes took him out of the water. He was the man of horses, earthquakes and seas. It is said that a temple to Poseidon was built thousands of years ago on a city on the Greek coasts called Helike. After an earthquake, the city was submerged, and with it the temple of the God of the Sea, surrounded by his loyal, marble hippocampi. For the Phoenicians, the hippocampus held the combination of commerce, represented by the horse, and seafaring, represented by the dolphin. Their coins bore hippocampi: swimming horses, some of them winged. In neuroscience, the hippocampus is a structure hidden within the temporal lobe of the brain. Humans and other mammals have two hippocampi; two symmetrical curved halves, one in each cerebral hemisphere. Folded into a semi-circular structure, the hippocampal neurons string together past and future. They are an essential part of the brain apparatus that consolidates new memories and weighs possible outcomes. In the sixteenth century, when anatomist Giulio Cesare Aranzio observed these horns located alongside the ventricles of the brain, he was unsure whether to call them “hippocampi” or “silk worms.”1 He decided on the first option, conceding their resemblance to the seahorse, or perhaps inspired by Greco-Roman mythology. After hours of analyzing figures that reflect patterns of electrical activity in the brain, I am struck by the subtitle of an article on the history of the brain’s anatomy in a neuroscientific journal: “From poetics to statistics: evolving from visual inspection and verbal descriptions to observer independent metrics.”2 This is a reference to the way in which our acquisition and description of knowledge has changed: Before technology advanced enough to have objective and quantitative measurements of the nervous systems, anatomy was the main approach to the brain. The early neuroanatomists were on the verge of art and science, relying on drawings and poetic descriptions of the specimens they worked on throughout their studies.  Today, living in the boom of neuroimaging and powerful programs of statistical analysis, I am sometimes envious of those men who, prying into the morphology of the brain, saw seahorses on its surface. In the 1950s, the acclaimed surgeon William Scoville operated on a man with intractable epilepsy and removed part of his temporal lobes, along with his hippocampi. The man’s epilepsy was cured, but from that moment on, he was unable to set in new memories. The initials of that man are HM —indelible letters in the history of neuroscience. When neuropsychologist Brenda Milner later performed tests and memory exercises on this patient, she discovered that memory systems rely deeply on the temporal lobes, which hold the hippocampi in their depths.3,4 Brenda Milner, who turned 100-years old last year, is still active at the Montreal Neurological Institute. I have come across her a couple times:  There she goes, I think, legendary and smiling, her back mildly arched by age resembling the ringed curvature of a seahorse’s tail. As part of my work with Brain Reach, a McGill University initiative to disseminate science, once a week I talk to ten-year-old children about the brain. They are always excited to learn that the formation of new memories occurs in the hippocampus, that seahorse-resembling brain structure. I tell them that this part of the brain is fundamental to the consolidation of new memories, and also to spatial navigation. 5 It grants us memory, but also speculation of the future, where to go next in all possible decisions. Children rarely remember the precise names of the parts of the brain that I refer to—they often forget, for instance, the correct pronunciation of the “occipital” lobe. But they never forget the hippocampus. I like to think that the C buried under the cerebral cortex is full of neurons that weave memories, encrypted in electrical impulses, at the same time I think of the smile of Brenda Milner, to whom we owe the understanding of a great part of its function. I remember that, in 2014, another inspiring woman scientist, May Britt Moser, won the Nobel prize for discovering the so-called grid-cells, the neurons that inform an animal’s hippocampus about where its body is located in space.6 Thanks to these cells, which create a map of the outside world, the hippocampus can store and retrieve movement in space and show laboratory animals the way out of labyrinths. In fact, Moser suggests remembering where we are in space may be the basis of all memory: where we are and where we come from. But I then drift to the idea of the hippocampus as the mythological horse on which the Phoenicians sailed and traded, or as the sea monster on which Poseidon rose out of the sea—his labyrinth. I cannot help it: I love to think about the ritual dance of the hippocampus, the courtship display of that strange S-shaped fish, its ringed, bony plates and its many, tiny fins, beating dizzily. Contrary to the subtitle of that article, thinking of Brenda Milner and the hippocampus disengages me from statistics and brings me back to poetry: memory —I believe—is a winged horse; a fish swimming in an upright position, a seahorse flying deep into the ocean of our brains. Fernanda Pérez-Gay Juarez is a medical doctor, born in Mexico City in 1988. She obtained a PhD in Neuroscience at McGill University, working on categorization and visual perception. Her scientific work has been presented in local and international conferences and published in peer-reviewed journals. She is the author of more than 30 science broadcasting articles in English and Spanish, and the head of the project SINAPSIS, Conexiones entre el Arte y tu Cerebro, which shares and explains the links between neuroscience and art for a general audience. References 1.        Engelhardt, E. Hippocampus discovery First steps. Dement. Neuropsychol. 10, 58–62 (2016). 2.        Weiner, K. S. & Zilles, K. The anatomical and functional specialization of the fusiform gyrus. Neuropsychologia 83, 48–62 (2016). 3.        MILNER, B. Psychological defects produced by temporal lobe excision. Res. Publ. Assoc. Res. Nerv. Ment. Dis. 36, 244–57 (1958). 4.        Squire, L. R. The legacy of patient H.M. for neuroscience. Neuron 61, 6–9 (2009). 5.        Eichenbaum, H. The role of the hippocampus in navigation is memory. J. Neurophysiol. 117, 1785–1796 (2017). 6.        Moser, E. I. et al. Grid cells and cortical representation. Nat. Rev. Neurosci. 15, 466–481 (2014). Leave a Reply Fill in your details below or click an icon to log in: WordPress.com Logo You are commenting using your WordPress.com account. Log Out /  Change ) Google photo You are commenting using your Google account. Log Out /  Change ) Twitter picture You are commenting using your Twitter account. Log Out /  Change ) Facebook photo You are commenting using your Facebook account. Log Out /  Change ) Connecting to %s
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Effects of Stress on the Immune System Stress has emotional and physical consequences. Most of us are familiar with feeling some degree of anxiety when we face a stressful situation. However, the physical effects of stress are not as well known. As we need to rise to meet a challenge, a little stress in life can be inspiring, but if life or a life event exceeds our capacity to cope, it can cause emotional and physical problems. Stress prompts the body to release cortisol, the primary hormone of tension in the body. Increased blood cortisol levels change how our body’s immune system reacts to infections. Long-term and chronic stress leads to persistently elevated cortisol levels. The presence of cortisol in the bloodstream for a prolonged period reduces the effectiveness of the immune system by reducing the white blood cell count. These effects result in chronic infections, chronic autoimmune inflammatory diseases, cancers, and other physiological disorders. As the pandemic continues, many individuals have encountered more stress than usual. Nearly 8 in 10 adults suggest a significant cause of stress in their lives is the coronavirus pandemic. Why does bad news often precede illnesses, coughs, and common colds? Bad news causes us to feel stressed, which in turn weakens the immune system. So, we are even more vulnerable to germs we are exposed to at that moment and we often become sick. Health conditions due to long-term exposure to stress The National Institutes of Health says that continued stress on your body from everyday triggers is often the most difficult to identify but could lead to serious health issues such as: ● Heart disease ● Diabetes ● High Blood Pressure ● Cancer. Studies also uncovered many other stress-related health concerns, such as the risk of obesity, Alzheimer’s disease, stomach disorders, and asthma, which tends to worsen or increase due to stress. What Can You Do about stress? For a long and healthy life, it’s vital to focus on supporting your immune system on an ongoing basis. One of the best ways to do this is with natural, powerful immune system boosters contained in camel milk. In the serum of camel milk, a completely new class of immunoglobulin has been discovered, which is fundamentally different from all other previously known antibody classes. Cameloid Immunoglobulins (only found in camels, llamas, alpacas, vicunas, and guanacos) are used by the immune system for easy and quick targeting of foreign substances. This is one of the ways camel milk strengthens and supports the gastrointestinal immune system. Learn more about Camel Milk Learn more about Immunity and a Healthy Immune System If you would like to receive the MCVitamins.com Weekly Newsletter,  Please Sign up by clicking here:  Newsletter Signup We take privacy and security seriously, read about it here Search this Website  MCVitamins is an affiliate of Qgenics Home    Health Tips   Health Concerns   Site Index   Glossary © 2000-2021  MCVitamins.com .  All Rights Reserved. Reproduction of this website in full or in part is prohibited without the express written permission of MCVitamins.com We have used our best judgment in compiling this information. The Food and Drug Administration may not have evaluated the information presented. Any reference to a specific product is for your information only and is not intended to diagnose, treat, cure, or prevent any disease   Hits: 131
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Klikfurniture Lab 2005 Lemari Anak Princess By Olympic Klikfurniture Lab 2005 Lemari Anak Princess By Olympic Klikfurniture Lab 2005 Lemari Anak Princess By Olympic This process involves the release of a molecule known as high-mobility group box 1 protein (HMGB1), which triggers a chronic inflammatory reaction that causes tumor growth Well, there's still some hope; once I've got the money together to pay off my parents' debt to him - another five or six years I suppose - that's definitely what I'll do Doing business like this takes much more effort than doing your own business at home, and on top of that there's the curse of travelling, worries about making train connections, bad and irregular food, contact with different people all the time so that you can never get to know anyone or become friendly with them Malignant mesothelioma has three known varieties They are malignant pleural mesothelioma, malignant pericardial mesothelioma, and malignant peritoneal mesothelioma What is the Typical Age at Diagnosis?The first diagnosis of mesothelioma typically occurs in men and women between the ages of 50 and 70 years Also of note is that mesothelioma is much less common among African Americans than in Caucasians, the reasons for which researchers are still investigating Peritoneal mesothelioma occurs in the peritoneum, the abdominal cavity wall However hard he threw himself onto his right, he always rolled back to where he was A collection of textile samples lay spread out on the table - Samsa was a travelling salesman - and above it there hung a picture that he had recently cut out of an illustrated magazine and housed in a nice, gilded frame Pleural mesothelioma, because it is more common than other varieties of the malignancy, has had more research invested in it Also, patients may be eligible for compensation if they were wrongfully exposed These may include imaging scans, such as computer topography or magnetic resonance imaging Malignant MesotheliomaGet This Image For Your SiteWhat Causes Malignant Mesothelioma?Mesothelioma is known only to be caused by asbestos exposure It showed a lady fitted out with a fur hat and fur boa who sat upright, raising a heavy fur muff that covered the whole of her lower arm towards the viewer One morning, when Gregor Samsa woke from troubled dreams, he found himself transformed in his bed into a horrible vermin In many cases, those diagnosed with mesothelioma are not those who were directly exposed to asbestos in a jobsite setting The study reported that asbestos damages cells through a process researchers dubbed programmed cell necrosis Klikfurniture Lab 2005 Lemari Anak Princess By Olympic Image Gallery Klikfurniture Lab 2005 Lemari Anak Princess By Olympic It usually takes long-term exposure to put someone at risk, asbestos is highly toxic Medical TimelineHistorical timeline containing important facts and developments related to the manufacture and use of asbestos and documented cases of mesothelioma cancer and other asbestos related diseases Gregor then turned to look out the window at the dull weather Had the alarm clock not rung? He could see from the bed that it had been set for four o'clock as it should have been; it certainly must have rung His many legs, pitifully thin compared with the size of the rest of him, waved about helplessly as he looked Mesothelioma VaccineRecent studies by researchers in the Netherlands have found promising results in preventative therapies for mesothelioma Klikfurniture Lab 2005 Lemari Anak Princess By Olympic xKlikfurniture Lab 2005 Lemari Anak Princess By Olympic For instance, extrapleural pneumonectomy is now possible in many pleural mesothelioma patients who are deemed eligible for aggressive surgery If a previous job or project exposed you to asbestos, an experienced doctor can schedule the appropriate screenings to detect mesothelioma or another asbestos-related disease Effective treatments are available to ease symptoms and improve your prognosis Although asbestos use declined dramatically in recent decades in this country, the incidence of mesothelioma remains steady "How about if I sleep a little bit longer and forget all this nonsense", he thought, but that was something he was unable to do because he was used to sleeping on his right, and in his present state couldn't get into that position The disease can take anywhere from 20 to 50 years after exposure to asbestos before it shows obvious symptoms and an oncologist can make a definitive diagnosis Among these are mesothelioma chemotherapy, radiation therapy, and surgical resection His boss would certainly come round with the doctor from the medical insurance company, accuse his parents of having a lazy son, and accept the doctor's recommendation not to make any claim as the doctor believed that no-one was ever ill but that many were workshy I should be incapable of drawing a single stroke at the present moment; and yet I feel that I never was a greater artist than now Klikfurniture Lab 2005 Lemari Anak Princess By Olympic "What's happened to me? " he thought Like pleural mesothelioma, peritoneal mesothelioma is known only to be caused by exposure to asbestos How is Malignant Mesothelioma diagnosed?Malignant Mesothelioma will typically be suspected if the patient complains of chest pain, difficulty breathing, shortness of breath, chronic cough, or difficulty swallowing Asbestos is a nature, yet toxic mineral that was used commonly in heavy industry But who knows, maybe that would be the best thing for me Adults who have asbestos exposure history are typically those most at risk for the development of malignant mesothelioma If diagnosed early enough, however, survival may potentially extend over many years Doing business like this takes much more effort than doing your own business at home, and on top of that there's the curse of travelling, worries about making train connections, bad and irregular food, contact with different people all the time so that you can never get to know anyone or become friendly with them This process involves the release of a molecule known as high-mobility group box 1 protein (HMGB1), which triggers a chronic inflammatory reaction that causes tumor growth Well, there's still some hope; once I've got the money together to pay off my parents' debt to him - another five or six years I suppose - that's definitely what I'll do Patients of malignant mesothelioma or any other asbestos related health complications should consult their physician regarding the many mesothelioma treatment options that are available Info: You are viewing Klikfurniture Lab 2005 Lemari Anak Princess By Olympic,is one of the post that listed in the . Dont forget to browse another image in the related post below or you can browse our other interesting images that we have. Please also read our Privacy Policy and DCMA for the copyright of the images. Using 13.21MB Memory | Posted on HD Desktop Wallpaper at Sat,Dec 2013 06:12 by HD Desktop Wallpaper Ratings: 8.9/10 from 491 users Thanks To Para Pengunjung dan Pemasang Iklan, juga Bing Images Copyright © 2011 HD Desktop Wallpaper, All trademarks are the property of the respective trademark owners.
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Dr Rhonda Patrick has recently been discussing the benefits of curcumin. In this article we will look at the products she uses + the scientific studies and information behind curcumin’s benefits. Let’s begin with the curcumin/turmeric product that Rhonda has been using: • Curcumin Phytosome (Meriva) – by Thorne, Jarrow or NOW (the tweet below was from 2016, in 2019 Rhonda generally uses Thorne brand, where possible, for supplements) The difference between a curcumin phytosome supplement, like the above, and a “regular” curcumin supplement is bioavailability. In a human study comparing Meriva absorption to regular curcumin, Meriva was shown to have a 18-fold higher absorption rate than standard curcumin1. The phytosome part of the name means that a fat based wrapper (in this case from sunflower oil) is formed around the curcumin chemical. I couldn’t find the exact mechanism of action that leads to greater uptake by our cells, which would be interesting to know. What is Curcumin? Curcumin vs Turmeric vs Cumin Before we go any further, lets just clarify what we mean by curcumin. Curcumin comes from the turmeric root, and is the bright yellow chemical that has a propensity to dye everything it comes into contact with (it’s what gives curries their yellow color). Not to be confused with cumin, which is a different plant entirely. Cumin, is also used a lot in Indian cooking, and literally contains some of the same letters as curcumin. Curcumin is one of three curcuminoids that come from turmeric, the other two have really long names (demethoxycurcumin (DMC) and bisdemethoxycurcumin (BDMC)). These other curcuminoids also exhibit anti-inflammatory properties2, so are useful. Fortunately they get extracted at the same time as curcumin, so if you’re consuming a curcumin extract, it will contain DMC & BDMC also. In the approximate ratio of 77% curcumin, 17% demethoxycurcumin and 3% bisdemothoxycurcumin3.   The turmeric root on the left and its dry, powdered version on the right. Powdered turmeric is not the same as curcumin extract. Difference between Turmeric and a “Curcumin Supplement”? When you’re consuming a curcumin supplement, it typically means that the (approximately) 5% of curcumin present in turmeric has been extracted using a solvent4. This way, the powder you end up with is in the range of 95% curcumin, rather than ~5% curcumin if it was a turmeric powder. Curcumin Benefits One of the key mechanisms of action behind curcumin is its ability to reduce chronic inflammation. Inflammation itself is not a bad thing, in fact its an essential survival mechanism that helps our bodies fight illness and heal injuries. Essentially what we mean by this is, when there’s an infection or physical trauma, we want inflammatory signals to communicated, such that the immune system, and other key systems can take action. However if there’s chronic inflammation, or inflammation in the wrong places, we have a problem. Proteins within our body called cytokines control cell signalling to stimulate or reduce inflammation. When this system has issues regulating itself correctly, it results in unnecessary inflammation of the body. Curcumin has been shown to regulate the release of pro-inflammatory cytokines. Examples of this include: • Curcumin downregulates the inflammatory cytokines CXCL1 and -2 in breast cancer cells via NFκB (source) • Curcuminoids inhibit activity of steroidogenic pathways CYP17A1 and CYP19A, indicating potential anti-carcinogenic effects in case of prostate and breast cancer (source) • Curcumin Blocks Cytokine-Mediated NF-κB Activation and Proinflammatory Gene Expression by Inhibiting Inhibitory Factor I-κB Kinase Activity (source) • Epigenetic regulation of high glucose-induced proinflammatory cytokine production in monocytes by curcumin (source) Whilst the above is a “core mechanism” behind why curcumin is beneficial, there may others. Lets now look at some of the practical uses behind curcumin: Pain Relief (Including for Arthritis) People with arthritis are often battling chronic, day to day pain, and thus are among the most frequent users5 of non steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen, aspirin and indometacin. The major risk with chronic use of NSAIDs is gastrointestinal complications – ranging from regurgitation/heartburn to bleeds and ulcers6. Therefore, a substance that can reduce pain, with less side effects than NSAIDs is highly desirable. Below Rhonda cites studies where curcumin supplements were comparable to NSAIDs. If you click the pictures they will take you directly to her tweet, which includes the study links. Improved Memory & Attention Curcumin appears to help reduce the cognitive decline associated with aging. Reducing Depression / Anxiety Curcumin appears to have benefits in reducing depression. Summary • For the most potent effects, we want to be taking curcumin extract, rather than turmeric powder/root • To maximise bioavailability, we want to be consuming a Meriva or Theracurmin version of curcumin. See Post Sources Below: 1. Comparative absorption of a standardized curcuminoid mixture and its lecithin formulation – 2011 – https://www.ncbi.nlm.nih.gov/pubmed/21413691/ 2. Curcumin, demethoxycurcumin, bisdemethoxycurcumin, tetrahydrocurcumin and turmerones differentially regulate anti-inflammatory and anti-proliferative responses through a ROS-independent mechanism – https://academic.oup.com/carcin/article/28/8/1765/2526767 3. Effects of curcumin, demethoxycurcumin, bisdemethoxycurcumin and tetrahydrocurcumin on 12-O-tetradecanoylphorbol-13-acetateinduced tumor promotion – https://academic.oup.com/carcin/article-abstract/16/10/2493/411526 4. Extraction of curcumin from turmeric roots – https://www.researchgate.net/file.PostFileLoader.html?id=54246744d5a3f2ab2f8b469e&assetKey=AS%3A273559857893418%401442233160841 5. NSAID gastropathy: the second most deadly rheumatic disease? Epidemiology and risk appraisal – http://europepmc.org/abstract/med/2038014 6. Nonsteroidal anti-inflammatory drugs and upper and lower gastrointestinal mucosal damage – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3890944/ Alex Posted by Alex 6 Comments 1. Avatar I dislocated my shoulder and am looking for ways to aid recovery. I’m not asking for medical advice, but would the anti-inflammatory effect of curcumin interfere with the “good” inflammatory responses going on in my body right now? I’m curious as to how the balance is struck between allowing the body to have an inflammatory response and taking anti-inflammatory. Reply 1. Alex Hi Dave, thanks for the comment. I delayed answering this until I could sit down and do some more research. Unfortunately I won’t have time for the foreseeable future, so thought it best to reply briefly now. As you mention, inflammation is absolutely essential to the body, both in dealing with outside invaders, and in repairing damage to the body. So we do want it. So how does curcumin play into that picture, in particular with regards to injuries? The honest answer is that I don’t know. I can see solid rationale for using it for dealing with unwanted inflammation that are the result of daily lifestyle factors. There’s also increasing evidence for using curcumin as a method of pain reduction (for example women use it for PMS pain). But beyond that, I’m not too sure. For example, even if we thought about using curcumin for pain reduction in your shoulder injury – that could be problematic. Reduce the pain too much, and you could over use the joint, thus slowing its healing process. So the pain in this case is useful to a point. Reply 2. Avatar Ignatius Turchi August 2, 2018 at 1:54 pm I read that Theracurmin is the most bioavailable form of curcumin. I am now taking theracurmin and BCM-95 curcumin/ ginger from Life Extension and I am getting some good results from the combination. Reply 1. Alex Hi Ignatius, thanks for the message. Glad to hear the curcuminoids are helping. How are you measuring your results? With regards to theracurmin, it’s definitely right up there in potency. List in order of strength, low to high is: – Turmeric – Curcumin Extract – Curcumin Phytosome & Theracurmin There hasn’t yet been a randomized control trial with Curcumin Phytosome vs Theracurmin, so it’s impossible to say which is better… Yet. Reply 3. Avatar Sarah Cummings July 15, 2018 at 3:03 pm This is amazing! I’ve been using turmeric for health reasons. Looks like I’ll be considering curcumin supplement. Thanks! Reply 1. Alex Hi Sarah! Thanks for the comment, hope some of the info was useful. Would be interesting to see if a curcumin extract provides greater benefit than the turmeric you’re using currently. I’ve learnt through trial and error that just because something has good results in scientific studies, doesn’t guarantee it works for me (n=1 is always highly variable). Btw, nice niche site you’ve built around sleep 🙂 Reply Leave a reply Your email address will not be published. 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Why Flamingos Don’t Get Hip Fractures Osteoporosis is one of the biggest issues plaguing the mature and elderly population today. One of the biggest risks that occurs alongside osteoporosis is a fall that may result in a dangerous, possibly life-threatening fracture. Fractures of the femur are among the most dangerous. The femur, or thigh bone, is one of the strongest and… Gastric Bypass Surgery And The Digestive System We tend to use the term gastric bypass surgery somewhat loosely these days and include both true bypass operations such as the Roux-En-Y and popular and less radical forms of weight loss surgery such as gastric banding. While both have a role to play in curing the problem of obesity, bypass surgery takes full advantage… Two Common Horse Ailments Digestive Problems Many horses suffer from stress related digestive problems. Studies show over 50% of show and race horses have ulcers in their GI tract. When the proper acid-base balance of a horse’s digestive tract is disturbed, gastric and/or intestinal ulcers may develop. This increased intestinal permeability creates a pro-inflammatory state that may lead to… Coding for Lower Gastrointestinal Endoscopic Procedures Lower gastrointestinal endoscopy claims have to show medical necessity, if they are to be reimbursed without fail. This means that the appropriate ICD-9 codes will have to be reported. Usually, Medicare carrier websites publish these codes for GI procedures. Therefore when coding for lower GI procedures, payer specific coding becomes very important. Lower Gastrointestinal Endoscopic… Fibroid Treatment Without Surgery Fibroid treatment without surgery can take many forms. Some women may use drug treatment, such as anti-inflammatories, the contraceptive pill, progestins, androgen therapy or hormonal therapy. Some will give symptomatic relief whereas others may reduce the size of fibroids. However, it is important to understand that these treatments are only ever intended to be temporary… Cure for Ovarian Cysts Most ovarian cysts are benign and harmless however you might desire to check a cure for ovarian cysts if you have been diagnosed. These cysts are collections of fluid with thin walls, and they may possibly be as large as cantaloupes or as tiny as peas. Pain and bleeding are among the issues that you… Over the Counter Thrush Treatment Also, mouth yeast infection can also be caused by wearing dentures and eating foods like cheese, sugar, beer, and mushroom. There are many over the counter thrush treatment you could purchase if you are suffering from the condition. Creams & Mouthwash Certainly, anti-fungal creams could help eliminate the type of fungus that causes thrush. However,… Hepatitis C – What You Should Know What is hepatitis C? First, hepatitis as defined in most dictionaries and medical literature is simply “inflammation of the liver.” Inflammation is, again from the dictionary, “localized heat, redness, swelling and pain as the result of irritation, injury or infection.” In other words inflammation is an abnormal or diseased state of the body. In the… Liver Diseases: Effects of Alcohol Three out of four liver diseases is completely avoidable. Among the effects of alcohol are major and life-threatening liver diseases. Nearly fifty percent of those who undergo or receive liver transplant are frequent alcohol drinkers while ten percent of them are severe alcoholics. A few major effects of alcohol on the liver are the following:… Avoid Surgery For Kidney Stones What is renal calculus or kidney stone? Renal calculus, in simple terms, kidney stone, consists of aggregates of crystals and small amounts of proteins and glycoproteins, which may damage kidney. But there genesis is poorly understood till date. Crystalline component usually consists of calcium oxalate(more than 50% of cases),calcium phosphate(10%),magnesium ammonium phosphate(10%) or rarely cystine… How to Clean Vomit Off Spirit Sleep Mattresses It’s a problem that not many people think about, until it happens to them. What do you do if your child or pet vomits on your mattress? And the even better question: what if that mattress is all memory foam, like a Spirit Sleep brand mattress? 1. First, remove the cover if possible, and wash… Clostridium In Dogs – Symptoms and Treatment The genus Clostridium is a group of anaerobic bacteria (they can thrive in conditions where oxygen is not present) which have been linked to several important diseases in dogs. Two of the most common clostridial infections in dogs are caused by Clostridium perfringens and Clostridium difficile. Some healthy dogs have been found to harbor C.…
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8 Minutes October 17, 2021 by THE BALANCE Fact checked Stress and anxiety are conditions of overlapping nature. People often confuse these symptoms for each other because they share similar symptoms. However, what we need to know is that stress and anxiety are distinct conditions and can impact the life of a sufferer in various ways. Learn more about the differences and similarities between stress and anxiety symptoms below along with the management and treatment options. Many people mistakenly believe that stress and anxiety are the same things. However, despite their near proximity, these intense emotions are vastly different. Insomnia from Anxiety Stress is a natural reaction to challenge. As we prepare to act, changes in brain chemistry cause our hearts to beat quicker and our palms to sweat. We may be jittery, furious, or frustrated. Stress also has positive outcomes such as pumping a person to meet the challenges. For example, we if continue with the example mentioned previously. Stress for the assignment may motivate the student to make an outstanding assignment and get applause from the teacher in front of the entire class.  Anxiety is a stress response. It occurs when people believe they are unable of dealing with the pressure they are under. They are concerned and terrified due to their lack of control. Stress and anxiety are the body’s natural responses to challenges. However, when your stress or anxiety is getting out of hand and began to significantly impact your daily life functioning that might be the sign that you are suffering from chronic stress and anxiety. Chronic anxiety is further divided into several types such as generalized anxiety disorder(GAD) or panic attacks. Below are the common signs of stress and anxiety.  Symptoms of Anxiety Psychological symptoms • Nervousness, restlessness, or being tense • Feelings of danger, panic, or dread • Difficulty focusing or thinking clearly about anything other than the thing you’re worried about • A strong desire to avoid the things that trigger your anxiety • Obsessions about certain ideas, a sign of obsessive-compulsive disorder (OCD) • Performing certain behaviors over and over again • Anxiety surrounding a particular life event or experience that has occurred in the past, especially indicative of post-traumatic stress disorder (PTSD) Physical symptoms • Rapid heart rate • Rapid breathing, or hyperventilation • Increased or heavy sweating • Trembling or muscle twitching • Weakness and lethargy • Insomnia • Digestive or gastrointestinal problems, such as gas, constipation, or diarrhea Symptoms of Stress Cognitive symptoms • Memory problems • Concentration Problems • Poor judgment • Focusing more on negative aspects • Anxious or racing thoughts • Worrying all the time Emotional symptoms • Depression or general sadness • Anxiety and agitation • Moodiness, irritability, or anger • Feeling overwhelmed • Loneliness and isolation Physical symptoms • Aches and pains • Diarrhea or constipation • Nausea, dizziness • Chest pain, rapid heart rate • Loss of sex drive • Frequent colds or flu • Behavioral symptoms: • Eating more or less • Sleeping too much or too little • Withdrawing from others • Procrastinating or neglecting responsibilities • Using alcohol, cigarettes, or drugs to relax • Nervous habits (such as nail-biting, pacing) Most people use the terms stress and anxiety interchangeably as if they are the same things. However, they are not the same and we are going to explore the differences among anxiety and stress below 1. Stress is the response to anything happening in your life. It’s rational and can be motivational to increase performance. Anxiety is something that no one should have to live with on daily basis. Anxiety can make you nervous and decrease your performance. 2. Stress is challenging but often manageable. Whereas, anxiety can start from stress and may go out of your control. 3. Stress is mostly short-term and anxiety on the other can linger. 4. Stress is in response to a recognized trigger and anxiety may not have an identifiable trigger. 5. Certain events, such as dealing with arrangements for the loss of a loved one, are difficult for everyone. Anxiety is a more exaggerated reaction. It’s possible that the worry and distress you’re experiencing in a specific scenario is anxiety rather than stress if it’s uncommon, excessive, or out of proportion to other people’s reactions. Anxiety or stress causes you to do more than worry. It can also cause or exacerbate other mental and physical problems, such as: • Depression or other mental health illnesses (which frequently coexist with anxiety disorders) • Misuse of drugs • Sleeping problems (insomnia) • Problems with the intestines or bowels • Chronic pain and headaches • Problems with social isolation, school or work performance, and overall quality of life • Suicide Natural Remedies Natural cures are generally considered safe to employ in conjunction with more traditional medical treatments. However, dietary changes and some natural supplements might alter the way antianxiety drugs work, so it’s important to speak with a doctor before using these remedies. Other natural therapies may also be recommended by the doctor. Relaxation techniques In response to anxiety or stress, some people unconsciously tense their muscles and clench their jaws. Relaxation techniques that are progressive in nature can be beneficial. Can Menopause Cause Anxiety Start with the toes and work your way up to the shoulders and jaw by resting in a comfortable position and slowly tightening and relaxing each muscle group. Meditation Meditation can help to calm racing thoughts, making stress and anxiety easier to manage. A variety of meditation techniques, including mindfulness and yoga-based meditation, may be beneficial. In therapy, mindfulness-based meditation is becoming increasingly popular. According to a 2010 meta-analytic evaluation, it can be quite useful for persons with mood and anxiety problems. Writing Finding a means to communicate your worry can help you feel more in control. According to several studies, journaling and other forms of writing can help people cope with anxiety better. Creative writing can help children and teens cope with anxiety or stress. Supplements made from herbs Many herbal products, like herbal teas, claim to help with anxiety or stress. However, there is little scientific data to back up these assertions. It’s critical to consult with a doctor who is familiar with herbal supplements and their potential medicine interactions. Therapy and counseling Anxiety and stress are commonly treated with psychological counseling and therapy. Psychotherapy, such as cognitive-behavioral therapy (CBT), or a combination of treatment and counseling may be used. CBT tries to identify and change negative thought patterns that can lead to anxiety and troubling feelings, as well as limit erroneous thinking and adjust the scale and severity of stressor reactions. These aids people in controlling how their bodies and minds react to various triggers. Another treatment option is psychotherapy, which is speaking with a skilled mental health expert and addressing the source of an anxiety disorder. Sessions could focus on anxiety triggers and possible coping techniques. Medications Anxiety or stress problem treatment can be aided by a variety of medications. Other medications may aid in the management of some physical and mental problems. These are some of them: Tricyclics are a class of medications that have shown to be effective in treating most anxiety disorders (such as OCD). Drowsiness, dizziness, and weight gain are all documented side effects of these medications. Imipramine and clomipramine are two examples of tricyclics. Benzodiazepines: These are only available with a prescription and are highly addictive, thus they are rarely used as a first-line treatment. Diazepam, also known as Valium, is a popular benzodiazepine used to treat anxiety. Mania vs Hypomania Antidepressants: While antidepressants are most typically used to treat depression, they are also used to treat a variety of anxiety disorders. One alternative is serotonin reuptake inhibitors (SSRIs), which have fewer negative effects than previous antidepressants. At the start of treatment, they’re still likely to cause nausea and sexual dysfunction. Fluoxetine and citalopram are two examples. Other anxiety-relieving drugs include: • monoamine oxidase inhibitors beta-blockers (MAOIs) • buspirone Withdrawal symptoms, such as brain zaps, can occur when you stop taking some medications, particularly antidepressants. These are sharp jolts in the head that feel like electric shocks. After a lengthy period of taking anti-depressants, someone who wants to change their approach to managing anxiety disorders should talk to their doctor about the best way to transition away from medicines. If you have any severe, negative, or unexpected side effects after taking any prescription medications, notify your doctor right once. Although it’s impossible to foretell what will lead someone to get a stress or anxiety disorder, you can take efforts to lessen the severity of symptoms if you’re worried. Get aid as soon as possible. If you wait, anxiety, like many other mental health issues, can become more difficult to cure. Continue to be active. Participate in things that make you feel good about yourself and that you enjoy. Take pleasure in social interaction and caring relationships, which can help you relax. FAQs
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Can You Have an Allergic Reaction to Fillers? Can You Become Puffy on Face and Around Eyes? can you have an allergic reaction to any fillers juverden restylane ex. puffines of face and under eyes and will this be permantly? Doctor Answers 3 Hyaluronic Acid fillers (Juvederm and Restylane) can cause temporary puffiness around the eyes Allergic reactions to hyaluronic fillers are rare. Hyaluronic acid fillers are what is called, hydrophilic. That means they absorb water from the surrounding tissue. Different people have different reactions. This is often more exaggerated around the eyes. Because of the way these products are made, Restylane more commonly has more initial swelling and fluid retention. Juvederm does't have as much initial swelling, but around the eyes swelling can occur for a longer period of time. If the swelling lasts too long and is unsightly, the hyaluronic acid filler can be dissolved by an enzyme called Hyaluronidase. New York Facial Plastic Surgeon 5.0 out of 5 stars 55 reviews Allergic Reaction to Restylane or Juvederm Both Juvederm and Restylane are made from a substance known as hyaluronic acid (HA), which is a form of 'tissue glue" found inside and outside human cells. Both fillers are free of antigenic tags, which could lead to an allergic response. Therefore, a true allergic reaction to a HA filler is highly unlikely.  Periorbital swelling after injection to the tear troughs is a known side effect of injecting the area under the eyes.  Stephen Prendiville, MD Fort Myers Facial Plastic Surgeon 5.0 out of 5 stars 51 reviews Puffiness under your eyes after an Injectable Filler treatment with Juvederm will slowly dissipate. Hyaluronic Acid products like Restylane and Juvederm, tend to attract and hold onto water after it's injected. My personal preference for lower eyelid rejuvenation is Silikon-1000, but I've used Juvederm on several occasions and noted mild overcorrection several days after injection. There was no redness, pain or itchiness. These patients had complete resolution, and resorbtion of Juvederm over the ensuing 6-12 months. I hope this is helpful for you. Eric M. Joseph, MD West Orange Facial Plastic Surgeon 5.0 out of 5 stars 317 reviews You might also like... These answers are for educational purposes and should not be relied upon as a substitute for medical advice you may receive from your physician. If you have a medical emergency, please call 911. These answers do not constitute or initiate a patient/doctor relationship.
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  Home » Dietary Supplements » Bio Supplements Selenium: Controversial, but Critical With the atomic number 34 and an atomic mass of 78.96, this chemical element rarely occurs in its elemental state in nature. This nonmetal, chemically related to tellurium and sulfur, is known as Selenium. selenium Selenium means “moon” in Greek and was discovered by Jons Jakob Berzelius in 1817. Berzelius found the element was a byproduct of sulphuric acid production. Since then, the element has acquired several uses including glassmaking, pigment production, rubber compounding, steel alloying, brass plumbing and even as a material in the drums of laser copiers and printers. However, the most recent and exciting application is in the field of health and nutritional supplementation. In 1957, selenium began being recognized as an essential micronutrient in all mammalian life forms due to its role in cellular function. Selenium, however, is also vital for some plant species such as astragalus, false goldenweed, prince’s plume and woody asters. It forms the active center of the anti-oxidizing glutathione peroxidase and thioredoxin reductase as well as three known deiodinase enzymes, which help the thyroid gland to function correctly. More recent research suggest s that selenium may play an important hand in human cancer prevention. Maintaining selenium levels can, of course, be easy through supplementation. In addition, by eating foods such as nuts (most notably Brazil nuts), cereals, eggs, fish, lobster and crab, one can get a good amount of dietary selenium. Therefore, selenium deficiency is fairly rare unless one has undergone malnourishment, intestinal malfunction, or is reaching more than 90 years of age. Selenium toxicity has been a hot-button issue of late. Like most things in life, moderation is the key here. Excess selenium can lead to selenosis – a condition marked by hair loss, fatigue, gastrointestinal distress and an odd garlic odor on the breath. More severe cases of selenosis can result in cirrhosis of the liver or pulmonary edema. The Tolerable Upper Intake Level of selenium is 400 micrograms per day, but the safe limit is probably more like 800 micrograms per day. It is unlikely that the health benefits of selenium will be outweighed by the risks of toxicity when simply consuming the micronutrient through diet or dietary supplement. It remains an extremely valuable element. The information supplied in this article is not to be considered as medical advice and is for educational purposes only.
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Show simple item record dc.contributor.authorBrown, H. dc.contributor.authorPaul, L. dc.contributor.authorHislop, Jane dc.date.accessioned2018-06-29T21:44:43Z dc.date.available2018-06-29T21:44:43Z dc.date.issued2004-12 dc.identifierER2688 dc.identifier.citationBrown, H., Paul, L. & Hislop, J. (2004) Erector spinae activity during three methods of lifting a baby car seat in postnatal women and matched controls, Physiotherapy, vol. 90, , pp. 204-209, dc.identifier.issn0031-9406 dc.identifier.urihttp://dx.doi.org/10.1016/j.physio.2004.06.003 dc.identifier.urihttps://eresearch.qmu.ac.uk/handle/20.500.12289/2688 dc.description.abstractObjectives The lifting of baby car seats could be a contributing factor in persistent back pain experienced by many postnatal women. The purpose of this study was to compare the activity of the erector spinae muscles of postnatal women and a control group during three methods of lifting a baby car seat. Design A repeated measures design was used to compare three methods of lifting a baby car seat: symmetrical, asymmetrical and cradling. Setting Ante-natal clinic, Victoria Mansionhouse Unit, Glasgow. Participants Convenience sample of nine postnatal mothers and nine matched controls. Main outcome measure Surface electromyography was used to record erector spinae muscle activity. Results Independent two-sample t-tests revealed no statistically significant difference in resting erector spinae activity between the two groups. Analysis of covariance suggested a significant difference between the two groups for both sides and between the different lifting methods. For example, for symmetrical lifting, activity in the right erector spinae was 353 mV [95% confidence interval (CI) 253-453 mV] in the postnatal group and 458 mV (95% CI 339-577 mV) in the control group. For the cradling lift, these values rose to 443 mV (95% CI 340-546 mV) for the postnatal group and 568 mV (95% CI 452-684 mV) for the control group. Asymmetrical lifting evoked the least erector spinae activity, and the cradling method evoked the most activity. However, electromyographic activity was most evenly distributed during symmetrical lifting. Conclusions Symmetrical lifting is recommended as the preferred method of lifting baby car seats due to the even distribution of load between left and right erector spinae activity. Further research is required to investigate the activation of other muscle groups and to discriminate between the lifting and the stabilising phases of the lifting manoeuvre. dc.format.extent204-209 dc.publisherElsevier dc.relation.ispartofPhysiotherapy dc.subjectErector spinae dc.subjectLifting dc.subjectBaby car seat dc.subjectPostnatal dc.titleErector spinae activity during three methods of lifting a baby car seat in postnatal women and matched controls dc.typearticle dcterms.accessRightsrestricted dc.description.facultysch_phy dc.description.volume90 dc.description.ispublishedpub dc.description.eprintid2688 rioxxterms.typearticle qmu.authorHislop, Jane dc.description.statuspub dc.description.number4  Files in this item Thumbnail This item appears in the following Collection(s) Show simple item record
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Search Results You are looking at 1 - 1 of 1 items for • Author or Editor: Rita N. Azzam x Clear All Modify Search Restricted access Andrew A. Zalewski, Yoshiaki Kadota, Nabil A. Azzam and Rita N. Azzam ✓ The authors investigate whether there are any permeability changes in the endoneurial blood-nerve barrier and the perineurium-nerve barrier of surviving nerve allografts. In a normal nerve, the blood-nerve barrier regulates the passage of substances from endoneurial blood vessels into the endoneurium, whereas the perineurium-nerve barrier protects the endoneurium from agents that escape from permeable epineurial vessels and accumulate around the nerve. Nerves from ACI rats were transplanted into immunologically deficient nude rats or normal Fischer rats immunosuppressed with cyclosporin A. None of the nerve allografts was rejected. The blood-nerve barrier of nerve allografts at 2 and 6 weeks postoperatively was permeable to intravenously injected horseradish peroxidase, which spread into endoneurial tissue. Electron microscopy revealed that horseradish peroxidase escaped from endoneurial vessels through intercellular junctions between endothelial cells. At 24 weeks, the blood-nerve barrier of nerve allografts had recovered and the endoneurial vessels, like those in normal nerves, were impermeable to horseradish peroxidase. The perineurium-nerve barrier of nerve allografts remained impermeable to horseradish peroxidase at all times. Axons were grouped into numerous minifascicles at nerve anastomosis zones at 24 weeks. Each nerve fascicle was surrounded by an impermeable perineurium. These results demonstrate that regenerated axons in long-term surviving nerve allografts and at anastomosis zones are protected by permeability barriers. It is concluded that permeability barriers of nerve allografts are not permanently altered by a foreign environment (grafts to nude rats) even when immunosuppression with cyclosporin A is required to prevent allograft rejection (grafts to Fischer rats).
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celiac rickets ce·li·ac rick·ets arrested growth and osseous deformities associated with defective absorption of fat and calcium in celiac disease. ce·li·ac rick·ets (sēlē-ak rikĕts) Arrested growth and osseous deformities associated with defective absorption of fat and calcium in celiac disease. Patient discussion about celiac rickets Q. Is celiac genetic? I have one son with celiac disease from my first marriage and me second wife is now pregnant,I was wondering what are the chances for this soon to be born daughter of mine to have celiac as well- if I maybe carry the genetic flaw and is there a way to find out? A. Celiac disease is a very common illness (about 1 in a 100 people suffer from it in different levels), and it is known to have a strong genetic connection. However, there is not one specific mutation that you can get genetic testing to see if you are carrying it. Your soon to be born daughter will have a higher chance than the regular population to suffer from the disease, but it does not necessarily mean she will. Q. How do you diagnose celiac? My daughter is 3 years old and is constantly vomiting, has diarrhea and stomach aches. Could this be celiac? A. This could in fact be celiac. The initial step in screening should include: IgA endomysial antibodies (EMA), IgA tissue transglutaminase (tTG), IgG tissue transglutaminase and Total IgA antibodies. The patients with positive antibody tests, and those with an IgA deficiency, should have a small bowel biopsy to confirm the diagnosis and assess the degree of damage, which is performed endoscopically (looking inside the body by inserting a tube into it). Q. Is FTT a symptom of celiac? My 1.5 year old son has FTT (failure to thrive) and stomach aches. What could be causing it? A. Failure to thrive lacks a precise definition, in part because it describes a condition rather than a specific disease. Children who fail to thrive don't receive or are unable to take in, retain, or utilize the calories needed to gain weight and grow as expected. FTT can be caused from many different things: social factors, conditions involving the gastrointestinal system like gastroesophageal reflux, chronic diarrhea, cystic fibrosis, chronic liver disease, and celiac disease. From a chronic illness or medical disorder, an intolerance of milk protein, infections or metabolic disorders. More discussions about celiac rickets
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Wednesday, June 15, 2022 HomePopularCan You Get Free Prescriptions If You Have Asthma Can You Get Free Prescriptions If You Have Asthma How To Handle Asthma In The Winter How does asthma work? – Christopher E. Gaw What can you do to ease symptoms if winter weather affects your asthma? • Limit outdoor exercise. Work out at home or in the gym. • Wear a scarf and use it to warm the air youre breathing. • Use humidifiers in your home. Keep them free of mold. • Wash hands frequently. Washing with soap for 20 seconds or using hand sanitizer while out can keep winter illnesses at bay. • Be conscious of your hands. Keep them away from your face and eyes to avoid spreading germs. • Get the flu vaccine in early fall. • Have an Asthma Action Plan in place. Know what to do in case of a flare-up. • Limit time with pets if youre allergic to pet dander. Keep your bedroom pet-free. • If dust mites and mold trigger your symptoms, keep your home cool and dry to inhibit their growth. • Clean and replace filters in your heating and cooling air ducts. Make sure filters are cleaned at the start of every season. Check periodically to keep indoor air quality optimal. How Do I Get A Free Prescription You are likely eligible to receive prescriptions from the Free Clinic Pharmacy if: • You are a current Charlottesville Free Clinic patient • You have given us proof of income and current tax holdings Call the pharmacy to determine your eligibility: . You must be a Free Clinic patient to get a prescription. Learn more about our medical clinic and our dental clinic to request an appointment. Manufacturer Copay Assistance Cards Many name brand drugs manufacturers have created programs to entice patients to try and stay on their medications even if their copays through their insurance is very high. The programs work like a secondary insurance that pays for most or all of the remaining copay after your insurance is applied. These programs are drug specific and can be found by visiting the drugs website online or googling the drugs name with the phrase copay card. Also Check: Breathing Treatments Side Effects Vaccine Distribution In Canada As part of the Canadian Thoracic Societys COVID-19 Respiratory Roundtable panel representing Canadians living with lung disease, Asthma Canada signed a joint statement titled Prioritization of Canadians with Lung Disease in COVID-19 Vaccination Rollout. Alongside other lung health organizations, Asthma Canada is urging federal, provincial and territorial governments to prioritize people living with lung disease who are at higher risk for more serious COVID-19 complications in the vaccination rollout. From Canadians living with a lung disease such as asthma, chronic obstructive pulmonary disease , cystic fibrosis, lung cancer, pulmonary fibrosis, pulmonary hypertension, and pre- and post-lung transplant, there is widespread concern regarding when in the vaccine rollout in the provinces and territories they will have the opportunity to receive the vaccine. We will continue to advocate for our community on this subject and will share more information as it becomes available. Read the full statement here:English | French Free Prescriptions For Certain Medical Conditions If your child has an asthma attack People with certain medical conditions can get free NHS prescriptions. Medical exemption certificates are credit-card-size cards. They are issued if you have: • cancer, including the effects of cancer or the effects of current or previous cancer treatment • a permanent fistula requiring continuous surgical dressing or an appliance • a form of hypoadrenalism for which specific substitution therapy is essential • diabetes insipidus or other forms of hypopituitarism • diabetes mellitus, except where treatment is by diet alone • hypoparathyroidism Find out more about medical exemption certificates. Don’t Miss: What Molecules Are Affected By Asthma What Pharmacies Offer Free Medications Many grocery chain pharmacies offer free medications including Meijer, Publix, Kroger, Family Fare, Sams Club, and more. Some give them away without any strings attached , while others require a paid membership. Ill give you the details of what is free at each location and their requirements below. Information About The Cost Of Dupixent The amount you pay for DUPIXENT will largely depend on a number of factors, including: • Whether you have prescription drug insurance • The type of insurance you have • Whether your insurance provider considers the medication to be preferred or not preferred • Whether youve met your deductible Considering these factors, 2 people could pay very different prices for exactly the same prescription medication. Use the DUPIXENT Cost and Coverage Tool below for more information. It is recommended to speak with your insurance provider for any outstanding questions you may have about the cost or dispensing of DUPIXENT because they know the full details of your plan. Select your current prescription insurance to see possible cost and coverage You May Like: Eos Levels In Blood Is Albuterol A Steroid No, albuterol does not contain any steroids. It is a sympathomimetic bronchodilator and works to relax the muscles in the airway that tighten during an asthma attack. Inhaled corticosteroids are another type of inhaler that contain steroids and are often used as a preventative treatment.Treatment of asthma and COPD can be complex and require using several medications in combination. What You Need To Know About Your Medicines Asthma & COPD Treatment / Pharmacology (Inhaler Progression) Talk with your doctor, nurse, or other healthcare provider before starting a new medicine. Go over your allergies and any problems you have had with other medicines, such as rashes, trouble breathing, indigestion, dizziness, or mood changes. You will also want to find out whether youll need to change or stop taking any of your other prescriptions or over-the-counter drugs while using this new medicine. Mixing some drugs can cause unpleasant and sometimes serious problems. For instance, it is dangerous to use aspirin when taking a blood-thinning medicine. Because of this, it is important to keep a list of all prescription drugs and over-the-counter remedies you take. Print and fill out the Tracking Your Medications: Worksheet to help you keep track of your medications. When starting a new medication, make sure to write down the name of the drug and why its being prescribed for you. Also, make note of any special instructions for how to take the medicine. You May Like: What Is The Blood Test For Eosinophilic Asthma Where Can I Purchase Ventolin Once you have a prescription for Ventolin you can have it fulfilled at any pharmacy. If you purchase it from a pharmacy with an NHS prescription, you will pay the standard levy. If you are entitled to free treatment on the NHS, you wont have to pay anything. Private pharmacies also offer Ventolin to buy. Some online pharmacies, such as ours, provide a doctor consultation facility, where you can have your prescription renewed by a doctor, and then dispensed at a UK pharmacy and delivered to you. When you use online services, you will still be required to answer several questions about your general health. When you order asthma inhalers using our UK service, it is our policy to inform your GP that you are ordering treatment online, so that they are kept up-to-date regarding your asthma care. Refunds Of Prescription Charges If you need to pay prescription charges before your medical exemption certificate arrives, you can get a refund as long as: • you ask for an FP57 refund receipt when you pay • the start date of your medical exemption certificate is the same or earlier than the date you pay for your prescription You must claim your refund within three months of paying. The FP57 refund receipt tells you what to do. Recommended Reading: Can A Humidifier Help With Asthma Cold Weather And Asthma Cold weather is a common trigger for asthma symptoms. There are things you can do to help control your symptoms in the cold: • carry your reliever inhaler with you at all times and keep taking your regular preventer inhaler as prescribed • if you need to use your inhaler more than usual, speak to your doctor about reviewing your treatment • keep warm and dry wear gloves, a scarf and a hat, and carry an umbrella • wrap a scarf loosely over your nose and mouth this will help warm up the air before you breathe it • try breathing in through your nose instead of your mouth your nose warms the air as you breathe How Do I Know If Other Medicines Im Taking Are Making My Asthma Worse How to use asthma inhalers? Any medicine can cause wheezing or shortness of breath if youre allergic to it. If you notice that your asthma gets worse every time you take a certain medicine, tell your doctor as soon as possible. If you use a peak flow meter to check your asthma, tell your doctor if you see changes in your peak flow readings after you take a certain medicine. Your doctor can decide whether your medicine should be changed. Don’t Miss: Does Albuterol Contain Steroids Keep Your Distance From Kitty Litter Pets are a common source of allergens cats more than dogs. Although the best asthma relief advice might be to find your furry friend another loving home, few people want to make that change. So, to live with a cat and be as wheeze-free as possible, consider making some key changes. Many people are allergic to cat urine, says Lee, so keep the litter box in a remote area of your home and put someone else in charge of emptying it. Cat dander and cat saliva also often provoke asthma reactions. When a cat licks and cleans itself, particles of saliva float on air currents for six to eight hours. To limit dander, use a dry cat shampoo weekly to help remove excess dander from the cat. That way, itâs less likely to stir up around the house. Thunderstorms And Extreme Weather Can Be A Threat To Asthma Control In hot summer conditions, extreme weather such as thunderstorms become more prevalent. Experts arent entirely sure why but have identified that such weather conditions can trigger asthma attacks, sometimes severe. It may be the airflow patterns during thunderstorms that cause this effect, rather than electrical activity such as thunder and lightning. It seems likely that these airflow patterns could result in more concentrated levels of pollen and mold, which could be one explanation for the increase in asthma attacks during thunderstorms. Regardless of the reason, extreme weather definitely has had an impact on some of us asthmatics. Recommended Reading: Can You Join The Army If You Have Asthma How Long Does A Medical Exemption Card Last When your form has been received and approved, your medical exemption certificate will be active for five years before it needs to be renewed. Its your responsibility to keep track of how long your certificate has been active for, although the NHS should send you a reminder before your five years have lapsed. If you continue to claim free prescriptions after your certificate has expired then you may be faced with a fine. How Do I Monitor My Daily Asthma Symptoms These People Are Testing Drugs So You Don’t Have to | Free Drugs National asthma guidelines suggest using a daily symptom diary such as Allergy & Asthma Networks AsthmaTracker to keep track of symptoms, peak expiratory flow rates and medications used. What is an AsthmaTracker? The AsthmaTracker can help your track how well your symptoms respond to your treatment plan. By writing down your symptoms, peak expiratory flow rate and medication use each day, youll notice a pattern to your symptoms and develop strategies to stop the symptoms before they can stop you. What is a peak flow meter? A peak flow meter is a handheld device that measures the peak expiratory flow rate , or how much air you can forcibly push out of your lungs at a particular time. Asthma Storylines an app for managing asthma The free Asthma Storylines app is a self-care tool for managing asthma. Track symptoms, learn more about daily patterns and record topics to discuss with your healthcare team. Don’t Miss: Can You Join The Army If You Have Asthma Why Humidity And Cold Air Trigger Asthma Every asthmatic should be aware that both humidity and cold air are two very common asthma triggers. So why is this? What can you do about it? Its been common wisdom for years that a cool mist humidifier helps with croup, inflammation and narrowing of a childs airways. Put a croupy kid in the hot and steamy bathroom and the swelling gets better. Another method that often works for croup is taking the child outside in the cold winter air. This is why many times when a parent decides to take the child to the hospital, in the dead of winter, the child is fine by the time they arrive in the emergency room. This is true for croup, so it was also theorized in past decades that it must also be true for asthma attacks. Most doctors are aware of this fallacy. In fact, doctors recognize that both cold air and humidity can actually trigger an asthma attack. When I was little boy way back in the 1970s, my pediatrician recommended my parents have me sit in the hot steamy bathroom when I was having trouble breathing. It was also recommended I have a humidifier in my room. Both of these made my asthma worse, not better. Yet I was a kid, so how was I to tell my parents that? My doctor and parents thought they were doing something good, yet their wisdom was flawed . I wrote a post before how low and high humidity can trigger asthma. Studies show that a humidity of 50 percent or greater may lead to a greater incidence of asthma trouble. Two common theories for this are: Video: Pay For My Heating Or My Medicine In conjunction with the Royal College of Nursing, the Association of Respiratory Nurse Specialists and Primary Care Respiratory Society UK, Asthma UK have conducted a survey of over 750 healthcare professionals to understand their views of asthma prescription charges. The key findings from the survey of healthcare professionals revealed: • 98% think the current medical exemptions list should be reviewed • 57% have had patients who have had an asthma attack or needed emergency care because their patient skipped their medication • 48% reported patients missing an asthma appointment because they were worried about the cost of the medicines they might be prescribed This report makes for a sobering read. It is unthinkable that people in England are risking their health and potentially their lives because they cannot afford their medication. There is absolutely no justification for the current prescription charges system to continue as it is people with asthma are being discriminated against, which is a blatant breach of ethical principles. This report conveys a powerful message which should act as a call to action for those who can make change happen. We now need politicians and policy makers to step up to the mark and address our findings as a matter of urgency. Beverley Bostock, Nurse Practitioner who sat on the National Review of Asthma Deaths and Asthma Lead for the Association of Respiratory Nurse Specialists Read Also: Fluticasone Side Effects Anxiety How Is This Medicine Best Taken Use Vicks Sinex ) as ordered by your doctor. Read all information given to you. Follow all instructions closely. • Do not take Vicks Sinex ) by mouth. Use in your nose only. Keep out of your mouth and eyes . • Some of these drugs need to be shaken before use. Be sure you know if this product needs to be shaken before using it. • Some products may have different ways to prime the pump. Some pumps may also need to be primed if not used for different periods of time. Follow how and when to prime as you have been told. • Blow your nose before use. • Do not tilt your head back before using Vicks Sinex ). • Put the cap back on after you are done using your dose. What do I do if I miss a dose? • If you use Vicks Sinex ) on a regular basis, use a missed dose as soon as you think about it. • If it is close to the time for your next dose, skip the missed dose and go back to your normal time. • Do not use 2 doses at the same time or extra doses. • Many times Vicks Sinex ) is used on an as needed basis. Do not use more often than told by the doctor. Exercise Can Trigger Asthma Asthma Inhaler Names Rapidly breathing in air dries inspired air as it moves through the upper airways, which ultimately dries the airway, which then releases histamine that can increase inflammation of the air passages in your lungs. This then leads to bronchospasm. The fact runners tend to breathe through their mouths only exacerbates this problem because the nose is a better humidifier than the mouth. You May Like: What Happens If You Smoke Weed With Asthma How Can A Pharmacist Help A pharmacist can answer many of your questions about prescriptions and over-the-counter drugs. Try to have all your prescriptions filled at the same pharmacy so your records are in one place. This will help alert the pharmacist if a new drug might cause a problem with something else you are taking. If youre not able to use just one pharmacy, show the pharmacist at each pharmacy your list of medicines and over-the-counter drugs when you drop off your prescription. When you have a prescription filled: • Tell the pharmacist if you have trouble swallowing pills. There may be liquid medicine available. Do not chew, break, or crush tablets without first finding out if the drug will still work. • Make sure you can read and understand the name of the medicine as well as the directions on the container and on the color-coded warning stickers on the bottle. If the label is hard to read, ask your pharmacist to use larger type. • Check that you can open the container. If not, ask the pharmacist to put your medicines in bottles that are easier to open. • Ask about special instructions on where to store a medicine. For example, should it be kept in the refrigerator or in a dry place? • Check the label on your medicine before leaving the pharmacy. It should have your name on it and the directions given by your doctor. If it doesnt, dont take it, and talk with the pharmacist. Talk with your doctor or pharmacist if you have questions about the written information that comes with your prescription. RELATED ARTICLES Most Popular
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Mum-and-kid-laughing-on-bed Probiotics for babies and infants Before birth, the foetal gastrointestinal tract (GIT) is more or less sterile. Bacterial colonisation begins with the rupture of the amniotic membrane and during vaginal birth, bacteria from the mother's intestinal and vaginal sites colonise the neonatal GIT within a few hours of birth. Baby and infant gastrointestinal (GI) microbiome The GI microbiome represents the greatest area of contact with the environment and consists of bacteria, single-cell microorganisms, yeasts, fungi and viruses, collectively known as the GI microbiota. The microbiome reflects the entire collection of genetic material of the GI microbiota which shifts and changes easily during infancy and dysbiosis in infancy that may affect the long-term health of the GI microbiome. Maternal breastmilk helps to promote the colonisation and maturation of the infant GIT microbiome. The introduction of solid food shifts the infant microbiome to more closely resemble an adult profile, however, the paediatric microbiome remains in flux for at least the first three years of life. Probiotics Microbial colonisation of the infant GIT expands rapidly following birth and bacterial colonisation of the GIT in a newborn infant is important for future microflora and functions. Probiotics in babies and infants help maintain a balanced, healthy composition of GI microbiota by re-establishing friendly GI bacteria and inhibiting the growth of unwanted GI bacteria. Bifidobacterium and Lactobacillus species have been found to significantly increase GI populations of beneficial bacteria, while simultaneously decreasing populations of less health-promoting bacteria. In order to have a good therapeutic effect, probiotics need to withstand the harsh environment of the stomach’s acidity and the intestine’s bile salts and have good adherence to the intestinal mucosa. Good adherence to the intestinal mucosa is important as it prolongs the time a probiotic strain can reside in the intestine, giving it an opportunity to modulate the immune response and protect against pathogens by limiting their ability to colonise the intestine. Beneficial effects of probiotics include: • Maintaining a healthy balance of GI flora • Improving the composition and diversity of intestinal flora • Supporting immune health • Maintaining healthy digestive function • Maintaining digestive barrier function • Inhibiting, displacing and competing for adhesion sites with pathogens • Producing antimicrobial compounds • Producing beneficial compounds e.g. short chain fatty acids (SCFAs) such as butyrate enzymes and vitamins • Involvement in carbohydrate and lipid metabolism Digestive system health Babies and infants may experience digestive related complaints as their digestive systems mature and strengthen. Maintaining a fully functional digestive system is a delicate balance during the development of the GI flora and this delicate balance can be disrupted by many aspects, including diet, illness and antibiotic use. An infant's digestive tract undergoes enormous change in the first six months of life as it develops the ability to produce enzymes to digest food. Anything that enters a baby's mouth makes its way to the GIT, which is still learning to fight off bacteria and other pathogens, further influencing digestive health. Altered digestive flora leads to poor digestion and increased GI permeability. Immune health The immune system is actively downregulated during pregnancy which leaves the infant highly susceptible to infection during the first few months of life. After birth, the development of the immune system is closely related to GI maturation. Immunological factors found in breastmilk are key instigators in this maturation process, as well as the gut-associated and systemic immune systems The GI microbiota is one of the key elements in the body’s immune defence system. Antibiotic therapy Antibiotic use is commonly associated with disturbed GI flora and Probiotics can help maintain beneficial GI flora in babies and infants during antibiotic use and are best taken 2-3 hours away from antibiotics for greater effect1. How to use probiotic powders with infant formula Infant formula is given to babies at varying temperatures, from cool or cold, right through to warm. As probiotics are heat sensitive, it is recommended that probiotic powders not be put in a bottle of formula prior to warming. The best way to administer a probiotic powder is to place one dose in cool to warm (not hot) formula immediately before use. Placing the probiotic powder in warmed formula immediately before use should not impact the efficacy of the probiotics See Baby Probiotic 12 Billion. 1. Goldenberg, J., et al., Probiotics for the prevention of paediatric antibiotic-associated diarrhea, Cochrane Collaboration, (2015). Products you may be interested in Children's Multi Care $32.50 Children's Immune Care $31.45 Children’s Magnesium Care $19.95 Zinc Forte + C $33.50 Elderberry Echinacea & Olive Leaf $32.45 Children's Calm Care $32.45 Children's Probiotic 15 Billion $45.95
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Skip directly to local search Skip directly to A to Z list Skip directly to navigation Skip directly to site content Skip directly to page options CDC Home Resources “The findings and conclusions in this book are those of the author(s) and do not necessarily represent the views of the funding agency.”   These chapters were published with modifications by Oxford University Press (2004)   Human Genome Epidemiology: A Scientific Foundation for Using Genetic Information to Improve Health and Prevent Disease     Part IV: CASE STUDIES:  Using Human Genome Epidemiology Information to Improve Health   Chapter 23 Fragile X Syndrome: Application of Gene Identification to Clinical Diagnosis and Population Screening Dana Crawford, Stephanie L. Sherman Tables | References   Background Clinical Overview The fragile X syndrome, an X-linked dominant disorder with reduced penetrance, is one of the most common forms of inherited mental retardation. The disorder-causing mutation is the amplification of a cytosine-guanine-guanine (CGG) repeat in the 5’ untranslated region of FMR1 located at Xq27.31. The fragile X mutation in affected persons results in the loss of the FMR1 gene product fragile X mental retardation protein (FMRP), an RNA-binding protein (2). Although its precise function is not yet understood, FMRP is thought to regulate the translation of other proteins (3). Thus, the loss of FMRP and possibly the loss of regulation of other as-yet-unidentified proteins result in the clinical phenotype of the fragile X syndrome. The clinical phenotype associated with the fragile X syndrome is wide and includes a variety of cognitive, physical, and behavioral characteristics (4). With regard to cognitive function, affected males often exhibit developmental delay early in childhood. By the age of 3 years, most males will test in the mentally retarded range (5). Ultimately, mental retardation is diagnosed in almost all males with the fragile X syndrome, with severity ranging from profound (IQ <20) to mild mental retardation (IQ 50-70), with most being moderately retarded (IQ 40-54)(6). Physically, adult males often have a long narrow face, prominent ears, a prominent jaw, and increased testicular volume (6). Other common physical features include a high arched palate, hyper-extensible finger joints, double jointed thumbs, single palmar crease, hand calluses, velvet-like skin, flat feet, and mitral valve prolapse (7). Males with the fragile X syndrome also tend to exhibit behavioral features such as hyperactivity, social anxiety, tactile defensiveness, stereotypies (e.g., hand-flapping), and hand biting (6). Language delay and perseverative speech are also commonly observed among males with the fragile X syndrome. Compared with other children who have developmental delay without the fragile X syndrome, males with the fragile X syndrome exhibit some autistic-like features, such as social avoidance, at a very young age(8). As many as 25% of males with the fragile X syndrome meet the diagnostic criteria for autism9. The association of fragile X with autism, however, is not clear because the proportion of males with the fragile X syndrome meeting the diagnostic criteria for autism seems to diminish with age(9). Females with the full mutation are often less affected than males, presumably because of X-inactivation10;(11). Approximately 30% to 50% of females with the full mutation have an IQ of <70, and 50% to 70% of females with the full mutation have an IQ of <8512. With regard to the specific cognitive and neuropsychological profile, deficits in specific IQ sub-tests (such as the arithmetic score), executive function, and visual information processing also have been noted for females with the full mutation4;(13-15). The pattern of autistic-like behavior among males also occurs among a proportion of females with the full mutation(16). Interestingly, autistic-like behavior is not correlated with IQ in females with the full mutation, which suggests that the degree of mental retardation is not the underlying cause of this behavior(16). Epidemiology of the fragile X syndrome The fragile X syndrome is found in all world populations tested. Its prevalence among populations of northern European descent is approximately 1 in 6,000 to 1 in 4,000 males in the general population(17-19). A more detailed description of the prevalence of the fragile X syndrome within a general population is given below (Epidemiologic findings). The prevalence of the fragile X syndrome among phenotypically defined populations is difficult to describe as studies published in the literature employed different criteria for ascertaining persons for testing. For example, von Koskull et al.(20) examined clinically referred persons with mental retardation, while Mazzocco et al.(21) examined preschool children referred for language delay. Although both of these studies identified persons with the fragile X syndrome, the fraction of males identified with fragile X differed between these two phenotypically defined populations (4.9% vs 0.3%, respectively). Despite these difficulties in comparing across studies, the prevalence of the fragile X syndrome is higher for populations with developmental delay or mental retardation than in the general population(17). Genetics of the fragile X syndrome The genetics of the fragile X syndrome are unique in that they represent a new class of disorder-causing mutations known as trinucleotide or dynamic repeats. One characteristic of these disorders is anticipation, which is the increased disease occurrence or increased severity of the disease observed in pedigrees of affected families in succeeding generations(22). The understanding of this phenomenon came with the cloning of the fragile X mental retardation (FMR)-1 gene in 1991. A repeated sequence of CGG was found within the 5’ UTR of the gene. These repeats were unstable when transmitted from parent to offspring. The polymorphic fragile X CGG repeat can now be categorized in at least four forms on the basis of the size of the repeat: full mutation (>200-230 repeats), premutation (61-200 repeats), intermediate (41-60 repeats), and common (6-40 repeats). Among the general population, the common repeats are usually transmitted from parent to offspring in a stable manner. In contrast, premutation alleles are unstable when transmitted from parent to offspring and usually expand in the next generation. The size of the repeat expansion is positively correlated with maternal CGG repeat size, with >90 repeats almost always expanding to the full mutation in the next generation(23). Intermediate alleles are larger repeats that may or may not be transmitted stably from parent to offspring. Thus, these alleles overlap the boundary between common and premutation alleles(24). The full mutation allele is the form associated with the fragile X syndrome phenotype. All full mutations identified have been derived from premutation or full mutation alleles from the previous generation. In contrast to female transmission, paternal transmission of the full mutation to the offspring is rare. The end result of the full mutation allele is the hypermethylation(25) and deacetylation(26) of the promoter region of FMR1, which effectively prevents transcription of the gene(27). In summary, the fragile X syndrome is transmitted as an X-linked dominant mutation with reduced penetrance. The reduced penetrance is related to the form of the mutation; that is, only full mutation alleles lead to the syndrome. The increased occurrence of the syndrome in succeeding generations of an identified family, anticipation, results from the instability of the repeat mutation and the bias for expansion. There is a parent-of-origin effect in that only premutation alleles carried by females are at risk for expansion to the full mutation in the next generation. Premutation alleles carried by males are relatively stable. Epidemiologic findings Prevalence: Full mutation Both the full mutation and premutation genotypes are directly related to the expression of the fragile X syndrome phenotype (Tables 23-1 and 23-2). For the full mutation, all general population prevalence estimates have tested target populations with some type of cognitive impairment and extrapolated these findings to the general population. The general assumption among these studies is that males affected with the fragile X syndrome will be found only among the targeted population being tested (e.g., special education). According to the results of these studies, point estimates for the fragile X syndrome range from 1 in 3,717(28)to 1 in 8,918(29) males in the general white population (Table 22-1). The confidence limits, available for only four of these studies, vary widely, with a lower boundary of 1 in 1,333(30) to an upper boundary of 1 in 8,922(18). In contrast to the populations of northern European descent, few estimates exist for other racial/ethnic groups. There have been only two other population-based estimates, both for African-derived populations. Elbaz et al.(31) examined an Afro-Caribbean population in the French West Indies, and Crawford et al.(28) examined an African-American population in metropolitan Atlanta, Georgia, USA. Surprisingly, both studies suggested that the point estimate in these admixed, African-derived populations is approximately 1 in 2,500 males, which is higher than that observed in white populations (Table 22-1). Further studies are needed to explore this possible higher general population prevalence as the confidence intervals for both studies overlap with estimates in populations of northern European descent. Even less is known about the prevalence of the full mutation among females in the general population. On the basis of the prevalence of the full mutation among white males in the general population (approximately 1 in 4,000) and the transmission only by females of the full mutation to their offspring, the expected prevalence of the full mutation allele among females is 1 in 4,000. Assuming that 50% of females with the full mutation will be affected with the fragile X syndrome phenotype, the expected prevalence of females affected by the fragile X syndrome is approximately 1 in 8,000 females. Among 8,462 women in Israel who had no family history of mental retardation, Pesso et al.(32) identified one woman with the full mutation. In a separate study of 14,334 normal healthy women in Israel, Toledano-Alhadef et al.(33) identified three women with a full mutation, resulting in a higher prevalence (1 in 4,778 females) compared with Pesso et al.(32) Neither study was population-based and both were biased toward testing unaffected females. Thus, conclusions cannot be made about the prevalence of the fragile X syndrome among females based on these studies. Large population-based studies are needed to better understand the prevalence of the full mutation and its expression among females. Prevalence: Premutations Similar to the data for the prevalence of the full mutation, most of the data on the prevalence of premutations were collected from white populations. Results from two large, population-based studies published in the literature suggest that the prevalence of premutations (61-200 repeats) in males is probably 1 in 1,00028;34 to 1 in 2,000(18,35) males in the general white population. For this review, we defined premutations in females as either 61-200 repeats or 55-200 repeats. The former definition of premutations characterizes repeats that are always unstable and expand to the full mutation. The latter definition of premutations characterizes premutations of smaller size that can be found in families with the fragile X syndrome(24,36). The smallest premutation among families with the fragile X syndrome to expand to the full mutation in a single generation is 59 repeats (24,36). In the general population, however, these smaller premutations may or may not be unstable(37). Thus, the former estimate of premutations (Table 22-2) represent the lower limits of premutation carriers whereas the latter estimates of premutations possibly represent the upper limits of premutation carriers. Results from recent, large studies suggest that the lower limits of the prevalence of the premutation range from 1 in 231(33) to 1 in 468(32) females, and the upper limits range from 1 in 116(33)to 1 in 259(38) females (Table 2). Interactions No interactions with environmental factors or other genes have been identified to explain the variation in the phenotype of the fragile X syndrome. However, such interactions are expected for two reasons. First, the range in clinical severity of fully methylated, full mutation males and females, even among monozygotic twins, has been observed and is significant (39-41). Among repeat-size or methylation mosaic males and females, variability in IQ can be partially explained by the variability in FMRP levels(42). However, neither features of FMR1 or its gene product FMRP can account for the majority of the variability among fully methylated, full mutation males. Although the low but measurable level of FMRP seems to be related to the level of development among affected males, it does not seem to be related to the rate of development or the expression of autism(43;44). In fact, the co-occurrence of autistic behavior and the fragile X syndrome more accurately predicts developmental status than does the level of FMRP(44), possibly suggesting the existence of additional factors involved in the fragile X phenotype. The second reason to expect gene-gene interactions is that the normal function of FMRP is to regulate translation of other proteins. FMRP is an RNA-binding protein (2,45) that is capable of binding to itself as well as other proteins(46). In addition to its RNA-binding capabilities, FMRP has both a nuclear localization signal (NLS) and a nuclear export signal (NES)(47). The current model suggests that oligomerized FMRP, in conjunction with other proteins, shuttles specific mRNAs from the nucleus to the cytoplasm for translation. The identification of the specific mRNAs and their corresponding genes necessary for the complete understanding of the molecular consequences related to the fragile X syndrome phenotype(3). Laboratory tests The Quality Assurance Subcommittee of the American College of Medical Genetics Laboratory Practice Committee has recently published technical standards and guidelines for fragile X syndrome testing(36). According to the subcommittee, DNA-based tests that determine the size of the fragile X CGG repeat are considered diagnostic and are 99% sensitive and 100% specific(36). These DNA-based tests are also applicable for prenatal diagnosis in both amniotic fluid cells and chorionic villus samples (CVS). However, all DNA-based tests for the fragile X syndrome have important caveats that impact the interpretation of the test, most of which are reviewed below. For a more comprehensive checklist, refer to the standards and guidelines published by the Quality Assurance Subcommittee(36). The most popular and accepted method for DNA-based testing for the expanded CGG repeat is the Southern blot. Many different restriction enzymes can be used in combination to determine both expansion (EcoRI, PstI, BglII, HindIII, BclI) and methylation (SacII, BssHII, EagI, BstZI) status for an individual(7;48). Methylation status is particularly useful for distinguishing between borderline premutation and full mutation alleles (200-230 repeats)(36). Methylation sensitive enzymes can also describe the degree of methylation of the full mutation allele for both males and females as well as the X-inactivation pattern for females. However, neither of these measures can be used to predict the degree of mental retardation status for either sex(36). The main disadvantage of the Southern blot is that it requires a large amount of DNA and is laborious, both of which prevent the rapid and inexpensive screening of large populations. Because of these limitations, other diagnostic tests based on DNA and protein properties of the fragile X syndrome have been developed for fragile X screening. New DNA diagnostic tests have concentrated on the use of the polymerase chain reaction (PCR). Many different PCR protocols have been developed for the fragile X CGG repeat, with different degrees of amplification abilities and sizing accuracies. Regardless of the variations in protocol, compared with Southern blots, the PCR test is inexpensive, automated, and fast. Also, PCR can be performed on very small amounts of DNA, making collection of the samples relatively painless and convenient for the patients. The disadvantage of PCR is that the test results may not be straightforward for several reasons. The amplification of large repeats is difficult, especially in the presence of a second, smaller repeat. For many PCR protocols, the DNA fragment with the expanded repeat does not amplify. This is especially problematic for females and persons with repeat-size mosaicism who could appear to have a single, normal repeat size. To avoid these false negatives, many screening programs follow up by Southern blot any sample that fails to amplify by PCR and any female who appears to be homozygous. This strategy could potentially produce a false-negative result for persons who are normal/full mutation mosaic; however, few data exist to suggest that this occurs frequently. Most DNA-based methods can distinguish between premutations and full mutations. Because of ethical issues in identifying asymptomatic carriers, some proposed screening strategies are designed to identify only affected persons or those with the full mutation. Also, affected persons with point mutations and deletions that result in the loss of FMRP would not be routinely identified using the above methods that examine repeat size and potential sequencing of FMR1 is not routinely practiced for screening strategies or even for clinical diagnosis(49). For 99% of persons with the fragile X syndrome, affected status depends not only on the expansion of the repeat but on the subsequent lack of FMRP as well. The development of antibodies against FMRP has made screening possible on the basis of affected status only(45,50). In this protein-based assay, the percentage of FMRP detected in lymphocytes from blood smears is used to determine affected status(51-54). Typically, fewer than 40% of the lymphocytes from males with the fragile X syndrome have detectable amounts of FMRP(52). This protein-based test has recently been adapted for hair root(55;56) and prenatal(57;58) samples. Although promising, this technique cannot accurately identify affected females(42;54) and may not be appropriate for males who are normal/full or premutation/full mosaic. Potential contribution of genetic information to improve health outcomes One potential contribution resulting from the cloning of FMR1 could be the prompt identification of children eligible for early intervention services. Although no cure exists for the fragile X syndrome, all infants and toddlers identified with the fragile X syndrome in the United States are eligible for early intervention services as described in Part C of the Individuals with Disabilities Education Act (IDEA, PL 101-476)(59). Early intervention programs in the United States vary among the states and are generally meant to facilitate access to existing services and programs(59). These programs can also provide direct services as a supplement to existing programs. Only one report in the literature describes intervention services specifically for children with the fragile X syndrome. Given the fact that services vary from state to state, this report from North Carolina may not accurately describe services available to children with fragile X who reside in other states. In this report, Hatton et al.(60) described in detail the types of services and therapies received by young boys with fragile X, including special education, speech-language therapy, occupational therapy, and physical therapy. The report further describes the amount of services and therapies provided, and demonstrates that the amount of services provided is positively correlated with age(60). Hatton et al.(60) also identify the need of interventionists to learn about the fragile X syndrome and its specific behavioral features, a finding consistent with other surveys of special education teachers in the United States(61) and the United Kingdom(62). Although the medical and education communities recommend participation in programs and services after diagnosis of developmental delay or the fragile X syndrome, the effectiveness of early intervention services has not been yet demonstrated. This gap in research, however, is difficult to fill because it requires diagnosis with the fragile X syndrome soon after birth(63). In many countries, including the United States, the fragile X syndrome is commonly diagnosed through a referral for fragile X testing.  A referral is indicated if a person has unexplained mental retardation, developmental delay, or autism, especially if physical or behavioral characteristics commonly associated with the fragile X syndrome are evident(64). Despite these recommendations, studies of school-aged children receiving special education in the Netherlands(19), the United States(28), and the United Kingdom(18) suggest that the current referral system can fail to identify toddlers and school-aged children who do not yet manifest the physical hallmarks of the syndrome(65;66). A second potential contribution resulting from the cloning of FMR1 could be the identification of families at risk of having a child with the fragile X syndrome. Based on the genetics of the fragile X syndrome, strategies for identifying at risk families usually focus on identifying female premutation and full mutation carriers. Ideally, women at risk would be identified before pregnancy, which would give these women the most options including egg donation, adoption, and prenatal diagnosis. Also, these women would be advised of their risk for premature ovarian failure (POF). Whereas the mean age of menopause is 51 years, women with POF experience the cessation of menses before age 40 years. Twenty-one percent (95% CI: 15%-27%) of premutation carriers develop POF compared with 1% of women in the general population67. Women identified as premutation carriers could be advised to plan their families earlier rather than later in their reproductive lives because of their risk for POF. Although knowledge of genotype status for the fragile X syndrome offers benefits to many families, this knowledge may also solicit poorly understood harms. One such harm is the impact carrier status may have on the psychology of an individual. Retrospective interviews of parents with children in whom the fragile X syndrome had been diagnosed indicate that many carrier parents feel guilty for passing the mutation to their children and are worried about the implications fragile X test results have on their families(68;69). Furthermore, a cross-sectional study of obligate carriers found that knowledge of carrier status was upsetting and caused a proportion of women to change their views about themselves(70). Finally, an important study by McConkie-Rosell and colleagues describes the emotions and attitudes of women without children with fragile X but who know before testing that they have a 50% chance of carrying the premutation allele. In this longitudinal study, white women over age 18 years who were at risk of carrying the premutation allele completed a structured interview and standardized measures both at the time of testing and 6 months after learning the results of the test(71). Results of the study suggest that the idea of being “at risk” before testing was upsetting and continued to be so only for the women found to be carriers(72). Surprisingly, non-carrier women surveyed after genetic testing viewed the fragile X syndrome as a more serious problem than they did the first time they were surveyed and than did carrier women(72). Results also suggest that women’s responses regarding feelings of self were not related to global self-concept but to the implications the positive carrier test would have on themselves and their families(71). These responses could be categorized into five areas of specific concerns: implications their positive test had for their children, reproductive options, possible expression of the fragile X syndrome phenotype in themselves, genetic identity, and regret of having not known sooner(71). Most non-carrier women and a small proportion of carrier women expressed relief or a positive emotion after learning carrier status(71;72). Although the only study of its kind in the literature, the results of the study may be limited to educated and married White women. Additional studies in this area are needed so that the impact of carrier testing can be fully understood in terms of race/ethnicity, education, economics, and marital status. Also, studies must be designed to explore the impact of carrier testing on individuals from the general population who have a very low prior risk of carrying the fragile X premutation or full mutation. A second potential harm associated with knowledge of genotype is related to insurance coverage. The focus of much concern is the use of genetic information that reveals susceptibility or carrier status of a presently healthy individual in determining health insurance coverage. In the United States, several states have enacted laws that prohibit the use of genetic information in pricing, issuing, or structuring of health insurance(73;74). At the federal level, the Health Insurance Portability and Accountability Act enacted in 1996 (HIPAA: Stat 1936, Pub L, No 110: 104-191) prohibits group health insurers from applying pre-existing condition exclusions to genetic conditions that are identified solely by genetic tests. Although fear of genetic discrimination has generated much attention, a recent survey of insurers, agents, and professionals in medical genetics (e.g., genetic counselors and clinicians) suggests that discrimination based solely on a genetic test is not common with regard to health insurance coverage(73;74). Consistent with these findings is one report about the effects of fragile X testing on health insurance coverage for 39 families living in Colorado(75). All families surveyed by Wingrove et al.(75) had a child affected with the fragile X syndrome. None of the families reported having their health insurance coverage cancelled as a result of genetic testing. Six families reported that carriers of the fragile X syndrome were declined for coverage; however, all six included a child affected with fragile X with their applications(75). Also, six families reported a member who refused testing because of fear of genetic discrimination(75). This result highlights the need to dispel the myths associated with genetic testing and health insurance that may otherwise discourage a person from seeking genetic testing. Future directions Clinical practice Recent research findings dictate two trends in clinical practice related to the fragile X syndrome: 1) effective medical treatments and 2) earlier diagnosis. With regard to effective medical treatments, most current treatments available target the behavioral problems often observed in children with fragile X. Treatments include interventions such as occupational therapy with an emphasis in sensory integration and speech and language therapy. This multidisciplinary approach, detailed in Hagerman and Cronister(76), will help children with fragile X develop to their full potential by minimizing some of the behavioral problems that would impede their developmental progress. In addition to intervention, stimulation medications used to treat attention deficit hyperactivity disorder (ADHD) are commonly prescribed to children with fragile X syndrome to alleviate some of the behavioral problems that would interfere with learning and socialization. Other problems such as aggression and anxiety have also been successfully treated(77;78) Beyond treatment of the symptoms of the syndrome, a new emphasis in research has been directed toward correcting the fragile X defect. Basic research suggests that reduced acetylation of histones H3 and H4 at the 5’ end of FMR1 leads to the condensation of chromatin and subsequent inhibition of transcription(26). The deacetylation is mediated through a methylcytosine binding protein, MeCP2, at the abnormally methylated CpG island observed in individuals with fragile X(79). Much interest lies in reactivating FMR1 by demethylating the CpG island. Although research groups have successfully reactivated FMR1 using 5 azadeoxycytidine (5 azadC), the chemical is too toxic for human use(26;80). Also, 5 azadC requires cell division, which makes it an unlikely candidate for neurons, the cells presumably most affected by the fragile X mutation. Chemical therapy of the primary defect is not yet a reality, but researchers remain hopeful that accumulating basic research and knowledge of the fragile X defect will translate into an effective treatment in the future. With regard to earlier diagnosis, as mentioned above, the referral system often used by physicians does not identify all young children with the fragile X syndrome. The current referral system relies, in part, on the classic physical features present in adults with the fragile X syndrome, which are not usually present in young children with fragile X(66). Often times the parents or guardians of young children with the fragile X syndrome will notice developmental delay or behavioral problems within the first few months of the children’s lives(81). In fact, an analysis of retrospective interviews of North Carolina mothers with children in whom fragile X was diagnosed reported that, on average, parents noted developmental delay at 9 months(81). Despite the early signs of developmental delay among this study group, the diagnosis of developmental delay averaged 24 months and the diagnosis of fragile X averaged 35 months(81). The lag time between the first signs of fragile X and a diagnosis could be related to the physician’s reluctance to test the child at such an early age. In the North Carolina study, 28 parents (68%) of affected children voiced frustration with their pediatricians or other health care providers for dismissing the parents’ concern for their children’s development(81). This frustration has also been documented in a similar survey of parents with children with fragile X in the United Kingdom(82). The importance of a prompt diagnosis for the fragile X syndrome cannot be understated. The benefits of an accurate diagnosis radiate beyond the person diagnosed because both immediate and extended family members will be affected by its consequences. The lag time between the birth of the first child with fragile X and a diagnosis must be short as possible to ensure that couples at risk have ample time to learn about the syndrome and to explore their reproductive options. As a result of this movement for a more timely diagnosis, researchers and parents have begun the discussion of general population screening programs for the fragile X syndrome. Population testing For the fragile X syndrome, development of many different types of screening programs could be based on the timing of the test and the persons to whom the test is offered. Conceivably, the fragile X test could be offered at four different periods: preconceptional, prenatal, newborn, and symptomatic. Because of the unique genetics of the fragile X syndrome, only women transmit the full mutation to their offspring. Thus, either during the preconceptional period or during pregnancy women could be offered carrier testing for the fragile X syndrome. Prenatal screening of the fetus could then be offered to women identified as premutation or full mutation carriers. If the goal is to diagnose the fragile X syndrome, systematic testing of newborns could be considered. The fragile X test could also be offered to toddlers or school-aged children who have unexplained developmental delay (symptomatic screening). However, because the goal is to shorten the lag time between birth and diagnosis, this option will not be discussed here. With regard to screening preconceptional or pregnant women in the United States, the policy for fragile X syndrome testing has not changed since a working group for the American College of Medical Genetics published their recommendations in 1994(64). That is, in the United States, the fragile X syndrome test is offered on a referral basis and not routinely to the general population. Examples of carrier screening offered to U.S. women with histories of fragile X or mental retardation(83;84) have been published in the literature. Only one program in the United States has reported screening reproductive-age women without a history of mental retardation. This program at the Genetics & IVF Institute in Fairfax, Virginia, reported offering fragile X carrier screening to women on a self-pay basis85;(86). Most women were referred to the clinic because of their advanced reproductive age. From December 1993 through June 1995, 3,345 women were offered testing, and 668 (21%) accepted. Most (69%) of these women did not have family histories of mental retardation. Among these women, three premutation carriers (60-199 repeats) were identified(85). Unlike the screening studies performed in the United States, investigators in Finland have implemented a large population-based carrier-screening program. The program implemented by the Kuopio University Hospital in Finland offered an FMR1 gene test free of charge to all pregnant women seeking prenatal care from July 1995 until December 199687. According to Ryynanen et al.(87), almost all pregnant women in Finland seek prenatal care and are registered in antenatal clinics during the 6th through 10th weeks of pregnancy because this registration is required for maternity allowance provided by the state. Among women without family histories of the fragile X syndrome, 1,477 (85%) elected genetic testing. Of these women, six were identified as premutation carriers (60-199 repeats) and all six women elected prenatal testing. The program has since screened an additional 1,358 women through December 1997. Six more women with the premutation allele were identified, and all six elected prenatal diagnosis(88). The program has also expanded to offer an FMR1 genetic test to pregnant women undergoing invasive prenatal testing because of advanced maternal age or history of trisomy pregnancy. In this expanded program, 241 (80%) of the 302 women offered the test consented, and one woman was identified as a premutation carrier(88). As in Finland, carrier testing is also widely employed and accepted in Israel. At least three groups have published results obtained from their large screening programs. Unlike the program in Finland, these programs offer the test on a self-pay basis and rely on either a self-referral or physician referral for testing. In one published report, the Rabin Medical Center screened 14,334 preconceptional or pregnant women who were self-referred and had no family histories of mental retardation between January 1992 and October 200033;(89). Women identified as carriers were offered prenatal testing free of charge as instructed by the Israeli Ministry of Health. A total of 204 women were identified as premutation carriers (51-200 repeats), and three women were identified as full mutation carriers(33). Of the pregnant women identified as premutation/full mutation carriers (n=173), only 14 women refused prenatal diagnosis(33). In a second report, the Genetic Institute of the Tel Aviv Sourasky Medical Center offered an FMR1 genetic test to 9,660 women during September 1994 through October 1998(37). A total of 38 premutation carriers (60-200 repeats) were identified, and all of these women consented to prenatal diagnosis(37). Finally, during January 1994 through March 1999, the Danek-Gertner Institute of Human Genetics screened 8,426 women of reproductive age who had no family histories of the fragile X syndrome or mental retardation(32). Among these women, 18 were identified as premutation carriers (61-199 repeats), and one was identified as a full mutation carrier (>200 repeats). Newborn screening for the fragile X syndrome has not yet been implemented in any country. Compared against the criteria published by the National Academy of Sciences (NAS)(90), the Institute of Medicine (IOM)(91), and Task Force on Genetic Testing(92), the fragile X syndrome meets at least two criteria essential for a successful program in newborn screening. Specifically, based on its morbidity and prevalence, the fragile X syndrome is an important public health problem. Also, approximately 99% of cases diagnosed thus far are caused by a single, inherited mutation, making the fragile X syndrome particularly amenable to DNA-based testing for an accurate diagnosis. Despite meeting these criteria, the fragile X syndrome does not meet several other key criteria for newborn screening. One crucial gap in research is the lack of a cure or effective treatment available for persons with the disorder, as mentioned previously. A second gap is the lack of knowledge of the potential harms associated with the diagnosis in an apparently healthy child. Many researchers and parents worry that a diagnosis at the newborn period would disrupt the parent-child bond. However, little evidence supports this, and many parents contend that a diagnosis would strengthen the parent-child bond through a greater understanding of the child’s special needs. Nevertheless, because the fragile X genetic test cannot predict the severity of mental retardation (especially regarding females with the full mutation), the effects of a diagnosis on the family’s perception of the child’s prognosis and future development are important to consider. Finally, a third gap is the lack of general consensus for the appropriate time to screen that would maximize the benefits of a diagnosis(93). Newborn screening will identify affected infants who are eligible for early intervention services. Newborn screening would also provide parents with information about their children’s future development and methods to optimize this development. However, identification of an affected person will also identify at risk families. Although these identified families could benefit from genetic counseling, newborn screening is neither ideal nor designed for identifying most at risk families for the fragile X syndrome in the general population(68;94). Also, many parents may want to know before pregnancy or birth about the fragile X syndrome. Indeed, a proportion of parents with fragile X children surveyed in the United Kingdom believed that a diagnosis based on newborn screening would be “too late.”(82) The debate concerning screening for the fragile X syndrome will no doubt continue. In the meantime, more information about the risk for expansion based on premutation size should be collected to better assess a women’s risk of conceiving a child with the fragile X syndrome. Also, the psychological impact genetic testing should be thoroughly explored because these results have implications that reach far beyond the fragile X syndrome in this new genetic age. Finally, effective treatments need to be developed and properly evaluated so that persons affected by the fragile X syndrome and their families can live life to the fullest potential. Tables   References 1. 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USA.gov: The U.S. Government's Official Web PortalDepartment of Health and Human Services Centers for Disease Control and Prevention   1600 Clifton Road Atlanta, GA 30329-4027, USA 800-CDC-INFO (800-232-4636) TTY: (888) 232-6348 - Contact CDC–INFO A-Z Index 1. A 2. B 3. C 4. D 5. E 6. F 7. G 8. H 9. I 10. J 11. K 12. L 13. M 14. N 15. O 16. P 17. Q 18. R 19. S 20. T 21. U 22. V 23. W 24. X 25. Y 26. Z 27. #
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Read more from Lifestyle & Nutrition Gut Health and Fertility 17 November 2020 Our gut starts at our mouth and encompasses the whole of our digestive tract including our stomach, intestines and colon. As well as being responsible for the breakdown and absorption of the food we eat, it is also home to trillions of microorganisms and bacteria which make up our gut microbiome. Our gut is responsible for much more than just our digestive health, there are links between the gut and the brain, the immune system and the cardiovascular system, meaning the wellbeing of our gut and its microbiome can potentially affect many other aspects of our health, including fertility.  Leaky gut syndrome and fertility: is it a thing? ‘Leaky gut syndrome’ is a proposed condition where it is said that gaps appear between the cells lining your gut allowing toxins and other substances to leak into the surrounding tissue producing inflammation. Some health practitioners claim this is the cause of a wide range of long-term conditions, including infertility (1). Currently however there is a lack of scientific evidence to support the concept that the gut can become ‘leaky’ or, in scientific terms, more permeable, to the extent that it can be the cause of medical conditions. While some studies have linked a higher prevalence of intestinal permeability in women with issues of infertility such as recurrent pregnancy loss (2) no studies have linked this to being the cause and it may just be a symptom of that situation.  Gut health, weight & fertility Women of a higher weight are at increased risk of reproductive problems, which may in part be due to poor egg quality because of increased exposure to oxidative stress and inflammation. We know that what we eat can change the function of our gut microbes and excess intake of calories, processed meat, high levels of sugar and salt, along with little to no fibre, has the potential to negatively affect our gut microbiome. People with obesity and chronic inflammation have been found to have an imbalance in their gut microbiome in comparison to people without these conditions. Recently, a study in mice has shown that a high fat diet can induce gut microbiome imbalance and ovarian inflammation through changes in gene expression providing preliminary evidence for a link between an obesogenic diet, gut health and infertility (3,4). Gut health & PCOS Major characteristics of PCOS include insulin resistance and hyperandrogenism. The consequences of this include compromised fertility, along with being at a higher risk of developing cardiovascular disease and Type 2 diabetes. Interestingly, studies have found that the gut microbiome of women with PCOS is different to those without the condition (5) and recent research now suggests that a gut microbiome imbalance may drive the development of both PCOS and insulin resistance (6,7) Gut health & reproductive hormones The bacteria in our gut play a role in the breakdown of oestrogen through the action of the enzyme β-glucuronidase. Alterations in gut microbiome diversity can reduce or increase the activity of this enzyme resulting in lower or higher levels of oestrogen (8) leading to disruptions in the menstrual cycle, irregular periods, impaired ovulation, PCOS and endometriosis, ultimately affecting fertility success. How can we promote gut health? • Aim to consume 30g of fibre a day along with prebiotic foods. Fibre is found in whole grains, legumes, vegetables, fruit, nuts and seeds. Prebiotics, not to be confused with probiotics, are foods that feed our good bacteria and have been shown to result in specific changes in the composition and/or activity of the gut microbiota conferring a benefit to the person. Many forms of dietary fibre act as prebiotics such as apricots, nectarine, watermelon, artichokes, asparagus, brussel sprouts, garlic, almonds, barley, hazelnuts and legumes. Incorporating these fibres in your diet has the potential to improve the balance of the gut microbiome and the success of pregnancy in females with infertility (9). • Incorporating probiotic foods, which contain live microorganisms into the diet such as kefir and natural yoghurt has the potential to populate the gut with beneficial bacteria rebalancing the gut microbiome and promoting diversity.   What about probiotics?  Probiotics are live bacteria and yeasts, which when taken and reach our gut alive, have the potential to restore the balance of our gut microbiota by increasing the number of ‘good’ or ‘friendly’ bacteria. But beware that not all products that claim to be a probiotic may reach the gut alive. A lot of research is underway to understand whether probiotics could have a positive role in fertility disorders and for hormonal imbalances. We now know that an altered vaginal microbiome may influence fertility (10) and studies have found that oral probiotic supplementation with two Lactobacillus strains can restore a healthy vaginal flora in up to 82% of women with previous vaginal microbiome imbalance (11,12). While there is preliminary evidence that probiotics could help with issues of fertility, more research is required to determine what specific gut bacterial species play helpful or harmful roles in conditions of infertility and this will help to determine what specific probiotics have the potential to benefit specific conditions (13).  Conclusion  Prioritising gut health could positively influence both reproductive and overall health however the precise link between gut microbiome and fertility remains unclear. Basing your diet on whole grains, fruit, vegetables, nuts, seeds, lean protein, favouring unsaturated fats, whilst limiting foods that can promote gut imbalance and inflammation such as high-fat, high-sugar foods and alcohol is the best route to a healthy gut.  References 1. “Leaky gut syndrome” - NHS [Internet]. [cited 2020 Oct 27]. Available from: https://www.nhs.uk/conditions/leaky-gut-syndrome/ 2. Tersigni C, D’Ippolito S, Di Nicuolo F, Marana R, Valenza V, Masciullo V, et al. Recurrent pregnancy loss is associated to leaky gut: A novel pathogenic model of endometrium inflammation? J Transl Med [Internet]. 2018 Apr 17 [cited 2020 Oct 2];16(1). Available from: https://pubmed.ncbi.nlm.nih.gov/29665864/ 3. Davis JS. Connecting female infertility to obesity, inflammation, and maternal gut dysbiosis [Internet]. Vol. 157, Endocrinology. Endocrine Society; 2016 [cited 2020 Oct 2]. p. 1725–7. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6285284/ Send to a friend
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Wellness Ear Seeds for Easy, At-Home Acupressure Written by: Kelly Martin | Published on: July 5, 2020 | Updated on: July 8, 2022 Ear Seeds for Easy, At-Home Acupressure Shari Auth headshot When we’re on-site at an In goop Health summit, there’s one walk-up activation we make sure to hit before the day is out: ear seeds. Once applied, they look like a constellation of small earrings—but they’re actually strategically placed teeny beads based in the tradition of auricular acupuncture. Today, ear seeds are often offered as a complement to acupuncture, cupping, and other traditional Chinese medicine treatments. And they’re something you can do at home. Shari Auth, the founder of the New York City acupuncture studio WTHN, has a kit that makes that process easy. 1. WTHN EAR SEED KIT WTHN EAR SEED KIT goop, $45 SHOP NOW A Q&A with Shari Auth, DACM, LAc, LMT Q What are ear seeds? A The first ear seeds were used to support health and well-being as a way of delivering auricular acupuncture—acupuncture on the ear—without needles. The ear is important in traditional Chinese medicine because it’s one of the areas of the body considered to be a microcosm of the body as a whole. (Others include the hand, the foot, the abdomen, and the iris of the eye.) On the ear, there are dozens of pressure points that correspond to different areas of the body. When you apply pressure to one of those points by applying an ear seed, that point activates. (Ear seeds used to be actual seeds from the Vaccaria plant, but now some use gold beads attached to a clear plastic sticker.) Q When do you use them? A Often, acupuncturists will offer ear seeds as a complement to any treatment. But they’re also easy and safe to do at home. You choose points on the ear according to whatever therapeutic benefit you’re looking for and apply the seeds with a pair of tweezers. They’re surprisingly resilient. People expect them to fall off in the shower, but they don’t. You keep them on for three to five days, and then they’ll either fall off or you remove them yourself. And they look nice. We’ve made a kit that has gold seeds as well as ones topped with Swarovski crystals that are very pretty—they look like a little constellation of earrings. Q Where and how do you place them? A With the WTHN Ear Seed Kit, we include an instruction booklet with ten of the most commonly used auricular acupuncture points. It’s important to remember that the points are more accurately described as areas. It’s not as if the point is the size of the seed and you have to hit it exactly. Wherever a point is marked on the ear map, you’ve got some leeway—the actual area you’re targeting is probably ten times larger than the seed itself. Aiming for that area, you take an ear seed off its paper, holding the seed itself with your tweezers, and then you just place it on the ear at your targeted point. If you need to, you can smooth down the sticker. For maximum benefit, I suggest placing them on points on both ears. Q Do ear seeds provide enough pressure to stimulate the points? A Unlike acupuncture, which uses a needle in the skin for twenty or thirty minutes at a time, ear seeds provide lighter stimulation over a much longer period of time. They work on their own just by sitting on the skin, but you can also press on them to give them an additional boost. Be gentle—you don’t want to irritate the skin under the seed. You don’t want to leave ear seeds on for more than five days at a time. It could desensitize the point. If you’d like to wear ear seeds continuously, I suggest taking a day or two off between applications. Q How do you know they’re working? A Ideally, you notice a change yourself. I’ve been in situations where I’ve been lecturing about traditional Chinese medicine, and while I talk, somebody is going around and putting ear seeds on everybody’s Shen Men, the relaxation point on the ear. It’s one of the most common points we use in auricular acupuncture. There’s often a palpable feeling in the room once everyone’s ear seeds are placed. Shari Auth, DACM, LAc, LMT, is a cofounder and the chief healing officer at WTHN, an acupuncture studio and wellness brand in New York City. Auth has practiced holistic health for more than two decades and integrates a number of modalities into her work, including acupuncture, cupping, herbal medicine, and sound therapy. This article is for informational purposes only, even if and regardless of whether it features the advice of physicians and medical practitioners. This article is not, nor is it intended to be, a substitute for professional medical advice, diagnosis, or treatment and should never be relied upon for specific medical advice. The views expressed in this article are the views of the expert and do not necessarily represent the views of goop.
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What Happens When You Get Dust In Your Lungs? What happens if you get dust in your lungs? Particles that evade elimination in the nose or throat tend to settle in the sacs or close to the end of the airways. But if the amount of dust is large, the macrophage system may fail. Dust particles and dust-containing macrophages collect in the lung tissues, causing injury to the lungs.. Can breathing in dust harm you? How can dust be harmful? Breathing dust into the lungs – inhaling dust can create respiratory problems. Swallowing dust – inhaled dust can enter the digestive tract causing gastrointestinal tract irritation. Alternatively, they can enter the bloodstream causing damage to other organs and tissues. How do I know if my lungs are damaged? If your lungs are damaged, or if you have a serious illness like COPD, emphysema or lung cancer, you may experience one or more of the following symptoms: Shortness of breath during simple activities. Pain when breathing. Dizziness with a change in activity. What vitamins help repair lungs? Experts believe vitamins A, C, and E—the so-called ACE antioxidants—combat oxidative stress in the lungs that can lead to COPD. Several studies have shown that these vitamins, as well as vitamin D, may help improve lung health. How do you tell if your house is making you sick? What are the symptoms of sick building syndrome?throat irritation.breathing difficulties.tightness in the chest.runny nose.allergy-like symptoms, such as sneezing.burning sensations in the nose.dry, itchy skin rashes.headaches.More items… What kills dust mites naturally? Eucalyptus oil, in specific concentrations, has been scientifically proven to kill 99.99% of dust mites. Bosisto’s Eucalyptus Dust Mite Wash has been specifically formulated based on scientific research, with pure eucalyptus oil to kill dust mites in bedding, linen and other washables. Where is lung pain felt? The lungs do not have a significant amount of pain receptors, which means that any pain felt in the lungs probably originates somewhere else in the body. However, some lung-related conditions can result in pain in the left lung. The chest contains several vital organs, including the heart and lungs. Can drinking water clean your lungs? Water is the key to staying hydrated, flushing out toxins and keeping your body clean. Spice up your water for your lungs to make sure you are taking in enough water daily. When dealing with a condition like COPD, drink the recommended amount of water to keep up with your health. Can dust cause a cough? Asthma and allergy coughs are typically caused by swelling or irritation of the airways. Allergies like hay fever can cause a chronic dry cough. If you’re sensitive to dust, pet dander, pollen, mold, or other common allergens, then your allergy symptoms may include a cough. What happens if you breathe in plastic? “When plastic waste and food waste are burned, they produce dioxin and furan. These elements, even in small quantities, can cause death,” he said on Sunday. If dioxin is inhaled, it can instantly cause coughing, shortness of breath and dizziness. Long-term exposure to dioxin can also cause cancer. How do you get dust out of your lungs? Ways to clear the lungsSteam therapy. Steam therapy, or steam inhalation, involves inhaling water vapor to open the airways and help the lungs drain mucus. … Controlled coughing. … Drain mucus from the lungs. … Exercise. … Green tea. … Anti-inflammatory foods. … Chest percussion. How can I check my lungs at home? A home lung function test uses a peak flow meter or a home spirometer to monitor and evaluate any breathing problems you may have on a day-to-day basis. A peak flow meter allows you to measure your peak expiratory flow (PEF). PEF measures how much air you breathe out when you try your hardest. Does holding breath help lungs? Holding breath benefits Holding your breath, as well as generally improving breathing and lung function, has useful, potentially lifesaving benefits, including: increasing life span by preserving the health of stem cells. Can you get pneumonia from breathing in dust? Many different germs can cause pneumonia, including bacteria, viruses, and fungi. You can also get it from breathing in (aspirating) food, liquid, chemicals and dust. If you have pneumonia caused by a virus it is called viral pneumonia. What can I drink to detox my lungs? Here are a few detox drinks that can help improve your lungs and overall health during the winter season:Honey and hot water. This powerful drink can help detoxify the body and fight off the effects of pollutants. … Green tea. … Cinnamon water. … Ginger and turmeric drink. … Mulethi tea. … Apple, beetroot, carrot smoothie. What drink is good for lungs? It is best to drink cayenne pepper tea that is also a great source of beta-carotene, which has great effects on reducing the many symptoms of asthma. Ginger is not only anti-inflammatory but also helps detoxifying and promotes the elimination of pollutants from the lungs. Can dust make you ill? That’s according to a new study in the journal Environmental Science and Technology. Those chemicals and others in dust have been linked to serious illnesses such as asthma and cancer, as well as to hormonal changes and developmental and reproductive problems, the researchers say. Which juice is best for lungs? Beet, Apple and Blackberry Juice Today, — along with ginger and blackberries, — they are known for their anti-inflammatory properties. In conjunction with the antioxidant quercetin found in the skin of apples, this sweet juice is perfect for building lung health while healing the body from within. What can breathing in dust cause? You may not think it’s a big deal when you breathe in dust, but for some people, it could bring on a lung disease called hypersensitivity pneumonitis. It’s an allergic reaction to particles in the dust, and it can cause symptoms like coughing and shortness of breath. Is living in a dusty room bad? Household dust is mostly made up of human skin, microscopic creatures and dead bugs. … Repeated, long-term exposure to high levels of dust of any form can harm your health. Normal household exposure will probably not cause you any problems, but working in a dusty environment may well do so. Do your lungs clean themselves? Lungs are self-cleaning organs that will begin to heal themselves once they are no longer exposed to pollutants. The best way to ensure your lungs are healthy is by avoiding harmful toxins like cigarette smoke and air pollution, as well as getting regular exercise and eating well.
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Welcome to the World of Nanomedicines Bioresponsive Polymer Therapeutics: Synthesis and Characterisation of Novel Nanomedicines EPSRC Platform Grant 2006 – 2010 The descriptor "polymer therapeutics" is an umbrella term used to describe polymeric drugs, polymer-drug conjugates, polymer-protein conjugates, polymeric micelles to which drug is covalently bound, and multi-component polyplexes being developed as non-viral vectors. All sub-classes use specific water-soluble polymers, either as the bioactive itself or as an inert functional part of a multi-faceted construct for improved drug, protein or gene delivery.  
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Wheat Allergy vs. Celiac vs. Non Celiac Gluten Sensitivity | Allergy Wheat Allergy vs. Celiac vs. Non Celiac Gluten Sensitivity by Allergy Guy Differences between wheat allergy, celiac and non celiac gluten sensitivity are subtle but worth understanding to better manage symptoms and health outcomes. The most important thing to understand is the possibly serious health outcomes for celiacs if they eat gluten. As far as we know, the same is not true of wheat allergy or non celiac gluten sensitivity, on the other hand it may be too soon to be sure of this. However, our current understanding of celiac disease is that continued ingestion of gluten can lead to very serious health issues such as diabetes, thyroid problems and bowl cancer, to name just a few. The symptoms of these three conditions are generally similar, although with celiac disease, any organ in the body could be effected in some way. This is probably not the case with non celiac gluten sensitivity, although this condition is much less studied than celiac disease, and there is still much to learn about celiac disease too. Symptoms of wheat allergy can be as fast as a few minutes or a few hours. It is also possible to have an anaphylactic reaction; this is not generally considered a symptom of celiac disease. Celiac disease can take a few days or even weeks before symptoms become obvious. Non celaic gluten sensitivity is somewhere in between, hours to days. Since every individual is different, this information can only be considered general, and you may have a different experience. Non celiac gluten sensitivity is considered the correct diagnosis when both celiac disease and wheat allergy have been ruled out. However, celiac disease is diagnosed by detecting celiac-specific antibodies in the blood and/or by doing an intestine biopsy to look for villus atrophy. Both of these classic markers of celiac can be absent in some celiac patients, so celiac is hard to definitively diagnose. If you find that you have celiac symptoms, wheat allergy symptoms or gluten allergy symptoms, it is probably safest to assume that your long-term health will be far better if you completely eliminate gluten from your diet; and you will feel much better without the short-term symptoms. Being completely gluten-free is very hard for most people where a wheat-based diet predominates, so ruling out celiac disease is helpful so that you know if you can slide on your diet or not. What is your experience with wheat allergy, celiac or non celiac gluten sensitivity? Please leave a comment. (Visited 131 times, 1 visits today) Leave a Comment Previous post: Next post:
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3. Implement strategies to lower inflammation. Several cross-sectional and longitudinal studies connect high blood pressure with chronic inflammation, a driving force for nearly every disease on the planet. Lowering inflammation starts with what you put on your fork. Focus on anti-inflammatory foods like wild-caught seafood (rich in omega-3 fatty acids), freshly ground flax and chia seeds, spices like turmeric, and plenty of colorful plant foods. Good sleep, stress management, exercise, and the right nutrients can also help lower inflammation. In Europe hypertension occurs in about 30-45% of people as of 2013.[12] In 1995 it was estimated that 43 million people (24% of the population) in the United States had hypertension or were taking antihypertensive medication.[141] By 2004 this had increased to 29%[142][143] and further to 32% (76 million US adults) by 2017.[7] In 2017, with the change in definitions for hypertension, 46% of people in the United States are affected.[7] African-American adults in the United States have among the highest rates of hypertension in the world at 44%.[144] It is also more common in Filipino Americans and less common in US whites and Mexican Americans.[6][145] Differences in hypertension rates are multifactorial and under study.[146] Being overweight increases the risk of getting hypertension and increases the workload required of your heart. Diets designed to control blood pressure are often designed to reduce calories as well. Most of these diets require decreasing consumption of fatty foods and sugars while increasing your intake of lean protein, fiber, fruits, and vegetables. A weight loss of just 10 pounds can make a significant difference in your blood pressure. Instead of an arbitrary goal to “lose weight,” talk with your doctor about a healthy weight for you. The Centers for Disease Control and Prevention (CDC) recommends a weight loss goal of one to two pounds a week. That means starting off eating 500 calories less per day than what you normally eat. Then decide on what physical activity you can start in order to reach that goal. If exercising five nights a week is too hard to work into your schedule, aim for one more night than what you’re doing right now. When that fits comfortably into your schedule, add another night. Being overweight increases the risk of getting hypertension and increases the workload required of your heart. Diets designed to control blood pressure are often designed to reduce calories as well. Most of these diets require decreasing consumption of fatty foods and sugars while increasing your intake of lean protein, fiber, fruits, and vegetables. A weight loss of just 10 pounds can make a significant difference in your blood pressure. ^ Mente, Andrew; O'Donnell, Martin; Rangarajan, Sumathy; Dagenais, Gilles; Lear, Scott; McQueen, Matthew; Diaz, Rafael; Avezum, Alvaro; Lopez-Jaramillo, Patricio; Lanas, Fernando; Li, Wei; Lu, Yin; Yi, Sun; Rensheng, Lei; Iqbal, Romaina; Mony, Prem; Yusuf, Rita; Yusoff, Khalid; Szuba, Andrzej; Oguz, Aytekin; Rosengren, Annika; Bahonar, Ahmad; Yusufali, Afzalhussein; Schutte, Aletta Elisabeth; Chifamba, Jephat; Mann, Johannes F E; Anand, Sonia S; Teo, Koon; Yusuf, S (July 2016). "Associations of urinary sodium excretion with cardiovascular events in individuals with and without hypertension: a pooled analysis of data from four studies". The Lancet. 388 (10043): 465–75. doi:10.1016/S0140-6736(16)30467-6. PMID 27216139. Your doctor may diagnose you with high blood pressure when you have consistent systolic readings of 140 mm Hg or higher or diastolic readings of 90 mm Hg or higher. Based on research, your doctor may also consider you to have high blood pressure if you are an adult or child age 13 or older who has consistent systolic readings of 130 to 139 mm Hg or diastolic readings of 80 to 89 mm Hg and you have other cardiovascular risk factors. ^ Mente, Andrew; O'Donnell, Martin; Rangarajan, Sumathy; Dagenais, Gilles; Lear, Scott; McQueen, Matthew; Diaz, Rafael; Avezum, Alvaro; Lopez-Jaramillo, Patricio; Lanas, Fernando; Li, Wei; Lu, Yin; Yi, Sun; Rensheng, Lei; Iqbal, Romaina; Mony, Prem; Yusuf, Rita; Yusoff, Khalid; Szuba, Andrzej; Oguz, Aytekin; Rosengren, Annika; Bahonar, Ahmad; Yusufali, Afzalhussein; Schutte, Aletta Elisabeth; Chifamba, Jephat; Mann, Johannes F E; Anand, Sonia S; Teo, Koon; Yusuf, S (July 2016). "Associations of urinary sodium excretion with cardiovascular events in individuals with and without hypertension: a pooled analysis of data from four studies". The Lancet. 388 (10043): 465–75. doi:10.1016/S0140-6736(16)30467-6. PMID 27216139. Lifelong control of hypertension will minimize the risk of developing heart attack, stroke, kidney failure, blindness, and a variety of other illnesses. Unlike other illnesses in which medications are taken for only a short period of time, high blood pressure medication is usually expected to be taken for the rest of the individual's life. It is uncommon, but not rare, that significant lifestyle changes can lower blood pressure readings to normal. Many kids and teens with high blood pressure have an unhealthy lifestyle — a bad diet, excess weight, stress, and too little physical activity. So the health care provider might recommend weight loss, exercise, reduced screen time (time spent watching TV, or using a computer or mobile devices), dietary changes, and even relaxation techniques. Teens with hypertension should not smoke because it can make the long-term associated heart problems worse. Another form of postural hypotension occurs typically in young healthy individuals. After prolonged standing, the individual's heart rate and blood pressure drop, causing dizziness, nausea, and often fainting. In these individuals, the autonomic nervous system wrongly responds to prolonged standing by directing the heart to slow down and the veins to dilate thereby removing blood from circulating in the arteries. During relaxation of the heart (diastole), the left ventricle of the heart fills with blood returning from the lungs. The left ventricle then contracts and pumps blood into the arteries (systole). The blood pressure in the arteries during contraction of the ventricle (systolic pressure) is higher because blood is being actively ejected into the arteries. It is lower during relaxation of the ventricle (diastolic pressure) when no blood is being ejected into the arteries. The pulse we feel when we place our fingers over an artery is caused by the contraction of the left ventricle and the ejection of blood. The NHLBI is part of the U.S. Department of Health and Human Services’ National Institutes of Health (NIH)—the Nation’s biomedical research agency that makes important scientific discovery to improve health and save lives. We are committed to advancing science and translating discoveries into clinical practice to promote the prevention and treatment of heart, lung, blood, and sleep disorders, including high blood pressure. Learn about the current and future NHLBI efforts to improve health through research and scientific discovery. Patient-activated event recorder: If the episodes of bradycardia or tachycardia are infrequent, a 24-hour Holter recording may not capture these sporadic episodes. In this situation, a patient can wear a patient-activated event recorder for up to 4 weeks. The patient presses a button to start the recording when he or she senses the onset of an abnormal heart rhythm or symptoms possibly caused by low blood pressure. The doctor then analyzes the recordings later to identify the abnormal episodes. We stimulate high-impact research. Our Trans-Omics for Precision Medicine (TOPMed) Program includes participants with high blood pressure, which may help us understand how genes contribute to differences in disease severity and how patients respond to treatment. The NHLBI Strategic Vision highlights ways we may support research over the next decade, including new efforts for studying high blood pressure. In normal blood pressure for elderly & adults over 50, increased systolic blood pressure is a major risk factor for heart disease. Systolic blood pressure tends to increase steadily over time due to stiff arteries, a build-up of plaque, and a higher rate of cardiac and vascular disease. This means older adults need to be even more vigilant about monitoring their blood pressure. High blood pressure can cause problems for a mother and her baby. High blood pressure can harm a mother’s kidneys and other organs and can cause early birth and low birth weight. If you are thinking about having a baby and have high blood pressure, talk with your doctors so you can take steps to lower or control your high blood pressure before and during the pregnancy. Blood pressure monitors for use at home can be bought at drug stores, department stores, and other places. Again, these monitors may not always give you a correct reading. You should always compare your machine’s reading with a reading from your doctor’s machine to make sure they are the same. Remember that any measurement above normal should prompt a visit to the doctor, who can then talk with you about the best course of action. Hypertension does not usually cause any noticeable symptoms. When it does, you might experience dizziness, shortness of breath, headaches, and nosebleeds, which could indicate that your blood pressure is rising. Complications such as heart disease, stroke, and kidney failure can occur if long-term hypertension is not adequately treated. A hypertensive emergency, which is an uncommon and dangerous event, may cause blurry vision, nausea, chest pain and anxiety. Postural hypotension is considered to be a failure of a person's cardiovascular system or nervous system to react appropriately to sudden changes. Usually, when a person stands up, some of their blood pools in their lower extremities. If this remains uncorrected, it would cause the person's blood pressure to fall or decrease. A person's body usually compensates by sending messages to their heart to beat faster and to their blood vessels to constrict, offsetting the drop in blood pressure. If this does not happen, or does not happen quickly enough, postural hypotension is the result. Low blood pressure readings in healthy people without symptoms or organ damage need no treatment. A doctor should evalute all patients with symptoms that are possibly due to low blood pressure. Patients who have had a major drop in blood pressure from their usual levels even without the development of symptoms also should be evaluated. The doctor needs to identify the cause of the low blood pressure; remedies will depend on the cause. For example, if a medication is causing the low blood pressure, the dose of medication may have to be reduced or the medication stopped. Do not adjust medication dose on your own, and do not stop taking any medication without first consulting your doctor. 3. Implement strategies to lower inflammation. Several cross-sectional and longitudinal studies connect high blood pressure with chronic inflammation, a driving force for nearly every disease on the planet. Lowering inflammation starts with what you put on your fork. Focus on anti-inflammatory foods like wild-caught seafood (rich in omega-3 fatty acids), freshly ground flax and chia seeds, spices like turmeric, and plenty of colorful plant foods. Good sleep, stress management, exercise, and the right nutrients can also help lower inflammation. If your blood pressure is elevated, your doctor may request you have more readings over the course of a few days or weeks. A hypertension diagnosis is rarely given after just one reading. Your doctor needs to see evidence of a sustained problem. That’s because your environment can contribute to increased blood pressure, such as the stress you may feel by being at the doctor’s office. Also, blood pressure levels change throughout the day. Unfortunately, a problem doesn’t always announce itself with a fanfare of trumpets. Even the highest blood pressure can be entirely asymptomatic. Similarly, low blood pressure also known as hypotension can occur in your patient despite no symptoms seemingly being present. This is particularly true if the patient is lying still in an unmonitored bed. She'll inflate the cuff to a pressure higher than your systolic blood pressure, and it will tighten around your arm. Then she'll release it. As the cuff deflates, the first sound she hears through the stethoscope is the systolic blood pressure. It sounds like a whooshing noise. The point where this noise goes away marks the diastolic blood pressure. In Europe hypertension occurs in about 30-45% of people as of 2013.[12] In 1995 it was estimated that 43 million people (24% of the population) in the United States had hypertension or were taking antihypertensive medication.[141] By 2004 this had increased to 29%[142][143] and further to 32% (76 million US adults) by 2017.[7] In 2017, with the change in definitions for hypertension, 46% of people in the United States are affected.[7] African-American adults in the United States have among the highest rates of hypertension in the world at 44%.[144] It is also more common in Filipino Americans and less common in US whites and Mexican Americans.[6][145] Differences in hypertension rates are multifactorial and under study.[146] Electrocardiogram (ECG): This tests the heart's electrical activity. This test is more commonly used for patients at high risk of heart problems, such as hypertension and elevated cholesterol levels. The initial ECG is called a baseline. Subsequent ECGs may be compared with the baseline to reveal changes which may point to coronary artery disease or thickening of the heart wall. Low blood pressure readings in healthy people without symptoms or organ damage need no treatment. A doctor should evalute all patients with symptoms that are possibly due to low blood pressure. Patients who have had a major drop in blood pressure from their usual levels even without the development of symptoms also should be evaluated. The doctor needs to identify the cause of the low blood pressure; remedies will depend on the cause. For example, if a medication is causing the low blood pressure, the dose of medication may have to be reduced or the medication stopped. Do not adjust medication dose on your own, and do not stop taking any medication without first consulting your doctor. High blood pressure is more common in older people. At age 45, more men have hypertension than women. By age 65, this is reversed and more women are affected. People with diabetes have a greater risk of hypertension than those without diabetes. Having a close family member with high blood pressure also increases your risk of developing it. About 60% of all people with diabetes also have hypertension. Blood pressure refers to the force exerted by circulating blood on the walls of blood vessels and constitutes one of the principal vital signs. The pressure of the circulating blood decreases as blood moves through arteries, arterioles, capillaries, and veins; the term blood pressure generally refers to arterial pressure, i.e., the pressure in the larger arteries, arteries being the blood vessels which take blood away from the heart. If your systolic and diastolic blood pressure are in two different categories, doctors consider the number that is in the higher category. For example, if your blood pressure is 135/91, your systolic blood pressure is in the prehypertensive range and your diastolic blood pressure is in the range of Stage 1 hypertension. Your measurement or 135/91 would place you in the category of Stage 1 hypertension. High blood pressure, or hypertension, is a condition in which the force of blood against artery walls is too strong. It is common ailment, and it is common for many Veterans to hear about hypertension at their health care appointments. Over time, without treatment, high blood pressure can damage the arteries, heart, and kidneys and can lead to heart disease and stroke. James, P.A., Oparil, S., Carter, B.L., Cushman, W.C., Dennison-Himmelfarb, C., Handler, J., & Ortiz, E. (2013, December 18). 2014 evidence-based guideline for the management of high blood pressure in adults: Report from the panel members appointed to the eighth joint national committee. Journal of the American Medical Association. Retrieved from http://jamanetwork.com/journals/jama/fullarticle/1791497 Some people may ask why doctors are lowering the threshold for high blood pressure, when it was already difficult for many patients to achieve the previous blood pressure targets of below 140 mm Hg/90 mm Hg, said Dr. Pamela B. Morris, a preventive cardiologist and chairwoman of the ACC's Prevention of Cardiovascular Disease Leadership Council. However, Morris said that the guidelines were changed because "we now have more precise estimates of the risk of [high] blood pressures," and these new guidelines really communicate that risk to patients. So, just because it's going to be difficult for people to achieve, "I don't think it's a reason not to communicate the risk to patients, and to empower them to make appropriate lifestyle modifications," Morris told Live Science. Moderate or severe bleeding can quickly deplete an individual's body of blood, leading to low blood pressure or orthostatic hypotension. Bleeding can result from trauma, surgical complications, or from gastrointestinal abnormalities such as ulcers, tumors, or diverticulosis. Occasionally, the bleeding may be so severe and rapid (for example, bleeding from a ruptured aortic aneurysm) that it causes shock and death rapidly. 6. Cultivate stress management. You don’t need a meta-analysis of cohort studies to prove stress can raise blood pressure, but they exist. You can’t eliminate stress, but you can minimize its impact. Research shows yoga and meditation create effective strategies to manage stress and blood pressure. If those aren’t your thing, consider other stress-relieving tactics including deep breathing or practicing mindfulness. 1. Concentrate on foods that lower blood pressure. Sugary, processed foods contain salt, sugar, damaged fats, and food sensitivities like gluten that contribute to or exacerbate high blood pressure. Shifting to a whole, unprocessed foods diet can dramatically impact your blood pressure. Many whole, unprocessed foods are rich in potassium, a mineral that supports healthy blood pressure. Some research shows that too much sodium and low amounts of potassium – can contribute to high blood pressure. Research shows people with high blood pressure can benefit from increased potassium in foods including avocado, spinach, wild-caught salmon, and sweet potatoes. The cuff is placed around the upper arm and inflated with an air pump to a pressure that blocks the flow of blood in the main artery that travels through the arm. The arm is held at the side of the body at the level of the heart, and the pressure of the cuff is gradually released. As the pressure decreases, a health practitioner listens with a stethoscope over the artery at the front of the elbow or an electronic machine senses the pulsation. The pressure at which the practitioner (or machine) first hears a pulsation from the artery is the systolic pressure (the top number). As the cuff pressure decreases further, the pressure at which the pulsation finally stops is the diastolic pressure (the bottom number). Hypertension occurs in around 0.2 to 3% of newborns; however, blood pressure is not measured routinely in healthy newborns.[33] Hypertension is more common in high risk newborns. A variety of factors, such as gestational age, postconceptional age and birth weight needs to be taken into account when deciding if a blood pressure is normal in a newborn.[33] Recognizing heart attack symptoms and signs can help save your life or that of someone you love. Some heart attack symptoms, including left arm pain and chest pain, are well known but other, more nonspecific symptoms may be associated with a heart attack. Nausea, vomiting, malaise, indigestion, sweating, shortness of breath, and fatigue may signal a heart attack. Heart attack symptoms and signs in women may differ from those in men. It's tough to get a reading on your average blood pressure if you only measure it at the doctor's office. Buy a home monitoring kit at your local pharmacy. Take two readings a day, morning and night, for a few days. Repeat these steps a few times a year, and share the results with your doctor. Better understanding of your blood pressure is the first step to preventing heart disease and stroke. ^ Jump up to: a b c d e National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents (August 2004). "The fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents". Pediatrics. 114 (2 Suppl 4th Report): 555–76. doi:10.1542/peds.114.2.S2.555. PMID 15286277. 3. Implement strategies to lower inflammation. Several cross-sectional and longitudinal studies connect high blood pressure with chronic inflammation, a driving force for nearly every disease on the planet. Lowering inflammation starts with what you put on your fork. Focus on anti-inflammatory foods like wild-caught seafood (rich in omega-3 fatty acids), freshly ground flax and chia seeds, spices like turmeric, and plenty of colorful plant foods. Good sleep, stress management, exercise, and the right nutrients can also help lower inflammation. Even occasional dizziness or lightheadedness may be a relatively minor problem — the result of mild dehydration from too much time in the sun or a hot tub, for example. Still, it's important to see your doctor if you have signs or symptoms of hypotension because they can point to more-serious problems. It can be helpful to keep a record of your symptoms, when they occur and what you're doing at the time. Medications used to lower blood pressure include diuretics (e.g., hydrochlorothiazide*), beta-blockers (e.g., atenolol, metoprolol), ACE inhibitors (e.g., ramipril, enalapril, lisinopril), calcium channel blockers (e.g., nifedipine, amlodipine), angiotensin II receptor blockers (e.g., losartan, valsartan), and direct renin inhibitors (e.g., aliskiren). If you have high blood pressure, it is important to get routine medical care and to follow your prescribed treatment plan, which will include heart-healthy lifestyle changes and possibly medicines. Heart-healthy lifestyle changes can prevent high blood pressure, reduce elevated blood pressure, help control existing high blood pressure, and prevent complications, such as heart attack, heart failure, stroke, vascular dementia, or chronic kidney disease. Another form of postural hypotension occurs typically in young healthy individuals. After prolonged standing, the individual's heart rate and blood pressure drop, causing dizziness, nausea, and often fainting. In these individuals, the autonomic nervous system wrongly responds to prolonged standing by directing the heart to slow down and the veins to dilate thereby removing blood from circulating in the arteries. One especially important cause of low blood pressure is orthostatic hypotension, which is sometimes referred to as postural hypotension. This happens when blood pressure drops rapidly during changes in body position—usually when changing from sitting to standing—inducing classic signs that the blood pressure is too low, like dizziness, blurry vision, and fainting. Unlike high blood pressure symptoms, which are poorly defined and often totally absent, low blood pressure symptoms tend to be more upfront and easily recognizable. The development of symptoms is often a warning sign of a potentially serious underlying disorder. Generally speaking, your blood pressure would need to fall pretty dramatically before symptoms develop. ×
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Monday, November 11, 2013 Preventing Toothbrush Abrasion The Cause Brushing improperly (especially with a hard-bristled toothbrush) can cause erosion/abrasion of your tooth or teeth. This is a very common problem. It begins as a small V- or U-shaped area of wear near the gingival (gum) tissue right next to the tooth, usually where the tooth and gum meet. Improper brushing causes the gum tissue to recede; and the tooth may become sensitive to heat, cold, or air stimulation. With time, more enamel wears away and a small horizontal notch is seen on the tooth at the gumline. This is not an area of decay, but a mechanical “cavity” cut in the tooth. Eventually the enamel is worn completely through and the dentin becomes exposed. When that occurs, some people experience severe tooth sensitivity. It may so severe that it is painful to drink cold beverages, breathe in air, or brush your teeth. Not everyone, however, experiences tooth sensitivity.   Once enough of the gum is brushed away, the root of the tooth becomes exposed. The root surface is not covered with enamel and is much softer than the enamel. It can also be unsightly to have the tissue recede. Since the root surface is not protected by hard enamel, if the improper brushing continues, the root cementum will be worn through and a notch will be made in the dentin. This notch will increase in size, weaken the tooth, and sometimes make the area more prone to decay. An Example of Tooth Abrasion Tooth Sensitivity Some patients with very little loss of tooth structure experience extreme sensitivity. This problem can usually be corrected with the application of a dentin-bonding material or other desensitizing chemicals. The sensitivity problem is often completely cured. The treatment can last (depending on your brushing habits) for 6 months or longer. If necessary, the tooth can be re-treated if the sensitivity returns. Some patients with a tremendous loss of tooth structure notice very little tooth sensitivity. Whether or not the teeth become sensitive, it is advisable to correct the brushing problem to slow down or eliminate the wear process. It is also recommended that the notches be restored with a tooth-colored filling material. This will restore the appearance of the tooth and protect the previously exposed dentin. In this way, even if you continue to brush improperly, the tooth will be protected. In cases of minor sensitivity, we might recommend the use of desensitizing toothpaste as a low-cost alternative to the placement of bonded materials. Some cases might also be managed through the use of topical fluoride applications. Preventing Abrasion The problems of improper toothbrushing are easily and inexpensively corrected when they are diagnosed in the early stages of development. If allowed to progress, the tooth damage will increase, as will the cost to repair it. The best solution is prevention!     Use a soft brush and proper technique to prevent abrasion. (See this blog.) Brush your teeth thoroughly but not abusively. Do not scrub them or cross brush them (an exaggerated horizontal brushing motion). We will select a method of toothbrushing that will best meet your needs and teach you to care for your mouth. Use a soft toothbrush. Change to a new brush every 3 months. But if it happens that you are creating the problem of toothbrush abrasion, get it corrected as soon as it is diagnosed. If you have any questions about toothbrush erosion or abrasion, please feel free to ask us at (512)250-5012. -Omni Dental Group 2 comments: 1. I appreciate you that you have discussed about such important issue. Nowadays dental plans are available to make dental treatment very reasonable to all. People adopt them to get discount. ReplyDelete 2. Wow, this is really interesting reading. I am glad I found this and got to read it. Great job on this content. I like it. teeth in a day dental ReplyDelete
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2003 132nd St SE Ste E Everett, WA 98208 US | Direction Massage Therapy FAQ Everett Chiropractor Answers Your Most Frequently Asked Massage Therapy Questions What is massage therapy? Massage therapy refers to the process of kneading the muscles and soft tissues of the back and extremities to reduce tension and alleviate muscle pain. Depending on the type of massage, they are good for overall relaxation, reducing muscle soreness after workouts and healing injuries. What are the benefits of receiving massages? Massage therapy provides benefits for individuals of all ages, and it can help aide chiropractic care in speeding recovery times and correcting spinal misalignments. Receiving regular massages also helps reduce overall body and muscle pain. It helps the muscles release lactic acid after strenuous exercise. It reduces the symptoms of depression and anxiety, and it helps improve flexibility and mobility. The benefits of massages are also cumulative. The more regularly you receive massages, the more pronounced the benefits. How does massage therapy help with flexibility and mobility? When the muscles, ligaments and tendons are tight, they restrict joint and vertebrae movement. This causes a loss of flexibility and range of motion that can dramatically increase your pain and make it difficult to perform daily tasks. Massage therapy can help loosen ligaments, tendons and soft tissues and reduce the number of tight and sore spots in your muscles. This helps improve the range of motion of your joints and the flexibility. It also helps improve the longevity of chiropractic adjustments so that your body has more time to heal. Does massage help alleviate stress? Receiving regular massages helps dramatically reduce tension, anxiety and headaches. It is no secret that most of our lives are filled with stress. We work stressful jobs. We go home to take care of our families, and we run around to perform errands on a weekly and sometimes daily basis. All of these activities can cause mental tension and feeling of being overwhelmed, and the body’s reaction to mental tension is to pump more stress hormones into the blood, which can raise blood pressure, impede sleep, cause tension headaches and contribute to feelings of exhaustion. Massages can help you manage and lower your stress by reducing muscle soreness, promoting blood flow and oxygenation to the muscles and giving you time to unwind from your daily obligations. Why types of massage do you offer? We offer Swedish, deep tissue and pregnancy massages. Swedish massages are very relaxing and help alleviate muscle tension, stress and symptoms of depression and anxiety. Deep tissue massages are not as relaxing as Swedish massages. That is because the focus is to reduce tight muscles and ligaments and facilitate recovery after exercise or after a sports injury. Pregnancy massages are great for alleviating the symptoms of pregnancy, including muscle soreness, back pain and stress and tension, and when they are combined with chiropractic adjustments, they can help make the delivery smoother. To schedule a massage with our massage therapist or an initial evaluation with our chiropractor, call our Everett chiropractic office at 425-379-6301. CONTACT US TODAY We look forward to hearing from you Office Hours Monday 9:00 am - 12:30 pm 3:00 pm - 6:30 pm Tuesday 9:00 am - 12:30 pm 3:00 pm - 6:30 pm Wednesday 9:00 am - 12:30 pm 3:00 pm - 6:30 pm Thursday Closed Friday 9:00 am - 12:30 pm 3:00 pm - 6:30 pm Saturday 9:00 am - 11:00 am Sunday Closed Monday 9:00 am - 12:30 pm 3:00 pm - 6:30 pm Tuesday 9:00 am - 12:30 pm 3:00 pm - 6:30 pm Wednesday 9:00 am - 12:30 pm 3:00 pm - 6:30 pm Thursday Closed Friday 9:00 am - 12:30 pm 3:00 pm - 6:30 pm Saturday 9:00 am - 11:00 am Sunday Closed
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Counsellor in Teddington. Photo Credit: Justus Hayes, Shoes on Wires Counselling for Anxiety - Counsellor in Teddington Welcome to my article on anxiety. I am a counsellor in Teddington and Twickenham areas. I can help you understand your triggers and how you manage the symptoms of anxiety. During our sessions, I offer interventions which help you balance your thoughts and emotions. You will learn to improve your self-awareness and confidence deal with daily exercises. We all know what anxiety feels like. When you suffer with anxiety, a stress response is triggered in your nervous system. Your body produces a flood of stress hormones such as cortisol and adrenalin. Now your brain is primed on high alert.  As your breathing and heart rate goes up, you feel an added sense of urgency. Your body and brain goes into overdrive, searching for immediate solutions that never seem to come. And don't bring relief. This is why you tend to overthink situations, or worry excessively. You start to anticipate worst case scenarios and imagine negative outcomes, even before they happen. Your mind is lost in a world of anxious thoughts. You may know your response is disproportionate, but you panic anyway. As the cycle continues, you begin to spiral downwards. You start reacting badly to uncertainty. Unable to clear your head, you delay decisions, doubt yourself and feel overwhelmed. Then you start to procrastinate over decisions and feel mortified when you make mistakes. Very soon, you avoid engaging with people at all. You're afraid to confront people and find it difficult to speak up for yourself. What is Anxiety? Feelings of anxiety are normal. Most stress is a natural response to challenging situations and a part of being human. We need a certain amount of stress to respond and act. Although you can develop an anxiety disorder, you can also reduce your symptoms. For most people, the symptoms of anxiety are very uncomfortable, but short-lived. For others, the symptoms are prolonged and distressing. When you experience the symptoms of anxiety try to slow down and notice what is happening. By developing your awareness of physiological changes, you can begin to adapt. For example, you may notice your heart starts pounding before a meeting with new people or an important event. Soon, you get butterflies in your stomach, shortness of breath or start to blush in a conversation. You might be in a constant state of  arousal: worrying and avoiding conflict in relationships. Or feeling jittery at the prospect of a meeting with your boss. Your feelings can be overwhelming at times. Perhaps you lead a frenetic lifestyle, or have to cope with challenging situations on a daily basis. You may even find yourself in the midst of a personal crisis. If your worries and fears, have a disproportionate impact on your life, then you may be suffering from a panic disorder. Dealing with anxiety Fortunately, for you there is a solution beyond medical treatment. I am a counsellor in Teddington. Over time, I help you with interventions that reduce anxious symptoms. Adapting to your anxiety, rather than ignoring it helps you regain control over your life. If you receive effective counselling, this can help you become more independent. As you talk things through in therapy, a counsellor can offer you insight. Feeling more self-empowered, you will learn self-regulate and manage your emotions. You might be aware that anxiety manifests itself in different ways: generalised anxiety, panic, phobias and compulsions. You may also be suffering from traumatic memories in the past. When you experience trauma it is processed differently in the brain. Your anxiety can often be rationalised and understood, whereas trauma has a highly disruptive impact on your life. You tend to react to trauma automatically, because it is triggered unconsciously by a stress response in the body. When you're triggered, it acts like a ‘panic alarm’ responding to overwhelming sensory stimuli. The causes of Anxiety The nervous system We all feel basic emotions like love, hate, anger, fear and sadness. Our emotions help us make sense of the world and survive. Our nervous system is based on stimulus and response. When we process emotions they have a beginning, peak and resolution. But if we do not process stress our emotions remain on high alert. They trigger chemical changes in the body which help us react to danger e.g. the ‘flight or fight’ response. However, when you become stuck in a cycle of fear, or there is resolution, your ability to adapt is limited. You remain trapped in a constant state of arousal and slide into a vicious spiral of anxiety. Social anxiety Your relationships can also be affected by anxiety. You may notice a tendency to explode, or withdraw from social contact. The people around you start to feel on edge and avoid you too. If your behaviour is dominated by anxiety it can affect how you interact with your partner, family and colleagues. You may treat them with anger, rejection or despair. The physical symptoms Anxiety is often accompanied by intense mental and physical sensations. You may be convinced that you cannot cope with work, and family life. Slowly, you become immersed in your pre-occupations and isolate yourself from others. Your physical symptoms increase with cold sweats, trembling, and heart palpitations. And you may start waking in the middle of the night. This creates a vicious cycle. As you dwell on your symptoms and anticipating catastrophe, anxiety begins to dominate your life. You may feel unable to resolve problems, which has a detrimental impact on friends and relatives. The people closest to you may feel drained. As you spiral downward, anxiety feeds on fear and leads to impulsive behaviours. You need to be confront anxiety with new interventions and thinking patterns. Symptoms of Anxiety • panic attacks • a constant sense of foreboding • headaches, stomach aches or acid reflux • pain and tension in the back, neck and shoulders • heart palpitations or pains • trembling, shaking, sweating and churning stomach • dizziness and nausea • paranoia and distorted thoughts or beliefs • restlessness • sleeplessness • dry throat or lump in throat • giddiness or nausea • obsessive thoughts • diarrhoea • anti-social behaviour When should I ask for help? Anxiety is a problem which feeds on itself. You cannot afford to hide away your problems in isolation. And you need to get help, as soon as possible. If physical symptoms are severe you need to consult a counsellor. At Counselling Teddington, EnduringMind I can help you to face your fears and rebuild your self-esteem. Counsellor in Teddington & Twickenham for anxiety I offer a safe environment for you to explore the causes of anxiety, as well as learning the techniques to manage them. You need to restore your self-confidence and regain a sense of normality. I offer counselling to help you find constructive ways of relieving the symptoms. With increased understanding you can manage your life better. You become more effective at meeting your needs and self-care routines. I can also help you to tolerate your fears. Sometimes understanding the cause of anxiety can help you gain a new perspective. When you understand stress, you can explore the impact on your personal life and relationships. The more you create space and time for yourself, the more you slow down and process emotions. I provide you with breathing techniques and muscle relaxation to break the cycle. If you practice mindfulness you become more self-aware. By learning about your unconscious triggers and patterns of thinking, you learn to face your fears. Counselling for Anxiety - Counsellor Teddington Anxiety in relationships Anxiety is a common problem in relationships. As the stresses and strains of everyday life begin to mount, your relationship unravels. And if you avoid your problems, no-one will mend your relationship for you. You may try to avoid your problems, or walk around on egg-shells, but nothing will change by itself. You explode in anger when things don't seem to go your way, but the conflict doesn't bring you closer. Very quickly, as you pick up on the fears and concerns of others, you rely on defensive patterns of behaviour. Your loving feelings begin to fade, while resentment and anger replaces the closeness you once had. You both experience anxiety in different ways. One of you feels despair, while the other views the malaise as a temporary blip. You also depend on each other in different ways. When couples get together very quickly and fall in love, they often ignore the problems. But feelings of euphoria are not easy to maintain. Once the excitement subsides, your disappointment begins to fester. And you notice there is very little intimacy to build on. A skilled counsellor, helps you develop more realistic expectations and renegotiate the boundaries. The symptoms of relationship problems. • you may fear abandonment. • your feelings of rejection and paranoia. • when you experience communication breakdown. • you experience a lack of sexual intimacy. • if your arguments continue without resolution. • when there is violence in your relationship. • you have financial pressures. • when you have health problems. • if your bond of trust is eroded, or broken.   When should I ask for help with Relationships? • when there has been a betrayal of trust; an affair, debt or secret. • if talking causes confusion or unbearable anger. • there is a constant sense of anxiety. • separation or divorce seems like the only option. • when you lack of emotional intimacy. • if you keep repeating the same arguments over and over again. • when you feel like you're walking around on eggshells.   I offer couples counselling to help you address anxiety. If possible, you can attend counselling together, unless one of you is unwilling or there is a threat domestic violence. Sometimes, you may feel more comfortable with individual counselling. When you're able to manage conflict and arguments, you begin to set a good foundation for your relationship. It is unrealistic to hope you will avoid conflict. When you come with your own values and beliefs, you must respect your differences. You must work through the issue if you want to thrive. And you need to develop new skills together. You need to acknowledge your differences; otherwise you will feel unheard. One partner may dominate, while the other 'disappears'. You learn that arguments are a healthy part of any relationship and can re-energise it. But patterns of aggression and denial are destructive. I help you to understand the nature of conflict in counselling. I will also direct you to the patterns you have inherited from your family and resolve them. • you can address destructive patterns of relating. • I help you improve communication. • you learn new relationship skills • I examine the impact of change and loss • when you address abusive relationships and domestic violence How to overcome anxiety Relationships need solid foundations. Two unhappy people with unresolved issues rarely forge long-term, happy relationships. It may be tempting to believe your partner will resolve unhappiness for you, but this hope often leads to disappointment. The pleasure in healthy relationships is wanting to be with someone, rather than being needy. Self-respect is an important ingredient for a good relationship. A counsellor helps foster healthier ways of managing the pain and loss. Sex can be a source of great enjoyment in a long-term relationship, but it also poses problems that leaves one partner feeling rejected or angry. Loss of desire is often an early sign of problems. A good therapist will help you resolve these tensions. When you are no longer able to empathise with a loved one, your relationship is in crisis. The cracks begin to show when one of you has an affair, or a secret debt. New Skills Interventions are available to help you listen and be heard in safe way. It is not about blaming each other or taking sides. A new depth of understanding can be reached or a couple may feel they have to separate or divorce. At Counselling in Teddington, EnduringMind separation & divorce counselling can help explore whether trust can be repaired or the relationship needs to end. It can allow the couple to split with less hostility.
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Your question: What happens if you get listeria during pregnancy? How do you know if you get Listeria while pregnant? Symptoms of listeriosis may show up 2-30 days after exposure. Symptoms in pregnant women include mild flu-like symptoms, headaches, muscle aches, fever, nausea, and vomiting. If the infection spreads to the nervous system it can cause a stiff neck, disorientation, or convulsions. What if you get Listeria while pregnant? During pregnancy, a listeria infection is likely to cause only mild signs and symptoms in the mother. The consequences for the baby, however, can be devastating — the baby can die in the womb or have a life-threatening infection within a few days of being born. Should I worry about Listeria while pregnant? Listeriosis can make people feel sick, but rarely causes severe health problems. What’s scary for moms-to-be, however, is that having it during pregnancy increases the risk of miscarriage, stillbirth and preterm birth. Babies of moms who had listeriosis during pregnancy are also at risk for listeria infection. How common is it to get Listeria while pregnant? Pregnant women are about 10 times more likely to get listeriosis than other healthy adults. An estimated 1/6 of all Listeria cases occur in pregnant women. IT IS INTERESTING:  Your question: Does Aveeno baby have carcinogens? What are the first signs of Listeria? What are the symptoms of listeriosis? Listeriosis can cause mild, flu-like symptoms such as fever, chills, muscle aches, and diarrhea or upset stomach. You also may have a stiff neck, headache, confusion, or loss of balance. Symptoms may appear as late as 2 months after you have eaten something with Listeria. What happens if you eat cold cuts while pregnant? Why can’t pregnant women eat deli meat? It’s best not to eat deli or lunch meats while you’re pregnant, unless the food has been heated until steaming (165 degrees F) right before serving. These meats can harbor bacteria, which can continue to grow even when refrigerated. How does Listeria cause stillbirth? It is hypothesized that after ingestion of the contaminated food, the Listeria enters into the bloodstream through bacterial translocation, and then disseminates, having a particular predilection for the fetoplacental unit, causing fetal infection. How do you get rid of Listeria? COOKED MEAT – Listeria is killed by cooking. Thoroughly cooking product to 165ºF/74ºC will kill the bacteria. Consumers at high risk for contracting listeriosis (e.g. pregnant women and the elderly) should reheat deli meats immediately before consumption. FREEZING – Listeria is not killed by freezing. What foods have listeria? Listeria • Unpasteurized (raw) milk and dairy products. • Soft cheese made with unpasteurized milk, such as queso fresco, feta, Brie, Camembert. • Raw fruits and vegetables (such as sprouts). • Ready-to-eat deli meats and hot dogs. • Refrigerated pâtés or meat spreads. • Refrigerated smoked seafood.
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Free shipping all orders over $50 (USA) The Simple SIBO Solution (Our 7 Step Protocol) Researched and Written by: Jenna Swift, APD Dietitian Jenna Swift, APD Dietitian SIBO is an increasingly problematic issue people face, especially those with IBS.  So let's see what the research say for tackling this big issue. Article Featured Image Table of Contents Diagnosis & Confirmation of SIBO  It can be hard to differentiate symptoms of SIBO from other gastrointestinal disorders. After all, bloating, diarrhea, abdominal pain and nausea can be attributed to any number of digestive disorders. That is why diagnosis should be the first step in the road to SIBO recovery. Currently, two tools exist that measure bacterial overgrowth.   1. Small Intestine Aspirate and Fluid Culture- As the name implies, it involves taking a sample of fluid from the small intestine by inserting a flexible tube down your throat and feeding it through to your small intestine. This is accepted as the gold standard diagnostic tool. However the main drawback is the invasive nature of the procedure.   2. Breath Testing- This method is more popular for its non-invasiveness. It measures hydrogen or methane in breath samples after drinking a solution of glucose. If there is an abundance of bacteria in the small intestine, they will break down the sugar and produce hydrogen and/or methane and carbon dioxide.  Correct Underlying Cause  The gastrointestinal system has built-in defence mechanisms that naturally protect against bacterial overgrowth. • Acid in the stomach helps to destroy pathogens. • Ileocaecal valve, aka the gatekeeper between the last portion of your small intestine and first portion of your large intestine. It helps to stop the billions of bacteria tracking backwards to the upper digestive tract. • Intestinal motility which refers to the contraction of smooth muscles, propels food along the digestive tract and clears remnants from the small intestine. SIBO can occur when one or more of these natural defences fail. Without identifying and correcting the underlying cause, then the chance of relapse is very high. Research has found that approximately 44% of people with SIBO may experience a relapse of symptoms within 9-months. Conventional approaches aim to remove overgrowth and repair motility without targeting the underlying condition(s). Working with a health professional who specialises in SIBO can help identify the contributing cause which can be categorised into 3 main areas: 1) Disorders of the protective antibacterial mechanisms • Low stomach acid caused by antacid and proton pump inhibitor (PPI) medications.  • Low fibre diet  • Stress reduces production of hydrochloric acid • Pancreatitis and pancreatic insufficiency  • Coeliac disease • Crohn’s disease  2) Motility Disruption • Altered bowel movements (constipation / diarrhea)  • Opiate painkillers slow transit time  • Snacking interrupts the migrating motor complex (MMC) which is the recurring motility pattern that occurs in the stomach and small intestine during fasting.  • Age (motility decreases with age) 3) Anatomical Abnormalities  • Diverticula • Gastrectomy • Short bowel syndrome • Ileocaecal valve resections  • Small intestinal obstruction  __________________________________ *** At this point, management of SIBO will likely occur in phases and will differ between health professionals. Regardless of the order of each phase, the common goal will be to remove overgrowth, provide symptom relief using diet and promote gut healing. Individuals will move through each phase as symptoms improve.*** __________________________________ Remove Overgrowth There are three main approaches to eradicating overgrowth of bacteria in the small bowel. Due to the stubborn nature of SIBO, some people may need to use a combination of these approaches to successfully remove overgrowth. 1. Conventional antibiotics : Rifaximin is the most commonly used antibiotic for SIBO treatment. It is a non-systemic antibiotic which means that it does not pass the gastrointestinal wall into the bloodstream. It has reported success rates of around 50% for those with hydrogen-dominant SIBO. While less effective for methane-dominant SIBO, one study has reported success rates as high as 85% using a combination of Rifaximin and another antibiotic called Neomycin.  1. Natural herbal antimicrobials: Antimicrobials are herbs that help the body to destroy pathogens and target overgrowth. Berberine, cinnamon, pomegranate, garlic, oregano, thyme and neem are common herbs used to target overgrowth and support the immune system. 1. Elemental diet: Often reserved for when the above approaches (antibiotics and antimicrobials) are unsuccessful. The elemental diet is a nutritionally adequate liquid meal replacement diet. Nutrients are broken down into their most elemental form and do not require further digestion. They are easily absorbed and rid the bacteria of an opportunity to feed on them. Without a fuel source bacteria are starved of nutrients. Restore Movement  Promoting movement through the gastrointestinal tract is achieved using medications and/or natural prokinetic agents. They help to stimulate the migrating motor complex, which are the waves of contractions that propel undigested food and bacteria along the gastrointestinal tract during fasting.  In other words, this allows bacteria to migrate towards the large bowel and prevents accumulation in the small bowel.  Pharmaceutical Prokinetics- Motilium (Domperidone), Reglan (Metoclopramide), Zithromax (Erythromycin) Natural Prokinetics- ginger, globe artichoke Restrict Diet  There are several elimination style diets that provide symptom management for SIBO. Unfortunately many of these diets lack the evidence to support them as a specific treatment protocol for SIBO. They include; • Low FODMAP Diet: This may improve SIBO symptoms however there is no evidence to support it being a treatment option for SIBO.  • The Specific Carbohydrate Diet (SCD): No studies have evaluated the use of the SCD to treat or manage SIBO. • The SIBO Specific Food Guide: No research studies are available to support the use of the SSFG for any disease process, including SIBO. • The Biphasic Diet: Developed by Dr Nirala Jacobi, it is a combination of the Low FODMAP diet and The Specific Carbohydrate Diet.  • Low Fermentation Diet (also known as The Cedars Sinai Diet): Developed by Dr Mark Pimentel, this diet aims to reduce SIBO symptoms by avoiding fermentable carbohydrates like beans and pulses, fiber supplements, oats, high FODMAP sweeteners, gums and some dairy. Another feature of this diet is to allow a 4 hour gap between meals to stimulate your MMC.  Alcohol should be avoided during SIBO treatment. Alcohol can disrupt gastric motility, disrupt the normal microbiome of the intestinal tract and promote inflammation. All of these factors can worsen SIBO symptoms and delay the healing process.    Repair the Gut  The gut healing stage aims to restore the intestinal lining using healing nutrients. • Probiotics: There is research to suggest that probiotics such as Lactobacillus casei may enhance the effectiveness of antibiotics. Patients showed greater improvement in their symptoms with dual probiotic + antibiotic therapy compared to antibiotics alone.   Conversely, some argue that taking probiotics while SIBO symptoms persist can contribute to an excess of bacteria in the small intestine. Recent studies have shown that taking probiotics may provoke symptoms like bloating and gas. In that case, some practitioners may advise against using probiotics until the repair phase to repopulate and heal the gut.  Therefore timing of probiotics will depend on your individualised SIBO treatment protocol. It also highlights the need for additional large scale studies regarding the effects of probiotics on SIBO risk.  • Digestive Supports: SIBO may cause digestive enzyme deficiencies, in particular lactase, maltase and sucrase which are produced in your small intestine. Adding in a digestive enzyme supplement  can facilitate the breakdown of food so that it can be easily absorbed and digested. This is particularly important as you start to reintroduce more variety back into your diet.  • L-Glutamine: Dietary supplementation with glutamine directly supports gut health and digestion. It helps to regulate the composition of the gut friendly microbiota and minimises the inflammatory response when the gut lining is irritated. Glutamine is also considered the most important nutrient for healing of ‘leaky gut syndrome’. This is because it is the preferred fuel for the single layer of cells that line your small intestine. These cells are held together by tight junctions which serve as a protective physical barrier between the intestines and bloodstream This essentially determines what nutrients or molecules can be absorbed into the bloodstream and blocks the entry of pathogens.  • Zinc: sf Correct Nutrient Deficiencies  Microscopic damage to the small intestine wall can diminish its absorptive capacity. This may lead to complications such as diarrhea, nutrient deficiencies, unintentional weight loss and conditions such as osteoporosis. Fat malabsorption occurs when bile salts that are needed to break down fat are disrupted by bacteria. This may lead to deficiencies in fat soluble vitamins A, D, E and K. Majority of the most symptoms of deficiency are rare. However in severe cases it can lead to night blindness (vitamin A), osteomalacia and tetany due to hypocalcemia (vitamin D) and prolonged prothrombin times (vitamin K).  Vitamin B12 deficiency and iron deficiency are also common complications of bacterial overgrowth. For this reason it is important to check vitamin and mineral status at baseline and throughout SIBO treatment (for example every 3-months). This will require a simple blood test and stool sample to check for fat malabsorption.  Incorporating rich sources of omega-3s and vitamin D into the diet from salmon, mackerel or sardines will help to prevent and correct deficiencies. Along with liver which is a valuable source of vitamin B12, iron and vitamin A. Evidence Based An evidence hierarchy is followed to ensure conclusions are formed off of the most up-to-date and well-designed studies available. We aim to reference studies conducted within the past five years when possible. • Systematic review or meta-analysis of randomized controlled trials • Randomized controlled trials • Controlled trials without randomization • Case-control (retrospective) and cohort (prospective) studies • A systematic review of descriptive, qualitative, or mixed-method studies • A single descriptive, qualitative, or mixed-method study • Studies without controls, case reports, and case series • Animal research • In vitro research Leave a comment Please note, comments must be approved before they are published References 1. Rao S, Bhagatwala J. Small Intestinal Bacterial Overgrowth. Clin Transl Gastroenterol. 2019;10(10):e00078. doi:10.14309/ctg.0000000000000078 2. Deloose E, Janssen P, Depoortere I, Tack J. The migrating motor complex: control mechanisms and its role in health and disease. Nature Reviews Gastroenterology & Hepatology. 2012;9(5):271-285. doi:10.1038/nrgastro.2012.57 3. Achufusi T, Sharma A, Zamora E, Manocha D. Small Intestinal Bacterial Overgrowth: Comprehensive Review of Diagnosis, Prevention, and Treatment Methods. Cureus. 2020. doi:10.7759/cureus.8860 4. Andrew C. Dukowicz G. Small Intestinal Bacterial Overgrowth: A Comprehensive Review. PubMed Central (PMC). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3099351/. Published 2022. Accessed January 13, 2022.
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Disease, Illness & ConditionsAches & PainsOral HealthInjuriesDigestive HealthEye CareWellnessChildren's HealthOlder AdultsFirst AidMental HealthHealth Care IndustryDisabilitiesAlternative MedicineReproductive Health Wet Brain: Thiamine, Diet, and Abstinence Updated on February 4, 2017 kimh039 profile image Kim is licensed in mental health and addiction counseling. Her education is in business, counseling, and health administration. What is Wet Brain? Wet brain is a term used to describe brain disease that is often associated with heavy alcohol consumption. The medical name for one of these conditions is Wernicke-Korsakoff syndrome (WKS). This syndrome is considered by some to be two separate conditions: Wernicke’s encephalopathy and Korsakoff’s psychosis. Some consider Wernicke-Korsakoff syndrome as one condition that involves different parts of the brain as it progresses. Wernicke's encephalopathy affects the cerebellum, the part of the brain that controls coordination and balance, and some forms of learning. Korsakoff's psychosis involves the part of the brain responsible for memory. Wernicke's encephalopathy affects the cerebellum, the part of the brain that controls coordination and balance, and some forms of learning. Korsakoff's psychosis involves the part of the brain responsible for memory. Human Brain Schematic drawing of the human brain, showing regions vulnerable to alcoholism-related abnormalities. Schematic drawing of the human brain, showing regions vulnerable to alcoholism-related abnormalities. | Source Wernicke-Korsakoff Syndrome Both conditions are caused by nutritional deficiencies, especially thiamine, or vitamin B1 deficiency in combination with nerve tissue damage caused by the toxic effects of alcohol. Alcohol affects the way thiamine is absorbed in the body and can also contribute to poor diet; a “liquid diet” consisting of little more than alcohol. So, heavy consumption of alcohol can lead to vitamin B1 deficiency which can lead to wet brain. Proper diet and thiamine supplements can prevent wet brain in heavy alcohol consumers. Abstinence, which means stopping alcohol use, can prevent further brain and nerve damage. Wet brain can also be caused by liver disease, poor diet or vomiting for several days; such as during morning sickness in pregnancy, or with bulimia – an eating disorder that involves “purging” or vomiting to avoid weight gain. It can also develop following gastric bypass surgery, and in elderly persons who live alone and are malnourished. Some research suggests there may also be a genetic component involving an inherited lack of the enzyme, transketolase, that contributes to the development of brain disease. Whether it is considered a separate condition or the earlier part of a progression, Wernicke’s encephalopathy has a better prognosis than Korsakaff’s psychosis. Wernicke’s encephalopathy affects the cerebellum, the part of the brain that controls coordination and balance, and some forms of learning. Korsakoff’s psychosis involves the part of the brain responsible for memory. When recognized and treated early, Wernicke’s encephalopathy responds well and very rapidly to thiamine treatment. Korsakoff’s psychosis does not respond as well or as quickly to thiamine treatment, although 20% of people with Korsakoff’s psychosis do recover. The recovery process is slow; taking 6-12 months. Discontinuing use of alcohol is required. Wernicke’s encephalopathy is a short-lived and severe condition while Korsakoff’s psychosis is long lasting and debilitating. When brain damage is more severe, the course of care shifts from treatment to support and care for the patient and caregivers. People with Korsakoff’s syndrome often require nursing home or custodial care. Up to 80% of alcoholics have a thiamine deficiency. Some of these will develop serious brain disorders such as WKS. Approximately 80-90% of alcoholics who do develop Wernicke’s encephalopathy will go on to develop Korsakoff’s psychosis. There may be a genetic component that explains why some alcoholics with thiamine deficiency do not develop WKS, but more research needs to be done to understand why some people are more vulnerable than others. Symptoms of Korsakoff's Psychosis Korsakoff’s psychosis involves severe memory loss and confabulation – making up stories or talking fluently without facts. A person with Korsakoff’s retains other cognitive functions, to include intellect. Their use of confabulation is an attempt to fill in memory gaps. They are not deliberate or intentional lies: that would require more memory than they have. If you asked the person if you had met before, the person with Korsakoff’s psychosis would make up an elaborate story about how you met that is entirely fantasy. The person is not able to process and store new information, and cannot recall things that happened five minutes after they happen. They will often repeat themselves as a result of not remembering they said something or the response to what they said. Korsakoff’s psychosis often follows DTs (delirium tremens) when a person is withdrawing from alcohol without adequate medical supervision. Symptoms of Wernicke's Encephalopathy Wernicke’s encephalopathy is characterized by three symptoms: 1. mental confusion – confused, delirious, and apprehensive. 2. paralysis of the nerves that move the eyes – nystagmus; difficulty moving eyes to follow a visual stimulus. 3. difficulty with muscle coordination, walking (ataxia) and balance; an unsteady gait. Nystagmus is often the first symptom to appear. It is also the first symptom to disappear in response to treatment. It is not necessary to have all three symptoms of Wernicke’s encephalopathy. The disorder may be present in a person who has only one or two of the symptoms. Autopsies have shown that many cases of thiamine deficiency related encephalopathy were not diagnosed in life because not all of the symptoms were present. Wernicke-Korsakoff Syndrome (WKS) Other Alcohol Related Brain Disorders Cerebral atrophy (brain shrinkage) or alcoholic dementia is related to alcoholism, as well, and is typically seen in people in their 50s and 60s. This condition also responds to thiamine treatment, healthy diet and discontinuation of alcohol use. The damage that has already been done is not reversible, but treatment can stabilize the condition and prevent further progression. There are other alcohol related brain disorders, to include: alcoholic cerebellar degeneration, portosystemic encephalopathy (PSE), central pontine myelinolysis, and Marchiafava-Bignami disease. The term “wet brain” is an informal term, not a medical term, used to describe a number of irreversible, organic brain diseases related to alcohol that cause mental impairment and physical disabilities, and can result in the need for nursing home care. © 2010 Kim Harris Comments 0 of 8192 characters used Post Comment • kimh039 profile image Author Kim Harris 5 years ago I am so sorry to hear about the loss of your brother to Korsakoff's, Mare12360. The 12 steps talk a lot about how alcoholism leads to death, insanity or imprisonment, but most people don't really grasp what this means. Those who do are often so devastated by the disease's effects that they are at a loss as to how to respond. Thanks for taking a minute to read and post a comment, mare 12360. • profile image mare12460 5 years ago Sadly my brother was just diagnosed with Korsakoff's psychosis. No one in my family had heard about this illness prior to his run-in with it. If only the education level was more wide spread... Even the medical community - especially in a small town - didn't seem to be in-tune. Now I've lost my brother and his family has lost their husband/father. He will need permanent long-term care 24/7 - probably in a nursing home. Alcohol is evil and this illness needs a voice to educate the masses... Thanks for taking the first step in that regard. • kimh039 profile image Author Kim Harris 6 years ago Thanks so much fucsia. I was really glad I found the video on Robert's story. It takes some to listen to the whole video, but he does a good job explaining it from the caregiver's point of view. • fucsia profile image fucsia 6 years ago Very informative and detailed Hub. Great work! • kimh039 profile image Author Kim Harris 6 years ago Thank you ImChemist... for reading, rating and commenting. I appreciate it! • ImChemist profile image ImChemist 6 years ago Thanks for your informative hub , that i rated it useful. • kimh039 profile image Author Kim Harris 6 years ago I'm thinking they had been talking openly for quite some time about their conditions before they agreed to the filming. They may even have done it in the spirit of helping others or something. But yeah, it would be weird to be talked about like that. And they both did seem really nervous about the camera. Thanks for stopping by to read and comment psychicdog. • psychicdog.net profile image psychicdog.net 6 years ago Good lesson re Vitamin B. Bit hard to take the Doctor1979 talking like he does - pointing out a man's defects in front of him! - cold, analytical and a bit dehumanizing - the guy is still a person with feelings (isn't he?) and pointing out his defects was a bit harsh I thought. • kimh039 profile image Author Kim Harris 6 years ago Thanks vocalcoach. Isn't it amazing how much we learn from each other?! So much to learn, so little time. Can you imagine if one day you woke up and there was nothing left to learn! • vocalcoach profile image Audrey Hunt 6 years ago from Nashville Tn. A simply wonderful hub Kim! I have learned so much from this information. Thank you and God Bless! • kimh039 profile image Author Kim Harris 7 years ago It sounds like that could be another hub, Bard. Thanks for stopping by to read and comment. I'm glad you're keeping up with your vitamins. • Bard of Ely profile image Steve Andrews 7 years ago from Lisbon, Portugal I found out about the benefits of B1 many years ago when I was into Scientology. Taking vitamins was one of the benefits I got from my time in it and something I learned from L Ron Hubbard. I always make sure I have Vitamin B complex tablets here. • kimh039 profile image Author Kim Harris 7 years ago Ah. Thanks Baileybear. Big bear hugs! • profile image Baileybear 7 years ago yes, I tweeted and facebooked • kimh039 profile image Author Kim Harris 7 years ago Not many people know about wet brain. Everyone who reads my hub will know! twitter, tweet and stumble upon! Thanks Baileybear. • profile image Baileybear 7 years ago Wet brain - I'd never heard of that. I imagine alcoholics would have at least a pickled liver! • kimh039 profile image Author Kim Harris 7 years ago interesting is good. thanks daydreamer. I have to say though, I'm wondering what exactly you found to be so interesting! • daydreamer13 profile image daydreamer13 7 years ago I found this very interesting! • kimh039 profile image Author Kim Harris 7 years ago I know, pretty brutal, eh Micky! Thanks for passing through, Micky. • Micky Dee profile image Micky Dee 7 years ago Wow. That's rough. This is a great message. Thank you Kim. God bless. • kimh039 profile image Author Kim Harris 7 years ago thanks must65gt..... and no sense starting now! • must65gt profile image must65gt 7 years ago never was a serious drinker, now I'm glad! lol...great hub and much useful information. thanks • kimh039 profile image Author Kim Harris 7 years ago @epi. The pro bono thing was supposed to be funny, but I went back to check and I don't get it either now! Erase it if u want. Thanks for the thanksgiving blessings and for being a loyal reader. Happy Holidays to you too. • kimh039 profile image Author Kim Harris 7 years ago Thank you Kaie........ eaaential for all of us, and especially for heavy drinkers! • Kaie Arwen profile image Kaie Arwen 7 years ago Very informative........... the B vitamins are essential! Kaie • epigramman profile image epigramman 7 years ago .....most of what you write (as of late) is way over my head but believe me it's fun to learn and be educated especially from someone like you my friend - I didn't even understand your PRO-BONO comment to me - but yes I liked Sonny Bono too much more than I ever liked Cher!!!! Abstinence - isn't that when you stay away from 'nooky' and wet brain - isn't that when men watch too much Sunday afternoon football???? Either way you always put together a solid hub - I love your expertise and your passion - and I am here post Thanksgiving to wish you all of the good things life like health and happiness - and every day for me is a thankful day for having good people like you in my Hub life - and I will never ever forget that wonderful tribute hub you did for me - awesome are you and lucky is me!!!! (poor grammar - who cares) • kimh039 profile image Author Kim Harris 7 years ago Thanks for reading it and commenting Jess. Have a safe, healthy and happy holiday season. • Jess Killmenow profile image Jess Killmenow 7 years ago from Nowheresville, Eastern United States I'll have to think twice about my drinking this holiday season! Thanks for this thorough and thought provoking article! • kimh039 profile image Author Kim Harris 7 years ago The advertising behind drinking makes it appear like everyone who drinks is beautiful, sexy, fun, popular, etc, and is aimed at a 20 something audience. That 20 something audience has a lot of legal consequences related to alcohol that makes getting a job more challenging. But if you put the 20 something mentality of "it will never happen to me" together with the fact that the physical consequences take many years to present, you have a captive audience for a lifetime. Thanks for your comments, Tony. Good point re rights to privacy. Even if the people signed a valid consent back in the 70s, it's unlikely they anticipated being posted on YouTube. Yikes! • tonymac04 profile image Tony McGregor 7 years ago from South Africa This is really very good. I was never a heavy drinker (though I had my moments when young!) but I have known quite a few. It is the attitude of society that I think is so harmful. People look at "drunks" as people to be laughed at, and drinking becomes something to joke about. For example, at one place where I worked many years ago the acceptable lunch was to go out for what was called a "hydraulic sandwich" which was described as "a piece of bread between two beers." Now that might sound funny but that's the attitude which somehow makes excessive drinking acceptable. The video you have posted here is a grim reminder that drinking has some really serious consequences. I did wonder, while watching the vid, about the men shown - were their rights to privacy not rather infringed by the vid? I felt uncomfortable watching, a bit voyeuristic. A good and "sobering" Hub with lots of useful information. Love and peace Tony • kimh039 profile image Author Kim Harris 7 years ago If you're still hubbing, you're in good shape. (a cue for me to check out your latest hubs) If I make it to 81 I'll come looking for you vern! • vrbmft profile image Vernon Bradley 7 years ago from Yucaipa, California I am "drinking" several packets of emergence each day which seems to have a good combo of B complex, including Thiamine and electrolytes, C, and a bunch of other "stuff." I have been taking good care of myself with diet and exercise since about 1987, even sober for 7 years, so perhaps I gave myself a little padding for the subsequent abuse. I am still eating well, drink lots of water, and still working at getting more sleep, altho this "place" keeps me up!! 100 is awesome age to look forward to. See you there!! Vern • kimh039 profile image Author Kim Harris 7 years ago take your thiamine too! I thought I was noticing fewer typos lately, Vern. Congrats on your continued sobriety, and say hi to your group from me. Disturbing you is my greatest pleasure. It's what I live for, ma raison d'etre. I've never aspired to live to 100 - 80 seems fair to me - but if I have to live to 100 to keep disturbing you, then that's just what I'll do! Seriously, thanks for stopping to read and comment, vern. love your comments. • vrbmft profile image Vernon Bradley 7 years ago from Yucaipa, California Well, you did an absolutely mawvelous job of scaring the sh*t out of me!! Before I read your hub, I was able to walk just fine, type pretty well, and did not feel confused. Now....! Well, I have been studying about the brain for a long time and knew well about the irreversible damage to the cerebellum and would keep checking in each day while I was drinking!! How is that for what? Insanity!! But I have to tell you, reading this hub leaves a pit in my stomach. I plan to live at least to one hundred, and it hurts deep inside how I may have on my own, with no help from nature, diminished my chances. but I am a hopeful person and I can still remember beyond what I think a person my age can readily remember in terms of numbers, etc., and even peoples' names and their connection to my life. Met a young man in the grocery store the other day and was able to remember who he was and how he was connected to me. Could not believe that I could do that!! Felt relieved! Anywho, this hub was a bit TOO GOOD. Chill out!!! lol Wake up calls are life giving, and I am still sober. Still going to the most wonderful meetings in the world, and they are just down the street! THANKS FOR A GREAT HUB, DISTURBING AS IT IS. Vern • kimh039 profile image Author Kim Harris 7 years ago Thank you, Quill for reading my hub and giving your feedback. I like the idea that my hub can help spread understanding! • profile image "Quill" 7 years ago Thanks kimh039... very well put together, an enjoyable read and something which is far to common today, yet little understood. Blessings • kimh039 profile image Author Kim Harris 7 years ago @Tony again. Oops. I meant Robert's story. • kimh039 profile image Author Kim Harris 7 years ago @alekhouse - Thank you! You're my role model for well thought out and put together hubs. I'm really glad you found it so interesting. • kimh039 profile image Author Kim Harris 7 years ago @Tony - Thank you much! I included the link to David's story to show his patience and understanding. 12 videos is a lot to watch (although I did! I found them fascinating), but he articulates in detail what it is really like from a loved one's perspective. • alekhouse profile image Nancy Hinchliff 7 years ago from Essex Junction, Vermont Really good hub, Kim...well thought out and put together. I found it extremely interesting • Tony DeLorger profile image Tony DeLorger 7 years ago from Adelaide, South Australia Thanks Kim. As always well structured and explanitory. Mental illnesses in general need so much more focus and understanding in society.
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What is HIV? HIV or Human Immunodeficiency Virus is an incredibly risky condition that impairs a person’s defense mechanism. It can lead to different complications that keep a man or woman from performing appropriately. It can afflict numerous internal organs and bring about a great deal of damage and harm. How can I get HIV? There are various means to get affected by HIV. Having sexual relations with an HIV affected person is a sure way to obtain the virus. Receiving blood from an HIV-infected man or woman is also a guaranteed means of getting HIV. An HIV-positive female who is expecting a baby can pass the virus on to her little one. What happens if HIV is not diagnosed?  If HIV is dismissed for an extended time, it might move on into AIDS. AIDS, which an acronym for Acquired Immune Deficiency Syndrome, is, in fact, the last stage of HIV. It involves various complications that can gradually lead to demise. Somebody who may have been afflicted with HIV needs to go through HIV screening without delay. By doing so, they can get medication and a treatment method at its onset before the virus assaults more parts of the body. Keep an eye out for prevalent HIV symptoms just like flu. Many people might not think that having flu is a manifestation of HIV, and they are inclined to forget about it, thinking that it is not anything dangerous or major. With this sort of thinking, they are putting themselves in peril and at remarkable risk. How can I test for HIV?  HIV testing and screening is obtainable in hospitals and STD medical centers. You can pay a visit to any of these facilities and make inquiries about how you can get yourself HIV tested. You may also use the internet and search for online HIV testing. A different way of testing for HIV is by buying home HIV test kits and carrying out the test by yourself. This last option essentially supplies you with the privacy which you require in this time of difficulty. Early identification of HIV guards you against harsh changes and mishaps that HIV can do. For that reason, you should be aware of how HIV is acquired so that you could protect yourself and realize if you are in extremely high danger of being tormented by it. People that are employed in the medical industry and are put through HIV patients and other disease problems are encouraged to be mindful when making use of blood samples and other specimens taken from the victims. They should wear the correct type of gear every time they have to be around those. HIV is a terrible disease that can be averted if you are well-educated and perceptive.
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fbpx This website uses cookies to provide the highest level of service. Your continued use of the website means that you agree to their use. To find out more click here. Zdjęcie główne artykułu Somatic Wisdom: A Journey through 7 Vital Body Segments Somatic Wisdom: A Journey through 7 Vital Body Segments Text from the series “Holistic Healing Chronicles: Nourishing Your Body, Mind, and Soul for Lasting Wellness” by Nisarga Eryk Dobosz. Greetings to all fellow seekers of healing and self-discovery!   When we’ve faced traumatic events or accidents in the past, our Autonomic Nervous System often activates a compassionate mechanism known as the high tone of the Dorsal Vagal Complex, inducing a freeze response. This typically results in fear or panic imploding within the body, hindering the expression and completion of the fight/flight response from the Sympathetic Nervous System. The body, in its wisdom, decides where to store this tension, forming fulcrums of tension. The Reichian approach is a fantastic way to identify these blocks in the body and address primary emotions from the trauma vortex. To release these tensions, we employ elements like touch, breath, movement, sound, and emotional expression. This process can unlock energies stored in our bodies for decades, allowing the life force to flow through us, fostering more joy, happiness, and vitality. Our bodies are mysterious and magical. In therapy, we explore the body from various perspectives—emotional, physical, psychosomatic, and energetic. This innovative approach to treating pain or trauma has its roots in the work of Wilhelm Reich, the father of body-oriented psychotherapy. Reich proposed the concept of orgone energy, a life force crucial for living organisms. He observed that “armoring” occurs when energy is bound by muscular contraction, impeding its flow through the body. Reich’s theory of segmental armoring describes seven segments where muscular tensions develop, each corresponding to the flow of life force in the body. This concept aligns with the Eastern philosophy of the 7 chakra system. Reich also introduced the idea of physical blocks visible in appearance, with overcharged and undercharged segments manifesting as atrophy in muscles and skin. Identifying the seven main segments of body armoring, we will delve into the emotional expressions associated with each: 1.Ocular Segment (Location: Head): The first segment encompasses the muscles of the eyes, forehead, cheeks, scalp, temples, and the occipital lobe (the center of vision in the brain). Emotional expressions associated with this segment include suspicion, amusement, contempt, detachment, guarding, fight, anger, and grief. 2.Oral Segment (Location: Face and Mouth): Moving down to the face and mouth, the oral segment involves muscles such as the mouth, chin, nose, jaw, and ears. Emotional expressions tied to this segment range from contempt, disgust, and longing to desire, fear, pain, anger, connection, self-awareness, and presence. 3.Cervical Segment (Location: Neck and Tongue): The third segment centers on the deep neck muscles and the tongue, along with its operational muscles. Emotional expressions associated with the cervical segment include self-pity, helplessness, longing, hurt, fear, pain, rage, freedom, creativity, and self-expression. 4.Thoracic Segment (Location: Chest and Heart): Moving further down, the thoracic segment involves the intercostal muscles, large chest muscles (pectorals), shoulder muscles (deltoids), and the heart and lungs. Emotional expressions linked to this segment encompass deep heart feelings, grief, mourning, longing, love, fear, rage, anger, and joy. 5.Diaphragmatic Segment (Location: Diaphragm and Solar Plexus): Centered around the diaphragm and solar plexus, the diaphragmatic segment influences emotional expressions related to pain and pleasure. The blocking of the diaphragm is significant, as it cuts the body in two, impeding sensing and feeling in the lower segments, including sexual feelings, excitation, rage, hate, terror, strength, and empowerment. 6.Abdominal Segment (Location: Abdomen and Lower Back): The abdominal segment encompasses the large abdominal muscles (rectus abdominis), transversus abdominis, and the lower section of the muscles along the spine (latissimus dorsi and sacrospinalis). Emotional expressions tied to this segment include pain, fear, pleasure, trust, and feelings related to nourishment and being nourished, creating a sense of relaxation in the center. 7.Pelvic Segment (Location: Pelvis and Lower Extremities): Finally, the pelvic segment involves almost all the muscles of the pelvis, including the genitals, urinary tract, buttocks (gluteus maximus), adductors and abductors in the thighs, hamstrings, and lower legs. This segment plays a crucial role in the overall bodily armoring, influencing emotional expressions associated with sexuality, power, and grounding.   In Biodynamic Breathwork, we systematically focus on releasing these belts of tension, moving from the top down. This process creates a pathway for repressed sexual energy to rise as it’s released, allowing it to flow freely. Energy, like water, seeks the path of least resistance. Clearing this pathway not only releases muscular constriction but also addresses emotional blockages, essentially facilitating trauma release.   With heartfelt compassion and dedication, Nisarga Eryk Dobosz   Follow Nisarga’s Facebook page – here Nisarga Eryk Dobosz – founder of the Integral Body Institute. He has been practicing bodywork, breathwork, meditation and tantra for over 20 years. He is a bodywork and breathwork therapist, specialising in Myofascial Energetic Release, Biodynamic Breathwork and Trauma Release and deep tissue work. An experienced teacher of Lomi Lomi Nui massage and Tantra. Share this article Comment Comments • Autor: vorbelutrioperbir Opublikowany: 2024-07-07 18:37:34 I've recently started a blog, the info you provide on this web site has helped me greatly. Thank you for all of your time & work. "Everyone is responsible and no one is to blame." by Will Schutz. http://www.vorbelutrioperbir.com
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How To Have A Superb Supplement Reviews With Marginal Spending A few of the supplements mohl byste se sem podívat can easily cause adverse effects. The main issue with taking any supplement is that it is actually challenging to predict the responses that might occur. A few of the supplements might offer you a symptom and they can’t detect what the trigger was actually. If you want to take the supplements without thinking about the effects, you are going to need to know which ones to take and which ones not to take. A few of the supplements will increase your power amounts as well as give you a much better metabolism. It is going to help you maintain yourself healthy and fit. A few of the supplements are going to aid enhance your testosterone level levels, which is among the keys to improving your muscular tissues. It will also help you remove body fat as well as sweets coming from your body system. This way, you will end up being leaner and more strong. 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You can easily go online as well as assess the product prior to obtaining it. The producer might have an internet site where you may review everything about the item and also review it. This may help you produce the very best decision feasible. They may give nutritional advise as well as health pointers, and also they may even inform you regarding the various brands of supplements. When you pick an item, the maker will not want you to get your chances up excessive. The item might possess been produced effectively, yet it can have a trouble along with its element checklist. A lot of supplements featured a specific checklist of active ingredients, therefore you can easily make certain that you are getting merely the most ideal quality. A bunch of these items contain organic components. A lot of items utilize fatty tissue and also coffee as the cornerstones. The two are actually not unsafe in their very own right, but it may produce all of them complicated to digest, causing a variety of side effects. Supplements are not a poor point. Many individuals gain from utilizing nutritional supplements to maintain their health and wellness. Unfortunately, there are actually a considerable amount of people that abuse the supplements that they are actually taking. Since there are so several business that generate these items, it can be actually tough to evaluate the high quality of an item. You need to have to very carefully investigate the business to see to it that they utilize excellent quality substances. They must also have a lot of customer help, as well as a guarantee. They need to have the ability to offer you along with the relevant information that you need to have to create a notified decision concerning the product. You will discover that you can easily make a better decision if you take the opportunity to go through supplement reviews. The major problem along with taking any supplement is that it is actually tough to predict the reactions that could happen. If you prefer to take the supplements without worrying about the consequences, you are going to have to recognize which ones to take and which ones not to take. To be actually secure, read through the supplement examines to observe what supplements are good for your physical body. If you are browsing for some assistance locating the best supplements, then these customer reviews can be an answer. Occasionally these ingredients will certainly certainly not be stated in the supplement evaluations, yet they will still be actually key variables in the performance of the item. Leave a Reply Your email address will not be published. Required fields are marked *
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Pin Me What are Some of the Best Treatments for Selective Eating Disorder in Children? written by: Mercedes Hamshar • edited by: Paul Arnold • updated: 1/9/2011 Selective eating disorder is often mistaken for fussy eating. However, it can persist into adulthood with serious consequences. Cognitive behavioral therapy and family therapy are effective selective eating disorder treatments. • slide 1 of 4 Selective eating disorder is an under recognized and under studied eating disorder. It is often thought simply to be 'fussy eating'. It is most common in young children but can persist through adolescence and adulthood. People with selective eating disorder will refuse to eat or even try new foods; foods that are not considered 'safe' by them. In extreme cases a person may refuse entire food groups and survive on only a few different foods. Obviously, this pattern of eating if left untreated can lead to malnutrition and other health problems. Therefore, it is important to pursue selective eating disorder treatments as soon as possible, and not to disregard severe 'fussy eating' in children as a phase that will be grown out of. Selective eating disorder is often considered more similar to phobias and obsessive compulsive disorder as opposed to other eating disorders such as anorexia nervosa and bulimia nervosa. This is because the refusal of certain foods in selective eating disorder appears to stem from a fear of the food, often due to a previous experience of choking on the food or because the food is similar in smell, taste or texture to another feared stimulus, or from a fear that the food is in some way dirty. In eating disorders such as anorexia nervosa and bulimia nervosa refusal of certain foods is based on body image and a desire to be thin. • slide 2 of 4 Cognitive Behavioral Therapy for Selective Eating Disorder Given its similarities to phobias and obsessive compulsive disorder, selective eating disorder can be effectively treated with cognitive behavioral therapy. This is done by challenging the irrational thoughts patients have about the foods they will not eat, in the same way that those suffering from phobias are challenged about their irrational fears. An exposure component, such as systematic desensitization may also be used. This involves encouraging the patient to try new foods in small steps, so as not to overwhelm them, which is especially important in children. A patient may be asked to first smell a food, and then to pick it up, and then to lick it before being asked to actually consume it. Treating children with cognitive behavioral therapy will often also involve a reward system to reinforce the desired behavior. With adults, treatment is usually reward enough. • slide 3 of 4 Family Therapy for Selective Eating Disorder Family therapy is also an option for selective eating disorder treatments; particularly in conjunction with cognitive behavioral therapy. A child's selective eating can cause great anxiety in their parents as they worry about their child's health. This anxiety can lead to increased conflict within the family unit and may be projected onto the child or the other parent. Feelings of depression, anxiety, anger, resentment, guilt and shame may follow which can harm familial relationships and may even lead to the breakdown of the family unit. Family therapy serves to remove blame from any one person and allows family members to strengthen their bonds in order to best cope with the child's selective eating disorder. • slide 4 of 4 References Jaffa, T. & McDermott, B. (2007) Eating disorders in children and adolescents. Cambridge: Cambridge University Press. Garner, D.M. & Garfinkel, P.E. (1997) Handbook of treatment for eating disorders. Guilford: Guilford Press. privacy policy
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