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Saturday 20 April 2013

Study says more efforts needed to regulate dietary supplements


Dietary supplements accounted for more than half the Class 1 drugs recalled by the US Food and Drug Administration

Dietary supplements accounted for more than half the Class 1 drugs recalled by the U.S. Food and Drug Administration from 2004-12, meaning they contained substances that could cause serious health problems or even death, a new study from St. Michael's Hospital has found.
The majority of those recalled supplements were bodybuilding, weight loss or sexual enhancement products that contain unapproved medicinal ingredients, including steroids, said the study's lead author, Dr. Ziv Harel.
Almost one-quarter of the substances are manufactured outside of the United States, he said in the study published online in the journal JAMA Internal Medicine.
Unlike pharmaceutical products, dietary supplements do not require FDA approval before they can be sold. The FDA defines a dietary supplement as a product taken by mouth that contains a "dietary ingredient" such as vitamins, minerals, herbs, other botanicals, amino acids or substances such as metabolites. There are about 65,000 dietary supplements on the market consumed by more than 150 million Americans.
Of the 465 drugs subject to a Class 1 recall in the U.S. between Jan. 1, 2004, and Dec. 19, 2012, 237 or 51 per cent were dietary supplements. The majority of recalls occurred after 2008 for reasons unknown, the researchers said.
Supplements marketed as sexual enhancement products were the most commonly recalled dietary supplements (95, or 40 per cent).
Dr. Harel, a nephrologist whose research focus is patient safety, said that when the FDA learns of an adulterated dietary supplement, it is required to contact the manufacturer to trace the source of the product and initiate a recall. However, a recent investigation by the Office of the Inspector general determined that the FDA does not possess accurate contact information for 20 per cent of supplement manufacturers.
The FDA has recently introduced a number of initiatives aimed at mitigating the impact of the most common adulterated supplements, including the creation of multinational enforcement groups and widespread media campaigns focusing on improving awareness.
"Despite these initiatives, products subject to Class I recalls continue to be readily available for sale, which may be due to an increasingly complex distribution network associated with these products, as well as ineffective communication by the FDA to consumers," Dr. Harel said.
"We also found a number of recalled products to be manufactured outside of the U.S. where manufacturing practices may not be subject to the same oversight and regulation required of domestic companies."
Dr. Harel said increased efforts are needed to regulate this industry. "Keeping the status quo may taint the dietary supplement industry as a whole."
Source:JAMA Internal Medicine.

Alternative medicine use by MS patients now mapped

A major Nordic research project involving researchers from the University of Copenhagen has, for the first time ever, mapped the use of alternative treatment among multiple sclerosis patients - knowledge which is important for patients with chronic disease and the way in which society meets them.People with multiple sclerosis (MS) often use alternative treatments such as dietary supplements, acupuncture and herbal medicine to facilitate their lives with this chronic disease. This is the result of a new study of how MS patients use both conventional and alternative treatments which has been carried out by researchers from five Nordic countries. The results have been published in two scientific journals, theScandinavian Journal of Public Health and Autoimmune Diseases.
“What we see is that patients do not usually use alternative treatments for treating symptoms, but as a preventative and strengthening element,” says Lasse Skovgaard, industrial PhD candidate from the Faculty of Health and Medical Sciencesand the Danish Multiple Sclerosis Society, who has been involved in conducting the questionnaire-based study among 3,800 people with MS in Denmark, Sweden, Norway, Finland and Iceland.Multiple sclerosis is a chronic disease which attacks the central nervous system, and which can lead to a loss of mobility and sight. Denmark is one of the countries with the highest incidence of the disease worldwide, with approx. 12,500 MS patients. At the same time, the number of MS patients in the West is increasing, posing considerable challenges in respect of treatment, prevention and rehabilitation.

Access to knowledge bank

Together with researchers from the five other Nordic countries, Lasse Skovgaard has spent three years gathering the new data, and he is delighted at what it offers:“Within the field of health research, it is often a question of studying the extent to which a particular type of drug affects a particular symptom. However, it is equally as important to look at how people with a chronic disease, for example, use different treatments to cope with their situation. Here, MS patients offer valuable experience. Their experiences constitute a knowledge bank which we must access and learn from,” he says.Lasse Skovgaard draws attention to the significance of this new knowledge because, if people with chronic disease are better able to manage their lives, it can potentially save society large sums of money.“There is a lot of talk about ‘self-care competence’, in other words patients helping themselves to get their lives to function. Here, many people with a chronic disease find they benefit from using alternative treatments, so we should not ignore this possibility,” says Lasse Skovgaard.At the same time, he emphasises that knowing more about why patients choose particular treatments is important in relation to improving patient safety because of the possible risks involved in combining conventional and alternative medicine.

Growing use of alternative treatments

According to the latest Health and Sickness Study from the Danish National Institute of Public Health (NIPH) in 2010, one in four Danes say that they have tried one or more types of alternative treatments within the past twelve months. Among MS patients, the use of alternative medicine has been growing steadily over the past fifteen years. In the researchers’ latest study, more than half of the respondents say that they either combine conventional and alternative medicine or only use alternative medicine.“We cannot ignore the fact that people with chronic disease use alternative treatments to a considerable extent, and that many of them seem to benefit from doing so. It doesn’t help to only judge this from a medical point of view or say that alternative treatments are nonsense – rather, we must try to understand it,” says Lasse Skovgaard.Highly qualified women top the listThe study shows that, among MS patients using alternative treatments, there is a significantly bigger proportion of people with a high level of education compared to those who do not use alternative treatments. There is also a larger proportion of highly paid people and of younger women.“Some critics are of the opinion that when alternative treatments are so popular, it is because they appeal to naïve  people looking for a miraculous cure. But our results indicate that it is primarily the well-educated segment that is subscribing to alternative treatments. And that using alternative treatments is part of a lifestyle choice,” says Lasse Skovgaard.He hopes that the new knowledge will improve communication regarding how the chronically ill use alternative treatments in combination with conventional medicine:“We see that so many people are combining conventional medicine with alternative treatment that it should be taken seriously by the health service. Until now, there hasn’t been much focus on the doctor-patient dialogue in relation to the alternative methods used by the chronically ill to manage their lives,” says Lasse Skovgaard. He says that the research group is continuing to analyse the results and, among other things, is conducting several interview studies based on the results of the questionnaires. The interview studies will, for example, provide additional knowledge on how patients perceive the risks associated with using alternative medicine and explore why some patients turn their backs completely on conventional medicine.  
 Source: Scandinavian Journal of Public Health.

Protein That Interferes With Appetite-suppressing Hormone Identified

Scientists from the University of Texas Medical Branch at Galveston have discovered a protein that can interfere with the brain's response to leptin. They've also created a compound that blocks the protein's action — a potential forerunner to an anti-obesity drug.In experiments with mice fed a high-fat diet, scientists from UTMB and the University of California, San Diego explored the role of the protein, known as Epac1, in blocking leptin's activity in the brain. They found that mice genetically engineered to be unable to produce Epac1 had lower body weights, lower body fat percentages, lower blood-plasma leptin levels and better glucose tolerance than normal mice. 
When the researchers used a specially developed "Epac inhibitor" to treat brain-slice cultures taken from normal laboratory mice, they found elevated levels of proteins associated with greater leptin sensitivity. Similar results were seen in the genetically engineered mice that lacked the Epac1 gene. In addition, normal mice treated with the inhibitor had significantly lower levels of leptin in their blood plasma — an indication that Epac1 also affected their leptin levels. 
"We found that we can increase leptin sensitivity by creating mice that lack the genes for Epac1 or through a pharmacological intervention with our Epac inhibitor," said UTMB professor Xiaodong Cheng, lead author of a paper on the study that recently appeared on the cover of Molecular and Cellular Biology, available on the journal's Web site at http://mcb.asm.org/content/33/5.toc. "The knockout mice gave us a way to tease out the function of the protein, and the inhibitor served as a pharmacological probe that allowed us to manipulate these molecules in the cells." 
Cheng and his colleagues suspected a connection between Epac1 and leptin because Epac1 is activated by cyclic AMP, a signaling molecule linked to metabolism and leptin production and secretion. Cyclic AMP is tied to a multitude of other cell signaling processes, many of which are targeted by current drugs. Cheng believes that understanding how it acts through Epac1 (and another form of the protein called Epac2) will also generate new pharmaceutical possibilities — possibly including a drug therapy that will help fight obesity and diabetes. 
"We refer to these Epac inhibitors as pharmacological probes, and while they are still far away from drugs, pharmaceutical intervention is always our eventual goal," Cheng said. "We were the first to develop Epac inhibitors, and now we're working very actively with Dr. Jia Zhou, a UTMB medicinal chemist, to modify them and improve their properties. In addition, we are collaborating with colleagues at the NIH National Center for Advancing Translational Sciences in searching for more potent and selective pharmacological probes for Epac proteins." 

Source:Molecular and Cellular Biology

 
 

Nonsurgical Treatment Turns Back the Clock And Shrinks Enlarged Prostate: Study

A study suggests that men with a common condition that causes frequent nighttime trips to the bathroom can get relief with a minimally invasive treatment that shrinks the prostate. The study is being presented at the Society of Interventional Radiology's 38th Annual Scientific Meeting in New Orleans. The early findings hail from the first prospective U.S. trial of prostatic artery embolization (PAE), which reduces blood flow to the prostate, thus shrinking it."Nearly all men eventually suffer from an enlarged prostate as they age, and this treatment is almost like turning back the clock and giving them the prostate of their youth," said Sandeep Bagla, M.D., the study's lead author and an interventional radiologist in the department of cardiovascular and interventional radiology at Inova Alexandria Hospital in Alexandria, Va. 
"Medications are of limited benefit and surgery—while it can correct the problem—can be risky and may cause significant side effects. PAE is a minimally invasive alternative with low risk that appears to reduce symptoms in the overwhelming majority of patients," he said. Benign prostatic hyperplasia (BPH) affects more than half of 50-year-old men and more than 80 percent of 80-year-old men. "All patients are looking for the least invasive treatment with lowest risk, and this U.S. clinical study confirms the results reported by interventional radiologists in Europe and South America," said Bagla. He noted that millions of men shy away from surgical and other transurethral procedures because they understandably do not want to risk urine leak, impotence or other complications that may arise from invasive procedures. 
In early findings of the study, 13 of 14 men (92 percent) who had PAE noticed a significant decrease in symptoms after one month. None of the men suffered any major complications, such as impotence, leaking urine or infection. Most went home the day of treatment. Enrollment of 30 men for the first prospective U.S. study to evaluate PAE for enlarged prostates is underway and will be completed by fall, said Bagla. The study will look at clinical success and safety and will follow patients for two years to assess long-term results. When the prostate becomes enlarged, it blocks urine flow through the urethra, leading to aggravating symptoms including nighttime urinary frequency, weak flow and inability to completely empty the bladder. Untreated, BPH can lead to bladder stones, poor kidney function and infections. Interventional radiologists have long treated a variety of cancerous and noncancerous conditions through embolization, which blocks blood flow to tumors and organs. For instance, uterine fibroid embolization (UFE) is used to shrink benign fibroid tumors in the uterus. By temporarily blocking blood flow through the prostate artery, PAE causes the prostate to shrink, providing a larger passageway for urine. 
"The participants in our study report a true lifestyle-changing effect after this treatment, with some men stopping medication for their prostate symptoms altogether," said Bagla. "Patients who have not been helped by surgery or laser treatments have benefited. Since the treatment does not involve placing a catheter or device into the penis, there is no risk of narrowing of the urethra, incontinence or bleeding," he noted.

Source:The Society of Interventional Radiology
 

Thursday 18 April 2013

Ricin (A poison found in castor bean) :New Technique of Bio terrorism


The U.S. Capitol Police announced on Wednesday that they had intercepted three suspicious letters this week, one of them addressed to President Obama, which may contain the poisonous substance Ricin.In addition to the letter sent to Mr. Obama, two letters being tested for ricin were sent to Sen. Roger Wicker, R-Miss. At least one of the letters addressed to Wicker tested positive in a preliminary field test for Ricin. Field tests are regularly inaccurate; therefore, the FBI is conducting more thorough tests on the letters. Ricin is a poison that is found in castor beans. It can be made from the waste produced when castor oil is made. It can be made into a mist, pellet, or powder and dissolved in water or weak acid. While it is still dangerous when it consumed, it is most deadly when it is inhaled because the body doesn't have stomach acids available to help diminish the effects.The poison remains stable under most temperatures, but becomes deactivated when it is placed in temperatures above 176 degrees F. No antidote exists.Dr. Kenneth Spaeth, director of the Occupational and Environmental Medicine Center in the department of population health at North Shore University Hospital in Manhasset, N.Y., told   that deaths from ricin poisoning are very rare, but animal tests have shown just how fatal the substance can be."Fortunately, it's not something that we see all the time," he explained. "But, it does happen. The fact that it's naturally made and extracted from a plant means that there is access."Spaeth, who wrote "Bioterrorism Sourcebook," which details the effects of many poisons, has not advised authorities on the current ricin investigations.When ricin enters a person's system, it gets inside their cells and stops them from making the proteins the body needs. This causes cell death, which eventually leads to other symptoms.Typically, ricin can be very damaging to the lungs and make breathing very difficult if it is inhaled. It can cause asthmatic symptoms, chest tightening, shortness of breath and death.If it is ingested, ricin causes less severe symptoms but still toxic effects. This includes nausea, vomiting, diarrhea and stomach pain.Symptoms can appear as early as four to eight hours after contact and as late as 24 hours when ricin is inhaled. Subjects will typically feel effects in less than 10 hours upon consumption."It doesn't happen very often, but for what it's worth when it is severe, death typically happens two to three days later. There can be long term effects, like breathing problems." "On the show, he is a very knowledgeable and great chemist, but in real life, it doesn't involve that much sophistication," Spaeth admitted.Spaeth added that it's very hard to weaponize ricin for a mass target because it requires specific technology, but instructions on how to make the poison are readily available on the Internet. The amount that is probably contained in the letters suggests that the amount of ricin being produced in these cases is on a smaller scale, but still dangerous.
Source:North Shore University Hospital,NY

Ayush dept issues good clinical practice guidelines for clinical trials in Ayurveda, Siddha & Unani medicines

The department of Ayush has issued good clinical practice (GCP) guidelines for clinical trials in Ayurveda, Siddha and Unani (ASU) medicines which will facilitate the researchers and institutions in adopting a standard way of good clinical practice while conducting the ASU clinical trials.
The guidelines are addressed to investigators and all those, who are interested, concerned, involved and affected with the conduct of clinical trials on ASU drugs. These are timely in view of the focus being given for scientific validation and for promoting evidence-based use of ASU treatments and are meant for voluntary use, not linked with any provisions of Drugs & Cosmetics (D&C) Act, 1940, and the rules thereunder.
The GCP is a set of guidelines which encompasses the design, conduct, termination, audit, analysis, reporting and documentation of the studies involving human subjects. The fundamental tenet of GCP is that in research on man, the interest of science and society should never take precedence over considerations related to the well being of the study subject.
It aims to ensure that the studies are scientifically and ethically sound and that the clinical properties of the ASU medicine under investigation are properly documented. The guidelines seek to establish two cardinal principles: protection of the rights of human subjects and authenticity of ASU medicine clinical trial data generated.
The objective of this 114-page log document is to encourage that clinical studies in ASU systems are undertaken in accordance with ethical and scientific standards and safety aspects and rights of participants are protected. Adhering to methodical documentation of trials will help bringing credibility to the efforts of persons and institutions involved in the process, which otherwise was lacking for want of any ASU-specific guiding document.
The guidelines are significant as although the ASU systems are known for their long history of safe and effective use, yet validation of safety and efficacy using scientific and evidence-based methodologies is needed for the purpose of universal acceptability, gaining confidence of practitioners and satisfaction of end users in the products.
The arguments of having long standing in the medical practice or market are often unconvincing and there has been persistent and increasing demand of documented proof of clinical safety and efficacy of ASU medicine. In this perspective, the clinical trials in ASU systems need to be guided on the principle of ‘Good Clinical Practice’. Researchers, sponsors and drug manufacturers, therefore, have to be well versed with the standard scientific procedures that are required to be followed while conducting clinical trials with ASU interventions to achieve objective and reproducible results.
These guidelines are formulated based on CDSCO Document on GCP Guidelines (2001) for Clinical Trials on Pharmaceutical Products. They should be followed for carrying out all ASU medicine research in India at all stages of drug development, whether prior or subsequent to product registration in India.
With the introduction of Drugs & Cosmetics Rule 158 B since August 2010, the requirement of proof of effectiveness for licensing of patent or proprietary ASU medicine has necessitated the development of present guidelines of Good Clinical Practice. However, these guidelines are for voluntary use by the researchers interested in taking up clinical trials by using ASU medicine. Conducting clinical trials and generating evidence on the basis of these guidelines would help convincing the world about the potential scope of ASU remedies in scientific parlance and address the questions of lack of evidence and validation. Immense opportunities thus lie ahead for the stakeholders to adopt the guidelines as a tool for promoting scientific and quality clinical research for credible outcomes.
The guidelines fulfill a long felt need to guide the direction of clinical trials on ASU remedies and therapies.
Source:Pharmabiz

Scientists Explore Basic Science Behind Acupuncture

The basic science and mechanisms of action of medical acupuncture has been explored by researchers. Acupuncture is increasingly being validated as an effective treatment for a broad range of medical conditions.In a special issue of Medical Acupuncture, a peer-reviewed journal published by Mary Ann Liebert, Inc., publishers presents a series of articles by authors from around the world who provide diverse and insightful perspectives on the science and physiologic responses underlying medical acupuncture. 
Understanding acupuncture in the same manner that we understand the mechanism of action and pharmacokinetics of a particular drug will, similarly, enable us to match treatments better with conditions, stated Guest Editor Richard F. Hobbs, III, MD. 
"The net effect will be improved outcomes," he wrote in his editorial "Basic Science Matters." 
In the editorial "Basic Science: Mysteries and Mechanisms of Acupuncture," Richard Niemtzow, MD, PhD, MPH, Editor-in-Chief of Medical Acupuncture, a retired Air Force Colonel and current Director of the USAF Acupuncture Center, Joint Base Andrews, Maryland, suggested that natural events have scientific explanations and that "the two explanations-one scientific, the other environmental-might both elucidate how acupuncture works." 
A Review article by John Longhurst, MD, PhD, University of California, Irvine, also describes how acupuncture's effects on cardiovascular function can decrease elevated blood pressure, improve blood flow, and relieve pain. 
Steven Harte, PhD and colleagues from the University of Michigan (Ann Arbor) and Massachusetts General Hospital and Harvard Medical School (Boston, MA) reported the results of a study aimed at understanding the differences in patient responses to traditional vs. sham acupuncture. 
They used pressure-pain testing to identify patients who may be less likely to respond to sham acupuncture based on levels of neurotransmitters in the brain. 
The study is described in the article "Pressure Pain Sensitivity and Insular Combined Glutamate and Glutamine (Glx) Are Associated with Subsequent Clinical Response to Sham But Not Traditional Acupuncture in Patients Who Have Chronic Pain." 
Keith Spaulding, ND, MAc and coauthors assessed the electrophysiological differences between actual and nearby (or sham) acupuncture points in the article "Acupuncture Needle Stimulation Induces Changes in Bioelectric Potential."
Source-ANI


 
 

New Technique Holds Promise for Liver Cancer Patients

According to a recent study a new invasive tumor ablation technique is providing hope for liver cancer patients who cannot undergo surgery. The study of 22 patients at the Universitatsklinikum Regensberg in Regensberg, Germany, found that irreversible electroporation (IRE) successfully destroyed tumor tissue in 70% of these patients.These patients were not responsive to conventional therapy or their tumor was in a location that was not suitable for standard treatment, said Dr. Philipp Wiggermann, lead author of the study. "If one considers that IRE was really the only option for these patients, the results are very promising," he said.There were two major complications in the study, but neither of them was life-threatening, said Dr. Wiggermann. One patient suffered partial thrombosis of the left portal vein. "It is not clear that the IRE procedure caused the partial thrombosis, but since it appeared after the ablation treatment, it was considered as a therapy-associated side effect," he said. 
There was accidental injury to another patient's gallbladder during the ablation treatment. "Accidental injury to surrounding organs is a risk of all percutaneous ablation techniques. Treatment of liver tumors is especially difficult due to the respiratory movement of the diaphragm leading to continuous shifting of the organ position," said Dr. Wiggermann.IRE disrupts the cell membrane and results in cell death. It is currently undergoing clinical investigation for treatment of malignant liver and lung lesions, Dr. Wiggermann said. Dr. Wiggermann's study will be presented April 18 at the ARRS Annual Meeting in Washington, DC.
Source:Universitatsklinikum Regensberg
 

Vibrating Fork Helps Combat Obesity

 Vibrating Fork Helps Combat ObesityAn electronic fork that vibrates when you eat quickly makes its debut, its French inventors claim that it can help combat obesity and digestive problems.Those who contribute at least $89 on the crowd funding website will get a HAPIfork, which comes in blue, green and pink, ahead of its planned general release to consumers in the United States and Europe later this year. 
"While our product is still a prototype, we're thrilled by the global response so far," said Fabrice Boutain, founder of the product's California-based developer HAPILABS, in a statement. 
"We believe this is affirmation of the growing consumer health awareness movement to gain better control of issues impacting weight and digestive issues as well as more serious issues such as diabetes and other chronic conditions." 
First shown at the Consumer Electronics Show, the HAPIfork -- the brainchild of French inventor Jacques Lepine -- is based on research that suggests people living in a fast-paced world can lose weight by eating more slowly. 
The gadget, which is dishwasher safe, includes LED warning lights, a USB connector and software for computers and smartphones enabling users to monitor their progress towards a healthier pace of eating.
Source-AFP
  

High Glucose Levels Could Impair Ferroelectricity in Body's Connective Tissues: Research

High sugar levels in the body come at a cost to health. More sugar in the body could damage the elastic proteins that help us breathe and pump blood suggests new research. The findings could have health implications for diabetics, who have high blood-glucose levels.Researchers at the University of Washington and Boston University have discovered that a certain type of protein found in organs that repeatedly stretch and retract - such as the heart and lungs - is the source for a favorable electrical property that could help build and support healthy connective tissues. But when exposed to sugar, some of the proteins no longer could perform their function, according to findings published April 15 in the journal Physical Review Letters
The property, called ferroelectricity, is a response to an electric field in which a molecule switches from having a positive to a negative charge. Only recently discovered in animal tissues, researchers have traced this property to elastin and found that when exposed to sugar, the elastin protein sometimes slows or stops its ferroelectric switching. This could lead to the hardening of those tissues and, ultimately, degrade an artery or ligament. 
"This finding is important because it tells us the origin of the ferroelectric switching phenomenon and also suggests it's not an isolated occurrence in one type of tissue as we thought," said co-corresponding author Jiangyu Li, a UW associate professor of mechanical engineering. "This could be associated with aging and diabetes, which I think gives more importance to the phenomenon." 
About a year ago, Li and collaborators discovered ferroelectric switching in mammalian tissues, a surprising first for the field. Ferroelectricity is common in synthetic materials and is used for displays, memory storage and sensors. Li's research team found that the wall of a pig's aorta, the largest blood vessel carrying blood to the heart, exhibits ferroelectric switching properties. 
Li said that discovery left researchers with a lot of questions, including whether this property is found in other soft tissues and the health implications of its presence. Observing differences in ferroelectric behavior at the protein level has helped to answer some of those questions. 
The research team separated the aortic tissue into two types of proteins, collagen and elastin. Fibrous collagen is widespread in biological tissues, while elastin has only been found in animals with a backbone. Elastin, as its name suggests, is springy and helps the heart and lungs stretch and contract. Ferroelectric switching gives elastin the flexibility needed to perform repeated pulses as with an artery. 
When researchers treated the elastin with sugar, they found that glucose suppressed ferroelectric switching by up to 50 percent. This interaction between sugar and protein mimics a natural process called glycation, in which sugar molecules attach to proteins, degrading their structure and function. Glycation happens naturally when we age and is associated with a number of diseases such as diabetes, high blood pressure and arteriosclerosis, a thickening and hardening of the arteries. 
The research team has focused solely on the aortic tissues, but this finding likely applies to other biological tissues that have the protein elastin, such as the lungs and skin. 
"I would expect the same phenomena will be observed in those tissues and organs as well," Li said. "It will be more common than what we originally thought." 
Researchers next will drill down even more to look at the molecular mechanics of ferroelectric switching and further try to connect the process with disease onset. 

Source:Physical Review Letters. 
 

Wednesday 17 April 2013

Indian supply drives down the cost of childhood vaccine

The cost of immunizing children in developing countries with a five-in-one vaccine is set to fall after a deal by an Indian supplier to slash the price it charges the GAVI global vaccines group.The agreement between Biological E and the GAVI Alliance, which funds bulk-buy vaccination programs for poor nations, highlights the growing role of India's low-cost drugs sector in supplying products around the world.India's staunch support for its generics sector has led to clashes with Western pharmaceutical companies, most recently following a high-profile defeat for Novartis in a cancer drug patent case this month.GAVI said on Thursday that Biological E would sell the pentavalent shot for $1.19 per dose, compared to a 2012 weighted average price of $2.17, saving it up to $150 million over the next four years.The five-in-one vaccine is the most widely used by GAVI. It protects against diphtheria, tetanus, whooping cough, hepatitis B and Haemophilus influenzae type B (Hib).GAVI also buys the shot from Johnson & Johnson's Crucell, GlaxoSmithKline, LG Life Sciences and Serum Institute of India.
Source:Reuters Health

Osteoporosis costs EU countries €37 billion every year


New report from the International Osteoporosis Foundation reveals the immense and growing burden of osteoporosis across Europe and forecasts a 25 percent increase in health economic costs by 2025

A new report prepared in collaboration with the International Osteoporosis Foundation (IOF) and the European Federation of Pharmaceutical Industry Associations, is the first to describe in detail the epidemiology, burden, and treatment of osteoporosis in all 27 member states of the European Union (EU27).
Published today in Rome in conjunction with the opening of Europe's largest osteoporosis congress, the report 'Osteoporosis in the European Union: Medical Management, Epidemiology and Economic Burden' shows that as Europe's population ages, fractures due to osteoporosis will result in increasing costs, disability and premature deaths. Approximately 3.5 million new fragility fractures occur annually in the EU. In 2010 alone, fragility fractures resulted in costs of €37 billion.
Osteoporosis is a common condition that causes bones to become weak and fragile. People with osteoporosis are at high risk of breaking a bone, even after a minor fall, bump or a sudden movement. These fractures can have a huge impact on the sufferer, leading to substantial pain, disability and even premature death. Based on data collected in 2010, the report found that 22 million women and 5.5 million men in the EU27 have osteoporosis.
IOF President Professor John Kanis of the WHO Collaborating Centre for Metabolic Bone Diseases, University of Sheffield Medical School, stated, "It is very worrying that health systems are unprepared to meet the growing tide of fractures due to osteoporosis. High risk individuals are not being routinely identified and offered treatment. The current model of osteoporosis management is not sustainable as Europe's population ages and fracture incidence and costs increase still further."
Even people who have broken a bone due to osteoporosis and present to hospitals or clinics for care, are not being systematically diagnosed and treated to prevent further fractures. A first fracture doubles the risk of suffering another, making prevention of this kind critical. Safe and cost effective medications to reduce the risk of fracture are widely available throughout Europe. However, one of the startling findings of the report is that, despite the rising number of people in need of treatment, the actual number of patients taking preventive medication is declining.
"The low rate of diagnosis and treatment in high risk individuals is compounded by the fact that, even when prescribed, approximately 50% of patients do not follow their treatment regimen," said Professor Juliet Compston, Professor of Bone Medicine at the University of Cambridge and Chair of the European Osteoporosis Consultation Panel.
Professor Compston went on to say, "It is apparent that Europe's health authorities must make provision in their healthcare planning to deal with the increase in fractures and associated disability. Key elements of any national strategy must include the better implementation of national guidelines, the establishment of fracture liaison services to identify high-risk patients, and improvement of adherence to proven cost-effective treatment by patients."

Several of the key findings are:


  • 22 million women and 5.5 million men in the EU27 have osteoporosis;
  • 43,000 people died as a result of osteoporotic fracture;
  • 3.5 million new fragility fractures are sustained annually, comprising 610,000 hip fractures, 520,000 vertebral fractures, 560,000 forearm fractures and 1,800,000 other fractures;
  • The annual direct economic burden of new and prior fragility fractures is € 37 billion;
  • The direct costs of caring for new fractures represented 66% of this cost, long-term fracture care 29% and pharmacological prevention 5%;
  • Fractures also accounted for 1.18 million quality-adjusted life years lost during 2010;
  • The costs of fragility fractures are expected to increase by 25% from 2010 to 2025;
  • The majority of individuals who have sustained an osteoporosis-related fracture, or who are at high risk of fracture, are untreated;
  • Despite an increase in the number of individuals requiring treatment, the number of patients on treatment is declining.
  • Source:International Osteoporosis Foundation 

University of Southern California scientists reveal natural process that blocks viruses


The human body has the ability to ward off viruses by activating a naturally occurring protein at the cellular level, setting off a chain reaction that disrupts the levels of cholesterol required in cell membranes to enable viruses to enter cells. The findings, discovered by researchers in molecular microbiology and immunology at the Keck School of Medicine of USC, hold promise for the development of therapies to fight a variety of viral infections.
"Previous studies have shown that our bodies are already equipped to block viruses such as Ebola, influenza, West Nile, and SARS," said Jae U. Jung, principal investigator and distinguished professor and chair of the Molecular Microbiology and Immunology Department. The study, "The antiviral effector IFITM3 disrupts intracellular cholesterol homeostasis to block viral entry," was published in the journal Cell Host & Microbe on April 17, 2013.
"We showed how this occurs," Jung said. "When a virus tries to enter, the immune system gets stimulated by interferon, which produces almost 300 host proteins, including IFITM3. This protein then disrupts the interaction between two other proteins, which, in turn, significantly increases the level of cholesterol in cells, and thereby blocks the virus."
Jung added that the increase in cholesterol is only within the endosome compartment of cells and has no impact on or effect from the level of cholesterol in the bloodstream.
Joining Jung in the study were Samad Amini-Bavil-Olyaee, Keck School postdoctoral research associate and first author of the paper, as well as Youn Jung Choi, Keck School graduate student and second author, and researchers from the University of California, Riverside and Scripps Research Institute. The research was funded by the National Institutes of Health (grants CA082057, CA31363, CA115284, DE019085, AI073099, AI083025, HL110609) and the Fletcher Jones Foundation.
Scientists long have known that interferon, a protein released by the body's cells and named after its ability to "interfere" with viral replication, can inhibit the spread of viruses, but didn't understand how. The Keck School investigators found that interferon-inducible transmembrane protein 3 (IFITM3) can disrupt the interaction between Vesicle-membrane-associated protein (VAPA) and oxysterol-binding protein (OSBP) that regulates the transport and stability of cholesterol, which are required for many viruses to take hold.
One of the main goals of his lab, Jung said, is to understand how the immune system recognizes viruses and blocks entry. In previous research, he and his colleagues have shown that a specific immune protein recognizes genetic information of the virus and then sets off an alarm signal in the host immune system.
Jung explained that in the most recent investigation, the rise in cholesterol was found to occur in the endosome compartment within the cell membrane. "The membrane is usually very flexible," he said. "With an increase in cholesterol it becomes rigid, and doesn't allow viruses to pass through the endosome compartment into cytosol, the fluid portion inside cells. We were surprised to find that changing the balance of cholesterol concentration affects viral entry."
The next step, he said, "will be to identify a therapeutic molecule that activates the expression and function of the IFITM3 protein, which potentially can be used to create an anti-viral therapy. It could target the endosome compartment in order to control, combat, or prevent the spread of viral infection."
Source:journal Cell Host & Microbe 

Researchers identify and block protein that interferes with appetite-suppressing hormone


Ever since the appetite-regulation hormone called leptin was discovered in 1994, scientists have sought to understand the mechanisms that control its action. It was known that leptin was made by fat cells, reduced appetite and interacted with insulin , but the precise molecular details of its function —details that might enable the creation of a new treatment for obesity — remained elusive.
Now, University of Texas Medical Branch at Galveston researchers have revealed a significant part of one of those mechanisms, identifying a protein that can interfere with the brain's response to leptin. They've also created a compound that blocks the protein's action — a potential forerunner to an anti-obesity drug.
In experiments with mice fed a high-fat diet, scientists from UTMB and the University of California, San Diego explored the role of the protein, known as Epac1, in blocking leptin's activity in the brain. They found that mice genetically engineered to be unable to produce Epac1 had lower body weights, lower body fat percentages, lower blood-plasma leptin levels and better glucose tolerance than normal mice.
When the researchers used a specially developed "Epac inhibitor" to treat brain-slice cultures taken from normal laboratory mice, they found elevated levels of proteins associated with greater leptin sensitivity. Similar results were seen in the genetically engineered mice that lacked the Epac1 gene. In addition, normal mice treated with the inhibitor had significantly lower levels of leptin in their blood plasma — an indication that Epac1 also affected their leptin levels.
"We found that we can increase leptin sensitivity by creating mice that lack the genes for Epac1 or through a pharmacological intervention with our Epac inhibitor," said UTMB professor Xiaodong Cheng, lead author of a paper on the study that recently appeared on the cover of Molecular and Cellular Biology, available on the journal's Web site athttp://mcb.asm.org/content/33/5.toc. "The knockout mice gave us a way to tease out the function of the protein, and the inhibitor served as a pharmacological probe that allowed us to manipulate these molecules in the cells."
Cheng and his colleagues suspected a connection between Epac1 and leptin because Epac1 is activated by cyclic AMP, a signaling molecule linked to metabolism and leptin production and secretion. Cyclic AMP is tied to a multitude of other cell signaling processes, many of which are targeted by current drugs. Cheng believes that understanding how it acts through Epac1 (and another form of the protein called Epac2) will also generate new pharmaceutical possibilities — possibly including a drug therapy that will help fight obesity and diabetes.
"We refer to these Epac inhibitors as pharmacological probes, and while they are still far away from drugs, pharmaceutical intervention is always our eventual goal," Cheng said. "We were the first to develop Epac inhibitors, and now we're working very actively with Dr. Jia Zhou, a UTMB medicinal chemist, to modify them and improve their properties. In addition, we are collaborating with colleagues at the NIH National Center for Advancing Translational Sciences in searching for more potent and selective pharmacological probes for Epac proteins."
Source:University of Texas Medical Branch at Galveston 


 

Happiness Linked With Sexual activity: Study

A recent study finds that people who have higher levels of sexual frequency report higher levels of happiness.That's one finding of Tim Wadsworth, an associate professor of sociology at the University of Colorado Boulder, who recently published the results of a study of how sexual frequency corresponds with happiness. 
As has been well documented with income, the happiness linked with having more sex can rise or fall depending on how individuals believe they measure up to their peers, Wadsworth found. 
His paper, "Sex and the Pursuit of Happiness: How Other People's Sex Lives are Related to Our Sense of Well-Being," was published in the February edition of Social Indicators Research
Using national survey data and statistical analyses, Wadsworth found that people reported steadily higher levels of happiness as they reported steadily higher sexual frequency. But he also found that even after controlling for their own sexual frequency, people who believed they were having less sex than their peers were unhappier than those who believed they were having as much or more than their peers. 
"There's an overall increase in sense of well-being that comes with engaging in sex more frequently, but there's also this relative aspect to it," he said. "Having more sex makes us happy, but thinking that we are having more sex than other people makes us even happier." 
Wadsworth analyzed data from the General Social Survey, which has been taking the "pulse of America" since 1972. All respondents in all years are asked whether they are "very happy, pretty happy or not too happy." 
The survey has included questions about sexual frequency since 1989. Wadsworth's sample included 15,386 people who were surveyed between 1993 and 2006. 
After controlling for many other factors, including income, education, marital status, health, age, race and other characteristics, respondents who reported having sex at least two to three times a month were 33 percent more likely to report a higher level of happiness than those who reported having no sex during the previous 12 months. 
The happiness effect appears to rise with frequency. Compared to those who had no sex in the previous year, those reporting a once-weekly frequency were 44 percent more likely to report a higher level of happiness. Those reporting having sex two to three times a week are 55 percent more likely to report a higher level of happiness. 
But while personal income can be inferred by a neighbor's flashy new car or home renovation, sex is a more cloistered activity. So how do, say, men or women in their 20s know how frequently their peers have sex? 
Though sex is a private matter, the mass media and other sources of information provide clues. For instance, Wadsworth noted, Cosmopolitan, Glamour, Men's Health, Men's Journal and The AARP Magazine — with a combined circulation of 30 million—frequently report the results of their own or others' sex surveys. 
Television and film depictions might also play a role, and, Wadsworth writes, "there is plenty of evidence that information concerning normative sexual behavior is learned through discussions within peer groups and friendship networks." 
As a result of this knowledge, if members of a peer group are having sex two to three times a month but believe their peers are on a once-weekly schedule, their probability of reporting a higher level of happiness falls by about 14 percent, Wadsworth found. 
Wadsworth is also a research associate at CU-Boulder's Institute of Behavioral Science and his research interests include the general study of happiness. 
He noted that the data do not necessarily prove that social comparisons cause the effects he observed. However, "I can't think of a better explanation for why how much sex other people are having would influence a person's happiness," he said. 
The way most people engage in social comparison can be problematic, he noted. "We're usually not looking down and therefore thinking of ourselves as better off, but we're usually looking up and therefore feeling insufficient and inadequate." 
On the other hand, people are social creatures and any sense of self or identity is dependent on others. In his introductory sociology classes, Wadsworth asks students to write three adjectives, any adjectives, to describe themselves. 
"And then I ask them, 'Do your adjectives have any meaning whatsoever if you're alone on a desert island, in the sense that there's no one to compare yourself to?' " 
Regardless of the adjective — attractive, smart, funny, poor — "these things are meaningful only if there's some sense of what other people are like," he said. "As such, we can only be wealthy if others are poor, or sexually active if others are inactive." 

Source:University of Colorado 

 



 

Non-food Plants Could be a Source of Nutrients

 Non-food Plants Could be a Source of NutrientsScientists have found that a plant cell component could be transformed into starch and serves as a source of nutrients.
A team of Virginia Tech researchers has succeeded in transforming cellulose into starch, a process that has the potential to provide a previously untapped nutrient source from plants not traditionally thought of as food crops. 
Y.H. Percival Zhang, an associate professor of biological systems engineering in the College of Agriculture and Life Sciences and the College of Engineering, led a team of researchers in the project that could help feed a growing global population that is estimated to swell to nine billion by 2050. 
Starch is one of the most important components of the human diet and provides 20-40 percent of our daily caloric intake. 
The research was published this week in the Early Edition of the Proceedings of the National Academy of Sciences. 
Cellulose is the supporting material in plant cell walls and is the most common carbohydrate on earth. This new development opens the door to the potential that food could be created from any plant, reducing the need for crops to be grown on valuable land that requires fertilizers, pesticides, and large amounts of water. 
The type of starch that Zhang's team produced is amylose, a linear resistant starch that is not broken down in the digestion process and acts as a good source of dietary fiber. It has been proven to decrease the risk of obesity and diabetes. 
This discovery holds promise on many fronts beyond food systems, reports Science Daily. 
"Besides serving as a food source, the starch can be used in the manufacture of edible, clear films for biodegradable food packaging," Zhang said. 
"It can even serve as a high-density hydrogen storage carrier that could solve problems related to hydrogen storage and distribution."
Source-IANS

 

 

Tuesday 16 April 2013

PSA test leads to further procedures, harms: study


Most older men with prostate cancer found by prostate-specific antigen (PSA) tests and biopsies opted for treatment in a new study - even if signs pointed to their disease being slow-growing and not immediately life-threatening.Still, among men with high PSA levels, only about one-third ended up getting a biopsy to determine if they had cancer at all, researchers found.They said those findings point to the difficult decisions, anxiety and side effects that can come after a seemingly simple choice to undergo prostate cancer screening."A lot of times older men just think, ‘It's a blood test, how bad can it be?'" said Dr. Louise Walter, a geriatrician from the San Francisco VA Medical Center."It's not just a simple blood test and then you're done and you know if you have cancer or not and you know what to do. It's one test in a cascade of tests that can lead to increasingly intensive interventions," Walter, who led the new study, told Reuters Health.The value of screening older men for prostate cancer has been in question for years. Last year, the U.S. Preventive Services Task Force (USPSTF), a government-backed panel, recommended against PSA tests in all men, regardless of age.Data have been conflicting about whether screening saves any lives. It's clearer that treatment after a positive test and biopsy can cause side effects such as impotence and incontinence, and that some cancers picked up on screening would never have caused symptoms because they are so slow-growing.For their new study, Walter and her colleagues analyzed insurance claims and medical records for almost 300,000 men, age 65 and older, who were screened for prostate cancer through the VA in 2003. Of those, just over 25,000 had a PSA level above the typical cutoff of 4 nanograms per milliliter of blood.The typical next step after a high PSA test is a biopsy, to show more clearly if a man has cancer and how serious it is. But over the next five years, just one-third of men with high PSA levels underwent biopsies, the study team reported in JAMA Internal Medicine."The only way PSA is going to benefit anyone is, if it's high, you follow it up with a biopsy to see, do you have an aggressive cancer as well?" Walter said. Otherwise, men just live with the worry of having high PSA levels - which they wouldn't know about if they had never been screened."We should talk with our patients before we send a PSA test to see if they would even remotely consider a prostate biopsy," she said. "You should definitely not be screening men who say, ‘I would not want to get a prostate biopsy.'"Of the one-third of men who did have their high PSA levels followed up on, about 63 percent were diagnosed with prostate cancer. More than 80 percent of those men chose to be treated - typically with prostate-removing surgery or radiation.That trend held even among men who were at least 85 years old, had multiple other health problems and had cancers with a low chance of growing and causing damage.
SIDE EFFECTS WITHOUT BENEFIT
In the U.S., about 239,000 men will be diagnosed with prostate cancer in 2013 but less than 30,000 will die of the disease, according to the American Cancer Society.Based on the new results, men should consider all of the implications of a positive PSA test before they decide to get screened, Walter said. About one in seven men who were treated for prostate cancer - including cancers that wouldn't have caused any symptoms - developed incontinence or impotence as a result, her team found.Dr. Timothy Wilt, who has studied prostate cancer screening at the Minneapolis VA Health Care System and the University of Minnesota School of Medicine, said the findings support the USPSTF's recent call against PSA testing."What this study shows is that there are serious, frequent and often persistent harms associated with the PSA blood test and that it's not simply a blood test but that there are downstream consequences," he said.Along with complications from treatment, the study shows about one in 1,000 men who had a biopsy died as a result, he said - cancelling out any possible small benefit from screening on cancer-related deaths.In another research letter published alongside Walter's study, researchers found more men would choose to get a prostate biopsy after an inconclusive PSA test - which provides no information about cancer - than after not getting tested at all."These results suggest that the ubiquitous use of simple but unreliable screening tests may lead to consequences beyond the initial cost and patient anxiety of inconclusive results; they may also lead to investigation momentum," wrote Dr. Sunita Sah from Georgetown University in Washington, DC, and colleagues."The most serious harm from testing is being diagnosed with prostate cancer and nearly all those men undergo treatment, yet treatment offers little to no reduction in prostate cancer mortality in the vast majority of those men," Wilt, who was not involved in the new research, told Reuters Health."Making a wise decision about PSA testing can often be to say no to the PSA test," he advised. "Men should not be tested unless they have the information about the harms and the potential small benefit and make an informed decision."
Source:Reuters Health

Hospitals need trained professionals to manage biomedical waste: Guru Moorthy

It is high time that all the hospitals in the country employed well trained professionals to manage biomedical and other hazardous waste generated from the hospitals, according to Guru Moorthy, director, MedSkills Learning.
As there are large number of hospitals and nursing homes mushrooming in every corner with huge quantum of biomedical waste generated from them, it is high time that the hospital managements across the country should have employed well trained professionals to manage biomedical wastes from them. At the same time, the government should also implement strict regulations to prevent environment pollution due to biomedical wastes.
Though the hospitals are rated for their quality standards based on three important criteria like good doctors, competent support staff and hygiene standards, the true test of a hospital’s hygiene standards can be judged only based on how it manages its biomedical waste, opined Guru Moorthy.
With growing concerns of the humungous waste generated in hospitals, effective waste management could become the differentiator in this sector. According to a recent report, every day about 904 tonnes of healthcare waste is produced by hospitals in India. Only about 15 per cent of this waste is infectious and as there is no proper segregation of this waste and not disposed properly it is accounting to an overall generation of 33,000 tonnes of healthcare waste annually.
Lack of waste management in hospitals is fraught with danger. Apart from the obvious infections it can cause, sharp objects in the waste could cause injuries to handlers. Disposed drugs and syringes could be repacked and wrongly used by unscrupulous agents.
The Ministry of Environment and Forests has set guidelines for healthcare establishments but very few implement a stringent waste management procedure.
To contain the snowballing of hazardous waste due to non segregation and improper disposal methods, the need of the hour is to employ well trained waste management professionals in the hospitals. The healthcare sector needs to sit up and notice the long term implications of bio-medical waste. There is an urgent need to have trained staff and that can execute an organisation’s waste management strategy. There is also a need to create awareness about the crucial role that the paramedical staff and plays in the medical ecosystem.
“There is a critical demand for skilled, trained and talented healthcare professionals. According to the Planning Commission, there is a shortage of over 40 lakh paramedical professionals in hospitals, nursing homes, pharma and other healthcare organisations,” said the Director.
Source:Pharmabiz

Botox Injections May Cause Depression, Suggests a Study

 Botox Injections May Cause Depression, Suggests a StudyA new study has found that the famous cosmetic anti-wrinkle treatment Botox injections could indirectly trigger depression. 
Botox injections given to eliminate crows' feet around the eyes makes one look younger but it prevents the smile from spreading beyond the mouth.
Dr Michael Lewis, a psychologist at Cardiff University explains that the facial expressions are also responsible for the emotions we feel. We smile when we are happy conversely smiling makes us feel happy. Botox injections, which work by freezing the muscles, prevent the signals, which make us happy while smiling, from being sent to the brain. This in turn may cause depression. Twenty-five women who had Botox injections for frown lines or crows' feet, or facial fillers were asked to answer questionnaires, rating their symptoms for depression. It was found that women who had their crows' feet treated had 50% higher depression level than those treated for frown lines. 
Researchers insist that people should respect and celebrate their emotional expressions as changing expressions could change the feelings. 
From a previous study, it is known that treating frown lines can reduce anger and make one feel happy. Hence, Dr Michael has planned to explore the possibility of using Botox to treat obsessive compulsive disorder. 

Source:Cardiff University 

 

Beetroot Juice Helps Lower Blood Pressure

 Beetroot Juice Helps Lower Blood PressureDaily intake of beetroot juice could help reduce blood pressure, says study. 
People with high blood pressure who drank about 8 ounces of beetroot juice experienced a decrease in blood pressure of about 10 mm Hg.But the preliminary findings don't yet suggest that supplementing your diet with beetroot juice benefits your health, researchers said. 
"Our hope is that increasing one's intake of vegetables with a high dietary nitrate content, such as green leafy vegetables or beetroot, might be a lifestyle approach that one could easily employ to improve cardiovascular health," Amrita Ahluwalia, Ph.D., lead author of the study and a professor of vascular pharmacology at The Barts and The London Medical School in London, said. 
The beetroot juice contained about 0.2g of dietary nitrate, levels one might find in a large bowl of lettuce or perhaps two beetroots. 
In the body the nitrate is converted to a chemical called nitrite and then to nitric oxide in the blood. Nitric oxide is a gas that widens blood vessels and aids blood flow. 
"We were surprised by how little nitrate was needed to see such a large effect," Ahluwalia said. 
"This study shows that compared to individuals with healthy blood pressure much less nitrate is needed to produce the kinds of decreases in blood pressure that might provide clinical benefits in people who need to lower their blood pressure. However, we are still uncertain as to whether this effect is maintained in the long term," she said. 
The study involved eight women and seven men who had a systolic blood pressure between 140 to 159 millimeters of mercury (mm Hg), did not have other medical complications and were not taking blood pressure medication. 
The study participants drank 250 mL of beetroot juice or water containing a low amount of nitrate, and had their blood pressure monitored over the next 24 hours. 
Blood pressure is typically recorded as two numbers. Systolic blood pressure, which is the top number and the highest, measures the pressure in the arteries when the heart beats. Diastolic blood pressure, the bottom and lower number, measures blood pressure in the arteries between heart beats. 
Compared with the placebo group, participants drinking beetroot juice had reduced systolic and diastolic blood pressure - even after nitrite circulating in the blood had returned to their previous levels prior to drinking beetroot. The effect was most pronounced three to six hours after drinking the juice but still present even 24 hours later. 
The study is published in the American Heart Association journal Hypertension.
Source-ANI
 

Circadian Rhythm And Its Effects On Our Body

From regulating when plants open their flowers to foiling people when they try to beat jet lag, circadian rhythms keep time for all living things. Day-night cycles are controlled through ancient biological mechanisms, evolutionarily speaking, so in essence, a human has the same internal clock as a fly does.These circadian clocks govern daily rhythms through genes that synchronize molecular pathways that promote or repress protein production, influencing a multitude of body functions. Even before waking, for example, our clock-driven metabolism turns on enzymes and transporters that prepare our bodies to eat and digest food. 
One of the circadian clock's transcription factors, proteins that regulate gene activity, is called period. Stem cell biologist Phillip Karpowicz, HMS research fellow in genetics, did not expect to find period in the gut of a fly. Working in the lab of Norbert Perrimon, the James Stillman Professor of Developmental Biology in the Harvard Medical School Department of Genetics, Karpowicz studies flies to see how the intestine regenerates cells when they are injured. 
Screening for transcription factors active in damage repair revealed that the gene period was needed. Further experiments showed that this component of the circadian clock is critical to intestinal regeneration, meaning that in flies, gut healing fluctuates according to the time of day. Karpowicz, Perrimon and their colleagues published their results April 11 in Cell Reports
"We thought this was really weird. I would not have thought that regeneration would tend to work better at one part of the day versus another part of the day," Karpowicz said. "But now we've shown that there's a rhythm in stem cells that's really important for the regeneration process." 
"This is a beautiful example of why we do genetic screens in the first place. By taking an unbiased approach, the fly tells us what is important to study," Perrimon said. 
Intestines are hotbeds of regeneration because they are constantly vulnerable to damage. Harmful bacteria or harsh chemicals that animals ingest can injure cells lining their intestines, which are essential for absorbing nutrients or blocking infectious agents from crossing through thin intestinal walls. 
To understand how a circadian clock might operate in intestinal stem cells, the scientists bred mutant flies to lack the period gene. The flies were normal except for their arrhythmic bursts of activity throughout the 24-hour day. Their intestines also appeared normal, until they ingested a chemical that caused inflammation. 
Compared to other flies, the mutants mounted a weaker response to repair their damaged cells. Their stem cells divided poorly and in a more haphazard manner, impairing the healing process. 
In further experiments, the scientists tested whether period was active in cells called enterocytes that surround the intestinal stem cells and absorb nutrients. Disrupting period in enterocytes also weakened the cells' response to damage. The scientists showed that this rhythm originates in the intestine, rather than in the brain, which typically controls circadian rhythms. 
The scientists widened their lens to look at all the genes that were turned on or off during the day. Performing genome-wide expression studies, they discovered 430 genes—about 3 percent of the fly genome—that are rhythmically expressed in fly intestines. 
"We think these cells may be more acutely sensitive to damage at a certain time of day," Karpowicz said. 
The next step will be to confirm these fly findings in mice. The scientists have already contemplated the potential applications to human health, including the timing of chemotherapy so a patient might best tolerate the treatment's side effects. 
"This could be quite relevant in terms of when you should time the absorption of those drugs to work in sync with the intestinal regeneration process," Karpowicz said.

Source:Cell Reports

 

 

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