CRAMS industry needed to focus on innovation, quality and compliance: Expert

With the slowdown in the growth of Indian Contract Research and Manufacturing Service (CRAMS) industry from an envious 35 per cent in 2009 to 15 per cent in 2012, companies are now driven with a strong need to focus on innovation, quality and compliance in the current global regulatory environment.

“The global regulatory environment is changing rapidly and industry is grappling with re-tooling itself to meet quality expectations,” said Hitesh Windlass, co-founder and CEO at Windlas Healthcare Pvt Ltd., a pharmaceutical formulations manufacturer for oral solids for regulated markets and Alumni of University of Chicago Booth School of Business.

“The earlier model of vertical integration is also quickly giving way to strategic partnerships on joint product development and even co-marketing. We at Windlas are actively building a portfolio of value added generics and investing in R&D to target different patient segments - paediatrics, geriatrics. R&D resources with focus on nutraceuticals and cosmeceuticals is one of the main thrusts at our company," says Hitesh.

He further explains, "We wanted to expand our presence as a CMO (contract manufacturing organisation) in the Indian market for the developed countries like the US, Europe and Australia. Windlas was started with this view and we are well on our way to achieve this goal. Today our facilities are approved by five of the top six pharma companies of the world. We are in the process of registering products in our target markets and take pride in providing high quality and innovative products to our customer.”

We invest almost 50 per cent of our profits in research and development. We have two R&D labs and are looking at enhancing molecules for targeted group of patients, products used in clinical nutrition and complex generics. Our R&D has been segmented into basic systems, nano systems, probiotics, prebiotics, modified release concepts and taste enhancement and are also looking at ignored areas like anti malarials. We closely work with National Institute of Pharmaceutical Education and Research (NIPER) in areas of pre-formulation studies. We have also been benefited by the subsidy programme of the Department of Scientific and Industrial Research (DSIR).

Talking about market opportunities and challenges in India, Hitesh pinpoints that a lot of growth in the Indian market was driven earlier by the launch of new products i.e. fixed dose combination products. It has come to a grinding halt now. Looking from a patient’s perspective, this might not be a bad thing. We see certain product segments like nutraceuticals, cosmeceuticals, etc. growing at a rapid pace and we have recently augmented our production facilities to specifically target these market segments. We also see renewed emphasis on innovative approaches to old products. Since we develop the formulations ourselves, we help our customers bring these innovations to market and thereby building their brand presence.

Our greatest challenge is to find the right talent. Identifying innovations and executing the development program within defined timeframes. Capital cost has also gone up in view of the economic and fiscal environment in India.

Many players who are operating on the fringes of quality will therefore be weeded out gradually. A case in point is that Chinese regulators have downed shutters of manufacturing units on the quality issue over the past few years. Similar actions have been observed by the US FDA and many of the European regulatory agencies. Cost of production in pharma sector is going higher as it is linked to manpower, infrastructure and electricity cost. Thus, when you have R&D and innovation as your primary differentiation strategies, it becomes more and more difficult because the higher operating expenses squeezes out the R&D budget.

Globally, it is evident that the cost advantage that India has as a formulation manufacturing hub is becoming smaller. Industry will soon need to compete on quality with other world class players. The cost advantage will no longer be enough to bring home the customer. These challenges exist for all players. We need to be faster at making decisions and smarter about picking our battles. "The competitive landscape was earlier determined by capacity, today innovation, quality and regulatory compliance have become the winning factors," Hitesh further said.
Source:Pharmabiz

Monoclonal Antibody Therapy Induces Macrophages to Target Tumor Cells

Extensive research has shown that monoclonal antibodies directed against tumor antigens have proven effective for treating some forms of cancer

 

 Despite the increasing use of monoclonal antibody therapy, it is not clear how these antibodies drive tumor removal. In this issue of the Journal of Clinical Investigation, Marjolein van Egmond and colleagues at the VU University Medical Center found that macrophage populations mediate tumor cell removal following monoclonal antibody treatment by actively phagocytosing tumor cells. Macrophage-dependent tumor cell removal required both the high affinity and low affinity Fc receptors. This study suggests that monoclonal antibody therapies that are optimized to enhance macrophage recruitment and activity may enhance removal of circulating tumor cells in cancer patients.  
Source:Journal of Clinical Investigation

 

Test to Predict Early Onset of Heart Attacks Developed

Test to Predict Early Onset of Heart Attacks DevelopedA new fluid biopsy test developed by The Scripps Research Institute (TSRI) scientists could help identify patients at high risk of a heart attack. The test identifies specific cells as markers in the bloodstream. The technique, which is described in the latest edition of IOP Publishing''s journal Physical Biology, works by identifying circulating endothelial cells (CECs) and has been successful in distinguishing patients undergoing treatment for a recent heart attack with a healthy control group.

The researchers believe the technique can now be tested on patients who exhibit symptoms but are yet to experience a heart attack. Currently, there is no predictive test for a heart attack-at least not of satisfying accuracy.

"The goal of this paper was to establish evidence that these circulating endothelial cells can be detected reliably in patients following a heart attack and do not exist in healthy controls-which we have achieved," said TSRI Associate Professor Peter Kuhn, who led the study. "Our results were so significant relative to the healthy controls that the obvious next step is to assess the usefulness of the test in identifying patients during the early stages of a heart attack."

Endothelial cells, which line the walls of the arteries, have been strongly linked to ongoing heart attacks when circulating in the bloodstream; they are thought to arrive there when diseased plaque builds up, ruptures and ulcerates, causing inflammation in the arteries. This damage can cause blood clots to form that prevent blood from flowing through the arteries and ultimately results in a heart attack.

As such, the researchers developed a procedure called the High-Definition Circulating Endothelial Cell (HD-CEC) assay to detect and characterise CECs in the blood samples of 79 patients who had experienced a heart attack at the time of sampling.
Source: journal Physical Biology,
For comparison, they also used the assay on two control groups, which consisted of 25 healthy patients and seven patients undergoing treatment for vascular disease.

The assay was able to identify CECs by their morphological features and their reactions with specific antibodies. The cells were shown to be significantly elevated in the heart attack patients compared to the healthy controls and were detected with high sensitivity and high specificity.

 The researchers also compared their results with a commercially available test, called CellSearch®, which has previously been approved by the U.S. Food and Drug Administration (FDA) to enumerate circulating tumour cells in cancer patients.

The HD-CEC test showed a higher specificity for CECs compared to CellSearch® because it used a direct analysis method and was free of bias from an enrichment stage. "Our assay effectively analyzes millions of cells, which is more work but guarantees that you are analysing all of the potential cells," said Kuhn.

The first authors of the paper, "Fluid phase biopsy for detection and characterization of circulating endothelial cells in myocardial infarction," are Kelly Bethel of Scripps Clinic and Madelyn S Luttgen of TSRI. In addition to Kuhn, Bethel and Luttgen, authors include Samir Damani and Sarah Topol of TSRI and Scripps Translational Science Institute; Anand Kolatkar, Rachelle Lamy and Mohsen Sabouri-Ghomi of TSRI; and Eric J Topol of Scripps Clinic, TSRI and Scripps Translational Science Institute.

Mitral Valve Prolapse (MVP) - Causes - Symptoms and Complications, Treatment t |

Mitral Valve Prolapse (MVP) is a relatively common problem. The cause is unknown but genetically determined collagen disorder maybe responsible for it. If signs and symptoms arise it is due to leakage of blood through the valve. An echocardiogram is confirmatory of the diagnosis. MVP is not life-threatening in most of the cases and may not require treatment.

Other Names - Barlow's Syndrome, Floppy Valve Syndrome and Ballooning Mitral Valve Syndrome.

The mitral valve controls the flow of blood between two chambers of the heart called the left atrium and the left ventricle. Blood flow has to occur only in one direction (from the atrium to the ventricle). In mitral valve prolapse (MVP) the valve fails to close properly. The flaps of this valve bulge (prolapsed) upward or back into the atrium during contraction of the ventricle. This may lead to leakage of blood backward into the left atrium. Mitral Valve Prolapse (MVP) is a relatively common but highly varying clinical syndrome. MVP is more common in females especially those between the ages of 15 and 30 years. Older people (commonly males) above 50 years may also be affected. MVP is not life-threatening in most of the cases and may not requirement treatment.

 

Key Proteins Responsible for Electrical Communication in the Heart Discovered

Six proteins responsible for cell-to-cell communication that regulates the heart and plays a role in limiting the size of heart attacks and strokes have been identified by Cedars-Sinai Heart Institute researchers. The smallest of these proteins directs the largest in performing its role of coordinating billions of heart cells during each heartbeat. Together, the proteins synchronize the beating heart, the researchers determined.

"We now know these proteins exist," said Robin Shaw, MD, PhD, the senior author of the study published in the journal Cell Reports. "The findings advance our understanding of cell-to-cell communication at the root of healthy heart function. When there is less cell communication, which occurs in failing hearts, chances are greater of disturbances in heart rhythm that can result in disability or death."

Until now, scientists had recognized just one protein involved in cell-to-cell communication that occurs through conduits known as "gap junctions." The Cedars-Sinai researchers identified five additional proteins that regulate the rapid flow of electrical communication signals, coordinating heart cells to produce a stable heartbeat.

"The finding of alternative translation start sites within this important group of proteins adds startling diversity to a key biological process, namely that whereby heart cells communicate with each other electrically," said Eduardo Marbán, MD, PhD, director of the Cedars-Sinai Heart Institute. "The implications are major for arrhythmias and heart failure."

Through a phenomenon called "alternative translation," the protein-making machinery in each cell can produce shorter proteins from the same gene that encodes the largest of the proteins. Biologists had known of the existence of alternative translation but had not completely understood its physiological relevance. The Cedars-Sinai research team led by Shaw has expanded the understanding of this process and continues to study the precise role of the proteins produced by it.

The researchers also have determined that a class of drugs known as "mTOR inhibitors" - those already used for immunosuppression in organ transplants - can affect alternative translation, changing the balance of proteins in hearts cells, increasing the amount of electrical coordination in the heart. The findings suggest that mTOR inhibitors can be used to prevent erratic and sometimes fatal heart rhythms.

A properly beating heart is necessary to pump blood to the brain, lungs and other organs. When arrhythmias occur in the heart's main pumping chamber, the heart can stop, resulting in sudden cardiac arrest, the most common cause of death among heart patients. Preventing arrhythmias is a top clinical priority. The possibility of using mTOR inhibitors suggests that drugs used to treat transplanted hearts could also be used to treat failing hearts.

Cell-to-cell communication occurs in all other organs. The same proteins that help heart cells communicate also play a role in brain function, bone development and insulin production in the pancreas. These proteins also affect the contraction of muscle cells within the uterus during childbirth and may potentially suppress cancer cells. The finding that mTOR inhibitors improve cell-to-cell communication indicates that this class of drugs could be useful to treat multiple disorders

 Source :journal Cell Reports.

Your Personality Can Affect Your Weight Loss

Are you one of those night owls who love their late night snacks or do you have an impulsive nature and find it hard to resist temptations when it comes to food? According to ABC News, if you are planning on shedding off a few kilos you might want to keep your personality in mind, because it can affect the success of your diet.

First of all impulsive people should eliminate little temptations like stocking pantry with junk food, and avoiding the break room at work when you know there will be leftover treats.

Reliable people find it easier to stick with a fitness plan, but outgoing people tend to accumulate stress and then indulge in comfort food so they should try putting themselves in social situations that don't involve food.

While morning people are less likely to be overweight than night owls, being self-centered may not be such a bad thing health-wise as such people tend to consider their own interests, which could lead them to have more willpower to make healthy choices.

Also, easygoing people who like to go with the flow tend to be leaner than those who are more neurotic.

 Source:ABC news
 

Researchers Debunk Popular Blood Type Diet

The theory behind the popular blood type diet has been debunked by University of Toronto (U of T) researchers. The findings are published this week in PLoS One. "Based on the data of 1,455 study participants, we found no evidence to support the 'blood-type' diet theory," said the senior author of the study, Dr. Ahmed El-Sohemy, Associate Professor and Canada Research Chair in Nutrigenomics at the U of T. 
"The way an individual responds to any one of these diets has absolutely nothing to do with their blood type and has everything to do with their ability to stick to a sensible vegetarian or low-carbohydrate diet," said El-Sohemy. 
Researchers found that the associations they observed between each of the four blood-type (A, B, AB, O) diets and the markers of health are independent of the person's blood type. 
The 'blood-type' diet was popularized in the book Eat Right for Your Type, written by naturopath Peter D'Adamo. The theory behind the diet is that the ABO blood type should match the dietary habits of our ancestors and people with different blood types process food differently. According to the theory, individuals adhering to a diet specific to one's blood type can improve health and decrease risk of chronic illness such as cardiovascular disease. The book was a New York Times best-seller that has been translated into 52 languages and sold over 7 million copies. 
The U of T researchers took an existing population of mostly young and healthy adults who provided detailed information about their usual diets and provided fasting blood that was used to isolate DNA to determine their ABO blood type and the level of cardiometabolic risk factors, such as insulin, cholesterol and triglycerides. Diet scores were calculated based on the food items listed in Eat Right for Your Type to determine relative adherence to each of the four 'blood-type' diets. 
El-Sohemy says that a previous lack of scientific evidence doesn't mean the diets didn't work. "There was just no evidence, one way or the other. It was an intriguing hypothesis so we felt we should put it to the test. We can now be confident in saying that the blood type diet hypothesis is false." Last year, a comprehensive review published in the American Journal of Clinical Nutrition found no evidence to support the 'blood-type' diet and called for properly designed scientific studies to address it.
 Source:Plos One

 

Traditional Chinese medicines stall progression of diabetes

Traditional Chinese herbal medicines hold promise for slowing the progression from prediabetes to an official diabetes diagnosis, according to new research accepted for publication in the Endocrine Society's Journal of Clinical Endocrinology & Metabolism (JCEM).
Prediabetes is diagnosed an individual has developed elevated blood sugar levels, but glucose levels have not yet risen to the point of developing type 2 diabetes. People who are prediabetic face a heightened risk of developing type 2 diabetes as well as heart disease and stroke. According to the Centers for Disease Control and Prevention, about 79 million American adults age 20 years or older have prediabetes.
"With diabetes evolving into a serious public health burden worldwide, it is crucial to take steps to stem the flood of cases," said one of the study's authors, Chun-Su Yuan, MD, PhD, of the University of Chicago. "Patients often struggle to make the necessary lifestyle changes to control blood sugar levels, and current medications have limitations and can have adverse gastrointestinal side effects. Traditional Chinese herbs may offer a new option for managing blood sugar levels, either alone or in combination with other treatments."
During the double-blind, randomized, placebo-controlled trial, 389 participants at 11 research sites in China were randomly assigned to take either a capsule containing a mixture of 10 Chinese herbal medicines or a placebo. For a year, subjects took capsules of either the Chinese herb mixture, called Tianqi, or the placebo three times a day before meals. All participants received a month of lifestyle education at the outset of the trial and met with nutritionists several times during the course of the study. Subjects' glucose tolerance was measured on a quarterly basis.
At the end of the trial, 36 participants in the Tianqi group and 56 in the placebo group had developed diabetes. The analysis found taking Tianqi reduced the risk of diabetes by 32.1 percent compared with the placebo, after adjusting for age and gender. The overall reduction in risk was comparable to that found in studies of diabetes medications acarbose and metformin, and study participants reported few side effects from the Tianqi herbs. Tianqi includes several herbs that have been shown to lower blood glucose levels and improve control of blood glucose levels after meals.
"Few controlled clinical trials have examined traditional Chinese medicine's impact on diabetes, and the findings from our study showed this approach can be very useful in slowing the disease's progression," said one of the study's lead authors, Xiaolin Tong, MD, PhD, of Guang'anmen Hospital in Beijing, China, said. "More research is needed to evaluate the role Chinese herbal medicine can play in preventing and controlling diabetes."
Source:The Endocrine Society

Silencing inhibitor of cell replication spurs beta cells to reproduce

Klaus Kaestner, PhD, professor of Genetics and postdoctoral fellow Dana Avrahami, PhD, from the Perelman School of Medicine, University of Pennsylvania, published a study this week in the Journal of Clinical Investigation, with colleague Benjamin Glaser, MD, from the Hadassah-Hebrew University Medical Center, Jerusalem, and colleagues. In this study, they were able to replicate human pancreatic beta cells – the cells in our body that produce the critical hormone insulin – in a mouse model in which donor cells were transplanted. The newly replicated cells retained features of mature beta cells and showed a physiological response to glucose.
The results of this proof-of-principle experiment have implications for helping both type 1 and type 2 diabetic patients. In type 1 diabetes, beta cells are destroyed by the patient's own immune system and thus restoration of their numbers must be coupled with a method of preventing immune-mediated destruction. Similarly, a decrease in the number of functional insulin-producing beta cells contributes to the development of type 2 diabetes, so in principle, restoration of beta-cell mass can reverse or ameliorate both forms of diabetes.
The idea for this study came from newborns with a well-characterized, but rare, condition called hyperinsulinism of infancy, in which beta cells produce too much insulin – the exact opposite of diabetes. The blood sugar levels in these babies are too low. In about one-third of these newborns, most of their pancreatic beta cells are normal, but a small portion of cells lack a specific protein called p57, due to a mutation that occurs in a single or a few beta cells during fetal development. The p57 protein is a cell-cycle inhibitor, and therefore its elimination accelerates beta-cell replication, creating a large clone of beta-cells within the pancreas that secrete too much insulin.
"This 'experiment' of nature inspired our study," says Kaestner. The team used short hairpin RNA, shRNA, to suppress the p57 gene in human beta cells obtained from deceased adult donors. The manipulated beta cells were then transplanted into diabetic mice.
After three weeks, the team found that the beta cells in the human-cell graft had a replication rate at least three-fold higher than those of controls without p57 suppression. The new beta cells also made beta-cell proteins seen in normal mature cells in humans: insulin, PDX1, and NKX6 1, and they had a normal glucose-induced calcium influx, as expected from functional beta cells.
These data show that even beta cells from older human donors, which are normally non-replicating, can be coaxed to divide while maintaining mature beta-cell properties, something that was previously thought by many researchers to be nearly impossible.
Ten to 15 years down the road, say the authors, physicians may be able to treat diabetic patients with a vehicle that homes in exclusively on beta cells and delivers a molecule that silences p57, thereby enhancing beta-cell mass and insulin production, and perhaps even curing the disease.
Source:University of Pennsylvania School of Medicine

Probiotics may Help Prevent Infant Gastrointestinal Disorders

A new study finds feeding your newborn with curd or any other form of probiotic in first three months can reduce the most common gastrointestinal disorders like infant colic, acid reflux and constipation.
   Infant colic, acid reflux and constipation are the most common gastrointestinal disorders that lead to a paediatrician referral during the first six months of life.
"They are often responsible for hospitalisation, feeding changes, use of drugs, parental anxiety and loss of parental working days," said Flavia Indrio of Aldo Moro University of Bari, Italy.

Researchers randomised 554 newborns in nine paediatric units in Italy to the probiotic lactobacillus reuteri or placebo for 90 days.
They asked parents to record in diary entries the number of vomiting episodes and evacuations (emptying of the bowels), the duration of inconsolable crying and the number of pediatrician visits.
Change in daily crying time, vomiting, constipation and the cost benefits of probiotic supplement use was measured during the three-month period, said the study published in the journal JAMA Paediatrics.
At three months of age, the average duration of crying time, regurgitations and evacuations per day was less in children who were given probiotic, it added.
"Probiotic improves intestinal permeability, visceral sensitivity and mast cell density. The probiotic use in infants may represent a new strategy for preventing many gastrointestinal conditions," the authors said.
Source:University of Bari, Italy.


 

Researchers Announce Breakthrough in Treatment of a Rare Type of Leukemia

At the University of Leicester, a team of scientists has demonstrated a novel treatment for Hairy Cell Leukaemia (HCL), a rare type of blood cancer, using a drug administered to combat skin cancer. The research, which is published (Thursday 16 January) in the New England Journal of Medicine, indicates Vemurafenib, a BRAF inhibitor that has been approved as a treatment for advanced melanomas, is also successful in treating leukaemia. The study shows the treatment, which can be taken orally, cleared the malignant cells from the patient's blood and led to a complete clinical recovery in a number of days.

The study was led by the University of Leicester and involved treatment of a patient at the Leicester Royal Infirmary.

Dr Salvador Macip, from the University of Leicester's Department of Biochemistry, explained: "A genetic study of the patient's blood cells allowed us to identify a mutation in the BRAF gene that is commonly found in skin cancers. This knowledge enabled us to combat the cancer cells with Vemurafenib, which has had proven success as a BRAF inhibitor in melanomas, and showed similar success for this patient who had exhausted all other treatment options, which is fantastic.

 Source:Journal of Medicine
 

New study claims chicory oligofructose to lower blood glucose response

Following collaboration between Beneo, Cosucra and Sensus,  a dossier for an EU Art 13.5 claim was filed that contains new data to show the link between oligofructose and improved blood glucose response after intake.
The dossier submitted to the European Food Safety Agency (EFSA) was based on several studies including newly developed science, and shows that oligofructose has a significant part to play in the area of glycaemic control.  The application targeted an EU Art 13.5 claim on the contribution of oligofructose to a reduction of post-prandial blood glucose response. EFSA’s positive evaluation allows the approval by the Commission, the Member States and the European Parliament within the health claim procedure. This opens the way for new food and drink applications to benefit both the industry and consumers alike.
This proprietary new research from Beneo, Cosucra and Sensus, has shown the positive impact on blood glucose response when a proportion of the sugars in a product is replaced with the prebiotic fibre oligofructose that is derived from chicory.  The new oligofructose data demonstrate a significantly lower blood glucose response with only 20% replacement. The conditions of use proposed in the evaluation refer to the “reduced sugars” claim as published in the annex of Regulation (EC) No 1924/2006, i.e. a 30% replacement.
A second dossier focusing on chicory inulin and also including additional newly developed scientific research was ready for submission at the moment when EFSA’s opinion on chicory oligofructose was published. As EFSA broadened the scope to non-digestible carbohydrates when evaluating the oligofructose dossier chicory inulin is included and benefits de facto from this evaluation.
With increasing challenges placed on society by diet related diseases such as obesity, overweight, impaired glucose tolerance and diabetes,  there is increased emphasis on food and drink producers supporting the development of new, lower glycaemic response products. According to a spokesperson of the companies that invested in the research, “this approach is in line with the thinking of the nutritional advisors to expand consumers’ choice for healthy products. The research has provided additional physiological evidence why oligofructose is a very suitable sugar replacer and therefore represents new opportunities for the food industry to meet consumers’ demand for more low glycaemic and tasty products”.
Oligofructose derived from chicory is not digested in the human digestive system; this means that its building blocks are not released into the blood stream as opposed to sugar for example, whose glucose and fructose are released into the blood stream.  Moreover, oligofructose can be used to replace sugar in a range of food products and by doing so, the glycaemic response of the food product is lowered.  So, sugar with its glycaemic response is replaced by a dietary fiber without a glycaemic response.
Source:Pharmabiz

Scientists show how insulin-producing cells may fail in diabetes, how they might someday be restored

These cells may sometimes revert to a non-functional state, but other pancreatic cells may someday step in to replace them

Two new studies led by UC San Francisco (UCSF) scientists shed new light on the nature of beta cells, the insulin-producing cells in the pancreas that are compromised in diabetes.
The first suggests that some cases of diabetes may be caused when beta cells are deprived of oxygen, prompting them to revert to a less mature state that renders them incapable of producing insulin. The second study demonstrates that acinar cells, pancreatic cells that do not normally produce insulin, can be converted to functional beta cells, a potential new avenue for treating the disease.
In the first study, led by Sapna Puri, PhD, a scientist in the laboratory of Matthias Hebrok, PhD, director of the UCSF Diabetes Center, a gene known as VHL was selectively deleted from beta cells in mice. Insulin production in these beta cells was sharply reduced, and over time the mice developed the physiological equivalent of type 2 diabetes. Puri and Hebrok were joined in the study by Haruhiko Akiyama, MD, PhD, of Kyoto University, who provided a critical mouse model for the work.
Type 2 diabetes, which usually emerges in adulthood but is becoming increasingly common in childhood, is generally thought to arise when tissues become resistant to the effects of insulin, causing higher levels of glucose to circulate in the blood. Type 1 diabetes, diagnosed in childhood, is an autoimmune disease in which pancreatic beta cells are attacked and damaged by the immune system.
Despite the fact that much research on type 2 diabetes is focused on insulin resistance, the team behind the first new study suggests that a decline in the function of beta cells over time may be a factor in many cases, such as in the subset of lean adults who develop diabetes.
"Some humans with a high body mass index have well-performing beta cells, and some lean people have poorly performing beta cells," said Hebrok, senior author of a paper describing the research in the December 1, 2013 issue of Genes & Development. "This mouse is a model of lean humans who develop type 2 diabetes."
During the development of the pancreas, changes in gene expression cause some cells to differentiate into beta cells, but when the researchers examined the VHL-deprived beta cells they found the cells had "de-differentiated." Critical proteins that are always found in mature, functional beta cells were absent, and conversely, a protein known as Sox9, which is only seen in beta cells before they are fully developed, was robustly expressed in the VHL-deprived cells.
"Levels of markers of mature cells go down in these cells, and markers that shouldn't be there go up," Hebrok said.
VHL is a vital cellular oxygen-sensor. In low-oxygen conditions, VHL unleashes intracellular pathways that make compensatory metabolic changes to protect the cell. If these metabolic adjustments fail, alternative pathways prompt the cell to self-destruct.
With its targeted deletion of VHL from beta cells, the research team was emulating conditions of oxygen deprivation in just one cell type, said Hebrok. "We made beta cells 'believe' they are hypoxic, without actually reducing the amount of oxygen."
Even modest weight gains in individuals with subpar beta cells may increase demand on the cells for insulin to a point that they begin to exceed their capacity, Hebrok said. Whether oxygen starvation or metabolic changes within the beta cells are the key drivers during the development of diabetes in some patients remains to be discovered.
"The beta cell is a highly sophisticated cell that produces tremendous amounts of insulin in a tightly regulated way," said Hebrok, "Starving it of oxygen turns a Porsche into a VW Beetle, a high-octane race car into a car that you now have to fuel with low octane—it can still get from A to B, but it can't get there as well as it should."
Though researchers and physicians have drawn broad categories of "pre-diabetic" and "diabetic" when classifying patients, Hebrok believes that many cases of diabetes are the result of steady, long-term declines in the function of already compromised beta cells as they cope with an increasing demand for insulin.
"What we are unraveling here is a different way of looking at how diabetes occurs," said Hebrok. "It's not that you're perfectly fine and then you're pre-diabetic and then you're diabetic and then your beta cells die. Instead it's a slippery slope where the beta cell function erodes over time."
The work was funded by grants from the National Institutes of Health and the Juvenile Diabetes Research Foundation.
In the second study, published in the November 17 issue of Nature Biotechnology, researchers were able to restore normal insulin and glucose levels in mice with no functional beta cells by transforming other pancreatic cells into "beta-like" cells.
Led by Luc Baeyens, a new postdoctoral fellow in the laboratory of Michael S. German, MD, professor of medicine and associate director of the UCSF Diabetes Center, the work was completed as part of Baeyens's research in the laboratory of Harry Heimberg, PhD, at Vrije Universiteit Brussel, in Brussels, Belgium.
Mice were first injected with a beta-cell-specific toxin that caused them to display symptoms of diabetes. Five weeks later, the diabetic mice were implanted with miniature pumps that continuously administered two signaling molecules known as cytokines for seven days.
Treatment with the two cytokines, epidermal growth factor and ciliary neurotrophic factor, restored glucose and insulin to normal levels in the mice, and the mice maintained normal blood sugar control eight months later when the study concluded.
In additional experiments the group showed that the cytokine treatment had exerted its effects by "reprogramming" acinar cells—pancreatic cells that normally secrete digestive enzymes rather than insulin—and causing them to take on the properties of beta cells, including glucose sensing and insulin secretion.
Previous work had shown that certain transcription factors delivered by viruses could reprogram acinar cells in mice, but the work by Baeyens and colleagues is the first demonstration that acinar-to-beta cell reprogramming is possible in a living animal through pharmacological treatment. Because viral delivery can be both risky and difficult, the new research represents a promising approach to therapy for type 1 diabetes, or for cases of type 2 diabetes marked by beta cell dysfunction.
"Type 1 diabetes patients would greatly benefit from pharmacological therapies that create new beta cells, provided that the current findings in mouse models could be translated into the identification of druggable targets in the human pancreas, and provided we could put a stop to the ongoing autoimmune destruction of the beta cells." Baeyens said. "In the short run, this model could serve as a platform to identify and study new compounds with therapeutic potential. In the long run, despite these encouraging results, we are still quite a long way from taking this research from the bench to the bedside."
Source:University of California - San Francisco

Fish derived serum omega-3 fatty acids help reduce the risk of type 2 diabetes

High concentrations of serum long-chain omega-3 fatty acids may help reduce the risk of type 2 diabetes, according to a University of Eastern Finland study published recently in Diabetes Care. The sources of these fatty acids are fish and fish oils.
Type 2 diabetes is becoming increasingly widespread throughout the world, including Finland. Overweight is the most significant risk factor, which means that diet and other lifestyle factors play important roles in the development of type 2 diabetes. Earlier research has established that weight management, exercise and high serum linoleic acid concentrations, among other things, are associated with reduced risk of diabetes. However, findings on how fish consumption or long-chain omega-3 fatty acids affect the risk of diabetes have been highly contradictory. A protective link has mainly been observed in Asian populations, whereas a similar link has not been observed in European or US studies – and some studies have even linked a high consumption of fish to increased diabetes risk.
Ongoing at the University of Eastern Finland, the Kuopio Ischaemic Heart Disease Risk Factor Study (KIHD) determined the serum omega-3 fatty acid concentrations of 2,212 men between 42 and 60 years of age at the onset of the study, in 1984–1989.
During a follow-up of 19.3 years, 422 men were diagnosed with type 2 diabetes.
Serum long-chain omega-3 fatty acid concentrations were used to divide the subjects into four categories. The risk of men in the highest serum omega-3 fatty acid concentration quarter to develop type 2 diabetes was 33% lower than the risk of men in the lowest quarter.
The study sheds new light on the association between fish consumption and the risk of type 2 diabetes. A well-balanced diet should include at least two fish meals per week, preferably fatty fish. Fish rich in long-chain omega-3 fatty acids include salmon, rainbow trout, vendace, bream, herring, anchovy, sardine and mackerel, whereas for example saithe and Atlantic cod are not so good alternatives. Weight management, increased exercise and a well-rounded diet built around dietary recommendations constitute the cornerstones of diabetes prevention.
Source:University of Eastern Finland

Illinois study identifies 3 risk factors most highly correlated with child obesity

A University of Illinois study has identified the three most significant risk factors for child obesity among preschoolers: (1) inadequate sleep, (2) a parental BMI that classifies the mom or dad as overweight or obese, and (3) parental restriction of a child's eating in order to control his weight.
"We looked at 22 variables that had previously been identified as predictors of child obesity, and the three that emerged as strong predictors did so even as we took into account the influence of the other 19. Their strong showing gives us confidence that these are the most important risk factors to address," said Brent McBride, a U of I professor of human development and director of the university's Child Development Laboratory.
"What's exciting here is that these risk factors are malleable and provide a road map for developing interventions that can lead to a possible reduction in children's weight status. We should focus on convincing parents to improve their own health status, to change the food environment of the home so that healthy foods are readily available and unhealthy foods are not, and to encourage an early bedtime," he added.
The researchers reached their conclusions after compiling the results from an extensive survey distributed to 329 parent-child dyads recruited from child-care programs in east-central Illinois as part of the U of I's STRONG (Synergistic Theory and Research on Obesity and Nutrition Group) Kids Program. The current research is based on the first wave of data generated in this longitudinal study, taken when the children were two years old.
The survey yielded wide-ranging information on demographics, health histories of both child and parent, and pertinent feeding practices. Research assistants also did home visits with each participant, checking height and weight and taking further information about the parents' history. The data was then subjected to statistical analysis.
As a result of that analysis, McBride and U of I nutritional sciences graduate student Dipti A. Dev offer some recommendations for families.
Parents should recognize that their food preferences are being passed along to their children and that these tastes are established in the preschool years, Dev said.
"If you, as an adult, live in a food environment that allows you to maintain an elevated weight, remember that your child lives in that environment too. Similarly, if you are a sedentary adult, you may be passing on a preference for television watching and computer games instead of playing chasing games with your preschooler or playing in the park," she added.
Consider too that restricting your children's access to certain foods will only make them want those foods more, she said.
"If kids have never had a chance to eat potato chips regularly, they may overeat them when the food appears at a friend's picnic," McBride said.
Instead, work on changing the food environment in your home so that a wide variety of healthy choices such as fruits and vegetables are available while unhealthy options are not, he added.
"And remember that it takes a certain number of exposures to a food before a child will try it, let alone like it, so you have to offer it to them over and over and over again. And they have to see you eat it over and over," McBride noted.
Don't use food to comfort your children when they are hurt or disappointed, do allow your preschoolers to select their foods as bowls are passed at family-style meals (no pre-plating at the counter—it discourages self-regulation), and encourage all your children to be thoughtful about what they are eating, the researcher said.
Source:University of Illinois College of Agricultural, Consumer and Environmental Sciences

Study finds that information is as important as medication in reducing migraine pain

The information that clinicians provide to patients when prescribing treatments has long been thought to play a role in the way that patients respond to drug therapies. Now an innovative study of migraine headache confirms that a patient's expectations – positive, negative or neutral – influence the effects of both a medication and a placebo.
Led by a research team at Beth Israel Deaconess Medical Center (BIDMC) and published on-line today in the journal Science Translational Medicine the study, for the first time, quantifies how much pain relief is attributed to a drug's pharmacological effect and how much to placebo effect, and demonstrates that a positive message and a powerful medication are both important for effective clinical care.
Senior authors Rami Burstein, PhD, Director of Pain Research in the Department of Anesthesia, Critical Care and Pain Medicine at BIDMC and Ted Kaptchuk, Director of the Program in Placebo Studies and Therapeutic Encounter (PiPS) at BIDMC and Harvard Medical School, took advantage of the recurring nature of migraine headaches to compare the effects of drug treatments and placebos in seven separate migraine attacks in each of 66 individuals. Their findings uncovered several key points: 1) The benefits of the migraine drug Maxalt (rizatriptan) increased when patients were told they were receiving an effective drug for the treatment of acute migraine; 2) When the identities of Maxalt tablets and placebo pills were switched, patients reported similar reductions in pain from placebo pills labeled as Maxalt as from Maxalt tablets labeled as placebo; and 3) Study subjects reported pain relief even when they knew the pill they were receiving was a placebo, compared with no treatment at all.
"One of the many implications of our findings is that when doctors set patients' expectations high, Maxalt [or, potentially, other migraine drugs] becomes more effective," says Burstein, the John Hedley-Whyte Professor of Anaesthesia at Harvard Medical School (HMS). "Increased effectiveness means shorter migraine attacks and shorter migraine attacks mean that less medication is needed," he adds.
"This study untangled and reassembled the clinical effects of placebo and medication in a unique manner," adds Kaptchuk, a Professor of Medicine at HMS. "Very few, if any, experiments have compared the effectiveness of medication under different degrees of information in a naturally recurring disease. Our discovery showing that subjects' reports of pain were nearly identical when they were told that an active drug was a placebo as when they were told that a placebo was an active drug demonstrates that the placebo effect is an unacknowledged partner for powerful medications."
The investigators studied over 450 attacks in 66 patients with migraines, throbbing headaches commonly accompanied by nausea, vomiting and sensitivity to light and sound. After an initial "no treatment" episode in which patients documented their headache pain and accompanying symptoms 30 minutes after headache onset and again two hours later (2.5 hours after onset), the participants were provided with six envelopes containing pills to be taken for each of their next six migraine attacks.
Of the six treatments, two were made with positive expectations (envelopes labeled "Maxalt"), two were made with negative expectations (envelopes labeled "placebo"), and two were made with neutral expectations (envelopes labeled "Maxalt or placebo"). In each of the three situations – positive, negative or neutral – one of the two envelopes contained a Maxalt tablet while the other contained a placebo, no matter what the label actually indicated. The patients then documented their pain experiences in the same manner as they had initially in the no-treatment session.
The results consistently showed that giving the pills accompanied by positive information incrementally boosted the efficacy of both the active migraine medication and the inert placebo.
"When patients received Maxalt labeled as placebo, they were being treated by the medication – but without any positive expectation," notes Burstein. "This was an attempt to isolate the pharmaceutical effect of Maxalt from any placebo effect." Conversely, the inert placebo labeled as Maxalt was an attempt to isolate the impact of the placebo effect from pharmaceutical effect.
Adds Kaptchuk, "Even though Maxalt was superior to the placebo in terms of alleviating pain, we found that under each of the three messages, the placebo effect accounted for at least 50 percent of the subjects' overall pain relief. When, for example, Maxalt was labeled 'Maxalt,' the subjects' reports of pain relief more than doubled compared to when Maxalt was labeled 'placebo.' This tells us that the effectiveness of a good pharmaceutical may be doubled by enhancing the placebo effect."
Furthermore, the authors were surprised to find that even when subjects were given a placebo that was labeled as "placebo," they reported pain relief, compared with no treatment.
"Contrary to conventional wisdom that patients respond to a placebo because they think they're getting an active drug, our findings reinforce the idea that open label placebo treatment may have a therapeutic benefit," say the authors, adding that while further research will be needed to explore how these findings could be applied to clinical care, the findings suggest that in the future placebos may provide a therapeutic boost to drug treatments.
Source:Science Translational Medicine

Dance and virtual reality: A promising treatment for urinary incontinence in elderly women

Virtual reality, dance and fun are not the first things that come to mind when we think of treating urinary incontinence in senior women. However, these concepts were the foundations of a promising study by Dr. Chantal Dumoulin, PhD, Canada Research Chair in Urogynaecological Health and Aging, a researcher at the Institut universitaire de gériatrie de Montréal, and an associate professor in the Physiotherapy Program of the Rehabilitation School at Université de Montréal, and her master's student, Miss Valérie Elliott. Dr Eling D. de Bruin, Ph.D., researcher at the department of Health Sciences and Technology, Swiss federal Institute of Technology, Zurich, Switzerland collaborated in this study for his expertise in the use of exergame in geriatric rehabilitation. The results of their feasibility study were published in Neurourology and Urodynamics.
For the study, the researchers added a series of dance exercises via a video game console to a physiotherapy program for pelvic floor muscles. What were the results for the 24 participants? A greater decrease in daily urine leakage than for the usual program (improvement in effectiveness) as well as no dropouts from the program and a higher weekly participation rate (increase in compliance). According to the researchers, fun is a recipe for success. "Compliance with the program is a key success factor: the more you practice, the more you strengthen your pelvic floor muscles. Our challenge was to motivate women to show up each week. We quickly learned that the dance component was the part that the women found most fun and didn't want to miss. The socialization aspect shouldn't be ignored either: they laughed a lot as they danced!" explained a delighted Chantal Dumoulin. The dance period also served as a concrete way for women to apply pelvic floor muscle exercises that are traditionally static. "Dancing gives women confidence, as they have to move their legs quickly to keep up with the choreography in the video game while controlling their urine. They now know they can contract their pelvic floor muscles when they perform any daily activity to prevent urine leakage. These exercises are therefore more functional." Although a lot of research already employs different aspects of virtual reality, this is the first time that it has been used to treat urinary incontinence. This successful feasibility study opens the door to a randomized clinical trial.
Source:Neurourology and Urodynamics

Brain structure shows who is most sensitive to pain

– Everybody feels pain differently, and brain structure may hold the clue to these differences.
In a study published in the current online issue of the journal Pain, scientists at Wake Forest Baptist Medical Center have shown that the brain's structure is related to how intensely people perceive pain.

"We found that individual differences in the amount of grey matter in certain regions of the brain are related to how sensitive different people are to pain," said Robert Coghill, Ph.D., professor of neurobiology and anatomy at Wake Forest Baptist and senior author of the study. The brain is made up of both grey and white matter. Grey matter processes information much like a computer, while white matter coordinates communications between the different regions of the brain. The research team investigated the relationship between the amount of grey matter and individual differences in pain sensitivity in 116 healthy volunteers. Pain sensitivity was tested by having participants rate the intensity of their pain when a small spot of skin on their arm or leg was heated to 120 degrees Fahrenheit. After pain sensitivity testing, participants underwent MRI scans that recorded images of their brain structure. "Subjects with higher pain intensity ratings had less grey matter in brain regions that contribute to internal thoughts and control of attention," said Nichole Emerson, B.S., a graduate student in the Coghill lab and first author of the study. These regions include the posterior cingulate cortex, precuneus and areas of the posterior parietal cortex, she said. The posterior cingulate cortex and precuneus are part of the default mode network, a set of connected brain regions that are associated with the free-flowing thoughts that people have while they are daydreaming. "Default mode activity may compete with brain activity that generates an experience of pain, such that individuals with high default mode activity would have reduced sensitivity to pain," Coghill said. Areas of the posterior parietal cortex play an important role in attention. Individuals who can best keep their attention focused may also be best at keeping pain under control, Coghill said. "These kinds of structural differences can provide a foundation for the development of better tools for the diagnosis, classification, treatment and even prevention of pain," he said.
Source:National Institutes of Health

Advantages of Eating Fish Foods

Researchers worldwide have discovered that eating fish regularly - one or two servings weekly - may reduce the risk of diseases ranging from childhood asthma to prostate cancer.

Fish is low in fat, high in protein and an excellent source of omega 3 fatty acids.

 Regular consumption of fish can reduce the risk of various diseases and disorders. Selected research findings indicate the following:

Asthma - children who eat fish may be less likely to develop asthma.

Brain and eyes - fish rich in omega 3 fatty acids can contribute to the health of brain tissue and the retina (the light sensitive tissue lining the inner surface of the eye).

Cancer - the omega 3 fatty acids in fish may reduce the risk of many types of cancers by 30 to 50 per cent, especially of the oral cavity, oesophagus, colon, breast, ovary and prostate.

Cardiovascular disease - eating fish every week reduces the risk of heart disease and stroke by reducing blood clots and inflammation, improving blood vessel elasticity, lowering blood pressure, lowering blood fats and boosting 'good' cholesterol.

Dementia - elderly people who eat fish or seafood at least once a week may have a lower risk of developing dementia, including Alzheimer's disease.

Depression - people who regularly eat fish have a lower incidence of depression (depression is linked to low levels of omega 3 fatty acids in the brain).

Diabetes - fish may help people with diabetes manage their blood sugar levels.

Eyesight - breastfed babies of mothers who eat fish have better eyesight, perhaps due to the omega 3 fatty acids transmitted in breast milk.

Inflammatory conditions - regular fish consumption may relieve the symptoms of rheumatoid arthritis, psoriasis and autoimmune disease.

Prematurity - eating fish during pregnancy may help reduce the risk of delivering a premature baby.

Healthy ways to enjoy fish include baked, poached, grilled and steamed forms.