Understanding how neurons regulate metabolism in response to a high-fat diet

The brain plays a central role in regulating appetite and whole-body metabolism. A protein known as PPARγ is important in the brain's control of food intake and body weight, but the identity of the neurons regulating this process has been unclear. A new study in the Journal of Clinical Investigation demonstrates that PPARγ activity in a type of neuron known as pro-opiomelanocortin (POMC) neurons is critical in mediating the response to high-fat diet. Sabrina Diano and colleagues at Yale University School of Medicine found that mice lacking PPARγ specifically in POMC neurons gained less weight, were more active, and had improved glucose metabolism when fed a high-fat diet. Moreover, animals without PPARγ in POMC neurons did not gain weight when given PPARγ activators. The results of this study indicate that PPARγ expression in POMC neurons regulates whole-body energy balance. The findings also shed light on why PPARγ activators, which are used clinically to increase insulin sensitivity in patients with type 2 diabetes, have a side effect of promoting weight gain.
Source:Journal of Clinical Investigation

Expressive writing may help breast cancer survivors

Asian-American breast cancer survivors focus of study

Writing down fears, emotions and the benefits of a cancer diagnosis may improve health outcomes for Asian-American breast cancer survivors, according to a study conducted by a researcher at the University of Houston (UH).
"The key to developing an expressive writing intervention is the writing instruction. Otherwise, writing is just like a journal recording facts and events. Writing a journal can be therapeutic, but oftentimes we don't get the empirical evidence to determine whether it's effective or not," said Qian Lu, assistant professor and director of the Culture and Health Research Center at UH.
"In my research study, I found long-term physical and psychological health benefits when research participants wrote about their deepest fears and the benefits of a breast cancer diagnosis," she said.
Lu and colleagues published a study titled, "A Pilot Study of Expressive Writing Intervention Among Chinese-Speaking Breast Cancer Survivors," inHealth Psychology. The goal of her research is to reduce the psychological burden among minority patients particularly among breast cancer survivors.
"Cancer patients, like war veterans in Iraq, can experience post-traumatic stress symptoms. Many times when cancer patients get diagnosed, they face lots of emotional trauma. There's a sense of loss, depression, anxiety about going into treatment and how they are going to face the future," said Lu. "They have a lot of emotional events going on in their life."
In her research, Lu, found little attention paid to Asian-American breast cancer survivor's psychological needs. Previous studies largely focused on non-Hispanic white samples, and she found a need to research this understudied population. Some of the challenges she noted with this population were feeling stigmatized, shame associated with cancer, cultural beliefs of bearing the burden alone to avoid disrupting harmony, suppressing emotions, and a lack of trained mental health professionals with cultural and linguistic competency.
"We thought of a very interesting way to help this problem. It's actually fairly basic. It's to express emotions using writing," she said. "What's so interesting is that it has been proven as a scientific paradigm."
According to Lu, previous research found that writing about emotionally difficult events for just 20 to 30 minutes at a time over three or four days increased the immune function. The release offered by writing had a direct impact on the body's capacity to withstand stress and fight off infection and disease.
"I based my study for Chinese-speaking breast cancer survivors on Pennebaker's research paradigm, and we have conducted a series of studies to modify the paradigm for Asian-Americans" said Lu.
Rather than going to a hospital, Lu worked with a community-based partner to recruit participants. Lu's research team asked participants to complete a standardized health assessment and then they were asked to write 20 minutes each week for three weeks. Three sealed envelopes were mailed simultaneously to the participants with each envelope containing different writing instructions for the corresponding week. Questionnaires assessing health outcomes were mailed to participants at three and six months after the completion of the writing assignments. Semi-structured phone interviews were conducted after the 6-month follow-up.
"The findings from the study suggest participants perceived the writing task to be easy, revealed their emotions, and disclosed their experiences in writing that they had not previously told others. Participants reported that they wrote down whatever they thought and felt and perceived the intervention to be appropriate and valuable," said Lu.
Lu added that health outcomes associated with the expressive writing intervention include a decrease of fatigue, intrusive thoughts, and reducing posttraumatic stress after three months. She also noted a decrease of fatigue, posttraumatic stress, and the increase of qualify of life and positive affect after six months.
Lu notes this research study contributes to the growing literature of expressive writing by illustrating the feasibility and potential benefits among Chinese-speaking breast cancer survivors using a community-based participatory research approach and a mixed method design. The results of the intervention demonstrate that writing was associated with health benefits at long-term follow-ups and how to adapt and utilize expressive writing intervention for minorities.
Source:University of Houston (UH).

ICMR to collaborate with private cos to commercialise indigenously developed technologies

he Indian Council of Medical Research (ICMR) will soon collaborate with private companies for further development and commercialisation of a large number of indigenous healthcare technologies developed by ICMR through a special programme aimed at development of affordable technologies for healthcare. 

According to senior officials in the ICMR, the collaborating private parties including their partnering group should have the capacity for absorption of the technology to be assessed by infrastructure, human resource and clear defined plan for further development and commercialization of healthcare technologies indigenously developed by ICMR institutes.  

The ICMR through its special programme aimed at development of indigenous affordable technologies for healthcare had developed technologies which include diagnostic assays/reagents/devices for diabetes mellitus, cervical cancer and thalassemia; vaccines for hepatitis E; infectious diseases for tuberculosis, leptospirosis, hepatitis E, rotavirus diarrhoea, food borne pathogens, chlamydia infections, Kalazar, Malaria, Filaria and Lung Fluke infection; etc.

For instance, the NIV, Pune (an ICMR institute) had developed recombinant vaccine for Hepatitis E vaccine and combination of Hepatitis E & Hepatitis B vaccines using a novel approach. Some of the salient features of the technology include the liposome formulation of T1NE protein of an Indian strain of genotype 1 HEV serves as an effective candidate vaccine for hepatitis E; the liposome formulation of T1NE protein of an Indian strain of genotype 1 HEV along with the S protein of HBV serves as an effective combined candidate vaccine for hepatitis E and hepatitis B; etc.  Research is upto laboratory scale; successful clinical trial in rhesus monkeys has been completed.

Likewise,  another ICMR institute NIOP, New Delhi has developed dot ELISA for diagnosis of sequelae to chlamydia trachomatis infection in women using chlamydial Heat Shock Protein-60.  This assay is cost-effective and is a serological test which would help in the diagnosis of women at higher risk of developing sequelae to C. trachomatis.  This has a clinical relevance as it will help the gynaecologist for timely therapy, thus improving the reproductive health of women.

The NIV, Pune has developed ELISA Test for Rotavirus which is used for detection of rotavirus from the fecal samples of diarrhoea patients. It is easy to perform, has high sensitivity and specificity and is cost effective as large number of fecal samples could be tested using indigenously developed reagents.  This can essentially avoid unnecessary use of antibiotics in diarrhoea patients. 

There are a large number of such technologies indigenously developed ICMR institutes.  The ICMR has invited expression of interest from interested companies/manufacturers/ entrepreneurs for  further developing these technologies.
Source:Pharmabiz

Tree Nuts Better Than Diets in Controlling Blood Sugar Levels in Type 2 Diabetes

Researchers have found that tree nuts are a better way to lower and stabilize blood sugar levels among type 2 diabetes patients compared to control diet.
A systematic review meta-analysis of the totality of the evidence from 12 clinical trials in 450 participants found that eating about two servings a day of tree nuts improved the two key markers of blood sugar: the HbA1c test, which measures blood sugar levels over three months, and the fasting glucose test, where patients are not allowed to eat or drink anything but water for eight hours before their blood glucose levels are tested.The best results were seen when tree nuts replaced refined carbohydrates rather than saturated fats, said Dr. John Sievenpiper, a physician and researcher in the Clinical Nutrition and Risk Factor Modification Centre of St. Michael's Hospital.The results of his study were published today in the online journal PLOS ONE.Dr. Sievenpiper said participants in the clinical trials reviewed ate 56 grams of tree nuts a day. One serving of tree nuts is about ¼ cup or 30 grams. He said that people in North America consume on average less than one serving a day, so this is one way they can adapt their diets to take advantage of the metabolic benefits. 

Tree nuts are such things as almonds, Brazil nuts, cashews, chestnuts, coconuts, hazelnuts, pecans, macadamia nuts, walnuts, pine nuts and pistachios. They do not include peanuts, which are legumes.Dr. Sievenpiper said that while nuts are high in fat, it's healthy unsaturated fat and while they can also be high in calories, participants in the clinical trials did not gain weight."Tree nuts are another way people can maintain healthy blood sugar levels in the context of a healthy dietary pattern," he said.
Source:journal PLOS ONE
 

Slow Metabolism, Obesity and Diabetes Linked to Pesticide DDT

Increased risk of obesity, diabetes, high cholesterol and related conditions in female offspring later in life has been found to be linked to exposure of pregnant mice to the pesticide DDT, in a study led by the University of California, Davis.The study, published online July 30 in the journal PLOS ONE, is the first to show that developmental exposure to DDT increases the risk of females later developing metabolic syndrome -- a cluster of conditions that include increased body fat, blood glucose, and cholesterol. 

DDT was banned in the United States in the 1970s but continues to be used for malaria control in countries including India and South Africa. 

Scientists gave mice doses of DDT comparable to exposures of people living in malaria-infested regions where it is regularly sprayed, as well as of pregnant mothers of U.S. adults who are now in their 50s. 

"The women and men this study is most applicable to in the United States are currently at the age when they're more likely to develop metabolic syndrome, because these are diseases of middle- to late adulthood," said lead author Michele La Merrill, assistant professor of environmental toxicology at UC Davis. 

The scientists found that exposure to DDT before birth slowed the metabolism of female mice and lowered their tolerance of cold temperature. This increased their likelihood of developing metabolic syndrome and its host of related conditions. 

"As mammals, we have to regulate our body temperature in order to live," La Merrill said. "We found that DDT reduced female mice's ability to generate heat. If you're not generating as much heat as the next guy, instead of burning calories, you're storing them." 

The study found stark gender differences in the mice's response to DDT. Females were at higher risk of obesity, type 2 diabetes, and cholesterol, but in males, DDT exposure did not affect obesity or cholesterol levels and caused only a minor increase in glucose levels. 

A high fat diet also caused female mice to have more problems with glucose, insulin and cholesterol but was not a risk factor for males. The sex differences require further research, the authors said.
 Source:journal PLOS ONE

 

Stem Cell Transplantation Soon After Birth Provides Best Survival Chance to ‘Bubble Boy’ Disease Patients

Conducting a hematopoietic stem cell transplant soon after birth provided the best possible chance of survival among children who are born with the 'bubble boy' disease, the conclusions of a decade-long study conducted by researchers at Dana-Farber/Boston Children's Cancer and Blood Disorders Center indicate.

These findings, the researchers say, argue for expanding newborn screening for severe combined immune deficiency (SCID), a disorder that leaves affected infants so vulnerable to infection that most die within the first year of life if untreated. 

The study, published today in the New England Journal of Medicine, analyzes data on 240 children with SCID transplanted at 25 centers across North America between Jan. 1, 2000 and Dec. 31, 2009, the decade before the U.S. Department of Health and Human Services recommended newborn screening for SCID in 2010. Currently, 21 states and the District of Columbia—together home to about two-thirds of all babies born in the United States—screen newborns for SCID. Another nine states are expected to implement newborn screening by the end of 2014. 

In addition to patient age, the analysis finds that infection status at the time of transplant and donor source had the strongest impact on transplant outcomes (i.e., five-year survival and successful immune system reconstitution). 

"Survival is much, much better if infants undergo transplant before they turn 3½ months old and before they contract any SCID-related infections," says study first author Sung-Yun Pai, MD, of Dana-Farber/Boston Children's. "The best way to identify patients that early when there is no family history of SCID is through newborn screening." 

Data gained from newborn screening suggest that SCID, while still rare, is twice as common as once thought. "Some children who succumbed to unexplained infections probably suffered from SCID," Pai notes. The disorder is now estimated to occur in one of every 50,000 births, up from earlier estimates of one in 100,000 births. 

"Time is not the ally of children with SCID," says Luigi Notarangelo, MD, of Boston Children's Hospital, one of the study's senior authors, who was among those who lobbied successfully to establish SCID newborn screening in Massachusetts in 2009. "Because they do not have a functional immune system, the longer the wait before a transplant the greater the risk they will contract a potentially devastating infection." 

The new study was conducted under the auspices of the Primary Immune Deficiency Treatment Consortium, a North American collaborative supported by the National Institutes of Health. It looked at the effect on outcomes of patient age, infection status, donor source, and the use of chemotherapy to condition patients prior to transplant. 

Children who underwent transplant before 3.5 months of age had excellent survival, regardless of donor source or infection status, as did patients transplanted with the stem cells of a matched sibling donor, long recognized as the gold standard of transplant. Children outside that age group also had very good survival regardless of donor source—sibling, parent or unrelated donor—as long as the patient did not have an active infection at the time of transplant. The effect on survival of donor type and pre-transplant conditioning was only discernible in actively infected patients. 

• Overall, 74 percent of the 240 patients studied survived at least five years.
• Among patients transplanted younger than 3.5 months, 94 percent survived.
• Virtually all (97 percent) of patients who received stem cells from a matched sibling donor survived.
• At 50 percent, survival was lowest among patients who were older than 3.5 months and had active infections at the time of transplant. Actively infected infants who did not have a matched sibling donor and who received immunosuppressive or chemotherapy prior to transplant had particularly poor survival (39-53%).
• Among patients who never had an infection, 90 percent survived, as did 82 percent of patients whose infection had resolved before transplant.

While survivors who received chemotherapy conditioning have stronger immune systems after transplant, further research is needed, Pai says, to determine whether the late effects of chemotherapy or the vulnerabilities of a weaker immune system pose the greater long-term risk. 

"This study accomplishes several things," Pai notes. "First, it creates a baseline with which to compare patient outcomes since the advent of newborn screening for SCID. Second, it provides guidance for clinicians regarding the use of chemotherapy conditioning before transplantation. Third, it highlights the relative impacts of infection status and patient age on transplant success. 

"Lastly," she adds, "it establishes the importance of early detection and transplantation, which points to the benefit of expanding newborn screening for SCID as broadly as possible." 
 Source:New England Journal of Medicine

Our Genes Have Made Us Susceptible to Atherosclerosis: Study

In this month's edition of  Global Heart (the journal of the World Heart Federation), the authors ask in the editorial: "Why do humans develop atherosclerosis?

 Is the human genome hardwired to develop atherosclerosis? Can atherosclerosis be entirely prevented? Is atherosclerosis fundamental to the aging process? Have the risk factors that have contributed to the development of atherosclerosis been the same all along human evolution?" The editorial is by Dr Gregory Thomas, Medical Director, MemorialCare Heart & Vascular Institute, Long Beach Memorial, Long Beach, CA; USA; Dr Samuel Wann, Columbia St. Mary's Healthcare, Milwaukee, WI, USA; and Professor Jagat Narula, Editor-in-Chief of Global Heart and Associate Dean for Global Health at Icahn School of Medicine at Mount Sinai, New York, USA. 

Reviewing the related studies in the issue, the editors comment: "Using x-ray computed tomography (CT), the investigators contributing to this issue of Global Heart have yet to find a culture that did not have pre-clinical atherosclerosis. Unfortunately, like Ponce de León, they did not find an atherosclerosis 'fountain of youth'." 

The international, interdisciplinary Horus mummy research team explored the prevalence and potential causes of atherosclerosis, by CT scanning ancient people across the globe. Professor Narula and Dr Wann comment on the findings, "The melding of archaeology, anthropology, paleopathology, and medical science created the opportunity to develop new insights into atherosclerosis. Cross fertilisation of seemly unrelated disciplines and re-examination of common and uncommon diseases in the light of new data and capabilities from such disciplines harbours great potential for new discoveries not only in cardiology but across the field of medicine." 

The editors conclude: "The work of the Horus and other research teams suggests that genetically humans are inherently susceptible to atherosclerosis. However, the environment in which humans live, the choices they make, to be active, to avoid smoking, and staying lean, all contribute to determining when in life atherosclerosis will strike." As Horus team member, Dr Michael I Miyamoto of Mission Heritage Medical Group suggests, "As humans we want to die with atherosclerosis, not because of atherosclerosis." 

 Source:Global Heart

India terms US 'Special 301' process a unilateral measure to create pressure on countries to increase IPR

India has termed the recently released United States Trade Representative (USTR) 2014 “Special 301 Report” a unilateral measure taken by the US to increase Intellectual Property Rights (IPR) protection beyond the TRIPS Agreement.  

“The Special 301 process is a unilateral measure taken by the United States under their Trade Act, 1974 to create pressure on countries to increase IPR protection beyond the TRIPS Agreement. It is an extra territorial application of the domestic law of a country and is not tenable under the overall WTO regime”, Union Minister for Commerce & Industry Nirmala Sitharaman said. 

India has a well-established legislative, administrative and judicial framework to safeguard Intellectual Property Rights which meets its obligations under the Agreement on Trade Related Intellectual Property Rights (TRIPS) while utilizing the flexibilities provided in the international regime to address its developmental concerns, the minister in a written reply said in Rajya Sabha on July 30.

On April 30 this year, the US had brought out the Special 301 Report for the year 2014 which classified India as a “Priority watch list country.” The concerns identified in the report are based on the inputs provided by the US industry on their perception of the level of protection provided by India to Intellectual Property.  Issues that have been flagged in the report include, inter-alia, concerns over the provision of section 3(d) of the Patent Act which relates to non-patentability of inventions involving chemical forms that do not show increased efficacy, issue of Compulsory License by the Controller General of Patent, Designs and Trademarks under section 84 of the Patents Act, inclusion of a statement relating to Compulsory Licence for green technologies in India’s National Manufacturing Policy and challenges relating to enforcement of IP Rights.

Section 3(d) of the Indian Patent Act 1970 (as amended in 2005) does not allow patent to be granted to inventions involving new forms of a known substance unless it differs significantly in properties with regard to efficacy. Thus, the Indian Patent Act does not allow evergreening of patents. This is a cause of concern to the US pharma companies, the minister said.
Source:Pharmabiz

Key to aging immune system is discovered

UCSF scientist leads team discovery of DNA replication problem

There's a good reason people over 60 are not donor candidates for bone marrow transplantation. The immune system ages and weakens with time, making the elderly prone to life-threatening infection and other maladies, and a UC San Francisco research team now has discovered a reason why.
"We have found the cellular mechanism responsible for the inability of blood-forming cells to maintain blood production over time in an old organism, and have identified molecular defects that could be restored for rejuvenation therapies," said Emmanuelle Passegué, PhD, a professor of medicine and a member of the Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research at UCSF. Passegué, an expert on the stem cells that give rise to the blood and immune system, led a team that published the new findings online July 30, 2014 in the journal Nature.
Blood and immune cells are short-lived, and unlike most tissues, must be constantly replenished. The cells that must keep producing them throughout a lifetime are called "hematopoietic stem cells." Through cycles of cell division these stem cells preserve their own numbers and generate the daughter cells that give rise to replacement blood and immune cells. But the hematopoietic stem cells falter with age, because they lose the ability to replicate their DNA accurately and efficiently during cell division, Passegué's lab team determined.
Especially vulnerable to the breakdown, the researchers discovered in their new study of old mice, are transplanted, aging, blood-forming stem cells, which lack the ability to make B cells of the immune system. These B cells make antibodies to help us fight all sorts of microbial infections, including bacteria that cause pneumonia, a leading killer of the elderly.
In old blood-forming stem cells, the researchers found a scarcity of specific protein components needed to form a molecular machine called the mini-chromosome maintenance helicase, which unwinds double-stranded DNA so that the cell's genetic material can be duplicated and allocated to daughter cells later in cell division. In their study the stem cells were stressed by the loss of activity of this machine and as a result were at heightened risk for DNA damage and death when forced to divide.
The researchers discovered that even after the stress associated with DNA replication, surviving, non-dividing, resting, old stem cells retained molecular tags on DNA-wrapping histone proteins, a feature often associated with DNA damage. However, the researchers determined that these old survivors could repair induced DNA damage as efficiently as young stem cells.
"Old stem cells are not just sitting there with damaged DNA ready to develop cancer, as it has long been postulated" Passegué said.
But not all was well in the old, surviving stem cells. The molecular tags accumulated on genes needed to make the cellular factories known as ribosomes. The ribosomes make all the cell's proteins. Passegué will further explore the consequences of reduced protein production as part of her ongoing research.
"Everybody talks about healthier aging," Passegué added. "The decline of stem-cell function is a big part of age-related problems. Achieving longer lives relies in part on achieving a better understanding of why stem cells are not able to maintain optimal functioning."

Passegué hopes that it might be possible to prevent declining stem-cell populations by developing a drug to prevent the loss of the helicase components needed to faithfully unwind and replicate DNA, thereby avoiding immune-system failure.

Source:Nature.