How omega-3 fatty acids reduce inflammation

London, May 3 (ANI): Researchers at the University of Pittsburgh School of Medicine have found new mediators that not only can explain how omega-3 fatty acids reduce inflammation, but also hint at novel treatments for a host of diseases linked to inflammatory processes.

Dr. Bruce A. Freeman said that there is strong evidence that eating foods rich in omega-3 fatty acids, such as some fish, plant-derived oils and nuts, or taking omega-3s as a dietary supplement reduces inflammation and lowers the risk of illness and death from cardiovascular and other inflammatory diseases.

“What has been a provocative question for people familiar with these impressive clinical actions is how omega-3 fatty acids actually induce such beneficial pharmacological effects. This study has given us fresh and revealing perspective into that process,” Nature quoted him as saying.

In the study, also led by Dr. Francisco J. Schopfer, the researchers examined metabolic byproducts of omega-3 fatty acids that are produced by activated macrophages, a type of immune cell that is always present in inflamed tissue, and discovered previously unknown biochemical mediators of inflammation.

They used a small molecule called beta-mercaptoethanol (BME) as a reactive bait, and “hooked” several derivatives of omega-3 fatty acids that were produced by immune cells.

These derivatives were chemically modified to become electrophilic fatty acid oxidation products (EFOX), meaning they are attracted to electrons and therefore react with critical molecular targets in many different cell types.

By interacting with certain protein residues that have electrons available for chemical binding, these derivatives stimulate changes in cellular protein function and the genetic expression patterns of cells, resulting in a broad range of antioxidant and anti-inflammatory responses.

The research team found that an enzyme called cyclooxygenase-2 (COX-2), which is the molecular target of common drugs such as aspirin, ibuprofen and acetaminophen, mediates the transformation of omega-3 fatty acids into EFOX.

Notably, cellular EFOX concentrations were significantly increased in the presence of aspirin, suggesting another mechanism for that drug”s beneficial effects.

“There is a lot of evidence that supports minimizing inflammation as a fundamental therapy for many diseases. Our new insights help explain in part the multitude of beneficial actions observed for both omega-3 fatty acids and aspirin, and the discovery of this new class of omega-3 fatty acid-derived anti-inflammatory mediators could point drug development activities in new and fruitful directions,” said Freeman.

For example, drugs that, like aspirin, enhance the production of EFOX could be of value, or new agents might be synthesized that are able to induce anti-inflammatory signals that are similar to those induced by EFOX, he explained.

The findings were published in the online version of Nature Chemical Biology. (ANI)

Regular aerobic exercise keeps the brain healthy

Washington, Apr 27 (ANI): Regular aerobic exercise improves blood flow to the brain and speeds learning process, says a new study.

The study led by researchers from the University of Pittsburgh School of Medicine is the first to examine these relationships in a non-human primate model.

The finding is available in the journal Neuroscience.

While there is ample evidence of the beneficial effects of exercise on cognition in other animal models, such as the rat, it has been unclear whether the same holds true for people, said senior author Judy L. Cameron, Ph.D., a psychiatry professor at Pitt School of Medicine and a senior scientist at the Oregon National Primate Research Center at Oregon Health and Science University. Testing the hypothesis in monkeys can provide information that is more comparable to human physiology.

“We found that monkeys who exercised regularly at an intensity that would improve fitness in middle-aged people learned to do tests of cognitive function faster and had greater blood volume in the brain”s motor cortex than their sedentary counterparts,” Dr. Cameron said. “This suggests people who exercise are getting similar benefits.”

To reach the conclusion, researchers trained adult female cynomolgus monkeys to run on a human-sized treadmill at 80 percent of their individual maximal aerobic capacity for one hour each day, five days per week, for five months. Another group of monkeys remained sedentary, meaning they sat on the immobile treadmill, for a comparable time. Half of the runners went through a three-month sedentary period after the exercise period. In all groups, half of the monkeys were middle aged (10 to 12 years old) and the others were more mature (15 to 17 years old). Initially, the middle-aged monkeys were in better shape than their older counterparts, but with exercise, all the runners became more fit.

During the fifth week of exercise training, standardized cognitive testing was initiated and then performed five days per week until week 24. In a preliminary task, the monkeys learned that by lifting a cover off a small well in the testing tray, they could have the food reward that lay within it. In a spatial delay task, a researcher placed a food reward in one of two wells and covered both wells in full view of the monkey. A screen was lowered to block the animal”s view for a second, and then raised again. If the monkey displaced the correct cover, she got the treat. After reliably succeeding at this task, monkeys that correctly moved the designated one of two different objects placed over side-by-side wells got the food reward that lay within it.

“Monkeys that exercised learned to remove the well covers twice as quickly as control animals,” Dr. Cameron said. “Also, they were more engaged in the tasks and made more attempts to get the rewards, but they also made more mistakes.”

She noted that later in the testing period, learning rate and performance was similar among the groups, which could mean that practice at the task will eventually overshadow the impact of exercise on cognitive function.

When the researchers examined tissue samples from the brain”s motor cortex, they found that mature monkeys that ran had greater vascular volume than middle-aged runners or sedentary animals. But those blood flow changes reversed in monkeys that were sedentary after exercising for five months.

“These findings indicate that aerobic exercise at the recommended levels can have meaningful, beneficial effects on the brain,” Dr. Cameron said. “It supports the notion that working out is good for people in many, many ways.” (ANI)

Experimental vaccine may delay bowel inflammation and colon cancer

Washington, March 25 (ANI): A new experimental vaccine could delay bowel inflammation and colon cancer, researchers at the University of Pittsburgh School of Medicine say.

Their findings have appeared in Cancer Prevention Research, a journal of the American Association for Cancer Research.

According to senior author Olivera Finn, professor and chair, Department of Immunology, Pitt School of Medicine, people with chronic inflammatory disorders such as IBD are at greater risk for developing cancer at the inflamed site. In other cases, genes that develop cancerous changes can trigger inflammation.

The vaccine made by her team is directed against an abnormal variant of a self-made cell protein called MUC1, which is altered and produced in excess in both IBD and colon cancer.

Dr. Finn said: “Our experiments indicate that boosting the immune response against this protein early in the disease can delay IBD development, control inflammation and thereby reduce the risk of future cancers.

“These findings suggest also that the early stages of chronic inflammation might be considered a premalignant condition.”

For the study, the scientists tested transgenic mice that spontaneously develop IBD and then progress to colitis-associated colon cancer, producing the human version of MUC1 in both disease states. It was seen that animals that received the vaccine showed the first signs of IBD significantly later than those in two control groups that did not get the vaccine.

Microscopic evaluation of the colon tissue demonstrated less inflammation in the vaccinated mice, and no indication of cancerous changes. Nearly half of the animals in each of the control groups had evidence of abnormal tissue, and two had colon cancer.

Dr. Finn said: “The MUC1 vaccine seems to change the local environment from one that promotes cancer development to one that inhibits it.

“Certain immune cells that we usually see in the inflamed colon aren”t present, and that could make the surroundings less friendly for potentially cancerous cells that also are directly targeted by the vaccine for destruction.” (ANI)

Multifunctional polymer can neutralize both biological and chemical weapons

Washington, March 19 (ANI): Scientists from the McGowan Institute for Regenerative Medicine, US, have synthesized a single, multifunctional polymer material that can decontaminate both biological and chemical toxins.

“Our lab applies biological principles to create materials that can do many things, just like our skin protects us from both rain and sun,” said senior investigator Alan Russell, University Professor of Surgery, University of Pittsburgh School of Medicine, and director, McGowan Institute.

“Typically, labs engineer products that are designed to serve only one narrow function,” he added.

Those conventional approaches might not provide the best responses for weapons of mass destruction, which could be biological, such as smallpox virus, or chemical, such as the nerve agent sarin, he noted.

Terrorists aren’t going to announce what kind of threat they unleash in an attack.

“That uncertainty calls for a single broad-spectrum decontamination material that can rapidly neutralize both kinds of threats and is easily delivered or administered, and it must not damage the environment where it is applied,” Dr. Russell said.

“Much work has gone into developing ways to thwart either germ or chemical weapons, and now we”re combining some of them into one countermeasure,” he added.

He and his team have devised a polyurethane fiber mesh containing enzymes that lead to the production of bromine or iodine, which kill bacteria, as well as chemicals that generate compounds that detoxify organophosphate nerve agents.

“This mesh could be developed into sponges, coatings or liquid sprays, and it could be used internally or as a wound dressing that is capable of killing bacteria, viruses and spores,” said lead investigator Gabi Amitai of the McGowan Institute and the Israel Institute for Biological Research.

“The antibacterial and antitoxin activities do not interfere with each other, and actually can work synergistically,” he added.

In their experiments, the material fended off Staph aureus and E. coli, which represent different classes of bacteria.

After 24 hours, it restored 70 percent of the activity of acetylcholinesterase, an enzyme that is inhibited by nerve agents leading to fatal dysfunction of an essential neurotransmitter.

The researchers continue to develop alternate decontamination strategies to address chemical and biologic weapons. (ANI)

Living without a car in areas with high fast food availability ups obesity risk

Washington, September 2 (ANI): People who do not own a car, and live in areas where there are a number of fast food restaurants, may be at an increased risk of becoming obese, according to a study.

American researchers at the University of Pittsburgh have observed that people who live in areas with high fast food concentration and do not have a car are as much as 12 pounds heavier, compared to those living in neighbourhoods that lack such restaurants.

“Owning a car is generally associated with a more sedentary lifestyle and excess weight gain because people spend more time in their cars and less time walking,” said Dr. Sanae Inagami, study lead author and assistant professor, University of Pittsburgh School of Medicine.

Yet, her research team looked at whether a high concentration of fast food restaurants impacted this association, and found that not owning a car in areas where fast food was more readily available increased the risk of obesity.

“Fast food may be specific to weight gain in particular populations and locations. People who are less affluent don’t own cars and can’t go distances for healthier foods. As a result, they may end up opting for the lower-priced and high caloric foods available at fast food chains,” she said.

As part of the study, the researchers surveyed 2,156 adults in 63 neighbourhoods in Los Angeles County.

They observed that car owners, on average, weighed 8.5 pounds more than non-car owners, except in areas with high fast food concentration-five fast food restaurants per mile.

The researchers say that non-car owners in high fast food concentration areas were found to weigh 2.7 pounds more than car owners who lived in the same areas, and 12 pounds more than residents of areas without fast food outlets.

According to them, people who did not own a car, and lived in areas without fast food outlets, weighed the least.

“There has been a major focus on fast food and its impact on individual health, but we need to consider the availability of all types of restaurants at individual and community levels,” Sanae said.

“Since our study showed that total restaurant density was associated with weight gain in all individuals, not just those who did not own cars, we also need to encourage people to pay more attention to their food environment,” she added. (ANI)

Scientists identify 50 microRNAs in saliva that may help diagnose oral cancer

Washington, August 26 (ANI): At least 50 microRNAs present in human saliva may prove helpful in detecting oral cancer, according to a study conducted in America.

The findings of the study have been detailed in an article published in Clinical Cancer Research, a journal of the American Association for Cancer Research.

“It is a Holy Grail of cancer detection to be able to measure the presence of a cancer without a biopsy, so it is very appealing to think that we could detect a cancer-specific marker in a patient’s saliva,” said Dr. Jennifer Grandis, professor of Otolaryngology and Pharmacology at the University of Pittsburgh School of Medicine and Cancer Institute, and a senior editor of Clinical Cancer Research.

MicroRNAs are molecules produced in cells that have the ability to simultaneously control activity and assess the behaviour of multiple genes. Scientists believe that they may hold the key to early detection of cancer.

The emergence of a microRNA profile in saliva represents a major step forward in the early detection of oral cancer.

“The oral cavity is a mirror to systemic health, and many diseases that develop in other parts of the body have an oral manifestation,” said David T. Wong, Felix and Mildred Yip Endowed Professor at the University of California, Los Angeles School of Dentistry.uring the study, the researchers measured microRNA levels in the saliva of 50 patients with oral squamous cell carcinoma, and 50 healthy control patients.

Their efforts led to the detection of approximately 50 microRNAs, says the study report.

The article points out that two specific microRNAs-miR-125a and miR-200a-were present at significantly lower levels in patients with oral cancer than in the healthier controls.

Wong admitted that the study’s findings would have to be confirmed by a larger and longer analysis. (ANI)

Obese people ‘at greater Alzheimer’s risk’

Washington, Aug 26 (ANI): Here’s some discouraging news for obese people: a new report has found that fat people are at greater risk for developing Alzheimer’s.

In the current online edition of the journal Human Brain Mapping, Paul Thompson, senior author and a UCLA professor of neurology, and lead author Cyrus A. Raji, a medical student at the University of Pittsburgh School of Medicine, and colleagues compared the brains of people who were obese, overweight, and of normal weight, to see if they had differences in brain structure; that is, did their brains look equally healthy.

They found that obese people had 8 percent less brain tissue than people with normal weight, while overweight people had 4 percent less tissue.

“That’s a big loss of tissue and it depletes your cognitive reserves, putting you at much greater risk of Alzheimer’s and other diseases that attack the brain,” said Thompson. But you can greatly reduce your risk for Alzheimer’s, if you can eat healthily and keep your weight under control,” he added.

To reach the conclusion, researchers used brain images from an earlier study called the Cardiovascular Health Study Cognition Study. Scans were selected of 94 elderly people in their 70s who were healthy not cognitively impaired-five years after the scan was taken. To define the weight categories, they used the Body Mass Index (BMI), the most widely used measurement for obesity. Normal weight people were defined as having a BMI between 18.5-25; overweight people between 25-30, and obese people greater than 30.

The researchers then converted the scans into detailed three-dimensional images using tensor-based morphometry, a neuroimaging method that offers high resolution mapping of anatomical differences in the brain.

In looking at both grey matter and white matter of the brain, they found that the people defined as obese had lost brain tissue in the frontal and temporal lobes, areas of the brain critical for planning and memory, and in the anterior cingulate gyrus (attention and executive functions), hippocampus (long term memory) and basal ganglia (movement). Overweight people showed brain loss in the basal ganglia, the corona radiata, white matter comprised of axons, and the parietal lobe (sensory lobe).

“The brains of obese people looked 16 years older than the brains of those who were lean, and in overweight people looked eight years older,” says Thompson.

“It seems that along with increased risk for health problems such as type 2 diabetes and heart disease, obesity is bad for your brain: we have linked it to shrinkage of brain areas that are also targeted by Alzheimer’s,” said Pittsburgh’s Raji.

“But that could mean exercising, eating right and keeping weight under control can maintain brain health with aging and potentially lower the risk for Alzheimer’s and other dementias,” the expert added. (ANI)

Enzyme key to ageing identified

Washington, July 11 (ANI): Scientists from University of Pittsburgh School of Medicine have identified an enzyme that plays a crucial role in the process of aging.

Lead researcher Dr. Abbe de Vallejo, associate professor of Paediatrics and Immunology, has found that eliminating pregnancy-associated plasma protein A (PAPPA) enzyme increases the lifespan of study mice.

The researcher revealed that PAPPA enzyme has the ability to promote a robust immune system into old age, by maintaining the function of the thymus throughout life.

Thymus is the organ that produces T cells to fight disease and infection. It degenerates with age.

The study showed that PAPPA-knockout mice live at least 30 percent longer, and have significantly lower occurrence of spontaneous tumours than typical mice.

PAPPA controls the availability in tissues of a hormone known as insulin-like growth factor (IGF) that is a promoter of cell division. Hence, IGF is required for normal embryonic and postnatal growth.

IGF is associated with tumour growth, inflammation, and cardiovascular disease in adults.

By deleting PAPPA, the researchers were able to control the availability of IGF in tissues and dampen its many ill effects.

In the thymus, deletion of PAPPA maintained just enough IGF to sustain production of T cells without consuming precursor cells, thereby preventing the degeneration of the thymus.

“Controlling the availability of IGF in the thymus by targeted manipulation of PAPPA could be a way to maintain immune protection throughout life,” de Vallejo said.

“This study has profound implications for the future study of healthy aging and longevity,” de Vallejo added.

The study has been published in the Proceedings of the National Academy of Sciences. (ANI)

Rapid weight loss in old age could raise dementia risk

Washington, May 19 (ANI): Older people who are thinner or are losing pounds quickly are at an increased risk of developing dementia, especially if they started out overweight or obese, according to a new study.

The research is published in the May 19, 2009, print issue of Neurology, the medical journal of the American Academy of Neurology.

To reach the conclusion, researchers followed for eight years 1,836 Japanese Americans in Washington state with an average age of 72. During that time, 129 people developed dementia.

The research found that people with lower body mass index (BMI) scores at the beginning of the study were 79 percent more likely to develop dementia than those with higher BMI scores.

In addition, those who lost weight over the study period at a faster rate were nearly three times more likely to develop dementia than those who lost weight more slowly over time. This result was more pronounced in those who were overweight or obese to start; those with a BMI of 23 or higher had an 82-percent reduced risk of developing the disease compared to those who were normal or underweight.

The results were the same after testing for other health risk factors such as smoking, exercise and gender.

“Our finding suggests that losing weight quickly in older age may be an early sign of dementia,” said study author Tiffany Hughes, PhD, MPH, who is with the University of Pittsburgh School of Medicine but conducted the research while she was a doctoral student at the University of South Florida.

“This doesn’t mean that being obese or overweight is healthy for the mind or body, but losing weight may be a sign of emerging brain disease,” the research added. (ANI)

Older men more likely to die after pneumonia than women

Washington, April 30 (ANI): Old men are more likely do die after being hospitalized with community-acquired pneumonia (CAP) than women, according to a new study, which suggests that the reason may be differing biological response to infection between males and females.

The findings may have important implications for understanding sex differences in life expectancy.

“Our study found that men with CAP were less likely to survive after an infection compared to women and this was not explained by differences in demographics, health behaviour, chronic health conditions or quality of care,” said Sachin Yende, M.D., assistant professor in the Department of Critical Care Medicine at the University of Pittsburgh School of Medicine and corresponding author of the study.

The researchers measured blood levels of inflammatory indicators, including tumour necrosis factor (TNF) and interleukins 6 and 10, coagulation indicators including Factor IX, and fibrinolysis indicators including D-dimer concentrations.

They found patterns in these biomarkers that suggest men generate a stronger inflammatory and coagulation response and, perhaps, break up blood clots more quickly than women in response to infection.

“These differences in inflammatory, coagulation and fibrinolysis biomarkers among men may explain the reduced short-term and long-term survival,” said Dr. Yende.

Data were gathered from the multicenter Genetic and Inflammatory Markers of Sepsis (GenIMS) study. Participants were enrolled upon emergency department admission at 28 academic and community hospitals in Pennsylvania, Connecticut, Michigan and Tennessee from 2001 to 2003.

The study included 2,320 subjects, with a mean age of 64.9 years, 1,136 of whom were men. The men were sicker on admission, more likely to be smokers, and had at least one chronic health condition, such as cardiac disease or cancer. Severe sepsis occurred in 588 (31 percent) subjects. Of these, about half had severe sepsis on their first day of hospitalization.

The researchers found that men had a higher risk than women of death at 30 days (7 percent vs. 4.5 percent), 90 days (11.4 percent vs. 8.6 percent) and one year (21 percent vs. 16 percent).

“Even compared to women with an equivalent illness severity, men were more likely to die. Survival differences persist up to one year after the initial hospitalization, when most patients had recovered from the pneumonia and left the hospital,” Dr. Yende said.

The study is published online in the Critical Care Medicine journal. (ANI)

Developmental drug effective against radiation damage

Washington, Apr 23 (ANI): A drug, currently under development, has been found effective in providing protection against damaging effects of radiation exposure.

The research team from University of Pittsburgh School of Medicine has found that experimental drug JP4-039 protects cells from being damaged by radiation exposure.

Lead researcher Dr Joel Greenberger, professor and chairman of the Department of Radiation Oncology at Pitt revealed that JP4-039 assists the mitochondria, the energy generator of all cells, in combating irradiation-induced cell death.

For this study, cells treated immediately after irradiation with JP4-039 demonstrated significant radioprotection, suggesting a potential role for the drug as a mitigator of radiation damage.

“Currently, no drugs on the market counteract the effects of radiation exposure,” said Dr. Greenberger.

“We know this drug can counteract the damage caused by irradiation, and now we want to develop the ideal dosage, one that is effective for the general population while remaining non-toxic.

“Our goal is to take this drug through a phase I clinical trial and, once the dosage is established, develop the drug for late-stage clinical trials and market licensing,” he added.

The findings were presented at 100th annual meeting of the American Association for Cancer Research (AACR). (ANI)

Stem cell therapy may help treat corneal blindness, vision impairment

Washington, April 9 (ANI): Researchers at the University of Pittsburgh School of Medicine have found that stem cells collected from human corneas restore transparency and don’t trigger a rejection response when injected into eyes that are scarred and hazy, raising hopes that cell-based therapies to treat human corneal blindness and vision impairment may soon be available.

“Our experiments indicate that after stem cell treatment, mouse eyes that initially had corneal defects looked no different than mouse eyes that had never been damaged,” said senior investigator James L. Funderburgh, Ph.D., associate professor, Department of Ophthalmology.

Few years ago, Funderburgh and his colleagues identified stem cells in a layer of the cornea called the stroma, and they recently showed that even after many rounds of expansion in the lab, these cells continued to produce the biochemical components, or matrix, of the cornea.

One such protein is called lumican, which plays a critical role in giving the cornea the correct structure to make it transparent.

Funderburgh said that mice that lack the ability to produce lumican develop opaque areas of their corneas comparable to the scar tissue that human eyes form in response to trauma and inflammation.

However, three months after the lumican-deficient mouse eyes were injected with human adult corneal stem cells, transparency was restored.

The cornea and its stromal stem cells themselves appear to be “immune privileged,” meaning they don’t trigger a significant immune response even when transplanted across species, as in the Pitt experiments.

“Several kinds of experiments indicated that the human cells were alive and making lumican, and that the tissue had rebuilt properly,” Dr. Funderburgh noted.

Their study will be published in the journal Stem Cells and appears online. (ANI)

Scientists testing vaccine to prevent colon cancer

Washington, Mar 20 (ANI): Researchers at the University of Pittsburgh School of Medicine have begun testing a vaccine to prevent colon cancer.

If shown to be effective, it might spare patients the risk and inconvenience of repeated invasive surveillance tests, such as colonoscopy, that are now necessary to spot and remove precancerous polyps.

In a new approach for cancer prevention, the new vaccine is directed against an abnormal variant of a self-made cell protein called MUC1, which is altered and produced in excess in advanced adenomas and cancer.

“By stimulating an immune response against the MUC1 protein in these precancerous growths, we may be able to draw the immune system’s fire to attack and destroy the abnormal cells. That might not only prevent progression to cancer, but even polyp recurrence,” Schoen said.

According to co-author Olivera Finn, Ph.D., professor and chair of the Department of Immunology at Pitt’s School of Medicine, MUC1 vaccines have been tested for safety and immunogenicity in patients with late-stage colon cancer and pancreatic cancer.

“Patients were able to generate an immune response despite their cancer-weakened immune systems. Patients with advanced adenomas are otherwise healthy and so they would be expected to generate a stronger immune response. That may be able to stop precancerous lesions from transforming into malignant tumours,” she said.

About a dozen people have received the experimental vaccine so far, and the researchers intend to enroll another 50 or so into the study. (ANI)

Details of age-related blindness may be obtained from 3-D snapshots of eyes

Washington, March 20 (ANI): A group of U.S. scientists have created ultra-detailed 3-D images of the eyes of more than 2,000 people from different ethnic groups, 400 of whom have age-related macular degeneration (AMD), hoping that they will pave the way for new diagnostic software that will help get a better look at the abnormalities that cause this condition, and prove useful for developing new treatments.

The team was led by James Fujimoto at the Massachusetts Institute of Technology and collaborators Jay Duker of the Tufts University School of Medicine, and Joel Schuman of the University of Pittsburgh School of Medicine.

AMD is a condition in which the macula, the region of highest visual acuity in the retina, stops functioning properly. No treatment currently exists for dry AMD, and those available for the wet form can only slow, not stop, vision loss.

The researchers say that publishing the electronic data in 3-D images may make it available to the image processing community to develop computer programs that can quickly and automatically detect the details and severity of the disease.

Fujimoto admits that developing such a program will be difficult because of the sheer quantity of data contained in each data set.

He, however, insists that this data is important because quantitative measurements can be used to track disease progression, and help establish correlations between the severity of vision loss and changes in the architecture of the eye.

A report on the research team’s work has been published in the journal Optics Express. (ANI)

Scientists unveil two molecular steps leading to protein clumps of Huntington’s disease

London, March 9 (ANI): Scientists at the University of Pittsburgh School of Medicine say that they have deconstructed the first steps in an intricate molecular dance that might lead to the formation of pathogenic protein clumps in Huntington’s disease, and possibly other movement-related neurological disorders.

Dr. Ronald Wetzel, a professor in the Department of Structural Biology, points out that Huntington’s is one of 10 diseases in which a certain protein, different for each disease, contains polyglutamine, a stretch of repeating blocks of the amino acid glutamine.

The researcher has revealed that the affected protein in Huntington’s disease is called huntingtin.

According to him, most people have a huntingtin protein whose polyglutamine segment contains 20 or so glutamines, and even a polyglutamine with as many as 35 repeats may not cause Huntington’s symptoms.

However, the odds of contracting Huntington’s disease increase significantly in individuals whose polyglutamine sequences are only slightly larger.

A block of 40 repeats, for example, is associated with a very high likelihood of having the disease.

“To a protein chemist, this is a fascinating situation. Polyglutamine doesn’t seem to play a sophisticated role in these proteins, and it doesn’t have a defined structure.

Yet by changing its length to only a very slight extent, it takes on some new physical properties that somehow initiate diseases,” Nature magazine quoted Dr. Wetzel as saying.

In the current study, the researchers worked out the details of how the aggregation behaviour of huntingtin depends, in a surprisingly intricate way, on the neighboring segments of amino acid sequence flanking the polyglutamine.

The research team observed that longer polyglutamine sequences have the ability to disrupt the structure of a neighboring region, 17 amino acids long, at the beginning of the protein known as the N-terminus.

According to the researchers, that sets the stage for new physical interactions with the rest of the huntingtin protein that drive it to aggregate.

“If the N-terminus is not there, huntingtin makes clumps very slowly, even if the polyglutamine stretch is rather long. When the N-terminus is disrupted by its polyglutamine neighbor, it takes a lead role in the aggregation process, with the polyglutamine then following to consolidate and stabilize the clumps – a kind of ‘aggregation two-step’,” Dr. Wetzel noted.

The researcher believes that the choreography may be similar in other polyglutamine diseases, which means that physical disruption of neighbouring regions may influence the tendency for the protein to clump.

He warranted further studies to establish whether the aggregates cause disease or are merely a marker for it, and to try to develop treatments that can redirect the protein dance or perhaps halt it entirely.

“For those of us interested in developing therapeutics, the strong role played by the N-terminus in initiating aggregation gives us another possible molecular target,” Dr. Wetzel notes.

An article on this research work has been published in the online edition of the journal Nature Structural and Molecular Biology. (ANI)

Sexual lyrics in popular songs linked to underage sex

Washington, Feb 24 (ANI): Teenagers who prefer popular songs with degrading sexual references are more likely to engage in intercourse or in pre-coital activities, according to a new study.

“This study demonstrates that, among this sample of young adolescents, high exposure to lyrics describing degrading sex in popular music was independently associated with higher levels of sexual behaviour,” Brian A. Primack, MD, EdM, MS, Center for Research on Health Care at the University of Pittsburgh School of Medicine, said.

“In fact, exposure to lyrics describing degrading sex was one of the strongest associations with sexual activity…These results provide further support for the need for additional research and educational intervention in this area,” Primack added.

Surveys were completed by 711 ninth-grade students at three large urban high schools. These participants were exposed to over 14 hours each week of lyrics describing degrading sex. About one third had previously been sexually active.

The researchers found that compared to those with the least exposure to lyrics describing degrading sex, those with the most exposure were more than twice as likely to have had sexual intercourse.

The relationship between exposure to lyrics describing degrading sex and sexual experience held equally for both young men and women.

Similarly, among those who had not had sexual intercourse, those in the highest third of exposure to lyrics describing degrading sex were nearly twice as likely to have progressed along a non-coital sexual continuum compared to those in the lowest third. Finally, the relationships between exposure to lyrics describing non-degrading sex and sexual outcomes were not significant.

Primack concluded that these findings build on those of previous studies suggesting that exposure to sex in media messages may be a risk factor for early sexual progression.

The study is published in the April 2009 issue of the American Journal of Preventive Medicine. (ANI)

Too much TV time increases depression risk among teens

Washington, Feb 3 (ANI): Too much exposure to television and other electronic media during adolescence might lead to depression in young adulthood, especially among men, say researchers.

A team led by Brian A. Primack, M.D., Ed.M., M.S., of the University of Pittsburgh School of Medicine analysed the data from 4,142 teens in National Longitudinal Survey of Adolescent Health (Add Health).

The participants were not depressed at the beginning of the study in 1995. The teens were asked how many hours they had spent during the last week watching television or videocassettes, playing computer games or listening to the radio (the survey was conducted before DVDs or the Internet became widely used).

They reported an average of 5.68 hours of media exposure per day, including 2.3 hours of television, 0.62 hours of videocassettes, 0.41 hours of computer games and 2.34 hours of radio.

Over the period of seven years participants were screened and 308 had developed symptoms consistent with depression

“In the fully adjusted models, participants had significantly greater odds of developing depression by follow-up for each hour of daily television viewed,” the authors wrote.

“In addition, those reporting higher total media exposure had significantly greater odds of developing depression for each additional hour of daily use,” they added.

Moreover, given the same amount of media exposure, young women were less likely to develop symptoms of depression than young men.

The researchers suggest that media exposure could influence the development of depression symptoms through many different mechanisms.

They said the time spent engaging with electronic media may replace time that would otherwise be spent on social, intellectual or athletic activities that may protect against depression.

Moreover, media exposure at night may disrupt sleep, which is important for normal cognitive and emotional development.

The messages transmitted through the media may reinforce aggression and other risky behaviours, interfere with identity development or inspire fear and anxiety.

The report appears in Archives of General Psychiatry, one of the JAMA/Archives journals. (ANI)