Benefits of nut consumption for people with abdominal obesity, high blood sugar, high blood pressure

For the first time, scientists report a link between eating nuts and higher levels of serotonin in the bodies of patients with metabolic syndrome (MetS), who are at high risk for heart disease. Serotonin is a substance that helps transmit nerve signals and decreases feelings of hunger, makes people feel happier and improves heart health. It took only one ounce of mixed nuts (raw unpeeled walnuts, almonds and hazelnuts) a day to produce the good effects. The report appears in ACS' Journal of Proteome Research.

04 nov 2011--Cristina Andrés-Lacueva and colleagues from the Biomarkers & NutriMetabolomics Research Group of the University of Barcelona in collaboration with the Human Nutrition Unit of the Rovira i Virgili University explain that the rise in obesity around the world means more and more patients have MetS. Symptoms include excess abdominal fat, high blood sugar and high blood pressure, which increase the risk of developing type 2 diabetes and heart disease. Dietary changes may help patients shed the excess weight and become healthier, among the changes, the regular consumption of nuts — which are jam-packed with healthful nutrients, such as healthy fats (unsaturated fatty acids) and antioxidants (polyphenols) — have been recommended to fight the metabolic abnormalities associated with MetS. To check the biochemical effects of nut consumption, the researchers put 22 MetS patients on a nut-enriched diet for 12 weeks and compared them to another group of 20 patients who were told to avoid nuts.

The scientists analyzed the broad spectrum of compounds excreted in the patients' urine and found evidence of several healthful changes. One surprise was evidence that nut consumption had boosted patients' levels of serotonin metabolites in urine, since these findings suggest the role of serotonin in the beneficial effects of nuts. They point out that the study provides the first evidence in humans of the beneficial effects of nut consumption in reducing levels of substances in the body associated with inflammation and other cardiovascular risk factors in patients with metabolic syndrome.

More information: Metabolomics Unveils Urinary Changes in Subjects with Metabolic Syndrome following 12-Week Nut Consumption, J. Proteome Res., Article ASAP. DOI: 10.1021/pr200514h

Abstract
Through an HPLC-Q-TOF-MS-driven nontargeted metabolomics approach, we aimed to discriminate changes in the urinary metabolome of subjects with metabolic syndrome (MetS), following 12 weeks of mixed nuts consumption (30 g/day), compared to sex- and age-matched individuals given a control diet. The urinary metabolome corresponding to the nut-enriched diet clearly clustered in a distinct group, and the multivariate data analysis discriminated relevant mass features in this separation. Metabolites corresponding to the discriminating ions (MS features) were then subjected to multiple tandem mass spectrometry experiments using LC-ITD-FT-MS, to confirm their putative identification. The metabolomics approach revealed 20 potential markers of nut intake, including fatty acid conjugated metabolites, phase II and microbial-derived phenolic metabolites, and serotonin metabolites. An increased excretion of serotonin metabolites was associated for the first time with nut consumption. Additionally, the detection of urinary markers of gut microbial and phase II metabolism of nut polyphenols confirmed the understanding of their bioavailability and bioactivity as a priority area of research in the determination of the health effects derived from nut consumption. The results confirmed how a nontargeted metabolomics strategy may help to access unexplored metabolic pathways impacted by diet, thereby raising prospects for new intervention targets.

Provided by American Chemical Society

First clinical trial of red wine ingredient shows metabolic shifts

When obese men take a relatively small dose of resveratrol in purified form every day for a month, their metabolisms change for the better. In fact, the effects appear to be as good for us as severe calorie restriction. Resveratrol is a natural compound best known as an ingredient in red wine.

04 nov 2011--"We saw a lot of small effects, but consistently pointing in a good direction of improved metabolic health," said Patrick Schrauwen of Maastricht University in The Netherlands.

The findings in the November issue of the Cell Press journal Cell Metabolism are the first to report the clinical effects of resveratrol.

Earlier studies in animals had shown that resveratrol alleviates insulin resistance and protects against the ill effects of a high-fat diet, among other benefits, he explained. The effects are comparable to what happens when animals or humans significantly restrict the number of calories they consume, a diet plan shown to delay the onset of age-related diseases. Still, no studies had systematically examined the metabolic effects of resveratrol in humans.

To fill that gap, the researchers gave 11 obese but otherwise healthy men a dietary supplement containing 150 milligrams of a 99 percent pure trans-resveratrol (trade name resVida) for 30 days while they measured the amount of energy they expended, the amount of fat they were storing and burning, and more.

The data show that, like calorie restriction, resveratrol supplements lower energy expenditure and improve measures of metabolism and overall health. Those changes include a lower metabolic rate, less fat in the liver, lower blood sugar levels and a drop in blood pressure. Trial participants also experienced changes in the way their muscles burned fat.

"The immediate reduction in sleep metabolic rate was particularly striking," Schrauwen said. Of course, in the case of obesity, it's not entirely clear whether burning fewer calories is a good or a bad thing. It does suggest that participants' cells were operating more efficiently, as they do following calorie restriction.

Those metabolic effects of resveratrol also came with no apparent side effects.

Schrauwen said they chose to study obese individuals given their increased risk for type 2 diabetes. In future studies, he hopes to explore the effects of resveratrol in people who have already progressed to diabetes.

ResVida and other resveratrol supplements are already widely available, but more work is needed to establish whether they indeed have the potential to overcome the metabolic aberrations associated with obesity and aging, according to the researchers.

"I don't see a reason for particular caution, but we do need long-term studies," Schrauwen says.

Provided by Cell Press

'Rejuvenated' stem cells coaxed from centenarian

Embryonic stem cells are pictured through a microscope viewfinder in a laboratory, in 2008. Scientists said Tuesday they had transformed age-worn cells in people over 90 -- including a centenarian -- into rejuvenated stemcells that were "indistinguishable" from those found in embryos.

Scientists said Tuesday they had transformed age-worn cells in people over 90 -- including a centenarian -- into rejuvenated stemcells that were "indistinguishable" from those found in embryos.

03 nov 2011--The technical feat, reported in the peer-reviewed journal Genes & Development, opens a new path toward regenerative medicine, especially for the elderly, the researchers said.

"This is a new paradigm for cell rejuvenation," said Jean-Marc Lemaitre, a researcher at the Institute of Functional Genomics at the University of Montpellier and the main architect of the study.

"The age of cells is definitely not a barrier to reprogramming," he told AFP by phone.

That human embryonic stem cells (ESC) can potentially become any type of cell in the body has long held out the tantalizing promise of diseased organs or tissue being repaired or replaced with healthy, lab-grown cells.

But the leap from theory to practice has proven difficult, and fraught with ethical and moral concerns because any such procedure requires the destruction of a human embryo.

The discovery in 2007 that it is possible to coax certain adult cells back into their immature, pre-specialised state has fuelled renewed efforts to generate brand new muscle, heart or even brain cells, this time from raw material provided by the patient.

Experiments to date, however, have shown that the usual chemical recipe for generating these so-called induced pluripotent stem cells (iPSC) works less well or not at all with the elderly and very elderly -- precisely the cohort with the most to gain from regenerative therapies.

The barrier was cellular senescence, a natural process linked to ageing that can trigger cell death when certain mechanisms within the cell become too degraded to function properly.

Lemaitre and colleagues decided to alter the standard genetic starter kit used to generate adult stemcells by adding two new ingredients -- known as transcription factors -- called NANOG and LIN28.

Experiments with human subjects ranging in age from 74 to 101 showed that the new cocktail worked.

Several critical markers of ageing in cells were "reset", including the size of telomeres, the tiny protective caps found on the ends of chromosomes that wear down with age, the researchers reported.

Telomeres and telomerase, the enzyme that control them, are a key agent in longevity.

Every time a cell divides, the telomeres get worn down a little bit. The enzyme's job is to partially rebuild them. Eventually, when the telomeres are worn beyond repair, a cell dies.

Gene expression profiles, levels of oxidative stress, and the metabolism of the cell's energy-generating mitochondria were all likewise rejuvenated, according to the study.

"The age markers in the cell has been erased," said Lemaitre. "The iPSC stemcells we got can produce functional cells of all types with a capacity to proliferate and enhance longevity."

By reversing the age-altered physiology of the cells, he added, the new reprogramming technique "may constitute an optimal strategy for developing cell-based therapies for aged patients."

A large gap remains between this "proof-of-concept" study and therapeutic applications, the researchers cautioned.

And recent experiments with mice suggests that generating adult stemcells may yet face unexpected barriers.

Certain kinds of iPSC may be rejected by the immune system even if they are derived from the same organism, the experiments showed.

Happiness contributes to longer life: study

03 nov 2011-- Don’t Worry. Be Happy. The words from this famous song may have more meaning than originally intended according to a new study published in the journal Proceedings of the National Academy of Sciences. According to study results, people who report feeling happy on a daily basis are 35 percent less likely to die compared to their unhappy counterparts.

Previous studies on happiness and longevity have looked at how people felt in the past. These recollections of feelings are not always accurate. Not everyone can remember exactly how they felt last Tuesday, so the information is a bit faulty.

For this study, researchers led by Professor of Psychology at the University College London, looked at 3,800 participants between the ages of 52 and 79. They were asked to record their levels of happiness, anxiety and a variety of other emotions at four specific points throughout one particular day.

Based on answers, the researchers divided the participants into three groups based on their level of happiness and positive feelings. Each group was comparable in ethnic makeup, employment status, overall health and education but varied in terms of age, wealth and whether or not they smoked.

After a period of five years, the researchers discovered that within in the groups, seven percent of the least happy group had passed away compared to only four percent in the happiest of the three groups. The middle group was at five percent.

Researchers then looked at each group again and controlled for age, chronic diseases, exercise, alcohol consumption, depression and socioeconomic factors. With these factors taken into consideration, they discovered that 35 percent of the happiest group was less likely to have died and the middle group of happiness was 20 percent less likely.

Researchers say that positive emotions affect regions of the brain that also work in blood vessel function and inflammation. The hormone cortisol is also affected by changes in emotion and could play a role.

While this study does not directly prove that happiness affects lifespan, it does suggest that physicians should pay close attention to the emotional state of their older patients. Steptoe believes that these findings provide a reason to target the positive well-being over older patients to improve health.

More information: Positive affect measured using ecological momentary assessment and survival in older men and women, PNAS, Published online before print October 31, 2011, doi: 10.1073/pnas.1110892108

The tangled web in Alzheimer's protein deposits is more complex than once thought

Scientists from the National Institutes of Health in the United States have made an important discovery that should forever change the scope and direction of Alzheimer's research. Specifically, they have discovered that the protein tangles which are a hallmark of the disease involve at least three different proteins rather than just one. The discovery of these additional proteins, called neurofilaments and vimentin, should help scientists better understand the biology and progression of the disease as well as provide additional drug discovery targets. This discovery was published in the November 2011 issue of the FASEB Journal.

02 nov 2011--"Since neurofilaments are the predominant protein in nerve cells, our study suggests that we should refocus our research on the biology of these filamentous proteins in an effort to understand how they are normally regulated and deregulated in response to human aging," said Harish C. Pant, Ph.D., a senior researcher involved in the work from the Cytoskeletal Regulatory Protein Section of the Laboratory of Neurochemistry at the National Institute of Neurological Disorders and Stroke at the National Institutes of Health in Bethesda, Maryland.

To make their discovery, Pant and colleagues identified normal and abnormal proteins present in autopsy samples of the brains of Alzheimer's disease victims. Then they isolated and purified the tangles (which are knots of abnormally aggregated filaments that fill and compromise nerve cells) from the autopsy samples and compared their protein composition to age- and post mortem-matched samples of brains from patients who died of other causes, such as accidents. Through a combination of improved instrumentation and informatics, it was possible to resolve the mixture of proteins successfully and identify the novel Alzheimer's disease proteins. Previous research suggested that only one protein, called "tau," is present in these tangles.

"This is a breakthrough of great importance: tau is not the only target," said Gerald Weissmann, M.D., Editor-in-Chief of the FASEB Journal. "Before this discovery, we approached these tangles as if they were woven of one piece of string. Now we know that there are at least three proteins involved, we're much closer to untangling the Alzheimer's web. Without question, discoveries like this bring us closer than ever to advanced Alzheimer's treatments, and it is a good example of why NIH funding is among the best investments our nation can make toward improving health and well being."

More information: Parvathi Rudrabhatla, Howard Jaffe, and Harish C. Pant. Direct evidence of phosphorylated neuronal intermediate filament proteins in neurofibrillary tangles (NFTs): phosphoproteomics of Alzheimer's NFTs. FASEB J. November 2011 25:3896-3905; doi:10.1096/fj.11-181297

Provided by Federation of American Societies for Experimental Biology

Abnormal oscillation in the brain causes motor deficits in Parkinson's disease

The research group headed by Professor Atsushi Nambu (The National Institute for Physiological Sciences) and Professor Masahiko Takada (Primate Research Institute, Kyoto University) has shown that the 'oscillatory' nature of electrical signals in subcortical nuclei, the basal ganglia, causes severe motor deficits in Parkinson's disease, by disturbing the information flow of motor commands. The group also found that chemical inactivation of the subthalamic nucleus (a structure of the basal ganglia) in parkinsonian monkeys improved the motor impairments by reducing the 'oscillations.' The results of this study were reported in European Journal of Neuroscience, November 2011 issue.

02 nov 2011--A member of the research group, Assistant Professor Yoshihisa Tachibana, succeeded to record electrical signals in monkey basal ganglia neurons under unanesthetized conditions. The group found that neurons in the parkinsonian basal ganglia showed abnormal 'oscillatory' activity, which was rarely seen in normal subjects. The abnormal rhythm was completely eliminated by systemic administration of a dopamine precursor (L-DOPA), which is clinically used for human parkinsonian patients. The group considered that loss of dopamine induced the 'oscillations' in the basal ganglia and that the following disturbances in information flow of motor commands impaired motor performances. Abnormal neuronal oscillations were already reported in parkinsonian patients and animal models, but this report has provided the direct evidence that 'oscillations' are associated with motor abnormalities. Moreover, it was also shown that the injection of a chemical inhibitor, muscimol, into the subthalamic nucleus silenced the oscillatory signals, and eventually reversed parkinsonian motor signs.

Professor Nambu claims, "By investigating the 'oscillatory' nature of electrical signals in the basal ganglia, we can advance our understanding of the pathophysiology of Parkinson's disease. We improved motor deficits by means of infusion of the chemical inhibitor (muscimol) into the subthalamic nucleus to silence the 'oscillatory' signals in the brain structure. This may provide us important clues to developing new treatments for Parkinson's disease."

Provided by National Institute for Physiological Sciences

Combination of available tests helps predict Alzheimer's disease risk

With age, forgetfulness and other signs of memory loss sometimes appear, prompting elderly individuals to seek a medical evaluation amid fears that they may be experiencing early symptoms of Alzheimer's disease (AD), the most common type of dementia among Americans aged 65 and older.

01 nov 2011--But even when early memory problems suggest the potential for impending AD, the actual risk is variable. Some patients are at high risk while others are not. The challenge for doctors has long been to differentiate that risk so they can determine the appropriate course of management.

In a paper to be published in the October 25 issue of the journal Neurology, a team of physicians and scientists from the University of California, San Diego School of Medicine and elsewhere describe using a combination of broadly available medical tests to produce a much improved predictive picture of the likelihood of impending AD in patients with mild cognitive impairment (MCI) – an intermediate stage between the expected cognitive decline of normal aging and the more pronounced decline of dementia.

"I'm extremely excited about these results," said neurologist James Brewer, MD, PhD, an associate professor of radiology and neurosciences and part of the Alzheimer's Disease Neuroimaging Initiative research team at UC San Diego. "The good news is that we can partially reassure those folks who are negative on these tests, at least regarding their next three years. We have never been able to do that before. These individuals, despite having a real memory problem, have no greater risk of near-term dementia than a similarly aged healthy person without a memory complaint."

To determine the likelihood of developing Alzheimer's disease, the UC San Diego researchers compared risk factors based on magnetic resonance imaging (MRI), cerebrospinal fluid (CSF) and neuropsychological testing. Unlike other efforts that have evaluated the predictive capabilities of research-based biomarkers, MRI, CSF and neuropsychological tests are all technologies widely available to clinicians.

The researchers found that these available biomarkers significantly improved accuracy in predicting near-term conversion to dementia. In combination, their prediction rate was almost perfect: None of the individuals who tested negative on all three measures went on to develop AD in the three-year follow-up. By comparison, almost 90 percent of individuals who tested positive on all three measures were demented at the end of three years.

The presence of medial temporal atrophy, determined by automated analysis of MRI using an FDA-approved software package, was associated with the likeliest chance of near-term dementia, with a median dementia-free survival time of only 15 months.

Brewer said the findings foretell a paradigm shift in the diagnosis of Alzheimer's disease.

"Instead of saying, 'Let's wait a year and see if this gets worse,' our neurologists can say, 'Let's get a volumetric MRI and check back in a month to see if your complaint is due to neurodegeneration.' That ability makes a huge difference in how we proceed. Maybe the memory complaint isn't due to neurodegeneration, but rather it's a side effect of a medication, a sign of depression or someone is simply anxious and worried. Being able to reassure at least some patients that they are not at significant near-term risk of AD is something we never could do in the past, given the high prevalence of the disease."

Provided by University of California - San Diego

Live longer with fewer calories

By consuming fewer calories, ageing can be slowed down and the development of age-related diseases such as cancer and type 2 diabetes can be delayed. The earlier calorie intake is reduced, the greater the effect. Researchers at the University of Gothenburg have now identified one of the enzymes that hold the key to the ageing process.

31 oct 2011--"We are able to show that caloric restriction slows down ageing by preventing an enzyme, peroxiredoxin, from being inactivated. This enzyme is also extremely important in counteracting damage to our genetic material," says Mikael Molin of the Department of Cell and Molecular Biology.

By gradually reducing the intake of sugar and proteins, without reducing vitamins and minerals, researchers have previously shown that monkeys can live several years longer than expected. The method has also been tested on everything from fishes and rats to fungi, flies and yeasts with favourable results. Caloric restriction also has favourable effects on our health and delays the development of age-related diseases. Despite this, researchers in the field have found it difficult to explain exactly how caloric restriction produces these favourable effects.

Using yeast cells as a model, the research team at the University of Gothenburg has successfully identified one of the enzymes required. They are able to show that active peroxiredoxin 1, Prx1, an enzyme that breaks down harmful hydrogen peroxide in the cells, is required for caloric restriction to work effectively.

The results, which have been published in the scientific journal Molecular Cell, show that Prx1 is damaged during ageing and loses its activity. Caloric restriction counteracts this by increasing the production of another enzyme, Srx1, which repairs Prx1. Interestingly, the study also shows that ageing can be delayed without caloric restriction by only increasing the quantity of Srx1 in the cell. Repair of the peroxiredoxin Prx1 consequently emerges as a key process in ageing.

"Impaired Prx1 function leads to various types of genetic defects and cancer. Conversely, we can now speculate whether increased repair of Prx1 during ageing can counteract, or at least delay, the development of cancer."

Peroxiredoxins have also been shown to be capable of preventing proteins from being damaged and aggregating, a process that has been linked to several age-related disorders affecting the nervous system, such as Alzheimer's and Parkinson's. The researchers are accordingly also considering whether stimulation of Prx1 can reduce and delay such disease processes.

More information: The article 'Life Span Extension and H2O2 Resistance Elicited by Caloric Restriction Require the Peroxiredoxin Tsa1 in Saccharomyces cerevisiae' has been published in the journal Molecular Cell.

Expert comments in the same issue "Translating a Low-Sugar Diet into a Longer Life by Maintaining Thioredoxin Peroxidase Activity of a Peroxiredoxin"

Provided by University of Gothenburg

New findings contradict dominant theory in Alzheimer's disease

For decades the amyloid hypothesis has dominated the research field in Alzheimer's disease. The theory describes how an increase in secreted beta-amyloid peptides leads to the formation of plaques, toxic clusters of damaged proteins between cells, which eventually result in neurodegeneration. Scientists at Lund University, Sweden, have now presented a study that turns this premise on its head.

30 oct 2011--The research group's data offers an opposite hypothesis, suggesting that it is in fact the neurons' inability to secrete beta-amyloid that is at the heart of pathogenesis in Alzheimer's disease.

The study, published in the October issue of the Journal of Neuroscience, shows an increase in unwanted intracellular beta-amyloid occurring early on in Alzheimer's disease. The accumulation of beta-amyloid inside the neuron is here shown to be caused by the loss of normal function to secrete beta-amyloid.

Contrary to the dominant theory, where aggregated extracellular beta-amyloid is considered the main culprit, the study instead demonstrates that reduced secretion of beta-amyloid signals the beginning of the disease.

The damage to the neuron, created by the aggregated toxic beta-amyloid inside the cell, is believed to be a prior step to the formation of plaques, the long-time hallmark biomarker of the disease.

Professor Gunnar Gouras, the senior researcher of the study, hopes that the surprising new findings can help push the research field in a new direction.

"The many investigators and pharmaceutical companies screening for compounds that reduce secreted beta-amyloid have it the wrong way around. The problem is rather the opposite, that it is not getting secreted. To find the root of the disease, we now need to focus on this critical intracellular pool of beta-amyloid.

"We are showing here that the increase of intracellular beta-amyloid is one of the earliest events occurring in Alzheimer's disease, before the formation of plaques. Our experiments clearly show a decreased secretion of beta-amyloid in our primary neuron disease model. This is probably because the cell's metabolism and secretion pathways are disrupted in some way, leading beta-amyloid to be accumulated inside the cell instead of being secreted naturally", says Davide Tampellini, first author of the study.

The theory of early accumulation of beta-amyloid inside the cell offers an alternate explanation for the formation of plaques. When excess amounts of beta-amyloid start to build up inside the cell, it is also stored in synapses.

When the synapses can no longer hold the increasing amounts of the toxic peptide the membrane breaks, releasing the waste into the extracellular space. The toxins released now create the seed for other amyloids to gather and start forming the plaques.

More information: "Impaired β-Amyloid Secretion in Alzheimer's Disease Pathogenesis" http://www.jneuros … 3/15384.full

Provided by Lund University

Yeast model connects Alzheimer's disease risk and amyloid beta toxicity

Using yeast cells, a team of Whitehead scientists in the lab of Whitehead Member Susan Lindquist investigated the harmful effects of amyloid beta (Aβ), a peptide whose accumulation in amyloid plaques is a hallmark of AD. Work by the lab indicates that Aβ disrupts normal cellular trafficking, with clathrin-mediated endocytosis being specifically vulnerable. Under normal conditions, the membrane bound receptor Ste3 (green) is subject to clathrin-mediated endocytosis and is trafficked to the cell’s vacuole (left). In Aβ expressing yeast cells, Ste3 is not localized to the vacuole, but is dispersed in foci throughout the cell, indicating that endocytic trafficking is perturbed (center). Expression of the yeast homolog of PICALM, one of the most highly validated human AD risk factors, restores normal trafficking in Aβ-expressing yeast, and Ste3 is again localized in the vacuole (right).

29 oct 2011--In a development that sheds new light on the pathology of Alzheimer's disease (AD), a team of Whitehead Institute scientists has identified connections between genetic risk factors for the disease and the effects of a peptide toxic to nerve cells in the brains of AD patients.

The scientists, working in and in collaboration with the lab of Whitehead Member Susan Lindquist, established these previously unknown links in an unexpected way. They used a very simple cell type—yeast cells—to investigate the harmful effects of amyloid beta (Aβ), a peptide whose accumulation in amyloid plaques is a hallmark of AD. This new yeast model of Aβ toxicity, which they further validated in the worm C. elegans and in rat neurons, enables researchers to identify and test potential genetic modifiers of this toxicity.

"As we tackle other diseases and extend our lifetimes, Alzheimer's and related diseases will be the most devastating personal challenge for our families and one the most crushing burdens on our economy," says Lindquist, who is also a professor of biology at Massachusetts Institute of Technology and an investigator of the Howard Hughes Medical Institute. "We have to try new approaches and find out-of the-box solutions."

In a multi-step process, the researchers were able to introduce the form of Aβ most closely associated with AD into yeast in a manner that mimics its presence in human cells. The resulting toxicity in yeast reflects aspects of the mechanism by which this protein damages neurons. This became clear when a screen of the yeast genome for genes that affect Aβ toxicity identified a dozen genes that have clear human homologs, including several that have previously been linked to AD risk by genome-wide association studies (GWAS) but with no known mechanistic connection.

With these genetic candidates in hand, the team set out to answer two key questions: Would the genes identified in yeast actually affect Aβ toxicity in neurons? And if so, how?

To address the first issue, in a collaboration with Guy Caldwell's lab at the University of Alabama, researchers created lines of C. elegans worms expressing the toxic form of Aβ specifically in a subset of neurons particularly vulnerable in AD. This resulted in an age-dependent loss of these neurons. Introducing the genes identified in the yeast that suppressed Aβ toxicity into the worms counteracted this toxicity. One of these modifiers is the homolog of PICALM, one of the most highly validated human AD risk factors. To address whether PICALM could also suppress Aβ toxicity in mammalian neurons, the group exposed cultured rat neurons to toxic Aβ species. Expressing PICALM in these neurons increased their survival.

The question of how these AD risk genes were actually impacting Aβ toxicity in neurons remained. The researchers had noted that many of the genes were associated with a key cellular protein-trafficking process known as endocytosis. This is the pathway that nerve cells use to move around the vital signaling molecules with which they connect circuits in the brain. They theorized that perhaps Aβ was doing its damage by disrupting this process. Returning to yeast, they discovered that, in fact, the trafficking of signaling molecules in yeast was adversely affected by Aβ. Here again, introducing genes identified as suppressors of Aβ toxicity helped restore proper functioning.

Much remains to be learned, but the work provides a new and promising avenue to explore the mechanisms of genes identified in studies of disease susceptibility.

"We now have the sequencing power to detect all these important disease risk alleles, but that doesn't tell us what they're actually doing, how they lead to disease," says Sebastian Treusch, a former graduate student in the Lindquist lab and now a postdoctoral research associate at Princeton University.

Jessica Goodman, a postdoctoral fellow in the Lindquist lab, says the yeast model provides a link between genetic data and efforts to understand AD from the biochemical and neurological perspectives.

"Our yeast model bridges the gap between these two fields," Goodman adds. "It enables us to figure out the mechanisms of these risk factors which were previously unknown."

Members of the Lindquist lab intend to fully exploit the yeast model, using it to identify novel AD risk genes, perhaps in a first step to determining if identified genes have mutations in AD patient samples. The work will undoubtedly take the lab into uncharted territory.

More information: "Functional Links Between Aβ Toxicity, Endocytic Trafficking and Alzheimer's Disease Risk Factors in Yeast" Science, October 28, 2011.

Provided by Whitehead Institute for Biomedical Research

Longevity's secrets sought in DNA of 100-year-olds

27 oct 2011-- George Eberhardt turned 107 last month, and scientists would love to know how he and other older folks like him made it that far. So he's going to hand over some of his DNA. He's one of 100 centenarians taking part in a project announced Wednesday that will examine some of the oldest citizens with one of the newest scientific tools: whole-genome sequencing, the deciphering of a person's complete collection of DNA.

Scientists think DNA from very old healthy people could offer clues to how they lived so long. And that could one day lead to medicines to help the rest of us stay disease-free longer.

By the time you reach, say, 105, "it's very hard to get there without some genetic advantages," says Dr. Thomas Perls, a geriatrics expert at Boston University.

Perls is helping find centenarians for the Archon Genomics X Prize competition. The X Prize Foundation, best known for a spaceflight competition, is offering $10 million in prize money to researchers who decipher the complete DNA code from 100 people older than 100. The contest will be judged on accuracy, completeness and the speed and cost of sequencing.

The contest is a relaunch of an older competition with a new focus on centenarians, and it's the second sequencing project involving the elderly to be announced this month.

Genome pioneer J. Craig Venter says the centenarian project is just a first step in revealing the genetic secrets of a long and healthy life.

"We need 10,000 genomes, not 100, to start to understand the link between genetics, disease and wellness," said Venter, who is co-chairing the X Prize contest.

The 107-year-old Eberhardt of Chester, N.J., played and taught tennis until he was 94. He said he's participating in the X Prize project because he's interested in science and technology. It's not clear his genes will reveal much. Nobody else in his extended family reached 100, and he thinks only a couple reached 90, he said in a telephone interview.

So why does he think he lived so long? He credits 70 years of marriage to his wife, Marie. She in turn cites his "intense interest in so many things" over a lifetime, from building radios as a child to pursuing a career in electronics research.

But scientists believe there's more to it, and they want to use genome sequencing to investigate. Dr. Richard Cawthon of the University of Utah, who is seeking longevity genes by other means, says it may turn up genetic features that protect against multiple diseases or that slow the process of aging in general.

Protective features of a centenarian's DNA can even overcome less-than-ideal lifestyles, says Dr. Nir Barzilai of the Albert Einstein College of Medicine in New York. His own study of how centenarians live found that "as a group, they haven't done the right things."

Many in the group he studied were obese or overweight. Many were smokers, and few exercised or followed a vegetarian diet. His oldest participant, who died this month just short of her 110th birthday, smoked for 95 years.

"She had genes that protected her against the environment," Barzilai said. One of her sisters died at 102, and one of her brothers is 105 and still manages a hedge fund.

Earlier this month, Scripps Health of San Diego announced a different genome project involving the elderly. The Scripps Wellderly Study will receive the complete genomes of 1,000 people age 80 and older from a sequencing company.

A complete genome reveals not only genes but also other DNA that's responsible for regulating genes. It's "the full monty," showing DNA elements that are key for illness and health, says Dr. Eric Topol, who heads the Wellderly Study.

Participants in that study have an average age of 87 and range up to 108, and they've never had diabetes, heart disease or cancer, or any neurological disease.

"Why are these people Teflon-coated?" Topol asked. "Why don't they get disease?"

The ability to turn out lots of complete genomes is "the new-new thing" in trying to find out, he said.

"There's been too much emphasis on disorders per se and not enough on the people who are exceptionally healthy," to learn from their genomes, Topol said. "Now we have the powerful tools to do that."

More information: X Prize competition: http://genomics.xprize.org/

Many Alzheimer's patients get drugs with opposing effects

You wouldn't brake your car while stepping on the gas—or wash down a sleeping pill with espresso. Yet many people taking common Alzheimer's disease medications—cholinesterase inhibitors—are given medications with anticholinergic properties, which oppose their effects. Group Health Research Institute scientists investigated how often that happens and reported on the consequences in an "Early View" study e-published in the Journal of the American Geriatrics Society.

26 oct 2011--"Cholinesterase inhibitors are today's primary therapy for slowing Alzheimer's disease," said study leader Denise Boudreau, PhD, RPh, an associate scientific investigator at Group Health Research Institute. "Anticholinergic properties are often found in drugs commonly used to treat gastrointestinal disorders, allergies, urinary incontinence, depression, and Parkinson's disease, and they can have negative effects on cognition and function in the elderly. There's concern that if someone is taking both types of drugs—cholinesterase inhibitors and anticholinergic medications—they will antagonize each other, and neither will work."

In clinical trials, cholinesterase inhibitors show modest effects against the functional and cognitive decline of people with Alzheimer's disease. These medications, such as donepezil (Aricept) work by inhibiting the breakdown of acetylcholine, which sends signals in the nervous system. By contrast, anticholinergics—such as diphenhydramine (Benadryl) and oxybutynin (Ditopan)—block the action of acetylcholine. Since the two types of drugs have opposite effects, it makes sense not to give both kinds of drugs to an individual person. But until Dr. Boudreau's study, few researchers had explored how often patients are prescribed both types of medications and which harms this might cause.

Dr. Boudreau and colleagues conducted a retrospective cohort study of 5,625 people aged 50 or older who received a new prescription for cholinesterase inhibitors between 2000 and 2007. The researchers used electronic pharmacy records of Group Health Cooperative and Kaiser Permanente Colorado, nonprofit health care systems that together provide care to more than a million people. The research team found patients who also had a prescription for anticholinergics from the year before their cholinesterase prescription until the analysis ended on December 31, 2008, or the patient left the health care system or died. The study was the first to use state death records and insurance claims for nursing home care to look for effects of taking both drug types.

The researchers found:

• Of the cholinesterase inhibitor users, 37 percent were also taking at least one anticholinergic drug, and more than 11 percent took two or more. This was similar to other studies of Medicare beneficiaries.
• For those using both medication types, dual use generally lasted three to four months, but 25 percent used both classes of drugs for more than a year.
• Anticholinergics were already being used in 23 percent of people receiving a new cholinesterase inhibitor prescription, and 77 percent continued, even after starting the cholinesterase inhibitor.
• Subjects using both medication types were not more likely to enter a nursing home or to die than those taking only cholinesterase inhibitors.

"It's reassuring that we did not observe an association between simultaneous use of the two types of drugs and increased risk of death or nursing home placement," said Dr. Boudreau. "But concomitant use of these drugs is, at the very least, not optimal clinical practice." Preventing concurrent use of opposing drugs could also be a chance to reduce waste in health care spending, since a month of donepezil treatment costs approximately $180.

One reason that health care providers might prescribe conflicting medications is that dementia patients often have multiple medical conditions. Also, anticholinergics are often given to counteract the side effects of cholinesterase inhibitors, which are one of the few available treatments for people with Alzheimer's. Dr. Boudreau hopes the study raises awareness about the potential inappropriateness of prescribing both types of drugs—and stimulate discussions about the best way to make therapeutic decisions for people with Alzheimer's.

"Providers, families, and patients should carefully consider the extent to which demonstrated benefits or harms in an individual patient justify long-term use of these drugs," said Dr. Boudreau. "A good first step is to have clearly agreed-upon goals for therapy and a plan to monitor for effects and side effects." Now Group Health Research Institute scientists have started to work with Group Health Cooperative on steps like these to improve the quality of care.

Provided by Group Health Research Institute

Structure of Parkinson's disease protein identified

erial view of computer generated alpha-synuclein bundle.

A team of researchers from the Petsko-Ringe and Pochapsky laboratories at Brandeis have produced and determined the structure of alpha-synuclein, a key protein associated with Parkinson’s disease.

25 oct 2011--Their findings, recently published in Proceedings of the National Academy of Sciences (PNAS), provide information that may someday be used to produce a new kind of treatment for the incurable degenerative brain disorder.


While people with Parkinson’s diseases exhibit many obvious symptoms such as tremors and weakness of face and throat muscles, definitive diagnosis of Parkinson’s comes post mortem, when alpha-synuclein proteins become denatured and form clumps called Lewy bodies in the brain.

“We don’t really know whether this is a side effect or whether it’s the cause of Parkinson’s disease, but we do know that the clumps of proteins are always there,” says Thomas C. Pochapsky, professor of chemistry and one of the authors of the paper. Pochapsky’s lab was responsible for examining the protein using nuclear magnetic resonance, a sort of MRI for molecules, housed at the Landsman Research Facility.

Alpha-synuclein is found in large quantities in the brain. Its association with Parkinson’s disease has stirred curiosity since it was discovered in 1997. 


“Nobody knows what it does, but there’s a lot of it,” says Pochapsky. “The question is whether the unfolded or coagulated Lewy body protein just represents the pathological form of something that’s normally doing something.”

To explore that question, the scientists wanted to find out what the form alpha-synuclein is in before it turns into Lewy body clumps, figuring that if it is possible to stabilize, the progression of Parkinson’s disease could be either slowed or reversed.

“Even if we don’t know what it is, we at least want to know in what form alpha-synuclein protein should be under normal conditions,” says Pochapsky.

Gregory Petsko, professor of biochemistry, compares alpha-synuclein to an origami bird that is benign when intact but dangerous if it unfolds. This knowledge could someday lead to the development of therapies that act like glue, helping the protein keep its shape. While some drugs perform in this manner in the treatment of other diseases, the possibility of one for Parkinson’s has not been investigated because, until now, scientists thought the Parkinson’s protein had no structure. The possibility that the protein actually has a structure and that this form of the protein is benign, means that such an approach can now be considered.

The research has the potential to create a paradigm shift, a dramatic change in how science views a given phenomenon.

More than half a million Americans suffer from Parkinson's disease and, according to the National Institutes of Health, about 50,000 new cases are reported annually. The altering of alpha-synuclein is also believed to be involved in Lewy Body Dementia, a relative of Parkinson’s that affects another one million Americans.

Quyen Q. Hoang, who was a post-doctoral researcher in the Petsko-Ringe lab, and is continuing with the research in his own lab at Indiana University School of Medicine, played a key role in developing the methodology for producing this protein.

Jeffrey Agar’s lab then used mass spectrometric studies, a method of determining molecule composition. Last, using nuclear magnetic resonance, Pochapsky’s lab examined the structure of the tetramer solution.

“We were able to establish that alpha-synuclein is actually a tetramer, meaning that four of these protein molecules stick together while moving around,” says Pochapsky. “We’ve found what we think is the normal form of alpha-synuclein, which no one has seen before it has clumped together in the form of Lewy bodies.”

Petsko points out that the ability to make this form of the protein may also shed light on its normal function.

“Synuclein makes up a sizeable percentage of the protein in neurons, but no one really understands what its role in the cell is,” Petsko says. “We hope that this form of the protein may be the form that has the benign function, so biochemists and cell biologists may now be able to figure out what it’s doing.”

Pochapsky explains that while researchers in other institutions have examined alpha-synuclein before, it has not been done with this ultra careful method, which maintains the structure.

Provided by Brandeis University

Study refutes testosterone as 'fountain of youth'

A new study of older Western Australian men has revealed that testosterone might not be the fountain of youth.

23 oct 2011--Published online this week in the Journal of Clinical Endocrinology and Metabolism, researchers from The University of Western Australia's Western Australian Centre for Health and Ageing set out to explore the association between testosterone levels and cause of death.

They confirmed earlier studies suggesting that men with low testosterone were more likely to die of cardiovascular disease.

But lead author and WA Centre for Health and Ageing researcher Zoë Hyde said low testosterone levels were not linked to death from other diseases, which was surprising.

"Previous studies suggested that men with low testosterone levels are likely to die earlier, and some researchers have argued that testosterone therapy might improve longevity," Ms Hyde said.

"However, our results suggest that low testosterone is a risk factor only for cardiovascular disease, and do not provide support for more widespread use of testosterone."

Testosterone therapy is available in Australia only for men whose levels have been found to be low on testing and are experiencing symptoms of testosterone deficiency.

Ms Hyde said it was premature to recommend testosterone therapy to prevent cardiovascular disease.

"Although our study suggests that preventing testosterone deficiency might have some health benefits, we need to first conduct clinical trials of testosterone therapy to see if these findings are real, and to also properly evaluate the risks of therapy," she said.

Ms Hyde said sex hormones played an important role in maintaining health and quality of life, particularly as their concentrations changed over time.

The research forms part of the Health In Men Study (HIMS) that has been following a group of men living in Perth, Western Australia since 1996 and is the largest study of ageing men in Australia. It involves community-dwelling men aged in their 70s and 80s but excludes men receiving hormonal therapy or men with prostate cancer.

Provided by University of Western Australia

Exceptional cognitive and physical health in old age leaves immunological fingerprint

Exceptional cognitive and physical function in old age leaves a tell-tale immunologic fingerprint, say researchers at the University of Pittsburgh and Children's Hospital of Pittsburgh of UPMC. Likewise, older adults who have mild impairments bear a distinct immunologic pattern, too, according to findings published today in the PLoS One.

22 oct 2011--Old age is not synonymous with impairment and disability, noted lead investigator Abbe N. de Vallejo, Ph.D., associate professor of pediatrics and immunology, University of Pittsburgh School of Medicine.

"Our study indicates that getting older does not necessarily mean that the immune system gets weaker, as many of us assumed," he said. "The immune system is dynamic, and the changes it undergoes over time very much influence function."

For the project, the team collected blood samples from 140 participants who had been followed in the Cardiovascular Health Study (CHS) for nearly two decades and were 78 to 94 years old. With only two participants younger than 82, the average age of the group was 86. The team also gathered information about the participants' health and function, medical history and hospitalizations, and self-rated health, and assessed their cognitive and physical function using standard tests.

Previous research has shown that with age, immune cells called T-cells become more like natural killer (NK) cells, which typically target tumor cells and virus-infected cells, Dr. de Vallejo said. A closer look in the new study shows that participants who were most physically and cognitively resilient had a dominant pattern of stimulatory NK receptors on the T-cell surface, and that these unusual T-cells can be activated directly through these NK receptors independently of the conventional ones. The functionally resilient elders also have a distinct profile of blood proteins called cytokines that reflect an immune-enhancing environment.

Conversely, the group that showed mild health impairment had a dominant pattern of inhibitory NK receptors on their T-cells, and they have a cytokine profile indicating a pro-inflammatory environment. Both of these immunologic features could suggest a greater susceptibility to illness.

"These findings indicate that there is remodeling or adaptation of the immune system as we age that can be either protective or detrimental," Dr. de Vallejo said. "Now we have an immunological fingerprint that can identify individuals who are more likely to stay physically and cognitively well."

He and his colleagues are now studying factors, such as genetics or traits developed during childhood that might influence the adaptation of the immune system with advancing age.

Provided by University of Pittsburgh Schools of the Health Sciences

Simple lifestyle changes can add a decade or more healthy years to the average lifespan

Vancouver − Health prevention strategies to help Canadians achieve their optimal health potential could add a decade or more of healthy years to the average lifespan and save the economy billions of dollars as a result of reduced cardiovascular disease, says noted cardiologist Dr. Clyde Yancy.

21 oct 2011--Dr. Yancy, who will deliver the Heart and Stroke Foundation of Canada Lecture at the opening ceremonies of the Canadian Cardiovascular Congress in Vancouver this Sunday, will tell delegates that people who follow seven simple steps to a healthy life can expect to live an additional 40 to 50 years after the age of 50.

"Achieving these seven simple lifestyle factors gives people a 90 per cent chance of living to the age of 90 or 100, free of not only heart disease and stroke but from a number of other chronic illnesses including cancer," says Dr. Yancy, a professor of medicine and chief of cardiology at the Northwestern University's Feinberg School of Medicine. He is also the past-president of the American Heart Association.

"By following these steps, we can compress life-threatening disease into the final stages of life and maintain quality of life for the longest possible time." He predicts that, if we act now, we can reverse the tide by 2020.

According to the Heart and Stroke Foundation, every year in Canada about 250,000 potential years of life are lost due to heart disease and stroke, which are two of the three leading causes of death in Canada.

Canadians can achieve optimal health, says Dr. Yancy, by following these steps:

1. GET ACTIVE: Inactivity can shave almost four years off a person's expected lifespan. People who are physically inactive are twice as likely to be at risk for heart disease or stroke.
2. KNOW AND CONTROL CHOLESTEROL LEVELS: Almost 40 per cent of Canadian adults have high blood cholesterol, which can lead to the build up of fatty deposits in your arteries − increasing your risk for heart disease and stroke.
3. FOLLOW A HEALTHY DIET: Healthy eating is one of the most important things you can do to improve your health – yet about half of Canadians don't meet the healthy eating recommendations.
4. KNOW AND CONTROL BLOOD PRESSURE: High blood pressure − often called a 'silent killer' because it has no warning signs or symptoms − affects one in five Canadians. By knowing and controlling your blood pressure, you can cut your risk of stroke by up to 40 per cent and the risk of heart attack by up to 25 per cent.
5. ACHIEVE AND MAINTAIN A HEALTHY WEIGHT: Almost 60 per cent of Canadian adults are either overweight or obese − major risk factors for heart disease and stroke. Being obese can reduce your life span by almost four years.
6. MANAGE DIABETES: By 2016 an estimated 2.4 million Canadians will live with diabetes. Diabetes increases the risk of high blood pressure, atherosclerosis (narrowing of the arteries), coronary artery disease, and stroke, particularly if your blood sugar levels are poorly controlled.
7. BE TOBACCO FREE: More than 37,000 Canadians die prematurely each year due to tobacco use, and thousands of non-smokers die each year from exposure to second-hand smoke. As soon as you become smoke-free, your risk of heart disease and stroke begins to decrease. After 15 years, your risk will be nearly that of a non-smoker.

A call for focused prevention strategies

While this goal of optimal health has been achieved by fewer than 10 per cent of the population, "it demonstrates the striking potential that prevention has if it is broadly embraced," says Dr. Yancy. "We know how to prevent heart disease and stroke – we now need to build the tools to empower our citizens to manage their risk and prevent heart disease."

Dr. Yancy calls on governments to invest in steady and focused prevention strategies. He says that necessary initiatives include a change in current sodium policies, continued progress in tobacco control initiatives, increased green space, and health education.

"Healthy living is key to preventing heart disease and stroke," says Bobbe Wood, president of the Heart and Stroke Foundation of Canada. "The Foundation is committed to raising awareness about heart health and to promoting public policies that facilitate healthy lifestyles and communities."

She says that the Foundation will continue to build on partnerships and policies that have led to a significant reduction of trans fats in the Canadian food supply; stronger tobacco control initiatives; healthy community design; and a continued reduction in the amount of salt in our food products, which has been achieved in part through Health Check™, the Foundation's flagship food information program.

Dr. Yancy adds that improved access to health care that focuses on prevention and control of important risk factors including high blood pressure, high cholesterol and diabetes is also key.

Raising the alarm over looming costs of treating heart disease

Dr. Yancy will also raise the alarm over the looming cost of treating heart disease now and in the future. With predictions that the direct medical cost of treating heart disease in the U.S. alone could climb to $818 billion in 2030, he says there is a health and economic imperative for governments and societies around the world to embrace prevention strategies.

Heart disease and stroke cost the Canadian economy more than $20.9 billion every year in physician services, hospital costs, lost wages and decreased productivity.

"The opportunity for prevention is not an unrealistic expectation," says Dr. Yancy. "Over the past 40 years the rates of heart disease and stroke have steadily declined." The rate has declined in Canada by 70 per cent since the mid-1950s. In the last decade alone, the rate has declined by 25 per cent.

Unfortunately, says Dr. Yancy, these benefits may be short-lived if the burden of risk, specifically obesity and diabetes, continues to grow, especially in children. "We need to act now."

Canadians can take a personalized My Heart&Stroke Risk Assessment™ to find out how their age, family history, and medical conditions affect their heart health at heartandstroke.ca/risk.

Provided by Heart and Stroke Foundation of Canada

Next-generation brain stimulation may improve treatment of Parkinson's disease

Parkinson's disease (PD) is a devastating and incurable disease that causes abnormal poverty of movement, involuntary tremor, and lack of coordination. A technique called deep brain stimulation (DBS) is sometimes used to improve motor symptoms in patients with advanced disease. Now, a study published by Cell Press in the October 20 issue of the journal Neuron describes a new and more effective DBS paradigm that makes real-time adjustments in response to disease dynamics and progression and may be better for managing symptoms of advanced PD.

20 oct 2011--DBS involves implantation of a medical device that functions as a "brain pacemaker." Essentially, this device sends electrical impulses to specific regions of the brain and alters brain activity in those regions in a controlled manner. Although the underlying principles are not entirely clear, DBS has provided significant therapeutic benefits for movement disorders like PD and for affective disorders like chronic pain and major depression.

After implantation of the DBS device, stimulation parameters, such as frequency and intensity of stimulation, must be programmed and adjusted over several months by a highly trained clinician. The goal is to maximize clinical improvement and minimize stimulation-induced side effects. Adjustments typically occur every 3 to 12 months when the patient visits the clinic, with the parameters remaining the same between visits. Unfortunately, this results in stimulation that does not keep up with the dynamic nature of PD.

"In recent years, the role of PD driven aberrant discharge patterns of neuronal activity have emerged as pivotal in the pathophysiology of the disease, and there is an urgent need for an automatic and dynamic system that can continually adjust the stimulus in response to ongoing pathological changes," explains Dr. Boris Rosin and Professor Hagai Bergman from The Hebrew University of Jerusalem. The authors tested several new paradigms for real-time adaptive DBS in a primate model of PD, in which the delivered stimulus was triggered by the ongoing brain activity.

The researchers discovered that real-time adaptive DBS paradigms alleviated PD motor symptoms and reduced abnormal neural activity more efficiently than standard DBS. The results provided new insight into brain activity underlying PD pathology and suggested that clinical improvement was achieved by disruption of a particular pattern from the variety of abnormal activity seen in the Parkinsonian brain. "It is our hope that in the near future we will see a new era of DBS strategies, based on real-time adaptive paradigms targeted at different pathological brain activity," conclude Dr. Rosin and Prof. Bergman. "Such strategies have potential not only for the treatment of PD, but perhaps other neurological disorders with a clear pathological pattern of brain activity."

Provided by Cell Press

New studies highlight risks of vitamin supplements

New research is prompting a fresh look at the value of vitamin supplements, with some surprising results indicating that taking too many supplements of some could be harmful.

18 oct 2011--The research is forcing scientists to rethink the use of supplements with antioxidants, which had been seen as beneficial in preventing cancer, heart disease and other ailments.

"Everybody is confused," admitted Toren Finkel, head of the Center for Molecular Medicine at the National Institutes of Health (NIH).

While logic would seem to dictate that taking vitamins and antioxidants should help fight illness and disease, Finkel said in an interview that the clinical data "are pretty consistently showing no benefit."

"So that means we have to go back and think about some of the assumptions we have made along the way in terms of what the mechanism for these diseases are and how things like oxidants play a role in those diseases," he told AFP.

Finkel explained that while it has long been believed that oxidants -- free radicals produced by the body or introduced through external sources such as pollution -- were unhealthy, the research paints a more complex picture.

"You have to go back to the lab and try to design experiments you can do a little simpler with cells or animals... to better understand the role of oxidants and vitamins," he said.

"For years, we were using these supplements without knowing the effects on the body."

A study published on October 11 in the United States indicates a 17 percent increase in the risk of developing prostate cancer among men who take high doses of vitamin E.

Another recent US study conducted among women and published on October 10 revealed that multivitamins -- commonly taken in the United States -- were useless and actually gradually contributed to a higher risk of mortality.

As far back as 2007, researchers had established a link between taking selenium supplements and an increased risk of adult diabetes.

For David Schardt, a nutritionist at the non-profit Center for Science in the Public Interest, the problem is that "people think more is better and that (supplements) are harmless."

"We are finding out that some of these vitamins taken alone in large amounts may have effects we did not predict, we did not understand and we did not anticipate," Schardt said.

He added that the country has "a lot of people who believe, almost like a religion, in their vitamins" -- a faith encouraged by an industry that generates $20 billion a year in the United States, where more than half of the population takes some kind of vitamin supplement.

Moreover, US manufacturers are "free to say almost anything they want" about the virtues of supplements, Schardt explained, adding: "The only thing the Food and Drug Administration does not let them make are claims about disease."

Patsy Brannon, a Cornell University professor who served on an NIH panel on multivitamins, mineral supplements and chronic diseases, said that those who take supplements are often those already getting nutrients from their food.

"So the people who are choosing supplements are maybe the people who don't need them," she said. "So they are not thinking about their total intake and that I think is a concern."

Experts agree that multivitamins and other supplements are useful for certain groups such as pregnant women and elderly people suffering from vitamin deficiencies.

But for the general population, a healthy balanced diet rich in fruits, vegetables and fiber as well as animal-based protein will provide the proper vitamins and nutrients needed, Brannon said.

A study published in late August in the Journal of Nutrition showed that a significant number of Americans did not eat well and did not take vitamin supplements.

Twenty-five percent of respondents had a vitamin C deficiency, 34 percent were not getting enough vitamin A and 60 percent needed more vitamin E. All three are found in fruits and vegetables.

Social media is mixed blessing in epidemics: WHO

A woman wears a protective mask in a street in Hong Kong in 2008. Facebook, Twitter and other social media websites boost public awareness of disease outbreaks but also make it more difficult to separate fact from fiction, world health officials say.

Facebook, Twitter and other social media websites boost public awareness of disease outbreaks but also make it more difficult to separate fact from fiction, world health officials said Thursday.

17 oct 2011--World Health Organization (WHO) director-general Margaret Chan said the Geneva-based UN body scans websites and online forums in different languages for indications of outbreaks across the world.

Any potential threat is analysed by experts and, if necessary, investigated, she told an international conference in Singapore on improving preparedness to fight disease outbreaks.

"I can assure you that with the rise of social media, the background noises for rumours have become much louder and making it so much harder to detect the really important segments," she said.

"But this development also makes it extremely hard for any country to hide a public health threat of international concern."

Chan, who was director of health in Hong Kong when a fatal outbreak of Severe Acute Respiratory Syndrome (SARS) effectively shut down the territory in 2003, did not elaborate.

China was heavily criticised by the international community during SARS for initially covering up the epidemic, which originated in the south of the country.

The flu-like disease eventually killed more than 800 people worldwide, according to the WHO.

WHO assistant director-general Keiji Fukuda said that during the H1N1 swine flu that swept the world in 2009/2010, the Internet was rife with rumours about how to build immunity against the disease.

"One of the rumours which started was that if you increase your salt intake it can help," Fukuda told reporters on the sidelines of the Singapore conference.

The agency had to counter the rumour, also using social media, by telling readers that taking too much salt "will be dangerous to your health", he added.

"The availability of information is better than in the past, and I think this is positive," Fukuda said.

"On the other hand, in social media anybody can say anything so it's also possible that you have a lot of miscommunication mixed in with correct information."

Herbal supplements may cause dangerous drug interactions in orthopaedic surgery patients

Complementary and alternative medical (CAM) treatments such as herbal supplements have become increasingly popular in the United States, especially among older patients and those with chronic pain. However, many of these products can have serious and potentially harmful side effects when combined with medications prescribed during and after surgery, according to a review article in the Journal of the American Academy of Orthopaedic Surgeons (JAAOS).

15 oct 2011--About 20 percent of prescription users also take an herbal supplement, and those rates are higher — studies suggest between 35 and 70 percent — among orthopaedic patients who are candidates for surgery.

"Herbal remedies are classified as dietary supplements, meaning they are exempt from the safety and efficacy regulations that the U.S. Food and Drug Administration (FDA) requires for prescription and over-the-counter medications," said David T. Rispler, MD, director of the Grand Rapids/Michigan State University Orthopedic Residency Program. "As a result, individual herbal remedies have not been thoroughly evaluated in large clinical trials, and little information is available on the interactions between drugs and herbs."

In addition, many herbal products are marketed as "natural" or "homeopathic," which may lead consumers to assume the products are safe, even when taken with prescription medicines, Dr. Rispler noted. "Herbal supplements can have a negative impact on patients both before and following surgery, and may interact with conventional medicines used to manage chronic conditions."

"Traditional physician-patient communications, like intake interviews, often do not include the subject of alternative medical products. As a result, patients may fail to report that they are using them and continue to take them along with any prescribed medicines and before surgery, thinking the herbal products pose no risk," said Dr. Rispler.

Many of the most popular herbal supplements used today can have serious side effects when combined with prescription medicines. For example:

• Feverfew (used for migraine prevention), ginger, cranberry, St. John's Wort and ginseng can interact with the anti-clotting drug warfarin;
• Feverfew, ginger, and gingko can interact with aspirin;
• Garlic can interfere with anti-clotting medications and the immunosuppressant drug cyclosporine (prevents transplant rejection);
• Valerian (used as a sedative) can intensify anesthetics; and
• St. John's Wort can interact with immunosuppressive drugs and potentially lead to transplant rejection.

Herbal products marketed for osteoarthritis also can pose serious risks when combined with prescription medications. For example:

• Glucosamine, chondroitin and flavocoxid can affect clotting agents;
• Black cohosh can interact with the cancer drug tamoxifen; and
• Cat's claw can interact with clotting agents, blood pressure medications and cyclosporine.

Most surgery-related side effects can be avoided by stopping the CAM product at least one to two weeks prior to surgery and during the postoperative period while prescription medications such as blood thinners or antibiotics are being used. The problem arises when physicians do not know that a patient is using a CAM product, Dr. Rispler said.

"One of the main reasons that patients do not disclose the use of a CAM product is that they may not believe it is important information to convey to the physician because they feel they are safe to use and all-natural," he said. "Patients may also decide not to report CAM product use if they are worried their physician may be prejudiced against the supplement's use, or believe their physician will not have an understanding of the supplement."

Although the use of herbal medicines should be monitored by patients' primary care physicians, Dr. Rispler said orthopaedic surgeons should have an understanding of the potential side effects of some of the most common CAM products used by their patients, and be able to guide them in suspending use prior to surgery.

To help ensure physicians are aware of the products their patients may be using, Dr. Rispler also recommends including CAM product-use questions on health/medical assessment forms to encourage patient disclosure.

"Physician-patient communication often does not include the use of CAM therapies, which results in underreporting of their use," he said. "To help avoid potential side effects, orthopaedists should develop questionnaires that can be used prior to surgery to help determine if their patients are using CAM products." Alternatively, patients should also report usage of any herbal products or other supplements they may be taking to all their physicians.

"By opening up a conversation on the use of herbal medications around the time of surgery and compiling a complete list of all prescribed and self-prescribed medications and supplements, patients and physicians may be able to work together to decrease the risk of complications that can occur during and following surgery," Dr. Rispler said.

More information: More information on understanding complementary and alternative medicine can be found at http://orthoinfo.a … topic=A00283

Provided by American Academy of Orthopaedic Surgeons