Health Technology Research Synopsis

136th Issue Date 24 AUG 2012

Compiled By Ralph Turchiano

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In This issue:

Yale team discovers how stress and depression can shrink the brain

Major depression or chronic stress can cause the loss of brain volume, a condition that contributes to both emotional and cognitive impairment. Now a team of researchers led by Yale scientists has discovered one reason why this occurs — a single genetic switch that triggers loss of brain connections in humans and depression in animal models.

The findings, reported in the Aug. 12 issue of the journal Nature Medicine, show that the genetic switch known as a transcription factor represses the expression of several genes that are necessary for the formation of synaptic connections between brain cells, which in turn could contribute to loss of brain mass in the prefrontal cortex.

“We wanted to test the idea that stress causes a loss of brain synapses in humans,” said senior author Ronald Duman, the Elizabeth Mears and House Jameson Professor of Psychiatry and professor of neurobiology and of pharmacology. “We show that circuits normally involved in emotion, as well as cognition, are disrupted when this single transcription factor is activated.”

The research team analyzed tissue of depressed and non-depressed patients donated from a brain bank and looked for different patterns of gene activation. The brains of patients who had been depressed exhibited lower levels of expression in genes that are required for the function and structure of brain synapses. Lead author and postdoctoral researcher H.J. Kang discovered that at least five of these genes could be regulated by a single transcription factor called GATA1. When the transcription factor was activated, rodents exhibited depressive-like symptoms, suggesting GATA1 plays a role not only in the loss of connections between neurons but also in symptoms of depression.

Duman theorizes that genetic variations in GATA1 may one day help identify people at high risk for major depression or sensitivity to stress.

“We hope that by enhancing synaptic connections, either with novel medications or behavioral therapy, we can develop more effective antidepressant therapies,” Duman said.

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The study was funded by the National Institutes of Health and the Connecticut Department of Mental Health and Addiction Services.

Other Yale authors of the paper are Bhavya Voleti, Pawel Licznerski, Ashley Lepack, and Mounira Banasr.

Common antibiotics pose a rare risk of severe liver injury in older patients

The commonly used broad-spectrum antibiotics moxifloxacin and levofloxacin are associated with an increased risk of severe liver injury in older people, according to a new study published in CMAJ (Canadian Medical Association Journal) (pre-embargo link only) http://www.cmaj.ca/site/press/cmaj111823.pdf.

Moxifloxacin and levofloxacin are commonly prescribed “fluoroquinolone” antibiotics often used for bacterial infections such as respiratory infections, sinus infections and others. However, both the European Medicines Agency and Health Canada have issued warnings about the risk of liver injury from moxifloxacin, although there are few published studies on the safety of fluoroquinolones, especially related to liver damage.

Researchers from the Institute for Clinical Evaluative Sciences (ICES), Toronto; the University of Toronto and McMaster University, Hamilton, Ont., examined the risk of acute liver injury in patients taking moxifloxacin compared with those taking other antibiotics commonly used to treat respiratory tract infections. They looked at 9 years of data from Ontario to identify people aged 66 years or older with no history of liver disease who were admitted to hospital for liver injury within 30 days after receiving a prescription for these antibiotics. Excluding patients admitted for previous liver disease or recent hospitalization, 144 patients were admitted for acute liver injury, with the median time from the dispensing of the antibiotic to admission to hospital being 9 days. Eighty-eight (61.1%) of patients died during their index admission to hospital for liver injury.

“Compared with clarithromycin, moxifloxacin was associated with a more than 2-fold increased risk of admission to hospital for acute liver injury,” writes Dr. David Juurlink, ICES, with coauthors. “Levofloxacin was also associated with a statistically significant but lower risk of hepatotoxicity than…moxifloxacin.”

The authors note that, although these cases are serious, they are relatively rare, with about 6 cases for every 100 000 patients treated with the antibiotics.

The authors believe their findings are an important contribution to the evidence regarding the risks of these antibiotics. “Despite recent regulatory warnings regarding the hepatic safety of moxifloxacin, there is a lack of controlled studies supporting the notion that moxifloxacin presents a particular risk relative to other broad-spectrum antibiotic agents and, in particular, to other fluoroquinolones,” write the authors.

They conclude: “Although our results require confirmation in other settings, the findings suggest that both moxifloxacin and levofloxacin be considered for regulatory warnings regarding acute liver injury.”

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Please credit CMAJ, not the Canadian Medical Association. CMAJ is an independent medical journal; views expressed here do not necessarily reflect those of its owner, the CMA.

Chemical widely used in antibacterial hand soaps may impair muscle function

Triclosan, an antibacterial chemical widely used in hand soaps and other personal-care products, hinders muscle contractions at a cellular level, slows swimming in fish and reduces muscular strength in mice, according to researchers at the University of California, Davis, and the University of Colorado. The findings appear online in the Proceedings of the National Academy of Sciences of the United States of America.

“Triclosan is found in virtually everyone’s home and is pervasive in the environment,” said Isaac Pessah, professor and chair of the Department of Molecular Biosciences in the UC Davis School of Veterinary Medicine and principal investigator of the study. “These findings provide strong evidence that the chemical is of concern to both human and environmental health.”

Triclosan is commonly found in antibacterial personal-care products such as hand soaps as well as deodorants, mouthwashes, toothpaste, bedding, clothes, carpets, toys and trash bags. The U.S. Environmental Protection Agency in 1998 estimated that more than 1 million pounds of triclosan are produced annually in the United States, and that the chemical is detectable in waterways and aquatic organisms ranging from algae to fish to dolphins, as well as in human urine, blood and breast milk.

The investigators performed several experiments to evaluate the effects of triclosan on muscle activity, using doses similar to those that people and animals may be exposed to during everyday life.

In “test tube” experiments, triclosan impaired the ability of isolated heart muscle cells and skeletal muscle fibers to contract. Specifically, the team evaluated the effects of triclosan on molecular channels in muscle cells that control the flow of calcium ions, creating muscle contractions. Normally, electrical stimulation (“excitation”) of isolated muscle fibers under experimental conditions evokes a muscle contraction, a phenomenon known as “excitation-contraction coupling” (ECC), the fundamental basis of any muscle movement, including heartbeats. But in the presence of triclosan, the normal communication between two proteins that function as calcium channels was impaired, causing skeletal and cardiac muscle failure.

The team also found that triclosan impairs heart and skeletal muscle contractility in living animals. Anesthetized mice had up to a 25-percent reduction in heart function measures within 20 minutes of exposure to the chemical.

“The effects of triclosan on cardiac function were really dramatic,” said Nipavan Chiamvimonvat, professor of cardiovascular medicine at UC Davis and a study co-author. “Although triclosan is not regulated as a drug, this compound acts like a potent cardiac depressant in our models.”

In addition, the mice had an 18-percent reduction in grip strength for up to 60 minutes after being given a single dose of triclosan. Grip strength is a widely used measure of mouse limb strength, employed to investigate the effects of drugs and neuromuscular disorders.

Finally, the investigators looked at the effects of triclosan exposure on fathead minnows, a small fish commonly used as a model organism for studying the potential impacts of aquatic pollutants. Those exposed to triclosan in the water for seven days had significantly reduced swimming activity compared to controls during both normal swimming and swim tests designed to imitate fish being threatened by a predator.

“We were surprised by the large degree to which muscle activity was impaired in very different organisms and in both cardiac and skeletal muscle,” said Bruce Hammock, a study co-author and professor in the UC Davis Department of Entomology. “You can imagine in animals that depend so totally on muscle activity that even a 10-percent reduction in ability can make a real difference in their survival.”

The UC Davis research team has previously linked triclosan to other potentially harmful health effects, including disruption of reproductive hormone activity and of cell signaling in the brain.

Chiamvimonvat cautioned that translating results from animal models to humans is a large step and would require further study. However, the fact that the effects were so striking in several animal models under different experimental conditions provides strong evidence that triclosan could have effects on animal and human health at current levels of exposure.

“In patients with underlying heart failure, triclosan could have significant effects because it is so widely used,” Chiamvimonvat said. “However, without additional studies, it would be difficult for a physician to distinguish between natural disease progression and an environmental factor such as triclosan.”

Pessah questioned arguments that triclosan – introduced more than 40 years ago – is safe partly because it binds to blood proteins, making it not biologically available. Although triclosan may bind to proteins in the blood, that may not necessarily make the chemical inactive, he said, and actually may facilitate its transport to critical organs. In addition, some of the current experiments were carried out in the presence of blood proteins, and disrupted muscle activity still occurred.

Although triclosan was first developed to prevent bacterial infections in hospitals, its use has become widespread in antibacterial products used in the home. However, according to the U.S. Food and Drug Administration (FDA), other than its use in some toothpastes to prevent gingivitis, there is no evidence that triclosan provides other health benefits or that antibacterial soaps and body washes are more effective than regular soap and water. Experts also express concern about the possibility of resistant bacterial strains developing with the overuse of antibacterial products.

Because the chemical structure of triclosan resembles other toxic chemicals that persist in the environment, the FDA and the U.S. Environmental Protection Agency are conducting new risk assessments of the chemical. Based on their study outcomes, the researchers argue that the potential health risks call for greater restrictions.

“We have shown that triclosan potently impairs muscle functions by interfering with signaling between two proteins that are of fundamental importance to life,” said Pessah. “Regulatory agencies should definitely be reconsidering whether it should be allowed in consumer products.”

Said Hammock: “Triclosan can be useful in some instances, however it has become a ubiquitous ‘value added’ marketing factor that actually could be more harmful than helpful. At the very least, our findings call for a dramatic reduction in its use.”

Consuming flavanol-rich cocoa may enhance brain function

Eating cocoa flavanols daily may improve mild cognitive impairment, according to new research in the American Heart Association’s journal Hypertension.

Each year, more than six percent of people aged 70 years or older develop mild cognitive impairment, a condition involving memory loss that can progress to dementia and Alzheimer’s disease.

Flavanols can be found in tea, grapes, red wine, apples and cocoa products and have been associated with a decreased risk of dementia. They may act on the brain structure and function directly by protecting neurons from injury, improving metabolism and their interaction with the molecular structure responsible for memory researchers said. Indirectly, flavanols may help by improving brain blood flow.

In this study, 90 elderly participants with mild cognitive impairment were randomized to drink daily either 990 milligrams (high), 520 mg (intermediate) or 45 mg (low) of a dairy-based cocoa flavanol drink for eight weeks. The diet was restricted to eliminate other sources of flavanols from foods and beverages other than the dairy-based cocoa drink. Cognitive function was examined by neuro-psychological tests of executive function, working memory, short-term memory, long-term episodic memory, processing speed and global cognition.

Researchers found:

• Scores significantly improved in the ability to relate visual stimuli to motor responses, working memory, task-switching and verbal memory for those drinking the high and intermediate flavanol drinks.
• Participants drinking daily higher levels of flavanol drinks had significantly higher overall cognitive scores than those participants drinking lower-levels.
• Insulin resistance, blood pressure and oxidative stress also decreased in those drinking high and intermediate levels of flavanols daily. Changes in insulin resistance explained about 40 percent of the composite scores for improvements in cognitive functioning.

“This study provides encouraging evidence that consuming cocoa flavanols, as a part of a calorie-controlled and nutritionally-balanced diet, could improve cognitive function,” said Giovambattista Desideri, M.D., study lead author and director of Geriatric Division, Department of Life, Health and Environmental Sciences, University of L’Aquila in Italy. “The positive effect on cognitive function may be mainly mediated by an improvement in insulin sensitivity. It is yet unclear whether these benefits in cognition are a direct consequence of cocoa flavanols or a secondary effect of general improvements in cardiovascular function.”

The study population was generally in good health without known cardiovascular disease. Thus, it would not be completely representative of all mild cognitive impairment patients. In addition, only some clinical features of mild cognitive impairment were explored in the study.

“Given the global rise in cognitive disorders, which have a true impact on an individual’s quality of life, the role of cocoa flavanols in preventing or slowing the progression of mild cognitive impairment to dementia warrants further research,” Desideri said. “Larger studies are needed to validate the findings, figure out how long the positive effects will last and determine the levels of cocoa flavanols required for benefit.”

Diabetes drugs taken by over 15 million Americans raises risk of bladder cancer

PHILADELPHIA — A popular class of diabetes drugs increases patients’ risk of bladder cancer, according to a new study published online this month in the Journal of the National Cancer Institute. Researchers from the Perelman School of Medicine at the University of Pennsylvania found that patients taking thiazolidinedione (TZDs) drugs – which account for up to 20 percent of the drugs prescribed to diabetics in the United States — are two to three times more likely to develop bladder cancer than those who took a sulfonylurea drug, another common class of medications for diabetes.

The authors say the findings are especially important since diabetic patients are known to already be at a slightly increased risk of this type of cancer as compared to the generation population, in which about 30 in 100,000 people develop bladder cancer. Among diabetes patients overall, the incidence of this cancer is typically about 40 out of 100,000.

The authors of the new study analyzed 60,000 Type 2 diabetes patients from the Health Improvement Network (THIN) database in the United Kingdom. They found that patients treated with the TZD drugs pioglitazone (Actos) or rosiglitzaone (Avandia) for five or more years had a two-to-three-fold increase in risk of developing bladder cancer when compared to those who took sulfonylurea drugs. Among patients taking TZDs for that length of time, the team’s analysis indicates that 170 patients per 100,000 would be expected to develop the disease. About 60 in 100,000 of those who take sulfonylurea drugs – such as glipizide (Glucotrol) — would be expected to develop bladder cancer.

“Diabetes is one the most common chronic diseases worldwide, affecting 285 million people. There are many factors clinicians must weigh in deciding which drug to use to control a patient’s diabetes, and these new data provide important information to include in that decision-making process,” said the study’s lead author, Ronac Mamtani, MD, an instructor in the division of Hematology-Oncology in Penn’s Abramson Cancer Center. “Our study shows that doctors who care for patients with diabetes should be very aware of any bladder-related symptoms patients might be having, like blood in the urine, and take steps to further evaluate those issues.”

Though most patients in the United States no longer take Avandia since it was linked to severe cardiovascular problems, Actos is the ninth most commonly prescribed drug in the nation, accounting for some 15 million prescriptions each year. The drug is a common choice when Type 2 diabetes patients’ illnesses can no longer be controlled with the first-line diabetes drug Metformin.

Based on previous data examining safety risks among patients taking Actos, the FDA has already warned that it may be associated with a risk of bladder cancer, and France and Germany have removed the drug from their markets. The new findings add to mounting evidence against the entire class of TZDs, as one of the first studies examining this type of risk among people taking both types of TZDs and among those taking sulfonylurea drugs.

“The risk does seem to be common among both drugs in the TZD class, and the fact that we have compared bladder cancer risk among patients taking each of those drugs provides essential information, because a safety warning on a drug is only useful to a doctor when they have knowledge of the same risks for an alternative drug,” Mamtani says. “We believe our study will help doctors and their patients weigh the potential benefits and risks when selecting between different diabetes medication.”

Butter flavoring in microwave popcorn, thought safe for food industry workers, is respiratory hazard

New findings reported in the American Journal of Pathology

Philadelphia, PA, August 13, 2012 – The ingredient 2,3-pentanedione (PD), used to impart the flavor and aroma of butter in microwave popcorn, is a respiratory hazard that can also alter gene expression in the brain of rats. Manufacturers started using PD when another butter flavoring, diacetyl, was found to cause bronchiolitis obliterans, a life-threatening and nonreversible lung disease in workers who inhaled the substance. New research on PD with implications for “popcorn workers’ lung” is published in The American Journal of Pathology and indicates that acute PD exposure has respiratory toxicity which is comparable to diacetyl in laboratory animals.

“Our study demonstrates that PD, like diacetyl, damages airway epithelium in laboratory studies. This finding is important because the damage is believed to be the underlying cause of bronchiolitis obliterans,” says lead investigator Ann F. Hubbs, DVM, PhD, DACVP, Health Effects Laboratory Division of the National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, Morgantown, WV. “Our study also supports established recommendations that flavorings should be substituted only when there is evidence that the substitute is less toxic than the agent it replaces.”

The study included groups of rats exposed for six hours to different concentrations of PD, a comparable concentration of diacetyl, or filtered air. Since the investigators observed signs of delayed toxicity, they exposed additional rats to PD, and further microscopically examined the brains, lungs, and nasal tissues from these rats 0-2 hours, 12-14 hours, and 18-20 hours after exposure. investigators then evaluated changes in gene expression in discrete brain regions.

The investigators found respiratory epithelial injury in the upper nose, comparable to that caused by diacetyl that progressed through 12 to 14 hours post-exposure. They also found that PD exposure caused necrosis and apoptosis in the olfactory neuroepithelium and activation of caspase 3, a protein that plays a role in cell death, in axons of olfactory nerve bundles. Signs consistent with neurotoxicity included increased expression of the inflammatory mediators, interleukin-6 and nitric oxide synthase-2, as well as decreased expression of vascular endothelial growth factor A in the olfactory bulb, striatum, hippocampus, and cerebellum.

“Our study is a reminder that a chemical with a long history of being eaten without any evidence of toxicity can still be an agent with respiratory toxicity when appropriate studies are conducted,” says Dr. Hubbs. “It suggests several intriguing potential mechanisms for the toxicity of inhaled volatile α-diketones, reveals mRNA changes in the brain, documents olfactory neurotoxicity, and clearly demonstrates that the remarkable airway toxicity of diacetyl is shared with its close structural relative, PD.”

Why are people overconfident so often?

It’s all about social status, a UC Berkeley study finds

UNIVERSITY OF CALIFORNIA, BERKELEY’S HAAS SCHOOL OF BUSINESS – Researchers have long known that people are very frequently overconfident – that they tend to believe they are more physically talented, socially adept, and skilled at their job than they actually are. For example, 94% of college professors think they do above average work (which is nearly impossible, statistically speaking). But this overconfidence can also have detrimental effects on their performance and decision-making. So why, in light of these negative consequences, is overconfidence still so pervasive?

The lure of social status promotes overconfidence, explains Haas School Associate Professor Cameron Anderson. He co-authored a new study, “A Status-Enhancement Account of Overconfidence,” with Sebastien Brion, assistant professor of managing people in organizations, IESE Business School, University of Navarra, Haas School colleagues Don Moore, associate professor of management, and Jessica A. Kennedy, now a post-doctoral fellow at the Wharton School of Business. The study will be published in the Journal of Personality and Social Psychology (forthcoming).

“Our studies found that overconfidence helped people attain social status. People who believed they were better than others, even when they weren’t, were given a higher place in the social ladder. And the motive to attain higher social status thus spurred overconfidence,” says Anderson, the Lorraine Tyson Mitchell Chair in Leadership and Communication II at the Haas School.

Social status is the respect, prominence, and influence individuals enjoy in the eyes of others. Within work groups, for example, higher status individuals tend to be more admired, listened to, and have more sway over the group’s discussions and decisions. These “alphas” of the group have more clout and prestige than other members. Anderson says these research findings are important because they help shed light on a longstanding puzzle: why overconfidence is so common, in spite of its risks. His findings suggest that falsely believing one is better than others has profound social benefits for the individual.

Moreover, these findings suggest one reason why in organizational settings, incompetent people are so often promoted over their more competent peers. “In organizations, people are very easily swayed by others’ confidence even when that confidence is unjustified,” says Anderson. “Displays of confidence are given an inordinate amount of weight.”

The studies suggest that organizations would benefit from taking individuals’ confidence with a grain of salt. Yes, confidence can be a sign of a person’s actual abilities, but it is often not a very good sign. Many individuals are confident in their abilities even though they lack true skills or competence.

The authors conducted six experiments to measure why people become overconfident and how overconfidence equates to a rise in social stature. For example:

In Study 2, the researchers examined 242 MBA students in their project teams and asked them to look over a list of historical names, historical events, and books and poems, and then to identify which ones they knew or recognized. Terms included Maximilien Robespierre, Lusitania, Wounded Knee, Pygmalion, and Doctor Faustus. Unbeknownst to the participants, some of the names were made up. These so-called “foils” included Bonnie Prince Lorenzo, Queen Shaddock, Galileo Lovano, Murphy’s Last Ride, and Windemere Wild. The researchers deemed those who picked the most foils the most overly confident because they believed they were more knowledgeable than they actually were. In a survey at the end of the semester, those same overly confident individuals (who said they had recognized the most foils) achieved the highest social status within their groups.

It is important to note that group members did not think of their high status peers as overconfident, but simply that they were terrific. “This overconfidence did not come across as narcissistic,” explains Anderson. “The most overconfident people were considered the most beloved.”

Study 4 sought to discover the types of behaviors that make overconfident people appear to be so wonderful (even when they were not). Behaviors such as body language, vocal tone, rates of participation were captured on video as groups worked together in a laboratory setting. These videos revealed that overconfident individuals spoke more often, spoke with a confident vocal tone, provided more information and answers, and acted calmly and relaxed as they worked with their peers. In fact, overconfident individuals were more convincing in their displays of ability than individuals who were actually highly competent.

“These big participators were not obnoxious, they didn’t say, ‘I’m really good at this.’ Instead, their behavior was much more subtle. They simply participated more and exhibited more comfort with the task – even though they were no more competent than anyone else,” says Anderson.

Two final studies found that it is the “desire” for status that encourages people to be more overconfident. For example, in Study 6, participants read one of two stories and were asked to imagine themselves as the protagonist in the story. The first story was a simple, bland narrative of losing then finding one’s keys. The second story asked the reader to imagine him/herself getting a new job with a prestigious company. The job had many opportunities to obtain higher status, including a promotion, a bonus, and a fast track to the top. Those participants who read the new job scenario rated their desire for status much higher than those who read the story of the lost keys.

After they were finished reading, participants were asked to rate themselves on a number of competencies such as critical thinking skills, intelligence, and the ability to work in teams. Those who had read the new job story (which stimulated their desire for status) rated their skills and talent much higher than did the first group. Their desire for status amplified their overconfidence.

De-emphasizing the natural tendency toward overconfidence may prove difficult but Prof. Anderson hopes this research will give people the incentive to look for more objective indices of ability and merit in others, instead of overvaluing unsubstantiated confidence.

UC Davis researchers identify cellular basis for how anti-aging cosmetics work

Pathway describes how alpha hydroxyl acids cause skin exfoliation

This release is also available in Chinese on EurekAlert! Chinese.

(SACRAMENTO, Calif.) — A team of investigators from UC Davis and Peking University have discovered a mechanism that may explain how alpha hydroxyl acids (AHAs) — the key ingredient in cosmetic chemical peels and wrinkle-reducing creams — work to enhance skin appearance. An understanding of the underlying process may lead to better cosmetic formulations as well as have medical applications.

The findings were published in the Journal of Biological Chemistry in an article entitled “Intracellular proton-mediated activation of TRPV3 channels accounts for exfoliation effect of alpha hydroxyl acids on keratinocytes.”

AHAs are a group of weak acids typically derived from natural sources such as sugar cane, sour milk, apples and citrus that are well known in the cosmetics industry for their ability to enhance the appearance and texture of skin. Before this research, little was known about how AHAs actually caused skin to flake off and expose fresh, underlying skin.

The cellular pathway the research team studied focuses on an ion channel — known as transient receptor potential vanilloid 3 (TRPV3) — located in the cell membrane of keratinocytes, the predominant cell type in the outer layer of skin. The channel is known from other studies to play an important role in normal skin physiology and temperature sensitivity.

In a series of experiments that involved recording electrical currents across cultured cells exposed to AHAs, the investigators developed a model that describes how glycolic acid (the smallest and most biologically available AHA) enters into keratinocytes and generates free protons, creating acidic conditions within the cell. The low pH strongly activates the TRPV3 ion channel, opening it and allowing calcium ions to flow into the cell. Because more protons also enter through the open TRPV3 channel, the process feeds on itself. The resulting calcium ion overload in the cell leads to its death and skin exfoliation.

“Our experiments are the first to show that the TRPV3 ion channel is likely to be the target of the most effective skin enhancer in the cosmetics industry,” said Jie Zheng, professor of physiology and membrane biology at UC Davis and one of the principal investigators of the study. “Although AHAs have been used for years, no one until now understood their likely mechanism of action.”

Besides being found in skin cells, TRPV3 also is found in cells in many areas of the nervous system and is sensitive to temperature as well as acidity. The authors speculate that the channel may have a variety of important physiological functions, including pain control.

Lead author Xu Cao, who conducted the study with UC Davis scientists as a visiting student from Peking University Health Science Center, focuses on TRPV3 channel research. With a team of researchers in China, he recently contributed to the discovery that a mutation in TRPV3 leads to Olmsted syndrome, a rare congenital disorder characterized by severe itching and horny skin development over the palms of the hands and soles of the feet. While in the UC Davis Department of Physiology and Membrane Biology, Cao discovered that AHAs also utilize the TRPV3 channel.

“Calcium channels are becoming increasingly recognized as having vital functions in skin physiology,” said Cao. “TRPV3 has the potential to become an important target not only for the cosmetics industry but for analgesia and treating skin disease.”

The other study author and co-principal investigator is KeWei Wang of Peking University School of Pharmaceutical Sciences, where the research was conducted.

Blood type may influence heart disease risk

People with blood type A, B, or AB had a higher risk for coronary heart disease when compared to those with blood type O, according to new research published in Arteriosclerosis, Thrombosis and Vascular Biology, an American Heart Association journal.

People in this study with the rarest blood type — AB, found in about 7 percent of the U.S. population — had the highest increased heart disease risk at 23 percent. Those with type B had an 11 percent increased risk, and those with type A had a 5 percent increased risk. About 43 percent of Americans have type O blood.

“While people cannot change their blood type, our findings may help physicians better understand who is at risk for developing heart disease,” said Lu Qi, M.D., Ph.D., the study’s senior author and an assistant professor in the Department of Nutrition at the Harvard School of Public Health in Boston.

Knowing your blood type can be an important part of staying healthy and avoiding heart disease, Qi said. “It’s good to know your blood type the same way you should know your cholesterol or blood pressure numbers,” he said. “If you know you’re at higher risk, you can reduce the risk by adopting a healthier lifestyle, such as eating right, exercising and not smoking.”

The findings are based on an analysis of two large, well-known U.S. studies — 62,073 women from the Nurses’ Health Study and 27,428 adults from the Health Professionals Follow-up Study. Participants were between ages 30 and 75, and both groups were followed for 20 years or more.

Researchers also considered the study participants’ diet, age, body mass index, gender, race, smoking status, menopause status and medical history. Researchers noted that the percentages of different blood types seen among the men and women enrolled in the two studies reflected levels seen in the general population.

The study did not evaluate the biological processes behind blood type and heart disease risk.

“Blood type is very complicated, so there could be multiple mechanisms at play,” Qi said.

However, there is evidence suggesting that type A is associated with higher levels of low-density lipoprotein cholesterol, the waxy substance that can clog arteries, and type AB is linked to inflammation, which may affect the function of the blood vessels. Also, a substance that plays a favorable role in blood flow and clotting may be higher in people with type O blood.

Understanding blood type could help healthcare providers better tailor treatments, Qi suggested. For example, a patient with type A blood may best lower heart disease risk by decreasing cholesterol intake.

The study group was predominantly Caucasian, and it’s not clear whether these findings would translate to other ethnic groups. Environment also contributes to risk, Qi said.

“It would be interesting to study whether people with different blood types respond differently to lifestyle intervention, such as diet,” Qi said, noting that further analysis is needed.

Cocoa compounds may reduce blood pressure

Compounds in cocoa may help to reduce blood pressure, according to a new systematic review in The Cochrane Library. The researchers reviewed evidence from short-term trials in which participants were given dark chocolate or cocoa powder daily and found that their blood pressure dropped slightly compared to a control group.

Cocoa contains compounds called flavanols, thought to be responsible for the formation of nitric oxide in the body. Nitric oxide causes blood vessel walls to relax and open wider, thereby reducing blood pressure. The link between cocoa and blood pressure stems from the discovery that the indigenous people of San Blas Island in Central American, who drink flavanol-rich cocoa drinks every day, have normal blood pressure regardless of age. However, flavanol concentrations in cocoa and chocolate products vary according to cocoa processing procedures and types of chocolate, so it is difficult to establish the optimal dosage for an effect.

To investigate the effect of flavanols on blood pressure, the researchers reviewed data from trials in which people consumed dark chocolate or cocoa powder containing between 30-1080 mg of flavanols in 3-100 g of chocolate each day. Altogether, 856 people were involved in 20 trials lasting 2-8 weeks, or in one case, 18 weeks. Flavanol-rich chocolate or cocoa powder reduced blood pressure on average by 2-3 mm Hg.

“Although we don’t yet have evidence for any sustained decrease in blood pressure, the small reduction we saw over the short term might complement other treatment options and might contribute to reducing the risk of cardiovascular disease,” said lead researcher Karin Ried of the National Institute of Integrative Medicine in Melbourne, Australia, who worked with colleagues at the University of Adelaide.

In a subset of trials, when chocolate or cocoa powder was compared to flavanol-free-products as controls, the beneficial effects were more pronounced (3-4 mm Hg), whereas the researchers found no significant effect on blood pressure in the second subset with low-flavanol products as control. It is possible that low-flavanol products also have a small effect on blood pressure, so that it was harder to observe differences between high and low-flavanol products in these trials. However, results of these subsets of trials may have been influenced by trial length and blinding of participants, as trials using flavanol-free control products tended to be of shorter duration with participants knowing their allocated group.

“We’ll also need to see long term trials, including effects on the risk of stroke and cardiovascular disease, before we can come to conclusions regarding clinical outcomes and potential side effects of long-term consumption,” said Ried. “These trials should use flavanol-free products in the control groups to eliminate any potential effects of low-dose flavanol on blood pressure.”

Potent human toxins prevalent in Canada’s freshwaters

‘High microcystin concentrations occur only at low nitrogen-to-phosphorus ratios in nutrient-rich Canadian lakes’

Ottawa, Ontario (August 14, 2012) – Nutrient pollution, one of the greatest threats to our freshwater resources, is responsible for the algal blooms that blanket our lakes and waterways in summer months. Large blooms of cyanobacteria (‘blue green algae’) can cause fish kills, increase the cost of drinking water treatment, devalue shoreline properties, and pose health risks to people, pets, and wildlife. A new paper just published in the Canadian Journal of Fisheries and Aquatic Sciences shows that microcystin, a toxin produced by cyanobacteria, is present in Canadian lakes in every province.

“Canadians enjoying their summer at the cottage need to know that those green scums of algae washing up on their beach are not only unsightly, but can also be a threat to their health and their children’s health,” says lead author, Diane Orihel, a researcher with the Department of Biological Sciences at the University of Alberta. “It’s time to get serious about cleaning up the nutrients polluting our lakes.”

Microcystins are well-established as potent liver toxins to humans and other mammals, and are classified as possible human carcinogens. “Blue-green algae present a growing health concern for domestic, agricultural and recreational water use in Canada and world-wide”, warns Dr. David Kinniburgh, the Director of the Alberta Centre for Toxicology at the University of Calgary. “The microcystin toxins they produce can cause acute liver failure in humans and may even cause cancer with long-term exposure.”

This study is the first to report on microcystin prevalence at a national scale–data from 246 bodies of water across Canada were collected. The authors determined that water quality was most at risk in lakes with the highest concentrations of nutrients. Nutrient-rich lakes and reservoirs, particularly in central Alberta and southwestern Manitoba, proved to have highest toxin concentrations, though all regions in Canada contained lakes that reached microcystin levels of concern.

A very important finding–that calls for further research–was the strong association between low nitrogen-to-phosphorus ratios and high microcystin concentrations. The authors recommend whole-ecosystem experiments be performed to understand how changing nutrient inputs to lakes affects microcystins and other cyanobacterial toxins. This information is essential for governments to develop effective management strategies for improving water quality in nutrient-polluted lakes.

“Harmful algae blooms are a growing problem worldwide. The more we look, the more we find,” remarked international water expert Dr. Stephen Carpenter, Director of the Center for Limnology at the University of Wisconsin-Madison, “Orihel and colleagues help define the conditions when we would expect highly toxic freshwater. These insights make it possible to focus management and research on the highest-risk situations.”

“This study addresses an issue that has important health consequences, but also highlights the importance of both the underlying basic science and monitoring programs essential to determine environmental changes,” says Don Jackson, Co-Editor of the Canadian Journal of Fisheries and Aquatic Sciences.

Study finds that yo-yo dieting does not thwart weight loss efforts or alter metabolism long term

Obesity is a known risk factor for many cancers as well as heart disease and diabetes

SEATTLE – Yo-yo dieting – the repetitive loss and regain of body weight, also called weight cycling – is prevalent in the Western world, affecting an estimated 10 percent to 40 percent of the population. The degree to which weight cycling may impact metabolism or thwart a person’s ability to lose weight in the long run has been unclear – until now.

A new study by researchers at Fred Hutchinson Cancer Research Center, published online in the journal Metabolism, for the first time has shown that a history of yo-yo dieting does not negatively affect metabolism or the ability to lose weight long term.

“A history of unsuccessful weight loss should not dissuade an individual from future attempts to shed pounds or diminish the role of a healthy diet and regular physical activity in successful weight management,” said the study’s senior author Anne McTiernan, M.D., Ph.D., a member of the Hutchinson Center’s Public Health Sciences Division.

Two-thirds of the U.S. population is currently overweight or obese and it is estimated that nearly half of American women are currently dieting to lose weight. Obesity is a known risk factor for many cancers as well as heart disease and diabetes. A relationship between body fat and the production of certain hormones and inflammatory markers is thought to contribute to increased cancer risk.

“We know there’s an association between obesity, sedentary behavior and increased risk of certain cancers,” McTiernan said. “The World Health Organization estimates that a quarter to a third of cancers could be prevented with maintenance of normal weight and keeping a physically active lifestyle.”

The study was based on data from 439 overweight-to-obese, sedentary Seattle-area women, ages 50 to 75, who were randomly assigned to one of four groups: reduced-calorie diet only, exercise only (mainly brisk walking), reduced-calorie diet plus exercise and a control group that received no intervention. At the end of the yearlong study, participants on the diet-only and diet-plus-exercise arms lost an average of 10 percent of their starting weight, which was the goal of the intervention.

The analysis aimed to determine whether women with a history of moderate or severe weight cycling were at a disadvantage compared to non-weight-cyclers when it came to losing weight. Of the study participants overall, 18 percent (77 women) met the criteria for severe weight cycling (having reported losing 20 or more pounds on three or more occasions) and 24 percent (103 women) met the criteria for moderate weight cycling (having reported losing 10 or more pounds on three or more occasions).

Although severe weight cyclers were, on average, nearly 20 pounds heavier than non-cyclers at the start of the study, at the end of the study the researchers found no significant differences between those who yo-yo dieted and those who didn’t with regard to the ability to successfully participate in diet and/or exercise programs. The cyclers also did not differ from the non-cyclers with regard to the impact of diet or diet-plus-exercise on weight loss, percentage of body fat and lean muscle mass gained or lost. Other physiological factors such as blood pressure, insulin sensitivity, and blood concentrations of hormones such as leptin (which helps make one feel full) and adiponectin (which helps regulate glucose levels) also did not differ significantly among those whose weight fluctuated and those whose did not.

These finding may represent a first in the scientific community. “To our knowledge, no previous studies have examined the effect of prior weight cycling on the body composition, metabolic and hormonal changes induced by a comprehensive lifestyle intervention in free-living women,” the authors wrote.

A pack of walnuts a day keeps the fertility specialist away?

UCLA researchers show that eating 2.5 ounces of walnuts per day improves semen quality in healthy young men

A paper published 15 August 2012 in Biology of Reproduction‘s Papers-in-Press reveals that eating 75 grams of walnuts a day improves the vitality, motility, and morphology of sperm in healthy men aged 21 to 35.

Approximately 70 million couples experience subfertility or infertility worldwide, with 30 to 50 percent of these cases attributable to the male partner. Some studies have suggested that human semen quality has declined in industrialized nations, possibly due to pollution, poor lifestyle habits, and/or an increasingly Western-style diet.

Dr. Wendie Robbins and her colleagues at the University of California, Los Angeles decided to investigate whether increasing polyunsaturated fatty acids (PUFAs), which are critical for sperm maturation and membrane function, would increase sperm quality in men consuming a Western-style diet.

The best sources of dietary PUFAs in a Western-style diet include fish and fish oil supplements, flax seed, and walnuts, the latter of which are rich sources of α-linolenic acid (ALA), a natural plant source of omega-3.

With support by the California Walnut Commission, Dr. Robbins’ team selected 117 healthy men between the ages of 21 and 35 who ate a Western-style diet and split them into two groups: one (58 men) who would avoid eating tree nuts and another (59 men) who would eat 75 grams of walnuts per day. Previous studies had indicated that 75 grams of walnuts would be a dose at which blood lipid levels would change, but at which healthy young men would not gain weight.

Before the experiment began and then again 12 weeks later, the men’s semen quality was analyzed according to conventional parameters of male fertility, including sperm concentration, vitality, motility, morphology, and chromosome abnormalities.

After 12 weeks, the team found no significant changes in body-mass index, body weight, or activity level in either group. The men consuming walnuts, however, had significantly increased levels of omega-6 and omega-3 (ALA) fatty acids and experienced improvement in sperm vitality, motility, and morphology. Those eating walnuts also had fewer chromosomal abnormalities in their sperm following the walnut dietary intervention. The control group, on the other hand, experienced no changes.

Although this research indicates that eating 75 grams of walnuts per day can positively affect a young man’s sperm quality, it is still unknown whether the benefits would apply to young men with fertility problems and whether they would actually translate into increased fertility.

Children’s physical activity levels are not enough to counteract sedentary lifestyles

Children who spend more than three-quarters of their time engaging in sedentary behaviour, such as watching TV and sitting at computers, have up to nine times poorer motor coordination than their more active peers, reveals a study published in the American Journal of Human Biology.

The study, involving Portuguese children, found that physical activity alone was not enough to overcome the negative effect of sedentary behaviour on basic motor coordination skills such as walking, throwing or catching, which are considered the building blocks of more complex movements.

“Childhood is a critical time for the development of motor coordination skills which are essential for health and well-being,” said lead author Dr Luis Lopes, from the University of Minho. “We know that sedentary lifestyles have a negative effect on these skills and are associated with decreased fitness, lower self-esteem, decreased academic achievement and increased obesity.”

Dr Lopes’ team studied 110 girls and 103 boys aged nine to ten from 13 urban elementary schools. The children’s sedentary behaviour and physical activity were objectively measured with accelerometers (a small device that children attach to their waist that quantifies movement counts and intensities) over five consecutive days. Motor coordination was evaluated with the KTK test (Körperkoordination Test für Kinder), which includes balance, jumping laterally, hopping on one leg over an obstacle and shifting platforms.

The tests were supplemented with a questionnaire for parents to assess health variables, before the authors compiled the results into three models to calculate odd ratios for predicting motor coordination. These were adjusted for physical activity and accelerometer wear time, waist to height ratio and home variables.

On average the children spent 75.6% of their time being sedentary, but the impact on motor coordination was found to be greater on boys than girls.

Girls who spent 77.3% or more of their time being sedentary were 4 to 5 times less likely to have normal motor coordination than more active girls. However, boys who were sedentary for more than 76% of their time were between 5 to 9 times less likely to have good or normal motor coordination than their active peers.

“It is very clear from our study that a high level of sedentary behaviour is an independent predictor of low motor coordination, regardless of physical activity levels and other key factors” said Lopes. “High sedentary behaviour had a significant impact on the children’s motor coordination, with boys being more adversely affected than girls.”

Until now there has been little research into the links between sedentary behaviour and motor coordination, but these findings reveal that physical activity did not counteract the negative effects that high levels of sedentary behaviour had on motor coordination.

“The results demonstrate the importance of setting a maximum time for sedentary behaviour, while encouraging children to increase their amount of physical activity,” concluded Lopes. “We hope that our findings will make a valuable contribution to the debate on child health and encourage future investigations on this subject.”

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BPA link to narrowing of the arteries

A research team from the Peninsula College of Medicine and Dentistry (PCMD), University of Exeter, and University of Cambridge has for the first time established a link between high levels of urinary Bisphenol-A (BPA) and severe coronary artery stenosis (narrowing of the arteries).

The study is published in PLoS ONE today, 15th August 2012.

The team analysed data from 591 patients who participated in the Metabonomics and Genomics Coronary Artery Disease (MaGiCAD) study in Cambridgeshire, UK. They compared urinary BPA with grades of severity of coronary artery disease (CAD).

The patients were classified into severe, intermediate or normal CAD categories based on narrowing of their coronary arteries measured using a technique called angiography, which is considered the gold standard method of diagnosis. In all, 385 patients were identified to have severe CAD, 86 intermediate CAD and 120 had normal coronary arteries.

The study shows that urinary BPA concentration was significantly higher in those with severe CAD compared to those with normal coronary arteries.

The results are important because they suggest that associations between urinary BPA and CAD may be specific to narrowing of the arteries.

This is the fourth study led by PCMD, University of Exeter to identify a statistical link between increased levels of urinary BPA and cardiovascular disease.

Other studies related to BPA carried out by the same research team have found associations with altered testosterone and changes in the expression of BPA target genes in men, suggesting that BPA may be more active in the body than previously thought.

The research team was led by Professor David Melzer, Professor of Epidemiology and Public Health at PCMD, University of Exeter. He said: “Our latest study strengthens a growing body of work that suggests that BPA may be adding to known risk factors for heart disease. Full proof will be very difficult to get, as experiments on this in humans are not feasible.”

Professor Tamara Galloway, lead toxicologist on the study from University of Exeter, said: “These results are important because they give us a better understanding of the mechanisms underlying the association between BPA and heart disease.”

Dr. David Mosedale, Chairman of the MaGiCAD Management Committee, added: “This demonstrates the utility of intensively characterised cohorts like MaGiCAD, and highlights the need for further research into the long-term effects of common environmental chemicals such as BPA.”

BPA is a controversial chemical commonly used in food and drink containers. It has previously caused concerns over health risks to babies, as it is present in some baby’s bottles. Following a PCMD study in September 2008 many nations moved to ban BPA from the manufacture of baby’s bottles and other feeding equipment.

BPA is used in polycarbonate plastic products such as refillable drinks containers, compact disks, some plastic eating utensils and many other products in everyday use. It is one of the world’s highest production volume chemicals, with 5.16 million tonnes produced in 2008 (source: Chemical Weekly 2009).

Spiteful behavior is ‘extreme’, according to study

Given the option to commit spiteful acts, reducing the money payoffs of others at no cost to themselves, many people avoid acting spitefully, but those that do, consistently impose the maximum harm, according to research reported on Aug. 15 in the open access journal PLoS ONE.

The authors, Erik Kimbrough of Simon Fraser University in Canada and Philipp Reiss of Maastricht University in the Netherlands, created an artificial auction market scenario, with participants “bidding” for objects and having the opportunity to raise the price paid by others, to test the frequency and extent of spiteful behavior among 48 student participants. Their results show extremes of spiteful and non-spiteful behavior across all participants, but individual spitefulness is typically consistent over time.

“We found it astonishing to see that people chose to be either maximally or minimally spiteful with really no one choosing something in between, and the fact that most people didn’t change their behavior over time suggests that we’re seeing something pretty fundamental”, say the authors.

Breastfeeding may protect infants from HIV transmission

Compound in human milk associated with reduced transmission from HIV-infected mother to breastfed infant

An international team of researchers has found that certain bioactive components found in human milk are associated with a reduced risk of HIV transmission from an HIV infected mother to her breast-fed infant. Their study will be published in the August 15 online edition of American Journal of Clinical Nutrition.

“In developing countries, HIV-infected mothers are faced with the decision of whether or not to breastfeed their babies,” said Lars Bode, PhD, assistant professor in the Department of Pediatrics at the University of California, San Diego School of Medicine. “Breastfeeding exposes the baby to the virus and increases the risk of the baby dying from HIV infection; but not breastfeeding increases the risk for the baby to die from other intestinal or respiratory infections.”

Bode and colleagues set out to find why the vast majority of breast-fed infants do not acquire HIV-1, despite continuous exposure to the virus in their mother’s milk over many months. Even in the absences of antiretroviral drugs, only 10 to15 percent of infants will acquire HIV infection from their HIV-infected mothers.

They discovered that immunologically active components called human milk oligosaccharides (HMO) – a type of carbohydrate made up of several simple sugars linked together – may protect from HIV transmission. These complex oligosaccharides are the third-most abundant component of breast milk, yet are not digestible and therefore become highly concentrated in the mucosal surfaces of the infant’s gastrointestinal tract.

“HMO act as prebiotics that promote the growth of desirable bacterial communities in the infant’s intestine,” said Bode. Additionally, HMO structurally resembles sugar chains called glycans that are normally found on epithelial cell surfaces, and can serve as “decoy” receptors to inhibit pathogens from binding. Last, HMO exhibit anti-inflammatory activity and have been shown to modulate immune cell responses in cell and animal models.

The researchers analyzed HMO amount and composition in breast milk samples collected from more than 200 women as part of a larger study of HIV-infected women and their infants in Lusaka, Zambia, following them from birth to 24 months. (Most were recruited to the study and followed before antiretroviral therapy became available to them, thus offering a unique look at associations between HMO and HIV transmission.)

Higher concentrations of HMO in milk were associated with protection against postnatal HIV transmission, independent of other known risk factors. In the future, a better understanding of how individual HMO facilitate or obstruct HIV transmission may guide the development of interventions to complement antiretroviral strategies and more effectively prevent transmission, according to the researchers.

Yoga: a cost-effective treatment for back pain sufferers?

Posted on 16 August 2012

Specialised group yoga classes could provide a cost-effective way of treating patients with chronic or recurrent low back pain, according to the UK’s largest ever study of the benefits of yoga.

Led by the University of York, and funded by Arthritis Research UK, the study provides an evaluation of a specially-developed 12-week group yoga intervention programme compared to conventional general practitioner (GP) care alone.

The results published in Spine, show that the yoga intervention programme – ‘Yoga for Healthy Lower Backs’ – is likely to be cost effective for both the UK National Health Service (NHS) and wider society.

The cost assumed for yoga intervention is important in determining whether this is an efficient use of NHS resources. As yoga classes are not currently available through the NHS, the researchers examined a range of possible costs. They conclude that if the NHS was to offer specialist yoga and managed to maintain the cost below £300 per patient (for a cycle of 12 classes), there is a high probability (around 70 per cent) of the yoga intervention being cost effective.

Researchers also found that those taking part in the yoga programme had far fewer days off work than those in the control group. On average, a control group participant reported 12 days off due to back pain, whereas those in the yoga group had four days off. The cost associated with taking time off was £1,202 for a control group member, compared with £374 for a yoga group member.

The study was carried out by researchers from the University of York’s Department of Health Sciences and the Centre for Health Economics, and the Hull York Medical School.

Chief Investigator Professor David Torgerson, Director of York Trials Unit, in the University of York’s Department of Health Sciences, said: “Back pain represents a significant burden to the NHS in the UK and to society as a whole. As well as the associated health care costs, it is also a major cause of work absenteeism which leads to a productivity loss to society.

“While yoga has been shown as an effective intervention for treating chronic and low back pain, until now there has been little evidence on its cost effectiveness. In our study we evaluated a specially-designed yoga class package by using individual-level data from a multi-centred randomized controlled trial. On the basis of the 12-month trial, we conclude that 12 weekly group classes of specialised yoga are likely to provide a cost-effective intervention for the treatment of patients with chronic or recurrent low back pain.”

Back pain is estimated to cost the NHS £1.37 billion and the health care sector £2.10 billion a year. It is also one of the most common conditions treated in primary care in the UK with about 2.6 million people seeking advice from their GP about back pain each year.

Professor Alan Silman, Medical Director of Arthritis Research UK, said: “We welcome the fact that not only has yoga been found to help people manage their back pain, but that it is also cost effective, and results in fewer sick days. It is another option for people who are struggling to manage their condition, and one that encourages the move to self-management. Yoga is an intervention that has been proven to make their everyday lives easier and their pain more manageable.

“We’d hope that on the back of this, more people with back pain are encouraged to take up the yoga programme.”

The trial involved two groups of people who were identified as having chronic or recurrent back pain. A group of 156 people were offered group yoga classes specially designed to improve back function, while a second control group of 157 people received GP care alone.

While yoga has been shown as an effective intervention for treating chronic and low back pain, until now there has been little evidence on its cost effectiveness

Professor David Torgerson

Both groups received usual GP care, which could have involved, for example, referral to pain clinics and physiotherapists or prescription of painkillers.

The 12-week yoga programme was delivered by 12 experienced yoga teachers. It was designed by Alison Trewhela, an Iyengar Yoga teacher and Senior Practitioner in Yoga on the British Register of Complementary Practitioners, in collaboration with yoga teacher Anna Semlyen, a Back Care Advisor to the British Wheel of Yoga.

Alison Trewhela said: “GPs and commissioners are showing great interest in this yoga programme. Many consider it could be the primary treatment option because it offers long-term positive outcomes, as well as a multi-disciplinary combination of taught skills that suits the bio-psycho-social nature of the condition of chronic low back pain.

“Within its confidence-boosting, gradually-progressing environment, the gentle ‘Yoga for Healthy Lower Backs’ course addresses joint mobility, muscle-strengthening, emphasis on the breath, mental attitude to pain and perspective on life lessons, postural awareness and low back education, relaxation techniques, and advice about other potentially health-giving techniques and benefits.”

More information on the York Trials Unit’s randomized controlled trial is available at www.yogatrial.co.uk. Lower back pain sufferers, yoga teachers and health professionals can also learn more about the ‘Yoga for Healthy Lower Backs’ programme at www.yogaforbacks.co.uk, a website created by the yoga teachers involved.

Turmeric Spices Up Virus Study

Posted: August 15, 2012 at 10:47 am, Last Updated: August 15, 2012 at 1:33 pm

By Michele McDonald

The popular spice turmeric packs more than just flavor — it shows promise in fighting devastating viruses, Mason researchers recently discovered.

Curcumin, found in turmeric, stopped the potentially deadly Rift Valley Fever virus from multiplying in infected cells, says Aarthi Narayanan, lead investigator on a new study and a research assistant professor in Mason’s National Center for Biodefense and Infectious Diseases.

Mosquito-borne Rift Valley Fever virus (RVF) is an acute, fever-causing virus that affects domestic animals such as cattle, sheep and goats, as well as humans. Results of the study were publishedthis month in the Journal of Biological Chemistry.

“Growing up in India, I was given turmeric all the time,” says Narayanan, who has spent the past 18 months working on the project. “Every time my son has a throat infection, I give (turmeric) to him.”

There’s more work to do before curcumin-based pharmaceuticals become commonplace, Narayanan emphasizes. She plans to test 10 different versions of curcumin to determine which one works the best. She also intends to apply the research to other viruses, including HIV.

Narayanan has long wanted to explore the infection-fighting properties of turmeric, in particular its key component, curcumin. “It is often not taken seriously because it’s a spice,” she says.

But science is transforming the spice from folk medicine to one that could help a patient’s body fight off a virus because it can prevent the virus from taking over healthy cells. These “broad-spectrum inhibitors” work by defeating a wide array of viruses.

Turmeric is often used as a spice in curry dishes. Photo by Sanjay Acharya from Wikipedia Commons

“Curcumin is, by its very nature, broad spectrum,” Narayanan says. “However, in the published article, we provide evidence that curcumin may interfere with how the virus manipulates the human cell to stop the cell from responding to the infection.”

Kylene Kehn-Hall, a co-investigator on the study, adds, “We are very excited about this work, as curcumin not only dramatically inhibits RVFV replication in cell culture but also demonstrates efficacy against RVFV in a mouse model.”

Narayanan and her colleagues study the connection between a virus and how it impacts the host — human or animal. Symptoms clue in the researcher about the body’s inner workings. Rift Valley Fever and Venezuelan Equine Encephalitis kick off with flu-like symptoms.

Symptoms can make it challenging for someone to recover. The body usually starts with an exaggerated inflammatory response because it doesn’t know where to start to rid itself of the virus, she says.

“Many times, the body goes above and beyond what is necessary,” Narayanan says. “And that’s not good because it’s going to influence a bunch of cells around the infection, which haven’t seen the bug. That’s one way by which disease spreads through your body. And so it is very important to control the host because a lot of times the way the host responds contributes to the disease.”

Controlling the symptoms means more than simply making the patients feels better. “You’re giving the antiviral a chance to work. Now an antiviral can go in and stop the bug. You’re no longer trying to keep the host alive and battling the bug at the same time.”

Narayanan works with a graduate student in Mason’s National Center for Biodefense and Infectious Diseases. Photo by Evan Cantwell

Once Narayanan knows how the body responds to a virus, it’s time to go after the bug itself.

She’s applying this know-how to a family of viruses called Bunyaviruses, which feature Rift Valley fever, and such alphaviruses as Venezuelan equine encephalitis and retroviruses, which notably include HIV.

She delves into uncovering why and how each virus affects the patient. “Why are some cell types more susceptible to one type of infection than another?”

HIV goes after the immune system. Bunyaviruses will infect a wide range of cells but do maximum damage to the liver. “What is it about the liver that makes it a sitting duck compared to something like the brain?” Narayanan asks.

Ultimately, curcumin could be part of drug therapies that help defeat these viruses, Narayanan says.

“I know this works. I know it works because I have seen it happen in real life,” Narayanan says. “I eat it every day. I make it a point of adding it to vegetables I cook. Every single day.”

Other Mason researchers involved in the study are Charles Bailey, Ravi Das, Irene Guendel, Lindsay Hall, Fatah Kashanchi, Svetlana Senina and Rachel Van Duyne. Several researchers from other institutions also collaborated.

Write to Michele McDonald at mmcdon15@gmu.edu

Why are elderly duped?

UI team pinpoints where doubt arises in human mind

By:

Richard C. Lewis | 2012.08.16 | 09:20 AM

Everyone knows the adage: “If something sounds too good to be true, then it probably is.” So, why, then, do some people fall for scams and why are older folks especially prone to being duped?

An answer, it seems, is because a specific area of the brain has deteriorated or is damaged, according to researchers at the University of Iowa. By examining patients with various forms of brain damage, the researchers report they’ve pinpointed the precise location in the human brain, called the ventromedial prefrontal cortex, that controls belief and doubt, and which explains why some of us are more gullible than others.

Patients with damage to the ventromedial prefrontal cortex were roughly twice as likely to believe a given ad, even when given disclaimer information pointing out it was misleading. And, they were more likely to buy the item, regardless of whether misleading information had been corrected. Photo by Bill Adams.

“The current study provides the first direct evidence beyond anecdotal reports that damage to the vmPFC (ventromedial prefrontal cortex) increases credulity. Indeed, this specific deficit may explain why highly intelligent vmPFC patients can fall victim to seemingly obvious fraud schemes,” the researchers wrote in the paper published in a special issue of the journal Frontiers in Neuroscience.

A study conducted for the National Institute of Justice in 2009 concluded that nearly 12 percent of Americans 60 and older had been exploited financially by a family member or a stranger. And, a report last year by insurer MetLife Inc. estimated the annual loss by victims of elder financial abuse at $2.9 billion.

The authors point out their research can explain why the elderly are vulnerable.

“In our theory, the more effortful process of disbelief (to items initially believed) is mediated by the vmPFC, which, in old age, tends to disproportionately lose structural integrity and associated functionality,” they wrote. “Thus, we suggest that vulnerability to misleading information, outright deception and fraud in older adults is the specific result of a deficit in the doubt process that is mediated by the vmPFC.”

The ventromedial prefrontal cortex is an oval-shaped lobe about the size of a softball lodged in the front of the human head, right above the eyes. It’s part of a larger area known to scientists since the extraordinary case of Phineas Gage that controls a range of emotions and behaviors, from impulsivity to poor planning. But brain scientists have struggled to identify which regions of the prefrontal cortex govern specific emotions and behaviors, including the cognitive seesaw between belief and doubt.

The UI team drew from its Neurological Patient Registry, which was established in 1982 and has more than 500 active members with various forms of damage to one or more regions in the brain. From that pool, the researchers chose 18 patients with damage to the ventromedial prefrontal cortex and 21 patients with damage outside the prefrontal cortex. Those patients, along with people with no brain damage, were shown advertisements mimicking ones flagged as misleading by the Federal Trade Commission to test how much they believed or doubted the ads. The deception in the ads was subtle; for example, an ad for “Legacy Luggage” that trumpets the gear as “American Quality” turned on the consumer’s ability to distinguish whether the luggage was manufactured in the United States versus inspected in the country.

Each participant was asked to gauge how much he or she believed the deceptive ad and how likely he or she would buy the item if it were available. The researchers found that the patients with damage to the ventromedial prefrontal cortex were roughly twice as likely to believe a given ad, even when given disclaimer information pointing out it was misleading. And, they were more likely to buy the item, regardless of whether misleading information had been corrected.

“Behaviorally, they fail the test to the greatest extent,” says Natalie Denburg, assistant professor in neurology who devised the ad tests. “They believe the ads the most, and they demonstrate the highest purchase intention. Taken together, it makes them the most vulnerable to being deceived.” She added the sample size is small and further studies are warranted.

Apart from being damaged, the ventromedial prefrontal cortex begins to deteriorate as people reach age 60 and older, although the onset and the pace of deterioration varies, says Daniel Tranel, neurology and psychology professor at the UI and corresponding author on the paper. He thinks the finding will enable doctors, caregivers, and relatives to be more understanding of decision making by the elderly.

“And maybe protective,” Tranel adds. “Instead of saying, ‘How would you do something silly and transparently stupid,’ people may have a better appreciation of the fact that older people have lost the biological mechanism that allows them to see the disadvantageous nature of their decisions.”

The finding corroborates an idea studied by the paper’s first author, Erik Asp, who wondered why damage to the prefrontal cortex would impair the ability to doubt but not the initial belief as well. Asp created a model, which he called the False Tagging Theory, to separate the two notions and confirm that doubt is housed in the prefrontal cortex.

“This study is strong empirical evidence suggesting that the False Tagging Theory is correct,” says Asp, who earned his doctorate in neuroscience from the UI in May and is now at the University of Chicago.

Kenneth Manzel, Bryan Koestner, and Catherine Cole from the UI are contributing authors on the paper. The National Institute on Aging and the National Institute of Neurological Disorders and Stroke funded the research

Common parasite may trigger suicide attempts

Contact: Jason Cody, Media Communications, Office: (517) 432-0924, Cell: (734) 755-0210, Jason.Cody@cabs.msu.edu; Lena Brundin, College of Human Medicine, Office: (616) 234-0996, lena.brundin@hc.msu.edu

Published: Aug. 16, 2012

The Toxoplasma gondii parasite has been linked to inflammation in the brain, damaging cells. Courtesy photo

EAST LANSING, Mich. — A parasite thought to be harmless and found in many people may actually be causing subtle changes in the brain, leading to suicide attempts.

New research appearing in the August issue of The Journal of Clinical Psychiatry adds to the growing work linking an infection caused by the Toxoplasma gondii parasite to suicide attempts. Michigan State University’s Lena Brundin was one of the lead researchers on the team.

About 10-20 percent of people in the United States have Toxoplasma gondii, or T. gondii, in their bodies, but in most it was thought to lie dormant, said Brundin, an associate professor of experimental psychiatry in MSU’s College of Human Medicine. In fact, it appears the parasite can cause inflammation over time, which produces harmful metabolites that can damage brain cells.

“Previous research has found signs of inflammation in the brains of suicide victims and people battling depression, and there also are previous reports linking Toxoplasma gondii to suicide attempts,” she said. “In our study we found that if you are positive for the parasite, you are seven times more likely to attempt suicide.”

The work by Brundin and colleagues is the first to measure scores on a suicide assessment scale from people infected with the parasite, some of whom had attempted suicide.

The results found those infected with T. gondii scored significantly higher on the scale, indicative of a more severe disease and greater risk for future suicide attempts. However, Brundin stresses the majority of those infected with the parasite will not attempt suicide: “Some individuals may for some reason be more susceptible to develop symptoms,” she said.

“Suicide is major health problem,” said Brundin, noting the 36,909 deaths in 2009 in America, or one every 14 minutes. “It is estimated 90 percent of people who attempt suicide have a diagnosed psychiatric disorder. If we could identify those people infected with this parasite, it could help us predict who is at a higher risk.”

T. gondii is a parasite found in cells that reproduces in its primary host, any member of the cat family. It is transmitted to humans primarily through ingesting water and food contaminated with the eggs of the parasite, or, since the parasite can be present in other mammals as well, through consuming undercooked raw meat or food.

Brundin has been looking at the link between depression and inflammation in the brain for a decade, beginning with work she did on Parkinson’s disease. Typically, a class of antidepressants called selective serotonin re-uptake inhibitors, or SSRIs, have been the preferred treatment for depression. SSRIs are believed to increase the level of a neurotransmitter called serotonin but are effective in only about half of depressed patients.

Brundin’s research indicates a reduction in the brain’s serotonin might be a symptom rather than the root cause of depression. Inflammation, possibly from an infection or a parasite, likely causes changes in the brain’s chemistry, leading to depression and, in some cases, thoughts of suicide, she said.

“I think it’s very positive that we are finding biological changes in suicidal patients,” she said. “It means we can develop new treatments to prevent suicides, and patients can feel hope that maybe we can help them.

“It’s a great opportunity to develop new treatments tailored at specific biological mechanisms.”

Brundin and co-senior investigator Teodor Postolache of the University of Maryland led the research team. Funding for the project came from several sources, most notably the Swedish Research Council and American Foundation for Suicide Prevention

Mariana Stern, Ph.D., associate professor of preventive medicine at the Keck School of Medicine of USC / photo by Jon Nalick

Pan-fried Meat Increases Risk of Prostate Cancer, New Study Finds

by Molly Rugg

Research from the University of Southern California (USC) and Cancer Prevention Institute of California (CPIC)found that cooking red meats at high temperatures, especially pan-fried red meats, may increase the risk of advanced prostate cancer by as much as 40 percent. Mariana Stern, associate professor of preventive medicine at the Keck School of Medicine of USC, led analyses for the study, “Red meat and poultry, cooking practices, genetic susceptibility and risk of prostate cancer: Results from the California Collaborative Prostate Cancer Study.” The study, which is available online in the journal Carcinogenesis, provides important new evidence on how red meat and its cooking practices may increase the risk for prostate cancer. Previous studies have emphasized an association between diets high in red meat and risk of prostate cancer, but evidence is limited. Attention to cooking methods of red meat, however, shows the risk of prostate cancer may be a result of potent chemical carcinogens formed when meats are cooked at high temperatures. Researchers examined pooled data from nearly 2,000 men who participated in the California Collaborative Prostate Cancer Study, a multiethnic, case-control study conducted in the San Francisco Bay Area by Esther John, CPIC senior research scientist, and in Los Angeles by Sue A. Ingles, associate professor of preventive medicine at the Keck School of Medicine of USC. Study participants completed a comprehensive questionnaire that evaluated amount and type of meat intake, including poultry and processed red meat. Information regarding cooking practices (e.g., pan-frying, oven-broiling and grilling) was obtained using color photographs that displayed the level of doneness. More than 1,000 of the men included in the study were diagnosed with advanced prostate cancer. “We found that men who ate more than 1.5 servings of pan-fried red meat per week increased their risk of advanced prostate cancer by 30 percent,” Stern said. “In addition, men who ate more than 2.5 servings of red meat cooked at high temperatures were 40 percent more likely to have advanced prostate cancer.” When considering specific types of red meats, hamburgers—but not steak—were linked to an increased risk of prostate cancer, especially among Hispanic men. “We speculate that these findings are a result of different levels of carcinogen accumulation found in hamburgers, given that they can attain higher internal and external temperatures faster than steak,” Stern added. Researchers also found that men with diets high in baked poultry had a lower risk of advanced prostate cancer, while consumption of pan-fried poultry was associated with increased risk. Stern noted that pan-frying, regardless of meat type, consistently led to an increased risk of prostate cancer. The same pattern was evident in Stern’s previous research, which found that fish cooked at high temperatures, particularly pan-fried, increased the risk of prostate cancer. The researchers do not know why pan-frying poses a higher risk for prostate cancer, but they suspect it is due to the formation of the DNA-damaging carcinogens—heterocyclic amines (HCAs)—during the cooking of red meat and poultry. HCAs are formed when sugars and amino acids are cooked at higher temperatures for longer periods of time. Other carcinogens, such as polycyclic aromatic hydrocarbons (PAHs) are formed during the grilling or smoking of meat. When fat from the meat drips on an open flame, the rising smoke leaves deposits of PAHs on the meat. There is strong experimental evidence that HCAs and PAHs contribute to certain cancers, including prostate cancer. “The observations from this study alone are not enough to make any health recommendations, but given the few modifiable risk factors known for prostate cancer, the understanding of dietary factors and cooking methods are of high public health relevance,” said Stern. Co-authors of the study include Amit Joshi who received his Ph.D. in molecular epidemiology from the Department of Preventive Medicine at the Keck School of Medicine; Chelsea Catsburg, Juan Pablo Lewinger and Sue Ingles of USC; and CPIC’s Esther John and Jocelyn Koo. The study was supported in part by the Prostate Cancer Foundation, American Cancer Society, and grant 5P30 ES07048 from the National Institute of Environmental Health Sciences and the National Cancer Institute.

Photographic cholesterol test

A noninvasive approach to total cholesterol determination

Researchers in India have developed a total cholesterol test that uses a digital camera to take a snapshot of the back of the patient’s hand rather than a blood sample. The image obtained is cropped and compared with images in a database for known cholesterol levels.

Writing in the International Journal of Medical Engineering and Informatics, N.R. Shanker of the Sree Sastha Institute of Engineering and Technology and colleagues describe how they have developed a non-invasive way to test cholesterol levels in patients at increased risk of heart disease. Their approach is based on the creation of a large database of cholesterol levels recorded using standard blood tests and linked to a standardized photograph of the hand for each patient; cholesterol is concentrated in the creases of one’s fingers. They developed an image-processing computer program that compares the image from a new patient with the thousands of entries in the database and matches it to a specific cholesterol reading.

Measuring the amount and type of cholesterol circulating in the blood is an important risk factor in cardiovascular disease. Excess cholesterol not used by the body in making hormones and building cells is laid down on the inner wall of arteries as a waxy plaque, which can reduce the normal flow of blood potentially causing heart problems and increasing the risk of cerebral stroke. Total cholesterol is a useful early indicator, although more detailed testing that distinguishes between the HDL high-density lipoprotein) and LDL (low-density lipoprotein) and triglycerides are needed for a more accurate health assessment of patients found to have high total cholesterol. It is LDL, so-called “bad” cholesterol that contributes to the formation of arterial plaques, atherosclerosis. The presence of different total levels of cholesterol can be revealed through image analysis of the skin.

A non-invasive and inexpensive method for cholesterol screening would allow this risk factor be determined in much larger patient populations without the need for costly and inconvenient blood tests. The team will also soon publish details of the extension of this work to classifying cholesterol type using their approach

Good mood foods: Some flavors in some foods resemble a prescription mood stabilizer

PHILADELPHIA, Aug. 19, 2012 — New evidence reveals the possibility of mood-enhancing effects associated with some flavors, stemming at least in part from natural ingredients bearing a striking chemical similarity to valproic acid, a widely used prescription mood-stabilizing drug, scientists reported here today. This effect joins those previously reported for chocolate, teas and some other known comfort foods.

They presented the study of more than 1,700 substances that make up the flavors of common foods at the 244^th National Meeting & Exposition of the American Chemical Society, the world’s largest scientific society. The meeting, expected to attract more than 14,000 scientists and others, continues here through Thursday.

“Molecules in chocolate, a variety of berries and foods containing omega-3 fatty acids have shown positive effects on mood. In turn, our studies show that some commonly used flavor components are structurally similar to valproic acid,” said Karina Martinez-Mayorga, Ph.D., leader of a research team that has been studying the effects of flavors on mood. She described research done while working at the Torrey Pines Institute for Molecular Studies, and now is with the Chemistry Institute at the National Autonomous University of Mexico.

Sold under brand names that include Depakene, Depakote and Stavzor, valproic acid is used to smooth out the mood swings of people with manic-depressive disorder and related conditions.

“The large body of evidence that chemicals in chocolate, blueberries, raspberries, strawberries, teas and certain foods could well be mood-enhancers encourages the search for other mood modulators in food,” noted Martinez-Mayorga.

Martinez-Mayorga pointed out that the need for a broad spectrum of mood modulators is fostering research not just in the pharmaceutical industry, but in the food and beverage industries as well. Food industry research, however, focuses on less-severe mood changes. People have recognized the mood-altering properties of various foods for years. Now Martinez-Mayorga’s team, and other research groups, is seeking to identify the chemical compounds that moderate mood swings, help maintain cognitive health, improve mental alertness and delay the onset of memory loss.

Her study involved use of techniques of chemoinformatics ― the application of informatic methods to solve chemical problems ― to screen the chemical structures of more than 1,700 food flavor ingredients for similarities to approved antidepressants, marketed drugs and agents with reported antidepressant activity. The main result so far in the ongoing project involves valproic acid. In the future, she said that the team plans to move from the area of analyzing the database to actually begin testing the flavor/mood hypothesis experimentally. The end result may be dietary recommendations or new nutritional supplements with beneficial mood effects, she added.

“It is important to remember that just eating foods that may improve mood is not a substitute for prescribed antidepressive drugs,” Martinez-Mayorga cautioned. And for people not requiring medication, she notes that eating specific foods and living a healthful lifestyle can generally boost mood.

The scientists acknowledged funding from Robertet Flavors, Inc., and the State of Florida, Executive Officer of the Governor’s Office of Tourism, Trade and Economic Development.

Red wine compound could help seniors walk away from mobility problems

PHILADELPHIA, Aug. 19, 2012 — In a stride toward better health in later life, scientists reported today that resveratrol, the so-called “miracle molecule” found in red wine, might help improve mobility and prevent life-threatening falls among older people. The finding, believed to be the first of its kind, was presented today to some 14,000 scientists and others gathered at the 244^th National Meeting & Exposition of the American Chemical Society, the world’s largest scientific society.

The researchers say this report — based on studies of laboratory mice — could lead to the development of natural products designed to help older Americans live safer and more productive lives.

“Our study suggests that a natural compound like resveratrol, which can be obtained either through dietary supplementation or diet itself, could actually decrease some of the motor deficiencies that are seen in our aging population,” said Jane E. Cavanaugh, Ph.D., leader of the research team. “And that would, therefore, increase an aging person’s quality of life and decrease their risk of hospitalization due to slips and falls.”

Cavanaugh notes that falls become more common with advancing age and are the leading cause of injury-related death among people older than 65. In addition, about one in three older Americans have difficulty with balance or walking, according to the American Geriatrics Society.

These mobility problems are particularly common among older people who have Parkinson’s disease and other age-related neurological disorders, Cavanagh said. She is with Duquesne University in Pittsburgh. However, while drugs can help alleviate some of the motor-related problems in Parkinson’s disease, Cavanaugh points out that there are no comparable treatments for balance and walking problems in otherwise healthy older adults. She and her colleagues set out to rectify that, focusing on natural chemical compounds such as resveratrol.

Previous studies have shown that resveratrol — an antioxidant found in red wine and dark-skinned fruits — might help reduce inflammation, lower cholesterol, slash the risk of heart disease and certain cancers and, perhaps, have some anti-aging effects in the body. Resveratrol is available as a dietary supplement and is abundant in foods such as red grapes, blueberries and nuts.

To determine its effects on balance and mobility, Cavanaugh, Erika N. Allen and colleagues fed young and old laboratory mice a diet containing resveratrol for eight weeks. They periodically tested the rodents’ ability to navigate a steel mesh balance beam, counting the number of times that each mouse took a misstep. Initially, the older mice had more difficulty maneuvering on the obstacle. But by week four, the older mice made far fewer missteps and were on par with the young mice.

While it is unclear how resveratrol works in the body, Cavanagh’s team found some clues. In laboratory experiments, they exposed neural cells to a neurotransmitter called dopamine, which in large amounts can induce cell death. However, neurons treated with resveratrol before being exposed to dopamine survived. On closer examination, the researchers found that resveratrol mitigated the damage done by oxygen free radicals, generated by the breakdown of the dopamine, and activated protein signaling pathways that appeared to promote cell survival.

Although she is encouraged by the results, Cavanaugh notes that resveratrol does have some drawbacks. For instance, it is poorly absorbed by the body. In fact, she calculates that a 150-pound person would have to drink almost 700 4-ounce glasses of red wine a day to absorb enough resveratrol to get any beneficial effects. That’s why she and her colleagues are investigating similar man-made compounds that mimic the effects of resveratrol and might be more bioavailable to the body. They’re also trying to determine how much resveratrol actually enters the brain.

Nevertheless, the researchers suspect that even if the effects of resveratrol in the brain are minute, this small margin could potentially be enough to help older people remain steady on their feet and avoid taking serious tumbles

Coconut water is an excellent sports drink — for light exercise

PHILADELPHIA, Aug. 20, 2012 — Coconut water really does deserve its popular reputation as Mother Nature’s own sports drink, a new scientific analysis of the much-hyped natural beverage concluded here today at the 244^th National Meeting & Exposition of the American Chemical Society (ACS).

However, people who engage in strenuous exercise that involves a lot of sweat might want to take it all with a grain of salt ― literally ― or stick with a more traditional sports drink like Gatorade, said Chhandashri Bhattacharya, Ph.D. She presented a report on an analysis of coconut water to the ACS, the world’s largest scientific society, which is meeting here this week.

“Coconut water is a natural drink that has everything your average sports drink has and more,” said Bhattacharya. “It has five times more potassium than Gatorade or Powerade. Whenever you get cramps in your muscles, potassium will help you to get rid of the cramps. It’s a healthy drink that replenishes the nutrients that your body has lost during a moderate workout.”

Bhattacharya said that the potassium in coconut water also may benefit other people who do not exercise. The typical American diet is low in potassium and high in sodium, which is found in table salt. Other research has shown that such an imbalance is unhealthy. In one study, people who ate foods low in potassium and high in sodium had twice the risk of death from heart disease and a 50 percent higher risk of death from all causes. Other analyses indicate that a 12-ounce serving of coconut water has more potassium than a banana.

And it is high in healthful antioxidants, added Bhattacharya, who is with Indiana University Southeast in New Albany.

Coconut water is the clear liquid found most abundantly inside young, green coconuts, which are fruits of the coconut palm. It long has been a popular drink in the tropics, where street and beach vendors sell green coconuts with a drinking straw in the top. Coconut water now is available in bottles, cans and other containers, and marketers have promoted it as a healthy beverage.

Bhattacharya’s team analyzed coconut water, Gatorade and Powerade and found that coconut water contained up to 1,500 mg/liter of potassium, compared to up to 300 mg/liter for Powerade and Gatorade. Coconut water, however, had 400 mg/liter of sodium compared to 600 for the other two drinks. It had comparable quantities of magnesium and carbohydrates as the other drinks. The price for all three beverages ranged from $2 to $3 for 8- to 12-oz containers, she said.

Coconut water’s lower sodium content is where it fails as a good sports drink for people who engage in strenuous exercise that produces a lot of sweating, Bhattacharya said. Sweating makes people lose more sodium than potassium, and coconut water alone can’t replace that lost sodium.

Drink made from berry wine may provide tasty drug for diabetes

URBANA – In evaluating the bioactive compounds of Illinois blueberry and blackberry wines, University of Illinois scientists have found compounds that inhibit enzymes responsible for carbohydrate absorption and assimilation. And that could mean a tasty way to help people with diabetes decrease their blood sugar.

“We’re thinking about a dealcoholized fermented fruit beverage that would optimize the inhibition of the alpha-amylase and alpha-glucosidase enzymes and also make use of the wines’ other healthful bioactive components,” said Elvira de Mejia, a U of I professor of food chemistry and food toxicology.

Graduate student Michelle Johnson evaluated the nutritional value of 19 Illinois wines, deciding on a blueberry-blackberry blend for maximum effectiveness.

In the in vitro study, the scientists compared the anti-carb effects of the alpha-amylase and alpha-glucosidase enzymes with acarbose, an anti-diabetes drug. The carb-degrading enzymes were inhibited in a range of 91.8 percent for alpha-amylase compared to acarbose and 103.2 percent for alpha-glucosidase compared to acarbose, de Mejia said.

The study is the first to assess the effect of berry fermentation at different temperatures on these carb-inhibiting enzymes. At both room and cold (4ºC) temperatures, berry wine retained the ability to degrade the enzymes, she said.

In a second study, Johnson quantified the antioxidant, polyphenol, and anthocyanin content of blueberry and blackberry wines. Her proposed blend contains an abundance of these bioactive compounds, which add to its healthful properties.

The researchers are particularly interested in the ability of anthocyanins to reduce inflammation, which contributes to the development of many chronic illnesses, including cancer, metabolic disease, and cardiovascular disease. To that end, they are experimenting with the berries’ effects on inflammatory cells, and they have found that anthocyanins reduce markers associated with the inflammatory response.

“Preliminary studies have indicated that anthocyanins may have a positive effect on cognition and overall brain health while protecting against some of the effects of aging, such as Alzheimer’s disease and memory loss. These berries have some very intriguing components,” de Mejia said.

A food chemist, de Mejia would like to remove the alcohol from the wines, leaving the carb-degrading enzyme compounds, the inflammation-fighting anthocyanins, and other beneficial bioactive components in a functional and flavorful drink for diabetics and others.

The bioactive ingredients could also be added to any prepared beverage to give it color, flavor, and nutritional punch, making them useful to the food industry, she said.

Vitamin D supplementation can decrease risk of respiratory infections in children

Wintertime infection risk cut in half among children with very low initial vitamin D levels

A study conducted in Mongolian schoolchildren supports the possibility that daily vitamin D supplementation can reduce the risk of respiratory infections in winter. In a report that will appear in the journal Pediatrics and has received early online release, an international research team found that vitamin D supplementation decreased the risk of respiratory infections among children who had low blood levels of vitamin D at the start of the study.

“Our randomized controlled trial shows that vitamin D has important effects on infection risk,” says Carlos Camargo, MD, of Massachusetts General Hospital (MGH), the study’s corresponding author. “In almost 250 children with low blood levels of vitamin D during winter, we found that taking a daily vitamin D supplement cut in half the risk of a respiratory infection.”

Several recent investigations have suggested that vitamin D – best known for its role in the development and maintenance of strong bones – has additional important roles, including in immune function. Studies led by Camargo and other researchers have associated higher vitamin D levels with reduced risk of respiratory infections such as colds or flu, but such observational studies cannot prove that the vitamin actually protects against infection. That kind of evidence must come from randomized controlled trials comparing two similar populations that either do or do not receive an intervention such as vitamin D supplementation. The first such trial, in Japanese schoolchildren, had equivocal results, showing a reduction in the risk of one type of influenza but no effect on another type, so many organizations have called for further randomized trials to settle the issue.

Since vitamin D is naturally produced by the body in response to sunlight, maintaining adequate levels in winter is particularly challenging in areas such as the northern U.S. and Canada that have significant seasonal variations in daily sunlight. The current study analyzed data from the Blue Sky Study, conducted in Ulaanbaatar, Mongolia, by a team led by Harvard investigators in collaboration with local health researchers. Mongolians are known to be at high risk for vitamin D deficiency, especially during winter, and the Blue Sky Study followed schoolchildren, all of whom were found to have low blood levels of 25-hydroxyvitamin D (25OHD), which is considered the best measure of vitamin D status, at the study’s outset.

In the current study, Camargo and colleagues compared the number of winter respiratory infections among a group of children who received daily doses of vitamin D added to locally produced milk with that of a control group receiving the same milk without added vitamin D. The supplement was undetectable so that children, teachers, and local researchers could not tell which group received vitamin D. While blood samples taken at the outset of the study revealed vitamin D deficiency in all participants, with average 25OHD levels around 7 ng/ml (17 nmol/L) in both groups, at the end of the seven-week treatment period, differences between the two groups were significant, with those receive vitamin D averaging 19 ng/ml (47 nmol/L), which although still low was significantly higher than at the start of the trial. Based on reports from their parents, the children receiving vitamin D had about half the incidence of respiratory infections that the control group had.

“Our study design provides strong evidence that the association between low vitamin D and respiratory infections is causal and that treating low vitamin D levels in children with an inexpensive and safe supplement will prevent some respiratory infections,” says Camargo, a professor of Medicine at Harvard Medical School. “The large benefit was undoubtedly related to the low baseline vitamin D levels of these children, so I would not expect the supplement to provide similar benefit in children who start with healthy levels of vitamin D. The key question for future research is at what initial vitamin D level would children no longer receive benefit from winter supplementation?”

The researchers note that while the vitamin D dosage used in this study (300 IU daily) was higher than the recommended daily dosage at the time the study was launched, since then the U.S. Institute of Medicine has raised the recommended dose for children to 400 IU, and other groups recommend daily dosages as high as 1,000 IU for children at risk for vitamin D deficiency. The authors also point out that, while Mongolia may appear to have little in common with the U.S., the low baseline vitamin D levels seen in study participants are relatively common in some groups of Americans, such as African-American children living in northern states.

Sea life ‘facing major shock’

Life in the world’s oceans faces far greater change and risk of large-scale extinctions than at any previous time in human history, a team of the world’s leading marine scientists has warned.

The researchers from Australia, the US, Canada, Germany, Panama, Norway and the UK have compared events which drove massive extinctions of sea life in the past with what is observed to be taking place in the seas and oceans globally today.

Three of the five largest extinctions of the past 500 million years were associated with global warming and acidification of the oceans – trends which also apply today, the scientists say in a new article in the journal Trends in Ecology and Evolution.

Other extinctions were driven by loss of oxygen from seawaters, pollution, habitat loss and pressure from human hunting and fishing – or a combination of these factors.

“Currently, the Earth is again in a period of increased extinctions and extinction risks, this time mainly caused by human factors,” the scientists stated. While the data is harder to collect at sea than on land, the evidence points strongly to similar pressures now being felt by sea life as for land animals and plants.

The researchers conducted an extensive search of the historical and fossil records to establish the main causes of previous marine extinctions – and the risk of their recurring today.

“We wanted to understand what had driven past extinctions of sea life and see how much of those conditions prevailed today,” says co-author Professor John Pandolfi, of the ARC Centre of Excellence for Coral Reef Studies and The University of Queensland, an authority on the fate of coral reefs in previous mass extinction events.

“It is very useful to look back in time – because if you forget your history, you’re liable to repeat it.”

Marine extinction events vary greatly. In the ‘Great Death’ of the Permian 250 million years ago, for example, an estimated 95 per cent of marine species died out due to a combination of warming, acidification, loss of oxygen and habitat. Scientists have traced the tragedy in the chemistry of ocean sediments laid down at the time, and abrupt loss of many sea animals from the fossil record.

“We are seeing the signature of all those drivers today – plus the added drivers of human overexploitation and pollution from chemicals, plastics and nutrients,” Prof. Pandolfi says.

“The fossil record tells us that sea life is very resilient – that it recovers after one of these huge setbacks. But also that it can take millions of years to do so.”

The researchers wrote the paper out of their concern that the oceans appear to be on the brink of another major extinction event.

“There may be still time to act,” Prof. Pandolfi says. “If we understand what drives ocean extinction, we can also understand what we need to do to prevent or minimise it.

“We need to understand that the oceans aren’t just a big dumping ground for human waste, contaminants and CO2 – a place we can afford to ignore or overexploit. They are closely linked to our own survival, wellbeing and prosperity as well as that of life on Earth in general.

“Even though we cannot easily see what is going on underwater, we need to recognise that the influence of 7 billion humans is now so great it governs the fate of life in the oceans. And we need to start taking responsibility for that.”

He adds “The situation is not hopeless. If fact we have seen clear evidence both from the past and the present that sea life can bounce back, given a chance to do so.

“For example, in Australia we have clear evidence of that good management of coral reefs can lead to recovery of both corals and fish numbers.

“So, rather, our paper is an appeal to humanity to give the oceans a chance.

“In effect, it says we need to stop releasing the CO2 that drives these massive extinction events, curb the polluted and nutrient-rich runoff from the land that is causing ocean ‘dead zones’ manage our fisheries more sustainably and protect their habitat better.

“All these things are possible, but people need to understand why they are essential. That is the first step in taking effective action to prevent extinctions.”

Their paper Extinctions in ancient and modern seas by Paul G. Harnik, Heike K. Lotze, Sean C. Anderson, Zoe V. Finkel, Seth Finnegan, David R. Lindberg, Lee Hsiang Liow, Rowan Lockwood, Craig R. McClain, Jenny L. McGuire, Aaron O’Dea, John M. Pandolfi, Carl Simpson and Derek P. Tittensor appears in the online edition of Trends in Ecology and Evolution (TREE).

Scientists find protein that promotes cancers, heart disease; create substance to block its effects

PHILADELPHIA, Aug. 21, 2012 — Strong scientific evidence suggests that high levels of a blood protein called galectin-3 may increase the risk of heart attacks, cancer and other diseases, and help forecast the outcome of those diseases, a scientist reported here today at the 244^th National Meeting & Exposition of the American Chemical Society, the world’s largest scientific society.

Isaac Eliaz, M.D., who outlined the scientific case against galectin-3, said a new galectin-3 blood test approved by the U.S. Food and Drug Administration can be useful in determining the risk and prognosis of numerous diseases. His presentation also included evidence that modified citrus pectin, produced from the white pulp inside orange peel and other citrus fruit, can bind and block excess galectin-3 activity.

The body cannot absorb natural citrus pectin, which passes through the GI tract undigested, Eliaz explained. Modification permits its absorption into the blood, where it blocks the negative effects of galectin-3, he added.

Eliaz said his conclusions were based on evidence from clinical trials involving close to 8,000 people.

In your future: More healthful foods to nourish the non-human you

PHILADELPHIA, Aug. 21, 2012 — The focus of nutrition for good health is quietly shifting to include consumption of food ingredients specifically designed to nourish the non-human cells that comprise 80 percent of the cells in the typical person, an authority on the topic said here today.

Speaking at the 244^th National Meeting & Exposition of the American Chemical Society, the world’s largest scientific society, Robert Rastall, Ph.D., cited several factors driving these so-called “prebiotic” ingredients toward more foods. Food scientists, for instance, are developing new sources of the healthful substances for use in a variety of foods, and scientific evidence on the benefits of eating prebiotics is growing.

“Just as people need food to thrive, so do the billions of healthful bacteria that live in our guts, our gastrointestinal tract,” Rastall explained. “There’s a large and expanding body of scientific evidence that bacteria in the gut play a role in health and disease. Prebiotics are foods that contain nutrients that support the growth and activity of these friendly bacteria.”

Rastall contrasted prebiotics to the more familiar “probiotics,” already being promoted on the labels of food like yogurt and some dietary supplements. He heads the Department of Food and Nutritional Sciences at the University of Reading in the U.K. and is co-author of widely used textbooks on prebiotics and probiotics.

Probiotic foods actually contain friendly bacteria like Lactobacillus acidophilus believed to release healthful substances as they grow in the GI tract. Prebiotics are indigestible food ingredients that provide no nutrition to people. Their purpose is to nourish the friendly bacteria among the estimated 100 trillion microbes living inside the human GI tract.

Foods promoted for a prebiotic effect already are on the market in the European Union, and Rastall predicted that prebiotics will gain a greater foothold in Europe and the United States. One major advantage: Prebiotics do not require refrigeration like probiotic yogurt and other dairy products and could be incorporated into a wider range of foods.

Rastall noted that people get small amounts of one of the most common prebiotics, called inulin, from wheat, onions, garlic, chicory and certain other foods. He cited studies showing that when people eat more inulin and other prebiotics, the balance of microbes in the gut shifts to one linked to a range of health benefits.

To help people get more prebiotics in their diet, Rastall’s team in the U.K., working with colleagues at the U.S. Department of Agriculture’s Agricultural Research Service, is finding ways to make prebiotics from plant carbohydrates like pectins, mannans and xylans.

They are using plant biomass, like stems and husks, as sources for those carbohydrates, which then are converted to the shorter carbohydrates that make up prebiotics. The goal is preparation of prebiotic carbohydrates that have neutral tastes and can withstand heating so they could be easily added to processed foods. These new prebiotics also could be used as stand-alone dietary supplements, he added.

“Prebiotics may prove to be most useful in specific population groups and people with specific health problems rather than the general population,” Rastall said. He cited, for instance, individuals with gastrointestinal diseases, Type-2 diabetes and low-grade inflammation linked to an increased risk of heart disease and other conditions, and people at risk for travelers’ diarrhea

New form of long-used food ingredient for ‘anti-hunger’ yogurts, smoothies

PHILADELPHIA, Aug. 21, 2012 — Promising results were reported here today from a proof-of-concept clinical trial of an “anti-hunger” ingredient for yogurt, fruit shakes, smoothies and other foods that would make people feel full longer and ease the craving to eat. Scientists described the ingredient, a new version of a food additive that has been in use for more than 50 years, at the 244^th National Meeting & Exposition of the American Chemical Society.

The potential new tool in the battle of the bulge is methyl cellulose, a white powder that dissolves in cold water to form a thick solution that turns into a “gel” or gelatin-like material upon heating.

Methyl cellulose provides a pleasant texture and holds together the ingredients in hundreds of food products like baked goods, sweet and savory snacks and ready meals.

Carsten Huettermann, Ph.D., who presented the report, said that this is the first use of methyl cellulose as a satiety ingredient in food.

“This ingredient would make people feel full after eating smaller amounts of food,” Huettermann explained. “With that sense of fullness and hunger-satisfaction, they would not crave more food. In our first study, we saw that fewer calories were consumed at the following meal after eating our new product. Our next step now is to investigate in further studies the mechanism of action and whether this may have an impact on weight management.”

The updated methyl cellulose, named SATISFIT-LTG, showed promise for doing that in a controlled clinical trial that Huettermann discussed at the meeting. He is with Dow Wolff Cellulosics in Bomlitz, Germany, which manufactures methyl cellulose. Volunteers who consumed SATISFIT-LTG experienced a reduction in the sensation of hunger that lasted until the consumption of a following meal in which the volunteers could eat as much as they wanted (two hours after eating SATISFIT-LTG) and a statistically significant reduced intake of calories at this meal. The consumption of SATISFIT-LTG resulted in a 13 percent decrease in calorie intake.

Huettermann explained that conventional versions of methyl cellulose pass through the stomach rapidly and do not work as a satiety ingredient. SATISFIT-LTG, however, forms a gel at body temperature, and the gel lingers in the stomach before passing into the small intestine.

The scientists are developing SATISFIT-LTG as a potential ingredient in cold foods, such as smoothies and yogurts, and Huettermann said that work will continue based on the promising clinical trial results

Antibiotic use in infants before 6 months associated with being overweight in childhood

New York City (August 21, 2012) – Treating very young infants with antibiotics may predispose them to being overweight in childhood, according to a study of more than 10,000 children by researchers at the NYU School of Medicine and the NYU Wagner School of Public Service and published in the online August 21, 2012, issue of the International Journal of Obesity.

The study found that on average, children exposed to antibiotics from birth to 5 months of age weighed more for their height than children who weren’t exposed. Between the ages of 10 to 20 months, this translated into small increases in body mass percentile, based on models that incorporated the potential impacts of diet, physical activity, and parental obesity. By 38 months of age, exposed children had a 22% greater likelihood of being overweight. However, the timing of exposure mattered: children exposed from 6 months to 14 months did not have significantly higher body mass than children who did not receive antibiotics in that same time period.

The NYU School of Medicine researchers, led by Leonardo Trasande, MD, MPP, associate professor of pediatrics and environmental medicine, and Jan Blustein, MD, PhD, professor of population health and medicine, caution that the study does not prove that antibiotics in early life causes young children to be overweight. It only shows that a correlation exists. Further studies will need to be conducted to explore the issue of a direct causal link.

“We typically consider obesity an epidemic grounded in unhealthy diet and exercise, yet increasingly studies suggest it’s more complicated,” said Dr. Trasande. “Microbes in our intestines may play critical roles in how we absorb calories, and exposure to antibiotics, especially early in life, may kill off healthy bacteria that influence how we absorb nutrients into our bodies, and would otherwise keep us lean.”

In recent years there has been a growing concern about the overuse of antibiotics, especially in children. Preliminary studies of the microbiome, the trillions of microbial cells inhabiting our bodies and outnumber our own cells 10 to 1, implicate obesity, inflammatory bowel disease, asthma, and other conditions with changes in the microbiome. It is still a field in its infancy, however, and no one has yet proved that altering the composition of bacteria in the body leads to disease.

This is the first time that a study has analyzed the association between the use of antibiotics and body mass starting in infancy. One previous study had identified a link between antibiotic use in early infancy and obesity at seven years of age, but was unable to examine potential impacts of antibiotic use later in infancy on body weight in childhood.

The NYU School of Medicine researchers evaluated the use of antibiotics among 11,532 children born in Avon, United Kingdom, during 1991 and 1992. The children are part of the Avon Longitudinal Study of Parents and Children (ALSPAC), a long-term study that provides detailed data on the health and development of these children.

The NYU School of Medicine researchers analyzed health information on these children during three periods: from birth to 5 months of age; 6 months to 14 months; and, finally from 15 to 23 months. They also examined body mass or weight at five different points of time—6 weeks, 10 months, 20 months, 38 months, and 7 years of age.

Antibiotic use only appeared to have an effect in very young infants (those given antibiotics from birth to 5 months of age.) Although children exposed to antibiotics at 15 to 23 months had somewhat greater BMI (Body Mass Indices) for their age and gender by the age of 7, there was no significant increase in their being overweight or obese.

“For many years now, farmers have known that antibiotics are great at producing heavier cows for market,” said Dr. Blustein. “While we need more research to confirm our findings, this carefully conducted study suggests that antibiotics influence weight gain in humans, and especially children too.”

In addition to Dr. Trasande, who is also associate professor of health policy, NYU Wagner School of Public Service, and Dr. Blustein, who is also a professor of health policy at the NYU Wagner School of Public Service, the authors of the study are: Mengling Liu, PhD, associate professor of environmental medicine, NYU School of Medicine; Elise Corwin, BA, NYU Wagner School of Public Service; Laura M. Cox, BA, Department of Microbiology, NYU School of Medicine; Martin J. Blaser, MD, the Frederick H. King Professor of Internal Medicine and chair Department of Medicine, and professor of microbiology, NYU School of Medicine.

Bewildered by the array of antioxidant fruit juices on display in the supermarket and the promises they make? To sort out the antioxidant properties of fruits and berries, scientists at Emory University School of Medicine turned to fruit flies for help.

They found that a commercially available acai berry product can lengthen the lives of fruit flies, when the flies’ lives are made short through additional oxidative stress. Under certain conditions (a simple sugar diet) acai supplementation could triple flies’ lifespans, from eight to 24 days. Acai could also counteract the neurotoxic effects of the herbicide paraquat on the flies.

The results were recently published by the journal Experimental Gerontology, which awarded the paper its inaugural “Outstanding paper” prize. The lead author is Alysia Vrailas-Mortimer, a postdoctoral fellow in Emory University School of Medicine’s department of cell biology.

Vrailas-Mortimer says she didn’t start out focusing on acai. But acai worked better than several other antioxidant products such as vitamins, coenzyme Q10 and lutein.

“One thing that makes our work distinctive is that we tried commercially available supplements,” she says. “We went to a health food store and filled up a basket.”

She says she began the project with the help of undergraduate student Rosy Gomez, and narrowed her focus after initial success with acai. Vrailas-Mortimer took advantage of a discovery she had made working with Subhabrata Sanyal, assistant professor of cell biology. They had previously found that flies with mutations in the “p38 MAP kinase” gene have shorter lives and are more sensitive to heat, food deprivation and oxidative stress.

P38 mutant flies lived an average of only eight days when they were given a simple sugar water diet. However, their lifespans tripled when their diet was supplemented with acai. Ginger was used as a control for the diet supplements.

Acai also protected normal flies against oxidative stress, in the form of hydrogen peroxide or paraquat. Acai can protect against oxidative stress when flies are exposed to hydrogen peroxide before being given acai, but the protective effect does not hold up if the order is reversed.

The effects of paraquat on circadian rhythms are visible here.

Paraquat is an herbicide that has neurotoxic effects that resemble Parkinson’s disease. Under the influence of paraquat, flies’ sleep-wake cycles gradually become chaotic (see graph). Acai can also help soften the effects of paraquat on flies’ circadian rhythms.

“I think this is important,” Vrailas-Mortimer says. “We show that whatever is in acai that is lengthening lifespan, it can also keep the flies functioning better for longer when faced with paraquat exposure. It is maintaining quality of life rather than just preventing them from dying.”

When flies were fed a more enriched diet of a standard cornmeal/molasses mush, the effects of supplementation with acai were more pronounced in males than in females. Males’ lifespans were almost doubled with acai (20 to 40 days) but the effects on females were not as strong (30 to 34 days). On an enriched diet, male flies were more sensitive to paraquat than females as well.

Implications for human clinical trials of antioxidants

Large clinical trials studying the effects of antioxidants such as vitamin C and E have not shown clear benefits on human health. Using fruit flies under oxidative stress as a model can be a way to dissect which components of acai are beneficial. Probing the effects on flies’ circadian rhythms can be a way to quickly screen several compounds or regimens, since the effects are apparent even before most of the flies die.

Acai berries contain a variety of antioxidant and anti-inflammatory compounds, such as anthocyanins. Sanyal says it may be better to study the components of acai together rather than in isolation.

“There may be a combinatorial effect, and if you separate the components from each other, you may lose the active principle,” he says. “In addition, it seems to me that anti-oxidant therapy will not work after the damage has been done. So human clinical trials that don’t take this into account are likely to have disappointing results.”

The research was supported by the National Institute of Environmental Health Sciences (T32-ES012870) and Emory University.

Reference: A. Vrailas-Mortimer, R. Gomez, H. Dowse and S. Sanyal. A survey of the protective ieffects of some commercially available antioxidant supplements in genetically and chemically induced models of oxidative stress in Drosophila melanogaster Exp. Gerontol. (2012).

Study shows long term effects of radiation in pediatric cancer patients

August 21, 2012 By Garth Sundem Leave a Comment

For many pediatric cancer patients, total body irradiation (TBI) is a necessary part of treatment during bone marrow transplant– it’s a key component of long term survival. But lengthened survival creates the ability to notice long term effects of radiation as these youngest cancer patients age. A University of Colorado Cancer Center study recently published in the journal Pediatric Blood & Cancer details these late effects of radiation.

“These kids basically lie on a table and truly do get radiation from head to toe. There is a little blocking of the lungs, but nothing of, for example, the brain or the kidneys,” says Jean Mulcahy-Levy, MD, research fellow at the CU Cancer Center and the paper’s first author.

Of 15 patients who received TBI before age 3, many developed endocrine and metabolic problems including testicular malfunction (78 percent), restrictive pulmonary disease due to high levels of blood triglycerides (74 percent), and cataracts (78 percent). Likewise, 90 percent of patients showed abnormally low levels of growth hormone, and 71 percent were considerably under height. Additional late effects of TBI included kidney, liver, skeletal and cardiac malfunction – and three of four patients whose IQ had been tested before TBI showed cognitive decline.

“Fifteen doesn’t seem like a large number, but because we have such a good pediatric bone marrow transplant program here at Children’s Hospital Colorado and radiation therapy program at the CU Cancer Center, we were able to get a large enough cohort of patients to see these overall effects,” Mulcahy-Levy says.

The study supports the recommendations of the Children’s Oncology Group for long term follow up care for children receiving TBI (survivorshipguidelines.org). Specifically, Mulcahy-Levy hopes that increasing awareness of likely effects will help patients and their doctors screen for, detect, and correct likely effects of TBI.

“It’s not so much that you want to stop TBI, which is frequently a necessary part of treatment, but this study shows it’s important know about these problems in order to address them appropriately and proactively,” Mulcahy-Levy says.

First identification of a strong oral carcinogen in smokeless tobacco

PHILADELPHIA, Aug. 22, 2012 — Scientists today reported identification of the first substance in smokeless tobacco that is a strong oral carcinogen ― a health risk for the 9 million users of chewing tobacco, snuff and related products in the U.S. ― and called upon the federal government to regulate or ban the substance.

The researchers reported here at the 244^th National Meeting & Exposition of the American Chemical Society, the world’s largest scientific society. The meeting, which continues through Thursday, features more than 8,600 reports on new developments in science, with an anticipated attendance of 14,000 scientists and others.

“This is the first example of a strong oral cavity carcinogen that’s in smokeless tobacco,” said Stephen Hecht, Ph.D., who led the study. “Our results are very important in regard to the growing use of smokeless tobacco in the world, especially among younger people who think it is a safer form of tobacco than cigarettes. We now have the identity of the only known strong oral carcinogen in these products.”

Evidence has been accumulating for years that people who use smokeless tobacco have an increased risk of cancer of the mouth, esophagus and pancreas. Scientists also knew that smokeless tobacco users are exposed to a variety of carcinogens and experience some damage to their genetic material impairing its normal function. But until now, no substance in these products was clearly implicated as a cause of mouth cancer, explained Hecht, who is at the University of Minnesota.

Hecht’s team identified the culprit as (S)-NNN, one of a family of hundreds of compounds called nitrosamines, most of which are carcinogenic, capable of causing cancer. Nitrosamines occur in a variety of foods, ranging from beer to bacon, and also form naturally in the stomach when people eat foods containing high levels of nitrite. But nitrosamine levels in smokeless tobacco are far higher than in food.

To do it, they gave laboratory rats a low dose of two forms of NNN, suspected carcinogens in smokeless tobacco, for 17 months in doses roughly equivalent to a person consuming half of a tin of smokeless tobacco every day for 30 years. One substance, (S)-NNN, induced large numbers of oral and esophageal tumors in the rats.

“The most popular brands of smokeless tobacco that are sold in the U.S. have unacceptably high levels of this particular carcinogen,” explained Hecht. “And smokeless tobacco is a known cause of oral cancer. Obviously, we need to decrease the levels of this material in all smokeless tobacco products — or eliminate it altogether.” Hecht adds that removing (S)-NNN from these products is feasible. In fact, some products on store shelves today have reduced levels of the carcinogen.

Hecht explained that the U.S. Food and Drug Administration has the authority to regulate tobacco products, but no regulations on the levels of specific carcinogens exist yet. “My suggestion is that levels of (S)-NNN in smokeless tobacco be decreased to below 10 parts per billion. That would make it more consistent with the levels of nitrosamines in food products,” he said. (S)-NNN also is in cigarettes and other smoked tobacco items, and he suggested that the substance be regulated in these products, as well

First evidence from humans on how alcohol may boost risk of cancer

PHILADELPHIA, Aug. 22, 2012 — Almost 30 years after discovery of a link between alcohol consumption and certain forms of cancer, scientists are reporting the first evidence from research on people explaining how the popular beverage may be carcinogenic. The results, which have special implications for hundreds of millions of people of Asian descent, were reported here today at the 244^th National Meeting & Exposition of the American Chemical Society.

Silvia Balbo, Ph.D., who led the study, explained that the human body breaks down, or metabolizes, the alcohol in beer, wine and hard liquor. One of the substances formed in that breakdown is acetaldehyde, a substance with a chemical backbone that resembles formaldehyde. Formaldehyde is a known human carcinogen. Scientists also have known from laboratory experiments that acetaldehyde can cause DNA damage, trigger chromosomal abnormalities in cell cultures and act as an animal carcinogen.

“We now have the first evidence from living human volunteers that acetaldehyde formed after alcohol consumption damages DNA dramatically,” Balbo said. She is a research associate in the laboratory of Stephen Hecht, Ph.D., a noted authority on cancer prevention at the University of Minnesota. “Acetaldehyde attaches to DNA in humans ― to the genetic material that makes up genes – in a way that results in the formation of a ‘DNA adduct.’ It’s acetaldehyde that latches onto DNA and interferes with DNA activity in a way linked to an increased risk of cancer.”

Balbo pointed out that people have a highly effective natural repair mechanism for correcting the damage from DNA adducts. Most people thus are unlikely to develop cancer from social drinking, although alcohol is associated with a risk of other health problems and accidents. In addition, most people have an enzyme called alcohol dehydrogenase, which quickly converts acetaldehyde to acetate, a relatively harmless substance.

However, about 30 percent of people of Asian descent ― almost 1.6 billion people ― have a variant of the alcohol dehydrogenase gene and are unable to metabolize alcohol to acetate. That genetic variant results in an elevated risk of esophageal cancer from alcohol drinking. Native Americans and native Alaskans have a deficiency in the production of that same enzyme.

To test the hypothesis that acetaldehyde causes DNA adducts to form in humans, Balbo and colleagues gave 10 volunteers increasing doses of vodka (comparable to one, two and three drinks) once a week for three weeks. They found that levels of a key DNA adduct increased up to 100-fold in the subjects’ oral cells within hours after each dose, then declined about 24 hours later. Adduct levels in blood cells also rose.

“These findings tell us that alcohol, a lifestyle carcinogen, is metabolized into acetaldehyde in the mouth, and acetaldehyde is forming DNA adducts, which are known major players in carcinogenesis,” said Balbo.

With a little training, signs of schizophrenia are averted

Animals that literally have holes in their brains can go on to behave as normal adults if they’ve had the benefit of a little cognitive training in adolescence. That’s according to new work in the August 23 Neuron, a Cell Press publication, featuring an animal model of schizophrenia, where rats with particular neonatal brain injuries develop schizophrenia-like symptoms.

“The brain can be loaded with all sorts of problems,” said André Fenton of New York University. “What this work shows is that experience can overcome those disabilities.”

Fenton’s team made the discovery completely by accident. His team was interested in what Fenton considers a core problem in schizophrenia: the inability to sift through confusing or conflicting information and focus on what’s relevant.

“As you walk through the world, you might be focused on a phone conversation, but there are also kids in the park and cars and other distractions,” he explained. “These information streams are all competing for our brain to process them. That’s a really challenging situation for someone with schizophrenia.”

Fenton and his colleagues developed a laboratory test of cognitive control needed for that kind of focus. In the test, rats had to learn to avoid a foot shock while they were presented with conflicting information. Normal rats can manage that task quickly. Rats with brain lesions can also manage this task, but only up until they become young adults—the equivalent of an 18- or 20-year-old person—when signs of schizophrenia typically set in.

While that was good to see, Fenton says, it wasn’t really all that surprising. But then some unexpected circumstances in the lab led them to test animals with adolescent experience in the cognitive control test again, once they had grown into adults.

These rats should have shown cognitive control deficits, similar to those that had not received prior cognitive training, or so the researchers thought. Instead, they were just fine. Their schizophrenic symptoms had somehow been averted.

Fenton believes their early training for focus forged some critical neural connections, allowing the animals to compensate for the injury still present in their brains in adulthood. Not only were the animals’ behaviors normalized with training, but the patterns of activity in their brains were also.

The finding is consistent with the notion that mental disorders are the consequence of problems in brain development that might have gotten started years before. They raise the optimistic hope that the right kinds of experiences at the right time could change the future by enabling people to better manage their diseases and better function in society. Adolescence, when the brain undergoes significant change and maturation, might be a prime time for such training.

“You may have a damaged brain, but the consequences of that damage might be overcome without changing the damage itself,” Fenton says. “You could target schizophrenia, but other disorders aren’t very different,” take autism or depression, for example.

And really, in this world of infinite distraction, couldn’t we all use a little more cognitive control?

Many medications for elderly are prescribed inappropriately

Approximately one in five prescriptions to elderly people is inappropriate, according to a study published Aug. 22 in the open access journal PLOS ONE.

The authors of the study, led by Dedan Opondo of the Academic Medical Center in Amsterdam, conducted a systematic review of English-language studies of medication use in the elderly and found that the median rate of inappropriate prescriptions was 20.5%. Some of the medications with the highest rates of inappropriate use were the antihistamine diphenhydramine, the antidepressant amitriptyline, and the pain reliever propoxyphene

Potency of statins linked to muscle side effects

A study from the University of California, San Diego School of Medicine, published August 22 online by PLoS ONE, reports that muscle problems reported by patients taking statins were related to the strength or potency of the given cholesterol-lowering drugs.

Adverse effects such as muscle pain and weakness, reported to the U.S. Food and Drug Administration (FDA) were related to a statin’s potency, or the degree by which it typically lowers cholesterol at commonly prescribed doses.

“These findings underscore that stronger statins bear higher risk – and should be used with greater caution and circumspection,” said investigator Beatrice Golomb, MD, PhD, professor in the Departments of Medicine and Family and Preventive Medicine at the University of California, San Diego.

Golomb teamed up with researchers from California-based AdverseEvents, Inc., using the company’s software platform to conduct a detailed examination of statin side-effect data from the FDA’s Adverse Event Reporting System (AERS). The study analyzed muscle-related adverse events linked to each of the major statin drugs in total of 147,789 AERS reports, gathered between July 2005 and March 2011.

Looking at the most commonly used statins – both brand names and, when available, generic forms of the drugs – rosuvastatin, the strongest statin, had the highest rates of reported problems. This was followed by atorvastatin, simvastatin, pravastatin, and lovastatin.

“These rankings closely match the individual potencies of each statin. Thus, the strength of the statin drug appears to be a dominant factor in determining how likely muscle problems are to occur,” said Golomb, who directs the Statin Adverse Effects Study at UC San Diego.

Rates were determined for each statin by tallying reports of muscle side effects, standardized to the number of prescriptions filled for that drug. This was done for individual muscle side effects, as well as for side effects overall.

Some experts have maintained that rosuvastatin, the strongest statin, should have superior safety, because it is less fat soluble, and was thereby assumed not to penetrate into muscle cells as much as other statins. In addition, rosuvastatin is not cleared by common drug-clearance pathways that are sometimes involved in adverse drug interactions.

“The FDA AERS data analyzed in this study, however, suggests that the higher potency of rosuvastatin may more than offset any safety advantages due to such factors,” Golomb said. She added that pooled analysis of statin studies in patients with stable heart disease do not indicate that higher strength statins result in a lower death rate. Therefore, “evidence showing that stronger statins may pose a greater risk of side effects is particularly important.”

“Post-marketed studies utilizing AERS data are becoming increasingly important to understand the lasting side effect risks of widely used medications in disparate populations. Until recently, conducting such studies has been difficult due to the fractured and inaccessible nature of the FDA’s raw data,” said Brian Overstreet, CEO of AdverseEvents. The study utilized the company’s unique data sourcing method called RxFilter™, which analyzed more than 140,000 AERS case reports filed with FDA over a six-year time period.

Statins are among the most widely taken prescription medications in the world, with over 30 million users in the United States alone and $19 billion in domestic sales. They are prescribed to lower cholesterol, and reduce the risk of cardiovascular disease. Their use has been linked to a variety of muscle-related side effects (together termed “statin myopathy”) that occur in as many as 10 to 15 percent of all statin users. These include commonly reported problems such as pain and weakness, as well as life-threatening muscle breakdown, known as rhabdomyolysis. Statin myopathies can significantly increase pain and injury risk and affect mobility, especially in older individuals.

“Only a fraction of adverse effects are reported to the FDA, and a range of factors can influence reporting rates and accuracy of this information,” Golomb said. “However, findings from this study align with – and extend— other forms of evidence.”

For instance, an earlier study from Golomb’s group at UC San Diego showed that patients with muscle problems related to statins often found relief from symptoms after stopping one statin. However, muscle pain or weakness consistently redeveloped if the patient was then placed on a higher potency statin, while patients placed on a lower potency statin had significantly lower risk of recurrence.

“Our findings suggest that individual statin potency is a critical determinant of how likely a statin is to cause problems,” Golomb concluded. “This information should help guide prescribing decisions for statins by offering more information on the risk-benefit profile of the class. It should also be important for guiding decisions about statin selection and use after a patient has experienced a muscle-related adverse event.”

Menopause evolved to prevent competition between in-laws

The menopause evolved, in part, to prevent competition between a mother and her new daughter-in-law, according to research published today (23 August 2012) in the journal Ecology Letters.

The study – by researchers from the University of Turku (Finland), University of Exeter (UK), University of Sheffield (UK) and Stanford University (US) – explains for the first time why the relationship women had with their daughter-in-laws could have played a key role.

The data showed that a grandmother having a baby later in life, and at the same time as her daughter-in-law, resulted in the newborns of each being 50 per cent less likely to survive to adulthood.

The analysis helps to solve one of nature’s great mysteries: why female humans, unlike most other animals, stop reproducing so early in life.

It also adds weight to the theory that the menopause evolved to allow women to focus on their grandchildren. Traditionally, this role included providing food for the family and protecting young children from accidents and disease.

The topic has rarely been analysed, because it requires detailed data on the reproductive success of several generations of women, with knowledge on who lived with whom and when. Scientists analysed 200-years’ worth of data collected by Dr Virpi Lummaa of the University of Sheffield and her student Mirkka Lahdenperä of Turku University, Finland, from church registers of pre-industrial Finland. They looked at information on birth and death rates from 1700 to 1900, before the advent of modern contraception or healthcare.

The study reveals that women had more grandchildren if they stopped reproducing around the age of 50. The research team believes this was partly because of reduced competition between the older woman and her daughter-in-law and partly because of the support she could offer her grandchildren.

A child born to families with a mother-in-law and daughter-in-law reproducing simultaneously was twice as likely to die before reaching the age of 15. However, this was not the case in the instances when a mother and daughter had babies at the same time. This suggests that related women breed cooperatively and unrelated women breed conflictually.

There is a clear biological benefit to a woman cooperating with her daughter: the women share 50 per cent of the same genes so being in competition for food and other resources makes little sense. This is not the case for a mother-in-law and daughter-in-law: they are not related, so it is logical they should compete to maximise on their chances of spreading their genes.

Consequently, the Finnish data shows that the average woman would benefit from stopping reproducing at the age of 51 if she risked breeding with her daughter-in-law, but not her daughter.

Different theories have been put forward for the evolution of the menopause in humans, including the idea that it evolved to protect older women against the danger of dying during pregnancy or childbirth. However, under two per cent of the pre-industrial Finns in this study died in childbirth in their mid-40s, and such risks of dying in childbirth are similarly low in hunter-gatherers today.

Co-author Dr Andy Russell from the University of Exeter’s Centre for Ecology and Conservation said: “We are so used to the fact that all women will experience menopause, that we forget it is seriously bizarre. Evolutionary theory expects animals to reproduce throughout their lifespan, and this is exactly what happens in almost every animal known, including human men. So why are women so different? Our study shows for the first time that the answer could lie in the relationship between a mother-in-law and daughter-in-law.”

Dr Virpi Lummaa, from the University of Sheffield’s Department of Animal and Plant Sciences, said: “The research adds weight to the argument that menopause evolved because of the vital role that grandmothers played in rearing grandchildren in traditional societies. Although family roles have changed, many grandmothers still play a vital role in caring for their grandchildren and in western society a large number provide daycare. It is interesting that even today, mothers rarely choose to have children at the same time as their offspring: even if they have not yet been through the menopause.”

Green tea compound shows promise for tackling cancer

A compound found in green tea could be a weapon in treatments for tackling cancer, according to newly-published research at the University of Strathclyde in Glasgow, Scotland.

The extract, known as epigallocatechin gallate, has been known to have preventative anti-cancer properties but fails to reach tumours when delivered by conventional intravenous administration.

However, in initial laboratory tests at the Universities of Strathclyde and Glasgow, researchers used an approach which allowed the treatment to be delivered specifically to the tumours after intravenous administration. Nearly two-thirds of the tumours it was delivered to either shrank or disappeared within one month and the treatment displayed no side effects to normal tissues.

The tests are thought to be the first time that this type of treatment has made cancerous tumours shrink or vanish.

In the tests, on two different types of skin cancer, 40% of both types of tumour vanished, while 30% of one and 20% of another shrank. A further 10% of one of the types were stabilised.

The researchers encapsulated the green tea extract in vesicles that also carried transferrin, a plasma protein which transports iron through the blood. Receptors for transferrin are found in large amounts in many cancers.

Dr Christine Dufès, a senior lecturer at the Strathclyde Institute of Pharmacy and Biomedical Sciences, led the research. She said: “These are very encouraging results which we hope could pave the way for new and effective cancer treatments.

“When we used our method, the green tea extract reduced the size of many of the tumours every day, in some cases removing them altogether. By contrast, the extract had no effect at all when it was delivered by other means, as every one of these tumours continued to grow.

“This research could open doors to new treatments for what is still one of the biggest killer diseases in many countries.”

The research paper has been published in the journal Nanomedicine. Imaging equipment used in the research was funded by a grant from the Wellcome Trust.

Thinking about kids? Men need to shed the kilos

22 Aug 2012

Melbourne scientists studying the impact obesity has on pregnancy, are urging men to get ‘match fit’ before conceiving to assist with fetal development.

Reproductive experts from the University of Melbourne’s Department of Zoology have discovered that a father’s obesity negatively impacts sperm, resulting in smaller fetuses, poor pregnancy success and reduced placental development. 



While the health risks surrounding obesity and pregnancy have largely been centred on overweight mothers, scientists from the University of Melbourne are putting the onus on men to shape up.



Word Health Organisation figures showing 75 per cent of Australian adult males are overweight or obese, greatly exceeding the global average rate of 48 per cent.



The findings will be presented at the Annual Scientific Meeting of the Endocrine Society of Australia and the Society for Reproductive Biology 2012, starting from August 26-29 on the Gold Coast.



The research was conducted by Professor David Gardner, Dr Natalie Hannan and PhD student Natalie Binder.

“Australia has a weight problem; the rate of obesity among men of reproductive age has more than tripled in the last three decades,” Professor Gardner said.

“A lot of men don’t understand what contribution they’re having, but they need to be healthy before conceiving. Sperm needs to be match fit for the games of life and creating life is the biggest thing that we can do.”



The study used in vitro fertilisation (IVF) on animals to determine the effects of paternal obesity on embryo implantation into the womb and fetal development.

PhD candidate Natalie Binder generated embryos from both normal weight and obese male mice – the latter had been fed the equivalent of a western fast food diet for ten weeks.



“We found that development was delayed in the fetuses produced from obese fathers. The rate of embryo implantation into the womb and fetal development decreased in these animals by up to 15 per cent,” she said.

“Furthermore, placental weight and development was significantly less for embryos derived from the sperm of obese males.

“These findings indicate that paternal obesity not only negatively affects embryo development, but also impacts on the successful implantation into the womb.

“This then results in a small placenta which impairs fetal growth and development with long term consequences for the health of the offspring.

“Our study provides more information about the impact of obesity in men and their ability to start a family and the need to shed kilos in preparation to conceive.”

How does body temperature reset the biological clock?

Researchers from the UNIGE, Switzerland, uncover the molecular cogs of clock genes responsive to temperature variations

Numerous processes in our body fluctuate in a regular pattern during the day. These circadian (or daily) variations can be driven by local oscillators present within our cells or by systemic signals controlled by the master pacemaker, located in the brain. Ueli Schibler, profes- sor at the University of Geneva (UNIGE), Switzerland, unveils a mo- lecular mechanism by which body temperature rhythms influence the expression of ‘clock genes’ and synchronize local oscillators. This study, made in collaboration with a team at the Ecole polytechnique fédérale of Lausanne (EPFL), also demonstrates how the production of DBP, a protein involved in detoxification and drug metabolism, is modulated by daily variations of temperature. This research has been published in Science magazine.

Many of our physiological functions, such as heart beat frequency, hormone secretion or body temperature, are regulated by internal clocks. Most of our body’s cells possess one of them, formed by a group of ‘clock genes’ displaying a cyclic activity that peaks every twenty-four hours. These local oscillators are synchronized by a central pacemaker, located in the brain which adapts to geophysical time by light-dark cycles.

The master clock also controls coordination signals that are sent to subsidiary oscillators. ‘Body temperature variations constitute one of these daily resetting cues, but we did not know how it functioned’, explains Ueli Schibler, professor at the Department of Molecular Biology of the UNIGE. To address this issue, the researcher’s team has developed a system allowing to expose cells to simulated body temperatures cycles.

A genetic engineering technique to probe living cells

‘We have discovered that temperature cycles modulate the rhythmic expression of a protein called CIRP, and that this molecule is required for a robust activation of clock genes on a daily basis’, says Jörg Morf, researcher at the NCCR Frontiers in Genetics and first author of the article. In contrast to most regulatory proteins, which control the expression of genes by binding them directly, CIRP acts downstream, by adhering to gene transcripts, the RNAs.

In collaboration with Felix Naef’s group at the EPFL, the researchers have then identified virtually all CIRP’s target RNAs in living cells, using an ultra sophisticated genetic engineering technique they developed. This achievement allowed probing the transcriptome, that is RNAs from all genes transcribed at a given time. ‘CIRP binds transcripts encoding different circadian oscillator proteins in the cell, which increases their stability and allows them to accumulate’, comments Ueli Schibler. The sensitivity of their experiments has even enabled the team to localize and count each RNA molecule of a targeted circadian gene named Clock.

Effect on detoxification and drug metabolism

This system functions a bit like that of a clockwork: temperature variations induce a rhythmic production of CIRP, which in turn reinforces cyclic activation of circadian oscillator genes. In humans, the difference of 1°C in body temperature observed between the morning and the evening takes on new significance. ‘We have recently demonstrated that such a small fluctuation was sufficient to synchronize cellu- lar oscillators’, reports the biologist.

One of these biochemical cogs controlled by CIRP induces cyclic accumulation of DBP, a protein involved in detoxification and drug metabolism. ‘Certain antitumor drugs administered to sick mice in the morning lead to a 100% mortality, while the rodents receiving the same dose in the evening all survive. This shows how much internal clocks can influence the efficacy and toxicity of drugs’, notes Ueli Schibler.