Health Technology Research Synopsis

117th Issue Date 02DEC2011

Compiled By Ralph Turchiano

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Editors Top Five:

In This Issue:

1. NOW EU SAYS BOTTLED WATER CAN KEEP YOU COOL (BUT IT DOESN’T PREVENT DEHYDRATION)
2. HUSKIES LEND INSIGHT INTO MERCURY RISK
3. TUNING OUT: HOW BRAINS BENEFIT FROM MEDITATION
4. TREATMENT OF ACNE USING ORAL ANTIBIOTICS ASSOCIATED WITH REPORTING SYMPTOMS OF SORE THROAT
5. IBD PATIENTS FACE INCREASED SKIN CANCER RISK
6. HYDROGEN PEROXIDE PROVIDES CLUES TO IMMUNITY, WOUND HEALING AND TUMOR BIOLOGY
7. HOPE FOR MUSCLE WASTING DISEASE
8. COFFEE MAY PROTECT AGAINST ENDOMETRIAL CANCER
9. CONSUMING CANNED SOUP LINKED TO GREATLY ELEVATED LEVELS OF THE CHEMICAL BPA
10. MCMASTER STUDY CALLS SODIUM INTAKE GUIDELINES INTO QUESTION
11. BABIES WHO EAT FISH BEFORE 9 MONTHS ARE LESS LIKELY TO SUFFER PRE-SCHOOL WHEEZE
12. BAT PLANT COULD GIVE SOME CANCERS A DEVIL OF A TIME
13. ARGININE RESTORES T-CELL ABILITY TO TARGET CANCER
14. INCIDENCES AND SEVERITY OF PROSTATE CANCER CORRELATED WITH MEAT CONSUMPTION
15. CLOSER TO A CURE FOR ECZEMA
16. RESEARCHERS SURPRISED TO FIND FATTY LIVER DISEASE POSES NO EXCESS RISK FOR DEATH
17. REPORT: HERBICIDE SPURS REPRODUCTIVE PROBLEMS IN MANY ANIMALS
18. NTU-LED RESEARCH PROBES POTENTIAL LINK BETWEEN CANCER AND A COMMON CHEMICAL IN CONSUMER PRODUCTS
19. EATING FISH REDUCES RISK OF ALZHEIMER’S DISEASE
20. SCIENTISTS DISCOVER ANTI-INFLAMMATORY POLYPHENOLS IN APPLE PEELS
21. PROBIOTICS REDUCE INFECTIONS FOR PATIENTS IN INTENSIVE CARE
22. FOOD SERVED IN CHILDREN’S HOSPITALS RATED LARGELY UNHEALTHY
23. 2 OUT OF 3 MEDICAL STUDENTS DO NOT KNOW WHEN TO WASH THEIR HANDS
24. GREEN TEA FLAVONOID MAY PREVENT REINFECTION WITH HEPATITIS C VIRUS FOLLOWING LIVER TRANSPLANTATION
25. “Just Chill?” Relaxing Can Make You Fatter
26. LOWER ANTIOXIDANT LEVEL MIGHT EXPLAIN HIGHER SKIN-CANCER RATE IN MALES
27. A NATURAL DYE OBTAINED FROM LICHENS MAY COMBAT ALZHEIMER’S DISEASE

Now EU says bottled water can keep you cool (but it doesn’t prevent dehydration)

• UKIP MEP Paul Nuttall: ‘I had to read this four or five times before I believed it. This makes the bendy banana law look positively sane’

It may not come as a surprise to many but bottled water can keep you cool and healthy.

But it was only today that European authorities made the ruling, which should allow companies to make such claims on their products.

It follows a bizarre ruling by the European Commission last week that drinking water does not ease dehydration.

The controversial decision – after three years of discussion – led to much head-scratching at advertising companies.

Now the European Food Standards Authority have added to the general confusion by approving two claims that bottled water can help keep you both cool and healthy.

The EFSA said there was enough evidence to prove water can regulate the body’s temperature and help it carry out normal ‘physical and cognitive functions.’

It is expected that the European Commission will allow companies to make both claims on packaging in the future.

What they cannot do is say that it is prevents dehydration – and they face a possible two year jail sentence if they do so.

This decision results from an attempt by two German academics to test EU advertising rules which set down when companies can claim their products reduce the risk of disease.

The academics asked for a ruling on a convoluted statement which, in short, claimed that water could reduce dehydration.

Dehydration is defined as a shortage of water in the body – but the European Food Standards Authority decided the statement could not be allowed.

The ruling, announced after a conference of 21 EU-appointed scientists in Parma and which means that bottled water companies cannot claim their product stops people’s bodies drying out, was given final approval last week by European Commission President Jose Manuel Barroso.

In response Tory MEP Roger Helmer, said: ‘This is stupidity writ large. The euro is burning, the EU is falling apart and yet here they are worrying about the obvious qualities of water. If ever there were an episode which demonstrates the folly of the great European project, then this is it.’

Under British law, advertisers who make health claims that breach EU law can be prosecuted and face two years in jail.

The decision was being hailed as the daftest Brussels edict since the EU sent down laws on how bendy bananas should be.

UKIP MEP Paul Nuttall said: ‘I had to read this four or five times before I believed it.

‘It is a perfect example of what Brussels does best. Spend three years, with 20 separate pieces of correspondence before summoning 21 professors to Parma, where they decide with great solemnity that drinking water cannot be sold as a way to combat dehydration.’

He added: ‘Then they make this judgment law and make it clear that if anybody dares sell water claiming that it is effective against dehydration they could get into serious legal bother.

‘This makes the bendy banana law look positively sane.’

The statement on which the eminent EU experts ruled claimed that ‘regular consumption of significant amounts of water can reduce the risk of development of dehydration and of concomitant decrease of performance.’

This is stupidity writ large. The euro is burning, the EU is falling apart and yet here they are worrying about the obvious qualities of water. If ever there were an episode which demonstrates the folly of the great European project, then this is it. – TORY MP ROGER HELMER

However the Parma gathering ruled: ‘The panel considers that the proposed claim does not comply with the requirements for a disease risk reduction claim.’

It declared that shortage of water in the body was just a symptom of dehydration.

Dr Andreas Hahn and Dr Moritz Hagenmeyer of the Institute for Food Science and Human Nutrition at Hanover Leibniz University said they were unhappy but not surprised.

‘We fear there is something wrong in the state of Europe,’ Professor Hahn said.

He added that the academics had been trying to test the working of EU food and advertising rules.

‘It was free of charge, there was no apparent red tape attached and it gave food business operators, whom we regularly advise, a chance to advertise their products in a new way,’ he added. ‘We thought we should give it a try and see what would happen.

‘But over almost four years, it became clear that the procedure was anything but straightforward. Any company depending on the claim would long have gone out of business. What is our reaction to the outcome? Let us put it this way: We are neither surprised nor delighted.’

He said: ‘The European Commission is wrong; it should have authorised the claim. That should be more than clear to anyone who has consumed water in the past, and who has not?’

Public release date: 20-Nov-2011

Researchers have highlighted the serious health risks associated with the diets of indigenous people by linking the accumulation of mercury in their primary food source to a decrease in the power of antioxidants.

Published today, 21 November, in IOP Publishing’s journal Environmental Research Letters, the study used Alaskan huskies to demonstrate the risk posed by contaminants, such as mercury, in the subsistence diets that both indigenous people and huskies live on.

Huskies are an ideal model for humans as they are exposed to the same environmental hazards and have already been proven as an effective indicator of human ageing, immune function, toxicology and cognitive disorders.

Data taken from the huskies maintained on a diet of black bear, moose, pike and salmon showed an inverse correlation between mercury exposure and antioxidant status: as the mercury exposure increased, the antioxidant status of the huskies decreased.

Antioxidants – substances that play a critical role in protecting cells – stop electrons being ripped from other molecules. If antioxidants are not functioning properly, electron removal, also known as oxidation, can trigger chain reactions leading to cell damage and eventually cell death.

This damage, also known as oxidative stress, is thought to contribute to the development of a wide range of diseases including Alzheimer’s, Parkinson’s, diabetes and motor neuron disease. As such, antioxidants are widely used ingredients in a large number of dietary supplements, and have been investigated in the prevention of cancer and cardiovascular disease.

People in rural Alaskan communities live a subsistence lifestyle firstly to survive, and also to uphold traditional, cultural and spiritual values; however, they are becoming increasingly concerned with the health implications from foods such as pike and other fish due to the vast array of pollutants, such as mercury, making their way into the ecosystem. The main sources of mercury injection into the ecosystem are coal-generated power plants.

The researchers, from the University of Alaska Fairbanks, analysed groups of 12 huskies in four villages along the Yukon River and in a reference kennel. The huskies were typical racing dogs with similar lineage, sex and age and in their peak racing years. The huskies kept in the reference kennel were fed on a balanced, commercial diet.

After two months of feeding the huskies on the subsistence diets, blood samples were taken to determine their antioxidant power whilst hair samples were taken to determine total mercury concentrations in their body.

The lead author of the study, Professor Kriya Dunlap, said: “The amounts of mercury in the salmon are well below Environmental Protection Agency limits and the health benefits compared to processed food are still quite significant; however, the fact that health indices may be impaired by mercury levels indicates that monitoring should continue and that mercury generation should be monitored.”

Experienced meditators seem to be able switch off areas of the brain associated with daydreaming as well as psychiatric disorders such as autism and schizophrenia, according to a new brain imaging study by Yale researchers.

Meditation’s ability to help people stay focused on the moment has been associated with increased happiness levels, said Judson A. Brewer, assistant professor of psychiatry and lead author of the study published the week of Nov. 21 in the Proceedings of the National Academy of Sciences. Understanding how meditation works will aid investigation into a host of diseases, he said.

“Meditation has been shown to help in variety of health problems, such as helping people quit smoking, cope with cancer, and even prevent psoriasis,” Brewer said.

The Yale team conducted functional magnetic resonance imaging scans on both experienced and novice meditators as they practiced three different meditation techniques.

They found that experienced meditators had decreased activity in areas of the brain called the default mode network, which has been implicated in lapses of attention and disorders such as anxiety, attention deficit and hyperactivity disorder, and even the buildup of beta amyloid plaques in Alzheimer’s disease. The decrease in activity in this network, consisting of the medial prefrontal and posterior cingulate cortex, was seen in experienced meditators regardless of the type of meditation they were doing.

The scans also showed that when the default mode network was active, brain regions associated with self-monitoring and cognitive control were co-activated in experienced meditators but not novices. This may indicate that meditators are constantly monitoring and suppressing the emergence of “me” thoughts, or mind-wandering. In pathological forms, these states are associated with diseases such as autism and schizophrenia.

The meditators did this both during meditation, and also when just resting — not being told to do anything in particular. This may indicate that meditators have developed a “new” default mode in which there is more present-centered awareness, and less “self”-centered, say the researchers.

“Meditation’s ability to help people stay in the moment has been part of philosophical and contemplative practices for thousands of years,” Brewer said. “Conversely, the hallmarks of many forms of mental illness is a preoccupation with one’s own thoughts, a condition meditation seems to affect. This gives us some nice cues as to the neural mechanisms of how it might be working clinically.”

Public release date: 21-Nov-2011

CHICAGO – Taking oral antibiotics for treatment of acne appears to be associated with reporting symptoms of pharyngitis (sore throat), according to a report published Online First by Archives of Dermatology, one of the JAMA/Archives journals.

“Many inconsistent concerns have been voiced about the safety of long-term use of antibiotics,” the authors write as background information in the study. “Because of the high prevalence of acne and the frequent use of antibiotics to control acne, individuals undergoing therapy to treat their acne are an ideal group in which to study the effects of long-term antibiotic use.”

David J. Margolis, M.D., Ph.D., and colleagues with the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, conducted two concurrent studies (a cross-sectional study and a longitudinal study) to examine the association between antibiotics used to treat acne and pharyngitis. The authors also examined the association between oral antibiotics and colonization rates of group A streptococcus (GAS; form bacteria responsible for most cases of streptococcal illness) as previous research has shown a link between oral antibiotics and higher rates of GAS. Participants in both studies included college students, who were asked to fill out a self-administered survey form, were swabbed for culture and had a visual examination for acne.

In the cross-sectional study, the authors found that 10 of 15 students receiving oral antibiotics for acne reported an episode of pharyngitis in the past 30 days, and 47 of 130 students not receiving oral antibiotics, but who had acne, reported an episode of pharyngitis in the previous month. Combining all 251 students not receiving oral antibiotics, 82 (32.7 percent) reported an episode of pharyngitis in the previous 30 days. Three of 145 students with acne (2.1 percent) were found to be colonized with GAS, however none of the three was receiving oral antibiotics.

The longitudinal study included 358 female and 218 male participants; 36 (6.2 percent) received oral antibiotics for acne during the study and 96 (16.6 percent) received topical antibiotics for acne. The authors found that the use of oral antibiotics was strongly associated with a health care evaluation for pharyngitis. Of students receiving oral antibiotic treatment, 11.3 percent reported pharyngitis. Conversely, pharyngitis was reported by 3.3 percent of students not receiving oral antibiotics. Additionally, no association with pharyngitis was noted for those who used a topical antibiotic for acne, and the authors found that less than 1 percent of participants were colonized by GAS, indicating that it is not associated with pharyngitis.

“Our studies show that the odds of developing self-reported pharyngitis is more than three times baseline in patients receiving oral antibiotics for acne vs. the odds for those who are not receiving oral antibiotics,” the authors conclude. “The true clinical importance of these findings needs to be evaluated further by prospective studies.”

Public release date: 21-Nov-2011

Certain patients with inflammatory bowel disease (IBD) may have an increased risk of skin cancer, which is intensified by the use of immunosuppressant medications , according to two new studies in Gastroenterology, the official journal of the American Gastroenterological Association. Immunosuppressants are commonly used in the treatment of IBD.

In the first study, researchers found that both past and present exposure to thiopurines (a widely used class of immunosuppressants) significantly increased the risk of nonmelanoma skin cancer (NMSC) in patients with IBD, even before the age of 50. Currently, there are no specific recommendations for screening for skin cancers in individuals with IBD.

“The increased risk of skin cancer that we found in our study was observed in all patients, even before the age of 50 years. As expected, this risk increased with age. All patients with irritable bowel disease currently receiving or having previously received thiopurines should protect their skin from UV radiation and receive regular dermatologic screening, regardless of their age,” said Laurent Peyrin-Biroulet, MD, PhD, of University Hospital of Nancy, Henri Poincaré University, Vandoeuvre-lès-Nancy, France, and lead author of this study.

NMSC mainly encompasses basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), which are by far the most common cancers diagnosed in North America. NMSC continues to be the most common cancer diagnosed among individuals on immunosuppressive medications; patients with IBD are increasingly treated with these immunosuppressant medications.

In a second study, researchers concluded that certain individuals with IBD, such as men with Crohn’s disease, may have a baseline increased risk of BCC, and the use of thiopurines increases the risk of SCC.

“All individuals should be protecting themselves against skin cancer,” said Harminder Singh, MD, MPH, FRCPC, of the University of Manitoba and lead author of this study. “But, it is especially important that physicians stress the need to be extra vigilant about skin care with their irritable bowel disease patients, especially among those exposed to immunosuppressants such as thiopurines.”

However, Dr. Singh and his colleagues note that the small absolute increased risk of NMSC may not merit stopping thiopurines for those who need them for their IBD disease control.

Public release date: 21-Nov-2011

MADISON – Hydrogen peroxide isn’t just that bottled colorless liquid in the back of the medicine cabinet that’s used occasionally for cleaning scraped knees and cut fingers.

It’s also a natural chemical in the body that rallies at wound sites, jump-starting immune cells into a series of events.

A burst of hydrogen peroxide causes neutrophils, the immune system’s first responders, to rush to the wound to fight microorganisms, remove damaged tissue and then start the inflammation process.

University of Wisconsin-Madison researchers now have discovered the molecular sensor that detects wound-induced hydrogen peroxide and orchestrates the marshaling of neutrophils and other immune cells, or leukocytes, including those that affect tumors.

Published in the Nov. 20, 2011, advanced online version of the journal Nature, the findings have broad implications for cancer biology as well as wound healing and the way the body fights infections.

“Our findings suggest that in the future we might be able to manipulate the new pathway we’ve found to make immune cells go where we want them to,” says lead author Dr. Anna Huttenlocher of the UW School of Medicine and Public Health (SMPH).

A tumor is a type of unhealed wound, says Huttenlocher. Tumors and wounds both generate high levels of hydrogen peroxide, and immune cells responsible for inflammation seek out wounds as well as tumors.

But inflammatory cells can often be detrimental. The cells can contribute to a tumor’s ability to grow and invade other tissue, and they can cause chronic inflammation at wound sites.

“We now speculate that the recruitment of immune cells for wound healing and tumor growth involves a different molecular pathway than recruitment of immune cells for fighting infections,” says Huttenlocher, SMPH professor of pediatrics and of medical microbiology and immunology.

The researchers used transparent zebrafish larvae in a model they have developed to study immunity to watch neutrophils move to wounds in the tails of fish larvae.

They found that hydrogen peroxide modified a protein called Lyn, and that the modification let neutrophils go to wound sites along a specific cellular pathway.

“If we blocked Lyn, it’s possible cells could still get to infection sites, where they could be helpful, but not to wounds or tumors, where they could be harmful,” Huttenlocher says.

The experiments showed clearly that Lyn activation was dependent on hydrogen peroxide after tissue injury, and that blocking Lyn reduced the recruitment of neutrophils to wounds. Lyn is expressed specifically in leukocytes as a sensor for hydrogen peroxide.

Lyn is also a member of a powerful class of proteins known as Src family kinases (SFKs). Many of these kinases have been identified as cellular oncogenes, or precursors to cancer.

“Lyn bridges SFKs and the new pathway we have identified, broadly linking wound healing and immunity to changes in cell behavior in cancer,” says Huttenlocher. “That connection may help move us forward with a better understanding of wound healing and cancer.”

Lyn’s connection to hydrogen peroxide should also elevate the chemical’s status from the back of the medicine cabinet to a position of much greater interest.

22 November 2011

A health supplement used by bodybuilders could be the key to treating a life-threatening muscular dystrophy affecting hundreds of Australian children, new research shows. The amino acid L-tyrosine had a “rapid and dramatic impact” on Nemaline Myopathy (NM) in laboratory tests on mice, significantly improving symptoms of the muscle wasting disease, medical researchers from the University of New South Wales (UNSW) found. Trials showed that consuming L-tyrosine could significantly improve muscle strength and mobility in NM, raising the possibility it also could be effective in a range of other muscular dystrophies. L-tyrosine is readily available in health food shops for less than $30 and is used as a body building supplement and as a memory booster. There is currently no cure for NM (or Rod Myopathy) – the most common congenital muscle wasting disease – which causes muscle weakness of varying severity in an estimated 500 Australian children. Children with NM experience delayed motor development and weakness in the arms and legs, trunk, throat and face muscles. The condition can lead to difficulties breathing and moving and, in its severest form, can cause death. A team of scientists led by Professor Edna Hardeman, from UNSW’s Neuromuscular and Regenerative Medicine Unit, were able to test the efficacy of the supplement after creating – for the first time – a genetically modified mouse which display the same genetic changes found in children with NM. “These mice and have a remarkably similar disease profile to the children, with many of the animals dying young,” Professor Hardeman said. After feeding the mice the L-tyrosine, the team observed improvements in muscle strength, increased mobility and a reduction in a range of muscle pathologies. The findings will now be used as the basis for a clinical trial to test L-tyrosine’s ability to alleviate symptoms in children. “This is the first clear demonstration that L-tyrosine supplements can significantly reduce both the clinical and pathological features of NM,” Professor Hardeman said. “L-tyrosine is readily available, it is easy to administer and our data suggest that long-term use is relatively safe,” Professor Hardeman said. “What’s more, the rapid and dramatic impact of L-tyrosine in NM mice also raises the possibility the supplement may be beneficial for dystrophy patients and other muscle degenerative conditions.” Other team members included Dr Mai-Anh Nguyen and Josephine Joya from UNSW’s School of Medical Sciences. The study was funded by the Australian National Health and Medical Research Council The findings are published online in the journal Brain

Public release date: 22-Nov-2011

PHILADELPHIA — Long-term coffee consumption may be associated with a reduced risk for endometrial cancer, according to a recent study in Cancer Epidemiology, Biomarkers & Prevention, a journal of the American Association for Cancer Research.

Edward Giovannucci, M.D., Sc.D., professor of nutrition and epidemiology at the Harvard School of Public Health, said coffee is emerging as a protective agent in cancers that are linked to obesity, estrogen and insulin.

“Coffee has already been shown to be protective against diabetes due to its effect on insulin,” said Giovannucci, a senior researcher on the study. “So we hypothesized that we’d see a reduction in some cancers as well.”

Giovannucci, along with Youjin Je, a doctoral candidate in his lab, and colleagues observed cumulative coffee intake in relation to endometrial cancer in 67,470 women who enrolled in the Nurses’ Health Study.

During the course of 26 years of follow-up, researchers documented 672 cases of endometrial cancer.

Drinking more than four cups of coffee per day was linked with a 25 percent reduced risk for endometrial cancer. Drinking between two and three cups per day was linked with a 7 percent reduced risk.

A similar link was seen in decaffeinated coffee, where drinking more than two cups per day was linked with a 22 percent reduced risk for endometrial cancer.

Giovannucci said he hopes this study will lead to further inquiries about the effect of coffee on cancer because in this and similar studies, coffee intake is self-selected and not randomized.

“Coffee has long been linked with smoking, and if you drink coffee and smoke, the positive effects of coffee are going to be more than outweighed by the negative effects of smoking,” said Giovannucci. “However, laboratory testing has found that coffee has much more antioxidants than most vegetables and fruits.”

Public release date: 22-Nov-2011

BPA, found in soup can lining, associated with adverse health effects in humans

A new study from researchers at the Harvard School of Public Health (HSPH) has found that a group of volunteers who consumed a serving of canned soup each day for five days had a more than 1,000% increase in urinary bisphenol A (BPA) concentrations compared with when the same individuals consumed fresh soup daily for five days. The study is one of the first to quantify BPA levels in humans after ingestion of canned foods.

The findings were published online November 22, 2011, in the Journal of the Medical Association (JAMA) and will appear in the November 23/30 print issue.

“Previous studies have linked elevated BPA levels with adverse health effects. The next step was to figure out how people are getting exposed to BPA. We’ve known for a while that drinking beverages that have been stored in certain hard plastics can increase the amount of BPA in your body. This study suggests that canned foods may be an even greater concern, especially given their wide use,” said Jenny Carwile, a doctoral student in the Department of Epidemiology at HSPH and lead author of the study.

Exposure to the endocrine-disrupting chemical BPA, used in the lining of metal food and beverage cans, has been shown to interfere with reproductive development in animals and has been linked with cardiovascular disease, diabetes, and obesity in humans. In addition to the lining of food and beverage cans, BPA is also found in polycarbonate bottles (identified by the recycling number 7) and dentistry composites and sealants.

The researchers, led by Carwile and Karin Michels, associate professor in the Department of Epidemiology, set out to quantify whether canned-soup consumption would increase urinary BPA concentrations relative to eating fresh soup.

They recruited student and staff volunteers from HSPH. One group consumed a 12-ounce serving of vegetarian canned soup each day for five days; another group consumed 12 ounces of vegetarian fresh soup (prepared without canned ingredients) daily for five days. After a two-day “washout” period, the groups reversed their assignments.

Urine samples of the 75 volunteers taken during the testing showed that consumption of a serving of canned soup daily was associated with a 1,221% increase in BPA compared to levels in urine collected after consumption of fresh soup.

The researchers note that the elevation in urinary BPA concentrations may be temporary and that further research is needed to quantify its duration.

“The magnitude of the rise in urinary BPA we observed after just one serving of soup was unexpected and may be of concern among individuals who regularly consume foods from cans or drink several canned beverages daily. It may be advisable for manufacturers to consider eliminating BPA from can linings,” said Michels, senior author of the study.

Sodium’s link to cardiovascular disease

Hamilton, ON (Nov. 22, 2011) – For years doctors have warned that too much salt is bad for your heart. Now a new McMaster University study suggests that both high and low levels of salt intake may put people with heart disease or diabetes at increased risk of cardiovascular complications.

The study, published in the Journal of the American Medical Association (JAMA) today, found that moderate salt intake was associated with the lowest risk of cardiovascular events, while a higher intake of sodium was associated with an increased risk of stroke, heart attack and other cardiovascular events and a low intake was associated with an increased risk of cardiovascular death and hospitalization for congestive heart failure.

The research, conducted by investigators in the Michael G. DeGroote School of Medicine at McMaster University and the Population Health Research Institute (PHRI) at McMaster and Hamilton Health Sciences, was co-led by Dr. Martin O’Donnell, an associate clinical professor of medicine, and Dr. Salim Yusuf, a professor of medicine and executive director of the PHRI.

“This research addresses an important population health issue – the association between salt intake and cardiovascular disease,” said O’Donnell, who is also appointed at the Health Research Board Clinical Research Facility, National University of Ireland.

“In general, previous observational studies have either reported a positive association, no association or an inverse association between sodium intake and heart disease and stroke. This has resulted in a lot of controversy. Our study is the first to report a J-shaped association between sodium intake and cardiovascular disease, which may explain why previous studies have found different results.”

For the McMaster observational study, the researchers examined 28,880 people at increased risk of heart disease from clinical trials conducted between 2001 and 2008. The researchers estimated 24-hour urinary sodium and potassium excretion from a morning fasting urine sample. Follow-up found more than 4,500 cardiovascular events occurred, making this one of the largest studies examining the relationship between sodium excretion (a surrogate measure of sodium consumption), as well as potassium excretion and cardiovascular events. Extensive and careful statistical analytic methods were used to determine the association of urinary sodium and potassium with cardiovascular events, in particular heart attack, stroke, hospitalization for congestive heart failure and death.

Compared with moderate sodium excretion (between 4 to 5.99 grams per day), the researchers found that sodium excretion of greater than seven grams per day was associated with an increased risk of all cardiovascular events, and sodium excretion of less than three grams per day was associated with an increased risk of cardiovascular death and hospitalization for congestive heart failure.

The findings call into question current guidelines for salt intake, which recommend less than 2.3 grams (or 2,300 mg) per day. The guidelines are mostly based on previous clinical trials that found blood pressure is lowered modestly when sodium intake is reduced to this level (which was also found in the present study). However, there are no large studies looking at whether such low levels of sodium intake reduce the incidence of heart attacks and stroke.

Clarifying the optimal daily intake of sodium is particularly important in patients with established heart disease, as they may be especially vulnerable to the cardiovascular effects of very high- and low-salt intake and are most likely to receive recommendations on restricting sodium in their diets, the authors concluded.

“Our study confirms the association between high-sodium intake and cardiovascular disease. Our findings highlight the importance of reducing salt intake in those consuming high-salt diets and the need for reducing sodium content in manufactured foods that are high in salt,” said Yusuf, who is also vice-president of research, Hamilton Health Sciences.

“However, for those with moderate (average) intake, whether further reduction of salt in the diet will be beneficial is an open question. We believe that large clinical trials are the most reliable way to determine if reducing sodium intake to lower levels is of benefit.”

Public release date: 22-Nov-2011

But pre-natal paracetamol and first-week antibiotics increase risk

Children who started eating fish before nine months of age are less likely to suffer from pre-school wheeze, but face a higher risk if they were treated with broad spectrum antibiotics in the first week of life or their mother took paracetamol during pregnancy. Those are the key findings from a large-scale Swedish study published in the December issue of Acta Paediatrica.

Researchers analysed responses from 4,171 randomly selected families, who answered questions when their child was six months, 12 months and four-and-a-half years of age.

“Recurrent wheeze is a very common clinical problem in preschool children and there is a need for better medical treatment and improved understanding of the underlying mechanisms” says lead author Dr Emma Goksor from the Queen Silvia Children’s Hospital, University of Gothenburg, Sweden. “The aim of our study was to identify both important risk factors and protective factors for the disease.

“Our demographic analysis suggests that the responses we received were largely representative of the population as a whole and we believe our findings provide useful information on three important factors involved in pre-school wheeze.”

The study examined children who had had three or more episodes of wheezing in the last year, including those who did and did not use asthma medication (inhaled corticosteroid), comparing them with children who did not wheeze. The wheezy sample was further broken down into children who only developed episodic viral wheeze when they had colds and multiple trigger wheeze, where children also wheezed when they didn’t have a cold, reacting to factors such as allergens, tobacco smoke or exercise.

Key findings of the study include:

Overall prevalence

• One in five of the children had at least one episode of wheezing and one in 20 had recurrent wheeze (three or more episodes) over the last year. Of these, three-quarters had used asthma medication and just over half reported doctor-diagnosed asthma.
• More than half of the children with recurrent wheeze had episodic viral wheeze (57%) and 43% had multiple-trigger wheeze.

Fish consumption before nine months of age

• Eating fish before the age of nine months almost halved the likelihood of suffering recurrent wheeze at 4.5 years. The fish most commonly eaten was white fish, followed by salmon and flat fish.
• The authors have previously reported that fish, which is thought to contain properties that reduce allergy risks, is beneficial in both eczema in infancy and allergic rhinitis at pre-school age. Other research has suggested a protective effect on the development of asthma.

Antibiotic treatment in the first week of life

• Being treated with broad-spectrum antibiotics in the first week was associated with double the risk of recurrent wheeze at 4.5 years. Just 3.6% of the children in the no wheeze group had received antibiotics, compared with 10.7% of those who had experienced three or more episodes.
• When this was broken down into subgroups, the risk was even higher in children with multiple-trigger wheeze, while the risk of episodic viral wheeze was not statistically increased.

Use of paracetamol during pregnancy

• Less than a third of the mothers (28.4%) had taken some medication during pregnancy, with 7.7% of the total taking paracetamol and 5.3% only taking paracetamol.
• The prevalence of prenatal paracetamol exposure in the wheeze group using asthma medication was 12.4% and taking paracetamol during pregnancy increased the risk by 60%.
• The effect was particularly noticeable in the multiple-trigger wheeze group, where it more than doubled the risk.

“The aim of this study was to determine the risk factors for pre-school wheeze, with particular reference to prenatal paracetamol use, early exposure to antibiotics and fish consumption. A secondary aim was to analyse possible differences between multiple-trigger wheeze and episodic viral wheeze.

“Our findings clearly show that while fish has a protective effect against developing pre-school wheeze, children who had antibiotics in the first week of life and whose mothers took paracetamol during pregnancy faced an increased risk, particularly of multiple-trigger wheeze.”

Bat plant could give some cancers a devil of a time Posted: Monday, November 21, 2011 Contact: Elizabeth Allen, CTRC, 210-450-2020 SAN ANTONIO (November 21, 2011) – In a new study published this month in the Journal of the American Chemical Society, researchers with The University of Texas Health Science Center at San Antonio have pinpointed the cancer-fighting potential in the bat plant, or Tacca chantrieri. Susan Mooberry, Ph.D., leader of the Experimental Development Therapeutics Program at the Cancer Therapy & Research Center and a professor of pharmacology in the School of Medicine at the UT Health Science Center, has been working to isolate substances in the plant, looking for a plant-derived cancer drug with the potential of Taxol. Taxol, the first microtubule stabilizer derived from the Yew family, has been an effective chemotherapy drug, but patients eventually develop problems with resistance over time and toxicity at higher doses. Researchers have long been seeking alternatives. “We’ve been working with these for years with some good results, but never with the potency of Taxol,” said Dr. Mooberry, lead author of the study. “Now we have that potency, and we also show for the first time the taccalonolides’ cellular binding site.” Microtubules are structures in the cells that act as conveyer belts. They help maintain cell shape and help guide chromosones in cell division to ensure that every new cell, including every new cancer cell, gets a full complement of genetic material. When microtubules are stabilized — essentially held still so they can’t do their jobs — this disrupts numerous cellular processes, and the cell can die. The taccalonolides stabilize microtubules in cancer cells, but they do not attack healthy cells, Dr. Mooberry said. “We’ve run normal prostate cells and normal breast cells through these tests, and they don’t die. The taccalonolides selectively kill cancer cells.” Until now, how they did this was unknown. The isolation of these highly potent taccalonolides for the first time by Dr. Mooberry’s team shows how they interact directly with microtubules.

In many cases, tumors suppress a patient’s immune system in a way that keeps the cancer safe from immune system attack. This is particularly true for patients with glioblastoma, a primary brain tumor that carries a prognosis of only 12-15 months survival after diagnosis.

A study at the University of Colorado Cancer Center, recently published as a featured article in the journal Clinical Cancer Research, shows that treatment with the over-the-counter amino acid arginine may reactivate cancer-fighting T-cells in patients with glioblastoma, thus potentially allowing the immune system to help cleanse the body of cancer.

T-cells are the primary agent responsible for anti-tumor immune responses.

“If you take T-cells from patients with glioblastoma and stimulate them in the lab, they aren’t effective (in killing cancer cells),” says lead author Allen Waziri, MD, investigator at the CU Cancer Center, assistant professor of neurosurgery at the University of Colorado School of Medicine. “But when we add back arginine, we restore T-cell function.”

In part, function is restored through the activity of neutrophils – an ancient and nonspecific type of white blood cell that kills invaders. After responding to inflammation, neutrophils stop the ongoing immune response. It’s as if once they arrive, they consider the infection treated and so suppress any response that exceeds what is needed – a response that if left unchecked would lead to the destruction of healthy tissues.

Neutrophils stop the immune response by secreting an enzyme called arginase. And after they secrete arginase, commonly they die and are excreted by the body. However, in many glioblastoma patients, these neutrophils persist and continue to produce immune-suppressing arginase.

“Persistence of activated neutrophils and increased arginase in the circulation of glioblastoma patients is a fascinating phenomenon, particularly considering that under normal conditions, neutrophils are expected to have an average lifespan of just several hours after activation,” he says.

Waziri’s group has hypothesized that persistent arginase production from neutrophils suppresses the immune system and keeps cancers from becoming immune targets.

“From one perspective, it appears that glioblastoma is taking advantage of a simple, evolutionarily-ancient method for controlling out-of-control immunity to avoid the specific anti-tumor immune response,” Waziri says.

Public release date: 23-Nov-2011

However, there is a step between increased arginase and immune system suppression, and this is where Waziri and colleagues intervene – arginase, in fact, deletes the common amino acid arginine.

T-cells are critically dependent on arginine for activation and function. Therefore, it’s not the increase in arginase per se that is responsible for blunting T-cell activity, but rather the resulting lack of arginine that suppresses the immune systems of glioblastoma patients, Waziri’s group found.

Waziri and colleagues at the CU Cancer Center recently started a phase 0 clinical trial in newly diagnosed glioblastoma patients to explore whether a week-long, high-dose course of arginine before cancer surgery can allow an immune system that previously missed cancer cells to recognize and attack them. Waziri and his team will look at the effect of arginine on patients’ immune systems as measured by T-cell function, immunological profile, and T-cell infiltration into resected tumor tissue.

“Our overall goal is to improve the efficacy of immunotherapy for glioblastoma,” he says. “It’s likely that this will require a two-stage approach, including stimulation of the immune system with something like a tumor vaccine while simultaneously targeting the suppressive effects of tumors on the immune system.”

With positive results from this initial trial, Waziri hopes to further explore whether longer courses of arginine could help reduce the recurrence of glioblastoma and potentially offer a new strategy for patients with this otherwise incurable disease.

Waziri credits seed grants he has received from the AMC Cancer Fund (a fundraising arm of the CU Cancer Center), he Cancer League of Colorado, and an American Cancer Society Institutional Research Grant for contributing to the preclinical work that has led to this exciting clinical trial.

Public release date: 23-Nov-2011

Increased consumption of ground beef or processed meat is positively associated with aggressive prostate cancer, according to a study published Nov. 23 in the online journal PLoS ONE.

The research team, led by John Witte of University of California, San Francisco, also found that the correlation was primarily driven by red meat that was grilled or barbequed, especially when well done.

They suggest that this result, which was determined based on the meat consumption habits of about 1,000 male participants, is due to increased levels of carcinogens in meat prepared these ways. The report furthers previous findings of the correlation between meat consumption and prostate cancer, and may help determine particular compounds that could be targeted for prostate cancer prevention.

Public release date: 23-Nov-2011

Scientists have found that a strain of yeast implicated in inflammatory skin conditions, including eczema, can be killed by certain peptides and could potentially provide a new treatment for these debilitating skin conditions. This research is published today in the Society for Applied Microbiology’s journal, Letters in Applied Microbiology.

20% of children in the UK suffer from atopic eczema and whilst this usually clears up in adolescence, 7% of adults will continue to suffer throughout their lifetime. Furthermore, this type of eczema, characterized by dry, itchy, flaking skin, is increasing in prevalence. Whilst the cause of eczema remains unknown, one known trigger factor is the yeast Malassezia sympodialis.

This strain of yeast is one of the most common skin yeasts in both healthy individuals and those suffering from eczema. The skin barrier is more fragile and often broken in those suffering from such skin conditions, and this allows the yeast to cause infection which then further exacerbates the condition. Scientists at Karolinska Institute in Sweden looked for a way to kill Malassezia sympodialis without harming healthy human cells.

The researchers looked at the effect on the yeast of 21 peptides which had either; cell-penetrating or antimicrobial properties. Cell-penetrating peptides are often investigated as drug delivery vectors and are able to cross the cell membrane, although the exact mechanism for this is unknown. Antimicrobial peptides, on the other hand, are natural antibiotics and kill many different types of microbe including some bacteria, fungi and viruses.

Tina Holm and her colleagues at Stockholm University and Karolinska Institute, added these different peptides types to separate yeast colonies and assessed the toxicity of each peptide type to the yeast. They found that six of the 21 peptides they tested successfully killed the yeast without damaging the membrane of keratinocytes, human skin cells.

Tina commented “Many questions remain to be solved before these peptides can be used in humans. However, the appealing combination of being toxic to the yeast at low concentrations whilst sparing human cells makes them very promising as antifungal agents. We hope that these peptides in the future can be used to ease the symptoms of patients suffering from atopic eczema and significantly increase their quality of life.”

The next step will be to further examine the mechanism(s) used by the peptides to kill yeast cells, in order to develop a potential treatment for eczema and other skin conditions.

Public release date: 23-Nov-2011

Condition prevalent among those with heart disease and obesity

Non-alcoholic fatty liver disease (NAFLD) is a common condition associated with obesity and heart disease long thought to undermine health and longevity. But a new study by Johns Hopkins researchers suggests the condition does not affect survival.

A report on the study was published online last week in BMJ, the British medical journal.

“Physicians have considered fatty liver disease a really worrisome risk factor for cardiovascular disease,” says study leader Mariana Lazo, M.D., Ph.D., a postdoctoral fellow at the Johns Hopkins University School of Medicine’s Welch Center for Prevention, Epidemiology, and Clinical Research. “Our data analysis shows this doesn’t appear to be the case. We were surprised to say the least because we expected to learn by how much non-alcoholic fatty liver disease increased the risk of death and instead found the answer was not at all.”

Using health information collected from 11,371 Americans between 1994 and 1998 and followed for up to 18 years as part of the Third National Health and Nutrition Examination Survey (NHANES III), the researchers checked liver enzyme levels and ultrasound tests for evidence of NAFLD, and ultimately looked at death rates associated with NAFLD. The participants ranged in age from 20 to 74 during the data collection years. Because the ultrasounds were originally taken to assess gallbladder health, Lazo and colleagues from Johns Hopkins looked at each recording to determine the presence of fat in each person’s liver. People whose livers are 5 percent fat or more are considered to have NAFLD.

The Johns Hopkins team found no increase in mortality among those with NAFLD, which was identified in approximately 20 percent of the NHANES participants. At the end of the follow-up period, mortality from all causes was 22 percent, or 1,836 individuals. Cardiovascular disease was the cause of death for 716 participants, cancer for 480 and liver disease for 44.

Although the researchers found no increase in deaths, Lazo says further study is needed to determine whether more advanced NAFLD has serious long-term consequences for the liver, a vital organ that turns what we eat and drink into nutrients and filters harmful substances from the blood.

NAFLD, which some researchers have called the nation’s next epidemic, is characterized by the liver’s inability to break down fats and fatty build up in the organ. Found in roughly one in three Americans, it is most prevalent in those who are obese, and those with diabetes and cardiovascular disease. The spectrum of disease ranges from simple fat build-up to inflammation to the scarring and poor liver function that characterize cirrhosis. Chronic liver disease has long been associated with long-term alcohol consumption, but as the name suggests, NAFLD is found in those who are not heavy drinkers.

“We don’t yet know why mortality is not affected or whether there might be some actual protective effect of non-alcoholic fatty liver disease,” she says, “but it looks like the liver’s ability to accumulate fat may somehow shield the body from the detrimental effects of other health problems such as obesity and diabetes,” she says.

There is no treatment for NAFLD, other than lifestyle changes, including weight loss, and only a liver biopsy can determine how serious NAFLD is. Lazo says she hopes new methods are developed that more easily identify more advanced stages of NAFLD, which may not be harmless.

Still, she says, her research suggests that with respect to long-term survival of people with non-alcoholic fatty liver disease, “it may not matter if you have the disease or not.”

CHAMPAIGN, lll. — An international team of researchers has reviewed the evidence linking exposure to atrazine – an herbicide widely used in the U.S. and more than 60 other nations – to reproductive problems in animals. The team found consistent patterns of reproductive dysfunction in amphibians, fish, reptiles and mammals exposed to the chemical.

University of Illinois professor emeritus of comparative biosciences Val Beasley and his colleagues reviewed the evidence linking atrazine exposure to reproductive problems in amphibians, fish, reptiles and mammals. | Photo by L. Brian Stauffer

Atrazine is the second-most widely used herbicide in the U.S. More than 75 million pounds of it are applied to corn and other crops, and it is the most commonly detected pesticide contaminant of groundwater, surface water and rain in the U.S. The new review, compiled by 22 scientists studying atrazine in North and South America, Europe and Japan, appears in the Journal of Steroid Biochemistry and Molecular Biology. The researchers looked at studies linking atrazine exposure to abnormal androgen (male hormone) levels in fish, amphibians, reptiles and mammals and studies that found a common association between exposure to the herbicide and the “feminization” of male gonads in many animals. The most robust findings are in amphibians, said University of Illinois comparative biosciences professor Val Beasley, a co-author of the review. At least 10 studies found that exposure to atrazine feminizes male frogs, sometimes to the point of sex reversal, he said.

Beasley’s lab was one of the first to find that male frogs exposed to atrazine in the wild were more likely to have both male and female gonadal tissue than frogs living in an atrazine-free environment. And in a 2010 study, Tyrone Hayes, a professor of integrative biology at the University of California at Berkeley and lead author of the review, reported in the Proceedings of the National Academy of Sciences that atrazine exposure in frogs was associated with “genetic males becoming females and functioning as females,” Beasley said. “And this is not at extremely high concentrations,” he said. “These are at concentrations that are found in the environment.” The new review describes the disruptions of hormone function and sexual development reported in studies of mammals, frogs, fish, reptiles and human cells exposed to the herbicide. The studies found that atrazine exposure can change the expression of genes involved in hormone signaling, interfere with metamorphosis, inhibit key enzymes that control estrogen and androgen production, skew the sex ratio of wild and laboratory animals (toward female) and otherwise disrupt the normal reproductive development and functioning of males and females. “One of the things that became clear in writing this paper is that atrazine works through a number of different mechanisms,” Hayes said. “It’s been shown that it increases production of (the stress hormone) cortisol. It’s been shown that it inhibits key enzymes in steroid hormone production while increasing others. It’s been shown that it somehow prevents androgen from binding to its receptor.” The review also consolidates the evidence that atrazine undermines immune function in a variety of animals, in part by increasing cortisol.

“Cortisol is a nonspecific response to chronic stress,” Beasley said. “But guess what? Wildlife in many of today’s habitats are stressed a great deal of the time. They’re stressed because they’re crowded into little remnant habitats. They’re stressed because there’s not enough oxygen in the water because there are not enough plants in the water (another consequence of herbicide use). They’re stressed because of other contaminants in the water. And the long-term release of cortisol causes them to be immuno-suppressed.” There also are studies that show no effects – or different effects – in animals exposed to atrazine, Beasley said. “But the studies are not all the same. There are different species, different times of exposure, different stages of development and different strains within a species.” All in all, he said, the evidence that atrazine harms animals, particularly amphibians and other creatures that encounter it in the water, is compelling. “I hope this will stimulate policymakers to look at the totality of the data and ask very broad questions,” Hayes said. “Do we want this stuff in our environment? Do we want – knowing what we know – our children to drink this stuff? I would think the answer would be ‘no.’ ”

Published on : 29-Nov-2011

A study led by a group of Nanyang Technological University (NTU) researchers has found that a chemical commonly used in consumer products can potentially cause cancer.

The chemical, Zinc Oxide, is used to absorb harmful ultra violet light. But when it is turned into nano-sized particles, they are able to enter human cells and may damage the user’s DNA. This in turn activates a protein called p53, whose duty is to prevent damaged cells from multiplying and becoming cancerous. However, cells that lack p53 or do not produce enough functional p53 may instead develop into cancerous cells when they come into contact with Zinc Oxide nanoparticles.

The study is led by Assistant Professor Joachim Loo, 34, and Assistant Professor Ng Kee Woei, 37, from NTU’s School of Materials Science and Engineering. They worked with Assistant Professor David Leong, 38, from the Department of Chemical and Biomolecular Engineering, National University of Singapore, a joint senior author of this research paper.

The findings suggest that companies may need to reassess the health impact of nano-sized Zinc Oxide particles used in everyday products. More studies are also needed on the use and concentration levels of nanomaterials in consumer products, how often a consumer uses them and in what quantities.

“Currently there is a lack of information about the risks of the nanomaterials used in consumer products and what they can pose to the human body. This study points to the need for further research in this area and we hope to work with the relevant authorities on this,” said Asst Prof Loo.

The groundbreaking research findings were published in this month’s edition of Biomaterials, one of the world’s top journals in the field of biomaterials research. The breakthrough also validated efforts by Asst Prof Loo and Asst Prof Ng to pioneer a research group in the emerging field of nanotoxicology, which is still very much in its infancy throughout the world.

Nanotoxicology studies materials to see if they are toxic or harmful when they are turned into nano-sized particles. This is because nanomaterials usually have very different properties when compared to when the materials are of a larger size.

Asst Prof Ng said the team will carry out further research as the DNA damage brought about by nano-sized Zinc Oxide particles is currently a result of an unknown mechanism. But what is clear is that besides causing DNA damage, nanoparticles can also cause other harmful effects when used in high doses.

“From our studies, we found that nanoparticles can also increase stress levels in cells, cause inflammation or simply kill cells,” said Asst Prof Ng who added that apart from finding out the cellular mechanism, more focused research is also expected to ascertain the physiological effects and damage that nano-sized Zinc Oxide particles can cause.

Asst Prof Loo pointed out that besides enhancing the understanding of the potential risks of using nanomaterials, advancements in nanotoxicology research will also help scientists put nanomaterials to good use in biomedical applications.

For example, although killing cells in our bodies is typically undesirable, this becomes a positive outcome if it can be effectively directed towards cancer cells in the body. At the same time, the team is also studying how nanomaterials can be “re-designed” to pose a lesser risk to humans, yet still possess the desired beneficial properties.

This research discovery is one of the latest in a series of biomedical breakthroughs by NTU in healthcare. Future healthcare is one of NTU’s Five Peaks of Excellence with which the university aims to make its mark globally under the NTU 2015 five-year strategic plan. The other four peaks are sustainable earth, new media, the best of the East and West, and innovation.

Moving forward, the team hopes to work with existing and new collaborative partners, within and outside of Singapore, to orchestrate a more concerted effort towards the advancement of the fledgling field of nanotoxicology here, with the aim of helping regulatory bodies in Singapore formulate guidelines to protect consumer interests.

The research team would also like to work with the European Union to uncover the risks involving nanomaterials and how these materials should be regulated before they are made commercially available. Asst Prof Joachim Loo, who received his Bachelor and Doctorate degrees from NTU, was the only Singaporean representative in a recent nanotechnology workshop held in Europe. At the workshop, it was agreed that research collaborations in nanotoxicology between EU and South-east Asia should be increased.

CHICAGO – People who eat baked or broiled fish on a weekly basis may be improving their brain health and reducing their risk of developing mild cognitive impairment (MCI) and Alzheimer’s disease, according to a study presented today at the annual meeting of the Radiological Society of North America (RSNA).

“This is the first study to establish a direct relationship between fish consumption, brain structure and Alzheimer’s risk,” said Cyrus Raji, M.D., Ph.D., from the University of Pittsburgh Medical Center and the University of Pittsburgh School of Medicine. “The results showed that people who consumed baked or broiled fish at least one time per week had better preservation of gray matter volume on MRI in brain areas at risk for Alzheimer’s disease.”

Alzheimer’s disease is an incurable, progressive brain disease that slowly destroys memory and cognitive skills. According to the National Institute on Aging, as many as 5.1 million Americans may have Alzheimer’s disease. In MCI, memory loss is present but to a lesser extent than in Alzheimer’s disease. People with MCI often go on to develop Alzheimer’s disease.

For the study, 260 cognitively normal individuals were selected from the Cardiovascular Health Study. Information on fish consumption was gathered using the National Cancer Institute Food Frequency Questionnaire. There were 163 patients who consumed fish on a weekly basis, and the majority ate fish one to four times per week. Each patient underwent 3-D volumetric MRI of the brain. Voxel-based morphometry, a brain mapping technique that measures gray matter volume, was used to model the relationship between weekly fish consumption at baseline and brain structure 10 years later. The data were then analyzed to determine if gray matter volume preservation associated with fish consumption reduced risk for Alzheimer’s disease. The study controlled for age, gender, education, race, obesity, physical activity, and the presence or absence of apolipoprotein E4 (ApoE4), a gene that increases the risk of developing Alzheimer’s.

Gray matter volume is crucial to brain health. When it remains higher, brain health is being maintained. Decreases in gray matter volume indicate that brain cells are shrinking.

The findings showed that consumption of baked or broiled fish on a weekly basis was positively associated with gray matter volumes in several areas of the brain. Greater hippocampal, posterior cingulate and orbital frontal cortex volumes in relation to fish consumption reduced the risk for five-year decline to MCI or Alzheimer’s by almost five-fold.

“Consuming baked or broiled fish promotes stronger neurons in the brain’s gray matter by making them larger and healthier,” Dr. Raji said. “This simple lifestyle choice increases the brain’s resistance to Alzheimer’s disease and lowers risk for the disorder.”

The results also demonstrated increased levels of cognition in people who ate baked or broiled fish.

“Working memory, which allows people to focus on tasks and commit information to short-term memory, is one of the most important cognitive domains,” Dr. Raji said. “Working memory is destroyed by Alzheimer’s disease. We found higher levels of working memory in people who ate baked or broiled fish on a weekly basis, even when accounting for other factors, such as education, age, gender and physical activity.”

Eating fried fish, on the other hand, was not shown to increase brain volume or protect against cognitive decline

New research published in the Journal of Leukocyte Biology suggests that oral ingestion of apple polyphenols can suppress T cell activation and ameliorate experimental colitis in mice

Bethesda, MD—Here’s another reason why “an apple a day keeps the doctor away”—according to new research findings published in the Journal of Leukocyte Biology (https://www.jleukbio.org), oral ingestion of apple polyphenols (antioxidants found in apple peels) can suppress T cell activation to prevent colitis in mice. This study is the first to show a role for T cells in polyphenol-mediated protection against an autoimmune disease and could lead to new therapies and treatments for people with disorders related to bowel inflammation, such as ulcerative colitis, Crohn’s disease and colitis-associated colorectal cancer.

“Many people with colitis use some form of dietary supplement to complement conventional therapies, but most of the information on the health effects of complementary medicine remains anecdotal. Also, little is known about exactly how these therapies work, if they work at all,” said David W. Pascual, Ph.D., a researcher involved in the work from the Department of Immunology and Infectious Diseases at Montana State University in Bozeman, Montana. “Our results show that a natural product found in apple peels can suppress colonic inflammation by antagonizing inflammatory T cells to enhance resistance against autoimmune disease.”

To make this discovery, scientists used a chemically induced model of colitis with Dextran sulfate sodium (DSS), researchers administered an oral placebo to one group of mice, and the other group of mice was given an oral dose of apple polyphenols every day during the course of the disease. Results showed that mice treated orally with apple polyphenols were protected from colitis. Importantly, scientists also found that the treated mice had fewer activated T cells in their colons. In mice lacking T cells, apple polyphenols were unable to protect against colitis or suppress proinflammatory cytokine expression, indicating apple polyphenols protect against colitis via the suppression of T cell activation and/or recruitment.

“It appears that the old adage rings true in more ways than one,” said John Wherry, Ph.D., Deputy Editor of the Journal of Leukocyte Biology, “In addition to the obvious health benefits of the nutrients and fiber in fruits and vegetables, this study indicates that even something as relatively common as the apple contains other healthy ingredients that can have serious therapeutic value.”

Traumatic brain injury is associated with a profound suppression of the patient’s ability to fight infection. At the same time the patient also often suffers hyper-inflammation, due to the brain releasing glucocorticoids in response to the injury. New research published in BioMed Central’s open access journal Critical Care shows that including probiotics with nutrients, supplied via the patient’s feeding tube, increased interferon levels, reduced the number of infections, and even reduced the amount of time patients spent in intensive care.

In a small scale trial, based at North Sichuan Medical College and Hospital in China, 52 patients who had suffered traumatic brain injuries, and who were being treated in the intensive care unit (ICU), were either treated as usual or had their nutrition supplemented with probiotics.

Suppression of the immune system can be measured by an alteration of helper T-cells (Th) from Th1, which stimulate the action of macrophages to fight infection, to Th2. Th2 cells recruit B-cells which in turn are involved in antibody production. This switch from Th1 to Th2 leaves patients vulnerable to infections including ventilator-associated pneumonia and sepsis. Researchers involved in this trial monitored the TH1/Th2 switch by measuring levels of the Th1-associated signaling molecules (cytokines) IL-12 and interferon gamma (IFNy).

No differences were found between the groups of patients when they began the trial, and throughout the study all the patients had lower levels of IL-12 and IFN? than uninjured healthy controls. However by day 15 the patients who received the probiotics had significantly higher levels of both IL-12 and IFNy than the control patients. They also showed a decrease in the Th2-associated factors IL-4 and IL-10.

Prof Jing-Ci Zhu, the supervisor of this study from the Third Military Medical University School of Nursing in China, explained, “Probiotic treatment appeared to swing the Th1/Th2 balance back towards normality and, in our study, had beneficial effects. Possibly due to the small size of our study there was no significant difference in the number of infections between the groups (9 for the probiotic group, 16 for the control patients). However probiotic therapy reduced the number of infections occurring after seven days, reduced the number of different antibiotics needed to treat infections, and shortened the length of time the patients were required to stay in ICU.”

Given the obesity epidemic among the nation’s young, one might hope that children’s hospitals would serve as a role model for healthy eating. But hospitals in California fall short, with only 7 percent of entrees classified as “healthy,” according to a new study published in the journal Academic Pediatrics.

Researchers from UCLA and the RAND Corp. assessed 16 food venues at the state’s 14 major children’s hospitals and found much room for improvement in their offerings and practices.

“As health professionals, we understand the connection between healthy eating and good health, and our hospitals should be role models in this regard,” said Dr. Lenard Lesser, the primary investigator on the study and a physician in the Robert Wood Johnson Foundation Clinical Scholars Program in the department of family medicine at the David Geffen School of Medicine at UCLA. “Unfortunately, the food in many hospitals is no better — and in some cases worse — than what you would find in a fast food restaurant.”

The study authors developed a modified version of the Nutrition Environment Measures Study for restaurants (NEMS-R) as an assessment tool for rating the food offerings in hospital cafeterias. This measurement system takes into account pricing, the availability of vegetables, nutrition labeling, combination promotions and healthy beverages.

Overall, the average score for the 16 hospital food venues was 19.1 — on a scale of 0 (least healthy) to 37 (most healthy). Of the total 384 entrees and sandwiches the hospitals served, only 7 percent were classified as healthy according to the NEMS-R criteria. And while nearly all the hospitals offered healthy alternatives such as fruit, less than one-third had nutritional information at the point of sale or signs to promote healthy eating.

Other key findings included:

• All 16 food venues offered low-fat or skim milk and diet soda.
• 81 percent offered high-calorie, high-sugar items such as cookies and ice cream near the cash register.
• 25 percent sold whole wheat bread.
• Half the hospitals did not provide any indication that they carried healthy entrees.
• 44 percent did not have low-calorie salad dressings.

Since no one had previously documented the health of food in these hospitals, researchers provided hospital administrators with their scores to encourage improvement. Since the study was conducted, in July 2010, some of the hospitals surveyed have taken steps to improve their fare and/or reduce unhealthy offerings. For example, some have eliminated fried food, lowered the price of salads and increased the price of sugary beverages or eliminated them altogether from their cafeterias.

“The steps some hospitals are already taking to improve nutrition and reduce junk food are encouraging,” Lesser said. “We plan to make this nutritional quality measurement tool available to hospitals around the country to help them assess and improve their food offerings.”

Researchers said hospitals can improve the health of their food offerings by providing more fruits, vegetables, whole grains and smaller portions; shrinking the amount of low-nutrient choices; utilizing low-cost options, such as signage, to promote healthy eating; and keeping unhealthy “impulse” items away from the checkout stand.

“If we can’t improve the food environment in our hospitals, how do we expect to improve the health of food in our community?” Lesser said. “By serving as role models for healthy eating, we can make a small step toward helping children prevent the onset of dietary-related chronic diseases.”

Washington, DC, December 1, 2011 — Only 21 percent of surveyed medical students could identify five true and two false indications of when and when not to wash their hands in the clinical setting, according to a study published in the December issue of the American Journal of Infection Control, the official publication of APIC – the Association for Professionals in Infection Control and Epidemiology.

Three researchers from the Institute for Medical Microbiology and Hospital Epidemiology at Hannover Medical School in Hannover, Germany collected surveys from 85 medical students in their third year of study during a lecture class that all students must pass before bedside training and contact with patients commences. Students were given seven scenarios, of which five (“before contact to a patient,” “before preparation of intravenous fluids,” “after removal of gloves,” “after contact to the patient’s bed,” and “after contact to vomit”) were correct hand hygiene (HH) indications. Only 33 percent of the students correctly identified all five true indications, and only 21 percent correctly identified all true and false indications.

Additionally, the students expected that their own HH compliance would be “good” while that of nurses would be lower, despite other published data that show a significantly higher rate of HH compliance among nursing students than among medical students. The surveyed students further believed that HH compliance rates would be inversely proportional to the level of training and career attainment of the physician, which confirms a previously discovered bias among medical students that is of particular concern, as these higher-level physicians are often the ones training the medical students at the bedside.

“There is no doubt that we need to improve the overall attitude toward the use of alcohol-based hand rub in hospitals,” conclude the authors. “To achieve this goal, the adequate behavior of so-called ‘role models’ is of particular importance.”

German researchers have determined that epigallocatechin-3-gallate (EGCG)—a flavonoid found in green tea—inhibits the hepatitis C virus (HCV) from entering liver cells. Study findings available in the December issue of Hepatology, a journal published by Wiley-Blackwell on behalf of the American Association for the Study of Liver Diseases, suggest that EGCG may offer an antiviral strategy to prevent HCV reinfection following liver transplantation.

HCV infection can lead to chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC) or primary liver cancer. HCV is one of the most common causes of chronic liver disease and a primary indication for liver transplantation, affecting up to 170 million individuals worldwide according to estimates from the World Health Organization (WHO). Prior studies report that nearly 2% of the world population is infected with chronic HCV and up to 20% of the population in some countries.

While standard treatment with interferon with ribavirin and newer protease inhibitors may clear infection in some individuals, a substantial number of patients still may not respond to these therapies. For individuals receiving liver transplants due to complications from HCV, reinfection of the healthy donor liver remains a significant concern. Antiviral strategies that target HCV in its early stages are urgently needed to prevent graft reinfection and improve long-term outcomes for patients.

To address this critical issue, Dr. Sandra Ciesek and Dr. Eike Steinmann from the Hannover Medical School in Germany investigated the effect of the EGCG molecule, which is a major component of green tea, in preventing HCV from attaching to liver cells. “Green tea catechins such as EGCG and its derivatives epigallocatechin (EGC), epicatechingallate (ECG), and epicatechin (EC) have been shown to exhibit antiviral and anti-oncogenic properties,” explains Dr. Ciesek. “Our study further explores the potential effect these flavonoids have in preventing HCV reinfection following liver transplantation.”

Results showed that unlike its derivatives, EGCG inhibits entry of HCV into liver cells. The authors suggest that EGCG may impede HCV cell entry by acting on the host cell as the green tea catechin was not found to alter the density of virus particles. Pretreatment of cells with EGCG before HCV inoculation did not reduce the infection; however application during inoculation inhibited the rapid spread of the HCV. Lastly, researchers showed that EGCG inhibits viral attachment—the initial step in the HCV infection process. “The green tea antioxidant EGCG inhibits HCV cell entry by blocking viral attachment and may offer a new approach to prevent HCV infection, particularly reinfection following liver transplantation.” concludes Dr. Ciesek.

50% more fat can be produced by sustained stretching, TAU researchers say

Conventional wisdom says that exercise is a key to weight loss — a no-brainer. But now, Tel Aviv University researchers are revealing that life as a couch potato, stretched out in front of the TV, can actually be “active inactivity” — and cause you to pack on the pounds.

Such inactivity actually encourages the body to create new fat in fat cells, says Prof. Amit Gefen of TAU’s Department of Biomedical Engineering. Along with his Ph.D. student Naama Shoham, Prof. Gefen has shown that preadipocyte cells — the precursors to fat cells — turn into fat cells faster and produce even more fat when subject to prolonged periods of “mechanical stretching loads” — the kind of weight we put on our body tissues when we sit or lie down.

The research, which has been published in the American Journal of Physiology — Cell Physiology, demonstrates another damaging effect of a modern, sedentary lifestyle, Prof. Gefen notes. “Obesity is more than just an imbalance of calories. Cells themselves are also responsive to their mechanical environment. Fat cells produce more triglycerides, and at a faster rate, when exposed to static stretching.”

Stretching the fat

Prof. Gefen, who investigates chronic wounds that plague bed-ridden or wheelchair-bound patients, notes that muscle atrophy is a common side effect of prolonged inactivity. Studying MRI images of the muscle tissue of patients paralyzed by spinal cord injuries, he noticed that, over time, lines of fat cells were invading major muscles in the body. This spurred an investigation into how mechanical load — the amount of force placed on a particular area occupied by cells — could be encouraging fat tissue to expand.

In the lab, Prof. Gefen and his fellow researchers stimulated preadipocytes with glucose or insulin to differentiate them into fat cells. Then they placed individual cells in a cell-stretching device, attaching them to a flexible, elastic substrate. The test group of cells were stretched consistently for long periods of time, representing extended periods of sitting or lying down, while a control group of cells was not.

Tracking the cultures over time, the researchers noted the development of lipid droplets in both the test and control groups of cells. However, after just two weeks of consistent stretching, the test group developed significantly more — and larger — lipid droplets. By the time the cells reached maturity, the cultures that received mechanical stretching had developed fifty percent more fat than the control culture.

They were, in effect, half-again fatter.

According to Prof. Gefen, this is the first study that looks at fat cells as they develop, taking into account the impact of sustained mechanical loading on cell differentiation. “There are various ways that cells can sense mechanical loading,” he explains, which helps them to measure their environment and triggers various chemical processes. “It appears that long periods of static mechanical loading and stretching, due to the weight of the body when sitting or lying, has an impact on increasing lipid production.”

Counting more than calories

These findings indicate that we need to take our cells’ mechanical environment into account as well as pay attention to calories consumed and burned, believes Prof. Gefen. Although there are extreme cases, such as people confined to wheelchairs or beds due to medical conditions, many of us live a too sedentary lifestyle, spending most of the day behind a desk. Even somebody with healthy diet and exercise habits will be negatively impacted by long periods of inactivity.

Next, Prof. Gefen and his fellow researchers will be investigating how long a period of time a person can sit or lie down without the mechanical load becoming a factor in fat production. But in the meantime, it certainly can’t hurt to get up and take an occasional stroll, he suggests.

This research was done in collaboration with TAU’s Ruth Gottlieb, Dr. Uri Zaretsky, and Dr. Orna Shaharabani-Yosef from the Department of Biomedical Engineering and Prof. Dafna Benayahu of the Department of Cell and Developmental Biology

COLUMBUS, Ohio – Men are three times more likely than women to develop a common form of skin cancer but medical science doesn’t know why. A new study may provide part of the answer.

Researchers at The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James) have found that male mice had lower levels of an important skin antioxidant than female mice and higher levels of certain cancer-linked inflammatory cells.

The antioxidant, a protein called catalase, inhibits skin cancer by mopping up hydrogen peroxide and other DNA-damaging reactive-oxygen compounds that form during exposure to ultraviolet B light (UVB), a common source of sunburn and cancer-causing skin damage. Studies by others have linked low catalase activity to skin cancer progression.

The research is published online in the Journal of Investigative Dermatology.

The findings suggest that women may have more natural antioxidant protection in the skin than men,” say study co-leaders Gregory Lesinski and Tatiana Oberyszyn, both of the OSUCCC – James.

“As a result, men may be more susceptible to oxidative stress in the skin, which may raise the risk of skin cancer in men compared to women,” says Lesinski, an assistant professor of molecular virology, immunology and medical genetics;.

The study also found that UVB exposure caused a unique inflammatory white blood cell population called ‘myeloid-derived suppressor cells’ to migrate from the bone marrow into the exposed skin. Furthermore, higher numbers of these cells moved into the skin of male mice than female mice.

“To our knowledge, we’ve shown for the first time that UVB exposure causes a migration of systemic myeloid-derived suppressor cells, and it suggests that these cells might be a novel source of UVB-induced immune suppression,” says first author Nicholas Sullivan, a research scientist in the Oberyszyn lab in the Department of Pathology.

This, in turn, might mean that these UVB-induced inflammatory cells contribute to the genesis of skin tumors and perhaps other tumors rather than simply facilitating cancer progression, as generally thought, Sullivan notes.

Normally, the body mobilizes the suppressor cells to limit immune responses to infection, sepsis or trauma so that healing can begin, Lesinski says.

“However, in the cancer setting, repeated UV light exposure or after other chronic or repeated inflammatory stimuli, these cells persist and become immunosuppressive,” he says. “They can render helpful immune cells such as T cells or natural killer cells unable to recognize and eliminate cancer cells in the skin.”

Lesinski, Oberyszyn, Sullivan and their colleagues conducted the study using a strain of hairless mice that develops squamous cell carcinoma of the skin – the second most common skin cancer in humans – when exposed to UVB.

The investigators also found that treating mice with topical catalase inhibited the migration of the suppressor cells into UVB-exposed skin, suggesting that the influx of these cells in males might be due to the relatively lower skin-catalase activity.

In fact, male mice with UVB-induced skin tumors had 55 percent more of the suppressor cells in the skin than did their female counterparts.

“This is the first report to our knowledge of a sex discrepancy in this group of inflammatory cells in tumor-bearing mice, and it suggests that our findings might translate to other types of cancer,” says Oberyszyn, associate professor of pathology. “Men face a higher risk of numerous types of cancers, and relatively higher levels of inflammatory myeloid cells might contribute to this susceptibility.”

Funding from the National Cancer Institute and The Valvano Foundation for Cancer Research supported this research.

Other Ohio State researchers involved in this study were Kathleen L. Tober, Erin M. Burns, Jonathan S. Schick, Judith A. Riggenbach, Thomas A. Mace, Matthew A. Bill, and Gregory S. Young.

The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (cancer.osu.edu) strives to create a cancer-free world by integrating scientific research with excellence in education and patient-centered care, a strategy that leads to better methods of prevention, detection and treatment. Ohio State is one of only 41 National Cancer Institute (NCI)-designated Comprehensive Cancer Centers and one of only seven centers funded by the NCI to conduct both phase I and phase II clinical trials. The NCI recently rated Ohio State’s cancer program as “exceptional,” the highest rating given by NCI survey teams. As the cancer program’s 210-bed adult patient-care component, The James is a “Top Hospital” as named by the Leapfrog Group and one of the top 20 cancer hospitals in the nation as ranked by U.S.News & World Report

A red dye derived from lichens that has been used for centuries to color fabrics and food appears to reduce the abundance of small toxic protein aggregates in Alzheimer’s disease. The dye, a compound called orcein, and a related substance, called O4, bind preferentially to small amyloid aggregates that are considered to be toxic and cause neuronal dysfunction and memory impairment in Alzheimer’s disease. O4 binding to small aggregates promotes their conversion into large, mature plaques which researchers assume to be largely non-toxic for neuronal cells. Further research with animal models is needed to determine whether this new approach by Dr. Jan Bieschke (Max Delbrück Center for Molecular Medicine, MDC, Berlin-Buch), Dr. Martin Herbst (Charité – Universitätsmedizin Berlin) and Professor Erich Wanker (MDC) in Berlin, Germany, will be useful for therapy development (Nature Chemical Biology, doi: http://dx.doi.org/10.1038/NCHEMBIO.719)*.

Protein misfolding is considered to be the cause of Alzheimer’s, Parkinson’s and also Huntington’s disease. In a multistep process, proteins misfold and accumulate into large extra- or intracellular plaques. Researchers assume that small misfolded protein aggregates that are precursors of mature plaques are toxic for nerve cells and are the reason why they are eventually destroyed.

Dye from the Canary Islands

The dye orcein is isolated from lichens that grow on the Canary Islands, among other places. Lichens have been used for centuries to color fabrics and food. Eight years ago Professor Wanker screened hundreds of natural compounds to find potential candidate drug molecules for the treatment of neurodegenerative diseases. Among those substances he found orcein, a compound made up of about 14 small molecules. As these molecules might have different biological effects, the researchers in Berlin began to search for pure chemicals with similar properties. They identified the substance O4, a blue dye, which is structurally very similar to one of the 14 molecules. Moreover, they showed that O4 stimulates the formation of large, non-toxic protein plaques from small toxic protein assemblies.

New Mechanism

A few years ago Professor Wanker and his colleagues discovered that EGCG (Epigallocatechin-3-gallate), a natural chemical compound found in green tea, renders toxic protein assemblies non-toxic. With orcein and O4 the researchers have now found another mechanism to eliminate small toxic protein aggregates. However, instead of remodeling protein plaques, the dyes reduce the abundance of small, toxic precursor protein assemblies by accelerating the formation of large plaques, as the researchers could now show in their laboratory.

“This is a new mechanism,” Professor Wanker explained. “Up to now it has been considered to be very difficult to stop the formation of small toxic protein assemblies. If our hypothesis is correct that the small aggregates, which are precursors of plaques, indeed cause neuronal death, with O4 we would have a new mechanism to attack the disease.”

The synthetic dye methylene blue is currently being tested in clinical trials. This dye also seems to stimulate the formation of large plaques in a way similar to O4. Other therapeutic approaches tested in clinical trials which aim at eliminating small precursor aggregates have so far not led to a significant improvement of disease symptoms.

However, it still remains to be seen whether the blue dye O4 can also be effective against small amounts of misfolded proteins in the brains of Alzheimer’s patients and whether the accelerated formation of larger plaques can indeed reduce the signs and symptoms of Alzheimer’s disease in humans. Further studies will be necessary to address the question whether the accelerated formation of large plaques can be a therapeutic approach. “We hope that our findings will stimulate research activities in this direction, especially in drug discovery,”Professor Wanker said.

*Small-molecule conversion of toxic oligomers to nontoxic b-sheet–rich amyloid fibrils

Jan Bieschke^1,12, Martin Herbst^1,2,12, Thomas Wiglenda¹, Ralf PFriedrich¹, Annett Boeddrich¹, Franziska Schiele¹, Daniela Kleckers¹, Juan Miguel Lopez del Amo³, Björn Grüning⁴, Qinwen Wang^5,11, Michael RSchmidt¹, Rudi Lurz⁶, Roger Anwyl⁵, Sigrid Schnoegl¹, Marcus Fändrich⁷, Ronald F Frank⁸, Bernd Reif^3,9, Stefan Günther⁴, Dominic M Walsh¹⁰ & Erich EWanker¹

¹Neuroproteomics, Max Delbrück Center for Molecular Medicine, Berlin, Germany. ²Department of Neurology, Charité-Universitätsmedizin Berlin, Germany. ³Leibniz Institute for Molecular Pharmacology, Berlin, Germany. ⁴Institute for Pharmaceutical Sciences, University of Freiburg, Germany. ⁵Department of Physiology, School of Medicine, Trinity College, Dublin, Republic of Ireland, ⁶Max Planck Institute for Molecular Genetics, Berlin, Germany. ⁷Max Planck Research Unit for Enzymology of Protein Folding, Halle (Saale), Germany. ⁸Department of Chemistry, Helmholtz Center for Infection Research, Braunschweig, Germany. ⁹Technical University Munich, Munich, Germany. ¹⁰Laboratory for Neurodegenerative Research, The Conway Institute for Biomolecular and Biomedical Research, University College Dublin, Republic of Ireland. ¹¹Present address: Department of Physiology and Pharmacology, Medical School, Ningbo University, Ningbo, China. ¹²These authors contributed equally to this work.