Health Technology Research Synopsis

115th Issue Date 04NOV2011

Compiled By Ralph Turchiano

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In this Issue:

Public release date: 23-Oct-2011

Sleeping sickness drug may provide long-term protection against skin cancer

BOSTON — An antiparasitic agent used to treat African sleeping sickness might someday be used to prevent nonmelanoma skin cancers. Researchers found that DFMO, or α-difluoromethylornithine, still appeared to protect against nonmelanoma skin cancers years after people stopped taking the drug, according to a poster presented at the 10th AACR International Conference on Frontiers in Cancer Prevention Research, held Oct. 22-25, 2011.

In this follow-up study, researchers evaluated prolonged evidence of a protective effect of DFMO among 209 people who had participated in an earlier study. The researchers also wanted to ensure there were no obvious deleterious effects associated with the drug, according to Howard H. Bailey, M.D., professor of medicine, and study presenter Sarah Lamont, a medical student, both from the University of Wisconsin School of Medicine and Public Health.

The original study was a phase III, randomized, double-blind, prospective study of 291 men and women with a history of nonmelanoma skin cancer. They were assigned to either DFMO or a placebo for four to five years. At the end of the study period, researchers found a reduced skin cancer incidence among those assigned to DFMO.

“We showed a significant protective effect against basal cell carcinoma, but not a significant amount of protection against squamous cell carcinoma of the skin,” Bailey said.

The main side effect was a slight ototoxicity that was found on testing, but this was not associated with a noticeable reduction in hearing by the subjects.

In the current retrospective study, researchers reviewed the electronic medical records of 209 of the original participants to establish cancer rates and to see if any other illnesses they might have developed could be attributed to DFMO.

“We found there is still evidence that the men and women assigned to DFMO for five years continued to have a lower incidence of nonmelanoma skin cancers compared with people assigned to placebo,” Bailey said. “What we saw was that the presumed benefit that people got in taking DFMO appeared to persist for years after stopping it.”

Study limitations include that participants may have been followed differently or changed their behaviors to limit sun exposure because of being in the original study, Bailey said.

“Our data suggest that the protective event that we saw in our prospective study appears to continue and there was no evidence of any rebound effect,” he said. “We did not find any evidence that the people who received DFMO were harmed [other than the original ototoxicity].”

However, Bailey cautioned, more studies are needed before DFMO can be recommended as a prophylaxis against nonmelanoma skin cancers.

He added that such prophylaxis measures are needed because public health efforts to teach people about limiting sun exposure have not resulted in fewer cases of skin cancer, with more than 2 million cases of nonmelanoma skin cancer diagnosed each year. “The incidence continues to rise despite public health efforts to get people to lessen their sun exposure,” Bailey said.

Public release date: 24-Oct-2011

Bath salts emerging as new recreational drugs

The use of bath salts as recreational drugs has greatly escalated in recent years. Researchers from the University of Oklahoma Health Sciences Center in Oklahoma City, Oklahoma describe an incident of a man experiencing significant agitation, paranoia, and hallucinations who also exhibited violent behavior upon his emergency department arrival.

His case is not unique. Despite disclaimers of “not for human consumption” package warnings, according to the American Association of Poison Control Centers, calls for bath salt poisoning incidents have skyrocketed, with 1,782 since January 2011 compared with 302 in all of 2010. The inexpensive powdery substances with benign names contain stimulants not detectable through drug screens. However, they can produce a “high” along with increased blood pressure, increased heart rate, agitation, hallucinations, extreme paranoia, and delusions, not unlike the Oklahoma patient.

Treatment for ingesting these bath salts is sedation until the side effects wear off, along with supportive care. Although currently federally unregulated, 26 states have made these substances illegal. This new research was presented at CHEST 2011, the 77th annual meeting of the American College of Chest Physicians (ACCP), in Honolulu, Hawaii.

Public release date: 24-Oct-2011

Coffee consumption associated with decreased risk for basal cell carcinoma

BOSTON — Caffeine could be related to an inverse association between basal cell carcinoma risk and consumption of coffee, a study found.

The prospective study, presented at the 10th AACR International Conference on Frontiers in Cancer Prevention Research, held Oct. 22-25, 2011, examined the risks of basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and melanoma in connection with coffee consumption and found a decreased risk for BCC only.

“Given the nearly 1 million new cases of BCC diagnosed each year in the United States, daily dietary factors with even small protective effects may have great public health impact,” said researcher Fengju Song, Ph.D., a postdoctoral fellow in the department of dermatology at Brigham and Women’s Hospital and Harvard Medical School. “Our study indicates that coffee consumption may be an important option to help prevent BCC.”

Data were taken from the Nurses’ Health Study (Brigham and Women’s Hospital) and the Health Professionals Follow-Up Study (Harvard School of Public Health). In the Nurses’ Health Study, 72,921 participants were followed from June 1984 to June 2008. In the Health Professionals Follow-Up Study, 39,976 participants were followed from June 1986 to June 2008.

The researchers reported 25,480 incident skin cancer cases. Of those, 22,786 were BCC, 1,953 were SCC, and 741 were melanoma.

Song and colleagues reported that women who consumed more than three cups of coffee per day had a 20 percent reduction in risk for BCC, and men who consumed more than three cups per day had a nine percent risk reduction compared with people who consumed less than one cup per month.

The amount of coffee consumption was inversely associated with BCC risk. Those in the highest quintile had the lowest risk, with an 18 percent reduction for women and a 13 percent reduction for men.

Song and colleagues were surprised by the inverse connection in BCC cases only. Animal studies have suggested an association between coffee intake and skin cancer risk, but epidemiologic studies have not conclusively shown the same results, they said.

“Mouse studies have shown that oral or topical caffeine promotes elimination of UV-damaged keratinocytes via apoptosis (programmed cell death) and markedly reduces subsequent SCC development,” Song said. “However, in our cohort analysis, we did not find any inverse association between coffee consumption and the risk for SCC.”

Song said that additional studies specifically addressing the association between coffee consumption and BCC and the mechanism behind this association are warranted.

Public release date: 24-Oct-2011

Analgesics use associated with increased risk for renal cell carcinoma

BOSTON — Use of acetaminophen and nonaspirin nonsteroidal anti-inflammatory drugs was associated with a significantly increased risk for developing renal cell carcinoma, according to data presented at the 10th AACR International Conference on Frontiers in Cancer Prevention Research, held Oct. 22-25, 2011.

Eunyoung Cho, Sc.D., assistant professor of medicine at Harvard Medical School and associate epidemiologist at Brigham and Women’s Hospital in Boston, and colleagues conducted a preliminary meta-analysis of 18 studies from six countries to examine analgesics use and its relation to the risk for renal cell carcinoma (RCC).

“Our meta-analysis was the largest analysis of analgesics and risk for RCC,” Cho said. “Our study is the first few of those studies raising [the] possibility that these commonly used painkillers may elevate the risk for certain types of cancer.”

Cho and colleagues conducted a Medline database search for case-control or cohort studies on acetaminophen, aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs), published between 1966 and July 1, 2011. They found 12 studies examining risk for acetaminophen, 12 for aspirin and five for NSAIDs.

Results demonstrated that any use of acetaminophen was associated with a 33 percent increased risk for RCC, and use of other NSAIDs was linked with a 26 percent increased risk. No significantly increased risk for RCC was found with the use of aspirin.

The meta-analysis revealed similar trends with high-dose analgesics intake. Researchers found no significant difference in associations based on study design, type of controls in case-control studies, study outcome or gender.

“The positive association with nonaspirin NSAIDs was somewhat expected since we recently published on the association from two prospective studies [in Archives of Internal Medicine], which were included in this meta-analysis,” Cho said. “However, the association with use of acetaminophen was not found in the publication and was thus unexpected. Several relatively small studies of use of acetaminophen and RCC did suggest positive associations. When we conducted a meta-analysis of these studies to improve statistical power, the summary results came out statistically significant.”

Public release date: 24-Oct-2011

High fluid intake appears to reduce bladder cancer risk

BOSTON — Drinking plenty of fluids may provide men with some protection against bladder cancer, according to a study presented at the 10th AACR International Conference on Frontiers in Cancer Prevention Research, held Oct. 22-25, 2011.

Although the study did not determine why increased fluid intake might be protective, Jiachen Zhou, M.B.B.S., M.P.H., a doctoral candidate in epidemiology at Brown University, hypothesized that the fluids may flush out potential carcinogens before they have the opportunity to cause tissue damage that could lead to bladder cancer.

Researchers evaluated the association between fluid intake and bladder cancer among 47,909 male participants in the prospective Health Professionals Follow-Up Study (HPFS) during a 22-year period. HPFS is a long-term study of male health professionals who were aged between 40 and 75 years at enrollment in 1986.

Participants answered a questionnaire about fluid intake every four years. Researchers found that high total fluid intake (more than 2,531 milliliters per day) was associated with a 24 percent reduced risk for bladder cancer among men.

Researchers first found an association between fluid intake and bladder cancer risk in this cohort 10 years ago. The association was present but weaker in the most recent study. Detailed analyses revealed the association was stronger among younger men, and this may explain the weakened association over time. The researchers also observed that the men drank fewer liquids, particularly water, as they aged.

Although he warned against generalizing these findings to the wider population, Zhou said that physicians should feel comfortable recommending that patients drink plenty of fluids.

Public release date: 24-Oct-2011

Could additives in hot dogs affect incidence of colon cancer?

BOSTON — The addition of ascorbate (vitamin C) or its close relative, erythorbate, and the reduced amount of nitrite added in hot dogs, mandated in 1978, have been accompanied by a steep drop in the death rate from colon cancer, according to data presented at the 10th AACR International Conference on Frontiers in Cancer Prevention Research, held Oct. 22-25, 2011.

However, the incidence rate for colon cancer has apparently not changed much since 1978, according to 2011 data from the SEER Cancer Statistics Review from the National Cancer Institute.

“It was proposed that N-nitroso compounds in hot dogs and other processed meats can cause colon cancer,” said Sidney S. Mirvish, Ph.D., professor emeritus at the Eppley Institute for Research in Cancer and Allied Diseases at the University of Nebraska Medical Center in Omaha. “We found that the level of total apparent N-nitroso compounds in hot dog links prepared in our laboratory fell as increasing levels of sodium erythorbate were included in the hot dog links.”

Mirvish and colleagues discussed the view that colon cancer was induced by components of the apparent nonvolatile N-nitroso compounds that occur in processed (nitrite-preserved) meat. Hence, Mirvish and colleagues investigated the effect of varying the erythorbate level on the N-nitroso compound content of hot dogs.

They found that the current level of erythorbate (500 milligrams per kilogram) added to hot dogs reduces the N-nitroso compounds to 2 nanomoles per gram compared with 180 nanomoles per gram when erythorbate was not used.

“When erythorbate was not added, 80 percent of the apparent N-nitroso compounds were found to be due to nitrosothiols, which are probably harmless, still leaving 40 nanomoles per gram that were attributed to possibly carcinogenic N-nitroso compounds,” Mirvish said.

If the level of N-nitroso compounds was an important cause of colon cancer, “the drop in N-nitroso compound content caused by the mandated changes in processed meat should have been accompanied by a drop in the incidence of colon cancer,” Mirvish said.

In fact, since the mandated changes were introduced 33 years ago, the death rate for colon cancer has dropped sharply. “This may have been due mostly to earlier detection and better treatment of this disease,” Mirvish said.

Mirvish concluded that the role of hot dog-derived N-nitroso compounds in the causation of colon cancer remains unclear.

Public release date: 24-Oct-2011

Exposure to chemical BPA before birth linked to behavioral, emotional difficulties in girls

Boston, MA – Exposure in the womb to bisphenol A (BPA) – a chemical used to make plastic containers and other consumer goods – is associated with behavior and emotional problems in young girls, according to a study led by researchers at Harvard School of Public Health (HSPH), Cincinnati Children’s Hospital and Medical Center, and Simon Fraser University in Vancouver, British Columbia.

BPA is found in many consumer products, including canned food linings, polycarbonate plastics, dental sealants, and some receipts made from thermal paper. Most people living in industrialized nations are exposed to BPA. BPA has been shown to interfere with normal development in animals and has been linked with cardiovascular disease and diabetes in people. In a 2009 study, HSPH researchers showed that drinking from polycarbonate bottles increased the level of urinary BPA.

In this study, published October 24, 2011, in an advance online edition of Pediatrics, lead author Joe Braun, research fellow in environmental health at HSPH, and his colleagues found that gestational BPA exposure was associated with more behavioral problems at age 3, especially in girls.

The researchers collected data from 244 mothers and their 3-year-old children in the Health Outcomes and Measures of the Environment Study, conducted in the Cincinnati area. Mothers provided three urine samples during pregnancy and at birth that were tested for BPA; their children were tested each year from ages 1 to 3. When the children were 3 years old, the mothers completed surveys about their children’s behavior.”None of the children had clinically abnormal behavior, but some children had more behavior problems than others. Thus, we examined the relationship between the mom’s and children’s BPA concentrations and the different behaviors,” Braun said.

BPA was detected in over 85% of the urine samples from the mothers and over 96% of the children’s urine samples. The researchers found that maternal BPA concentrations were similar between the first sample and birth. The children’s BPA levels decreased from ages 1 to 3, but were higher and more variable than that of their mothers.

After adjusting for possible contributing factors, increasing gestational BPA concentrations were associated with more hyperactive, aggressive, anxious, and depressed behavior and poorer emotional control and inhibition in the girls. This relationship was not seen in the boys.

The study confirms two prior studies showing that exposure to BPA in the womb impacts child behavior, but is the first to show that in utero exposures are more important than exposures during childhood, Braun said. “Gestational, but not childhood BPA exposures, may impact neurobehavioral function, and girls appear to be more sensitive to BPA than boys,” he said.

Although more research is needed to fully understand the health effects of BPA exposure, clinicians can advise those concerned to reduce their BPA exposure by avoiding canned and packaged foods, thermal paper sales receipts, and polycarbonate bottles with the number 7 recycling symbol, the authors wrote.

Bruce Lanphear of Simon Fraser University was senior author of the study.

Public release date: 24-Oct-2011

More time outdoors may reduce kids’ risk for nearsightedness

Researcher will discuss data on natural light exposure and rising myopia rates at American Academy of Ophthalmology 2011 Annual Meeting

ORLANDO, Fla. –October 24, 2011– A new analysis of recent eye health studies shows that more time spent outdoors is related to reduced rates of nearsightedness, also known as myopia, in children and adolescents. Myopia is much more common today in the United States and many other countries than it was in the 1970s. In parts of Asia, more than 80 percent of the population is nearsighted. The analysis suggests that more exposure to natural light and/or time spent looking at distant objects may be key factors. Today at the 115th Annual Meeting of the American Academy of Ophthalmology Dr. Anthony Khawaja of the University of Cambridge, will present a summary analysis of the evidence. The analysis was led by Dr. Justin Sherwin of the University of Cambridge.

The data included in the analysis was drawn from eight carefully selected studies on outdoor time and myopia in children and adolescents, representing 10,400 participants in total. Dr. Sherwin’s team concluded that for each additional hour spent outdoors per week, the chance of myopia dropped by approximately two percent. Nearsighted children spent on average 3.7 fewer hours per week outdoors than those who either had normal vision or were farsighted.

Though the reasons aren’t yet clear, the protective effect appears to result from simply being outdoors rather than performing a specific activity. Two of the eight studies examined whether children who spent more time outdoors were also those who spent less time performing near work, such as playing computer games or studying, but no such relationship was found in either study. The amount of time spent on near work is of interest to researchers as another potential cause for the recent uptick in nearsightedness.

“Increasing children’s outdoor time could be a simple and cost-effective measure with important benefits for their vision and general health” said Dr. Khawaja. “If we want to make clear recommendations, however, we’ll need more precise data. Future, prospective studies will help us understand which factors, such as increased use of distance vision, reduced use of near vision, natural ultra violet light exposure or physical activity, are most important.”

Another question, Dr. Khawaja considered is whether boosting outdoor time might stop nearsightedness from getting worse. He cited a recent Chinese study, not included in Dr. Sherwin’s analysis, of 80 nearsighted children between the ages of 7 and 11. Forty of them were assigned to spend less than 30 hours on near work and more than 14 hours on outdoor time per week. At the end of the two-year study, children in the intervention group were less nearsighted on average than the 40 control group children who did not follow the special schedule.

Public release date: 24-Oct-2011

Vitamin B-based treatment for corneal disease may offer some patients a permanent solution

3-year outcomes of clinical trial of collagen crosslinking treatment for keratoconus highlighted at American Academy of Ophthalmology 2011 Annual Meeting

ORLANDO, Fla. – October 24, 2011 – Patients in the United States who have the cornea-damaging disease keratoconus may soon be able to benefit from a new treatment that is already proving effective in Europe and other parts of the world. The treatment, called collagen crosslinking, improved vision in almost 70 percent of patients treated for keratoconus in a recent three-year clinical trial in Milan, Italy. The treatment is in clinical trials in the United States and is likely to receive FDA approval in 2012. The results of the Milan study are being presented today at the 115th Annual Meeting of the American Academy of Ophthalmology in Orlando, Florida.

In a session titled Long-term Results of Corneal Crosslinking for Keratoconus, Paolo Vinciguerra, MD will describe the treatment and three-year follow up of more than 250 keratoconus patients who received collagen crosslinking at his clinic. Sixty-eight percent of the 500 eyes treated gained significant visual acuity, with their results remaining stable at the end of the follow-up period. Patients over age 18 were most likely to improve.

In the collagen crosslinking procedure, riboflavin (vitamin B) is applied to the cornea, which is then exposed to a specific form of ultraviolet light. Collagen fibers regenerate with new bonds forming between them, increasing corneal stiffness and strength. The treatment also combats the causes of keratoconus, reducing the chance that it will recur. The rest of the eye receives only minimal UV exposure during treatment. Dr. Vinciguerra’s new study confirms that adverse effects are rare. Previous research by his team indicated no loss of corneal endothelial cell, a measurement used to assess the safety of corneal treatments, in patients who received collagen crosslinking.

“For many people with keratoconus, collagen crosslinking can provide a better and more permanent solution to their vision problems,” said Dr. Vinciguerra. “Given that no current treatment in use in the U.S. offers permanent correction, this effective option represents a significant advance for corneal medicine.”

One in 2,000 people in the United States and worldwide are diagnosed with keratoconus, a disease that damages the collagen fibers that form the structure of the cornea, which is the outer surface of the eye. The cornea’s crucial task is to focus, or “refract,” incoming light toward the eye’s lens. To perform properly, the cornea needs to be rounded, like the surface of a ball. As keratoconus worsens and the cornea becomes thinner, it may bulge outward in a cone shape, causing nearsightedness and/or astigmatism, making clear vision impossible. As the number of fibers and links between them decline, the cornea loses up to 50 percent of its normal stiffness.

Standard treatments in the U.S., such as specialized eyeglasses, contact lenses, or implanted lenses, cannot permanently correct keratoconus, and none of these treatments address the underlying causes. Severe keratoconus often requires corneal transplant.

Public release date: 24-Oct-2011

Morning UV exposure may be less damaging to the skin

Study suggests that restricting sunbathing or visits to the tanning booth to morning hours would reduce the risk of skin cancer.

(Embargoed) CHAPEL HILL – Research from the University of North Carolina at Chapel Hill suggests that the timing of exposure to UV rays – early in the morning or later in the afternoon – can influence the onset of skin cancer.

The study, performed in mice, found that exposure to UV radiation in the morning increased the risk of skin cancer by 500 percent over identical doses in the afternoon. Although mice and humans both reside on a 24-hour day, the “circadian” clocks of these nocturnal and diurnal creatures run counter each other. This key difference in biology means that humans are most protected from the sun’s harmful rays when mice are most susceptible, and vice versa.

“Therefore, our research would suggest that restricting sunbathing or visits to the tanning booth to morning hours would reduce the risk of skin cancer in humans,” said senior study author Aziz Sancar, M.D., PhD, a member of the UNC Lineberger Comprehensive Cancer Center and Sarah Graham Kenan professor of biochemistry and biophysics in the UNC School of Medicine. Sancar is also a member of the National Academy of Sciences and the Turkish Academy of Sciences “However, further studies in humans are needed before we can make any definitive recommendations.”

Sancar has previously shown that a protein called XPA, responsible for repairing the DNA damage wrought by UV radiation, waxes and wanes throughout the day. In a study published online the week of October 24-30 in the Proceedings of the National Academy of Sciences, he and his colleagues looked to see if the cyclical nature of this DNA repair molecule had an influence on the onset of skin cancer.

They exposed two groups of mice to UV radiation – either at 4 a.m. or at 4 p.m. – and waited for cancer to develop. Mice irradiated when the repair activity was at its minimum developed tumors much faster and at five-fold higher frequency compared with mice exposed to UV when the protein’s repair function was at its maximum.

The researchers predict that humans will have a higher rate of DNA repair in the morning and would be less prone to the carcinogenic effect of UV radiation in the morning hours. They plan to measure actual DNA repair rates in the skin of human volunteers to confirm that morning sun is safest for humans.

Public release date: 24-Oct-2011

Yoga eases back pain in largest US yoga study to date

Group Health randomized controlled trial in Archives of Internal Medicine

SEATTLE–Yoga classes were linked to better back-related function and diminished symptoms from chronic low back pain in the largest U.S. randomized controlled trial of yoga to date, published by the Archives of Internal Medicine as an “Online First” article on October 24. But so were intensive stretching classes.

“We found yoga classes more effective than a self-care book—but no more effective than stretching classes,” said study leader Karen J. Sherman, PhD, MPH, a senior investigator at Group Health Research Institute. Back-related function was better and symptoms were diminished with yoga at 12 weeks; and clinically important benefits, including less use of pain medications, lasted at least six months for both yoga and stretching, with thorough follow-up of more than nine in 10 participants.

In the trial, 228 adults in six cities in western Washington state were randomly assigned to 12 weekly 75-minute classes of either yoga or stretching exercises or a comprehensive self-care book called The Back Pain Helpbook. Nine in 10 of them were primary-care patients at Group Health Cooperative. Participants in the trial typically had moderate—not severe—back pain and relatively good mental health, and most had been at least somewhat active before the trial started.

The class participants received instructional videos and were encouraged to practice at home for 20 minutes a day between their weekly classes. Interviewers who didn’t know the patients’ treatment assignments assessed their back-related function and pain symptoms at six weeks, 12 weeks, and six months.

In 2005, Dr. Sherman and her colleagues conducted a smaller study that found yoga effective for easing chronic low back pain. “In our new trial,” she said, “we wanted both to confirm those results in a larger group and to see how yoga compared to a different form of exercise of comparable physical exertion: stretching.

Both the yoga and stretching classes emphasized the torso and legs:

• The type of yoga used in the trial, called viniyoga, adapts the principles of yoga for each individual and physical condition, with modifications for people with physical limitations. The yoga classes also used breathing exercises, with a deep relaxation at the end.

• The stretching classes used 15 different stretching exercises, including stretches of the hamstrings and hip flexors and rotators. Each was held for a minute and repeated once, for a total of 52 minutes of stretching. Strengthening exercises were also included.

“We expected back pain to ease more with yoga than with stretching, so our findings surprised us,” Dr. Sherman said. “The most straightforward interpretation of our findings would be that yoga’s benefits on back function and symptoms were largely physical, due to the stretching and strengthening of muscles.”

But the stretching classes included a lot more stretching than in most such classes, with each stretch held for a relatively long time. “People may have actually begun to relax more in the stretching classes than they would in a typical exercise class,” she added. “In retrospect, we realized that these stretching classes were a bit more like yoga than a more typical exercise program would be.” So the trial might have compared rather similar programs with each other.

“Our results suggest that both yoga and stretching can be good, safe options for people who are willing to try physical activity to relieve their moderate low back pain,” Dr. Sherman concluded. “But it’s important for the classes to be therapeutically oriented, geared for beginners, and taught by instructors who can modify postures for participants’ individual physical limitations.”

Public release date: 24-Oct-2011

High fizzy soft drink consumption linked to violence among teens

The ‘Twinkie Defense’: The relationship between carbonated non-diet soft drinks and violence perpetration among Boston high school students

Teens who drink more than five cans of non-diet, fizzy soft drinks every week are significantly more likely to behave aggressively, suggests research published online in Injury Prevention. This includes carrying a weapon and perpetrating violence against peers and siblings.

US lawyers have successfully argued in the past that a defendant accused of murder had diminished capacity as a result of switching to a junk food diet, a legal precedent that subsequently became known as the “Twinkie Defense” – a twinkie being a packaged snack cake with a creamy filling.

The researchers base their findings on 1,878 teens from 22 public schools in Boston, Massachusetts. The teens were part of the Boston Youth Survey, a biennial survey of 9th to 12th graders (14 to 18 year olds).

The teens were asked how many carbonated non-diet soft drinks they had drunk over the past seven days. Intake was measured in cans (355 ml or 12 ounces), and responses categorised according to quantity.

The responses were divided into two groups: those drinking up to four cans over the preceding week (low consumption); and those drinking five or more (high consumption). Just under one in three (30%) respondents fell into the high consumption category.

The researchers then looked at potential links to violent behaviour in this group, by asking if they had been violent towards their peers, a sibling, or a partner, and if they had carried a gun or knife over the past year.

Responses were assessed in the light of factors likely to influence the results, including age and gender, alcohol consumption, and average amount of sleep on a school night.

Those who drank 5 or more cans of soft drinks every week were significantly more likely to have drunk alcohol and smoked at least once in the previous month.

But even after controlling for these and other factors, heavy use of carbonated non-diet soft drinks was significantly associated with carrying a gun or knife, and violence towards peers, family members and partners.

When the findings were divided into four categories of consumption, the results showed a clear dose-response relationship across all four measures.

Just over 23% of those drinking one or no cans of soft drink a week carried a gun/knife, rising to just under 43% among those drinking 14 or more cans. The proportions of those perpetrating violence towards a partner rose from 15% in those drinking one or no cans a week to just short of 27% among those drinking 14 or more.

Similarly, violence towards peers rose from 35% to more than 58%, while violence towards siblings rose from 25.4% to over 43%.

In all, for those teens who were heavy consumers of non-diet carbonated soft drinks, the probability of aggressive behaviour was 9 to 15 percentage points higher – the same magnitude as the impact of alcohol or tobacco – the findings showed. “There may be a direct cause-and-effect-relationship, perhaps due to the sugar or caffeine content of soft drinks, or there may be other factors, unaccounted for in our analyses, that cause both high soft drink consumption and aggression,” conclude the authors.

Public release date: 24-Oct-2011

Perinatal antidepressant stunts brain development in rats

Miswired brain circuitry traced to early exposure

Rats exposed to an antidepressant just before and after birth showed substantial brain abnormalities and behaviors, in a study funded by the National Institutes of Health.

After receiving citalopram, a serotonin-selective reuptake inhibitor (SSRI), during this critical period, long-distance connections between the two hemispheres of the brain showed stunted growth and degeneration. The animals also became excessively fearful when faced with new situations and failed to play normally with peers – behaviors reminiscent of novelty avoidance and social impairments seen in autism. The abnormalities were more pronounced in male than female rats, just as autism affects 3-4 times more boys than girls.

“Our findings underscore the importance of balanced serotonin levels – not too high or low — for proper brain maturation,” explained Rick Lin, Ph.D., of the University of Mississippi Medical Center, Jackson, a Eureka Award grantee of the NIH’s National Institute of Mental Health.

Lin and colleagues report on their discovery online during the week of Oct. 24, 2011, in the Proceedings of the National Academy of Sciences.

Last July, a study reported an association between mothers taking antidepressants and increased autism risk in their children. It found that children of mothers who took SSRI’s during the year prior to giving birth ran twice the normal risk of developing autism – with treatment during the first trimester of pregnancy showing the strongest effect. A study published last month linked the duration of a pregnant mother’s exposure to SSRIs to modest lags in coordination of movement – but within the normal range – in their newborns.

“While one must always be cautious extrapolating from medication effects in rats to medication effects in people, these new results suggest an opportunity to study the mechanisms by which antidepressants influence brain and behavioral development,” said NIMH Director Thomas R. Insel, M.D. “These studies will help to balance the mental health needs of pregnant mothers with possible increased risk to their offspring.”

Earlier studies had hinted that serotonin plays an important role in shaping the still-forming brain in the days just after a rat is born, which corresponds to the end of the third trimester of fetal development in humans. Experimental manipulations of the chemical messenger during this period interfered with formation of sensory-processing regions of the cortex, or outer mantle, and triggered aggressive and anxiety-related behaviors in rodents.

There is also recent evidence in humans that serotonin from the placenta helps shape development of the fetal brain early in pregnancy. Disrupted serotonin has been linked to mood and anxiety disorders. SSRIs, the mainstay medication treatment for these disorders, boost serotonin activity. ,

Lin and colleagues gave citalopram to male and female rat pups prenatally and postnatally and examined their brains and behavior as they grew up. Male, but not female, SSRI exposed rat pups abnormally froze when they heard an unfamiliar tone and balked at exploring their environment in the presence of unfamiliar objects or scents. These behaviors persisted into adulthood. The male pups especially also shunned normal juvenile play behavior – mimicking traits often seen in children

A key brain serotonin circuit, the raphe system, known to shape the developing brain during the critical period when the animals were exposed to the drug, showed dramatic reductions in density of neuronal fibers. Evidence of stunted development in the circuit coursed through much of the cortex and other regions important for thinking and emotion, such as the hippocampus.

The researchers also discovered miswiring in the structure responsible for communications between the brain’s left and right hemispheres, called the corpus collosum. Extensions of neurons, called axons, through which such long-distance communications are conducted, were deformed. A protective sheath, called myelin, that normally wraps and boosts axons’ efficiency– like insulation on an electrical wire – was reduced by one-third in the treated animals. This damage was three times worse in male than in female pups and would likely result in abnormal communication between the two hemispheres, say the researchers.

Moreover, the perinatally exposed animals showed evidence of neurons firing out of sync and other electrophysiological abnormalities, suggesting faulty organization of neuronal networks in the cortex.

Public release date: 24-Oct-2011

Physical fitness could have a positive effect on eye health

New study links active lifestyle to reduced risk of glaucoma

Rockville, MD — Physical activity may be what the doctor orders to help patients reduce their risk of developing glaucoma. According to a recently published scientific paper, higher levels of physical exercise appear to have a long-term beneficial impact on low ocular perfusion pressure (OPP), an important risk factor for glaucoma.

Published in the Investigative Ophthalmology & Visual Science journal (Physical Activity and Ocular Perfusion Pressure: The EPIC-Norfolk Eye Study), this study examined the relationship between physical activity and current OPP in 5,650 men and women aged 48 to 90 who live in the U.K. and were part of initial cohort from 1993 – 1997.

Using a detailed self-administered health and lifestyle questionnaire, participants were assessed for combined physical activity at work and leisure. From 2006 to 2010, study participants were examined for eye pressure — medically termed intraocular pressure (IOP )– and systolic and diastolic blood pressure measurements. The results showed that moderate physical exercise performed approximately 15 years previously is associated with a 25% reduced risk of low OPP.

“It appears that OPP is largely determined by cardiovascular fitness,” said author Paul J. Foster, MD PhD, FRCS(Ed), of the University College London Institute of Ophthalmology. “We cannot comment on the cause, but there is certainly an association between a sedentary lifestyle and factors which increase glaucoma risk.”

While there have been a large number of studies that have examined the effect of physical activity on intraocular pressure (IOP) and on blood pressure — the two components of OPP — this is the first time the relationship between physical activity and OPP has been investigated, according to the authors.

“Before now, the only modifiable risk factor for glaucoma was IOP, altered by medication, laser or surgery,” said Foster. “We believe our study points toward a new way of reducing glaucoma risk, through maintaining an active lifestyle. This is a way that people can participate in altering their risk of glaucoma and many other serious health problems.”

Public release date: 24-Oct-2011

Research links water disinfection byproducts to adverse health effects

University of Illinois scientists report the first identification of a cellular mechanism linked to the toxicity of a major class of drinking water disinfection byproducts. This study, published in Environmental Science & Technology, suggests a possible connection to adverse health effects, including neurological diseases such as Alzheimer’s.

“I’m not implying that drinking disinfected water will give you Alzheimer’s,” said Michael Plewa, lead scientist and professor of genetics in the U of I Department of Crop Sciences. “Certainly, the disinfection of drinking water was one of the most significant public health achievements of the 20th century. But the adverse effects of disinfection byproducts (DBPs) that are unintentionally formed during this process are causing concerns as researchers unveil their toxicity.”

More than 600 DBPs have been discovered. Although researchers know some DBPs are toxic, little biological information is available on the majority of these water contaminants. The Environmental Protection Agency regulates only 11 of these DBPs, he said.

Plewa’s laboratory investigated the biological mechanism, or the cellular target that leads to toxicity, in the second-most prevalent DBP class generated in disinfected water – haloacetic acids (HAAs).

“The EPA has regulated HAAs for nearly 15 years. However, we did not know how they caused toxicity before this study,” he said. “Now that we’ve uncovered the mechanism for HAAs, we can make sense of past data that can lead to new studies relating to adverse pregnancy outcomes, different types of cancer, and neurological dysfunction.”

Plewa believes this will assist the EPA in establishing regulations based on science. Their research will also help the water treatment community develop new methods to prevent the generation of the most toxic DBPs.

“It’s fairly simple,” Plewa said. “To increase the health benefits of disinfected water, we must reduce the most toxic DBPs. If we understand their biological mechanisms, we can come up with more rational ways to disinfect drinking water without generating toxic DBPs.”

In this study, researchers focused on three HAAs – iodoacetic acid, bromoacetic acid and chloroacetic acid. After they rejected their first hypothesis that the HAAs directly damaged DNA, they looked at research in a different area – neuroscience. Plewa’s graduate student, Justin Pals, discovered an amazing connection, Plewa said.

In neurotoxicology, iodoacetic acid reduces the availability of nutrients or oxygen in neurons by inhibiting glyceraldehyde-3-phosphate dehydrogenase (GAPDH).

“Researchers are interested in understanding how to prevent damage after a stroke or other neurological damage,” Plewa said. “Iodoacetic acid kills these cells. One of the targets they found was that iodoacetic acid inhibited GAPDH.”

Plewa’s lab conducted quantitative GAPDH enzyme kinetics and discovered that the data were highly correlated with a diversity of adverse health markers.

“All the pieces of the puzzle fell into place in an instant,” Plewa said. “We had discovered our cellular target – GAPDH. Never before had this type of research been done with this level of precision and associated with a large body of adverse biological impacts.”

They discovered that the HAA disinfection byproducts were toxic because the cells cannot make ATP, and this causes oxidative stress.

“Cells treated with HAAs experience DNA damage,” Plewa said. “So they start expressing DNA repair systems. HAAs are not directly damaging DNA, rather they are inhibiting GAPDH, which is involved in increasing the oxidative stress that we are observing.”

A growing body of information has shown that GAPDH is associated with the onset of neurological diseases.

“If you carry a natural mutation for GAPDH and are exposed to high levels of these disinfection byproducts, you could be more susceptible to adverse health effects such as Alzheimer’s,” he said.

More research is needed to study iodinated disinfection byproducts because they are the most reactive in inhibiting GAPDH function and are currently not regulated by the EPA, Plewa said.

“We replaced the standard working model of direct DNA damage with a new working model based on a cellular target molecule,” he said. “This discovery is a fundamental contribution to the field of drinking water science.”

Public release date: 25-Oct-2011

How cannabis causes ‘cognitive chaos’ in the brain

Cannabis use is associated with disturbances in concentration and memory. New research by neuroscientists at the University of Bristol, published in the Journal of Neuroscience [Oct. 25], has found that brain activity becomes uncoordinated and inaccurate during these altered states of mind, leading to neurophysiological and behavioural impairments reminiscent of those seen in schizophrenia.

The collaborative study, led by Dr Matt Jones from the University’s School of Physiology and Pharmacology, tested whether the detrimental effects of cannabis on memory and cognition could be the result of ‘disorchestrated’ brain networks.

Brain activity can be compared to performance of a philharmonic orchestra in which string, brass, woodwind and percussion sections are coupled together in rhythms dictated by the conductor. Similarly, specific structures in the brain tune in to one another at defined frequencies: their rhythmic activity gives rise to brain waves, and the tuning of these brain waves normally allows processing of information used to guide our behaviour.

Using state-of-the-art technology, the researchers measured electrical activity from hundreds of neurons in rats that were given a drug that mimics the psychoactive ingredient of marijuana. While the effects of the drug on individual brain regions were subtle, the drug completely disrupted co-ordinated brain waves across the hippocampus and prefrontal cortex, as though two sections of the orchestra were playing out of synch.

Both these brain structures are essential for memory and decision-making and heavily implicated in the pathology of schizophrenia.

The results from the study show that as a consequence of this decoupling of hippocampus and prefrontal cortex, the rats became unable to make accurate decisions when navigating around a maze.

Dr Jones, lead author and MRC Senior Non-clinical Fellow at the University, said: “Marijuana abuse is common among sufferers of schizophrenia and recent studies have shown that the psychoactive ingredient of marijuana can induce some symptoms of schizophrenia in healthy volunteers. These findings are therefore important for our understanding of psychiatric diseases, which may arise as a consequence of ‘disorchestrated brains’ and could be treated by re-tuning brain activity.”

Michal Kucewicz, first author on the study, added: “These results are an important step forward in our understanding of how rhythmic activity in the brain underlies thought processes in health and disease.”

Public release date: 25-Oct-2011

You are what you eat: Low fat diet with fish oil slowed growth of human prostate cancer cells

A low-fat diet with fish oil supplements eaten for four to six weeks prior to prostate removal slowed down the growth of prostate cancer cells — the number of rapidly dividing cells — in human prostate cancer tissue compared to a traditional, high-fat Western diet.

 Done by researchers at UCLA’s Jonsson Comprehensive Cancer Center, the short-term study also found that the men on the low-fat, fish oil supplement diet were able to change the composition of their cell membranes in both the healthy cells and the cancer cells in the prostate. They had increased levels of omega-3 fatty acids from fish oil and decreased levels of omega-6 fatty acids from corn oil in the cell membranes, which may directly affect the biology of the cells, though further studies are needed, said Dr. William Aronson, the study’s first author and a researcher with UCLA’s Jonsson Comprehensive Cancer Center.

The study also found that blood obtained from patients after the low-fat, fish oil diet program slowed the growth of prostate cancer cells in a test tube as compared to blood from men on the Western diet, which did not slow cancer growth.

 “The finding that the low-fat, fish oil diet reduced the number of rapidly dividing cells in the prostate cancer tissue is important because the rate at which the cells are dividing can be predictive of future cancer progression,” Aronson said. “The lower the rate of proliferation, the lesser the chances that the cancer will spread outside the prostate, where it is much harder to treat.”

 The study appeared Oct. 25, 2011 in Cancer Prevention Research, a peer-reviewed journal of the American Association for Cancer Research.

The study, which evaluated blood samples before and after the diet commenced and examined tissue from the removed prostate, validated previous studies by Aronson and others done on cell lines and in animal models. Aronson said the study using human blood and tissue also proved that the changes prompted by what the men were eating were clearly evident in their prostate tissue – the “treatment” was indeed reaching the targeted organ because of the changes in the prostate cell membrane’s fatty acid composition.

 “You truly are what you eat,” said Aronson, a clinical professor of urology, who also serves as chief of urologic oncology at the West Los Angeles Veterans Affairs Medical Center. “Based on our animal studies, we were hopeful that we would see the same effects in humans. We are extremely pleased about our findings, which suggest that by altering the diet, we may favorable affect the biology of prostate cancer.”

Aronson measured proliferation, or the rate of prostate cancer cell division, by staining tissue obtained from the radical prostatectomy specimens with an antibody against Ki-67, a protein involved in the cell-cycle progression and growth.

“The percentage of prostate cancer cells that stained for Ki-67 was determined by the pathologist, and this gave us an objective measurement of the percentage of cells that were actively dividing and therefore more aggressive,” said Aronson. “Previous studies found that patients with higher levels of Ki-67 in their prostate cancer tissue were more likely to have their prostate cancer progress to advanced stages, and were more likely to die from their prostate cancer. Thus, we are extremely encouraged by our findings that a low-fat diet with fish oil lowered Ki-67 levels and may have the potential to slow the progression of prostate cancer.”

Diet studies often are difficult to evaluate because getting patients to comply with dietary changes can be challenging. However, the food eaten by men in both arms of this study was precisely controlled, Aronson said. The meals were prepared by chefs in the UCLA Clinical Translational Research Center and delivered in bulk to study participants several times a week. Participants also met with a dietician, kept food diaries and were required to return uneaten food.

 “The key to this study was having the meals prepared and delivered to the study participants,” Aronson said. “This resulted in a very high rate of compliance, making the study very well controlled.”

 The Western diet consisted of 40 percent of calories from fat, generally equivalent to what many Americans consume today. The fat sources also were typical of the American diet, and included high levels of omega-6 fatty acids from corn oil and low levels of fish oil that provide omega-3 fatty acids.

The low-fat diet consisted of 15 percent of calories from fat. Additionally, the men on this diet took five grams of fish oil per day in five capsules, three with breakfast and two with dinner, to provide fish oil omega-3 fatty acids. Omega-3 fatty acids have been found to reduce the incidence of heart disease and fight inflammation, and inflammation has been associated with certain cancers.

 “Preclinical studies suggest that lowering dietary omega-6 fatty acids from corn oil and increasing omega-3 fatty acids from fish oil decreases the risk of prostate cancer development and progression,” the study states. “We found this diet intervention resulted in a decrease in omega-6 vs. omega-3 fatty acid ratios in benign and malignant prostate tissue and a decrease in malignant cell proliferation.”

Aronson cautioned that he could not recommend dietary changes based on this study because of its short duration and small sample size. However, based on these results he is organizing a much larger study of 100 men with prostate cancers who have elected active surveillance, meaning they’re not getting any treatment for their disease but are getting regular biopsies and check-ups.

The future study will randomly divide the men into a low-fat, fish oil supplement group and a traditional Western diet group and follow them for a year to evaluate the diet effects on prostate cancer proliferation.

Public release date: 25-Oct-2011

1 in 5 medical journal articles include honorary and ghost authors

Research: Honorary and ghost authorship in high impact biomedical journals – a cross sectional survey

Just over one in five (21%) of articles published in six leading medical journals in 2008 have evidence of honorary and ghost authorship, finds a study published on http://www.bmj.com today.

These results demonstrate that inappropriate authorship remains a problem in high impact biomedical publications, say the authors.

Inappropriate (honorary and ghost) authorship and the resulting lack of transparency and accountability have been important concerns for the academic community for decades. Honorary authors are individuals who are named as authors but have not contributed substantially to be able to take responsibility for the work. Ghost authors are individuals who have made substantial contributions to the work but are not named as authors.

In the 1980s, the International Committee of Medical Journal Editors (ICMJE) developed guidelines for responsible and accountable authorship. These criteria are updated regularly and have been adopted by more than 600 biomedical journals. However, studies have found the prevalence of honorary authors to be as high as 39%, and ghost authors as high as 11% across a range of journals.

So a team of US researchers compared the prevalence of articles with honorary and ghost authors published in six leading general medical journals in 2008 with that reported by authors of articles published in 1996.

A total of 630 authors responded to the survey. The overall prevalence of articles with honorary authorship, ghost authorship, or both was 21%, a decline from 29% in 1996.

They found no change in the prevalence of honorary authors relative to 1996, but found a significant decline in the prevalence of ghost authorship.

The highest prevalence of both types of inappropriate authorship occurred in original research articles, as opposed to editorials and review articles.

These results demonstrate that inappropriate authorship remains a problem in high-impact biomedical publications, say the authors.

They conclude that “increased efforts by scientific journals, individual authors, and academic institutions are essential to promote responsibility, accountability, and transparency in authorship, and to maintain integrity in scientific publication.”

These results suggest that standards need tightening up, say Patricia Baskin and Robert Gross from the journal Neurology, in an accompanying editorial.

They point out that “as research becomes more collaborative and complex, the challenges to transparency in authorship and disclosure become greater,” and they call for further work “to assess whether greater definition of roles and conflicts of interest substantially change the prevalence of inappropriate authorship.”

Public release date: 25-Oct-2011

Strawberries protect the stomach from alcohol

In an experiment on rats, European researchers have proved that eating strawberries reduces the harm that alcohol can cause to the stomach mucous membrane. Published in the open access journal Plos One, the study may contribute to improving the treatment of stomach ulcers.

A team of Italian, Serbian and Spanish researchers has confirmed the protecting effect that strawberries have in a mammal stomach that has been damaged by alcohol. Scientists gave ethanol (ethyl alcohol) to laboratory rats and, according to the study published in the journal Plos One, have thus proved that the stomach mucous membrane of those that had previously eaten strawberry extract suffered less damage.

Sara Tulipani, researcher at the University of Barcelona (UB) and co-author of the study explains that “the positive effects of strawberries are not only linked to their antioxidant capacity and high content of phenolic compounds (anthocyans) but also to the fact that they activate the antioxidant defences and enzymes of the body.”

The conclusions of the study state that a diet rich in strawberries can have a beneficial effect when it comes to preventing gastric illnesses that are related to the generation of free radicals or other reactive oxygen species. This fruit could slow down the formation of stomach ulcers in humans.

Gastritis or inflammation of the stomach mucous membrane is related to alcohol consumption but can also be caused by viral infections or by nonsteroidal anti-inflammatory medication (such as aspirin) or medication used to treat against the Helicobacter pylori bacteria.

Maurizio Battino, coordinator of the research group at the Marche Polytechnic University (UNIVPM, Italy) suggests that “in these cases, the consumption of strawberries during or after pathology could lessen stomach mucous membrane damage.”

The team found less ulcerations in the stomachs of those rats which had eaten strawberry extract (40 milligrams/day per kilo of weight) for 10 days before being given alcohol.

Battino emphasises that “this study was not conceived as a way of mitigating the effects of getting drunk but rather as a way of discovering molecules in the stomach membrane that protect against the damaging effects of differing agents.”

Treatments for ulcers and other gastric pathologies are currently in need of new protective medicines with antioxidant properties. The compounds found within strawberries could be the answer.

Public release date: 25-Oct-2011

Many Alzheimer’s patients get drugs with opposing effects

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

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

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

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

The researchers found:

■Of the cholinesterase inhibitor users, 37 percent were also taking at least one anticholinergic drug, and more than 11 percent took two or more. This was similar to other studies of Medicare beneficiaries.

■For those using both medication types, dual use generally lasted three to four months, but 25 percent used both classes of drugs for more than a year.

■Anticholinergics were already being used in 23 percent of people receiving a new cholinesterase inhibitor prescription, and 77 percent continued, even after starting the cholinesterase inhibitor.

■Subjects using both medication types were not more likely to enter a nursing home or to die than those taking only cholinesterase inhibitors.

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

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

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

Public release date: 25-Oct-2011

Environmental toxin Bisphenol A can affect newborn brain

Newborn mice that are exposed to Bisphenol A develop changes in their spontaneous behavior and evince poorer adaptation to new environments, as well hyperactivity as young adults. This has been shown by researchers at Uppsala University. Their study also revealed that one of the brain’s most important signal systems, the cholinergic signal system, is affected by Bisphenol A and that the effect persisted into adulthood.

Our environment contains a number of pollutants, including Bisphenol A, which is used in plastics in a number of different applications. When plastic products are used, Bisphenol A can leak out, which is especially problematic as it is used in baby bottles, tin cans, plastic containers, plastic mugs, which are used by people of all ages. Both in Sweden and globally, Bisphenol A is widely used, and the substance has been found in human placentas, fetuses, and breast milk.

In recent years measurable amounts of Bisphenol have been found in dust from regular homes, but opinion differs regarding any negative effects of Bisphenol A, and risk assessments from various parts of the world present contradictory recommendations, even though the information used comes from the same research reports. Here in Sweden the Swedish Chemicals Agency and the Medical Products Agency are working on a ban for Bisphenol A in baby bottles and certain other plastic products.

In humans and mammals, the brain develops intensively during a limited period of time. In human babies, this brain development period runs from the seventh month of gestation through the first two years of life. The corresponding period for mice takes place during the 3-4 first weeks after birth. Uppsala researchers have shown in previous research studies that various toxic compounds can induce permanent damage to brain function when they are administered to newborn mice during this developmental period. Examples of such compounds are so-called brominated flame-retardants, polychlorinated biphenyls (PCBs), and DDT.

In an entirely new study these researchers examined whether exposure to Bisphenol A during the neonatal period can cause permanent damage to brain function. In the experiment different doses of Bisphenol A were given to mice when they were ten days old. The mice underwent a so-called spontaneous behavior test as young adults, in which they were made to change cages from their well-known home cage to another identical one during one hour. Normal mice are very active during the first 20 minutes, exploring the new home environment. This activity declines during the next 20 minutes, and in the final 20 minutes it drops even more, and the mice settle down and sleep.

“In our study we found that a single exposure to Bisphenol A during the short critical period of brain development in the neonatal period leads to changes in spontaneous behavior and poorer adaptation to new environments, as well as hyperactivity among young adult mice. When this is examined again later in their adult life, these functional disturbances persist, which indicates that the damage is permanent and do not in fact disappear,” says Henrik Viberg at the Department of Organism Biology.

Using the same behavioral method, it was also examined whether the individuals that had received Bisphenol A during their neonatal period reacted differently than normal individuals to adult exposure to nicotine, which would indicate that one of the brain’s most important signal systems, the cholinergic signal system, was affected. Normal animals exposed as adults to the given dose of nicotine experience dramatically increased activity compared with animals that were not exposed to nicotine. Animals that had been exposed to Bisphenol A during their neonatal period and then received nicotine as adults did not evince the same hyperactivity as normal animals at all. This indicates that the choligernic signal system had been affected and that these individuals had had developed increased sensitivity to this type of exposure in adulthood. Once again, this effect was induced during the neonatal period but persisted into adulthood.

“We have previously seen this type of effect from several other environmental toxins that are still prevalent in both indoor and outdoor environments. As these effects are similar to each other, it’s possible that several different environmental toxins, including Bisphenol A, may work together in causing disturbances during brain development. This in turn may mean that the individual dosages of the various environmental toxins that are required to cause disturbances may be lower than those we examined in our studies of, for example, Bisphenol and brominated flame-retardants,” says Henrik Viberg.

Public release date: 25-Oct-2011

Food Chemical Regulations Rely Heavily on Industry Self-Policing and Lack Transparency

Washington, DC – 10/26/2011 – Safety decisions concerning one-third of the more than 10,000 substances that may be added to human food were made by food manufacturers and a trade association without review by the U.S. Food and Drug Administration (FDA), according to an analysis spearheaded by the Pew Health Group.

The report, published today in the peer-reviewed journal Comprehensive Reviews in Food Science and Food Safety, illustrates potential problems with the U.S. food additive regulatory program.

“Congress established our food additive regulatory program more than 50 years ago, and it does not stand up well to scrutiny based on today’s standards of science and public transparency,” said Tom Neltner, Food Additives Project director in the Pew Health Group.

The research also found that the FDA developed an expedited process in the mid-1990’s that essentially eliminated the opportunity for public involvement in decision making prior to FDA’s safety determination. This shift doubled the rate of industry requests for FDA review. In contrast, standard operating procedure for other federal regulatory decisions regarding drug, workplace, and environmental safety requires public notice and an opportunity to comment.

 “While the shift to a new regulatory process–one in which companies make safety decisions and ask FDA to confirm them–has sped up agency review, it has also bypassed the public,” Neltner said.  “Subjecting safety decisions to comment from competitors, academic scientists, public interest groups, and the general public can result in stronger protections for consumers. In an age of growing demand for government transparency, there is virtually no meaningful opportunity for participation in decisions about large classes of substances added to the food supply.”

When Congress passed the Food Additives Amendment of 1958, it created a structure that has limited the FDA’s ability to effectively regulate substances added to food because the law:

1.Allows manufacturers to determine that the use of an additive is “generally recognized as safe” (GRAS), and then use that substance without notifying the FDA. As a result, the agency is unaware of many substances that may be added to food and lacks the ability to ensure that safety decisions were properly made.

2.Does not require that manufacturers inform the FDA when health reports suggest new hazards associated with additives already used in food. Therefore, the agency has no access to unpublished reports and must expend limited resources sifting through published information to identify potential problems and set priorities.

In addition to the article examining the state of the food additive regulation, a piece in the same publication summarizes a workshop, co-sponsored by the Institute of Food Technologists and the journal Nature, examined how FDA evaluates the potential hazards posed by substances added to food. The two-day session, held in April 2011, brought together science and food policy experts from government, industry, academia, and public interest organizations. Issues discussed at the workshop and presented in the journal article include:

The need for clear procedures to develop validated toxicological tests and regularly revise guidance documents to reflect advances in science;

Opportunities to improve academic research to make it more usable for regulatory decision making and enhance coordination between federal agencies; and

Challenges to reassessing a chemical’s safety after it is on the market.

Both journal articles appear in the November issue of Comprehensive Reviews in Food Science and Food Safety. They are the first in a series of the Pew Health Group’s assessments of the scientific evidence and FDA’s regulatory system, evaluating whether the agency ensures chemicals added to food are safe as required by law. Future articles will consider other aspects of the scientific analysis and the law, and will provide case studies of issues raised about the FDA’s food additives program. The Pew Health Group will develop policy recommendations to reduce unnecessary and hidden risks that are informed by their evaluation.

Public release date: 26-Oct-2011

Betcha won’t eat just one: Study shows people consume more candies when they’re indivdually wrapped

If you believe that good things always come in small packages, University of Alberta researcher Jennifer Argo’s new study may change your mind — especially this close to Halloween.

In an article forthcoming in the Journal of Marketing, Argo explores how our consumption behaviours change when it comes to treats like chocolates and candies are placed in smaller packages. She says that people eat more of a product when it is placed in small packages rather that a regular-sized packages.

However, she said, those with low-appearance self-esteem — the term researchers use to describe people who are concerned about their body, weight or physical appearance — tend to consume more than the average population, especially when certain conditions seemed favourable.

“The low-appearance self-esteem people ate the most when they were told that the caloric information was favourable (low in calories), when the caloric information was on the front of the package and when the product was visible (clear packaging),” said Argo. “People in the high-appearance self-esteem category — those who did not indicate concerns about weight or physical appearance — still ate more, but there was a big jump in the consumption quantity for [those with low self-esteem].”

Giving in to the dark chocolate side

Argo says that information contained on the packages in the study samples did have an effect on the low-appearance self-esteem participants. This group tended to eat less when the product wasn’t visible, the caloric information was missing or they believed there were more calories in the small packages than what they expected.

She said elements such as a visible product and content labeling information served as cues to the group’s susceptibility, which Argo noted gave this group a false sense of belief that the package would help them manage consumption and help them achieve potential weight-management goals. While this might be true if only a single small package is present, Argo says that, in reality, small packaged goods are often sold in multiples and her study showed that these helpful, small packages are detrimental to consumers’ waistlines.

“These consumers are basically saying, ‘this package is going to protect me; it’s going to help me achieve my goal,’ and so they relinquish control to the package,” she said. “They throw up their hands and say, ‘I don’t have to worry because the package is taking care of everything for me.’ As soon as they’ve given up initial control, they have no control to deal with that next package that’s presented to them.”

Self-defense against small packages

Argo says that buying the regular-sized packages of these types of snacks and exercising portion control will not only reduce calories, but also save money as well, although she says that some people may still opt to buy the small packages out of convenience. For this group, she counsels that they retake control and limit the number of packages they take out at any one time. And especially with the seductive call of leftover Halloween candies around the corner, Argo says the old adage of “watch what you eat” may not be a bad idea.

“Relinquishing control to small packages is “a very cognitive process; people are purposefully doing this,” she said. “(In the study) we found that if we interrupt the participants, if we distracted them with a task, they don’t fall prey (to overeating).

“When it’s a small package, distractions are actually beneficial in some respects.”

Public release date: 27-Oct-2011

Vitamin B derivative helps diabetics with mild kidney disease

Pyridorin may prevent kidney failure, but not in patients with advanced kidney disease

•Pyridorin, a vitamin B6 derivative, may help slow or prevent the progression of mild kidney disease in some patients with diabetes.

 •The drug does not appear to help diabetics with more advanced kidney disease.

•The prevalence of type 2 diabetes is expected to double by 2030. Kidney disease cases are sure to rise in parallel.

Washington, DC (Thursday, October 27, 2011) — A vitamin B6 derivative may help slow or prevent the progression of mild kidney disease in patients with diabetes, according to a study appearing in an upcoming issue of the Journal of the American Society Nephrology (JASN). The drug may benefit increasing numbers of patients as the prevalence of diabetes rises.

Approximately 40% of all patients who need dialysis or a kidney transplant can blame diabetes for their kidney problems. Because the number of patients with type 2 diabetes is expected to double by 2030, the prevalence of kidney failure is sure to increase. New therapies that can delay the progression of diabetic kidney disease may help prevent kidney failure and save lives. Researchers have wondered whether the drug Pyridorin, a derivative of vitamin B6, may be such a candidate. Pyridorin targets several cellular processes that may be relevant to the progression of diabetic kidney disease.

Edmund Lewis, MD (Rush University Medical Center) and his colleagues within the Collaborative Study Group (a large clinical trial group comprised of various kidney care centers) tested the potential of Pyridorin (generic name pyridoxamine dihydrochloride) for treating patients with diabetic kidney disease.

For one year during the double-blind, randomized, placebo-controlled trial, 317 patients received placebo twice a day, Pyridorin at a dose of 150 mg twice a day, or Pyridorin at a dose of 300 mg twice a day.

Overall, the drug did not provide any benefit over placebo for slowing or preventing the progression of diabetic kidney disease; however, Pyridorin did help patients with only mild forms of the disease.

“It appears the drug may be beneficial in a sub-group of patients with only mild kidney disease but does not appear to be beneficial for patients with more advanced kidney disease,” said Dr. Lewis. “The results warrant further trials in patients with mild diabetic kidney disease,” he added.

Public release date: 27-Oct-2011

Older men with higher testosterone levels lose less muscle mass as they age

Study shows higher testosterone levels may help older men preserve muscle mass and delay frailty as they age

A recent study accepted for publication in The Endocrine Society’s Journal of Clinical Endocrinology & Metabolism (JCEM) found that higher levels of testosterone were associated with reduced loss of lean muscle mass in older men, especially in those who were losing weight. In these men, higher testosterone levels were also associated with less loss of lower body strength.

Loss of muscle mass and strength contribute to frailty and are associated with falls, mobility limitations and fractures. Men lose more muscle mass and strength than women as they age, suggesting that sex steroids, and testosterone in particular, may contribute to body composition and physical function changes. This study sought to better understand the relationship between testosterone levels and healthy aging in older men and found that higher testosterone levels may help older men preserve muscle mass and delay frailty as they age.

“Our study finds that men, aged 65 years and older, with higher testosterone levels lost less muscle mass, especially in their arms and legs, than men this age who had lower testosterone levels,” said Erin LeBlanc, MD, of Kaiser Permanente Northwest in Portland, OR and lead author of the study. “Men who had higher testosterone levels before they lost weight also lost less leg function and could stand up more easily from a chair than men who had lower testosterone levels before they lost weight.”

In this study, researchers used data from 1,183 men aged 65 years or older and tested the hypothesis that higher baseline measures of sex steroids are associated with lesser declines in lean mass and maintenance of physical performance over an average follow-up of 4.5 years. Body composition was measured using dual energy x-ray absorptiometry (DXA) scans and physical performance was measured through a series of exercises that assessed grip strength, lower extremity power, walking speed and the ability to rise from a chair without the use of arms.

“The amount of testosterone men have in their bodies may contribute to how much muscle and strength they lose as they get older,” said LeBlanc. “Our study adds evidence to the growing body of literature that suggest higher levels of endogenous testosterone may be favorably associated with some key components of healthy aging in men.”

Public release date: 31-Oct-2011

Celiac patients face potential hazard as information on cosmetic ingredients difficult to find

Products used on lips and face can result in unexpected exposure to gluten

Washington, DC — The lack of readily available information about cosmetic ingredients may cause patients with celiac disease who use lip, facial or body products to unknowingly expose themselves to gluten — an ingredient they need to avoid, according to the results of a new study unveiled today at the American College of Gastroenterology’s (ACG) 76th Annual Scientific meeting in Washington, DC.

The study, “Information About Cosmetic Ingredients is Difficult to Obtain: A Potential Hazard for Celiac Patients,” focused on the top 10 cosmetic companies in the United States in order to evaluate the availability of information about cosmetic ingredients and the accessibility of gluten-free products.

“While information on the ingredients of food products has become increasingly available, recent reports have revealed that the use of some cosmetics, including products used on the lips and face, can result in unexpected exposure to gluten,” said researchers Marie L. Borum, MD, EdD, MPH and Pia Prakash, MD, of George Washington University.

Dr. Borum said this study was prompted in part by one of her patient cases, “Body Lotion Causing A Celiac Exacerbation and Dermatitis Herpetiformis: Natural is Not Always Healthy,” where a 28-year old woman experienced exacerbation of her celiac symptoms, including gastrointestinal complications and a recurring skin rash after using a body lotion advertised as “natural.”

“It was difficult to determine whether gluten was contained in the product she was using,” said Dr. Prakash. “But once she stopped using the body lotion her symptoms resolved. This case highlights the fact that celiac patients face a huge challenge in trying to determine whether cosmetic products contain gluten — and a risk of unknowingly exposing themselves to gluten.”

The lack of readily available information about cosmetic ingredients that Dr. Borum experienced first-hand with her patient led researchers to identify the top cosmetic companies in the United States and subsequently visit the official website for each company and search for “gluten” and “gluten free” to determine products specifically manufactured without gluten. Additionally, the ingredients for each cosmetic were also researched using an independent website.

Only two of the top ten cosmetic companies in the United States offered detailed ingredient information, however no gluten sources were identified, according to the study. The independent websites offered ingredients from five companies — but no gluten sources were identified. Ingredient information was unavailable for four companies and none of the cosmetic companies specifically offered gluten-free cosmetic options, according to the study findings.

“The findings are alarming because gluten-containing cosmetics can be inadvertently obtained by the consumer and use of these products can result in an exacerbation of celiac disease,” said Dr. Prakash. “This study revealed that information about the ingredients, including the potential gluten content, in cosmetics is not readily available.”

Dr. Prakash added that while smaller companies may specifically advertise gluten-free alternatives, “top-selling manufacturers should indicate whether their products can be safely be used by individuals with gluten sensitivity.”

Public release date: 31-Oct-2011

Cigarette smoking’s impact lingers after quitting

Current, former smokers may face impaired pancreatic duct cell function, elevated colorectal cancer risk that persists longer for women

Washington, DC — Cigarette smoking appears to impair pancreatic duct cell function–even for those who quit–putting all smokers at risk of compromised digestive function regardless of age, gender and alcohol intake, according to the results of a study unveiled today at the American College of Gastroenterology’s (ACG) 76th Annual Scientific meeting in Washington, DC.

In a separate smoking-related study also released today, “Smoking Cessation and the Risk for Advanced Neoplasia: Risk for Women Persists Longer than for Men,” researchers from the University of Connecticut found that the risk of advanced pre-cancerous tissue changes (neoplasia) was significantly elevated for women —even if they stopped smoking—but not for men–suggesting that the impact of smoking in women has a longer effect than in men.

In the study, “Cigarette Smoking Impairs Pancreatic Duct Cell Function,” researchers from Center for Pancreatic Disease at Brigham and Women’s Hospital in Boston assessed pancreatic duct cell function in smokers and non-smokers (current and past). A total of 131 subjects (74 smoked and 57 never smoked) underwent secretin-stimulated endoscopic pancreatic function testing (ePFT), for pancreatic fluid bicarbonate analysis. Cigarette smoking exposure was found to be associated with an abnormal ePFT result, and there was no statistical difference in peak bicarbonate concentration between current and former smokers, according to the results.

The risk of pancreatic duct cell dysfunction was 56.78 percent in former or current smokers and 26.32 percent in nonsmokers, according to Vivek Kadiyala, MD, who presented the findings. “Our data suggests the risk of duct cell dysfunction was doubled in patients who smoked compared to nonsmokers,” said Dr. Kadiyala.

“These findings indicate that anyone with a history of smoking, either current or past is at greater risk of impaired pancreatic duct cell function,” said Dr. Kadiyala.

“Additionally, the findings underscore the value that early smoking cessation may have for patients with chronic pancreatitis and as a result healthcare providers should advise patients to quit smoking as part of their overall treatment plan.”

Elevated Colorectal Cancer Risk for Women, Even After Smoking Cessation

Even after women quit smoking they are still at an increased risk for colorectal cancer, according to researchers at the University of Connecticut who examined the risk of advanced neoplasia in 2428 male and female patients over age 45 who have quit smoking.

The recent ACG colorectal cancer screening guidelines include smoking as a risk factor that should be considered when screening for colorectal cancer. Although the risk for neoplasia increases after 10 pack years of exposure, there is little data regarding the risk for advanced neoplasia after quitting.

“The risk of advanced neoplasia was significantly elevated for women and men whether they were current smokers and/ or former smokers who quit within five years of screening colonoscopy,” said Joseph C. Anderson, MD, FACG, also of the White River Junction VA Medical Center in Vermont, who presented the findings. “The risk was elevated for female smokers who quit six to ten years prior to screening but not for male smokers.”

Dr. Anderson said the data suggests that the impact of smoking has a longer effect in women than in men, and that the data could have an impact on colorectal cancer screening in male versus female smokers. “If smoking is used as a factor for determining when to begin screening, for example, we might have different parameters for men and women.”

Public release date: 31-Oct-2011

Probiotics effective in combating antibiotic-associated diarrhea

‘Good bugs’ look promising as anti-inflammatory agent for patients with ulcerative colitis, psoriasis, chronic fatigue syndrome

Washington, DC — In four different studies presented at the American College of Gastroenterology’s (ACG) 76th Annual Scientific meeting in Washington, DC, researchers explored the effectiveness of probiotics for antibiotic-associated diarrhea; as an anti-inflammatory agent for patients with ulcerative colitis, psoriasis and chronic fatigue syndrome; and for people with abdominal discomfort and bloating who have not been diagnosed with a functional bowel disorder, such as irritable bowel syndrome (IBS).

These four studies will be featured during an ACG press briefing on Tuesday, November 1, 2011 entitled: “Good, Bad and Ugly Bugs: Mother Nature as a Treatment for Better Health in the GI Tract,” which will highlight new clinical science that explores the role of the “gut microbiota” –the bacterial composition of the GI tract – and the efficacy of probiotics and fecal microbiota transplantation in treating various GI conditions.

Probiotics are considered “good bacteria” that help maintain the natural balance of microflora in the digestive tract where trillions of bacteria live. While most of the more than 400 different species in the gut are healthy bacteria, others, “bad bugs” have the potential to cause damage to the digestive system. At times, an imbalance between the good and bad bacteria can lead to uncomfortable symptoms or illnesses. Probiotics are bacteria, or even sometimes yeast, which may alleviate common GI symptoms and are found in many commercial products including yogurt, juices, soy products, fermented milk, tempeh and other dietary supplements. They also come in capsule, tablet or powder formulations.

Probiotic Therapy Reduce the Incidence of Antibiotic Associated Diarrhea

Antibiotic-associated diarrhea (AAD) and Clostridium difficile-associated diarrhea (CDAD) are complications of long-term antibiotic use and are associated with significant cost and morbidity.

While the role of probiotics in treating AAD and CDAD has been investigated in several trials with conflicting results, this review, “Probiotic Prophylaxis Significantly Reduces the Incidence of Antibiotic Associated Diarrhea: A Meta-Analysis,” by researchers from the Maimonides Medical Center in Brooklyn, New York, is the first meta-analysis examining the role of probiotics in treating these conditions.

Twenty-two studies were identified and a total of 3096 patients were included, 63 percent of whom were adults and all treated with various species of probiotics. Four studies (35 percent of the population of the study) used S. boulardii as the probiotic of choice. The average treatment period with probiotics was 1.5 weeks, with the shortest period being five days and the longest period being three weeks, according to Steven Shamah, MD, who presented the findings.

“Overall in twenty-two studies, probiotic prophylaxis significantly reduced the odds ratio of developing AAD by approximately 60 percent. This analysis clearly demonstrates that probiotics offer protective benefit in the prevention of these diseases,” said principal investigator Rabin Rahmani, MD.

“These findings suggest that all patients who are at high-risk for these infections demonstrated by recent antibiotic useage, old age, recent hospitalization, low albumin, and immunosuppression should be considered for probiotic therapy,” said Dr. Shamah. He added that further prospective studies are warranted to examine the most efficacious duration, dose and specific species of probiotics in prevention of AAD and CDAD in high risk patients.

Another related meta-analysis, “Probiotics in Antibiotic-Associated Diarrhea: An Updated Meta-Analysis of Randomized Controlled Trials,” confirmed earlier results suggesting the preventative effects of probiotics in AAD. Researchers from Beth Israel Deaconess Medical Center, Harvard Medical School, aimed to estimate the reduction in risk of developing AAD with probiotic therapy in randomized controlled trials (RCT), and identify factors associated with such reduction. The analysis included 28 randomized controlled trials with 3,338 total patients receiving single or combination antibiotics for various indications.

“The preventive effect of probiotic use remained significant regardless of species used, adult versus child populations, study quality score and antibiotic administered,” said researcher Elizabeth Videlock, MD, who presented the findings. “The preventive effect of probiotics is also apparent during combined antibiotic treatment for H.pylori eradication.”

B. infantis 35624 Investigated in Non-Patient Population

In the largest study on probiotics done in the United States in a non-patient population, researchers from the University of North Carolina at Chapel Hill assessed the efficacy of B. infantis 35624–a probiotic that has been effective in relieving symptoms in IBS patients—for the relief of abdominal discomfort and bloating in a non-patient population.

The double-blind, randomized, placebo controlled, parallel study with a two-week placebo run-in phase followed by a four-week intervention phase was conducted at ten clinical centers in the US. The study included 302 non-patients who experienced abdominal discomfort and bloating more than twice weekly on average for at least three months but had not seen a physician or received prescribed medication for their symptoms in the past 12 months. They called in daily to report symptom severity on a six point Likert scale during the run-in and treatment phase.

Although mean severity scores for both, abdominal discomfort and bloating improved during the intervention period, there were no significant differences between the placebo and probiotic group, according to Yehuda Ringel, MD, who presented the findings.

“Unlike previous clinical studies in IBS patients, we were not able to demonstrate a statistically significant improvement in mean severity of abdominal discomfort and bloating with B. infantis 35624 in a non-patient population,” said Dr. Ringel. He attributed this in part to the high placebo response and the possible “floor effect” which means the severity of symptoms is too low to measure any improvement. “This doesn’t mean that B. infantis 35624 cannot help ease abdominal discomfort and bloating in non-patients—we just couldn’t demonstrate it because the room for improvement is low compared to IBS patients, where symptom severity is much higher. Our secondary finding of significantly more bloating-free days in the B. infantis 35624 group needs further studies, particularly in the non-patient, healthy population.”

Probiotic B. infantis 35624 Promising as Anti-Inflammatory Agent for Patients with Ulcerative Colitis, Psoriasis, Chronic Fatigue Syndrome

Microbial imbalance has been proposed as one possible explanation for the increased incidence of a wide range of inflammatory disorders, including ulcerative colitis, suggesting that altering the balance between good and bad bacteria in the gut may promote an immune regulatory response that could reduce inflammation, according to researchers at the Alimentary Pharmabiotic Centre at University College Cork and Alimentary Health Ltd in Cork, Ireland, who aimed to determine if B. infantis could influence systemic pro-inflammatory biomarkers in patients with inflammatory disease.

The double-blind, placebo controlled study, “Oral Administration of the Probiotic Bifidobacterium Infantis 35624 to Humans Induces Immunoregulatory Responses in Vivo,” included healthy volunteers, and patients with psoriasis, ulcerative colitis and chronic fatigue syndrome. According to the results, plasma levels of the anti-inflammatory cytokine, IL-10, were significantly increased in healthy volunteers and psoriasis patients, but not placebo for eight weeks; while plasma levels of the pro-inflammatory cytokines TNF-alpha and IL-6 were significantly reduced in all patient groups that received B. infantis. In addition, C-reactive protein (CRP) levels were also significantly reduced in psoriasis, ulcerative colitis and chronic fatigue patients at the end of treatment with B. infantis compared to placebo treated patients.

“The human immunological response to B. infantis further supports the hypothesis that manipulation of the microbiota with specific therapeutic microbes can have a significant effect on host inflammatory processes,” said Eamonn M.M. Quigley, MD, FACG, who presented the findings. “This anti-inflammatory effect is not restricted to a specific disease state, suggesting that B.infantis induces a critical cellular response, which may include the induction of regulatory cell subsets.”

Public release date: 31-Oct-2011

Yoga aids chronic back pain sufferers

Yoga can provide more effective treatment for chronic lower back pain than more conventional methods, according to the UK’s largest ever study into the benefits of yoga.

The study, led by the University of York and funded by Arthritis Research UK, found that people offered a specially-designed 12-week yoga programme experienced greater improvements in back function and more confidence in performing everyday tasks than those offered conventional forms of GP care.

The research focused on back function – people’s ability to undertake activities without being limited by back pain, which was measured using the Roland Morris Disability Questionnaire. Although improvements in back function were more pronounced at three months, researchers found there was still an improvement in people’s ability to perform tasks such as walking more quickly, getting dressed without help or standing up for longer periods of time even nine months after the classes had finished.

The trial involved two groups of people who were both receiving GP care for chronic or recurrent back pain. A 156-strong group were offered group yoga classes specially designed to improve back function, while a second control group of 157 people were offered GP care alone.

The findings of the study, which was carried out by researchers from the Department of Health Sciences at the University of York and the Hull York Medical School, are published in the Annals of Internal Medicine this week.

Lower back pain is a common episodic condition, with 80 per cent of the UK population suffering from it at some point in their lives. It is estimated that around 4.9 million working days a year are lost due to back pain. However, few effective, evidence-based treatments exist.

The yoga programme, which involved 20 experienced yoga teachers, was designed and delivered by Truro-based Alison Trewhela, an Iyengar Yoga teacher and Senior Practitioner in Yoga on the British Register of Complementary Practitioners, in collaboration with York-based yoga teacher Anna Semlyen, a Back Care Advisor to the British Wheel of Yoga.

The classes were designed for complete beginners, with yoga teachers given extra training in back care. Participants were recruited from 39 general practices in seven Primary Care Trust areas, with classes held in non-NHS premises in Cornwall, North London, West London, Manchester and York.

Chief Investigator Professor David Torgerson, Director of York Trials Unit, in the University’s Department of Health Sciences, said: “Back pain is an extremely common and costly condition. Exercise treatment, although widely used and recommended, has only a small effect on back pain. We therefore set out to investigate an alternative approach using a specially-developed weekly yoga programme for back pain sufferers to see if this allowed them to manage their back pain more successfully.

“While previous studies have focused on the short-term benefits of yoga, we also wanted to see the long-term effects and measured improvements three, six and 12 months after entry into the study. Our results showed that yoga can provide both short and long-term benefits to those suffering from chronic or recurrent back pain, without any serious side-effects.”

Medical Director of Arthritis Research UK Professor Alan Silman said: “We’re delighted that our trial has shown that yoga provides such positive benefits for people with chronic low back pain. This extremely common condition cannot be managed with painkillers alone and there is an urgent need to have non-drug therapies that sufferers can utilise in their own home. This trial is part of our larger commitment to seek self-help solutions to this common musculoskeletal problem. There are compelling explanations why yoga may be helpful and this trial lends powerful support to the wider use of this approach.”

Trial participants completed a questionnaire at three, six and 12 months from the start of the programme. On average, members of the yoga group were able to undertake 30 per cent more activities compared with those in the usual care group after three months, a statistically significant difference between the two groups which has been recognised as clinically important.

The trial showed that there was more reduction in pain in the yoga group than the usual care group, but of marginal statistical significance.

Researchers also compared the results from the yoga programme with those for high-quality randomised trials for exercise and manipulation, the Alexander technique and cognitive-behavioural treatment. The results suggested that the 12-week yoga group programme may improve back function more than exercise and manipulation, cognitive-behaviour treatment and six sessions of 1-to-1 Alexander technique, but not as much as 24 sessions of 1-to-1 Alexander technique.

Trial participant Sue Faulkner, 68, retired from her job as an administrator four years ago with the intention of spending her time gardening. However, within six months of retiring her back was so bad she found that walking any distance was painful and she needed to stop regularly to rest. Gardening was out of the question.

Sue from Bishopthorpe in York said: “I felt a definite benefit after the programme as it made me more flexible and we were taught positions to relieve certain types of back pain. I’ve continued going to yoga classes and still do the positions I was taught during the 12-week programme. Walking around is no longer a problem and I can do my gardening now so long as I pace myself. I’ve even taken on an allotment with my daughter and son-in-law and no longer take pain killers.”

Those attending the specially-designed yoga programme, which involved step-by-step gentle classes, were encouraged to become self-sufficient in the long-term. Classes were supported with four home practice sheets, a manual, and a four-track audio CD teaching how to relax physically and mentally.

Iyengar Yoga teacher Alison Trewhela said: “The yoga programme offers poses for pain-relief and mental calming; mobilising, stretching, strengthening and relaxation; improving awareness of posture; education about how a healthy back functions; and positive mental focus. Yoga aims to treat the whole person – not just the physical.

“As most back pain conditions recur, these lifelong self-management skills are likely to be useful as a preventative measure. As a result of smaller previous trials, one million Americans currently practise yoga as a recommended treatment for low back pain.”

Participants in the yoga programme were surveyed nine months after classes had finished and more than half of those who responded were still regularly practising yoga, mostly at home, twice a week.

Public release date: 31-Oct-2011

Putting the body back into the mind of schizophrenia

A study using a procedure called the rubber hand illusion has found striking new evidence that people experiencing schizophrenia have a weakened sense of body ownership and has produced the first case of a spontaneous, out-of-body experience in the laboratory.

These findings suggest that movement therapy, which trains people to be focused and centered on their own bodies, including some forms of yoga and dance, could be helpful for many of the 2.2 million people in the United States who suffer from this mental disorder.

The study, which appears in the Oct. 31 issue of the scientific journal Public Library of Science One, measured the strength of body ownership of 24 schizophrenia patients and 21 matched control subjects by testing their susceptibility to the “rubber hand illusion” or RHI. This tactile illusion, which was discovered in 1998, is induced by simultaneously stroking a visible rubber hand and the subject’s hidden hand.

“After a while, patients with schizophrenia begin to ‘feel’ the rubber hand and disown their own hand. They also experience their real hand as closer to the rubber hand.” said Sohee Park, the Gertrude Conaway Vanderbilt Chair of Psychology and Psychiatry, who conducted the study with doctoral candidate Katharine Thakkar and research analysts Heathman Nichols and Lindsey McIntosh.

“Healthy people get this illusion too, but weakly,” Park continued. “Some don’t get it at all, and there is a wide range of individual differences in how people experience this illusion that is related to a personality trait called schizotypy, associated with psychosis‑proneness.”

Body ownership is one of two aspects of a person’s sense of self awareness. (The other aspect is self-agency, the sense that a person is initiating his or her own actions.) According to the researchers, the finding that schizophrenia patients are more susceptible to the rubber hand illusion suggests that they have a more flexible body representation and weakened sense of self compared to healthy people.

“What’s so interesting about Professor Park’s study is that they have found that the sense of bodily ownership does not diminish among patients with schizophrenia, but it can be extended to other objects more easily,” observed David Gray, Mellon assistant professor of philosophy at Vanderbilt, who is an expert on the philosophy of the mind. He did not participate in the study but is familiar with it. “Much of the literature concerning agency and ownership in schizophrenia focuses on the sense of lost agency over one’s own movements: But, in these cases, the sense of ownership is neither diminished nor extended.”

Before they began the procedure, the researchers gave participants a questionnaire to rate their degree of schizotypy: the extent to which they experience perceptual effects related to the illusion. The researchers found that the individuals who rated higher on the scale were more susceptible to the illusion.

The researchers gauged the relative strength of the RHI by asking participants to estimate the position of the index finger of their hidden hand on rulers placed on top of the box that conceals it before and after stimulation. The stronger the effect, the more the subjects’ estimate of the position of their hidden hand shifted in the direction of the rubber hand. Even the estimates of those who did not experience the effect subjectively shifted slightly.

The rubber hand illusion also has a physiological signature. Scientists don’t know why, but the temperature of the hidden hand drops by a few tenths of a degree when a person experiences the illusion. “It’s almost as if the hand is disowned and rejected, no longer part of the self,” Park commented.

The researchers were surprised when one of the patients undergoing the procedure experienced a full out-of-body experience. He reported that he was floating above his own body for about 15 minutes. According to Park, it is extremely rare to observe spontaneous out-of-body experiences in the laboratory. When they invited the patient back for a second session, he once again had an out-of-body experience during the rubber hand procedure, proving that the experience is repeatable.

“Anomalous experiences of the self were considered to be core features of schizophrenia decades ago but in recent years much of the emphasis has been on cognitive functions such as working memory,” said Park.

According to the psychologist, out-of-body experiences and body ownership are associated with a particular area in the brain called the temporoparietal junction. Lesions in this area and stimulation by strong magnetic fields can elicit out-of-body experiences. The new study suggests that disorders in this part of the brain may also contribute to the symptoms of schizophrenia.

The relationship between schizophrenia and body ownership may help explain the results of a German study published in 2008 that found a 12-week exercise program reduced the symptoms and improved the behavior of a small group of patients with chronic schizophrenia when compared to a control group that did not exercise. The study also found that the exercise increased size of the patients’ hippocampus slightly – a smaller-than-normal hippocampus is a well established symptom of schizophrenia.

“Exercise is inexpensive and obviously has a broad range of beneficial effects, so if it can also reduce the severity of schizophrenia it is all to the good,” said Park. These findings suggest that focused physical exercise which involves precise body control, such as yoga and dancing, could be a beneficial form of treatment for this disorder.

Public release date: 31-Oct-2011

Live longer with fewer calories

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

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

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

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

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

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

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

Public release date: 1-Nov-2011

First clinical trial of red wine ingredient shows metabolic shifts

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

“We saw a lot of small effects, but consistently pointing in a good direction of improved metabolic health,” said Patrick Schrauwen of Maastricht University in The Netherlands.

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

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

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

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

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

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

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

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

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

Public release date: 1-Nov-2011

Hormone in birth control shot linked to memory loss

TEMPE, Ariz. – The birth control shot Depo Provera offers a convenient alternative for women who don’t want to remember to take a daily pill. Ironically, research from Arizona State University has shown the shot actually may impair a person’s memory.

The ASU study connects medroxyprogesterone acetate (MPA), the hormone active in Depo Provera and many widely used menopausal hormone therapies, to impaired memory in rodents. The study is currently in press in the journal Psychopharmacology. An early on line version of the article is available at http://www.springerlink.com/content/53357212117581w6/.

The study was led by Blair Braden, an ASU psychology doctoral student, and Heather Bimonte-Nelson, an ASU associate professor of psychology and director of the Bimonte-Nelson Memory and Aging Lab. The work was done in collaboration with Laszlo Prokai from the University of North Texas Health Sciences Center, Fort Worth, Tex., and Alain Simard from Barrow Neurological Institute, Phoenix.

The Bimonte-Nelson lab first linked MPA to memory loss in rats while studying it as a component of hormone therapy for menopause. This earlier study showed that MPA impaired memory in menopausal-aged rats, and results were published in the November 2010 issue of Neurobiology of Learning and Memory. The current study specifically looks at the drug in relation to the birth control shot.

Bimonte-Nelson said she and Braden began asking questions about the effects of the drug because Braden was concerned about friends taking MPA as a contraceptive.

“This is an important question, because what we are going to have in our future are women who are menopausal that also have a history of taking MPA as birth control when they were younger,” said Bimonte-Nelson.

The U.S. Food and Drug Administration originally approved Depo Provera for use in October 1992. It requires an injection every 12 weeks. Its 99 percent effectiveness and the infrequency of doses make the shot an attractive alternative for women seeking to avoid pregnancy.

While other studies have examined Depo Provera’s effects on bone density, Bimonte-Nelson’s lab is the first to explore its effects on cognition. The researchers note that other forms of hormonal contraception, such as the pill, do not use MPA.

The study lasted approximately one year, using three groups of rats (which received doses at varying ages), plus a control group that did not receive the hormone. To test their memory, rats were placed in water-based mazes to swim and seek out hidden platforms in the water.

“What we found was pretty shocking – animals that had been given the drug at any point in their life were memory impaired at middle age compared to animals that never had the drug,” said Braden. “We also confirmed that in the subjects that only received the drug when young, the hormone was no longer circulating during memory testing when older, showing it had cleared from the system yet still had effects on brain function.”

The researchers also measured a marker of the gamma-aminobutyric acid (GABA) neurotransmitter system in the hippocampus of the rats’ brains to determine MPA’s physiological effects.

“What GABA does is slow the brain down,” Braden said. “So if there is too much of it, it can make it more difficult to produce memories. But then if there’s too little of it and there’s too much excitation, same thing – it makes you not able to produce memories correctly.”

The group plans to follow the animal studies with human trials, and the work is leading to results that could have profound implications for women of all ages.

“This research shows that even after this hormone is no longer on board, months and months later, resulting effects are impacting the brain and its function,” Bimonte-Nelson said. “This work is an important step forward in our understanding of the potentially long-lasting effects of clinically used hormones on brain function. However, more research is needed to determine whether these effects also occur in women that take this hormone as birth control or part of hormone therapy.”

Public release date: 1-Nov-2011

Health risk from eating well-done meat may be underestimated

Mice are often used to test whether substances in food are harmful to humans. This requires that mice and humans metabolise substances in the same way. Humans have certain enzymes in more parts of the body than mice. The health risk associated with harmful substances in food may therefore be underestimated.

Researchers at the Norwegian Institute of Public Health have adopted a mouse type where human enzymes have been inserted to examine whether people may be more sensitive to certain carcinogenic substances from heat-treated foods. They have obtained a better model to assess negative health effects in humans from substances in food using these mice. The results show that the incidence of intestinal tumours increased from 31 per cent to 80 per cent in “human-like” mice who consumed substances from meat crust (i.e. the surface formed during heat-treatment).

Food mutagens

Heat-processing of food can lead to the formation of carcinogenic substances. The formation of carcinogenic substances – so-called food mutagens – usually occurs at high temperatures when frying or grilling. There are enzymes called sulfotransferases (SULT) in several places in the human body. These are only found in the livers of normal laboratory mice. SULT-enzymes can make some substances in food less harmful, but they can also transform harmless substances into carcinogenic substances.

Better research

Humans have SULT-enzymes in many organs while normal mice only have them in the liver. Using results from laboratory mice to predict health risk to humans consuming food mutagens can therefore be underestimated. Researchers at the NIPH used laboratory mice with the same amount of SULT-enzymes in the intestines as humans in their experiments. The mice received the food mutagen often found in highest quantities in the crust of meat and fish. The researchers wanted to study tumour development in the intestines of the “human-like” mice, and compare this with tumour development in normal mice given the same food mutagen. The results showed that the incidence of intestinal tumours increased from 31 per cent to 80 per cent in “human-like” mice after consuming substances from the meat crust. This shows that normal laboratory mice are not a good model for assessing the health risk to humans following ingestion of food mutagens from well-done meat and fish. The study is funded by the Norwegian Research Council.

Reference

Svendsen C, Meinl W, Glatt H, Alexander J, Knutsen HK, Hjertholm H, Rasmussen T, Husøy T. Intestinal carcinogenesis of two food processing contaminants, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine and 5-hydroxymethylfurfural, in transgenic FVB min mice expressing human sulfotransferases. Mol Carcinog. 2011 Oct 17. doi: 10.1002/mc.20869.[Epub ahead of print]

Public release date: 1-Nov-2011

Catch the fever: It’ll help you fight off infection

New research published in the Journal of Leukocyte Biology demonstrates that elevated body temperature plays a vital role on the generation of effective T-cell mediated immune response

Bethesda, MD—With cold and flu season almost here, the next time you’re sick, think twice before taking something for your fever. That’s because scientists have found more evidence that elevated body temperature helps certain types of immune cells to work better. This research is reported in the November 2011 issue of the Journal of Leukocyte Biology (https://www.jleukbio.org).

“An increase in body temperature has been known since ancient times to be associated with infection and inflammation,” said Elizabeth A. Repasky, Ph.D., a researcher involved in the work from the Department of Immunology at the Roswell Park Cancer Institute in Buffalo, New York. “Since a febrile response is highly conserved in nature (even so-called cold blooded animals move to warmer places when they become ill) it would seem important that we immunologists devote more attention to this interesting response.”

Scientists found that the generation and differentiation of a particular kind of lymphocyte, known as a “CD8+ cytotoxic T-cell” (capable of destroying virus-infected cells and tumor cells) is enhanced by mild fever-range hyperthermia. Specifically, their research suggests that elevated body temperature changes the T-cells’ membranes which may help mediate the effects of micro-environmental temperature on cell function. To test this, researchers injected two groups of mice with an antigen, and examined the activation of T-cells following the interaction with antigen presenting cells. Body temperature in half of the mice was raised by 2 degrees centigrade, while the other half maintained a normal core body temperature. In the warmed mice, results showed a greater number of the type of CD8 T-cells capable of destroying infected cells.

“Having a fever might be uncomfortable,” said John Wherry, Ph.D., Deputy Editor of the Journal of Leukocyte Biology, “but this research report and several others are showing that having a fever is part of an effective immune response. We had previously thought that the microbes that infect us simply can’t replicate as well when we have fevers, but this new work also suggests that the immune system might be temporarily enhanced functionally when our temperatures rise with fever. Although very high body temperatures are dangerous and should be controlled, this study shows that we may need to reconsider how and when we treat most mild fevers.”

Public release date: 1-Nov-2011

Obese Adolescents Benefit from High-Dose Vitamin D Supplements

High doses safely combat nutritional deficiencies, MU researchers find

COLUMBIA, Mo. –Vitamin D deficiency is common in Americans, and especially in overweight and obese adolescents, according to the National Institutes of Health. University of Missouri researchers have found that providing obese adolescents with a high daily dose of vitamin D3 is safe and effective in improving their vitamin D status.

“Obese adolescents face an increased risk for deficiency because they tend to absorb vitamin D in their fat stores, which prevents it from being utilized in their blood,” said Catherine Peterson, associate professor of nutrition & exercise physiology. “We found that a daily dose of 4,000 IUs of vitamin D3, the maximum intake level set by the Institute of Medicine (IOM), is both safe and effective at improving vitamin D status in obese adolescents.”

Vitamin D is obtained by eating certain foods, taking supplements and through sunlight exposure. It is essential for maintaining healthy bones, muscles, nerves and immunity. The IOM recently set new dietary reference intakes for vitamin D. They recommend 600 IUs per day, with a tolerable upper intake of 4,000 IUs. Based on the guidelines, it is important to determine the effects of a vitamin D dose that is equivalent to the upper limit, especially in understudied groups, such as obese adolescents, Peterson said.

In the study, participants from the MU Adolescent Diabetes and Obesity clinic were randomly selected to receive a placebo or 4,000 IU/day of vitamin D3 for six months as part of their standard treatment. All obese participants initially were deficient or insufficient in vitamin D status. Participants supplemented with vitamin D3 had significantly greater increases in concentrations of 25OHD, the main indicator of vitamin D status, compared to those who received the placebo.

Obese adolescents are only about half as efficient at using vitamin D as their lean counterparts. For example, in lean adolescents it only takes about 100 IUs to increase their serum 25OHD levels by 1 ng/ml. In obese adolescents, it takes about 200 IUs to achieve the same increase

“If obese adolescents only consumed the recommended 600 IUs, they would be in trouble,” Peterson said. “It takes 4,000 IUs to raise their vitamin D status within a sufficient range. This is much higher than the currently recommended daily amount for this age group. This indicates that physicians need to carefully evaluate the vitamin D status in their overweight and obese patients.”

Peterson is the director of undergraduate studies for the Department of Nutrition and Exercise Physiology in the College of Human Environmental Sciences (HES). The department is a joint effort by HES, the School of Medicine and the College of Agriculture, Food and Natural Resources.

The paper, “Safety and efficacy of using high dose (4000 IU daily) vitamin D supplementation to improve the vitamin D status of obese adolescents,” was presented at the annual meeting of Experimental Biology. The research is funded by the J.R. Albert Foundation, which provides support to nonprofit education and research programs to enable people to live healthier lives.

Public release date: 2-Nov-2011

Global flu watch: Report of rare flu coinfection in Southeast Asia hot spot

While dual infections in Cambodia did not produce new strain, study cites need for continuous tracking against risk of different influenza viruses combining to create a new pandemic

(Deerfield, Ill., USA – November 2, 2011) Researchers conducting influenza-like illness surveillance in Cambodia have confirmed a rare incidence of individuals becoming infected with a seasonal influenza and the pandemic strain at the same time, a reminder of the ongoing risk of distinct flu viruses combining in human hosts to produce a more lethal strain, according to a report in the November issue of the American Journal of Tropical Medicine and Hygiene. A pandemic strain is a type of flu against which people have little or no natural immunity.

While the individuals recovered and the two strains did not recombine into a new and different virus, experts say coinfections in Southeast Asia deserve particularly close scrutiny given the ongoing transmission of the deadly avian influenza virus H5N1 and circulation of the pandemic H1N1 influenza that first emerged in 2009. The report comes as flu season gets underway in the United States, and while Cambodia and other tropical parts of Asia are reporting continued flu activity.

As of October 10, 2011, the World Health Organization (WHO) had tallied 566 known human infections with H5N1 and 332 deaths for a fatality rate of over 60 percent. In Cambodia, 16 of 18 infected individuals have died, with the most recent case reported in August. Thus far the virus has shown a very limited ability to pass from human to human—almost all the infections have been traced to contact with sick poultry and other diseased birds. But in the scientific community, fears remain that under the right conditions avian flu could acquire far greater human virulence through a co-mingling—or reassortment—with a human strain.

“Influenza viruses are continually changing,” said Patrick Blair, PhD, director of respiratory diseases at the US Naval Health Research Center in San Diego, California. “Finding a coinfection in an area where there is considerable seasonal flu, pandemic flu and H5N1 avian flu shows there is an opportunity for co-mingling in swine or human hosts that could create an ominous global health problem.” Blair co-authored the study with colleagues from the Cambodia National Institute of Public Health, US Navy Medical Research Unit-2-Phnom Penh, and the US (Maryland)-based J. Craig Venter Institute.

The scientists identified the coinfection from viruses isolated from a young Cambodian boy and his teacher in October of 2009, several months after the pandemic H1N1 influenza strain began circulating around the world. Tests revealed the two viruses to be H1N1 and a human seasonal flu variety known as H3N2. When the researchers conducted a complete sequencing of both virus genomes, they were able to determine there had been no “genetic recombination.”

“This kind of thorough surveillance and scientific investigation is the result of a commitment and collaboration of health authorities around the world—and particularly the US Department of Defense—to invest the resources required to remain vigilant against one of the biggest biological threats of our time,” said Peter J. Hotez, MD, PhD, noted infectious disease expert and president of the American Society of Tropical Medicine and Hygiene (ASTMH), which publishes the journal. “Highly infectious strains of the virus against which humans have little defense can spread from one continent to another with 24 hours.”

Staying Vigilant Against Worst-case Scenario

Blair said the mere existence of coinfection is of interest to disease experts for a number of reasons. First, as the study notes, coinfections are relatively rare. In one study conducted in 2010, scientists examined over 2,000 influenza samples without turning up a single coinfection. Other studies pinpointed a relatively small number of co-infections involving the pandemic H1N1 virus: one in Singapore, six in China, and 11 in New Zealand.

Researchers are keenly interested in identifying any coinfections because, regardless of their immediate risk, there is an urgent need to learn more about the human role in the “genetic reshuffling” that allows different influenza strains to interact and create a pandemic strain.

For example, researchers probing the dual infections in New Zealand found that the H1N1 pandemic strain was co-inhabiting with a strain that was resistant to the anti-viral oseltamivir (sold under the brand name Tamiflu). Such coinfections, they said, “raise the potential of an oseltamivir-resistant pandemic strain.”

As bad as that would be, Blair said the worst-case scenario for many disease experts is one in which a coinfection with avian flu and a human strain results in a highly lethal virus that easily jumps from person to person.

As the study on the Cambodian coinfection notes, the prevalence of H5N1 “in poultry in many areas of Southeast Asia provides increased opportunity for human exposure and adaptation of a lethal virus suitable for sustained human transmission.” The researchers point out that several pandemic flu strains, including the 2009 H1N1 outbreak, have displayed a mix of genetic material from human and animal influenza.

For example, they note that H1N1 virus samples isolated in Southern California in April of 2009 “contained genetic elements from four different sources, including North American swine influenza viruses, North American avian influenza viruses, human influenza viruses, and a Eurasian swine influenza viruses.” Similarly, the flu pandemics of 1957 and 1968 have both been traced to a “reassortment between human and avian strains.”

Blair said it’s hard to predict the chances of H5N1 providing the genetic platform for the next pandemic. “Even though there may be a very small chance of this occurring, avian flu is still percolating in Southeast Asia and it continues to exhibit an extraordinarily high fatality rate in humans,” he said.

Ralph’s Note – Here we go, again

Public release date: 2-Nov-2011

Chantix unsuitable for first-line smoking cessation use

WINSTON-SALEM, N.C. — The poor safety profile of the smoking-cessation drug varenicline (Chantix™) makes it unsuitable for first-line use, according to a study published in the Nov. 2 edition of the journal PLoS One, an online publication of the Public Library of Science.

Varenicline, which already carries a “black box warning” from the U.S. Food and Drug Administration (FDA), showed a substantially increased risk of reported depression or suicidal behavior compared to other smoking-cessation treatments, according to researchers at Wake Forest Baptist Medical Center, the Institute for Safe Medication Practices, Harvard Medical School and Johns Hopkins University School of Medicine.

The researchers found that 90 percent of all reported suicides related to smoking- cessation drugs since 1998 implicated varenicline, even though it was on the market only four years in the nearly 13-year study period. They also found that varenicline was eight times more likely to result in a reported case of suicidal behavior or depression than nicotine replacement products.

“Our study contradicts the implications of a recent review by the FDA showing no difference in psychiatric hospitalizations between varenicline and nicotine replacement patches,” said Curt D. Furberg, M.D., Ph.D., professor of Public Health Sciences at Wake Forest Baptist, co-author of the study and a nationally recognized leader in drug safety research. “The FDA hospitalization studies were flawed because they could not capture most of the serious psychiatric side effects, including suicide, depression, aggression and assaults. These can be catastrophic events but do not normally result in hospitalization.

“We found that Chantix is associated with more suicidal behavior reports than any other smoking-cessation drug on the U.S. market. The risks simply outweigh the benefits.”

In this study, the team of scientists analyzed 3,249 case reports of serious injury included in the FDA’s Adverse Event Reporting System from 1998 through September 2010 for self-injurious behavior or depression linked to varenicline, bupropion (Zyban™), an antidepressant approved for smoking cessation, and nicotine replacement products. They identified 2,925 (90 percent) cases of suicidal behavior or depression for varenicline, 229 (7 percent) for bupropion, and 95 (3 percent) cases for nicotine replacement products.

Furburg said that although a growing body of research from multiple sources establishes that varenicline substantially increases the risk of psychiatric side effects, it remains uncertain how frequently these events occur.

“While suicidal behavior or depression appear to be prominent side effects of varenicline, they are by no means the only safety issues,” said Thomas J. Moore, senior scientist at the Institute for Safe Medication Practices and lead author of the study. “Varenicline has been associated with aggression and violence in three studies and carries a warning about this behavior. Its effects on vision, cognition and motor control and other risks have led to its being banned for airline pilots, air traffic controllers, military pilots and missile crews, and restricted for truck drivers.”

Varenicline also is associated with an increase in the risk of serious cardiovascular events, as reported in the July 4, 2011, issue of the Canadian Medical Association Journal by Furberg and scientists at Wake Forest Baptist, Johns Hopkins University School of Medicine and the University of East Anglia in the United Kingdom.

“We strongly recommend that the FDA should revise the ‘black box warning’ to say what this study and the FDA’s own data show – that varenicline has higher risks for suicidal behavior and depression than other smoking-cessation treatments,” Furberg said.

“We agree with the recommendations of the U.S. Veterans Administration (VA) that varenicline should be prescribed only after failure of nicotine replacement, bupropion or a combination,” he added. “The VA also recommends a mental status examination to assess risk of suicidal or violent behavior prior to prescribing varenicline.”

Tobacco use is responsible for one in five deaths in the United States each year and adds $193 billion to health care costs. It is among the most treatment-resistant forms of drug dependency, with 36 percent of the nation’s smokers attempting to quit each year but only 3 percent succeeding for six months or more, according to the Department of Health and Human Services.

Public release date: 2-Nov-2011

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

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

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

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

Public release date: 2-Nov-2011

Clemson researcher says high blood pressure may lead to missed emotional cues

CLEMSON — Your ability to recognize emotional content in faces and texts is linked to your blood pressure, according to a Clemson University researcher.

A recently published study by Clemson University psychology professor James A. McCubbin and colleagues has shown that people with higher blood pressure have reduced ability to recognize angry, fearful, sad and happy faces and text passages.

“It’s like living in a world of email without smiley faces,” McCubbin said. “We put smiley faces in emails to show when we are just kidding. Otherwise some people may misinterpret our humor and get angry.”

Some people have what McCubbin calls “emotional dampening” that may cause them to respond inappropriately to anger or other emotions in others.

“For example, if your work supervisor is angry, you may mistakenly believe that he or she is just kidding,” McCubbin said. “This can lead to miscommunication, poor job performance and increased psychosocial distress.”

In complex social situations like work settings, people rely on facial expressions and verbal emotional cues to interact with others.

“If you have emotional dampening, you may distrust others because you cannot read emotional meaning in their face or their verbal communications,” he said. “You may even take more risks because you cannot fully appraise threats in the environment.”

McCubbin said the link between dampening of emotions and blood pressure is believed to be involved in the development of hypertension and risk for coronary heart disease, the biggest killer of both men and women in the U.S. Emotional dampening also may be involved in disorders of emotion regulation, such as bipolar disorders and depression.

His theory of emotional dampening also applies to positive emotions.

“Dampening of positive emotions may rob one of the restorative benefits of close personal relations, vacations and hobbies,“ he said.

Public release date: 4-Nov-2011

Medical researchers make important research link between active ingredient in saffron and MS

Medical researchers at the University of Alberta have discovered that an active ingredient in the Persian spice saffron may be a potential treatment for diseases involving neuroinflammation, such as multiple sclerosis.

Chris Power and a team of researchers in the Faculty of Medicine & Dentistry recently published their findings in the peer-reviewed publication, The Journal of Immunology.

“We found there is a compound in saffron, known as crocin, that exerts a protective effect in brain cell cultures and other models of MS. It prevented damage to cells that make myelin in the brain,” Power said. “Myelin is insulation around nerves. MS is characterized by inflamed brain cells that have lost this protective insulation, which ultimately leads to neurodegeneration.”

Power noted they are not close to a clinical trial stage yet, but the finding is still exciting.

It has been known in the research community for years that crocin protected neurons in certain situations, but Power and his team wanted to delve further into this area.

His team discovered that inflammation and a specific type of cell stress are closely linked and lead to neurodegeneration and inflammation which cause cells to lose their protective coating – a process known as demyelination. In experiments conducted by Power and his colleagues, the use of crocin suppressed both inflammation and this specific type of cell stress, resulting in decreased neurological impairment in lab models and cell cultures with MS.

“There are still many questions to be answered about how crocin exerts these neuroprotective effects, but this research highlights a potential treatment role for crocin in diseases involving chronic neuroinflammation – something that had not been recognized until now,” says Power.

He explained the research demonstrates a new mechanism in MS, provides new potential drug targets in the future, and helps explain why physicians see inflammation in MS.

The team’s research also revealed that this specific type of cell stress, called the unfolded protein response, may be caused by an ancient virus that was introduced into the DNA of early humans. This particular cell stress is found at high levels in MS brain lesions.

“We all have this ancient virus in our DNA, but for some reason it is excessively turned on in MS,” says Power. “We are doing more research investigating this link.”

Power has been investigating this specific area for six to seven years.

Public release date: 4-Nov-2011

Brain parasite directly alters brain chemistry

A research group from the University of Leeds has shown that infection by the brain parasite Toxoplasma gondii, found in 10-20 per cent of the UK’s population, directly affects the production of dopamine, a key chemical messenger in the brain.

Their findings are the first to demonstrate that a parasite found in the brain of mammals can affect dopamine levels.

Whilst the work has been carried out with rodents, lead investigator Dr Glenn McConkey of the University’s Faculty of Biological Sciences, believes that the findings could ultimately shed new light on treating human neurological disorders that are dopamine-related such as schizophrenia, attention deficit hyperactivity disorder, and Parkinson’s disease.

This research may explain how these parasites, remarkably, manipulate rodents’ behaviour for their own advantage. Infected mice and rats lose their innate fear of cats, increasing the chances of being caught and eaten, which enables the parasite to return to its main host to complete its life cycle.

In this study, funded by the Stanley Medical Research Institute and Dunhill Medical Trust, the research team found that the parasite causes production and release of many times the normal amount of dopamine in infected brain cells.

Dopamine is a natural chemical which relays messages in the brain controlling aspects of movement, cognition and behaviour. It helps control the brain’s reward and pleasure centres and regulates emotional responses such as fear. The presence of a certain kind of dopamine receptor is also associated with sensation-seeking, whereas dopamine deficiency in humans results in Parkinson’s disease.

These findings build on earlier studies in which Dr McConkey’s group found that the parasite actually encodes the enzyme for producing dopamine in its genome.

“Based on these analyses, it was clear that T. gondii can orchestrate a significant increase in dopamine production in neural cells,” says Dr McConkey.

“Humans are accidental hosts to T. gondii and the parasite could end up anywhere in the brain, so human symptoms of toxoplasmosis infection may depend on where parasite ends up. This may explain the observed statistical link between incidences of schizophrenia and toxoplasmosis infection.”

Dr McConkey says his next experiments will investigate how the parasite enzyme triggers dopamine production and how this may change behaviour.