One Drink Of Red Wine Or Alcohol Is Relaxing To Circulation, But Two Drinks Are Stressful

Daily Science Journal (Feb. 13, 2008) — One drink of either red wine or alcohol slightly benefits the heart and blood vessels, but the positive effects on specific biological markers disappear with two drinks, say researchers at the Peter Munk Cardiac Centre of the Toronto General Hospital.

Researchers conducted a real-time study of thirteen volunteers to determine whether a red wine with a verified high polyphenol content differs from alcohol in its effects on specific markers associated with a greater risk of high blood pressure, coronary artery disease and heart failure.

A large number of population studies have shown a protective effect of light or moderate alcohol drinking against the risk of death and the development of heart disease. Many studies have also reported specific benefits of red wine.

Population surveys found lower rates of heart disease, despite high-fat diets, in some European countries where red wine was consumed regularly. Widely known at the French paradox, this has created a huge interest in exploring if and how red wine has a protective effect against heart disease.

However, the findings of this study* showed virtually identical effects of red wine and alcohol on the specific markers tested. After one drink of either red wine or alcohol, blood vessels were more “relaxed” or dilated, which reduced the amount of work the heart had to do. But, after two drinks, the heart rate, amount of blood pumped out of the heart, and action of the sympathetic nervous system all increased. At the same time, the ability of the blood vessels to expand in response to an increase in blood flow diminished. This counteracted the beneficial effect of one drink of red wine or alcohol.

“We had anticipated that many of the effects of one ethanol drink would be enhanced by red wine. What was most surprising was how similar the effects were of red wine and ethanol. Any benefits that we found were not specific to red wine,” said Dr. John Floras, Director of Cardiology Research at the Peter Munk Cardiac Centre, and at Mount Sinai Hospital, in whose laboratory the study was performed. However, Dr. Floras cautioned this study measured the effects of these drinks on one occasion only. The effects of daily wine or alcohol intake may be quite different.

The laboratory of Dr. Floras, who holds the Canada Research Chair in Integrative Cardiovascular Biology and is a Professor of Medicine at the University of Toronto, and a Career Investigator of the Heart and Stroke Foundation, is one of the few in the world equipped to measure simultaneously a broad spectrum of factors such as blood pressure, heart rate, sympathetic nerve firing and arterial diameter.

Healthy, non-smoking adults who were not heavy drinkers or total alcohol abstainers were studied. Participants attended three separate morning sessions during which “standard” drinks of red wine, ethanol or water were administered at random, single-blind, two weeks apart. A 4-oz glass of wine (120 ml), and a 1.5-oz (44 ml) shot of spirits is considered to be one standard drink. All blood alcohol levels alcoholic were below .08, the legal limit for drivers.

The Quality Assurance Laboratory of the Liquor Control Board of Ontario selected a moderately priced pinot noir with a verified high t-resveratrol content, a polyphenol compound found in plants, including red grapes, which exhibits antioxidant properties. Alcohol or substances in alcohol such as resveratrol may improve blood vessel function and also prevent platelets in the blood from sticking together, which may reduce clot formation and the risk of heart attack or stroke.

Select study findings:

One drink of either red wine or alcohol:

* Has no effect on heart rate, blood pressure or sympathetic nerve activity, which activates the “fight or flight” reaction and generally modulates heart rate and sets the diameter of blood vessels in order to redistribute blood;
* Dilates the brachial artery.

Two drinks of either alcohol or red wine:

* Increase sympathetic nerve activity, heart rate, and the amount of blood the heart pumps out, and also blunt the ability of the brachial artery to expand further in response to blood flow.
* Increases in heart rate and sympathetic nerve activity are recognized markers for hypertension (high blood pressure), heart failure and sudden death.

“Our findings point to a slight beneficial effect of one drink – be it alcohol or red wine – on the heart and blood vessels, whereas two or more drinks would seem to turn on systems that stress the circulation. If these actions are repeated frequently because of high alcohol consumption these effects may expose individuals to a higher risk of heart attacks, stroke or chronic high blood pressure,” noted Dr. Floras, adding that the American Heart Association (AHA) does not recommend that anyone start drinking alcohol to prevent heart disease. Reducing risk can be done using other methods such as exercise and following a healthy diet.

The study entitled “Dose-related effects of red wine and alcohol on hemodynamics, sympathetic nerve activity, and arterial diameter”, was published in the February edition of the American Journal of Physiology, Heart and Circulatory Physiology. This study was supported by the Heart and Stroke Foundation of Ontario, the Canadian Institutes of Health Research, and the Canada Research Chairs Program.

Adapted from materials provided by University Health Network, via Newswise.

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Fake Malaria Drugs Made In China: Tracking Down The Threat To Global Health

Daily Science Journal (Feb. 13, 2008) — A unique collaboration between scientists, public health workers and police has led to the arrest by the Chinese authorities of alleged traders of fake anti-malarial drugs in southern China and the seizure of a large quantity of drugs. The work, involving teams from across the globe, has highlighted both the growing threat posed by fake pharmaceuticals and the complexities of tracking down those responsible for the trade.

Counterfeit artesunate anti-malarial tablet with fake 'X-52' stamp as seen under UV light. (Credit: Newton PN, Fernandez FM, Plancon A, Mildenhall DC, Green MD,et al.)

Dubbed Operation Jupiter, the investigation was coordinated by the International Criminal Police Organisation (INTERPOL), the World Health Organization's Western Pacific Regional Office, and the Wellcome Trust-University of Oxford SE Asian Tropical Medicine Research Programme, in close cooperation with Chinese authorities. Scientists from 5 other laboratories analysed the composition of the fake drugs and their packaging.

Fake anti-malarial drugs are an increasingly serious problem, particularly in South-East Asia and Africa. In countries with a large burden of malaria, such as Myanmar (Burma), the Lao PDR, Cambodia and Viet Nam, as many as half of all artesunate tablets -- one of the most effective anti-malarial drugs -- is counterfeit.

Most of the fakes examined as part of Operation Jupiter contained no artesunate, and some contained a wide range of potentially toxic wrong active ingredients. Also of grave concern was the fact that counterfeiters sometimes included dangerously small amounts of artesunate in the tablets. This may be done to foil screening tests of drug quality, but these doses are too low to be efficacious, yet high enough to contribute to malaria parasites becoming resistant to this class of drugs.

"Artesunate, as part of artemisinin-based combination therapy, is vital for malaria treatment and is one of the most effective weapons we have against this terrible scourge," says Dr Paul Newton of the Wellcome Trust-University of Oxford SE Asian Tropical Medicine Research Programme. "Those who make fake anti-malarials have killed with impunity, directly through the criminal production of a medicine lacking active ingredients and by encouraging drug resistance to spread. If malaria becomes resistant to artesunate, the effect on public health in the tropics will be catastrophic."

In addition to analysing the chemistry of the samples, researchers used a technique known as forensic palynology to study pollen contamination within the fake tablets with the aim of tracking down the likely location of manufacture. The pollen evidence suggested that at least some of the counterfeit artesunate came from southern China, and this was supported by examination of the mineral calcite, found in some of the samples.

Armed with these findings by INTERPOL, Chinese authorities arrested a suspect in China's Yunnan Province in 2006. He is alleged to have traded 240,000 blisterpacks of counterfeit artesunate, enough to "treat" almost a quarter of a million adults with a medicine with no activity against a potentially fatal disease. Whilst the Chinese authorities were able to seize 24,000 of these packs, the remainder are alleged to have been sold at crossings on the border of Yunnan and Myanmar (Burma), accounting for almost a half of all blisterpacks of artesunate sold to the region.

The work of the Jupiter group highlights the need for more to be done internationally to support countries with a high prevalence of counterfeit anti-malarials in their attempts to combat this severe but under-recognised public health problem.

"Criminal investigations and legal action are important in disrupting and inhibiting the trade in fake medicines, but to be effective these will require financial support and resources," says Dr Newton. "Forensic tools may make it easier to identify the fake drugs and allow over-stretched police forces to focus on objective leads, greatly increasing the risks to counterfeiters of being caught. However, there are very few laboratories with the resources to perform detailed forensic chemistry or pollen analysis of fakes, particularly in the countries where they are most needed."

Journal citation: Newton PN, Fernandez FM, Plancon A, Mildenhall DC, Green MD,et al. (2008) A collaborative epidemiological investigation into the criminal fake artesunate trade in South East Asia. PLoS Med 5(2): e32.

Adapted from materials provided by Wellcome Trust.

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New Technique Makes Tissues Transparent

Daily Science Journal (Feb. 13, 2008) — If humans had see-through skin like a jellyfish, spotting disease like cancer would be a snap: Just look, and see a tumor form or grow.

Diagram of chicken breast tissue (approximately 250 microns thick) with photo-refractive crystal to counteract the scattering of light and remove the distortion it creates in images. The lower diagram would show the clearest image. (Credit: Caltech Biophotonics Laboratory)

But humans, of course, are not remotely diaphanous. "The reason a person is not transparent is that their tissues are highly scattering," sending light waves careening through the tissue instead of straight through, as they would through the tissue of that jellyfish, explains Changhuei Yang of the California Institute of Technology.

This scattering, in addition to rendering all of us opaque, makes the detection of disease a much trickier issue, requiring a host of diagnostic tests and procedures. But not, perhaps, for much longer, thanks to a new optical trick developed by Yang, an assistant professor of electrical engineering and bioengineering, and his colleagues, that counteracts the scattering of light and removes the distortion it creates in images.

It is well known that light scattering in a material is not exactly the random and unpredictable process one might imagine. In fact, scattering is deterministic, which means that the path that a beam of light takes as it traverses a particular slice of tissue and bounces and rebounds off of individual cells, is entirely predictable; if you again bounce light through that same swath of cells, it will scatter in exactly the same way.

The process is even reversible; if the individual photons of light that scattered through the tissue could be collected and sent back through the tissue, they'd bounce back along the same path and converge at the original spot from which they were sent. "The process is similar to the scattering of billiard balls on a pool table. If you can precisely reverse the paths and velocities of the billiard balls, you can cause the billiard balls to reassemble themselves into a rack," Yang explains.

Yang, along with his colleagues at Caltech, École Polytechnique Fédérale de Lausanne in Switzerland, and MIT, exploited this phenomenon to offset the murky nature of our tissues.

Their technique, called turbidity suppression by optical phase conjugation (TSOPC), is surprisingly simple. The scientists used a holographic crystal to record the scattered light pattern emerging from a 0.46-mm-thick piece of chicken breast. They then holographically played the pattern back through the tissue section to recover the original light beam. "This is similar to grabbing hold of the direction of time flow and turning it around; the time-reversed photons must retrace their trajectories through the tissue," Yang says. "The task is formidable though, as this is comparable to starting with a rack of 10 to the 18th power billiard balls (or photons), scattering them around the table, and attempting to reassemble them into a rack."

"Until we did this study, it wasn't clear that the effect will be observable with biological tissues. We were pleasantly surprised that the effect was readily observable and remarkably robust," Yang says. "This study opens up numerous possibilities in the use of optical time reversal in biomedicine."

One possible use of the technique is in photodynamic therapy, in which a highly focused beam of light is aimed at cancerous cells that have absorbed cell-killing light-sensitive compounds. When the light hits the cells, the compounds are activated and destroy the cells. Photodynamic therapy is most effective in treating cancers on the skin surface. Yang's technique, however, offers a way to concentrate light onto cancer-killing compounds located more deeply within tissue.

Yang's idea is to inject strongly light-scattering particles that are coated with light-activated cancer-killing drugs into diseased tissue. Shine a beam of light into the tissue, and it would be reflected off the scattering compounds as it bounces through the tissue. Some of the scattered light would return to the source, where it could be recorded as a hologram.

This hologram would contain information about the path that the scattered light took through the tissue, and, in effect, describe the optimal path BACK toward the light-scattering molecule--and the cancer-killing compounds. Playing back the signal with a stronger burst of light will then activate the therapeutic drugs, which kill the cancer cells.

In addition, the technique could offer a way to power miniature implants buried deep within tissues. "If you take a quick survey of what is out there at present, you will see that implants are fairly large," Yang says. "For example, a pacemaker is about the size of a cell phone. Why are they so big? A large part of the reason is because they need to carry their own power sources."

The key to making smaller implants, then--say, the size of a pen tip--is to eliminate the power sources. "I think implants that carry photovoltaic receivers are particularly promising," he says. "The effect can be applied to tailor light-delivery mechanisms to efficiently channel light into tissues and onto these implants."

A study describing the process appears in the February issue of the journal Nature Photonics. Zahid Yaqoob, a postdoctoral fellow in electrical engineering at Caltech, performed most of the experiments reported in the paper. The other authors of the paper are Demetri Psaltis, professor of optics and dean of engineering, École Polytechnique Fédérale de Lausanne in Switzerland, and Michael S. Feld, a professor of physics at MIT.

Adapted from materials provided by California Institute of Technology.

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Antiretroviral Drugs May Protect Against Sexual Transmission Of HIV

Daily Science Journal (Feb. 12, 2008) — A new study in macaques suggests that antiretroviral drugs used to treat HIV could also protect people from getting the AIDS virus, especially if two drugs are taken in combination before exposure to the virus occurs.

A new study in macaques suggests that antiretroviral drugs used to treat HIV could also protect people from getting the AIDS virus, especially if two drugs are taken in combination before exposure to the virus occurs. (Credit: iStockphoto/Claire George)

The study found that macaques which were repeatedly exposed to SHIV (a virus closely related to HIV) but received antiretroviral drugs were less likely to become infected than exposed macaques that received no anti-HIV medication. The best protection was seen in macaques that had received a combination of two drugs. The study, led by José Gerardo García-Lerma and Walid Heneine from the US Centers for Disease Control and Prevention, is the culmination of a series of experiments designed to show how similar studies in humans -- some of which are planned and in progress -- can be optimally designed.

Although HIV treatment has rapidly advanced since the introduction of antiretroviral drugs in the 1990s, the absence of an effective vaccine means the virus continues to spread, infecting 2.5 million people each year. Pre-exposure prophylaxis (PrEP) -- the prevention of infection by treating people with drugs before they are exposed to the germ in question -- is often used to prevent malaria, but has not yet been shown to be effective against sexual transmission of HIV.

To simulate a common route of HIV transmission in humans, the researchers exposed the macaques to low weekly doses of SHIV that were given rectally. Five groups of macaques were all exposed to the virus in the same way, but they were given different dosages and combinations of antiretroviral drugs. Three groups received drugs daily: the first was only injected with one anti-HIV drug, emtricitabine (FTC); the second group received a daily dose of this drug by mouth in combination with an oral form of another anti-HIV drug called tenofovir; the third was injected with FTC and a high dose of tenofovir every day. A fourth group was also injected with FTC and a high dose of tenofovir, but macaques in this group were only treated shortly before and after the weekly exposures to HIV. For comparison a fifth group of macaques received no anti-HIV drugs.

The results showed that macaques from any of the four groups that received drugs were less likely to become infected than those in the fifth (control) group. All of the macaques receiving the combination of both FTC and the high dosage of tenofovir were protected from infection -- whether they were from the group that received these drugs daily, or only around the time of exposure to infection. The results suggest that higher doses and combinations of drugs worked better than single or low doses, and also that PrEP may not need to be taken every day to be effective.

The researchers also observed some risks that emphasize the need for careful design of human PrEP studies. They found some viral resistance to one of the drugs, FTC, in macaques that became infected. In addition, doses of tenofovir that resulted in maximum protection for macaques are higher than would be safe in humans.

In a related perspective article, Myron Cohen and Angela Kashuba from the University of North Carolina (Chapel Hill, NC, USA), uninvolved with the study, note that the results "highlight an exciting and potentially important use" of antiretroviral drugs to prevent sexual transmission of HIV.

Journal citation: García-Lerma JG, Otten RA, Qari SH, Jackson E, Cong M, et al. (2008) Prevention of rectal SHIV transmission in macaques by daily or intermittent prophylaxis with emtricitabine and tenofovir. PLoS Med 5(2): e28. doi:10.1371/journal.pmed.0050028 http://medicine.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pmed.0050028

Adapted from materials provided by Public Library of Science, via EurekAlert!, a service of AAAS.

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Tobacco Could Kill One Billion By 2100, WHO Report Warns

Daily Science Journal (Feb. 11, 2008) — WHO has released new data showing that while progress has been made, not a single country fully implements all key tobacco control measures, and outlined an approach that governments can adopt to prevent tens of millions of premature deaths by the middle of this century. Unless urgent action is taken, tobacco could kill one billion this century.

Cigarette butts. Unless urgent action is taken, tobacco could kill one billion this century, WHO report warns. (Credit: iStockphoto/James Curtis)

Current status of tobacco-related deaths

• 100 million dead in the 20th century

• Currently 5.4 million deaths every year

Unless urgent action is taken

• By 2030, there will be more than 8 million deaths every year

• By 2030, more than 80% of tobacco deaths will be in developing countries

• One billion estimated deaths during the 21st century

In a new report which presents the first comprehensive analysis of global tobacco use and control efforts, WHO finds that only 5% of the world’s population live in countries that fully protect their population with any one of the key measures that reduce smoking rates. The report also reveals that governments around the world collect 500 times more money in tobacco taxes each year than they spend on anti-tobacco efforts. It finds that tobacco taxes, the single most effective strategy, could be significantly increased in nearly all countries, providing a source of sustainable funding to implement and enforce the recommended approach, a package of six policies called MPOWER.

“While efforts to combat tobacco are gaining momentum, virtually every country needs to do more. These six strategies are within the reach of every country, rich or poor and, when combined as a package, they offer us the best chance of reversing this growing epidemic,” said Dr Margaret Chan, Director-General of WHO. Dr Chan launched the WHO Report of the Global Tobacco Epidemic at a news conference with New York Mayor Michael Bloomberg. Bloomberg Philanthropies helped fund the report.

“The report released today is revolutionary,” Mayor Bloomberg said. “For the first time, we have both a rigorous approach to stop the tobacco epidemic and solid data to hold us all accountable. No country fully implements all of the MPOWER policies and 80% of countries don’t fully implement even one policy. While tobacco control measures are sometimes controversial, they save lives and governments need to step up and do the right thing.”

The six MPOWER strategies

• Monitor tobacco use and prevention policies

• Protect people from tobacco smoke

• Offer help to quit tobacco use

• Warn about the dangers of tobacco

• Enforce bans on tobacco advertising, promotion and sponsorship

• Raise taxes on tobacco

The report also documents the epidemic's shift to the developing world, where 80% of the more than eight million annual tobacco-related deaths projected by 2030 are expected to occur.

This shift, the report says, results from a global tobacco industry strategy to target young people and adults in the developing world, ensuring that millions of people become fatally addicted every year. The targeting of young women in particular is highlighted as one of the “most ominous potential developments of the epidemic’s growth".

The global analysis, compiled by WHO with information provided by 179 Member States, gives governments and other groups a baseline from which to monitor efforts to stop the epidemic in the years ahead. The MPOWER package provides countries with a roadmap to help them meet their commitments to the widely embraced global tobacco treaty known as the WHO Framework Convention on Tobacco Control, which came into force in 2005.

WHO is also working with global partners to scale up the help that can be offered to countries to implement the strategies.

Dr Douglas Bettcher, Director of WHO’s Tobacco Free Initiative, said the six MPOWER strategies would create a powerful response to the tobacco epidemic. “This package will create an enabling environment to help current tobacco users quit, protect people from second-hand smoke and prevent young people from taking up the habit,” he said.

Other key findings in the report

• Only 5% of the global population is protected by comprehensive national smoke-free legislation and 40% of countries still allow smoking in hospitals and schools;

• Only 5% of the world’s population lives in countries with comprehensive national bans on tobacco advertising and promotion;

• Just 15 countries, representing 6% of the global population, mandate pictorial warnings on tobacco packaging;

• Services to treat tobacco dependence are fully available in only nine countries, covering 5% of the world’s people;

Tobacco tax revenues are more than 4000 times greater than spending on tobacco control in middle-income countries and more than 9000 times greater in lower-income countries. High- income countries collect about 340 times more money in tobacco taxes than they spend on tobacco control.

PDF of full report: http://www.who.int/entity/tobacco/mpower/mpower_report_full_2008.pdf

Adapted from materials provided by World Health Organization.

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New Finding May Help Explain Development Of Preeclampsia

Daily Science Journal (Feb. 11, 2008) — In a study of pregnant women, those with pregnancy-induced high blood pressure were found to have higher levels of a peptide that raises blood pressure in the pieces of tissue linking mother and fetus, according to researchers at Wake Forest University Baptist Medical Center. The finding, reported online in the journal Hypertension, may help explain how the disorder develops.

Preeclampsia, or high blood pressure induced by pregnancy, affects 7 to 10 percent of pregnancies in the United States and is the second-leading cause of maternal mortality. It is the leading cause of pre-term delivery and contributes significantly to stillbirths and death in newborns.

The researchers found that in women with preeclampsia, levels of angiotensin II (Ang II), a hormone that constricts blood vessels and causes blood pressure to rise, was doubled in the chorionic villi, part of the placenta that links mother and fetus and supplies food and oxygen.

"This finding may be part of the preeclampsia puzzle," said Lauren Anton, a graduate student who is first author on the research. "Anything that gets us closer to understanding this disease is important because there is no treatment and no cure and women are still delivering babies too early."

The researchers theorize that Ang II may restrict the fetal vessels that lie within the chorionic villi, which not only raises blood pressure, but also lowers oxygen and nutrient flow to the baby and may result in lower birth weight and other complications of preeclampsia.

The study involved 21 women with preeclampsia and 25 women without the disorder. After delivery, tissue sections were taken from the center of the placenta for analysis.

Ang II is part of the renin angiotensin system (RAS) that regulates blood pressure. The system has been shown to play an important role in preeclampsia. However, changes in the system also occur in women who don't develop the condition. In normal pregnancies, estrogen causes increased levels of several hormones, including Ang II, in the blood. Despite the increase of Ang II in the blood during pregnancy, most women do not develop preeclampsia.

This the first study to demonstrate that all three peptides involved in the RAS are found in the chorionic villi of both normal and preeclamptic women. And, it was the first to show that levels of Ang II are higher in the chorionic villi of women with preeclampsia.

"This implies that local tissues are contributing to the problem," said K. Bridget Brosnihan, Ph.D., senior researcher, who has been studying preeclampsia for 12 years. "The hormone is remarkably elevated in this relatively small tissue, which implies that it has an important role in the development of preeclampsia."

The researchers hope that the findings may one day lead to treatment for preeclampsia.

ACE inhibitor drugs are currently used to lower Ang II in non-pregnant women with hypertension, but these drugs cannot be given to pregnant women. The study authors suggest that other therapies aimed at regulating blood pressure might be beneficial if they target the chorionic villi rather than the system as a whole. They are currently working to determine if growth factors that cause the placenta's blood supply to develop may also be regulated by the increase in Ang II.

The study was supported, in part, by the National Institutes of Health and the American Heart Association. It was published in the Go Red issue of Hypertension that is dedicated to women's cardiovascular health.

Co-researchers are David Merrill, M.D., Ph.D., Liomar Neves, Ph.D., Kathryn Stovall, B.S., Patricia Gallagher, Ph.D., Debra Diz, Ph.D., Cheryl Moorefield, R.N., Courtney Gruver, R.N., and Carlos Ferrario, M.D., all with Wake Forest.

Adapted from materials provided by Wake Forest University Baptist Medical Center, via EurekAlert!, a service of AAAS.

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Botox Linked To Respiratory Failure And Death, FDA Advises

Daily Science Journal (Feb. 11, 2008) — The U.S. Food and Drug Administration has notified the public that Botox and Botox Cosmetic (Botulinum toxin Type A) and Myobloc (Botulinum toxin Type B) have been linked in some cases to adverse reactions, including respiratory failure and death, following treatment of a variety of conditions using a wide range of doses.

In an early communication based on the FDA's ongoing safety review, the agency said the reactions may be related to overdosing. There is no evidence that these reactions are related to any defect in the products.

The adverse effects were found in FDA-approved and nonapproved usages. The most severe adverse effects were found in children treated for spasticity in their limbs associated with cerebral palsy. Treatment of spasticity is not an FDA-approved use of botulism toxins in children or adults.

The adverse reactions appear to be related to the spread of the toxin to areas distant from the site of injection, and mimic symptoms of botulism, which may include difficulty swallowing, weakness and breathing problems.

The FDA is not advising health care professionals to discontinue prescribing these products.

The agency is currently reviewing safety data from clinical studies submitted by the drugs' manufacturers, as well as post-marketing adverse event reports and medical literature. After completing a review of the data, the FDA will communicate to the public its conclusions, resulting recommendations, and any regulatory actions.

Adapted from materials provided by US Food And Drug Administration.

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High Blood Pressure Pill Cuts Risk Of Parkinson's Disease

Daily Science Journal (Feb. 10, 2008) — People taking a widely used group of drugs known as calcium channel blockers to treat high blood pressure also appear to be cutting their risk of Parkinson's disease, according to a new study.

The study involved 7,374 men and women over age 40. Half of the group had Parkinson's disease; the other half did not have Parkinson's disease. Among both groups, nearly half used high blood pressure medications, such as calcium channel blockers, ACE inhibitors, AT II antagonists and beta blockers.

The study found people who were currently long-term users of calcium channel blockers to treat high blood pressure lowered their risk of Parkinson's disease by 23 percent compared to people who didn't take the drugs. There was no such effect among people taking ACE inhibitors, AT II antagonists and beta blockers.

"Long-term use of calcium channel blockers was associated with a reduced risk of developing Parkinson's disease while no such association was seen for other high blood pressure medicines," said study author Christoph R. Meier, PhD, MSc, with University Hospital Basel in Switzerland.

Meier says more research is needed to determine why calcium channel blockers appear to protect against Parkinson's disease, whether this is indeed a causal association, and why the other high blood pressure medications do not offer a reduced risk.

This research was published in the February 6, 2008, online issue of Neurology®, the medical journal of the American Academy of Neurology.

Adapted from materials provided by American Academy of Neurology.

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Teenage Fathers Are More Likely To Have Babies Affected By Birth Problems Than Fathers Over 40

Daily Science Journal (Feb. 10, 2008) — Teenage fathers are at increased risk of having babies born with birth problems ranging from pre-term delivery or low birth weight, through to death in or near to the time of delivery, according to new research.*

In contrast, the study also found that older fathers, aged 40 and over, were not at increased risk of having babies affected by these problems. The results were independent of the age of the mother or other maternal factors that might be expected to have an impact on birth outcomes.

The research is the largest study on the effects of paternal age on adverse birth outcomes. The researchers, from the Ottawa Health Research Institute, Canada, used data from the National Center for Health Statistics for nearly all the births (99%) in the USA between 1995-2000 -- a cohort of more than 23.6 million births. From these, they looked at 2,614,966 singleton babies born live to married women without previous childbearing histories, aged between 20-29, where there was complete information on paternal age, race, maternal education, prenatal care, and gestational and birth weight.

They chose women aged between 20-29 because they were the least likely to be affected by fertility problems, some of which can have an impact on birth outcomes. Since it is already known that fathers aged between 20-29 have the lowest risk of adverse birth outcomes, the researchers used this age group (the reference group) to compare all the other age groups against.

Compared to the reference group and after adjusting for confounding factors (such as race, education, smoking and alcohol drinking during pregnancy, adequacy of prenatal care and the sex of the baby), babies born to teenage fathers (aged less than 20) were more likely to be born early (a 15% increased risk), have low birth weight (13% increased risk), be small for gestational age (17% increased risk), have a low Apgar score (13% increased risk) or to die within the first four weeks after birth (22% increased risk) or to die in the period from four weeks to one year after birth (41% increased risk), although in all cases the absolute risk of death remained less than 0.5% . Fathers aged 40 or over did not have an increased risk of these adverse birth outcomes.

One of the authors of the study, Professor Shi Wu Wen, senior scientist at the Ottawa Health Research Institute and professor at the University of Ottawa, said: "Our study indicated that being a teenage father was an independent risk factor for adverse birth outcomes, whereas advanced paternal age was not. The paternal influence of younger fathers on adverse birth outcomes clearly warrants further investigation, and may lead to a deeper understanding of the causes of such outcomes.

"Although the increased relative risks for most outcomes were small, the magnitude of the risks to society could be huge, given the number of births worldwide, if the increases we found are truly attributable to paternal age."

The study looked at babies born to fathers in seven age groups, from teenagers through to those aged 50 and over, and Prof Wen said this, together with the large size of the study and the limited age range of the mothers, meant that the findings were unlikely to be affected by chance or confounding factors. However, there was no information available on the socio-economic status and lifestyle of the fathers, and this could have an impact.

"The mechanisms by which being a teenage father may contribute to an increased risk of adverse birth outcomes are not clear," said Prof Wen. "Both biological and socio-economic status might play some roles in the observed findings."

Previous studies have shown that younger men can have lower sperm counts, semen volume, total numbers of spermatozoa and percentage of motile sperm. Immature sperm may be associated with adverse birth outcomes, possibly as a result of the abnormal formation of the placenta in the uterus (placentation).

"It is biologically plausible that paternal age might play a role in the risk of adverse birth outcomes associated with abnormal placentation," said Prof Wen.

However, there are also possible social explanations too. "Young fathers are more likely to come from economically disadvantaged families and to have lower educational attainment. Socio-economic factors such as education and occupation are known to be associated with a number of health outcomes. People from less affluent backgrounds are less likely to utilise prenatal care services, which is associated with an increased risk of adverse birth outcomes," explained Prof Wen.

Other social factors that might play a role, perhaps by adversely affecting the mother's health, include domestic violence, lack of financial or emotional support, paternal illicit drug use, smoking and alcohol drinking. "These are more prevalent in teenage fathers, and previous studies have found associations between paternal smoking and alcohol and adverse reproductive outcomes," he said.

Of the finding that older fathers were not more likely to have babies affected by adverse birth outcomes, Prof Wen said: "In our present study, we did not find an association between older fathers and the increased risk of adverse birth outcomes. We could not exclude the possibility that older fathers who married women aged 20-29 years without childbearing history might have a higher socioeconomic status than our control groups. The advantaged socioeconomic conditions might offset some biological risk of adverse birth outcomes associated with older fathers."

Prof Wen said he and his colleagues were planning a pre-conception study to look at various paternal and maternal factors that might have an effect on the health of babies, including paternal age.

*Paternal age and adverse birth outcomes: teenager or 40+, who is at risk? Human Reproduction. doi:10.1093/humrep/dem403.

Adapted from materials provided by European Society for Human Reproduction and Embryology, via EurekAlert!, a service of AAAS.

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Herpes Medication Does Not Reduce Risk Of HIV Infection In Individuals With HSV-2, Study Finds

Daily Science Journal (Feb. 10, 2008) — An international clinical trial has found that acyclovir, a common medication for treating herpes simplex virus-2 (HSV-2), the most common cause of genital herpes, does not reduce the risk of HIV infection when taken by people infected with HSV-2. Multiple studies have shown that people with HSV-2 have a higher risk of acquiring HIV. Researchers had hoped that acyclovir's ability to suppress the herpes virus, and its associated genital sores and breaks in the skin, could cut down on the likelihood of HIV being transmitted to a person with HSV-2 during sexual intercourse.

The Phase III clinical trial was led by the University of Washington in Seattle, in coordination with the HIV Prevention Trials Network, an international consortium funded by the National Institute of Allergy and Infectious Diseases (NIAID) in the National Institutes of Health. The findings were presented this week at the Conference on Retroviruses and Opportunistic Infections in Boston.

"The study was successful in answering the question of whether acyclovir could cut down on the risk of HIV acquisition for people infected with HSV-2," explained Dr. Connie Celum, the leader of the study and a UW professor of global health and medicine in the Division of Allergy and Infectious Disease and director of the International Clinical Research Center in the UW Department of Global Health. "We were hopeful that acyclovir would help reduce HIV acquisition in people with HSV-2. Though the study did not find that acyclovir helped with HIV acquisition, we did find that it reduced genital ulcers associated with HSV-2. Now we need to continue our research on the mechanisms through which HSV-2 acts as a risk factor for HIV, and how we might be able to use that knowledge to reduce the spread of HIV."

HSV-2 is one of the most common sexually transmitted infections worldwide and is especially prevalent in areas with high rates of HIV infection. Most people who are infected with HSV-2 do not know they have the virus because symptoms can be mild or absent. In some infected individuals, the virus can produce recurring genital herpes, a condition characterized by sores and breaks in the skin of the genital region. An active HSV-2 infection also attracts immune-system cells called CD-4 T-cells to the genital region, and HIV easily attaches to this type of cell. Multiple studies have shown that people with HSV-2 have a two-fold increase in their risk of acquiring HIV.

This study followed up on those results to test the theory that suppressing HSV-2 could cut down on HIV acquisition. It was launched in 2003, and with nine study sites in Peru, South Africa, Zambia, Zimbabwe, and the United States, it was the largest study yet of herpes suppression. There were 3,277 people with HSV-2 initially enrolled in the study, 105 people excluded, and 3,172 people included in the final analysis. Volunteers in Peru and the United States were HSV-2-infected men who have sex with men, and volunteers in Africa were HSV-2-infected women.

Half of the participants were randomly assigned to receive either a placebo or a standard daily dose of acyclovir, 400 mg twice a day. The study was double-blinded, meaning that neither participants nor care providers knew which treatment the participants were receiving. Both the placebo and treatment groups received standard HIV-prevention treatment, which includes being supplied with condoms and given extensive counseling on how to reduce the risk of HIV infection.

Researchers found that there was a 3.9 percent HIV incidence rate, a total of 75 cases, in participants who received acyclovir suppression, and a 3.3 percent HIV incidence rate, or 64 cases, in the placebo group. The difference between the groups was not statistically significant. The acyclovir treatment did succeed in reducing genital ulcers -- participants in the treatment group had a 37 percent reduction in genital ulcer incidence, and a significantly lower proportion of ulcers due to HSV-2.

"The study answered the scientific questions it was designed to answer," says Dr. Anna Wald, a UW professor of medicine and epidemiology who also helped lead the study. "The sites were able to recruit and retain a large number of volunteers, who maintained a high level of adherence to the twice-daily drug regimen. While we are disappointed with the results, the study was well-conducted and provides a clear answer about using acyclovir to reduce the risk of becoming HIV-infected."

The study participants have been informed of the findings and are being counseled on the continued need to avoid HIV exposure. Volunteers who became infected with HIV during the trial have been referred for appropriate medical care and treatment.

The study was supported by NIAID, and the acyclovir was supplied by GlaxoSmithKline. The HIV Prevention Trials Network is led by Family Health International, the network laboratory of Johns Hopkins University, and the Statistical Center for HIV/AIDS Research and Prevention at the Fred Hutchinson Cancer Research Center in Seattle. The study was conducted at the following sites: Iquitos, Lima and Pucallpa, in Peru; Johannesburg, South Africa; New York, San Francisco, and Seattle, in the United States; Lusaka, Zambia; and Harare, Zimbabwe.

Adapted from materials provided by University Of Washington.

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Babies Recently Treated With Lotion, Shampoo, And Powder More Likely To Have Phthalates Chemicals In Urine

Daily Science Journal (Feb. 9, 2008) — Babies recently treated with infant personal care products such as lotion, shampoo, and powder, were more likely to have manmade chemicals called phthalates in their urine than other babies, according to University of Washington and Seattle Children's Hospital Research Institute study appearing in the February issue of the journal Pediatrics. Phthalates (pronounced "thah-lates") are added to many personal care and cosmetic products, as well many common household plastic and vinyl products, and some studies suggest they may affect reproductive development in humans.

Babies recently treated with infant personal care products such as lotion, shampoo, and powder, were more likely to have manmade chemicals called phthalates in their urine than other babies. (Credit: iStockphoto/Roman Barelko)

Animal-based studies of phthalates have found that the synthetic chemicals can harm reproductive system development, and studies in humans have found that prenatal exposure or exposure through breast milk can alter hormone concentrations. Early-childhood exposure has not been extensively studied, so additional research is needed to determine if phthalate exposure can indeed cause reproductive development problems or other adverse effects in infants.

In this study, the researchers set out to see if use of personal care products was associated with urine phthalate concentrations. To accomplish this, they collected urine samples from 163 infants aged 2 months to 28 months, and measured the levels of nine different phthalates in those urine samples. They also had the babies' mothers fill out questionnaires on their use of infant personal care products in the past 24 hours.

When they cross-referenced the data, they found that the use of baby powder, lotion, and shampoo were each strongly associated with higher phthalate levels in the urine. The use of baby wipes and diaper cream were not strongly associated with increased levels of phthalates. The scientists also found that every baby had detectable levels of at least one phthalate in their urine, and about 81 percent of the infants had detectable levels of seven or more phthalates. Babies who were 8 months old or younger had stronger associations between product use and phthalate concentrations, as did babies whose mothers used more infant personal care products.

"We found that infant exposure to phthalates is widespread, and that exposure to personal care products applied onto the skin may be an important source," said the study's lead author, Sheela Sathyanarayana, an acting assistant professor of pediatrics at the UW School of Medicine and a researcher with Seattle Children's Hospital Research Institute. "This is troubling, because phthalate exposure in early childhood has been associated with altered hormone concentrations as well as increased allergies, runny nose, and eczema. Babies may be more at risk than children or adults because their reproductive, endocrine, and immune systems are still developing."

Parents who want to decrease their baby's exposure to phthalates should limit the amount of baby care products used on the infant, and apply lotions or powders only if medically indicated. Since phthalates are also found in many household plastic products, like plastic food containers, parents can also stop putting plastics in the microwave oven and use glass alternatives whenever possible. Phthalate-free cosmetics and personal care products are also available.

This research project was supported by grants from the U.S. Environmental Protection Agency, the National Institutes of Health, and the National Institute of Environmental Health Sciences. The project included researchers from the UW Departments of Occupational and Environmental Health Sciences, Pediatrics, and Biostatistics; the Seattle Children's Hospital Research Institute; the Centers for Disease Control and Prevention; and the University of Rochester School of Medicine and Dentistry.

Adapted from materials provided by University Of Washington.

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Knee Brace Generates Electricity From Walking

Daily Science Journal (Feb. 9, 2008) — A new energy-capturing knee brace can generate enough electricity from walking to operate a portable GPS locator, a cell phone, a motorized prosthetic joint or an implanted neurotransmitter, research involving the University of Michigan shows.

The biomechanical energy harvester includes an aluminum chassis and generator mounted on a customized orthopaedic knee brace. The device weighs 3.5 lbs. (Credit: Greg Ehlers/Simon Fraser University)

The wearable mechanism works much like regenerative braking charges a battery in some hybrid vehicles, said Arthur Kuo, an associate professor of mechanical engineering at U-M and an author of the paper.*

Regenerative brakes collect the kinetic energy that would otherwise be dissipated as heat when a car slows down. This knee brace harvests the energy lost when a human brakes the knee after swinging the leg forward to take a step.

Kuo, who called the device "a cocktail-napkin idea," says knee joints are uniquely suited for this endeavor.

"There is power to be harvested from various places in the body, and you can use that to generate electricity. The knee is probably the best place," he said. "During walking, you dissipate energy in various places, when your foot hits the ground, for example. You have to make up for this by performing work with your muscles.

"The body is clever," Kuo said. "In a lot of places where it could be dissipating energy, it may actually be storing it and getting it back elastically. Your tendons act like springs. In many places, we're not sure whether the energy is really being dissipated or you're just storing it temporarily. We believe that when you're slowing down the knee at the end of swinging the leg, most of that energy normally is just wasted."

The scientists tested the knee brace on six men walking leisurely on a treadmill at 1.5 meters per second, or 2.2 miles per hour. They measured the subjects' respiration to determine how hard they were working. A control group wore the brace with the generator disengaged to measure how the weight of the 3.5-pound brace affected the wearer.

In the mode in which the brace is only activated while the knee is braking, the subjects required less than one watt of extra metabolic power for each watt of electricity they generated. A typical hand-crank generator, for comparison, takes an average of 6.4 watts of metabolic power to generate one watt of electricity because of inefficiencies of muscles and generators.

"We've demonstrated proof of concept," Kuo said. "The prototype device is bulky and heavy, and it does affect the wearer just to carry. But the energy generation part itself has very little effect on the wearer, whether it is turned on or not. We hope to improve the device so that it is easier to carry, and to retain the energy-harvesting capabilities."

A lighter version would be helpful to hikers or soldiers who don't have easy access to electricity. And the scientists say similar mechanisms could be built into prosthetic knees other implantable devices such as pacemakers or neurotransmitters that today require a battery, and periodic surgery to replace that battery.

"A future energy harvester might be implanted along with such a device and generate its own power from walking," Kuo said.

The paper "Biomechanical Energy Harvesting: Generating Electricity During Walking with Minimal User Effort" is published in the Feb. 8 issue of the journal Science. Authors include researchers from Simon Fraser University in Canada and the University of Pittsburgh, in addition to U-M.

Adapted from materials provided by University of Michigan.

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Reduced Sleep Can Increase Childhood Obesity Risk

Daily Science Journal (Feb. 9, 2008) — Less sleep can increase a child’s risk of being overweight or obese, according to a study by researchers at the Johns Hopkins Bloomberg School of Public Health. Their analysis of epidemiological studies found that with each additional hour of sleep, the risk of a child being overweight or obese dropped by 9 percent.

“Our analysis of the data shows a clear association between sleep duration and the risk for overweight or obesity in children. The risk declined with more sleep,” said Youfa Wang, MD, PhD, senior author of the study and associate professor with the Bloomberg School’s Center for Human Nutrition. “Desirable sleep behavior may be an important low cost means for preventing childhood obesity and should be considered in future intervention studies. Our findings may also have important implications in societies where children do not have adequate sleep due to the pressure for academic excellence and where the prevalence of obesity is rising, such as in many East Asian countries.”

“The influence of sleep quality on obesity risk is another important area where future research is needed,” added Xiaoli Chen, MD, PhD, the study’s lead author and a former postdoctoral fellow at the Bloomberg School.

For the study, Wang, Chen and colleague May A. Beydoun, also a postdoctoral fellow at the Bloomberg School, reviewed 17 published studies on sleep duration and childhood obesity and they analyzed 11 of them in their meta-analysis.

The recommended amount of daily sleep varied between studies analyzed and with children’s age. It is recommended that children under age 5 should sleep for 11 hours or more per day, children age 5 to10 should sleep for 10 hours or more per day, and children over age 10 should sleep at least 9 hours per day.

The results of the analysis showed that children with the shortest sleep duration had a 92 percent higher risk of being overweight or obese compared to children with longer sleep duration. For children under age 5, shortest sleep duration meant less than 9 hours of sleep per day. For children ages 5 to 10 it meant less than 8 hours of sleep per day and less than 7 hours of sleep per day for children over 10. The association between increased sleep and reduced obesity risk was strongly associated with boys, but not in girls.

The results are published in the February 2008 edition Obesity, the journal of The Obesity Society. “Is Sleep Duration Associated with Childhood Obesity? A Systematic Review and Meta-analysis” was written by Xiaoli Chen, May A. Beydoun and Youfa Wang.

The study was supported in part by the National Institute of Diabetes and Digestive and Kidney Diseases, the U.S. Department of Agriculture and the Johns Hopkins Bloomberg School of Public Health.

Adapted from materials provided by Johns Hopkins University Bloomberg School of Public Health.

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Lifetime Medical Costs Of Obese People Actually Lower Than Costs For Healthy And Fit, Mathematical Model Shows

Daily Science Journal (Feb. 8, 2008) — A new research paper suggests that preventing obesity might result in increased public spending on medical care. Many countries are currently developing policies aimed at reducing obesity in the population. However, it is not currently clear whether successfully reducing obesity will also reduce national healthcare spending or not. Pieter van Baal and colleagues, from the National Institute for Public Health and the Environment in the Netherlands, created a mathematical model to try to answer this question.

Researchers found that the group of healthy, never-smoking individuals had the highest lifetime healthcare costs, because they lived the longest and developed diseases associated with aging; healthcare costs were lowest for the smokers, and intermediate for the group of obese never-smokers. (Credit: iStockphoto/Eliza Snow)

In their study, van Baal and his co-workers created three hypothetical populations of 1000 men and women, all aged 20 years at the start: a group of obese, never-smoking individuals; a group of healthy-never smoking individuals of normal weight; and a group of smokers of normal weight. The model produced an estimate of the likely proportion of each group who would encounter certain long term (chronic) diseases, and then estimated what the approximate cost of medical care associated with each disease was likely to be. The researchers found that the group of healthy, never-smoking individuals had the highest lifetime healthcare costs, because they lived the longest and developed diseases associated with aging; healthcare costs were lowest for the smokers, and intermediate for the group of obese never-smokers.

However, the authors argue that although obesity prevention may not be a cure for increasing expenditures, it may well be a cost-effective cure for much morbidity and mortality and importantly contribute to the health of nations.

A Perspective by Klim McPherson, from Oxford University in the UK, who was not involved in the study, discusses the implications of these findings and comments that "it would be wrong to interpret the findings as meaning that public-health prevention (e.g., to prevent obesity) has no benefits"; the quality of life experienced by individuals, and other factors, must also be taken into account when planning interventions aimed at improving public health.

Citation: van Baal PHM, Polder JJ, de Wit GA, Hoogenveen RT, Feenstra TL, et al. (2008) Lifetime medical costs of obesity: Prevention no cure for increasing health expenditure. PLoS Med 5(2): e29. doi:10.1371/journal.pmed.0050029 http://medicine.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pmed.0050029

Adapted from materials provided by Public Library of Science, via EurekAlert!, a service of AAAS.

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'Weight Training' Reduces Fat And Improve Metabolism In Mice

Daily Science Journal (Feb. 8, 2008) — Researchers from the Boston University School of Medicine (BUSM) have demonstrated that in mice, the use of barbells may be as important to losing weight and improving health as the use of running shoes. The discovery builds upon the fact that skeletal muscle consists of two types of fibers. Endurance training such as running increases the amount of type I muscle fibers, while resistance training such as weightlifting increases type II muscle fibers. Using a mouse genetic model, BUSM researchers demonstrated that an increase in type II muscle mass can reduce body fat which in turn reduces overall body mass and improves metabolic parameters such as insulin resistance. These studies indicate that weight bearing exercise, in addition to endurance training, may benefit overweight people.

Weight-lifting. "We've shown that type II muscle does more than allow you to pick up heavy objects," said Kenneth Walsh of Boston University School of Medicine. "It is also important in controlling whole-body metabolism." (Credit: iStockphoto/Sean Locke)

Researchers used a genetic trick in obese mice that caused the mice's muscles to bulk up as though they had been lifting weights. The researchers found that the "genetically reprogrammed" mice lost fat and showed other signs of metabolic improvement throughout the body. What's more, those benefits were seen even though the mice continued eating a diet high in both fat and sugar and didn't increase their physical activity at all.

The researchers genetically engineered a mouse, called the MyoMouse, to grow type II fibers by activating a muscle growth-regulating gene. The gene, called Akt1, was engineered in such a way that it could be turned on and off at will by researchers. Even without exercise, activating the gene made the MyoMouse physically stronger. When the gene was de-activated, the mouse returned to its original strength. While stronger and faster than a regular mouse, the MyoMouse did not run with as much endurance on a treadmill, a finding that is consistent with the growth of type II rather than type I muscle. These findings demonstrate that the mouse was genetically programmed to have the characteristics of a lean and powerful sprinter rather than those of a gaunt marathon runner.

"We've shown that type II muscle does more than allow you to pick up heavy objects," said Kenneth Walsh of Boston University School of Medicine. "It is also important in controlling whole-body metabolism."

In the study, the Akt1 gene was turned off and the MyoMice were fed a high fat/high sugar diet with a similar caloric composition as a meal from a fast food restaurant. Over an eight-week period, the mice became obese and insulin resistant and developed fatty acid deposits in their liver, a condition referred to as hepatic steatosis or fatty liver disease.

The researchers then activated the Akt1 gene in the animals which led to the growth of type II muscle fibers. "Remarkably, type II muscle growth was associated with an overall reduction in body mass, due to a large decrease in fat mass. In addition, blood tests showed that these mice became metabolically normal and their fatty liver disease rapidly resolved," said senior author Kenneth Walsh, PhD, a professor of medicine and head of Molecular Cardiology at the Whitaker Cardiovascular Institute at BUSM.

The beneficial changes occurred despite the fact that the mice continued to eat the same high-calorie diet and did not display any increase in physical activity. "This work shows that type II muscle just doesn't allow you to pick up heavy objects, it is also important in controlling whole body metabolism," added Walsh.

Further analysis found that the mice burned fat because of changes in the physiology and gene expression of their fat and liver cells. "Thus, it appears that the increase in type II muscle fiber orchestrates changes in the body through its ability to communicate with these other tissues," he said.

These findings indicate that type II muscle has a previously unappreciated role in regulating whole body metabolism through its ability to alter the metabolic properties of remote tissues. These data also suggest that strength training, in addition to the widely-prescribed therapy of endurance training, may be of particular benefit to overweight individuals

Finally, these findings may be relevant for understanding aspects of the aging process. "Beyond the age of thirty, humans lose approximately 6 lbs of muscle mass per decade. Surprisingly, aging individuals predominantly lose type II muscle. Thus a 50 year old may be relatively good at playing tennis or jogging because type I muscle is preserved, but a measurement of grip strength or core body strength could show appreciable declines," explained Walsh. Therefore, this new study suggests that the loss of type II muscle contributes to the development of obesity and diabetes as we age.

The BUSM researchers suspect that the beneficial effects of muscle growth seen in the MyoMouse are mediated through the production and secretion of a variety of signaling factors. Walsh and his colleagues are currently identifying the novel proteins in muscle that communicate with other tissues. These new proteins, referred to as "myokines" from the Greek words "muscle" and "motion," may represent new targets for therapies that mimic the benefits of weight training for the treatment of obesity and diabetes as well as muscle wasting disorders.

"The work of [Walsh and his colleagues] reveals the intricate interplay between diet, energy balance, and the function/morphology of diverse tissue systems such as skeletal muscle and liver," said Brooke Harrison and Leslie Leinwand of the University of Colorado at Boulder in a commentary in the journal Cell Metabolism. "These findings indicate that interventions designed to increase skeletal muscle mass in at-risk human populations may prove to be critical weapons in the fight against obesity and obesity-related comorbidities including diabetes, heart disease, stroke, hypertension, and cancer."

The study appears in the February 6th issue of Cell Metabolism. The researchers include Yasuhiro Izumiya, Teresa Hopkins, Carl Morris, Kaori Sato, Ling Zeng, Jason Viereck, James A. Hamilton, Noriyuki Ouchi, Nathan K. LeBrasseur, and Kenneth Walsh, of Boston University School of Medicine, Boston, MA.

Adapted from materials provided by Boston University, via EurekAlert!, a service of AAAS.

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Giving Mice A Cold Virus Offers Hope Of New Asthma Treatments

Daily Science Journal (Feb. 8, 2008) — Scientists have been able to recreate rhinovirus infection, which is behind most common colds, in a small animal for the first time. For fifty years since they were discovered, it had been thought that rhinoviruses could only infect humans and chimpanzees. But now a team of scientists led by Professor Sebastian Johnston at the MRC/Asthma UK Centre in Allergic Mechanisms of Asthma at Imperial College London, has been able to infect mice with rhinoviruses.

Scientists have been able to recreate rhinovirus infection, which is behind most common colds, in a small animal for the first time. For fifty years since they were discovered, it had been thought that rhinoviruses could only infect humans and chimpanzees. (Credit: iStockphoto/Jennifer Sheets)

Rhinoviruses are an unwelcome inconvenience for the majority of the population as they cause around three quarters of common colds. However they can also have serious consequences. In susceptible people, they can be fatal. They can lead to the hospitalisation of infants, pneumonia in people with weakened immune systems and they trigger most asthma attacks. They are also the major cause of acute attacks of COPD (chronic bronchitis and emphysema), and are thus the major killer in these diseases.

Professor Johnston said: “Until now it has not been possible to study rhinovirus infection in small animals. This has been a major obstacle to developing new treatments and there is currently no effective treatment for rhinovirus infection.”

It had been thought that mice and other small animals were resistant to rhinoviruses. Of the 100 known strains of rhinovirus, 90 per cent use a binding molecule, called ICAM-1 that is found on the surface of human cells, as their receptor. But the viruses are unable to bind to the mouse version of this receptor.

Professor Johnston explained: "We previously found that once inside the mouse cell a rhinovirus reproduces itself as well as it does in human cells. But the virus couldn’t infect the mouse cell because the receptor (acting like a door key) couldn’t get into the cell.

“Now we’ve modified the mouse receptor so it is more like a human one. This means the virus can infect the cells of these modified mice.”

Professor Johnston added: "We found that mice with the modified receptor were susceptible to infection with a rhinovirus. If combined with an allergen (ovalbumin which is found in egg white) that could cause an allergic reaction in the lungs, the virus could make the response worse and lead to an 'asthma attack'."

The team was able to observe that when the virus was combined with an allergic reaction, the mouse responded similarly to humans. This means it provides a good model for the study of severe asthma attacks.

"These mouse models should provide a major boost to research efforts to develop new treatments for the common cold, as well as for more potentially fatal illnesses such as acute attacks of asthma and of COPD."

The chief executive of the Medical Research Council, Sir Leszek Borysiewicz said: “This important and fundamental discovery will enable us to understand the effects rhinoviruses and common colds have on our health. It will open up new paths to finding treatments which have been delayed for many years and provides us with the opportunities for further breakthroughs in the future.”

Leanne Male, Assistant Director of Research at Asthma UK commented: "Ninety per cent of people with asthma tell us that colds and flu triggers their asthma symptoms but as yet there is no specific treatment for virally induced asthma attacks and steroid treatments are only partially effective against them. We welcome this latest advancement as it will lead to a greater understanding of viral infections and their link with asthma and may help the development of a suitable treatment for virus-induced asthma attacks, thus greatly improving the lives of the 5.2 million people with the condition in the UK."

Journal article: Mouse models of rhinovirus-induced disease and exacerbation of allergic airway inflammation. Published online in Nature Medicine.

The research was funded by the Medical Research Council, Asthma UK and GlaxoSmithKline.

Adapted from materials provided by Imperial College London.

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Croatian Children Have Higher Weapons-related Death Rate During And After Homeland War

Daily Science Journal (Feb. 7, 2008) — The Homeland War in Croatia, which occurred from 1991 to 1995, led to an increase in weapon-related deaths of children during and five years after the end of the war, according to a new report.

"After World War II until the beginning of the Homeland War in 1991, most children in Croatia were not exposed to firearms and explosives in their homes or communities," the authors write as background information in the article. "Unlike many countries, personal weapon ownership was not a custom in Croatia." This changed as the Homeland War--also called the Third Balkan War--moved into Croatian land. Citizens began purchasing grenades, firearms and other weapons on the black market or taking them from military barracks after the Yugoslav army left Croatia. The population remained overly militarized in the wake of the war; in 2007, 371,684 weapons were legally owned by Croatians.

Aida Mujkic, M.D., of the University of Iowa, Iowa City, and colleagues studied Croatian children from birth through age 19 who died of weapon-related injuries between 1986 and 2005. Statistics were obtained from Croatia's national vital statistics system and included traumatic injury deaths classified by intent, including homicide, suicide and unintentional categories.

Compared with the period before the war, rates of homicide and suicide with weapons more than tripled during the war--from .22 to .73 homicides and .51 to 1.64 suicides per 100,000 children. Unintentional weapon-related deaths also increased by more than six-fold, from .25 to 1.63 per 100,000 children.

"These increases persisted for five years following the end of the war and decreased more than five years after the war," the authors write. Weapons-related deaths in the early postwar period--1996 to 2000--remained more than twice as high as before the war, and the weapon-related suicide rate remained more than three times that of the pre-war period. Homicide and unintentional injury deaths decreased significantly in the late post-war period, 2001 to 2005, and suicide rates were the same as in the pre-war period. The number of children who died from causes other than weapons did not change over the course of the study.

"Programs that focus on the prevention of weapon-related injuries should be integrated into programs that assist countries in rebuilding after political unrest," the authors conclude. "The combination of psychological effects of war on children with an increased presence of weapons may present a particularly important area for prevention."

Journal reference: Arch Pediatr Adolesc Med. 2008;162[2]:140-144.

This study was supported by an NIH grant from the University of Iowa/Fogarty International Traumatic Injury Training Program.

Adapted from materials provided by JAMA and Archives Journals.

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Subconscious Signals Can Trigger Drug Craving

Daily Science Journal (Feb. 7, 2008) — Using a brain imaging technology called functional magnetic resonance imaging (fMRI), scientists have discovered that cocaine-related images trigger the emotional centers of the brains of patients addicted to drugs -- even when the subjects are unaware they've seen anything.

Cocaine patients were shown photos such as these. The 24 randomly-presented 33 msec targets in each of four categories (cocaine, sexual, aversive and neutral, interspersed with grey-screen nulls) were immediately followed by a 467 msec neutral “masking” stimulus”. Under these conditions, the 33 msec stimuli can escape conscious detection. (Credit: Childress AR, Ehrman RN, Wang Z, Li Y, Sciortino N, et al.)

A team of researchers at the University of Pennsylvania, led by Dr. Anna Rose Childress and Dr. Charles O'Brien, showed cocaine patients photos of drug-related cues like crack pipes and chunks of cocaine. The images flashed by in just 33 milliseconds -- so quickly that the patients were not consciously aware of seeing them. Nonetheless, the unseen images stimulated activity in the limbic system, a brain network involved in emotion and reward, which has been implicated in drug-seeking and craving.

"This is the first evidence that cues outside one's awareness can trigger rapid activation of the circuits driving drug-seeking behavior," said NIDA director Dr. Nora Volkow. "Patients often can't pinpoint when or why they start craving drugs. Understanding how the brain initiates that overwhelming desire for drugs is essential to treating addiction."

To verify that the patterns of brain activity triggered by the subconscious cues reflected the patients' feelings about drugs, Childress and her colleagues gave the patients a different test two days later, allowing them to look longer at the drug images. The patients who demonstrated the strongest brain response to unseen cues in the fMRI experiment also felt the strongest positive association with visible drug cues. Childress notes, "It's striking that the way people feel about these drug-related images is accurately predicted by how strongly their brains respond within just 33 milliseconds."

Childress and her colleagues also found that the regions of the brain activated by drug images overlapped substantially with those activated by sexual images. This finding supports the scientific consensus that addictive drugs usurp brain regions that recognize natural rewards needed for survival, like food and sex.

According to Childress, these results could improve drug treatment strategies. "We have a brain hard-wired to appreciate rewards, and cocaine and other drugs of abuse latch onto this system. We are looking at the potential for new medications that reduce the brain's sensitivity to these conditioned drug cues and would give patients a fighting chance to manage their urges."

Citation: Childress AR, Ehrman RN, Wang Z, Li Y, Sciortino N, et al (2008) Prelude to Passion: Limbic Activation by ''Unseen'' Drug and Sexual Cues. PLoS One 3(1): e1506. doi:10.1371/journal.pone.0001506 http://www.plosone.org/doi/pone.0001506

The study was funded by the National Institute on Drug Abuse (NIDA), part of the National Institutes of Health (NIH).

Adapted from materials provided by Public Library of Science, via EurekAlert!, a service of AAAS.

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Chronic Pain Harms The Brain

Daily Science Journal (Feb. 7, 2008) — People with unrelenting pain don't only suffer from the non-stop sensation of throbbing pain. They also have trouble sleeping, are often depressed, anxious and even have difficulty making simple decisions.

Comparison of brains. These images show the brain from the left side, demonstrating striking differences between chronic pain patients and healthy subjects. They illustrate with colors how much activation (red-yellow) or deactivation (dark/light blue) was found at each location. (Credit: Image courtesy of Northwestern University)

In a new study, investigators at Northwestern University's Feinberg School of Medicine have identified a clue that may explain how suffering long-term pain could trigger these other pain-related symptoms.

Researchers found that in a healthy brain all the regions exist in a state of equilibrium. When one region is active, the others quiet down. But in people with chronic pain, a front region of the cortex mostly associated with emotion "never shuts up," said Dante Chialvo, lead author and associate research professor of physiology at the Feinberg School. "The areas that are affected fail to deactivate when they should."

They are stuck on full throttle, wearing out neurons and altering their connections to each other.

This is the first demonstration of brain disturbances in chronic pain patients not directly related to the sensation of pain.

Chialvo and colleagues used functional magnetic resonance imaging (fMRI) to scan the brains of people with chronic low back pain and a group of pain-free volunteers while both groups were tracking a moving bar on a computer screen. The study showed the pain sufferers performed the task well but "at the expense of using their brain differently than the pain-free group," Chialvo said.

When certain parts of the cortex were activated in the pain-free group, some others were deactivated, maintaining a cooperative equilibrium between the regions. This equilibrium also is known as the resting state network of the brain. In the chronic pain group, however, one of the nodes of this network did not quiet down as it did in the pain-free subjects.

This constant firing of neurons in these regions of the brain could cause permanent damage, Chialvo said. "We know when neurons fire too much they may change their connections with other neurons and or even die because they can't sustain high activity for so long," he explained.

'If you are a chronic pain patient, you have pain 24 hours a day, seven days a week, every minute of your life," Chialvo said. "That permanent perception of pain in your brain makes these areas in your brain continuously active. This continuous dysfunction in the equilibrium of the brain can change the wiring forever and could hurt the brain."

Chialvo hypothesized the subsequent changes in wiring "may make it harder for you to make a decision or be in a good mood to get up in the morning. It could be that pain produces depression and the other reported abnormalities because it disturbs the balance of the brain as a whole."

He said his findings show it is essential to study new approaches to treat patients not just to control their pain but also to evaluate and prevent the dysfunction that may be generated in the brain by the chronic pain.

The study will be published Feb. 6 in The Journal of Neuroscience. Chialvo's collaborators in this project are Marwan Baliki, a graduate student; Paul Geha, a post-doctoral fellow, and Vania Apkarian, professor of physiology and of anesthesiology, all at the Feinberg School.

Adapted from materials provided by Northwestern University.

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Early Detection Critical In Treating Pediatric Thyroid Cancer

Daily Science Journal (Feb. 6, 2008) — Efforts to treat pediatric papillary thyroid cancer are greatly improved by detecting the disease as early as possible, making the patient's age the most important factor in determining a prognosis, according to new research published in the February 2008 issue of the journal Otolaryngology -- Head and Neck Surgery.

The study, authored by Italian researchers, evaluated 2,709 patients who underwent a total thyroidectomy to treat papillary thyroid carcinoma (PTC). Among the group's pediatric patients (younger than 18 years old), the cancer was observed to be much more aggressive than that in adult patients. However, despite the aggressive course of the disease, this did not influence the patient's survival rate, since cases of pediatric cancer have a better prognosis than that in adults. As a result, the authors concluded that age of detection is the single most important factor to consider when issuing a prognosis.

Thyroid cancer is the third most common tumor malignancy in children. It is one of the few cancers that has increased in incidence rates over the past several years, with an estimated 11 percent increase from 2006 to 2007. Papillary thyroid cancer occurs in cells that produce thyroid hormones containing iodine. This type, the most common form of thyroid cancer in children, grows very slowly.

The study also confirms that PTC is more prevalent in younger patients, compared with other age groups; these patients also had significantly larger tumors. However, the study's authors concluded that the size of the tumor, which is considered a significant factor in determining prognosis in adult patients, does not play a significant role in a child's prognosis.

The study also suggests a longer period for follow-ups is in order to more accurately measure the success of treatment.

Adapted from materials provided by American Academy of Otolaryngology, Head and Neck Surgery, via EurekAlert!, a service of AAAS.

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