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The brains of alcohol-dependent individuals are affected not only by their own heavy drinking, but also by genetic or environmental factors associated with their parents' drinking, according to a new study by researchers at the National Institute on Alcohol Abuse and Alcoholism (NIAAA), part of the National Institutes of Health (NIH). Researchers found reduced brain growth among alcohol-dependent individuals with a family history of alcoholism or heavy drinking compared to those with no such family history. Their report appears in a recent online edition of Biological Psychiatry.

"This is interesting new information about how biological and environmental factors might interact to affect children of alcoholics," notes George Kunos MD, PhD, scientific director of the division of intramural clinical and biological research at the NIAAA.

Many studies have shown that alcohol-dependent men and women have smaller brain volumes than non-alcohol-dependent individuals. It is widely believed that this is due to the toxic effects of ethanol, which causes the alcoholic's brain to shrink with aging to a greater extent than the non-alcoholic's.

"Our study is the first to demonstrate that brain size among alcohol-dependent individuals with a family history of alcoholism is reduced even before the onset of alcohol dependence," explains first author Jodi Gilman, BS, a NIAAA research fellow and PhD candidate at Providence, R.I.-based Brown University working with senior author Daniel Hommer, MD, of the NIAAA Laboratory of Clinical and Translational Studies (LCTS) and co-author James Bjork, PhD, also of the NIAAA/LCTS.

Children of alcoholics are known to have a greater risk for alcohol dependence than individuals without a parental history of alcohol dependence. In addition to inheriting genes that predispose them to alcoholism, children of alcoholics may experience adverse biological and psychological effects from poor diets, unstable parental relationships and alcohol exposure before birth, all of which could contribute to their increased risk for alcoholism.

In a search for direct physical evidence of these assumed genetic and environmental mediators of family-transmitted alcoholism, the NIAAA researchers used MRI techniques to measure the volume of the cranium – the part of the skull that encloses the brain – in a group of individuals being treated for alcohol dependence.

The intracranial volume (ICV), they note, is determined by skull growth, which occurs as the brain expands to its maximum size around puberty. Because ICV does not change as the brain shrinks with age, it provides a good estimate of the lifetime maximum volume of the brain.

The researchers found that the average ICV of adult alcoholic children of alcoholic parents was about 4 percent smaller than the average ICV of adult alcoholics without family histories of alcoholism or heavy drinking. Family history did not affect the frequency, quantity or other aspects of drinking behavior of the alcoholics themselves, suggesting that differences in ICV between family history positive and negative alcoholics are not the result of different drinking patterns.

The researchers also found that adult alcoholic children of alcoholic parents had IQ scores that averaged 5.7 points lower than IQs of alcohol dependent individuals with no parental drinking, but that were still within the range of normal intelligence.

The authors note that a possible implication of their findings is that the increased risk for alcoholism among children of alcoholics may be due to a genetic or environmental effect, or both, related to reduced brain growth.

"Although ICV is known to be influenced primarily by genetic factors," says Hommer, "many studies have found that living in an enriched environment promotes central nervous system growth and development. It seems likely that alcoholics, in general, are raised in less than optimal environments and, thus, that genetics and environment both contribute to the smaller ICV observed in family history-positive alcoholics."

The authors report that ICV of women, but not men, in the study appeared to be affected more by their mothers' drinking than their fathers', perhaps due to a greater maternal influence on a child's nutritional, social and intellectual environment. None of the participants in the study were diagnosed with fetal alcohol syndrome.

"It is possible that some participants might have experienced subtle fetal alcohol effects," notes Hommer. "However, there were no differences between the effects of maternal and paternal drinking on ICV of men in our study. Thus, fetal alcohol effects do not appear to account for the reduced ICV we saw in men with a positive family history for drinking."? Because of this, Hommer says, "Future studies should determine more precisely how parental drinking affects brain size among children of alcoholics and whether smaller ICV is a more specific risk factor for the development of alcohol dependence than family history."

— NIH/NIAAA

U.S. Drug-Eluting Stent Market to Grow to $3 Billion by 2011

Waltham, Mass.-based Millennium Research Group (MRG) has conducted a detailed analysis of the interventional cardiology market in its "U.S. Markets for Interventional Cardiology Devices 2007" report. The report indicates that, despite a difficult 2006, the drug-eluting stent (DES) market will rebound from 2008 with the emergence of new DES competitors, Medtronic and Abbott Vascular. Both Medtronic's Endeavor DES and Abbott Vascular's Xience have successfully entered the European market, and will take significant market share in 2007.

DES penetration in the United States decreased almost 20 percent over 2006 from a high of 89 percent at the beginning of the year due to the release of clinical data linking DES to late stent thrombosis. In patients at high risk for late stent thrombosis, physicians who had previously used a DES often chose bare-metal stents (BMS) to be safe, reawakening the market for BMS, which grew more than 15 percent in 2007.

"While 2006 was a tough year for DES, we see this as a relatively short-term decline," says Bina Mistry, analyst at MRG. "With new competitors entering the market and the continual release of positive clinical data, physician preference will revert back to DES, significantly expanding the market. We forecast the U.S. market will follow the same path as Europe, with the DES market set to record notable market share shifts."

— Millennium Research Group

Natural Antibiotics Secret to Atom-Level Imaging

Frog skin and human lungs hold secrets to developing new antibiotics, and a technique called solid-state nuclear MR (NMR) spectroscopy is a key to unlocking those secrets.

That's the view of Ann Arbor-based University of Michigan researcher, Ayyalusamy Ramamoorthy, PhD, who discussed his group's progress toward that goal last month at the annual meeting of the Biophysical Society in Baltimore.

Ramamoorthy's research group is using solid-state NMR to explore the germ-killing properties of natural antibiotics called antimicrobial peptides (AMPs), which are produced by virtually all animals, from insects and frogs to humans. AMPs are the immune system's early line of defense, battling microbes at the first places they try to penetrate: skin, mucous membranes and other surfaces. They're copiously produced in injured or infected frog skin, for instance, and the linings of the human respiratory and gastrointestinal tracts also crank out the short proteins in response to invading pathogens.

In addition to fighting bacteria, AMPs attack viruses, fungi and even cancer cells, so drugs designed to mimic them could have widespread medical applications, says Ramamoorthy, who is an associate professor of chemistry and an associate research scientist in the biophysics research division.

While researchers have identified hundreds of AMPs in recent years, they're still puzzling over exactly how the peptides wipe out bacteria and other microbes. Unlike conventional antibiotics, which typically inhibit specific bacterial proteins, AMPs get downright physical with invaders, punching holes into their membranes. But they're selectively pugnacious, targeting microbes but leaving healthy host cells alone.

"They're like smart bombs," Ramamoorthy says. "We'd like to exploit their properties to design super-smart bombs, but before we can do that, we need to understand how these AMP smart bombs interact with membranes to destroy bacteria. We need to know how they're shaped before, during and after the process of attaching to bacteria and how they attach."

Solid-state NMR spectroscopy is an ideal tool for answering such questions because it provides atom-level details of the molecule's structure in the complex and challenging cell membrane environment, Ramamoorthy says. "Just as an MRI produces a detailed image of our internal organs, solid-state NMR spectroscopy is used to construct a detailed image of a peptide or protein and to reveal how it sits in the cell membrane," providing clues for modifications that might make synthetic AMPs even more effective in overcoming ever-increasing bacterial resistance. For instance, rearranging parts of the molecule might make it fit into the membrane better, resulting in greater effectiveness with smaller amounts of AMP.

"Our overall mission is to use the kind of basic physical data we obtain from solid-state NMR spectroscopy to help interpret biological functions," Ramamoorthy says.

—  University of Michigan