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    Tuesday, May 12, 2009

    Dissecting The Signaling Pathways Involved In The Anti-Hypertrophic Effects of Resveratrol


    Background: Pathological left ventricular hypertrophy is associated with all-cause mortality; however, effective treatment for this condition is currently lacking. We have shown that activation of AMP-activated protein kinase (AMPK) by resveratrol can inhibit myocardial hypertrophy by decreasing protein synthesis and suppressing nuclear factor ofactivated T-cells (NFAT) activation. However, the mechanism by which resveratrol affects AMPK isunknown. Since LKB1 is the upstream kinase of AMPK, we hypothesize that resveratrol signals via LKB1 toactivate AMPK and it is this signalling pathway that contributes to the anti-hypertrophic effects of resveratrol.

    Methods: Wildtype (WT), LKB1 null, and AMPK null mouseembryonic fibroblasts (MEFs) were treated with vehicle or 100?M resveratrol for 1 h. Cell lysates were subjected to immunoblot analysis to examine the phosphorylation status of the proteins of interest. NFAT-dependent transcription was also measured in these MEFs using a NFAT-luciferase reporter transgene.

    Results: While resveratrol treatment increased AMPK phosphorylation in WT MEFs, resveratrol was unable to activate AMPK in LKB1 null MEFs. In addition, resveratrol suppressed NFAT-dependent transcription in WT MEFs, yet failed to inhibit NFAT activity in AMPK null MEFs.

    Conclusion: These data combined with our previous data suggest that resveratrol signals through LKB1 to activate AMPK and that this activation results in suppressed protein synthesis and reduced NFAT activation. As the development of pathologicalcardiac hypertrophy is dependent on protein synthesis and NFAT activation, inhibition of these two pathways by resveratrol may be an exciting new approach for the treatment of pathological cardiac hypertrophy.


    Monday, May 11, 2009

    ACOG: Soy, Red Wine Have Anti-Estrogenic Effects

    Compounds in soy and red wine may positively affect gynecologic health and help prevent endometriosis, according to a prize-winning paper presented this week at the American College of Obstetricians and Gynecologists' Annual Clinical Meeting, held from May 2 to 6 in Chicago.

    Sharai C. Amaya, M.D., of the Greenville Hospital System in South Carolina, and colleagues studied the effects of geninstein and resveratrol on endometrial proliferation and activation in the cell line ECC-1 and in immunocompromised mice which had been implanted with human endometrium or endometriosis.

    Both studies showed that geninstein and resveratrol had anti-estrogenic activity. In mice treated with estradiol and progesterone, the researchers found that geninstein and resveratrol reduced the size and activity of implanted endometrial tissue but that only the highest dose of resveratrol was associated with a statistically significant effect on cell proliferation.

    "Resveratrol may be functioning as an aryl hydrocarbon receptor antagonist. Further studies are required in humans to investigate the role of dietary compounds such as soy (geninstein) or red wine (resveratrol) on both gynecologic health and disease," the authors conclude.


    Rx For Red Wine

    Many studies tout the health benefits of red wine, and Brock University PhD student Ellen Robb wants to find out why

    Scientists have found fermented red grape juice might be able to do everything from keeping your heart healthy to delaying the aging process to preventing prostate cancer.

    The 24-year-old biology student has spent much time studying resveratrol, the active ingredient in red wine that many scientists believe is key to positive health gains. She wants to find out how resveratrol affects cells.

    People have found, 'Oh, (red wine) protects against cardiovascular disease.' But no one really knows why," said Robb, incoming president of the Graduate Student Association.

    We want to be able to go back and look at a cellular level and say, 'This is what's going on, and this is what causing that,' so better treatments can be made and alterations to drugs and anything like that."

    The St. Catharines resident netted $150,000 over three years through the Vanier Canada Graduate Scholarship program to carry out her research.

    Robb is the first student from Brock to receive the award, which was launched by the federal government in 2008.

    This year, 166 graduate students will receive the scholarship, which is given to the world's leading doctoral students hailing from across Canada and abroad.

    This is going to mean that I can pretty much do anything I want," said Robb, a Niagara-on-the-Lake native.

    I can travel, go to workshops with really very renowned people in the field and go to any conferences. It also means for my supervisor that he doesn't have to pay me. He has more money to do things for other students as well."

    Robb is working under the supervision of Jeff Stuart from the department of biological sciences.

    Robb, who is not really a wine drinker, began looking at resveratrol as a undergraduate student at the urging of Stuart.

    Still, doctors recommend drinking any kind of alcohol, including red wine, in moderation, and some studies have linked fermented grape juice to health problems, such as breast cancer.

    I think because it is something that people drink, and because it's popular culture, it gets a lot of media attention. It can be a little bit overwhelming."

    Encouraging, at least for local wineries, is that Robb has found evidence that Ontario red wines might contain more resveratrol than wines made in other parts of the world.


    Small Amount of Wine Daily Boosts Life Expectancy

    Drinking alcohol in excess is associated with a host of health problems, including an increased risk of certain cancers, liver disorders and even brain damage. But new research just published in the online version of the Journal of Epidemiology and Community Health, concludes up to just half a glass of wine daily can have remarkable health benefits. In fact, at least for men, drinking a small amount of wine may boost life expectancy by five years.

    Dutch researchers at Wageningen University in the Netherlands studied a total of 1,373 randomly selected 50-year-old men whose cardiovascular health and life expectancy were monitored regularly between the years of 1960 and 2000. The scientists noted the research subjects' weight and diet and whether the men smoked and for how long. They also checked to see if the men had any serious illness. In addition, the research team documented how much alcohol the men drank, what type it was, and how long they drank. Then they assessed whether the men's alcohol consumption had any impact on their risk of dying from all causes -- including from cardiovascular disease and cerebrovascular disease.

    Over the 40 years their health was monitored, an increasing number of the men drank alcohol. In fact, the proportion that drank alcohol almost doubled from 45 percent in 1960 to 86 percent in 2000. What's more, the proportion of those drinking wine soared from only two percent when the study began to 44 percent by 2000.

    During the 4 decades long study, some 1,130 of the men died and about half these deaths were apparently caused by cardiovascular disease. But while analyzing the data, the researchers found that light long term alcohol consumption of all types -- up to 20 grams (g) a day -- boosted life expectancy life by around two extra years compared to drinking no alcohol at all. However, life expectancy was slightly lessened for the men who drank more than 20 g.

    Another finding could justify wine lovers offering a toast to long life -- the men who drank only wine, and less than half a glass of it a day, lived approximately 2.5 years longer than those who drank beer and spirits. And they lived about five years longer than those who drank no alcohol at all.

    According to a statement to the media, the researchers concluded that drinking wine in moderation was strongly associated with a lower risk of dying from coronary heart disease, cerebrovascular disease, and death from all causes. What's more, these results held true, no matter the socioeconomic status, diet and other lifestyle habits of the men.


    Monday, May 4, 2009

    Wine Adds Five Years to Life, More Than Beer, Dutch Study Finds

    Half a glass of wine a day may add five years to your life, a new study suggests. Drink beer, and you’ll live only 2 1/2 years longer.

    Dutch researchers followed 1,373 men for more than four decades, noting their eating and drinking habits. Men who had about 20 grams of alcohol daily -- equivalent to a half a glass of wine -- had 2 1/2 years added to their life expectancy at age 50, compared with men who didn’t drink at all, according to the research published today in the Journal of Epidemiology and Community Health. Men who consumed only wine had twice as much added longevity.

    Light alcohol intake was linked to lower cardiovascular, cerebrovascular and overall mortality in the study. Researchers had known that moderate drinking is tied to a lower risk of heart disease, possibly because of an increase in high density lipoprotein or so-called good cholesterol as well as a reduction in platelet clumping, making it more unlikely for clots to form. It is the first study to show that one kind of alcohol is superior to others in prolonging life, the researchers said.

    “In this study, 70 percent of all wine consumed was red wine,” the researchers, led by Marinette Streppel of the University of Wageningen in the Netherlands, said in the paper. “This suggests that the cardioprotective effect of wine could be due to a protective effect of polyphenol compounds in red wine, but other explanations cannot be ruled out.”

    Polyphenols are chemical substances found in plants such as tannins and flavonoids.

    The research, dubbed Zutphen Study after the Dutch town from which the participants were recruited, followed men born between 1900 and 1920 and examined them several times between 1960 and 2000.


    Drink A Little Wine, Live A Little Longer

    Men who regularly drank up to a half a glass of wine each day boosted their life expectancy by five years, Dutch researchers report.

    Light, long-term alcohol consumption of all types of beverages, whether wine, spirits or beer, increased life by 2.5 years among men compared with abstention, the researchers found. By "light," they meant up to 20 grams, or about 0.7 ounces a day.

    While numerous other studies have found similar benefits, study author Martinette Streppel, of the division of human nutrition at Wageningen University in the Netherlands, said 40 years of follow-up is noteworthy for many reasons.

    "The main strength of our study was the collection of detailed information on the consumption of different alcohol beverages at each of seven measurement rounds," Streppel said.

    The long-term, regular follow-up, Streppel added, enabled the researchers to study the effect of long-term alcohol intake on mortality.

    The study is published online in April in the Journal of Epidemiology and Community Health.

    The Dutch researchers evaluated 1,373 men, all part of the Zutphen Study, started in 1960 and named for an industrial town in the Netherlands. The researchers followed them from 1960 to 2000, tracking weight, diet, cigarette smoking, the diagnosis of serious illness and other data, along with their drinking habits.

    Over the follow-up period, 1,130 of the men died, half from cardiovascular disease.

    The proportion of men who drank alcohol nearly doubled from 45 percent of the men in 1960 to 86 percent in 2000. Those drinking wine rose even more dramatically -- from just 2 percent to 44 percent.

    The findings in more detail:

    • All long-term light alcohol drinking boosted life expectancy by about 2.5 years in comparison to abstainers. Drinking more than 0.7 ounces a day extended life expectancy by nearly two years compared with nondrinkers.
    • Wine drinkers who averaged just 0.7 ounces a day had a 2.5 year-longer life expectancy at age 50 compared to those who drank beer or spirits. And their life expectancy was nearly five years longer than nondrinkers.
    • Drinking moderately was linked with lower death risk, and drinking wine was strongly linked with a lower risk of dying from heart disease, stroke or other causes.
    Streppel couldn't say if the findings apply to women, but suspects the polyphenolic compounds found in wine, especially red wine, produce the heart-healthy effects.

    The study adds to the literature of the health benefits of alcohol, but has both strengths and weaknesses, said Dr. Arthur Klatsky, a long-time investigator on the health benefits of alcohol.

    "Once again, it shows that people who drink [moderately] do a lot better than people who don't in terms of survival," he said.

    However, as with other research, Klatsky wondered if it's the pattern of drinking or something related to the wine drinking -- such as wine drinkers being more likely to exercise or eat a healthy diet -- that is the real link.

    In the new Dutch study, he says, alcohol from spirits contributes the most to the total alcohol intake, more than wine or beer.

    "It's a little hard to think that a little bit of wine is what is responsible for extending their life," Klatsky said.

    The finding, like similar ones, applies more to middle-aged people than younger ones, he said. "People over 50 are the ones most likely to have health benefits from light drinking anyways."

    Much more important in reducing heart disease risk, he said, is not smoking, exercising regularly, eating healthfully and maintaining a healthy weight.