10.26.07
Posted in Uncategorized at 5:01 am by Luis
A brain-imaging study of genetically obese rats conducted at the U.S. Department of Energy's Brookhaven National Laboratory provides more evidence that dopamine - a brain chemical associated with reward, pleasure, movement, and motivation - plays a role in obesity.
The scientists found that genetically obese rats had lower levels of dopamine D2 receptors than lean rats. They also demonstrated that restricting food intake can increase the number of D2 receptors, partially attenuating a normal decline associated with aging.
"This research corroborates brain-imaging studies conducted at Brookhaven that found decreased levels of dopamine D2 receptors in obese people compared with normal-weight people," said Brookhaven neuroscientist Panayotis (Peter) Thanos, lead author of the current study, which will be published online in the journal Synapse on Thursday, October 25, 2007.
It's not clear whether reduced receptor levels are a cause or consequence of obesity: Overeating may chronically reduce receptor levels, which, over the long term, could eventually contribute to obesity. But having genetically low receptor levels may also lead to obesity by predisposing the individual to overeating in an attempt to stimulate a "blunted" reward system. Either way, revving up receptor levels by restricting food intake could enhance the impact of this common strategy for combating obesity.
"Consuming fewer calories is obviously important for people trying to lose weight, plus improving the brain's ability to respond to rewards other than food may help prevent overeating," Thanos said. Because food intake can have such a dramatic effect on dopamine receptor levels, "this study also provides further evidence for the interplay of genetic factors with the environment in the development of obesity in our society," he said.
The finding that food restriction can attenuate the effects of aging on the brain's ability to respond to dopamine may also help explain why food restriction slows down other changes associated with aging, such as declines in locomotor activity and sensitivity to reward.
The researchers measured dopamine D2 receptor levels in adolescent and young adult genetically obese Zucker rats and lean rats. Between measures, half of the rats in each group were given free access to food while the other half were given 70 percent of the daily average amount of food eaten by the unrestricted group.
The scientists measured D2 receptor levels using two different techniques: micro-positron emission tomography (microPET) in living animals, which uses a radioactively tagged molecule that competes with the brain's natural dopamine for D2 receptor binding sites, and autoradiography, which uses a tracer that binds more strongly than natural dopamine but can only be used in tissue samples rather than in living animals. Together these two methods indicate the absolute number of D2 receptors found in the brain and how many are available or free during day-to-day function, which might be relevant to further elucidating the role of dopamine in obesity.
One main finding was that the overall number of D2 receptors was lower in obese than in lean rats. Also D2 receptor levels decreased with age, but this decline was significantly blunted in food-restricted rats compared with those given free access to food. This attenuation was most apparent in the obese rats.
Another main finding was that D2 receptor availability - that is, the number of receptors available for binding dopamine - was greater at adulthood in the obese rats compared to the lean rats. This suggests that perhaps the release of dopamine had significantly decreased with age in the obese unrestricted animals more than in the restricted ones or the lean rats. The possibility of lower release of dopamine in obese subjects is presently being examined, the researchers say.
This research was funded by the Office of Biological and Environmental Research within the U.S. Department of Energy's Office of Science and by the Intramural Research Program of the National Institute on Alcohol Abuse and Alcoholism, which is part of the National Institutes of Health.
http://www.bnl.gov
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10.25.07
Posted in Uncategorized at 8:51 am by Luis
The Parkinson's Institute and Clinical Center today announced research showing that intermittent nicotine treatment reduces medication-induced dyskinesias by as much as 50 percent in models of Parkinson's disease.
Lead by senior research scientist, Maryka Quik, Ph.D., the research will be published in an upcoming issue of the Annals of Neurology.
Levodopa, the most common drug used to treat Parkinson's disease, is initially very effective. However, long-term treatment often lessens efficacy and causes multiple complications, including abnormal involuntary movements, called dyskinesias. These uncontrolled movements of the head and limbs tend to worsen over time and can become as debilitating as Parkinson's disease itself. Currently, there are only limited therapeutic options for dyskinesias, including reduction in levodopa dose, amantadine administration, and deep brain stimulation for a limited number of patients.
Most of the research on tobacco has focused on its detrimental health effects. Studies conducted over the last 40 years show that the incidence of Parkinson's disease is about 50 percent less in smokers than in the general population. Recent studies in experimental models suggest that the nicotine in smoke may be responsible for this neuroprotective effect. In addition, this is the first research to show that nicotine may also reduce levodopa-induced dyskinesias. With an estimated 1.5 million Parkinson's disease patients in the United States, and levodopa being the top prescribed medication for Parkinson's disease, this study has far-reaching implications for the treatment of Parkinson's disease.
"Our hope is that this research represents a useful treatment strategy to reduce the dyskinesias that so many Parkinson's disease patients suffer, "said Dr. Maryka Quik of the Parkinson's Institute and Clinical Center in Sunnyvale. "Reducing the side effects of levodopa makes it a much more effective and long-term treatment."
http://www.thepi.org/
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Posted in Uncategorized at 8:17 am by Luis
In a new study comparing elderly abstinent alcoholics with light- or nondrinking peers, the recovering alcoholics generally demonstrated equal or superior cognitive functioning to those who were not alcoholic.
"We [had] expected to find impairment because we'd see the additive effect of alcohol and aging," said lead researcher George Fein, Ph.D., of the study in the November issue of Alcoholism: Clinical and Experimental Research .
Researchers looked at 91 abstinent alcoholics, men and women, with an average age of 67.3 years. Their lifetime drinking average was between 124 and 249 standard drinks per month, and their alcohol abstinence average was 14.8 years. The study group underwent cognitive and clinical testing along with 52 participants who were light drinkers or nondrinkers.
Both groups underwent attention, verbal ability, reaction time and immediate memory testing. The researchers also collected information about drinking behavior and any associated medical and psychiatric diagnoses and symptoms, and measured cranium size with MRI.
"Our results don't say that elderly individuals fully recover from the effects of alcohol. Our results say that there's a select sample of elderly alcoholics who are functioning very well," said Fein, president and senior scientist of Neurobehavioral Research, Inc., in Honolulu.
Petros Levounis, M.D., director of the Addiction Institute of New York at St. Luke's and Roosevelt Hospitals, agreed that the study showed "there is such a thing as being elderly, to have been an alcoholic and to maintain intact cognition."
Levounis added, "Of course, it can also be possible to be elderly, to [remain] a heavy drinker and to continue to have intact cognition. My clinical impression from my work with patients is that the damage alcohol does to the brain is very real and abstinence will help slow down or even halt the deterioration."
The study researchers found that the alcoholic group tended to have larger craniums than their control group peers and theorized that the difference could account for the equal or better performance of the alcoholic group. "When you're recruiting in people [aged] 65 to 85 amongst alcoholics, you end up getting people who are really exceptionally well functioning and those tend to be the ones with enhanced functional reserve capacity," Fein said.
Fein has previously investigated the relationship between cranium size, or "reserve capacity," and brain function, a correlation that is controversial in scientific circles. He suggested that brain growth in very early childhood might mean the difference between normal functioning and cognitive impairment for abstinent alcoholics in their later years.
Levounis, who is not connected with the new study, said that it offers no record of cranium measurements for members of the control group - biological data he sees as critical to the study's conclusions. "That a larger brain somehow is associated with a higher ability to retain cognitive function is a proposition I would be very, very cautious before adopting?. Without these numbers, we cannot even start looking at it," he said.
Fein emphasized that the study results are not an invitation for people with good cerebral reserve - big brains - to abuse alcohol. "These are people who also stopped drinking - who have significant abstinence," he said.
Alcoholism: Clinical and Experimental Research : Contact Mary Newcomb at (317) 375-0819 or mnewcomb-acer@earthlink.net or visit http://www.alcoholism-cer.com
Fein G, McGillivray S. Cognitive performance in long-term abstinent elderly alcoholics. Alcoholism: Clinical and Experimental Research 31(11), 2007.
http://www.hbns.org
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Posted in Uncategorized at 8:17 am by Luis
Oncolytics Biotech Inc. has announced that it has received a letter of approval from the U.K. Medicines and Healthcare products Regulatory Agency (MHRA) for its Clinical Trial Application (CTA) to begin a clinical trial using intravenous administration of REOLYSIN in combination with cyclophosphamide, a chemotherapeutic agent as well as immune modulator, in patients with advanced cancers.
The Principal Investigators are Dr. James Spicer of King's College in London, Dr. Johann de Bono and Dr. Kevin Harrington of The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, London, and Professor Hardev Pandha of the Royal Surrey County Hospital NHS Trust, Surrey and Mount Alvernia Hospitals.
The Company also intends to host a conference call Wednesday, October 24, 2007 to provide an update on its expanding clinical program. The dial-in details appear below.
"We are really looking forward to treating patients in this trial," said Principal Investigator Dr. James Spicer. "The hope is that it will provide valuable information about the relationship between oncolytic viral therapy and the immune response of the patient."
The trial (REO 012) is an open-label, dose-escalating, non-randomized trial of REOLYSIN? given intravenously with escalating doses of cyclophosphamide. A standard dose of REOLYSIN? is administered intravenously over five consecutive days, while an intravenous dose of cyclophosphamide is administered three days before REOLYSIN? treatment and continues through the course of the treatment cycle. The total number of patients studied will depend on the number of dose levels tested, but it is anticipated to be approximately 30 patients.
http://www.oncolyticsbiotech.com/
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Posted in Uncategorized at 8:17 am by Luis
New research now has shown for the first time that such a diet also can maintain physical fitness into advanced age, slowing the seemingly inevitable progression to physical disability and loss of independence.
The study, using a rat model of life-time caloric restriction, showed that the diet reduces the amount of visceral fat, which expresses inflammatory factors that in humans cause chronic disease and a decline in physical performance and vitality across the lifespan.
The study appears in the October issue of Journals of Gerontology Series A: Biological Sciences and Medical Sciences.
Have we finally discovered the Fountain of Youth?
No. But we may be getting a little closer.
"This is the first study to report that caloric restriction reduced production in visceral fat of the inflammatory cytokine IL-6 and enhanced performance on overall physical function assessments," said Tongjian You, Ph.D., assistant professor of exercise and nutrition sciences in the UB School of Public Health and Health Professions and principal investigator.
"In addition, rats that ate a normal diet lost a significant amount of lean muscle mass and acquired more fat, while calorie-restricted rats maintained lean muscle mass as they aged."
The study was conducted with male rats in three age groups -- 18, 24 and 29 months, comparable to ages 50-70 years in humans -- that had been fed either a normal or
40-percent calorie-restricted diet from birth. The animals were put through tests to determine grip strength, muscle tone, stamina and swimming speed. Data also were collected on whole body mass, lean body mass, fat mass, percent body fat, the ratio of fat-to-lean body mass, amount of visceral fat and the amount of pro-inflammatory cytokines and C-reactive protein, a marker of chronic inflammation.
Results showed that animals on the restricted calorie diet had significantly higher physical performance scores than animals fed a normal diet. They also had less fat, a lower fat-to-lean ratio, and lower adipose tissue secretion of IL-6 and circulating levels of C-reactive protein.
The stumbling block on this path to remaining forever young is that humans could not adhere to such a severe diet.
"Based on an average of 2,000 calories per day for adult women and 2,500 for men, cutting by 40 percent would mean surviving on 1,200 and 1,500 calories per day, respectively, said You.
"It's very difficult for people to maintain that type of diet for short periods of time, and it would be nearly impossible over a lifetime, while staying healthy. Starting on a diet like that in the senior years would be harmful."
You said that a more moderate form of caloric restriction, 8 percent, is achievable in humans, based on recent findings, and may have positive effects on specific oxidative stress and inflammatory biomarkers.
"Preclinical testing of this 8-percent regimen could be informative and beneficial in translating to humans," he said.
http://www.buffalo.edu/
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