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Flavonoids Could Represent Two-Fisted Assault on Diabetic Complications and Nervous System Disorders



Salk Scientists Say: It's not an Apple a day after all - it's Strawberries!

Newswise — LA JOLLA, CA-A recent study from scientists at the Salk Institute for Biological Studies suggests that a strawberry a day (or more accurately, 37 of them) could keep not just one doctor away, but an entire fleet of them, including the neurologist, the endocrinologist, and maybe even the oncologist.

Investigations conducted in the Salk Institute's Cellular Neurobiology Laboratory (CNL) will appear in the June 27, 2011, issue of PLoS ONE. The report explains that fisetin, a naturally-occurring flavonoid found most abundantly in strawberries and to a lesser extent in other fruits and vegetables, lessens complications of diabetes. Previously, the lab showed that fisetin promoted survival of neurons grown in culture and enhanced memory in healthy mice. That fisetin can target multiple organs strongly suggests that a single drug could be used to mitigate numerous medical complications.

"This manuscript describes for the first time a drug that prevents both kidney and brain complications in a type 1 diabetes mouse model," says David Schubert, Ph.D., professor and head of the Cellular Neurobiology Laboratory and one of the manuscript's co-authors. "Moreover, it demonstrates the probable molecular basis of how the therapeutic is working."

Pam Maher, Ph.D., a senior staff scientist in the CNL, is the study's corresponding author. Maher initially identified fisetin as a neuroprotective flavonoid ten years ago. "In plants, flavonoids act as sunscreens and protect leaves and fruit from insects," she explains. "As foods they are implicated in the protective effect of the 'Mediterranean Diet.'"

Other celebrity flavonoids include polyphenolic compounds in blueberries and red wine.

Although her group's focus is neurobiology, Maher and colleagues reasoned that, like other flavonoids, fisetin might ameliorate a spectrum of disorders seen in diabetic patients. To test this, they evaluated effects of fisetin supplementation in Akita mice, a very robust model of type 1 diabetes, also called childhood onset diabetes.

Akita mice exhibit increased blood sugar typical of type 1 diabetes and display pathologies seen in serious human complications of both type 1 and 2 diabetes. Those include diabetic nephropathy or kidney disease, retinopathy, and neuropathies in which patients lose touch or heat sensations.

Mice fed a fisetin-enriched diet remained diabetic, but acute kidney enlargement-or hypertrophy-seen in untreated mice was reversed, and high urine protein levels, a sure sign of kidney disease, fell. Moreover, fisetin ingestion ameliorated anxiety-related behaviors seen in diabetic mice. "Most mice put in a large area become exploratory," says Maher. "But anxious mice tend not to move around. Akita mice showed enhanced anxiety behavior, but fisetin feeding restored their locomotion to more normal levels."

The study also defines a likely molecular mechanism underlying these effects. Researchers observed that blood and brain levels of sugars affixed to proteins known as advanced glycation end-products-or AGEs-were reduced in fisetin-treated compared to untreated Akita mice. These decreases were accompanied by increased activity of the enzyme glyoxalase 1, which promotes removal of toxic AGE precursors.

The discovery of an AGE-antagonizing enzyme upregulated by fisetin is very intriguing, because substantial evidence implicates high blood AGE levels with many if not most diabetic complications. "We know that fisetin increases activity of the glyoxalase enzyme and may increase its expression," says Maher. "But what is important is that ours is the first report that any compound can enhance glyoxalase 1 activity."

Interestingly, excessively high AGE levels also correlate with inflammatory activity thought to promote some cancers. In fact, studies published by others confirm that fisetin decreases tumorigenicity of prostate cancer cells both in culture and in animal models, which if supported would represent a major added incentive to eat your strawberries.

To ingest fisetin levels equivalent to those fed Akita mice, Maher estimates that humans would have to eat 37 strawberries a day, assuming that strawberry fisetin is as readily metabolizable by humans as fisetin-spiked lab chow is by mice. Rather than through diet, Maher envisions that fisetin-like drugs could be taken as a supplement.

Schubert notes that fisetin is also effective in mouse models of Alzheimer's disease. "We and others have shown that diabetes may be a risk factor for Alzheimer's disease, making identification of a safe prophylactic like fisetin highly significant," he says.

Maher acknowledges that the public may be suffering from flavonoid-fatigue, given media coverage of the promises of these compounds. "Polyphenolics like fisetin and those in blueberry extracts are found in fruits and vegetables and are related to each other chemically," she says. "There is increasing evidence that they all work in multiple diseases. Hopefully some combination of these compounds will eventually get to the clinic."

Schubert concurs that their findings only reinforce what common sense and our mothers told us was a healthy lifestyle. "Eat a balanced diet and as much freshly prepared organic food as possible, get some exercise, keep socially and mentally active and avoid sodas with sugar and highly processed foods since they can contain high levels of AGEs," he advises.

But he also worries that hoops that must be jumped through to bring a natural product like fisetin, as opposed to a totally synthetic drug, to clinical trials are daunting because it is difficult to protect patents on natural products. "We will never know if a compound like fisetin works in humans until someone is willing to support a clinical trial."

Also contributing to this study were Richard Dargusch and Jennifer L. Ehren, Ph.D.,of the Cellular Neurobiology Laboratory, and Kumar Sharma, M.D., and Shinichi Okada, M.D., Ph.D., of the Department of Medicine at University of California, San Diego.

Funding for the study came from the Fritz B. Burns Foundation, the Juvenile Diabetes Research Foundation, the Hewitt Foundation, and the National Institutes of Health.

About the Salk Institute for Biological Studies:
The Salk Institute for Biological Studies is one of the world's preeminent basic research institutions, where internationally renowned faculty probe fundamental life science questions in a unique, collaborative, and creative environment. Focused both on discovery and on mentoring future generations of researchers, Salk scientists make groundbreaking contributions to our understanding of cancer, aging, Alzheimer's, diabetes and infectious diseases by studying neuroscience, genetics, cell and plant biology, and related disciplines

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E-Prescribing Doesn't Slash Errors, Study Finds

Computer-generated scripts for outpatients often make same mistakes as manual systems

http://www.nlm.nih.gov/medlineplus/news/fullstory_113785.html

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كيف خطر على بالهم هيك دراسة


Language barriers related to increased hospital readmissions for Chinese- and Spanish-speaking patients


http://www.ahrq.gov/research/jul11/0711RA4.htm

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How to Stay Hydrated in Hot Weather

Figuring out your personal 'sweat rate' is the secret to avoiding dehydration, expert says

http://www.healthfinder.gov/news/newsstory.aspx?docID=654351

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Stop-Smoking Drug Chantix Ups Risk of Heart Problems: Study

Risks outweigh benefits, even for people without pre-existing heart disease, researchers say.

http://www.healthfinder.gov/news/newsstory.aspx?docID=654454

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Celecoxib May Prevent Lung Cancer in Former Smokers



Newswise — PHILADELPHIA — Celecoxib may emerge as a potent chemopreventive agent for lung cancer, according to a recent study in Cancer Prevention Research, a journal of the American Association for Cancer Research.

Researchers tested celecoxib, a COX-2 inhibitor, among patients who were former smokers and found a significant benefit in bronchial health as measured by the Ki-67 labeling index, a marker of cellular proliferation or growth, as well as a number of other biomarkers. The findings follow a previous report published in Cancer Prevention Research that showed a similar effect on Ki-67 among former smokers and current smokers (Kim et al., Feb. 2010).

“Taken together, these findings strongly suggest that celecoxib can be used as a chemopreventive agent in these high-risk groups,” said Jenny Mao, M.D., a professor of medicine at the University of New Mexico and section chief of pulmonary and critical care medicine at the New Mexico VA Health System.

Mao cautioned, however, that both the current study, where she was the lead researcher, and the Feb. 2010 study were phase II trials, and that large phase III trials are still needed to confirm the findings.

J. Jack Lee, Ph.D., a professor of biostatistics at The University of Texas M. D. Anderson Cancer Center and the statistical editor of Cancer Prevention Research, estimates that there are currently 45 million former smokers and 45 million current smokers in the United States alone.

“The oncology community does not have a good treatment for lung cancer. Unless it is caught in the earliest stages, the five-year survival is only about 15 percent,” said Lee. “The best way is to intercept at the earliest stages and try to reverse the processes that can lead to cancer. These studies suggest celecoxib may be a tool to do that.”

For the current study, Mao and colleagues enrolled 137 patients and randomly assigned them to 400 mg celecoxib twice daily or a placebo. Patients had to be at least 45 years old, and had to have stopped smoking for at least a year.

Researchers conducted bronchoscopies at baseline and six months to measure changes in the Ki-67 labeling index. Treatment with celecoxib reduced this index by 34 percent compared to a 3.8 percent increase with the placebo group. Decreases in this index were also linked with a reduction in lung nodules, a potential precursor to cancer.

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Tots Who Are 'Late Talkers' Typically Turn Out Fine: Study

Children not talking by age 2 usually catch up with no lasting issues, researchers say.


Youngsters who aren't talking at age 2 generally aren't at risk for future behavioral or emotional problems as a result, suggests new research.

http://www.healthfinder.gov/news/newsstory.aspx?docID=654492

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Celecoxib May Prevent Lung Cancer in Former Smokers

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غريبة
                                                           
شو جاب السيليكوكسيب لسرطان الرئة
                                                           
!!!!!!!!!!!!!!!!
                                                                   

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Natural Ways to Fight Allergies


Tired of Being Stuck Indoors?

Many allergy and asthma sufferers face spring's blooming season with dubious cheer. After all, it's hard to get swept up into the season when you're sneezy and wheezy. Even those on medication find that they need an extra boost during the most pollen-heavy months. Read on for common methods of easing allergy symptoms.

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Fructose Consumption Increases Risk Factors for Heart Disease

A recent study accepted for publication in The Endocrine Society’s Journal of Clinical Endocrinology & Metabolism (JCEM)
found that adults who consumed high fructose corn syrup for two weeks
as 25 percent of their daily calorie requirement had increased blood
levels of cholesterol and triglycerides, which have been shown to be
indicators of increased risk for heart disease.

The American Heart
Association recommends that people consume only five percent of
calories as added sugar. The Dietary Guidelines for Americans 2010
suggest an upper limit of 25 percent or less of daily calories consumed
as added sugar. To address this discrepancy in recommended consumption
levels, researchers examined what happened when young overweight and
normal weight adults consumed fructose, high fructose corn syrup or
glucose at the 25 percent upper limit.

“While there is evidence
that people who consume sugar are more likely to have heart disease or
diabetes, it is controversial as to whether high sugar diets may
actually promote these diseases, and dietary guidelines are
conflicting,” said the study’s senior author, Kimber Stanhope, PhD, of
the University of California, Davis. “Our findings demonstrate that
several factors associated with an elevated risk for cardiovascular
disease were increased in individuals consuming 25 percent of their
calories as fructose or high fructose corn syrup, but consumption of
glucose did not have this effect.”

In this study, researchers
examined 48 adults between the ages of 18 and 40 years and compared the
effects of consuming 25 percent of one’s daily calorie requirement as
glucose, fructose or high fructose corn syrup on risk factors for
cardiovascular disease. They found that within two weeks, study
participants consuming fructose or high fructose corn syrup, but not
glucose, exhibited increased concentrations of LDL cholesterol,
triglycerides and apolipoprotein-B (a protein which can lead to plaques
that cause vascular disease).

“These results suggest that
consumption of sugar may promote heart disease,” said Stanhope.
“Additionally our findings provide evidence that the upper limit of 25
percent of daily calories consumed as added sugar as suggested by The
Dietary Guidelines for American 2010 may need to be re-evaluated.”

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Cholesterol-Lowering Drugs May Help Prevent Recurrent Strokes in Younger People


 
American Academy of Neurology (AAN)