Archive for May, 2008


Thursday, May 29th, 2008

Thanks to powerful cholesterol-lowering statin drugs, driving down low-density lipoprotein (LDL), or “bad” cholesterol, has been the primary approach to improving cholesterol levels. But there’s more to the story of cholesterol and cardiovascular risk than LDL alone. Another key player is high-density lipoprotein (HDL), the “good” cholesterol. Higher levels of HDL are associated with lower cardiovascular risk. The good news about this good cholesterol is that simple lifestyle changes can help boost HDL, reports the June 2008 issue of Harvard Women’s Health Watch.

HDL removes LDL from artery walls and ferries it to the liver for processing or removal. HDL also fights potentially dangerous inflammation and clot formation. According to a recent review of research on HDL, there’s some evidence that increasing HDL can reduce the risk of heart attack and stroke even without changes in LDL.

Harvard Women’s Health Watch suggests several things people can do to nudge up HDL levels. Most of these strategies also improve health in other ways.

1. Get aerobic exercise. Moderate to vigorous aerobic exercise can boost HDL by 5% to 10%. Aim for five 30-minute sessions per week.

2. Lose weight if you need to. If you’re overweight or obese, you can boost your HDL level by about 1 mg/dL for every seven pounds lost, although any amount of weight loss will help.

3. If you smoke, quit. HDL levels rise by as much as 15% to 20% after you quit.

4. Eat a healthy diet. Avoid trans fats, which increase bad cholesterol and decrease good cholesterol. Avoid highly refined carbohydrates, such as white-flour products.

5. Consider medications. Niacin, available over the counter, is the most effective HDL-raising medication available. Niacin can be strong medicine work with your clinician if you want to try it.



Wednesday, May 21st, 2008

Discovery of enzyme role could lead to development of new drugsMany top-selling drugs used to treat cancer and lower cholesterol are made from organic compounds called polyketides, which are found in nature but historically difficult for chemists to alter and reproduce in large quantities.
For the first time, scientists at UC Irvine have discovered how polyketides form their ringlike shape, making it easier for chemists to manipulate them into new drugs.
 Polyketide (Tetracycline) The key, they found, is an enzyme called aromatase/cyclase, which forms a C-shape mold in which polyketides can form one molecule at a time. By changing this mold, chemists can control the size and shape of the polyketide, resulting in the formation of new drugs.
“Almost every polyketide has rings in its chemical structure, and if we can control ring formation, we can produce more polyketide drugs,” said Sheryl Tsai, lead author of this study and an assistant professor of molecular biology and biochemistry and chemistry at UCI. “Until now, polyketide ring formation was a mystery that hampered our efforts to produce new drugs.”
The research appears online this week in the Proceedings of the National Academy of Sciences.
Polyketide-based drugs and products account for more than $35 billion in sales annually. They include antibiotics that can cure a bacteria infection (tetracycline and erythromycin); anti-cancer drugs used in chemotherapy (doxorubicin and mithramycin); anti-oxidants that help prevent cancer and promote heart strength (EGCG and resverastrol); and drugs that lower cholesterol levels (Zocor). Green tea and red wine also contain beneficial polyketides.
Polyketides are made naturally by bacteria, fungi, plants and marine animals. Those organisms produce polyketides to kill their predators, be it another bacteria or fungi. They can produce different types of polyketides that kill different types of enemies.
“Because bacteria do not have arthritis or diabetes, they would not evolutionally select polyketides that could be used for arthritis or diabetes treatment,” Tsai said. “But we can coax the bacteria to do precisely that, if we can control the ring formation in the polyketides.”
Prior to this study, it was not known how nature controls the polyketide ring shape, which is essential for antibiotic and anti-cancer properties.
By using molecular cloning and chemical biology techniques, Tsai and her scientific team discovered that the aromatase/cyclase enzyme has a pocket that shapes the polyketide, promoting a unique ring pattern.
Said Tsai: “We hope this will lead to the development of new drugs in such areas as cancer therapeutics, obesity treatment and stem cell research.”
UCI scientists Brian Ames, Tyler Korman, Peter Smith, Thanh Vu, along with UCLA researchers Yi Tang and Wenjun Zhang, also worked on this study, which was funded by the Pew Foundation and the National Institutes of Health.Source: University of California, Irvine/News Release


Tuesday, May 20th, 2008

In patients who have had heart bypass surgery, taking the cholesterol-lowering drug Lipitor at a dose of 80 milligrams per day, rather than 10 milligrams per day, can markedly improve outcomes, new research shows.

Major heart-related “events” fell by 27 percent and the need for repeat heart procedures dropped by 30 percent with use of higher-dose Lipitor, researchers found.

Because heart bypass surgery patients represent an “especially high-risk population that tends to be under treated with lipid-lowering therapy, this treatment should be the new standard of care,” with the goal of reducing heart-related illness and death, they conclude.

The findings stem from a post-hoc analysis of the Treating to New Targets, or TNT, trial.

As part of the trial, 4,654 patients who had heart bypass surgery were randomized to receive Lipitor (also called atorvastatin) at the lower or higher dose and were followed for a median of 4.9 years.

By the end of the study, the average levels of “bad” LDL-cholesterol were much lower in patients taking 80 milligrams of Lipitor daily than in those taking 10 milligrams daily, Dr. Sanjiv J. Shah, from San Francisco General Hospital, and colleagues report.

Moreover, 9.7 percent of those taking high-dose Lipitor suffered a major cardiovascular event (cardiac death, nonfatal heart attack, resuscitated cardiac arrest, or stroke) compared with 13 percent of patients taking low-dose Lipitor.

There were also fewer repeat bypass operations or angioplasty procedures in the higher dose arm of the study (11.3 percent vs. 15.9 percent).

This study, conclude Shah and colleagues, shows that “aggressive lipid-lowering” with atorvastatin 80 mg decreases major cardiovascular events and the need for repeat heart procedures in patients who’ve had heart bypass surgery.
SOURCE: Journal of the American College of Cardiology, May 20, 2008.