Fenofibrate drug may reduce risk of cardiovascular events in patients with type 2 diabetes

In continuation of my update on Fenofibrate

A new study shows that the drug fenofibrate might reduce the risk of cardiovascular events in patients with type 2 diabetes who have high levels of triglycerides and low levels of "good" cholesterol, despite being treated with statins. The study, funded by the National Heart, Lung, and Blood Institute (NHLBI), appears in the December 28 issue of JAMA Cardiology.

Fenofibrate is primarily used to help reduce elevated levels of triglycerides, or fat, in the blood. But the researchers wanted to know if the drug, when combined with statin treatment, could also reduce the risk of heart disease in people with type 2 diabetes. People with type 2 diabetes are at high risk of cardiovascular-related events, such as heart attacks, stroke, and even death, often because their levels of triglycerides are so high, and their high-density lipoprotein (HDL) cholesterol levels are low.

To answer their question, the researchers followed 4,640 participants from the NHLBI-funded Action to Control Cardiovascular Risk in Diabetes (ACCORD) Lipid Study for five years after the conclusion of the trial in 2009. The findings suggest that fenofibrate therapy may be beneficial in the way the researchers hoped: by reducing cardiovascular events in patients with type 2 diabetes who take statins but still have especially high triglycerides levels and low HDL cholesterol levels. However, a randomized study is needed to confirm these findings, according to the authors.

In addition to NHBLI, the study received funding from the NIH's National Institute of Diabetes and Digestive and Kidney Disease, the National Institute of Aging, and the National Eye Institute.

WHO: Jerome Fleg, MD and Yves Rosenberg, MD, M.P.H., Division of Cardiovascular Sciences, NHLBI, NIH, are available to comment on the findings and implications of this research.

New molecule-building method may have great impact on pharmaceutical industry

Scientists at The Scripps Research Institute (TSRI) have devised a new molecule-building method that is likely to have a major impact on the pharmaceutical industry and many other chemistry-based enterprises.

The method, published as an online First Release paper in Science on April 21, 2016, allows chemists to construct novel, complex and potentially very valuable molecules, starting from a large class of compounds known as carboxylic acids, which are relatively cheap and non-toxic. Carboxylic acids include the amino acids that make proteins, fatty acids found in animals and plants, citric acid, acetic acid (vinegar) and many other substances that are already produced in industrial quantities.

"This is one of the most useful methods we have ever worked with, and it mostly involves materials that every chemist has access to already, so I think the interest in it will expand rapidly," said principal investigator Phil S. Baran, Darlene Shiley Professor of Chemistry at TSRI.

"This exciting new discovery represents a significant advance in our ability to transform simple organic molecules and to rapidly build complex structures from readily available materials—we expect to use it in both the discovery and development of biologically active compounds that help patients prevail over serious disease," said co-author Martin D. Eastgate, a Director in Chemical and Synthetic Development at Bristol-Myers Squibb, who participated in the study as part of a long-standing research collaboration between Bristol-Myers Squibb and TSRI.

The new method is a modification of what is already one of the most widely used sets of chemical reactions: amide bond-forming reactions. These occur naturally in cells to stitch together amino-acids into proteins, for example. Since the 1940s, when they became a popular tool for laboratory chemists, they have been instrumental in the discovery of many new compounds as well as new methods for synthesizing compounds.

Amide bond-forming reactions couple carbon atoms on carboxylic acids to nitrogen atoms on another broad class of compounds called amines. The reactions are relatively safe and easy, and produce water, H2O, as a co-product. Chemists have long dreamed of using similarly cheap and easy techniques to make carbon-to-carbon couplings. That would enable them to synthesize, and potentially turn into drugs and other useful products, an enormous number of organic molecules that have previously been inaccessible.

Carbon to Carbon

The method devised by Baran and his team essentially repurposes the traditional amide bond-forming strategy to achieve carbon-carbon couplings. The new reactions again involve easy, safe conditions—the co-product now is carbon dioxide, CO2—and the same inexpensive and widely available starting materials, carboxylic acids. This time the reaction partners are not nitrogen-containing amines but organic compounds containing carbon and zinc, which are also relatively easy to buy or make.

The path to the new invention began with a long-known reaction called the Barton decarboxylation. "We started by asking ourselves what would happen if we could use a metal to trap a radical [a highly reactive charged molecule] generated in the Barton decarboxylation," said TSRI Research Associate Josep Cornella. "We realized that if we could do that, it would open up a totally new approach to organic synthesis and carbon-carbon coupling."

The method the team ultimately developed employs an inexpensive and commercially available activating agent that primes the chosen carboxylic acid for the reaction. A metal catalyst—inexpensive nickel—then facilitates the reaction between the carboxylic acid and its carbon-zinc partner compound.

A key ingredient turned out to be a "ligand" compound that helps the metal catalyst do its job. "We found that common, readily available bipyridine ligands work best—these help to stabilize the nickel so it can catalyze the reaction," said TSRI Research Associate Tian Qin.

Flaxseed lowers high cholesterol in men.....

Flax (also known as common flax or linseed) (Linum  usitatissimum) is a member of the genus Linum in the family Linaceae. It is native to the region extending from the eastern Mediterranean to India.  This is called as Agasi/Akshi in Kannada, Jawas/Javas (जवस) or Alashi (अळशी) in Marathi.  

Flax seeds come in two basic varieties brown yellow or golden. Most types have similar nutritional characteristics and equal amounts of short-chain omega-3 fatty acids. The exception is a type of yellow flax called Linola or solin, which has a completely different oil profile and is very low in omega-3. Although brown flax can be consumed as readily as yellow, and has been for thousands of years, it is better known as an ingredient in paints, fiber and cattle feed. Flax seeds produce a vegetable oil known as flaxseed or linseed oil, which is one of the oldest commercial oils and solvent-processed flax seed oil has been used for centuries as a drying oil in painting and varnishing. 

Flaxseeds are rich in alpha linolenic acid (ALA), an omega-3 fat that is a precursor to the form of omega-3 found in fish oils called eicosapentaenoic acid or EPA. Many benefits like 1. anti-iflammatory benefits, 2. omega-3-rich flaxseeds protect bone health, 3.protection against heart disease, cancer and diabetes, 4. flaxseeds help prevent and control high blood pressure. And even it helps to control some types of cancers.

Earlier report says,  Flaxseed provides comparable cholesterol-lowering benefits to statin drugs. Now this has been further substantiated by researchers from Iowa State University's (ISU) Nutrition and Wellness Research Center (NWRC).

Suzanne Hendrich, an ISU professor in food science and human nutrition, led a study that examined the effects of flaxseed lignan in 90 people diagnosed with high cholesterol. The results showed that consuming at least 150 milligrams of flaxseed lignans per day (about three tablespoons) decreased cholesterol in men, but not women, by just under 10 percent over the three months that they were given the flaxseed.  Suzanne concludes that though the result is  considerably less than the expected outcome from cholesterol-lowering drugs -- approximately 10 to20 percent for three months, depending on the individual -- it's still enough to make flaxseed a more natural option for some men. While the study found that the flaxseed lignans lowered cholesterol in men, it did not produce a significant change in women. More.... 

Ref : http://www.news.iastate.edu/news/2010/mar/flaxseed

(Those interested in knowing the other benefits of flax seed can read the article..)

Statins may shield unborn babies from mother's stress, study suggests

In continuation of my update on statins

Scientists have discovered that the widely-prescribed drugs help to counteract the negative impact of stress hormones on fetal growth and heart development in mice.

The therapy could lower the chances of babies being born underweight and reduce their risk of health problems in later life, including heart disease, researchers say.

Further studies are needed to assess the long-term effects of statins in pregnancy, but the drugs are already used occasionally in pregnant women and should be suitable for clinical trials, the team says.

Babies that are exposed to excessive stress hormones in the womb are often born underweight and have a greater risk of heart disease in later life.

Normally, the unborn baby is protected by a key enzyme produced by the placenta that breaks down stress hormones and greatly limits the amount of active hormones that reach the baby's blood supply.

When the expectant mother is stressed, they produce less of this enzyme and the baby is less well protected.

Scientists at the University of Edinburgh studied mice that cannot produce the enzyme as a model of maternal stress.

They found that stress hormones stop the placenta from developing normal blood vessels, which cuts back the blood supply to the growing fetus.

The developing fetus does not grow to full size as a result, and its heart function does not develop normally.

Treating the mother with a type of statin triggers production of a molecule called VEGF, which stimulates the development of blood vessels in the placenta.

By re-establishing the blood supply, the treatment promotes normal development of the heart and helps the baby to grow to a healthy birthweight, the team showed.

Around 2.5 million people in the UK take statins to lower high cholesterol.

The study is published in the journal Proceedings of the National Academy of Sciences and was funded by the Wellcome Trust. The research also received funding from the Raine Medical Research Foundation, University of Western Australia.

Professor Megan Holmes, of the University of Edinburgh's British Heart Foundation Centre for Cardiovascular Sciences, said: "These are very exciting results suggesting that there may finally be a potential therapy for women whose placenta is unable to maintain the normal growth of her baby.

"At present there is no treatment and babies may be born prematurely or small, and will be at greater risk of developing cardiovascular disease, diabetes and even psychiatric disorders later in life. Although more work needs to be done to show statins are safe in human pregnancy, these results show a new way forward for the major unmet need of fetal growth retardation."

Professor Jeremy Pearson, Associate Medical Director at the British Heart Foundation, said: "Low birthweight has been associated with maternal stress, and babies with low birthweights may be more prone to cardiovascular complications later in life.

"In this study the researchers have discovered that a drug called Pravastatin may counteract the consequences of increased levels of the stress hormone corticosterone within the placentas of mice. How Pravastatin counteracts the stress hormone is not yet understood, therefore more research is needed to see whether the drug will have the same effect in humans."

Ref : http://www.pnas.org/content/early/2016/05/10/1520356113

Aspirin May No Longer Have Effect in Primary CVD Prevention

Aspirin may not be effective for primary prevention of cardiovascular disease and cancer mortality, according to research published online Nov. 21 in Family Practice.

Frank Moriarty, Ph.D., from the Royal College of Surgeons in Dublin, and Mark H. Ebell, M.D., from the University of Georgia in Athens, compared the benefits and harms of aspirin for primary prevention before (1978 to 2002) and after (2005 onward) widespread use of statins and screening for colorectal cancer.

The researchers found that for older versus newer studies, the relative risks for vascular outcomes were 0.89 (95 percent confidence interval [CI], 0.83 to 0.95) versus 0.93 (0.86 to 0.99) for major adverse cardiovascular events; 1.73 (1.11 to 2.72) versus 1.06 (0.66 to 1.70) for fatal hemorrhagic stroke; 0.86 (0.74 to 1.00) versus 0.86 (0.75 to 0.98) for any ischemic stroke; 0.84 (0.77 to 0.92) versus 0.88 (0.77 to 1.00) for any myocardial infarction; and 0.79 (0.71 to 0.88) versus 0.94 (0.83 to 1.08) for nonfatal myocardial infarction. In newer studies, there was no significant decrease observed for cancer mortality (relative risk, 1.11; 95 percent CI, 0.92 to 1.34). Significant increases were seen in major hemorrhage (older studies, relative risk, 1.48 [95 percent CI, 1.25 to 1.76] versus newer studies, relative risk, 1.37 [95 percent CI, 1.24 to 1.53]).

"In a modern era characterized by widespread statin use and population-wide cancer screening, aspirin no longer reduces the absolute risk of cancer death or myocardial infarction when given as primary prevention," the authors write.

https://academic.oup.com/fampra/advance-article/doi/10.1093/fampra/cmz080/5637484

Common cholesterol-lowering drug may help protect against cerebral malaria

In continuation of my update lovastatin

Researchers have discovered that adding lovastatin, a widely used cholesterol-lowering drug, to traditional antimalarial treatment decreases neuroinflammation and protects against cognitive impairment in a mouse model of cerebral malaria. Although there are differences between mouse models of cerebral malaria and human disease, these new findings indicate that statins are worthy of consideration in clinical trials of cerebral malaria. 

Statins, a class of drugs best known for their ability to lower cholesterol, have also been shown to be active in modulating a variety of immune system responses. In their research, Zimmerman and his Brazilian colleagues evaluated the effect of statins in a mouse model of cerebral malaria. The researchers found that adding a drug called lovastatin to traditional antimalarial therapy prevented cognitive dysfunction in mice infected with cerebral malaria. They discovered that addition of lovastatin decreased white blood cell accumulation and leakiness in blood vessels in the brain. Lovastatin also reduced production of damaging oxygen-containing molecules and other factors that promote inflammation.

"The molecular mechanisms that give rise to cerebral malaria and subsequent cognitive dysfunction are not yet known," says Zimmerman. "However, the fact that statin treatment decreases both injurious blood vessel inflammation and cognitive dysfunction suggests that a combination of vascular and inflammatory triggers leads to cerebral pathology and intellectual deficits."

Ref : http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1003099

Common cholesterol-lowering drug may help protect against cerebral malaria

Lovastatin: A New Weapon Against Plague?

We know that, Lovastatin is a member of the drug class of statins,  used for lowering  cholesterol (hypolipidemic agent) in those with hypercholesterolemia and so preventing cardiovascular disease. Lovastatin is a naturally occurring drug found in food such as oyster mushrooms  and red yeast rice.

Now scientists at the Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (CNRS/Université Aix-Marseille 2), have found that Lovastatin protects animals against the deadly effects of plague.

After inoculating small rodents with the Yersinia pestis bacterium, the team led by Didier Raoult and Michel Drancourt at the URMITE (CNRS/Université Aix-Marseille 2) showed that animals treated with lovastatin presented fewer and less severe infections. Lovastatin therefore has preventive properties against plague mortality in an animal model. This experimental study also reveals that this statin has no direct antibiotic effect against Yersinia pestis but that it prevents the development of septicemia.  

Researchers conclude that Lovastatin had no in-vitro antibiotic effect against Y. pestis. The difference in the mortality between control mice (11/15; 73.5%) and lovastatin-treated mice (3/15; 20%) was significant (P<0.004; Mantel-Haenszel test). Dead mice exhibited Y. pestis septicemia and inflammatory destruction of lung and spleen tissues not seen in lovastatin-treated surviving mice. These data suggest that lovastatin may help prevent the deadly effects of plague, with a caution that field observations are warranted to assess the role of lovastatin in the prophylaxis of human plague....

Ref : http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0010928