Grape compound may block the formation of fat cells

Purdue University researchers have come up with the ability of a compound known as piceatannol (see structure)  to help prevent the formation of mature fat cells by blocking the pathways needed for their growth. Piceatannol is an analog of resveratrol, found in grapes and other fruit, which is converted to piceatannol in humans following its consumption.

Purdue assistant professor of food science Kee-Hong Kim and his associates tested piceatannol in cultured preadipocytes, which are immature fat cells. These cells pass through several stages before reaching maturity over a ten day or longer period. "These precursor cells, even though they have not accumulated lipids, have the potential to become fat cells," Dr Kim explained. "We consider that adipogenesis is an important molecular target to delay or prevent fat cell accumulation and, hopefully, body fat mass gain."

Dr Kim's team found that piceatannol bound to the preadipocytes' insulin receptors during their initial stage of fat cell formation, which blocked insulin's ability to control cell cycles and activate genes necessary for the further stages of adipogenesis. "Piceatannol actually alters the timing of gene expressions, gene functions and insulin action during adipogenesis, the process in which early stage fat cells become mature fat cells," Dr Kim stated. "In the presence of piceatannol, you can see delay or complete inhibition of adipogenesis."

"Our study reveals an antiadipogenic function of piceatannol and highlights insulin receptor and its downstream insulin signaling as novel targets for piceatannol in the early phase of adipogenesis," the authors conclude.

Dr Kim hopes to test piceatannol in an animal model as well as find a way to prevent the compound from degrading so that enough is available to the body to prevent fat gain. "We need to work on improving the stability and solubility of piceatannol to create a biological effect," he added.

Ref : http://www.jbc.org/content/287/14/11566.abstract?sid=48fa8a22-7a4d-4561-9585-80d643245a89

Isis Initiates Phase 1 Study in Patients With Cancer With the First Generation 2.5 Antisense Drug, ISIS-STAT3Rx

 In continuation of my update on antisense drugs...

Isis Pharmaceuticals, Inc.  announced the initiation of a Phase 1 study of ISIS-STAT3Rx, a Generation 2.5 antisense drug designed to treat cancer.  ISIS-STAT3Rx specifically reduces the production of signal transducer and activator of transcription 3 (STAT3). Because STAT3 is over expressed in numerous types of cancers, ISIS-STAT3Rx has the potential to be broadly useful for both solid and liquid tumors.  The ISIS-STAT3Rx development plan is initially focused on key cancers where there is a high unmet medical need and a strong link to STAT3, such as hepatocellular carcinoma (HCC) and ovarian cancer.  Advancements in Isis' technology platform have resulted in the improved potency of Generation 2.5 antisense drugs creating opportunities for drugs like ISIS-STAT3Rx to be effective in the more difficult to treat types of cancer. 

 

"The role of STAT3 as a key factor critical for tumor cell growth and survival of cancer cells has made STAT3 widely viewed as an important target of interest," said David S. Hong, M.D., Assistant Professor, Department of Investigational Cancer Therapeutics at the University of Texas MD Anderson Cancer Center.  "STAT3 is a well understood transcription factor involved in multiple survival mechanisms that intersect with the growth, metastasis and invasiveness of cancer. The ability to selectively inhibit STAT3 could allow us to effectively treat some of the most difficult to treat cancers."

 
Isis Initiates Phase 1 Study in Patients With Cancer With the First Generation 2.5 Antisense Drug, ISIS-STAT3Rx

Ref : http://ir.isispharm.com/phoenix.zhtml?c=222170&p=irol-newsArticle&ID=1691711&highlight=

Two-Drug Therapy Helped Kids With Type 2 Diabetes

Two-Drug Therapy Helped Kids With Type 2 Diabetes:  Children with type 2 diabetes may achieve better blood sugar control with a combination of two drugs, metformin and Avandia, than with metformin alone, a new study suggests. However, Avandia (rosiglitazone) was recently linked...

Scientists Spot How Cox-2 Painkillers Raise Heart Risks

In continuation of my update on COX-II inhibitors....

New research has uncovered how some cox-2 painkillers increase the risk for both heart attacks and stroke. The once popular cox-2 drugs, Vioxx and Bextra, were pulled off the market in 2004 and 2005, respectively, after research showed that both raised the chances of cardiovascular trouble. Meanwhile, Celebrex, a painkiller in the same drug class that remains on the market, carries a "black box" warning alerting patients to potential heart risks.

Now, a team of scientists from the University of Pennsylvania in Philadelphia say that, although cox-2 inhibitors are very good at inhibiting the workings of the cox-2 enzyme -- and thereby easing pain -- they also throw off the cardiovascular system's delicate balance by inhibiting an enzyme that relaxes blood vessels and guards against clotting.

"It's really about a rock and a hard place," said Dr. Christopher Cannon, a cardiologist at Brigham and Women's Hospital in Boston. "There's a balance in the bloodstream of clotting and vasoconstriction, as well as protection against clotting and vasodilation, which means that there's a constant balance of clotting and preventing clotting, and constricting arteries and dilating arteries."

"But with cox-2 inhibitors, they have found that you knock the protective side of that balance off," Cannon said. "And then you're left only with the constrictive part, which means the drugs up the risk for clotting and arterial constriction."

"This problem is bigger than just Vioxx, which no longer exists," he added. "It applies to every single NSAID (non-steroidal anti-inflammatory drug), because with all NSAIDs -- including Celebrex and ibuprofen, which zillions of people take -- the same issue exists. You block out the good stuff and leave the bad stuff unchecked. The one exception is Naproxen, which has an anti-platelet effect that seems to work against stroke and heart attack risk."

"Sometimes you have to take a cox-2 because you have really bad daily pain," said Cannon. "But this is a dose-dependent problem, with the more cox-2 you take the greater the cardiovascular risk. So you have to limit the dose and take the least amount you can get away with, so you can try to control crippling pain but also try not to poison your blood vessels and predispose yourself to clotting and high blood pressure."

Ref : http://stm.sciencemag.org/content/4/132/132ra54.abstract?sid=25c1e6c3-e6ee-449c-ae09-b83f14efc9f2

Avastin not as beneficial to older lung cancer patients | Dana-Farber Ca...

In continuation of my update on Avastin

Beehive Extract Shows Potential as Prostate Cancer Treatment

 Caffeic acid phenethyl ester, or CAPE (see below structure), is a compound isolated from honeybee hive propolis, the resin used by bees to patch up holes in hives. Propolis has been used for centuries as a natural remedy for conditions ranging from sore throats and allergies to burns and cancer. But the compound has not gained acceptance in the clinic due to scientific questions about its effect on cells. 

In a paper published in Cancer Prevention Research, researchers combined traditional cancer research methods with cutting-edge proteomics to find that CAPE arrests early-stage prostate cancer by shutting down the tumor cells' system for detecting sources of nutrition.

"If you feed CAPE to mice daily, their tumors will stop growing. After several weeks, if you stop the treatment, the tumors will begin to grow again at their original pace," said Richard B. Jones, PhD, assistant professor in the Ben May Department for Cancer Research and Institute for Genomics and Systems Biology and senior author of the study. "So it doesn't kill the cancer, but it basically will indefinitely stop prostate cancer proliferation." 

Natural remedies isolated from plant and animal products are often marketed as cure-alls for a variety of maladies, usually based on vague antioxidant and anti-inflammatory claims. While substances such as ginseng or green tea have been occasionally tested in laboratories for their medicinal properties, scientific evidence is commonly lacking on the full biological effects of these over-the-counter compounds.

"It's only recently that people have examined the mechanism by which some of these herbal remedies work," Jones said. "Our knowledge about what these things are actually doing is a bit of a disconnected hodge-podge of tests and labs and conditions. In the end, you're left with a broad, disconnected story about what exactly these things are doing and whether or not they would be useful for treating disease."

To study the purported anti-cancer properties of CAPE, first author Chih-Pin Chuu (now at the National Health Research Institutes in Taiwan) tested the compound on a series of cancer cell lines. Even at the low concentrations expected after oral administration, CAPE successfully slowed the proliferation of cultured cells isolated from human prostate tumors.

CAPE was also effective at slowing the growth of human prostate tumors grafted into mice. Six weeks of treatment with the compound decreased tumor volume growth rate by half, but when CAPE treatment was stopped, tumor growth resumed its prior rate. The results suggested that CAPE stopped cell division rather than killing cancerous cells.

To determine the cellular changes that mediated this effect, the researchers then used an innovative proteomics technique invented by Jones and colleagues called the "micro-western array." Western blots are a common laboratory tool used to measure the changes in protein levels and activity under different conditions. But whereas only one or a few proteins at a time can be monitored with Western blots, micro-western arrays allow researchers to survey hundreds of proteins at once from many samples.

Chuu, Jones and their colleagues ran micro-western arrays to assess the impact of CAPE treatment on the proteins of cellular pathways involved in cell growth -- experiments that would have been prohibitively expensive without the new technique.

"What this allowed us to do is screen about a hundred different proteins across a broad spectrum of signaling pathways that are associated with all sorts of different outcomes. You can pick up all the pathways that are affected and get a global landscape view, and that's never been possible before," Jones said. "It would have taken hundreds of Westerns, hundreds of technicians, and a very large amount of money for antibodies."

The micro-western array results allowed researchers to quickly build a new model of CAPE's cellular effects, significantly expanding on previous work that studied the compound's mechanisms. Treatment with CAPE at the concentrations that arrested cancer cell growth suppressed the activity of proteins in the p70S6 kinase and Akt pathways, which are important sensors of sufficient nutrition that can trigger cell proliferation.

"It appears that CAPE basically stops the ability of prostate cancer cells to sense that there's nutrition available," Jones said. "They stop all of the molecular signatures that would suggest that nutrition exists, and the cells no longer have that proliferative response to nutrition."

The ability of CAPE to freeze cancer cell proliferation could make it a promising co-treatment alongside chemotherapies intended to kill tumor cells. Jones cautioned that clinical trials would be necessary before CAPE could be proven effective and safe for this purpose in humans. But the CAPE experiments offer a precedent to unlock the biological mechanisms of other natural remedies as well, perhaps allowing these compounds to cross over to the clinic.

"A typical problem in bringing some of these herbal remedies into the clinic is that nobody knows how they act, nobody knows the mechanism, and therefore researchers are typically very hesitant to add them to any pharmaceutical treatment strategy," Jones said. "Now we'll actually be able to systematically demonstrate the parts of cell physiology that are affected by these compounds."

Ref : http://cancerpreventionresearch.aacrjournals.org/content/5/5/788

MEDA Announces Dymista Approved by the FDA

MEDA Announces Dymista Approved by the FDA:   The U.S. Food and Drug Administration (FDA) has approved Dymista, a new patented product for treatment of seasonal allergic rhinitis (SAR). In several clinical studies, MP29-02 (tentatively called Dymista), a novel intranasal formulation of azelastine hydrochloride (above left structure)  and fluticasone propionate (right structure).  

The first study demonstrated that continuous treatment with MP29-02 for 1 year was well tolerated in patients with chronic allergic or non-allergic rhinitis, only 2.7% of patients treated with MP29-02 and 2.9% of patients treated with fluticasone propionate discontinued the study due to an adverse event. MP29-02 also provided sustained efficacy over the one-year study period. MP29-02-treated patients experienced consistently greater relief from their nasal symptoms than fluticasone treated patients over the course of the study. Statistically significant (P<.05) differences favoring MP29-02 over fluticasone were observed at months 1 through 7 and at months 9 and 11. 

The second and third studies in patients with seasonal allergic rhinitis (SAR) provided evidence that MP29-02 demonstrated significantly more effective relief of nasal symptoms (P<.05 vs. azelastine, fluticasone, and placebo) and significantly greater ocular benefits compared to placebo (P<.05) over a 2-week study period. The new data was the subject of platform presentations on Sunday, March 4, 2012 at the annual meeting of the American Academy of Allergy Asthma and Immunology (AAAAI) in Orlando, Florida. MP29-02 is currently under review by the U.S. Food and Drug Administration (FDA) for the treatment of SAR.

Ref : http://mb.cision.com/Main/357/9255877/10183.pdf

Magnesium supplement helps boost brainpower ....

Neuroscientists at MIT and Tsinghua University in Beijing show that increasing brain magnesium with a new compound enhanced learning abilities, working memory, and short- and long-term memory in rats. The dietary supplement also boosted older rats’ ability to perform a variety of learning tests.

Magnesium, an essential element, is found in dark, leafy vegetables such as spinach and in some fruits. Those who get less than 400 milligrams daily are at risk for allergies, asthma and heart disease, among other conditions. In 2004, Guosong Liu and colleagues at MIT discovered that magnesium might have a positive influence on learning and memory. They followed up by developing a new magnesium compound — magnesium-L-threonate (see structure, MgT) — that is more effective than conventional oral supplements at boosting magnesium in the brain, and tested it on rats.  

“We found that elevation of brain magnesium led to significant enhancement of spatial and associative memory in both young and aged rats,” said Liu, now director of the Center for Learning and Memory at Tsinghua University. “ 

If MgT is shown to be safe and effective in humans, these results may have a significant impact on public health.” Liu is cofounder of Magceutics, a California-based company developing drugs for prevention and treatment of age-dependent memory decline and Alzheimer’s disease.

Magnesium supplement helps boost brainpower - MIT Media Relations

Garlic Oil Component May Form Treatment to Protect Heart

A potent-smelling component of garlic oil may help release protective compounds to the heart after heart attack, during cardiac surgery, or as a treatment for heart failure.

At low concentrations, hydrogen sulfide gas has been found to protect the heart from damage. However, this unstable and volatile compound has been difficult to deliver as therapy.

Now researchers at Emory University School of Medicine have turned to diallyl trisulfide (right structure), a garlic oil component, as a way to deliver the benefits of hydrogen sulfide to the heart. Their findings suggest that doctors could use diallyl trisulfide  in many of the situations where researchers have proposed using hydrogen sulfide.

The data was presented Wednesday, Nov. 16 at the American Heart Association (AHA) Scientific Sessions conference in Orlando.

“We are now performing studies with orally active drugs that release hydrogen sulfide,” says

David Lefer, PhD, professor of surgery at Emory University School of Medicine and director of the Cardiothoracic Surgery Research Laboratory at Emory University Hospital, Midtown. “This could avoid the need to inject sulfide-delivery drugs outside of an emergency situation.”

Garlic Oil Component May Form Treatment to Protect Heart | Emory University | Atlanta, GA

Garlic compound 100 times more effective than antibiotics at fighting food borne illness...

A recent research reveals a potent effect for garlic against the bacteria Campylobacter jejuni, a leading cause of intestinal illness caused by eating undercooked poultry or foods that have been contaminated during poultry preparation. "Campylobacter is simply the most common bacterial cause of food-borne illness in the United States and probably the world," explained coauthor Michael Konkel of Washington State University's College of Veterinary Medicine.

The researchers compared the effects of diallyl sulfide (see structure),  a compound that occurs in garlic, and the antibiotics ciprofloxacin and erythromycin on biofilms formed by Campylobacter jejuni. Biofilms are colonies of bacteria protected by a film that renders them a thousand times more resistant to antibiotics than free cells. Cell death following the administration of diallyl sulfide occurred at a concentration of resveratrol that was 100-fold less than that which was effective for either antibiotic, and often took less time to work. The team found that diallyl sulfide combined with a sulfur-containing enzyme, which altered the cells' function and metabolism.

Researchers conclude that, diallyl sulphide elicits strong antimicrobial activity against planktonic and sessile C. jejuni and may have applications for reducing the prevalence of this microbe in foods, biofilm reduction and, potentially, as an alternative chemotherapeutic agent for multidrug-resistant bacterial strains.

Ref : http://jac.oxfordjournals.org/content/early/2012/04/27/jac.dks138.abstract?sid=71685bd6-4b80-4d25-b97b-9422ba1d8cc3

Combination of Two Drugs Reverses Liver Tumors.....

The combination of two inhibitors of protein mTOR stops the growth of primary liver cancer and destroys tumour cells, according to a study by researchers of the Group of Metabolism and Cancer at Bellvitge Biomedical Research Institute (IDIBELL).  

The study led by IDIBELL researchers compared the effects in mice of two inhibitors of mTOR. The first was a derivative of rapamycin, called everolimus (RAD001 - see structure below left),
which is already used as an immunosuppressant and to treat specific cancers. The second is a new generation drug that inhibits mTOR called BEZ235 (see right side structure). 

During the study, researchers found unexpectedly that the combination of the two drugs had a more potent effect than any of the two drugs separately. Coadministration of BEZ235 and RAD001 limits the development of tumour and causes the self-destruction of tumour cells.

Based on these results a clinical trial, funded by Novartis, has started in the United States to evaluate the efficacy of the combination of these two inhibitors of mTOR in humans. The study coordinator, Sara Kozma, noted that

"because rapamycin and its derivatives are already approved for the treatment of other diseases, their combination to BEZ235, would be a rapid strategy to test the efficacy of this drug and fast track its approval for clinical use."

Ref :1. http://www.idibell.cat/modul/news/en/362/combination-of-two-drugs-reverses-liver-tumours
2.http://stm.sciencemag.org/content/early/2012/04/27/scitranslmed.3003923

A new drug to manage resistant chronic pain

BL-7050 is a new chemical entity based on the molecular structure of diclofenac (Voltaren), a well-known non-steroidal anti-inflammatory drug (NSAID) widely used in the treatment of nociceptive and inflammatory pain. However, BL-7050 operates via a novel mechanism of action, namely opening specific potassium channels in nerve cells. The opening of these channels reduces the activity of the nerve cells, thereby reducing or preventing pain signals.

Neuropathic pain is a complex, chronic state of pain that results from dysfunctional or injured nerve fibers. Neuropathic pain is associated with various conditions, including shingles, diabetes and cancer and is reported to affect 1% to 3% of the population. Patients describe the symptoms as burning, stabbing, electric shock or itching sensations, which can cause extreme discomfort for extended periods of time. A variety of medications are used to treat neuropathic pain, including antidepressants and anti-seizure medicines. However, these medications have significant side effects and are not always effective.  

If this drug ultimately proves itself though all the phase clinical trials to be successful, Anaysts see it receiving possible Orphan drug status to be prescribed to patients suffering from extreme pain caused by such diseases as terminal late stage cancers and cystic fibrosis, for example.

Ref : http://www.biolinerx.com/default.asp?pageid=14&itemid=24

A new drug to manage resistant chronic pain

Two drugs better than one to treat youth with type 2 diabetes, study suggests

Two drugs better than one to treat youth with type 2 diabetes, study suggests: A combination of two diabetes drugs, metformin and rosiglitazone, was more effective in treating youth with recent-onset type 2 diabetes than metformin alone, a new study has found. Adding an intensive lifestyle intervention to metformin provided no more benefit than metformin therapy alone.

The antibiotic, amoxicillin-clavulanate, before a meal may improve small bowel motility

The antibiotic, amoxicillin-clavulanate, before a meal may improve small bowel motility: The common antibiotic, amoxicillin-clavulanate, may improve small bowel function in children experiencing motility disturbances, according to a new study.

Does Vitamin E Prevent or Promote Cancer?

In continuation of my update on Vitamin-E

The cancer preventive activity of vitamin E has been suggested by many epidemiologic studies. However, several recent large-scale human trials with α-tocopherol, the most commonly recognized and used form of vitamin E, failed to show a cancer preventive effect. The recently finished follow-up of the Selenium and Vitamin E Cancer Prevention Trial (SELECT) even showed higher prostate cancer incidence in subjects who took α-tocopherol supplementation. The scientific community and the general public are faced with a question: “Does vitamin E prevent or promote cancer?” Researchers lead by Dr. Chung S. Yang, Director of the center did experiments in animal models and tried to conclude about  the cancer preventive activity of γ- and δ-tocopherols as well as a naturally occurring mixture of tocopherols, and the lack of cancer preventive activity by α-tocopherol. 

On the basis of these results as well as information from the literature, we suggest that vitamin E, as ingested in the diet or in supplements that are rich in γ- and δ-tocopherols, is cancer preventive; whereas supplementation with high doses of α-tocopherol is not.

Ref : http://cancerpreventionresearch.aacrjournals.org/content/early/2012/04/14/1940-6207.CAPR-12-0045.abstract?sid=5d446d6b-8eb0-426f-b86a-378f60ad7d15

Clues to aspirin's anti-cancer effects revealed.....................

In continuation of my update on aspirin....

One of the world's oldest medicines may hold the secret to a very contemporary problem: preventing cancer. Exactly why salicylate shows such potential as an anti-cancer treatment remains unclear, but a new study in mice offers clues.

Salicylate, found in willow bark, has been a key ingredient in medicine cabinets for thousands of years – ancient Egyptian manuscripts describe it as a treatment for inflammation. In a modified form – aspirin – it remains a successful anti-inflammatory and analgesic. Recently, though, research has revealed a puzzling side-effect of taking aspirin: the drug seems to lower a person's chances of developing some forms of cancer.

Aspirin is rapidly broken down inside the body into salicylate, so to investigate aspirin's unexpected side-effects Grahame Hardie at the University of Dundee, UK, applied salicylate to cultured human cells derived from the kidney. He found that the drug activated AMPK, an enzyme involved in cell growth and metabolism that has been found to play a role in cancer and diabetes.

"This is an ancient herbal remedy which has probably always been part of the human diet," says Hardie. "But despite that we're still finding out how it works."

Co-author Greg Steinberg of McMaster University in Hamilton, Ontario, Canada, then tested high doses of salicylate on various types of mice. He found that those engineered to lack AMPK did not experience the same metabolic effects from salicylate as seen in mice with AMPK.

Salicylate, in a form called salsalate, has also shown promise as a treatment for insulin-resistance and type 2 diabetes. Those effects, however, appear not to be governed by AMPK. When insulin-resistant mice lacking AMPK were given salicylate, they showed the same improvement in blood glucose levels as normal mice.

"That's what makes aspirin so scientifically and clinically interesting," says Chris Paraskeva at the University of Bristol, UK, who was not involved in the work. "It potentially works through a number of different pathways."

Ref : http://www.sciencemag.org/content/early/2012/04/18/science.1215327

Berries, Tea May Cut Men’s Odds for Parkinson’s Disease..

In continuation of my update on Flavonoids...

Regularly consumption of food and drink rich in substances called flavonoids, such as berries, apples, tea and red wine, can lower a man’s risk of developing Parkinson’s disease by 40 percent, new research suggests.

  “For total flavonoids, the beneficial result was only in men. But, berries are protective in both men and women,” said the study’s lead author, Dr. Xiang Gao, a research scientist at the Harvard School of Public Health and an associate epidemiologist at Harvard Medical School and Brigham and Women’s Hospital in Boston.

“Berries could be a neuroprotective agent. People can include berries in their regular diet. There are no harmful effects from berry consumption, and they lower the risk of hypertension too,” Gao added.

For the study, the researchers reviewed nutrition and health data from almost 50,000 men enrolled in the Health Professional Follow-Up Study and more than 80,000 women participating in the Nurses’ Health Study.

The researchers looked at dietary intake of five major flavonoid sources: tea, berries, apples, orange juice and red wine.

Over 20 to 22 years of follow-up, 805 people developed Parkinson’s disease — 438 men and 367 women.

When researchers compared those who ate the most flavonoids with those who ate the least, they found that only men saw a statistically significant benefit, lowering their risk of Parkinson’s by 40 percent.

Gao said it wasn’t clear why only men benefited from the extra flavonoid intake, but he noted that other studies have also found differences between men and women. Gao said it’s not clear if there’s a biological mechanism causing these differences, or another factor.

But, when the researchers looked at the dietary compounds individually, it was clear that berries could benefit both men and women, lowering the risk of Parkinson’s disease by about 25 percent for those who had at least two servings of berries a week.

Gao said that anthocyanins protect the cells from oxidative damage and they also have an anti-inflammatory effect, which may be how berries help to reduce Parkinson’s risk.

The study findings should be interpreted cautiously because the participants were mostly white professionals, and the results might not apply to other ethnic groups. Also, recollections of dietary intake may be faulty, and it’s possible that other properties of fruits and vegetables might have influenced the results, the authors said.

But, he added, it’s important for people to realize that this research isn’t applicable to people who already have the disease.

He also said it will be important to confirm these findings in other studies and learn the mechanism of how berries and other flavonoids appear to offer some protection against Parkinson’s disease.

Ref : http://www.neurology.org/content/78/15/1138.abstract?sid=2d716606-4430-41cb-a06e-de20203cfb5b

Experimental Drug Eases Autistic Behaviors in Mice

Experimental Drug Eases Autistic Behaviors in Mice:  An experimental drug reduced two signature characteristics of autism   repetitive behavior and abnormal social interactions  in laboratory mice, new research finds. The drug, GRN-529, targets glutamate, a major...

Ref : http://stm.sciencemag.org/content/4/131/131ra51.abstract?sid=9becbd73-dc8d-4d31-8c4d-7725f32a0c8d

FDA Approves New Impotence Drug Stendra

The U.S. Food and Drug Administration on Friday announced that it had approved Stendra, a new medication for erectile dysfunction.

Stendra (avanafil, see the structure) joins Viagra, Cialis and Levitra, all from a class of drugs known as phosphodiesterase type 5. According to the FDA, fast-acting Stendra is designed to be taken 30 minutes before sexual activity and at the lowest effective dose.

Whether the new drug adds any value to the existing range of impotence medications is unclear, one expert said.

Dr. Bruce Kava, acting chairman of urology at the University of Miami School of Medicine, said that

"the only advantage Stendra may have is a more rapid onset of action over the other drugs. The question is whether there are any advantages to a more rapid onset."

He noted that many patients don't respond to one or another of these drugs. But there is no way right now of telling who will respond to which drug. "Sometimes it's hit or miss," he explained.

Men will have to try these drugs to find the one that best suits their lifestyle, Kava said. For example, for some men Cialis works best because its effects seem to last much longer than that of the other drugs, he said.

Ref : http://ir.vivus.com/releasedetail.cfm?ReleaseID=668292

New technique could identify drugs that help fight broad range of viruses

New technique could identify drugs that help fight broad range of viruses

Levaquin Approved to Treat or Prevent Plague

In continuation of my update on Levaquin 

Levaquin Approved to Treat or Prevent Plague:  Approval of the antibiotic Levaquin (levofloxacin) has been expanded by the U.S. Food and Drug Administration to include plague, a rare but deadly bacterial infection.

The disease is extremely rare in the United States, and only...

Bacteria beware: Researchers have a natural sidekick that may resolve the antibiotic-resistant bacteria dilemma

Mice infected with Escherichia coli (E. coli) or Staphylococcus aureus(S. aureus) bacteria were given molecules called specialized pro-resolving mediators (SPMs) along with antibiotics. SPMs are naturally found in our bodies, and are responsible for mediating anti-inflammatory responses and resolve inflammation. An anti-inflammatory response is the body's attempt to protect itself from infectious agents and initiate the healing process.

The researchers found that specific types of SPM molecules, called resolvins and protectins, were key in the anti-inflammatory response to limit tissue damage by stimulating the body's white blood cells to contain, kill and clear the bacteria.

Administered with antibiotics, resolvins and protectins heightened immune response by commanding white blood cells to attack and engulf the bacteria, thereby quickly reducing the amount of bacteria in the blood and tissues.

RvD5-a type of resolvin-in particular was also helpful in regulating fever caused by E.coli, as well as counter-regulating genes responsible for mounting excess inflammation associated with infections; hence, limiting the collateral damage to the body while fighting infection.

Serhan and colleagues are the first to demonstrate RvD5, as well as its actions against bacterial invasion. The BWH team, collaborating with Fredrik Bäckhed, PhD of the Sahlgrenska Center for Cardiovascular and Metabolic Research in Sweden, found that germ-free animals produce high levels of resolvins.

Ref : http://www.nature.com/nature/journal/v484/n7395/full/nature11042.html

Bacteria beware: Researchers have a natural sidekick that may resolve the antibiotic-resistant bacteria dilemma

Eating more berries may reduce cognitive decline in the elderly

In continuation of my update on berries

Eating more berries may reduce cognitive decline in the elderly: Blueberries and strawberries, which are high in flavonoids, appear to reduce cognitive decline in older adults according to a new study. The study results suggest that cognitive aging could be delayed by up to 2.5 years in elderly who consume greater amounts of the flavonoid-rich berries.

Mystery of Bacterial Growth and Resistance Resolved ?

In continuation of my update on the mechanism of bacterial resistance...

Scientists at The Scripps Research Institute have unraveled a complex chemical pathway that enables bacteria to form clusters called biofilms. Such improved understanding might eventually aid the development of new treatments targeting biofilms, which are involved in a wide variety of human infections and help bacteria resist antibiotics. 

Biofilm formation is a critical phenomenon that occurs when bacterial cells adhere to each other and to surfaces, at times as part of their growth stage and at other times to gird against attack. In such aggregations, cells on the outside of a biofilm might still be susceptible to natural or pharmaceutical antibiotics, but the interior cells are relatively protected. This can make them difficult to kill using conventional treatments.

Past research had also revealed that nitric oxide is involved in influencing bacterial biofilm formation. Nitric oxide in sufficient quantity is toxic to bacteria, so it's logical that nitric oxide would trigger bacteria to enter the safety huddle of a biofilm. But nobody knew precisely how. In the new study, the scientists set out to find what happens after the nitric oxide trigger is pulled. "The whole project was really a detective story in a way," said Plate.

To learn more, the researchers used a technique called phosphotransfer profiling. This involved activating the histidine kinase and then allowing them to react separately with about 20 potential targets. Those targets that the histidine kinase rapidly transferred phosphates to had to be part of the signaling pathway.

"It's a neat method that we used to get an answer that was in fact very surprising," said Plate. 

The experiments revealed that the histidine kinase phosphorylated three proteins called response regulators that work together to control biofilm formation for the project's primary study species, the bacterium Shewanella oneidensis, which is found in lake sediments.

Further work showed that each regulator plays a complementary role, making for an unusually complex system. One regulator activates gene expression, another controls the activity of an enzyme producing cyclic diguanosine monophosphate, an important bacterial messenger molecule that is critical in biofilm formation, and the third tunes the degree of activity of the second.

Since other bacterial species use the same chemical pathway uncovered in this study, the findings pave the way to further explore the potential for pharmaceutical application. As one example, researchers might be able to block biofilm formation with chemicals that interrupt the activity of one of the components of this nitric oxide cascade.

Ref : http://www.scripps.edu/news/press/2012/20120426marletta.html

http://www.sciencedirect.com/science/article/pii/S1097276512002602

Ranbaxy Marks World Malaria Day by Unveiling "Indigenously" Developed Anti-Malaria Drug

Ranbaxy Marks World Malaria Day by Unveiling "Indigenously" Developed Anti-Malaria Drug:

Indian pharmaceutical giant Ranbaxy announced at a conference in New Delhi that it has developed a new "indigenous" anti-malaria drug.

The new drug, called Synriam, which is effective against the deadliest malaria microbe, Plasmodium Falciparum, would be a boon for millions of malaria patients around the globe, said Ranbaxy chief executive and managing director Arun Sawhney.

New drug to tackle body fat problems

Leptin regulates energy homeostasis, fertility, and the immune system, making it an important drug target. However, due to a complete lack of structural data for the obesity receptor (ObR), leptin's mechanism of receptor activation remains poorly understood. Researchers have crystallized the Fab fragment of a leptin-blocking monoclonal antibody (9F8), both in its uncomplexed state and bound to the leptin-binding domain (LBD) of human ObR. They describe the structure of the LBD-9F8 Fab complex and the conformational changes in 9F8 associated with LBD binding. A molecular model of the putative leptin-LBD complex reveals that 9F8 Fab blocks leptin binding through only a small (10%) overlap in their binding sites, and that leptin binding is likely to involve an induced fit mechanism. This crystal structure of the leptin-binding domain of the obesity receptor will facilitate the design of therapeutics to modulate leptin signaling.

Ref : http://www.shef.ac.uk/mediacentre/2012/drug-tackles-fat-problems.html

New drug to tackle body fat problems

Novartis drug Afinitor® approved by FDA as first medication to treat patients with non-cancerous kidney tumors associated with TSC

In continuation of my update on AFINITOR^®(everolimus)...

Novartis Pharmaceuticals Corporation ("Novartis") announced today that the US Food and Drug Administration (FDA) approved Afinitor® (everolimus) tablets* for the treatment of adult patients with kidney tumors known as renal angiomyolipomas and tuberous sclerosis complex (TSC), who do not require immediate surgery. This marks the first approval of a medical treatment in this patient population......

Media Release...

Ref : http://www.novartisoncology.com/media/press-releases.jsp?id=1606656&year=2012&page=1

Pistachio Intake May Endorse a Valuable Gut Environment

Pistachio Intake May Endorse a Valuable Gut Environment: 

Eating pistachios can help adjust levels of potentially valuable bacteria in the gut, a finding that holds promise for supporting digestive health counsels a preliminary 16-person study. The research, presented as an abstract this week at the Experimental Biology conference, is the first study of pistachios and almonds and their modulating role on the gut microbiota composition.

"Gut microbiota, or the microbial environment in the gastrointestinal tract, provides ...

Re: FDA Approves Votrient for Advanced Soft Tissue Sarcoma...

In continuation of my update on Pazopanib..


U.S. Food and Drug Administration, approved Votrient (pazopanib) to treat patients with advanced soft tissue sarcoma who have previously received chemotherapy. Soft tissue sarcoma is a cancer that begins in the muscle, fat, fibrous tissue, and other tissues.

Votrient is a pill that works by interfering with angiogenesis, the growth of new blood vessels needed for solid tumors to grow and survive.


A rare cancer with many subtypes, soft tissue sarcoma occurs in about 10,000 cases annually in the United States. More than 20 subtypes of sarcoma were included in the clinical trial leading to approval of Votrient. The drug is not approved for patients with adipocytic soft tissue sarcoma and gastrointestinal stromal tumors.

"Soft tissue sarcomas are a diverse group of tumors and the approval of Votrient for this general class of tumors is the first in decades," said Richard Pazdur, M.D., director of the Office of Hematology and Oncology Products in the FDA's Center for Drug Evaluation and Research. "Drug development for sarcomas has been especially challenging because of the limited number of patients and multiple subtypes of sarcomas."

The safety and effectiveness of Votrient was evaluated in a single clinical study in 369 patients with advanced soft tissue sarcoma who had received prior chemotherapy. Patients were randomly selected to receive Votrient or a placebo. The study was designed to measure the length of time a patient lived without the cancer progressing (progression-free survival). The disease did not progress for a median of 4.6 months for patients receiving Votrient, compared with 1.6 months for those receiving the placebo.

The most common side effects in Votrient-treated patients were fatigue, diarrhea, nausea, weight loss, high blood pressure, decreased appetite, vomiting, tumor and muscle pain, hair color changes, headache, a distorted sense of taste, shortness of breath, and skin discoloration.

Votrient carries a boxed warning alerting patients and health care professionals to the potential risk of liver damage (hepatotoxicity), which can be fatal. Patients should be monitored for liver function and treatment should be discontinued if liver function declines.

Ref : http://www.gsk.com/media/pressreleases/2009/2009_pressrelease_10113.htm