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