Mecamylamine may help to treat diabetic macular edema ......

We know that mecamylamine (see structure) has been used as a  ganglionic blocker in treating hypertension, but, like most ganglionic blockers, is more often used now as a research tool. It is also sometimes used as an anti-addictive drug to help people stop smoking tobacco, and is now more widely used for this application than it is for lowering blood pressure. This effect is thought to be due to it blocking α3β4 nicotinic receptors in the brain.

Now researchers from the Wilmer Eye Institute of Johns Hopkins University School of Medicine in Maryland have come up with an interesting finding from an early-stage human clinical trials. i.e.,  the drug  'mecamylamine'  was safe and had biological effects in a type of diabetic eye disease, and may offer researchers a new approach to prevent and treat diabetic macular edema. 

Diabetic macular edema is a complication of a specific region of the retina in the eye, called the macula, that develops when small blood vessels become leaky such that fluid accumulates. Without treatment, diabetic macular edema can cause vision impairment, blurriness, or blindness.

As per the claim by the researcers,  approximately 40% of the participants showed significant improvement in overall vision and/or the thickness of the retina. The treatment also showed biological effects in the retina indicating that the drug was able to gain access to the retinal vessels.

"The safety and early signals of treatment effect arising from this study may create a strong interest in the development of multiple treatment options that are affordable and can be self-administered, helping to ease the burden of healthcare delivery and compliance," said Barbara Araneo, Director of Complications Research for JDRF. ...

Ref : http://www.jdrf.org/index.cfm?fuseaction=home.viewPage&page_id=9065027A-1321-C844-137596CDA72C825B 

Methionine Aminopeptidases from Mycobacterium tuberculosis as Novel Antimycobacterial Targets ..

Suspecting that a particular protein in tuberculosis was likely to be vital to the bacteria's survival, Johns Hopkins scientists screened 175,000 small chemical compounds and identified a potent class of compounds that selectively slows down this protein's activity and, in a test tube, blocks TB growth, demonstrating that the protein is indeed a vulnerable target.

 

This class of chemical compounds attacks TB by inhibiting methionine aminopeptidase (MetAP), an essential enzyme found in organisms ranging from bacteria to humans, and that clearly has been conserved throughout evolution because of its important task of ensuring the proper manufacture of proteins.

Methionine aminopeptidase (MetAP) is a metalloprotease that removes the N-terminal methionine during protein synthesis. To assess the importance of the two MetAPs in Mycobacterium tuberculosis, researchers overexpressed and purified each of the MetAPs to near homogeneity and showed that both were active as MetAP enzymes in vitro. 

 

Researchers screened a library of 175,000 compounds against MtMetAP1c and identified 2,3-dichloro-1,4-naphthoquinone class of compounds as inhibitors of both MtMetAPs. It was found that the MtMetAP inhibitors were active against replicating and aged nongrowing M. tuberculosis. Overexpression of either MtMetAP1a or MtMetAP1c in M. tuberculosis conferred resistance of bacterial cells to the inhibitors. As per the claim by the researchers, knockdown of MtMetAP1a, but not MtMetAP1c, resulted in decreased viability of M. tuberculosis and they conclude  that MtMetAP1a is a promising target for developing antituberculosis agents.

 

The scientists cautioned that although the MetAP inhibitors prevent TB growth in test tubes, they have a long way to go before being declared safe and effective to treat TB patients...

 

"Judging from potency, a MetAP inhibibitor alone probably won't wipe out TB," Liu says. "TB is so hard to treat that the standard therapy involves a cocktail of multiple drugs; no single compound is powerful enough. Our hope is that someday an inhibitor of MetAP will become a new component to enhance the existing therapy."

Ref : Jun O. Liu et.al., Chemistry & Biology, Volume 17, Issue 1, 29 January 2010, Pages 86-97

Clinical Data completes NDA submission for vilazodone.......

         Vilazodone (structure) is an antidepressant and anxiolytic of  the piperazine chemical class.

Clinical Data, Inc.   recently announced that the Company has submitted a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for vilazodone for the treatment of major depressive disorder (MDD). Vilazodone is a dual-acting potent and selective serotonin reuptake inhibitor and a 5-HT_1A receptor partial agonist. The Company expects that the NDA submission, if accepted, will be subject to a standard review. 

This is a major milestone in the development of vilazodone and, if approved, its dual mechanism of action and safety profile will offer a new alternative for patients suffering from depression,” said Carol R. Reed, M.D..more...

Gemcitabine and cisplatin a promising combination for endometrial cancer...

In continuation of my update on cis-platin and its importance, I find this  info interesting to share with...

Gemcitabine (see structure) and cisplatin in combination have been investigated extensively in other disease sites, and synergism of the two agents has been confirmed in cell lines of human endometrial, ovarian, colon, lung and squamous cell head and neck carcinoma

Now researchers from The University of Texas M. D. Anderson Cancer Center , lead by Dr.Jubilee Brown, report from a small study of women with advanced or recurrent endometrial cancer, that gemcitabine and cisplatin, when used in combination, produced a response rate in fifty percent of patients.

The Phase II study of 20 patients found that the combination of gemcitabine and cisplatin, two drugs currently used to treat other types of cancer, limited the disease's progression, increasing progression-free survival while maintaining tolerable toxicity levels. It is believed that when administered together, gemcitabine helps overcome cell resistance to cisplatin, throwing tumor cells a potent one-two punch.


Findings demonstrated a 50 percent overall response rate, or improvement in disease. Additionally, the clinical benefit of the two-drug combination was 80 percent, as 16 of the 20 women experienced either an improvement or stabilization of disease. All side effects resulting from the therapy were manageable. Lead researcher, Dr. Brown concluded  that results from the study warrant investigation of the chemotherapy combination in a larger, definitive trial at multiple institutions.....

Ref :  Dr. Jubilee Brown, http://www.mdanderson.org/

New study finds green tea extract may prevent Alzheimer's disease and dementia

In continuation of my update on green tea benefits......

New study finds green tea extract may prevent Alzheimer's disease and dementia

Salsalate may be useful for the treatment of patients with type 2 diabetes .....

We know that Salsalate (see structure; source Drugs.com)  is a  non-steroidal anti-inflammatory drug (NSAID) belonging to salicylates. It is used in the treatment of Osteo Arthritis and  Rheumatoid Arthritis. 

Now researchers from Harvard Medical School, lead by Dr. Allison Goldfine, have come up with interesting finding, i.e., Salsalate may be useful for the treatment of patients with type 2 diabetes as well. In a three-month trial of people with type 2 diabetes ,  those who took the drug showed significantly improved blood glucose levels. 

Starting off, the patients all had levels of hemoglobin A1C (a standard measurement that reflects blood sugar levels over several months) in the range of 7.0 to 9.5%. A significant number of those who took salsalate saw this number drop by 0.5%, a result that is in the range of several recently released diabetes therapeutics. Other tests related to glucose levels also showed substantial improvement.  

Overall the drug appeared to be safe and to be tolerated well by patients. The study included 108 individuals, aged from 18 to 75 years, at 17 clinical sites around the United States. Patients were randomly divided into four; three groups were each given differing amounts of salsalate in three daily doses, while the fourth received placebos. All patients continued with their current regimes for managing diabetes.

Though these preliminary findings  suggests  that,   salsalate may provide an effective, safe and inexpensive new avenue for diabetes treatment, however the researchers  want to complete the ongoing  additional studies so that they can further substantiate their claim........

Ref : March 16 in the Annals of Internal Medicine

Study provides better understanding of how mosquitoes find a host......

In continuation of my update on on developments in mosquito repellents ......

The potentially deadly yellow-fever-transmitting Aedes aegypti mosquito detects the specific chemical structure of a compound called octenol as one way to find a mammalian host for a blood meal, Agricultural Research Service (ARS) scientists report".......

Ref : http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0007032....

Eprotirome a promising addition to statin therapy ?

People with bad cholesterol have  risk of  future heart disease,  despite  cholesterol-lowering statin therapy. Now researchers from  Johns Hopkins have come up with interesting finding i.e.,  a drug that mimics the action of thyroid hormone [Eprotirome (new generic name for KB2115) structure source : chemBlink)  lowered cholesterol up to 32 percent in those already on statins, an effect equal to that expected from doubling the statin drug doses, without harmful side effects. 

Interestingly, the researchers caution that the results don't suggest that eprotirome will or should replace statins, which are the current gold standard for treating high LDL cholesterol.

However, the results of their small trial on 168 patients do suggest that eprotirome may eventually be a promising addition to statin therapy, a substitute for statins in people who can't tolerate their side effects, or a novel treatment for mixed dyslipidemia, a condition in which people have high levels of lipids other than cholesterol such as triglycerides or apolipoprotein B (apo B).

The researchers found that among the patients taking the 25, 50 or 100 mg doses of eprotirome reduced their LDL cholesterol levels by 22 percent, 28 percent, and 32 percent respectively, compared to only 6.5 percent in those taking placebo. Remarkably, they also found similar dose-related reductions in triglycerides, apo B, and Lp(a). They also found modest reductions in HDL cholesterol of approximately 3 percent.

As per the claim by the lead researcher Dr. Paul W. Ladenson,   'this drug represents a new class of medications that might offer hope to those at risk of future cardiovascular disease whose lipid profiles are not effectively altered with statin therapy, and perhaps for about a quarter of those who have tried statins but cannot tolerate their side effects'. Dr. Ladenson is a consultant to Karo Bio, maker of eprotirome.......

Ref : http://content.nejm.org/cgi/content/short/362/10/906

From carnivorous plants to the medicine cabinet? Anti-fungal agents in pitcher plants investigated

Carnivorous plant : Nepenthes khasiana (see picture)......

From carnivorous plants to the medicine cabinet? Anti-fungal agents in pitcher plants investigated.....

Positive phase III efficacy clinical trial for Fentanyl sublingual spray .....

INSYS Therapeutics, Inc. announced positive results from the pivotal phase III efficacy  trial for patients utilizing the Fentanyl Sublingual Spray (SL Spray) technology to treat breakthrough cancer pain.  The company claims that all primary and secondary endpoints were achieved in the study, and the drug is the first product to ever show statistically significant pain relief when measuring the summary of pain intensity difference at five minutes (SPID(5)) in a phase III breakthrough cancer pain trial using Fentanyl.

Dr. Richard Rauck, a principal investigator in the Phase III study observed,  the sublingual spray demonstrated very rapid, effective pain relief. Patients began to experience meaningful pain relief within five minutes. This observation was supported by the clinical research findings.  As claimed by the researchers, to date, no other transmucosal Fentanyl  (see the general structure) product has produced pain relief this quickly. This  finding is supported with continued pain relief at all subsequent time intervals. 

Hope this easy-to-use oral spray that can produce effective, potent and very rapid pain relief will be a tremendous advantage for the  patients who experience moderate to severe cancer breakthrough pain.....

Ref : http://www.insysrx.com/news.htm