Dabigatran etexilate a better drug than warfarin for VTE?.

We know that Dabigatran is an anticoagulant from the class of the direct thrombin inhibitors. It is being studied for various clinical indications and may replace warfarin as the preferred anticoagulant in many cases. It is orally administered as the prodrug dabigatran etexilate (marketed as Pradaxa since April 2008 in European countries and Pradax in Canada). It was developed by the pharmaceutical company Boehringer Ingelheim.

Now researchers lead by  Dr. Sam Schulman, a professor of medicine of the Michael G. DeGroote School of Medicine (McMaster University), who conducted a randomized, double-blind trial of 2,539 patients with acute VTE (venous thromboembolism) have found that dabigatran (see structure) is a safe and effective anticoagulant that does not require the routine monitoring or dose adjustments that are necessary with warfarin. In other words, patients can receive the same results in a more convenient manner. 

As per the claim by the researchers, the improvement seen in both groups from the treatments was similar. After six months of treatment, only 2.4 percent of the dabigatran etexilate group (30 patients) and 2.1 percent of the warfarin group (27 patients) experienced recurrent VTE. The safety of the two drugs was also comparable. In the dabigatran etexilate arm, 205 patients experienced bleeding (including 20 patients with major bleeding) versus 277 patients in the warfarin arm (including 24 with major bleeding). Other possible side effects, including death, acute coronary syndromes, and abnormalities in liver function tests, were infrequent in the two groups. Hope patients suffering from VTE will now breathe a sigh of relief....

Ref : http://dailynews.mcmaster.ca/story.cfm?id=6511

Engineered tobacco plants have more potential as a biofuel

Engineered tobacco plants have more potential as a biofuel

New RNA interference technique can silence up to five genes

New RNA interference technique can silence up to five genes

Nonanal (odour produced in humans and birds) - an attractant for the Culex mosquito ?

In continuation of my update on developments in mosquito repellents,  I  found this  interesting info. In  my earlier blog, I mentioned that carbon dioxide   emitted in human  breath  is  the main  attractant  for the    Culex mosquito to find people, aiding the transmission of these deadly diseases. Now scientists from University of California, Davis, have identified the dominant odor naturally produced in humans and birds that attracts the blood-feeding Culex mosquitoes, which transmit West Nile virus and other life-threatening diseases. As per the claim by the researchers, Nonanal (nonanaldehyde or pelargonaldehyde see below structure) is the powerful semiochemical that triggers the mosquitoes' keen sense of smell, directing them toward a blood meal. A semiochemical is a chemical substance or mixture that carries a message.The antennae of the Culex quinquefasciatus are highly developed to detect even extremely low concentrations of nonanal. Mosquitoes detect smells with the olfactory receptor neurons of their antennae.

The UC Davis researchers tested hundreds of naturally occurring compounds emitted by people and birds. They collected chemical odors from 16 adult human subjects, representing multiple races and ethnic groups. More interestingly, Leal and Syed found that nonanal acts synergistically with carbon dioxide, a known mosquito attractant.  Nonanal, in combination with carbon dioxide, increased trap captures by more than 50 percent, compared to traps baited with carbon dioxide alone. Hope this discovery will help those searching for cheaper, environment friendly  repellents.

Ref : http://www.news.ucdavis.edu/search/news_detail.lasso?id=9289 

Oleanolic acid capsules for Hepatitis B......

We  know that Oleanolic acid is a naturally occurring triterpenoid, widely  distributed in food and medicinal plants, related to betulinic acid. It can be found in Phytolacca americana (American pokeweed), and Syzygium spp, garlic, etc. It is relatively non-toxic, antitumor, and hepatoprotective (antihepatotoxic - protecting liver cells against toxins) as well as exhibiting antiviral properties.

Oleanolic acid was found to exhibit strong anti-HIV activity, the related compound betulinic acid was used to create the first commercial maturation inhibitor drug. It was first studied and isolated from several plants, including Rosa woodsii (leaves), Prosopis glandulosa (leaves and twigs), Phordendron juniperinum (whole plant), Syzygium claviflorum (leaves), Hyptis capitata (whole plant), and Ternstromia gymnanthera (aerial part). Other Syzygium species including java apple (Syzygium samarangense) and rose apples contain it.

Now Biostar Pharmaceuticals, Inc. has completed preparation to launch its flagship Xin Aoxing Oleanolic Acid ("Xin Aoxing") Capsules for the treatment of Hepatitis B in Beijing and Shanghai in early January 2010.....

Ref : http://www.biostarpharmaceuticals.com/newsdisp.asp?id=78

Happy New Year 2010

Wishing one and all a happy, prosperous and peaceful new year 2010...

Dr.Umesh




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Combination of Phentermine & Topiramate for obesity treatment......

We know that Phentermine (see structure) is  an appetite suppressant of the  amphetamine and phenethylamine class. It is approved as an appetite suppressant to help reduce weight in obese patients. Its  usually used for short-term and in combination with exercise, diet and behavioral modification. Is typically prescribed for individuals, who are at increased medical risk because of their weight and works by helping to release certain chemicals in the brain that control appetite.  

Mode of action : Phentermine, in doses clinically used, works on the hypothalamus portion of the brain to release norepinephrine, a neurotransmitter or chemical messenger that signals a fight-or-flight response, reducing hunger. Phentermine works outside the brain as well to release epinephrine or adrenaline causing fat cells to break down stored fat, but the principal basis of efficacy is hunger-reduction. At high doses, phentermine releases serotonin and dopamine as well, but such doses are never used in clinical medicine.  

Topiramate (structure below), is a known anticonvulsant agent and  also  reported  for  the  treatment   of

SSRI-  induced weight gain in anxiety disorders. However a combination   of these two drugs (Phentermine & Topiramate) has been  tried by VIVUS, Inc. and has submitted New Drug Application (NDA)   to the U.S. Food and Drug Administration (FDA) seeking approval of Qnexa (Phentermine & Topiramate combination) - its investigational drug for the treatment of obesity, including weight loss and maintenance of weight loss, in patients who are obese or overweight with co-morbidities such as hypertension, type 2 diabetes, dyslipidemia or central adiposity.

The NDA submission follows the successful completion of the phase 3 program for Qnexa, including the recently announced results from the two pivotal, year-long phase 3 studies (EQUIP and CONQUER). In these trials, patients treated with all three doses of Qnexa achieved significant percent and categorical weight loss compared to placebo and met regulatory requirements for weight loss products as defined in the current FDA Guidance for Developing Products for Weight Management. Patients treated with Qnexa also had significant dose-related improvements in a variety of secondary endpoints including reductions in cardiovascular and metabolic risk factors. Hope people with obesity, will breathe a sigh of relief in the near future....

Ref : http://ir.vivus.com/releasedetail.cfm?ReleaseID=433172

Gren tea for new type of H1N1 Flu ......

In continuatation of my update on Epigallocatechin gallate (EGCg), I find this info something different and interesting too. We are aware about the antioxidant and anticancer activities of this compound, but now researchers from Central Research Institute of ITO EN, Ltd., & School of Pharmaceutical Sciences, University of Shizuoka have found the same compound to inhibits flu infection. As per the researchers claim, the compound had an inhibitory effect against three types of influenza viruses, including the swine-origin H1N1 virus that caused pandemic flu in 2009, and that its effect did not depend on the type of virus. These findings once again suggest that green tea is effective in preventing flu.

Gargling with green tea has already proved to prevent the onset of seasonal flu. It has become clear that catechin, a major type of polyphenol in green tea, plays a major role in prevention of flu infection, and that, among different types of catechin, EGCg displays the strongest antiviral activity. More interestingly, the researchers have conducted examinations to see if EGCg also shows antiviral activity against the new type of H1N1 virus, regardless of viral subtypes.

Solutions containing three types of viruses including the H1N1 virus were mixed with EGCg extracted from green tea. The mixture was added to cultured cells, which were thus infected. The cells were incubated for a set period of time, and the number of infected cells was counted. The concentration of EGCg at which virus infection was inhibited to 50% of the level of infection without EGCg was calculated.

The experiments showed that EGCg prevented flu virus infections at lower concentrations than Amantadine (a drug used to prevent and treat flu). A typical concentration of EGCg in green tea infused from a teapot is reported as 5,000-7,000 micromoles/L. Therefore, these results indicate that green tea diluted 1,000-fold or more is effective to halve infections by three types of viruses, including H1N1.

Those interested to know the details about green tea can visit the site.

Ref : http://www.itoen.co.jp/eng/corporate_info/index.html

Bromo furanones a new class of antimicrobials.....

We know that Candida albicans is the most virulent  Candida species of medical importance, which presents a great threat to immunocompromised individuals such as HIV patients. Candida albicans is carried by about 75 percent of the public. Typically the fungus is harmless but, in individuals with HIV or otherwise compromised immune systems, it can cause candidiasis, which has a high mortality rate. The fungi can also form biofilms that attach to surfaces and are up to 1,000 times more resistant to anti-fungals.

Currently, there are only four classes of antifungal agents available for treating fungal infections: azoles (Diflucan, flucanazole), polyenes, pyrimidines, and echinocandins. The fast spread of multidrug resistant C. albicans strains has increased the demand for new antifungal drugs.

Now two Syracuse University scientists have developed new brominated furanones (see structure) that exhibit powerful anti-fungal properties.

As per the claim by the researchers, the compound exhibited more than 80 percent. Structure and activity of this class of furanones reveals that the exocyclic vinyl bromide conjugated with the carbonyl group is the most important structural element for fungal inhibition. Furthermore, gene expression analysis using DNA microarrays showed that 3 μg/mL of 4-bromo-5Z-(bromomethylene)-3-butylfuran-2-one (BF1) upregulated 32 C. albicans genes with functions of stress response, NADPH dehydrogenation, and small-molecule transport, and repressed 21 genes involved mainly in cell-wall maintenance.

Interestingly, only a small overlap is observed between the gene expression changes caused by the representative brominated furanone in this study and other antifungal drugs reported in literature. This result suggests that brominated furanones and other antifungal drugs may target different fungal proteins or genes.

The existence of such new targets provides an opportunity for developing new agents to control fungal pathogens which are resistant to currently available drugs.

The research team has also shown previously that these furanones inhibit bacterial biofilm formation; thus they may help control chronic infections where biofilms often appear, on surgical, dental and other implants. Hope broad spectrum of other potential capabilities make this class of compounds a new way to combat the microbes in the days to come...

Ref : http://springerlink.com/content/92735526v5013088/

Mitaplatin as a better anticancer agent.......

In continuation of my update on Platinum compounds as anticancer drugs, I find  this one more interesting info to share with. MIT chemists have developed a new platinum compound that is as powerful as the commonly used anticancer drug cisplatin but better able to destroy tumor cells.

As per the claim by the researchers, glycolytic metabolism of most solid tumors, known as the Warburg effect, is associated with resistance to apoptosis that enables cancer cells to survive. Dichloroacetate (DCA) is an anticancer agent that can reverse the Warburg effect by inhibiting a key enzyme in cancer cells, pyruvate dehydrogenase kinase (PDK), that is required for the process. DCA is currently not approved for cancer treatment in the USA. With this idea behind researchers have prepared the new compound by combining dichloroacetate, DCA and cisplatin. Mitaplatin, thus obtained has two DCA units which are appended to the axial positions of a six-coordinate Pt (IV) center.

As per the claim by the authors, the negative intracellular redox potential reduces the platinum to release cisplatin, a Pt (II) compound, and two equivalents of DCA. By a unique mechanism, mitaplatin thereby attacks both nuclear DNA with cisplatin and mitochondria with DCA selectively in cancer cells. The cytotoxicity of mitaplatin in a variety of cancer cell lines equals or exceeds that of all known Pt (IV) compounds and is comparable to that of cisplatin.

Mitaplatin alters the mitochondrial membrane potential gradient of cancer cells, promoting apoptosis by releasing cytochrome c and translocating apoptosis inducing factor from mitochondria to the nucleus. Cisplatin formed upon cellular reduction of mitaplatin enters the nucleus and targets DNA to form 1,2-intrastrand d(GpG) cross-links characteristic of its own potency as an anticancer drug. These properties of mitaplatin are manifest in its ability to selectively kill cancer cells cocultured with normal fibroblasts and to partially overcome cisplatin resistance. Further studies like mice transplanted with human tissues are to be substantiated, in my opinion its a good achievement...

Ref : http://www.pnas.org/content/early/2009/12/09/0912276106.abstract?related-urls=yes&legid=pnas;0912276106v1

Mode of action of Cordycepin (a drug from cordyceps mushroom) established.....

We know that Cordycepin, or 3'-deoxyadenosine (known polyadenylation inhibitor),   was initially extracted from fungi of genus Cordyceps, (Cordyceps is a strange parasitic mushroom that grows on caterpillars). 3'-Deoxy adnosine has shown to possess diverse activities such as anti-proliferative, pro-apoptotic and anti-inflammatory effects. Properties attributed to cordyceps mushroom in Chinese medicine made it interesting to investigate and it has been studied for some time. In fact, the first scientific publication on cordycepin was in 1950 . Now it can be prepared from a cultivated form and also by synthetically. The problem was that although cordycepin was a promising drug, it was quickly degraded in the body. Now researcher Dr. de Moor has come up with interesting explanation about how the drug works.

The team has observed two effects on the cells: at a low dose cordycepin inhibits the uncontrolled growth and division of the cells and at high doses it stops cells from sticking together, which also inhibits growth. Both of these effects probably have the same underlying mechanism, which is that cordycepin interferes with how cells make proteins. At low doses cordycepin interferes with the production of mRNA, the molecule that gives instructions on how to assemble a protein. And at higher doses it has a direct impact on the making of proteins. More interestingly, the team has developed a very effective method that can be used to test new, more efficient or more stable versions of the drug in the Petri dish...

Ref : http://www.bbsrc.ac.uk/media/releases/2009/091223-new-insights-mushroom-derived-drug-for-cancer.html

Trabectedin for advanced soft tissue sarcoma....

Patients with a rare form of cancer called advanced soft tissue sarcoma could now benefit from a new drug called trabectedin, after the National Institute for Health and Clinical Excellence (NICE) approved the drug for NHS use.The same drug was given orphan status for ovarian cancer & soft tissue sarcoma by USFDA. Hope patients suffering from soft tissue sarcoma will breathe a sigh of relief.

Research suggests that the drug may extend life by at least three months more than other NHS treatments and that it may therefore be beneficial for some of the 500 to 600 people in England and Wales with advanced soft tissue sarcoma.

Under the latest guidance, the drug is recommended as a treatment for people with advanced soft tissue sarcoma who have previously failed to respond to treatment with anthracyclines and ifosfamide, or who are unable to tolerate those treatments. More...

Pyramidine core- a new drug for drug resistant non small cell lung cancers

Dana-Farber investigators hypothesized current agents lose their potency because they don't bind as tightly or fully to the EGFR T790M protein as they ideally should. To improve the fit, researchers led by chemical biologist Nathanael Gray, PhD, prepared a group of inhibitors with a different structural scaffold, known as a pyrimidine core, which, it was thought, would mesh more thoroughly. They lab-tested the agents in NSCLC cells with EGFR T90M and found several that were up to 100 times more potent than quinazolines [erlotinib (Tarceva), gefitinib (Iressa), and cetuximab (Erbitux)] in restricting cell growth. As an unexpected bonus, these compounds were nearly 100 times less powerful at slowing the growth of cells with normal EGFR, suggesting they would be less likely to produce side effects than current drugs. The agent which performed the best is the pyrimidine WZ4002. Those interested, can watch the video description (Pasi Jänne).

http://www.dana-farber.org/abo/news/press/2009/research-yields-new-agent-for-some-drug-resistant-non-small-cell-lung-cancers.html

Novel nanotechnology heals abscesses caused by resistant staph bacteria

Novel nanotechnology heals abscesses caused by resistant staph bacteria

New three-drug combination for multiple myeloma ! ...

The regimen, known as RVD, combined the drugs Revlimid - (lenalidomide), Velcade - (bortezomib) and dexamethasone, which previously were found to be highly effective in multiple myeloma patients who had relapsed or no longer responded to first-line therapies.

Fifteen of the 35 newly diagnosed patients in the open-label phase 2 portion of the study subsequently underwent autologous (using their own blood-forming stem cells) transplants, a standard treatment for multiple myeloma and did very well.

For the entire group, after a median 19.3 months of follow up, the median time-to-progression (TTP) of the disease, progression-free survival (PFS), and overall survival (OS) had not yet been reached, according to the presentation. The estimated TTP and PFS at one year are 76 percent, and the estimated one-year overall survival is 100 percent, the results showed.

The more interesting part of the study is that the high response rate was not affected by the specific genetic characteristics of the patients' disease. Patients with so-called "adverse cytogenetics" are at higher risk for treatment failure and death, but in the current study the drug combination worked as well for them as it did in patients with more favorable cytogenetic features.

Except for the main adverse effect, peripheral neuropathy (numbness or pain in the extremities), which typically cleared up after dosages were lowered and the treatment was completed.

The combination has now gone into large phase 3 clinical trials, and the researchers think that this regimen has the potential to be a new standard of treatment in multiple myeloma....

http://www.dana-farber.org/abo/news/press/2009/multiple-myeloma-patients-experience-high-response-rate-with-new-three-drug-combination.html