Retinoic acid may provide relief for ulcerative colitis !

We know that Retinoic acid is the oxidized form of Vitamin A. It functions in determining position along embryonic anterior/posterior axis in chordates. It acts through Hox genes, which ultimately control anterior/posterior patterning in early developmental stages. Retinoic acid acts by binding to heterodimers of the retinoic acid receptor (RAR) and the retinoid X receptor (RXR), which then bind to retinoic acid response elements (RAREs) in the regulatory regions of direct targets (including Hox genes), thereby activating gene transcription.

Recently when I was reading a paper, found this interesting fact that is "retinoic acid, could be a beneficial treatment for people suffering from ulcerative colitis and other irritable bowel diseases. Specifically the researchers found that retinoic acid helps suppress out-of-control inflammation, which is a hallmark of active ulcerative colitis.

Pharmaceutical strategies based on this research may offer a promising alternative to the current approaches of managing immune diseases including, IBD, arthritis, multiple sclerosis, and so on, Aiping Bai, a researcher involved in the work from Nanchang University in Nanchang City, China claimed.

The studies ultimately found that treatment with retinoic acid reduced the inflammation in the colon by increasing the expression of FOXP3, a gene involved with immune system responses, as well as decreasing the expression of IL-17, a cytokine believed to cause inflammation. Because many experts believe that IL-17 directly relates to the uncontrolled inflammation seen in ulcerative colitis and irritable bowel disease, the discovery that retinoic acid reduces IL-17's ability to cause inflammation could accelerate the development of treatments for these chronic diseases.

Ref : http://www.jleukbio.org/cgi/content/abstract/86/4/959?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext=Aiping+Bai&searchid=1&FIRSTINDEX=0&resourcetype=HWCIT

RXi receives USPTO notices of allowance for certain siRNA sequence-specific patent applications..

In my earlier blog (January 25, 2009), titled "Diverse use of Nucleic acids....." I did mention about the RNA interference (RNAi) technology. Yes the dream has come true now "RXi Pharmaceuticals Corporation" has received Notices of Allowance from USPTO for small interfering RNA (siRNA) sequences targeting superoxide dismutase (SOD1), Amyloid beta (A4) precursor protein (APP), interleukin-1 receptor-associated kinase 4 (IRAK4), hepatocyte growth factor receptor (MET protooncogene) and cyclin-dependent kinase (cdk) inhibitor p27 (also known as MET protooncogene). Hope these class of compounds will get a boost and some new drugs from these class of compounds in the near future.....

More :
RXi receives USPTO notices of allowance for certain siRNA sequence-specific patent applications

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NDA of Cladribine as a drug for Multiple Sclerosis !

When I was working with Innovasynth Technologies, Khopoli, I worked in the field of "antisense drugs" and as the company has tie up with many MNCs (working with these class of compounds) I had many times interacted with Serono, Pharmaceuticals (US) for some of the intermediates (oligonucleotides). When I read this article, I am happy there are many drugs still to be established as antisense drugs and more over this NDA (new drug application) is something to cherish.

We know that 2-chlorodeoxyadenosine, Cladribine (Leustatin) is drug used to treat hairy cell leukemia (leukemic reticuloendotheliosis).

As a purine analog, it is a synthetic anticancer agent that also suppresses the immune system. Chemically, it mimics the nucleoside adenosine and thus inhibits the enzyme adenosine deaminase, which interferes with the cell's ability to process DNA. It is easily destroyed by normal cells except for blood cells, with the result that it produces relatively few side effects and results in very little non-target cell loss.

Though it has been used to treat leukemic reticuloendotheliosis, other activities like B cell leukemias and lymphomas, such as mantle cell lymphoma are still to be established. Now EMD Serono has applied for this NDA with FDA. As per the claim by the company, Cladribine Tablets has the potential to be the first orally administered disease-modifying therapy available for people living with relapsing MS, as all disease-modifying therapies currently approved for the treatment of MS are parenteral therapies. Hope FDA will approve the drug and will help many patients with relapsing forms of multiple scleorosis will have a relief in the days to come..

Ref : http://www.emdserono.com/cmg.emdserono_us/en/images/Cladribine%20Tablets%20FDA%20Submission%20FINAL%20US%20FINAL_tcm115_44365.pdf

Herbicide as a catalyst to generate electricity from carbohydrates ?

In the recent times we have seen many research groups working on biofuels or alternative energy sources. This article is really interesting, here in the researchers (Brigham Young University) claim that with a help of a herbicide (they have'nt mentioned the name, but say a common herbicide which is cheap also) have developed a fuel cell – basically a battery with a gas tank – that harvests electricity from glucose and carbohydrates.

Deriving electrical energy from glucose and other carbohydrates under mild conditions is an important research objective because these biomolecules are abundant, renewable, have high energy density, and are convenient as fuels. The researchers Gerald Watt et.al., claim that viologen catalysts meet these demanding criteria by catalytically oxidizing glucose and other carbohydrates in a mildly alkaline solution, making possible a direct carbohydrate fuel cell. Formate and carbonate are major products of carbohydrate oxidation, demonstrating that extensive carbon–carbon bond breaking has occurred. A rudimentary fuel cell utilizing viologen catalysts and glucose or dihydroxyacetone as fuels demonstrated electrical power production at up to 20 mA/cm² superficial current density. Improved catalyst function and cell design should significantly advance the efficiency and viability of direct carbohydrate fuel cell technology as a means of generating electrical energy from renewable biomass.

The effectiveness of this cheap and abundant herbicide is a boon to carbohydrate-based fuel cells. By contrast, hydrogen-based fuel cells like those developed by General Motors, require costly platinum as a catalyst. Congrats for this innovative idea....

Ref : http://byunews.byu.edu/archive09-Sep-sugar.aspx

Calcium Scans May Be Effective Screening Tool For Heart Disease

Calcium Scans May Be Effective Screening Tool For Heart Disease

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New markers for early detection Of type 1 diabetes !

As per the claim by the lead researchers Prof. Dr. Anette Ziegler and Dr. Peter Achenbach, genetic factors play a significant role in the development of type 1 diabetes. The scientists were able to show that specific variants of the zinc transporter gene SLC30A8 influence the risk for diabetes. The body needs this gene in order to produce ZnT8. This protein influences the zinc transport into the beta cells and plays a crucial role in their maturation and thus also in insulin secretion.

Beta cells of the islets of Langerhans in the pancreas secrete the vitally important insulin. Already prior to the onset of type 1 diabetes the body’s own immune system destroys the beta cells. If this destruction exceeds a certain threshold, the disease becomes manifest: The insulin deficiency leads to various metabolic disturbances, including elevated blood glucose levels. Autoantibodies to ZnT8 in combination with a specific variant of the zinc transporter gene were associated with an elevated diabetes risk. The researchers claims that "Autoantibodies to ZnT8 are an additional important marker for the progression of diabetes – especially in children who are already developing islet autoantibodies. Hence larger the number of different kinds of autoantibodies, the higher the risk for diabetes, and the younger the child with autoantibodies, the earlier disease onset will be. Its a good achievement. Congrats....

Ref : http://www.helmholtz-muenchen.de/en/press-and-media/press-releases/press-releases-2009/press-releases-2009-detail/article/12322/9/index.html

Nasal Spray That Improves Memory !

The first evidence that the immunoregulatory signal interleukin-6 plays a beneficial role in sleep-dependent formation of long-term memory in humans.

The cytokine IL-6 has been considered to exert neuromodulating influences on the brain, with promoting influences on sleep. Sleep enhances the consolidation of memories, and, in particular, late nocturnal sleep also represents a period of enhanced IL-6 signaling, due to a distinctly enhanced availability of soluble IL-6 receptors during this period, enabling trans-signaling of IL-6 to neurons.

Thus, a contribution of IL-6 to sleep-dependent memory consolidation like the influence of interleukin-6 is hypothesized.

To make this discovery, Marshall and colleagues had 17 healthy young men spend two nights in the laboratory. On each night after reading either an emotional or neutral short story, they sprayed a fluid into their nostrils which contained either interleukin-6 or a placebo fluid. The subsequent sleep and brain electric activity was monitored throughout the night. The next morning subjects wrote down as many words as they could remember from each of the two stories. Those who received the dose of IL-6 could remember more words.

Gene Behind Malaria-resistant Mosquitoes Identified

The mosquitoes can also be our allies in the fight against this common foe malaria. This article is interesting because of its basis i.e., malaria parasites must spend part of their lives inside mosquitoes and another part inside humans, so by learning how mosquitoes resist malaria, we may find new tools for controlling its transmission to humans in endemic areas.....

Gene Behind Malaria-resistant Mosquitoes Identified

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Pralatrexate gets FDA approval....

We did know that Pralatrexate, also known as 10-propargyl- 10-deazaaminopterin, common name PDX, is a drug candidate being studied for the treatment of cancer. PDX is a Folate Anolog Inhibitor of dihydrofolate reductase. As of August 2008^[update], it is undergoing Phase II clinical trials for the treatment of Hodgkin & Nonhodgkin lymphoma (including T -cell lymphoma), non-small cell lung cancer (NSCLC), and bladder cancer.

Now FDA has approved this drug. So at last, patients with relapsed or refractory peripheral T-cell lymphoma (PTCL) will breathe a sigh of relief. FOLOTYN (Pralatrexate) is the first and only drug approved by the FDA for this indication and represents a new treatment option for patients with relapsed or refractory PTCL. This indication is based on overall response rate. Clinical benefit such as improvement in progression free survival or overall survival has not been demonstrated. Allos expects to make FOLOTYN available to patients in the U.S. in October.

More info...

Novel Mass Spectrometry Application for drug discovery?

In one of my earlier blog, Dec., 28th 2008, ( FBDD- A New Approach Of Drug Discovery) I did mention about the use of a number of biophysical techniques as screening tools including high-throughput x-ray crystallography (the advantage of giving the best picture of how the fragment sits in the target) and when paired with NMR allows you to create a structure-based lead.

With different companies approaching this new route in different ways like :

1. high-throughput x-ray crystallography
2. NMR-fragment screening
3. fluorescence polarization assay and many other interesting ways like Protien-Protein interactions etc., this field I think have important role to play.

The drug discovery field got a momentum and has lead to a new direction.....

While reading Science Daily (Online issue, Sept 21, 2009), I found this interesting (article ) and really innovative finding , which I want to share...

Preliminary studies by the researchers (Dr. Ken & Dr.Rakesh )have shown that the new mass spectrometry tool—known as MALDI-QqQMS (matrix-assisted laser desorption ionization-triple quadruple mass spectrometer)—provides a superior means of measuring the enzyme reactions critical to drug discovery at speeds comparable to currently available high-throughput screening systems at significantly lower costs. As per the claim by the researchers, Dr. Ken Greis, "If introduced broadly, the new generation mass spectrometry-based method the researchers are proposing could significantly reduce the cost of running drug compound screening assays while also saving drug development teams substantial time by improving the accuracy of data collected. As per the claim by these researchers the above mentioned methods are costly.

Dr. Ken Greis and Dr. Rakesh Rathore have developed a custom high-throughput screening method using a generalized platform. Unlike the commercially available systems that analyze byproducts and coupled reactions, their system directly measures and quantifies the substrate and the end product of the reaction. They say using mass spectrometry to measure the mass and quantity of the product gives researchers a direct measure of the assay and more reliable compounds to explore, eliminating the chances for molecular interference common with chemiluminescence and fluorescence-based systems. Its a remarkable achievement and hope in the near future we will have an automated system for commercial use with least expense. Best of luck. For More....

Superheavy Element 114 Confirmed.........

Superheavy Element 114 Confirmed: A Stepping Stone To The 'Island Of Stability'

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Certain Colors More Likely To Cause Epileptic Fits......

Certain Colors More Likely To Cause Epileptic Fits, Researchers Find

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Alternates to pheromones ?

I studied about the pheromones when I was doing my post graduation and the professor, who taught us has worked with Dr. H.C. Brown (Nobel Laureate, for his contribution to the field of Organo Boranes) made us understand what are pheromones, how they are prepared and how actually they attract the insects. I think the field has been widely accepted. As for as my knowledge goes the preparation of pheromones is a costly affair (via , organo boranes). Recently I found this interesting article, where in the researchers claim that with the help of alternate chemicals (other than pheromones) one can send insects off the scent of crops.

Dr. Antony Hooper of Rothamsted Research, an institute of BBSRC said, one way in which insects find each other and their hosts is by smell, or more accurately: the detection of chemical signals – pheromones, for example. Insects smell chemicals with their antennae; the chemical actually gets into the antennae of the insect and then attaches to a protein called an odorant-binding protein, or OBP. This then leads to the insect changing its behavior in some way in response to the smell, for example, flying towards a plant or congregating with other insects (that is what we were taught..) But the more interesting part of the research is .....studying an OBP found in the silkworm moth Bombyx mori, Dr Hooper and his team were able to look at how the OBP and a relevant pheromone interact. They also tested the interaction between OBP and other molecules (that are similar to, but not the same as, the pheromone). They actually found that there are other compounds that bind to the OBP much more strongly than the pheromone.

The researchers could potentially apply these compounds, in some way to block the insects’ ability to detect chemical signals – the smell would be overwhelmed by the one they introduced. and by doing so the researchers expect the insects to be less likely to orientate themselves towards the crop plants, or find mates in this case, and therefore could reduce the damage. Though still lot of work has to be done, its a good beginning.

Hope this new and innovative way to prevent and control pests and diseases will be a success in the days to come. I wish every success in their endeavor...

Congrats Dr. Antony Hooper and co-workers..

Ref :
http://www.bbsrc.ac.uk/media/releases/2009/090924_scientists_discover_how_to_send_insects_of_the_scent.html

Stelara approved by the FDA for treating psoriasis

We know that Stelara (Ustekinumab), is a human monoclonal antibody that binds to the shared p40 protein subunit of human IL-12 and IL-23 with high affinity and specificity, thereby preventing interaction with their surface IL-12Rβ1 receptor. Hope this approval provides an alternative treatment for people with plaque psoriasis, which can cause significant physical discomfort from pain and itching and result in poor self-image for people who are self-conscious about their appearance...

Stelara approved by the FDA for treating psoriasis

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Years of caste system belie Indians' shared ancestry - life - 24 September 2009 - New Scientist

Though there were already some sort of genetic info, regarding the difference in the North & South Indians. This info should be used exclusively for medicinal purpose, but not to differentiate again between North & South Indians. After all human beings all over the world are same. We have already facing racial attacks in Australia and this info shldn't lead to difference amongst Indians !...

Years of caste system belie Indians' shared ancestry - life - 24 September 2009 - New Scientist

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