Botox for Chronic Regional Pain Syndrome (CRPS). ...

We know that Botulinum toxin is a medication and a neurotoxic protein produced by the bacterium Clostridium botulinum, and is held to be the most toxic substance known to mankind with an LD50 of roughly 0.005-0.05 µg/kg. Despite its greatest known toxic effect, it is also used in very small doses to treat muscle spasms. The acceptance of BTX-A use for the treatment of spasticity and muscle pain disorders is growing, with approvals pending in many European countries and studies on headaches (including migraine), prostatic symptoms, asthma, obesity and many other possible indications are ongoing.

But some interesting findings of the same drug has been presented at the American Society of Plastic Surgeons (ASPS) Plastic Surgery 2009 conference, Oct. 23-27, in Seattle, i.e., botox can be used as a pain medication to fight Chronic Regional Pain Syndrome (CRPS).

The study found injecting Botox into the area affected by pain provides significant pain control. Eight patients suffering from severe pain received an average of nine injections , one every four weeks. All of patients reported a significant improvement (31.25 percent) in their daily pain control that was maintained for up to 17 months. Though the drug has been used to treat many problems like cervical dystonia (CD), strabismus, blepharospasm, primary axillary hyperhidrosis, glabellar lines (wrinkle fighter). this finding is more significant....

Ref : http://www.plasticsurgery.org/Documents/Media/ps2009/19-Botox-Chronic-Pain.pdf

Triple-combo Drug for Antiviral-resistant H1N1 ?

In laboratory testing, the triple combination of oseltamivir (Tamiflu), amantadine (Symmetrel) and ribavirin showed a significant capacity to stop flu-virus growth, says Mark Prichard....

More...http://www.sciencedaily.com/releases/2009/10/091027132426.htm

New 'Schizophrenia Gene' Prompts Researchers To Test Potential Drug Target

The newfound gene, dubbed KIAA1212, serves as a bridge linking two schizophrenia genes: DISC1 and AKT. Suspecting KIAA1212 as one of many potential binding partners interacting with DISC1, whose name is an acronym for "Disrupted-in-Schizophrenia," the researchers genetically shut down the production of DISC1 proteins in newly born neurons in the hippocampus region of an adult mouse brain. The hippocampus contains a niche where native stem cells give rise to fully developed new neurons

Read : New 'Schizophrenia Gene' Prompts Researchers To Test Potential Drug Target

Minocycline for stroke patients?

Minocycline hydrochloride, also known as minocycline (right structure), is a broad spectrum tetracycline antibiotic, and has a broader spectrum than the other members of the group. It is a bactriostatic antibiotic. As a result of its long half-life it generally has serum levels 2-4 times that of most other tetracyclines (150 mg giving 16 times the activity levels compared to 250 mg of tetracycline at 24–48 hours). It is primarily used to treat acne and other skin infections. Apart from the antibacterial activity, 'minocycline' is recognized as a DMARD (Disease-Modifying Anti-Rheumatic Drug) by the American College of Rheumatology, which recommends its use as a treatment for mild rheumatoid arthritis.

A recent study by the Dr. Cesar V. Borlongan (University of South Florida, USA) has lead to some interesting result, i.e., minocycline can be used to treat the stroke patients !. As per the claim by the researchers this drug might be a better option, when compared with the thrombolytic agent tPA (the only effective drug for acute ischemic stroke) and more over only 2 % of ischemic stroke patients benefit from this treatment due to its limited therapeutic window.

During a stroke, a clot prevents blood flow to parts of the brain, which can have wide ranging short-term and long-term implications. This study recorded the effect of intravenous minocycline in both isolated neurons and animal models after a stroke had been experimentally induced. At low doses it was found to have a neuroprotective effect on neurons by reducing apoptosis of neuronal cells and ameliorating behavioral deficits caused by stroke. The safety and therapeutic efficacy of low dose minocycline and its robust neuroprotective effects during acute ischemic stroke make it an appealing drug candidate for stroke therapy claims the researchers. Congrats for this interesting finding...

Ref : http://www.biomedcentral.com/1471-2202/10/126/abstract

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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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

Naked mole rats may help cure cancer - health - 22 September 2009 - New Scientist

Naked mole rats may help cure cancer - health - 22 September 2009 - New Scientist

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Valturna gets FDA approval .....

FDA, has approved Valturna (valsartan & aliskiren respective structures above) tablets, the first and only medicine to target two key points within the renin system, also known as the renin angiotensin aldosteronesystem (RAAS), an important regulator of blood pressure. This is the first approval for Valturna, which is indicated for the treatment of Hypertension (high blood pressure) in patients not adequately controlled on aliskiren or angiotensin receptor blocker (ARB) monotherapy and as initial therapy in patients likely to need multiple drugs to achieve their blood pressure goals. This unique combination brings together the powerful blood pressure lowering effects of valsartan and aliskiren. Valturna combines in a single pill valsartan, the active ingredient in Diovan((R)), the number one selling branded Hypertension medicine worldwide, and aliskiren, the active ingredient in Tekturna((R)), the only approved direct renin inhibitor (DRI). Valturna offers significantly greater blood pressure reduction than either valsartan or aliskiren alone. Now for the first time, patients have a treatment option in one pill that targets two key points of the RAAS, which may be overactive in many hypertensive patients. The important fact about the combination is - by targeting two key points within the RAAS, Valturna helps blood vessels relax and widen so blood pressure is lowered. Research suggests that up to 85% of hypertensive patients may need multiple medications to help control their blood pressure, underscoring the need for effective combination treatments, hope this combined drugs will help the patients to a large extent. But those people with stroke, heart attack, heart failure, kidney failure or eye problems resulting from hypertension will have to wait for some more time....

Ref : http://www.novartis.com/newsroom/media-releases/en/2009/1342100.shtml

Podophyllotoxin in American Mayapple ?

A common plant called American mayapple (see the picture) may soon offer an alternative to an Asian cousin that's been harvested almost to extinction because of its anti-cancer properties. The near-extinct Asian plant, Podophyllyum emodi, produces podophyllotoxin (see the structure), a compound used in manufacturing etoposide, the active ingredient in a drug used for treating lung and testicular cancer. Podophyllyum emodi is a cousin of the common mayapple, sometimes considered a weed, found in the United States.

Podophyllotoxin and its derivatives are used in several commercially available pharmaceutical products such as the anticancer drugs etoposide, teniposide, and etopophos, which are used in the treatment of small-cell lung cancer, lymphoblastic leukemia, testicular cancer, and brain tumors. Podophyllotixin derivatives are also used for the treatment of psoriasis and malaria, and some are being tested for the treatment of rheumatoid arthritis. Currently, podophyllotoxin is produced commercially using the roots and rhizomes of Indian mayapple, an endangered species harvested from the wild in India, Pakistan, Nepal, and China.

Now the researchers from the US, found that mayapple colonies in the eastern part of the United States can be used for the development of high podophyllotoxin cultivars, which could subsequently provide the base for commercial production of podophyllotoxin in the United States.

Ref : http://hortsci.ashspublications.org/cgi/content/abstract/44/2/349

House plants to cut Indoor Ozone !

We know that ozone, the main component of air pollution or smog, is a highly reactive, colorless gas formed when oxygen reacts with other chemicals. And ozone pollution is most often associated with outdoor air, the gas also infiltrates indoor environments like homes and offices. And that is why those who have allergy like 'morning sneeze' will be advised by doctors to avoid going outside early in the morning and one can follow this advise sincerely. But when I read in an article that ozone can be released by ordinary copy machines (xerox machines), laser printers, ultraviolet lights, and some electrostatic air purification systems, all of which contribute to increased indoor ozone levels, I got an answer for one of my freind's problem.

We are aware that the extensive list of toxic effects of ozone on humans are pulmonary edema, hemorrhage, inflammation, and reduction of lung function. So I was wondering how one can take care of themselves even by staying in house (avoiding morning walk) ?.

Recently I found this interesting fact that three common indoor houseplants (see pictures), snake plant (Sansevieria trifasciata), spider plant (Chlorophytum comosum), and golden pothos (Epipremnum aureum) can reduce the ozone concentrations effectively.

Hope plants as a mitigation method could serve as a cost-effective tool, where expensive pollution mitigation technology may not be economically feasible in the days to come....

Ref : http://horttech.ashspublications.org/cgi/content/abstract/19/2/286

Tuberculosis Patients Can Reduce Transmissability By Inhaling Interferon Through A Nebulizer

As for as my knowledge goes "Interferons" - (glycoproteins - natural cell-signaling proteins produced by the cells of the immune system of most vertebrates in response to challenges such as viruses, parasites and tumor cells).

1.  assist the immune response by inhibiting viral replication within host cells, activating natural killer cells and macrophages, increasing antigen presentation to T lymphocytes.

2. increasing the resistance of host cells to viral infection.

And are said to possess the antiviral and antitumour activity.   

But this finding is really interesting.................."Tuberculosis Patients Can Reduce Transmissability By Inhaling Interferon Through A Nebulizer" 

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Tigecycline- as antimalarial drug ?

                As for my knowledge goes,  'Tigecycline'  is being used  as  drug for the antibiotic resistant strain 'Staphylococcus aureus'.  And this drug belongs to the class of "glycylcyclines" (similar to tetracyclines : central four-ring carbocyclic skeleton).  The broad spectrum activity is attributed to the  D-9 position substitution. It is a bacteriostatic and acts by the inhibition of protein synthesis. It has been found to be active against both Gram positive and Gram negative bacterii. 

Now thanx to the researchers from the Medical University of Vienna, Austria, who have achieved something interesting feat, i.e.,  Tigecycline has significant antimalarial activity on its own and may also be effective against multi drug-resistant malaria when administered in combination with traditional antimalarial drugs. 

Increasing resistance of Plasmodium falciparum to existing drugs has resulted in the search for new antimalarial therapies and I congratulate the team for this important achievement.  More interestingly the drug is 6 times more active against P. falciparum than doxycycline. As the drug itself is an established one,  its one more addition to the serendepity list. Congrats the team...

Ref : http://www.asm.org/index.php?option=com_content&view=article&id=91042

Tigecycline- as antimalarial drug ?

                As for my knowledge goes,  'Tigecycline'  is being used  as  drug for the antibiotic resistant strain 'Staphylococcus aureus'.  And this drug belongs to the class of "glycylcyclines" (similar to tetracyclines : central four-ring carbocyclic skeleton).  The broad spectrum activity is attributed to the  D-9 position substitution. It is a bacteriostatic and acts by the inhibition of protein synthesis. It has been found to be active against both Gram positive and Gram negative bacterii. 

Now thanx to the researchers from the Medical University of Vienna, Austria, who have achieved something interesting feat, i.e.,  Tigecycline has significant antimalarial activity on its own and may also be effective against multi drug-resistant malaria when administered in combination with traditional antimalarial drugs. 

Increasing resistance of Plasmodium falciparum to existing drugs has resulted in the search for new antimalarial therapies and I congratulate the team for this important achievement.  More interestingly the drug is 6 times more active against P. falciparum than doxycycline. As the drug itself is an established one,  its one more addition to the serendepity list. Congrats the team...

Ref : http://www.asm.org/index.php?option=com_content&view=article&id=91042

Discovery Of Natural Odors- a new way to develop cheaper mosquito repellents !..

Entomologists at the University of California, Riverside (Anandasankar Ray, an assistant professor in the Department of Entomology, and Stephanie Turner, his graduate student)  working on fruit flies in the lab have discovered a novel class of compounds that could pave the way for developing inexpensive and safe mosquito repellents for combating West Nile virus and other deadly tropica. 

The basis for the 'invention' though looks simple, but this finding is of great importance. As for my knowledge goes most of the mosquito repellents are cyclohalothrins, which are a costly affair to prepare [as a synthetic chemist,  I know how difficult its to prepare cyclohalothrins (pyrethroids)  e.g., Allethrin & Permethrin. When I was working in Rallis India Limited, one of my senior colleague was working on Permethrin and I know how difficult to introduce the halo group that too by using florochlorocarbons CFCs (banned chemicals !)]. Congrats Anandsankar Ray, for this interesting achievement. 

When fruit flies undergo stress, they emit carbon dioxide (CO2) that serves as a warning to other fruit flies that danger or predators could be nearby. The fruit flies are able to detect the CO2 and escape because their antennae are equipped with specialized neurons that are sensitive to the gas.

But fruits and other important food sources for fruit flies also emit CO2 as a by-product of respiration and ripening. If the innate response of the fruit fly is to avoid CO2, how then does it find its way to these foods?. The researchers have have identified a new class of odorants – chemical compounds with smells – present in ripening fruit that prevent the CO2-sensitive neurons in the antennae from functioning. In particular two odors, hexanol and 2,3- butanedione, are strong inhibitors of the CO2-sensitive neurons in the fruit fly.

CO2 emitted in human breath is the main attractant for the Culex mosquito to find people, aiding the transmission of these deadly diseases," Ray said. In their  experiments they  identified hexanol, and a related odor, butanal, as strong inhibitors of CO2-sensitive neurons in Culex mosquitoes. These compounds can now be used to guide research in developing novel repellents and masking agents that are economical and environmentally safe methods to block mosquitoes.

Those interested can listen to Anandsankar

Fruits better than prviously thought !.......

Polyphenol content in fruits usually refers to extractable polyphenols, but a Spanish scientist working at the Institute of Food Research in Norwich analysed apple, peach and nectarine. She found that nonextractable polyphenol content is up to five times higher than extractable compounds. Its really interesting and that might be the reason why our forefathers used to insist to eat whole fruits (though they might not have studied so exhaustively... !).  

The interesting findings like,  "polyphenols need to be treated with acid to extract them from the cell walls of fruit in the lab" will help at least now onwards to collect all the useful polyphenols (proanthocyanidins, ellagic acid and catechin)  which without this new findings might have gone as waste.  Dr Paul Kroon from IFR explains: “In the human body these compounds will be fermented by bacteria in the colon, creating metabolites that may be beneficial, for example with antioxidant activity. 

Hope these  nonextractable polyphenols, (which mostly escape analysis and are not usually considered in nutritional studies),  will play a major part of bioactive compounds in the diet  in the days to come. Congrats Professor Saura-Calixto, for this  achievement.....

Wearable Artificial Kidney good bye to dialysis !

I have seen people who had kidney failure and how its difficult to get dailysis & to mentain the sterile conditions to avoid infections. Now thanx to a group of researchers from David Geffen School of Medicine at UCLA,  who have come up with a novel idea of developing wearable artificial kidney!. 

As per the claim by the researchers, the device—essentially a miniaturized dialysis machine, worn as a belt—weighs about 10 pounds and is powered by two nine-volt batteries. Patients don't need to be hooked up to a full-size dialysis machine, they are free to walk, work, or sleep while undergoing continuous, gentle dialysis that more closely approximates normal kidney function. Despite enduring long hours on dialysis every week—with major limitations in activities, diet, and other areas of life—dialysis patients face high rates of hospitalization and death and more over its a costly affair too. 

The Wearable Artificial Kidney is successful in preliminary tests, including two studies in dialysis patients. The new study provides important information on the technical details that made these promising results possible. Though further studies like 'long-term effect' has to be established its a great achievement  and hope the researchers will succeed in their endeavor....

Congrats,  Victor Gura et.al., 

Mini-magnet test makes things sticky for TB - tech - 07 August 2009 - New Scientist

Mini-magnet test makes things sticky for TB - tech - 07 August 2009 - New Scientist

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Explanation for the side effect of COX-2 inhibitors !....

When I read this article, went back to my research days (1993-1998). We did prepare some triazoles, oxadiazoles, thiadiazoles and their derivatives. The parent triazoles and oxadiazoles were tested for thier antiinflammatory activity by Carrageenan induced rat paw edema, Cotton pellet induced granuloma tissue formation methods and the results were encouraging and were even better tolerated than the standards (Diclofenac and Ibuprofen). We had many research papers that time claiming that, the selective inhibitors of COX-2 and 5-LO are the best NSAIDs. After few years there were three COX-2 inhibitors in the market (namely-Vioxx (rofecoxib), Bextra (valdecoxib) and Celebrex (celecoxib) and we were happy that atleast the ulcerogenecity of NSAIDS has been taken care of. But the days were countable and the first two drugs were withdrawn from the market, because of the cardiovascular toxicity and only celecoxib is available in the market. Now thanx to Dr. Andrew J. Dannenberg (Director of the Weill Cornell Cancer Center) and group, who have come up with a novel explanation for the cardiovascular toxicity of the COX-2 inhibitors. I would say one more "serendipity" to the drug discovery, because the trial was originally designed to identify biomarkers in urine which could indicate the presence of incipient, smoking-related lung disease. The researchers had hypothesized that early-stage lung injury could "turn on" the COX-2 gene, increasing levels of the major prostaglandin metabolite PGE-M in the urine. In addition to determining PGE-M levels, the investigators also looked at levels of the biomarker leukotriene E4 (LTE4), formed by the 5-lipoxygenase (5-LO) pathway. Both biomarkers, representing these two different pathways, are synthesized from arachidonic acid. The 5-LO pathway has also been implicated in inflammation, cancer and cardiovascular problems. The authors found that Celebrex treatment led to increases in urinary LTE4 levels, primarily among individuals who had started out with high PGE-M levels, which indicated that Celebrex 'shunted' or redirected arachidonic acid into the 5-LO pathway from the COX pathway. When one went down, the other went up." This is important because other studies have suggested an important role for the 5-LO pathway in atherosclerosis, heart attacks and stroke. And it is this increased shunting of arachidonic acid into the 5-LO pathway that may help explain why COX-2 inhibitors contribute to cardiovascular problems, the researchers say. Though further studies are essential to substantiate the claims, is a good beginning and hope with selective inhibitors of both COX-2 (cyclooxygenase) and 5-LO (lipoxygenase) are the need of today's world (I did mention in the beginning about that..)...

Ref: http://news.med.cornell.edu/wcmc/wcmc_2009/04_29_09.shtml

Melatonin as a potential anti-fibrotic drug ?

Melatonin, N-(2-(5-methoxy-1H- indol-3-yl)ethyl)acetamide) is a hormone found in all living creatures. It is naturally synthesized from the amino acid tryptophan, via synthesis of serotonin, by the enzyme 5-hydroxyindole-O-methyl transferase.

Nobel Prize laureate Julius Axelrod performed many of the seminal experiments that elucidated the role of melatonin and the pineal gland in regulating sleep-wake cycles (circadian rhythms). In humans, melatonin is produced by the pineal gland, (a gland located in the center of the brain). Normally, the production of melatonin by the pineal gland is inhibited by light and permitted by darkness.

For this reason melatonin has been called "the hormone of darkness". The secretion of melatonin peaks in the middle of the night, and gradually falls during the second half of the night. Until recent history, humans in temperate climates were exposed to up to eighteen hours of darkness in the winter. In this modern world, artificial lighting typically reduces this to eight hours or less per day all year round.

And also we know that, in animal models, melatonin has been demonstrated to prevent the damage to DNA by some carcinogens. The antioxidant activity of melatonin may reduce damage caused by some types of Parkinson's disease, may play a role in preventing cardiac arrhythmia and may increase longevity; it has been shown to increase the average life span of mice by 20% in some studies. Melatonin appears to have some use against circadian rhythm sleep disorders, such as jet lag and delayed sleep phase syndrome. The primary motivation for the use of melatonin as a supplement is as a natural aid to better sleep, with other incidental benefits to health and well-being due to its role as an antioxidant and its stimulation of the immune system and several components of the endocrine system.

Now something interesting, melatonin has been tested as a potential anti-fibrotic drug. Congrats Professor. Jian-Ming Xu, (of Hospital of Anhui Medical University, China) and group.

The results suggested that treatment with melatonin (10 mg/kg) could decrease the scores of hepatic fibrosis grading, reduced the contents of hyaluronic acid (HA), laminin(LN) in serum and Hydroxyproline (HYP) in liver, treatment with melatonin (5,10 mg/kg ) could decrease serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and blocked the increase in malondialdehyde (MDA) in rats with hepatic injury caused by CCl4.

More over, the authors attribute this property of anti-fibrotic to the Antioxidant activity of melatonin..really interesting......

Improved efficacy of tuberculosis vaccine ?

We know that BCG (Bacille Calmette-Guérin) is a live but weakened form of a bacterium, M. bovis, which causes tuberculosis in cattle. It is sufficiently related to the human pathogen to stimulate production of specialized immune cells that fight off TB infection when it is injected into a person as a vaccine. The bacilli have retained enough strong antigenicity to become a somewhat effective vaccine for the prevention of human tuberculosis. At best, the BCG vaccine is 80% effective in preventing tuberculosis for a duration of 15 years, however, its protective effect appears to vary according to geography.

Many attempts have been made to improve the vaccine by incorporating antigens (molecular components of the bacteria) to induce a stronger immune response. However, tuberculosis and BCG have evasive mechanisms that prevent the development of stronger immune responses. We read oftenly in news paper, about the drug resistant strains and use of combined drugs. Now thanx to the two research groups from UT Health Science Center at Houston. The importance of this research is in the fact that the two groups investigated mechanisms by which BCG evades immune stimulating mechanisms and devised two means to neutralize them.

1. scientists used genetically-modified organisms and
2. a drug used for organ transplantation (Rapamycin, see the structure)to block BCG's evasive mechanisms, causing it to induce stronger immune responses.

This dual approach to the BCG vaccine was associated with a tenfold increase in the number of TB organisms killed and a threefold increase in the duration of protection in tests with an NIH-approved mouse model, Dr. Jagannath said.

The research is of great importance because of the fact that "it has countered the ability of TB organisms to subvert immunization", (Tuberculosis hides in cells so the antigens are not recognized by the immune system. The BCG vaccine also does the same thing). The role of the drug is of great importance, i.e., it modulates the movement of particles in cells, would cause BCG antigens to enter pathways leading to improved immunization. I would say one more significant contribution(or else one more serendipity !) of the drug apart from bieng used in 1. treatment of cancer and inflammation 2. in significantly reducing the frequency of acute kidney transplant rejection.

Though further research to substantiate the claim is essential. Its a good beginning in this direction for the improved efficay of the vaccine.. Congrats Dr. Jagannath and group.. More...