Ginseng as antiinflammatory medicine?

We did know about many uses of Ginseng, (like rejuvenating, aphrodisiac, CNS-stimulant & even diabetes mellitus type 2), but this is something new, ginseng as antiinflammatory medicine !. Allan Lau and co workers from University of Hong Kong, have come up with some interesting claims. The researchers have identified seven ginseng constituents, ginsenosides, which showed immune-suppressive effects. The anti-inflammatory role of ginseng may be due to the combined effects of these ginsenosides, targeting different levels of immunological activity, and so contributing to the diverse actions of ginseng in humans. Of the nine ginsenosides they identified, seven could selectively inhibit expression of the inflammatory gene CXCL-10. To substantiate the claim though, detailed studies are needed (to examine the potential beneficial effects of ginsenosides in the management of acute and chronic inflammatory diseases in humans) , its a good beginning..

Ref : http://www.translational-medicine.com/content/pdf/1479-5876-7-34.pdf

LXR Proteins- New target for antitubercular activity?

As we are aware that TB, has become a major threat to the world and a recent study also reports an estimated one-third of the world population is latently infected with Mycobacterium tuberculosis. And also I did mention (earlier blog) that the strain has got resistance for drugs Rifampicin and hence comibination of drugs (Rifampicin, Isoniazid, Euthumbutol) is being used. The most worst part of this is for those who are already infected with HIV. Not only these are the facts of concern, the worst part of this bacterium is "M. tuberculosis has the ability to adapt and survive for long periods of time within the host macrophage in a state of clinical dormancy". The researchers attribute the reason for this as the switching to lipids as their main carbon source of the nutrient-deficient macrophage phagosome. A recent report implicated that mycobacterial persistence is critically linked to its ability to acquire and catabolize cholesterol from the host. Cholesterol, besides being used as an energy or carbon source, is also essential for the phagocytosis of the bacterium by the macrophage and for the inhibition of phagosome maturation. Recently, liver X receptors (LXRs), LXRα and LXRβ, have emerged as master regulators of macrophage transcriptional programs involved in cholesterol, fatty acid, and glucose homeostasis. All these facts encouraged Kris Huygen and colleagues of Scientific Institute of Public Health, Belgium to identify the role of LXR proteins in the mouse immune response to airway infection with Mycobacterium tuberculosis.

In the study, when compared with normal mice, mice lacking both forms of LXR (LXR-alpha and LXR-beta) were more susceptible to airway infection with Mycobacterium tuberculosis and developed more severe disease. Further analysis revealed that these mice did not mount an effective immune response in the airways. There was no accumulation of immune cells (neutrophils) in the lungs and little evidence of Th1 and Th17 immune responses. Importantly, the marked protection from infection seen in normal mice treated with molecules that target LXRs was accompanied by increased Th1 and Th17 immune responses.

Congrats Kris for this achievement. More...

RNA interference approach for prevention and treatment of STDs ?

In my earlier blog “Diverse use of Nucleic acids”, did mention that there is much interest in the medical uses of nucleic acids. For example, antisense, ribozymes, aptamer and RNA interference (RNAi) technologies are all being developed for potential therapeutic applications. Lots of research is being done in each specified fields and in fact there are already few drugs in “antisense category” and this time something really interesting has been reported by a Post Doc., Dr. Kim Woodrow in the field of RNA interference category. The following lines briefly summerise, what actually RNAis..

RNA interference (RNAi) is a system within living cells that helps to control which genes are active and how active they are. Two types of small RNA molecules – microRNA (miRNA) and small interfering RNA (siRNA) – are central to RNA interference. RNAs are the direct products of genes, and these small RNAs can bind to specific other RNAs and either increase or decrease their activity, for example by preventing a messenger RNA from producing a protein. RNA interference has an important role in defending cells against parasitic genes, viruses and transposons – but also in directing development as well as gene expression in general

The RNAi pathway is found in many eukaryotes including animals and is initiated by the enzyme Dicer, which cleaves long double-stranded RNA (dsRNA) molecules into short fragments of ~20 nucleotides. One of the two strands of each fragment, known as the guide strand, is then incorporated into the RNA-induced silencing complex (RISC). The most well-studied outcome is post-transcriptional gene silencing, which occurs when the guide strand base pairs with a complementary sequence of a messenger RNA molecule and induces cleavage by Argonaute, the catalytic component of the RISC complex. This process is known to spread systemically throughout the organism despite initially limited molar concentrations of siRNA. The importance of the siRNA lies in the fact that “RNAi is selective on gene expression” and hence can be used in the similar fashion like the antisense drugs (already a few drugs by ISIS, Serono and others). I did work on a few oligonucleotides (phosparothiamidates), while working in Innovasynth Technologies Limited Khopoli and know how difficult is to get the precursors of the antisense drugs. In 2006, Andrew Fire and Craig C. Mello shared the Nobel Prize in Physiology or Medicine for their work on RNA interference in the nematode worm C. elegans.

Gene interference therapy is moving rapidly from basic research to application. The PLGA packaging these researchers chose is already approved as safe and non-toxic by the FDA, speeding the path to clinical trials for infectious agents such as HPV and HIV.

Congrats Dr.Kim and co workers for this achievement. The significance of this research is the fact that “a safe and effective administration of potential antiviral drugs - small interfering RNA (siRNA) molecules using densely-loaded nanoparticles made of a biodegradable polymer known as PLGA. The researchers created a stable "time release" vehicle for delivery of siRNAs to sensitive mucosal tissue like that of the female reproductive system.

Ref : http://www.nature.com/nmat/journal/vaop/ncurrent/abs/nmat2444.html

After Avian Flu its now Swine Flu ...!.

I am wondering how many flus?. Human flu, Dog flu, Horse flu, Avian flu and Swine flu. In all these cases, the strains have "mutated" which really scares me. If we analyze what happened after the avian flu, one need to be really worried and something has to be done either to avoid the outbreak or take precautions.

Swine influenza (swine flu) refers to influenza caused by any strain of the influenza virus endemic in pigs (swine). Strains endemic in swine are called swine influenza virus (SIV). Human flu is caused by, 3 types of virus Influenza Virus A, B & C. Its interesting to note that virus B has not been so for reported in pigs (swine) and also the strains those are endemic to both humans and swine of Virus A & C are largely distinct !.

Swine flu is common in swine and rare in humans, but however people who work with swine, especially people with intense exposures, are at risk of catching swine influenza if the swine carry a strain able to infect humans. However, these strains rarely are able to pass from human to human. Rarely, SIV mutates into a form able to pass easily from human to human. In humans, the symptoms of swine flu are similar to those of influenza like chills, fever, sore throat, muscle pains, severe headache, coughing, weakness and general discomfort.

The flu outbreak in humans is due to a new strain of influenza A virus subtype H1N1 that derives in part from human influenza, avian influenza, and two separate strains of swine influenza and the origins of this new strain are unknown. It passes with apparent ease from human to human, an ability attributed to an as-yet unidentified mutation. Though the strain in most cases causes only mild symptoms and the infected person makes a full recovery without requiring medical attention and without the use of antiviral drugs. But the out break is causing a real concern.

The reason for concern:

The flu virus is perhaps the trickiest known to medical science; it constantly changes form to elude the protective antibodies that the body has developed in response to previous exposures to influenza or to influenza vaccines. Every two or three years the virus undergoes minor changes. Then, at intervals of roughly a decade, after the bulk of the world's population has developed some level of resistance to these minor changes, it undergoes a major shift that enables it to tear off on yet another pandemic sweep around the world, infecting hundreds of millions of people who suddenly find their antibody defenses outflanked, which is the main reason for the out break And these analyses are being substantiated by the facts that 1.during the Spanish flu pandemic, the initial wave of the disease was relatively mild, while the second wave was highly lethal; and 2. most of us know about the avian flu’s history starting from 1957 ……I am wondering why we are giving undue importance for swine flu to be Mexican flu, North American influenza, swine-origin influenza, and 2009 H1N1 flu, whatever the name may be as human beings first we should think seriously and due importance should be given to this field of research. ……More....

FDA's approval of phase II clinical trials of Bryostatin ( Alzheimer's disease)...

Bryostatins are a group of macrolide lactones first discovered in the late 1960s in a species of bryozoan, Bugula neritina. It is believed to be produced by symbiont bacteriato protect the bryozoan larva from predation or infection, they have cytotoxic properties and are under investigation as anti-cancer agents and as a memory enhancement agent. Bryostatin in sub-nanomolar concentrations has been shown to be a potent activator of protein kinase C.

Bryostatin has appeared very promising enhancing memory in animal models. Bryostatin was able to increase the duration of memory retention of the marine slug Hermissenda crassicornis by over 500%, and was able to dramatically increase the rate of learning in rats. Bryostatin is thought to potentiate memory by activating PKC. Animal tests suggest it may alleviate brain damage after stroke if administered within 24hrs.

Bryostatin was originally created as an anti-cancer chemotherapy. When BRNI scientists extensively tested PKC activators against Alzheimer's disease models, they discovered the drug's hidden potential to stop Alzheimer's disease. Over the past six years, the drug has shown remarkable possibilities. In preclinical testing, BRNI scientists experimented with Bryostatin on three species of Alzheimer's disease transgenic mice, each species based on different human Alzheimer's disease genes. The test results revealed that Bryostatin, and a related class of drugs discovered at BRNI, can reduce the toxic Alzheimer's disease protein A Beta, restore lost synapses, and protect against the loss of memory functions. In related preclinical testing, Bryostatin has been shown to enhance and restore memory by rewiring connections in the brain previously destroyed by stroke, head trauma, or aging itself. With FDAs approval for the phase II clinical trials, this will go a long way in the history of drug research. Bryostatin trial on Alzheimer's disease patients represents a new direction for the treatment of a disease with no current cure. Congrats Dr. Daniel Alkon (Scientific Director of BRNI) and his group...

White light-activated antibacterial coating-a new weapon against superbugs ?

I read in an article that infection costs the NHS around £1 billion per year and it is estimated that as many as 5,000 patients die each year in the UK as a direct result of an HCAI.

Cutting rates of healthcare associated infections (HCAIs) such as Methicillin-resistant Staphylococcus aureus (MRSA) and Clostridium difficile (C.Diff) is a key priority for healthcare professionals. Recently in my earlier blog, I did mention that they were able to culture many bacterii from the cell phones of the health workers !.

Thogh govts., are taking many intiatives with sterlisation of the instrements, the rooms still something has to be done. But this is really something interesting which I read recently and want to share with...

Miss Zoie Aiken and her colleagues presented the work at the Society for General Microbiology meeting in Harrogate on 31 March, 2009. The veneer-like surface, made of titanium dioxide with added nitrogen. When it is activated by white light, similar to those used in hospital wards and operating theatres, it produced a decrease in the number of bacteria surviving on the test surface. Really interesting and the basis for this research is that "Titanium dioxide based coatings can kill bacteria after activation with UV light. The addition of nitrogen to these coatings enables photons available in visible light to be utilised to activate the surface and kill bacteria".

The following are the conclusions :

1. the activity of the coating is assessed against a range of different bacteria such as MRSA and other organisms which are known to cause infections in hospitals. At present researchers claim that the coating is active against Escherichia coli. However, E. coli is more difficult to kill than bacteria from the Staphylococcus group which includes MRSA and the results to date are encouraging.

2. the coating has currently been applied onto glass using a method called APCVD (atmospheric pressure chemical vapour deposition and the researchers want to try out plastic.

Once again congrats and best wishes for further research..

Source : http://www.sgm.ac.uk/

Vaccine for Enterotoxigenic E. coli?

We know that Escherichia coli is a bacterium that normally lives in the intestines of humans and other animals. Most types of E. coli are harmless, but some can cause disease. Disease-causing E. coli are grouped according to the different ways by which they cause illness. Enterotoxigenic Escherichia coli, or ETEC, is the name given to a group of E. coli that produce special toxins which stimulate the lining of the intestines causing them to secrete excessive fluid, thus producing diarrhea. The toxins and the diseases that ETEC causes are not related to ETEC was first recognized as a cause of human diarrheal illness in the 1960s. It have since emerged as a major bacterial cause of diarrhea among travelers and children in the developing world. ETEC is increasingly recognized as an important cause of foodborne illness in developed nations, such as the United States.

ETEC produces two toxins, a heat-stable toxin (known as ST) and a heat-labile toxin (LT). Although different strains of ETEC can secrete either one or both of these toxins, the illness caused by each toxin is similar.

Infection with ETEC can cause profuse watery diarrhea and abdominal cramping. Fever, nausea with or without vomiting, chills, loss of appetite, headache, muscle aches and bloating can also occur but are less common. Illness develops 1-3 days after exposure and usually lasts 3-4 days. Some infections may take a week or longer to resolve. Symptoms rarely last more than 3 weeks. Most patients recover with supportive measures alone and do not require hospitalization or antibiotics.

Antibiotics can shorten the duration of diarrheal illness and discomfort, especially if given early, but they are usually not required. ETEC is frequently resistant to common antibiotics, including trimethoprim-sulfamethoxazole and ampicillin. Because resistance to antibiotics is increasing worldwide, the decision to use an antibiotic should be carefully weighed against the severity of illness and the risk of adverse reactions, such as rash, antibiotic-associated colitis, and vaginal yeast infection. Fluoroquinolones have been shown to be effective therapy.

Now thanx to A. Mahdi Saeed, a professor of epidemiology and infectious disease in MSU's colleges of Veterinary Medicine and Human Medicine has achieved a milestone - he has successfully developed vaccine for this, congrats for his group. Saeed created a biological carrier to attach to the toxin that once introduced into the body induces a strong immune response. This was done by mapping the toxin's biology and structure during the design of the vaccine. After creating the carrier in a lab at MSU, Saeed and his team tested it on mice and found the biological activity of the toxin was enhanced by more than 40 percent, leading to its recognition by the body's immune system. After immunizing a group of 10 rabbits, the vaccine led to the production of the highest neutralizing antibody ever reported for this type of the toxin. Though human clinical trials are yet to be done the group is optimistic about the outcome. The Vaccine, also has some other properties like a laxative (helping the bowel movement for the post surgery anestheia impact) and urinary retention. Hope they will achieve the claims. Once again congratulation for this achievement. More ....

Simponi the first biologic therapy to be approved for rheumatologic diseases !

We did know about the three 3 TNF inhinitors (namely-Infliximab, Etanercept and Adalimumab), the last still to be approved by US.

Like Infliximab and Etanercept, Adalimumab binds to TNFα preventing it from activating TNF receptors; adalimumab was constructed from a fully human monoclonal antibody, while infliximab is a mouse-human chimeric antibody and etanercept is a TNF receptor-IgG fusion protein. TNFα inactivation has proven to be important in down regulating the inflammatory reactions associated with autoimmune diseases. As of 2008 adalimumab has been approved by the FDA for the treatment of rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn's disease, moderate to severe chronic psoriasis and juvenile idiopathic arthritis.

Humira (brand name is an abbreviation of "Human Monoclonal Antibody in Rheumatoid Arthritis") is marketed in both preloaded 0.8 ml syringes and also in preloaded pen devices (called Humira Pen), both injected subcutaneously, typically by the patient at home. It cannot be administered orally, because the digestive system would destroy the drug. But its now the turn of Golimumab, a new fully human monoclonal antibody. Being a fully human MAb directed against TNF, Golimumab resembles Adalimumab (Humira, Abbott), which was the first such product to reach the market. Now the Canadian government has approved Golimumab along with ‘methotrexate’ for the treatment of three forms of Rheumatiod arthritis (Rheumatoid Arthritis, Ankylosing Spondylitis & Psoriatic Arthritis) and more over making this treatment the first biologic therapy to be approved.

With this approval in Canada, Simponi (Golimumb), in combination with methotrexate (MTX), is indicated for reducing the signs and symptoms in adult patients with moderately to severely active RA; reducing signs and symptoms in adult patients with moderately to severely active PsA, alone or in combination with MTX; and reducing signs and symptoms in adult patients with active AS who have had an inadequate response to conventional therapies. More...

A New approach for the TB drug discovery ?

We are aware that the development of new drugs to combat tuberculosis (TB) has become urgent, as strains of TB resistant to all major anti-TB drugs have emerged worldwide. The World Health Organization estimates that one third of the world's population is asymptomatically infected with TB and that ten percent will eventually develop the disease. More over people with HIV are more prone to TB and hence the need is urgent. As it has happened in other fields of drug discoveries, its something really interesting now it’s the turn of TB drugs, thanx to Barbara Gerratana, Asst., Prof.,. of Chemistry and Biochemistry, university's College of Chemical and Life Sciences, Maryland for their achievement. The significance of the research lies in the fact that “ the NAD+ synthetase enzyme is essential for the survival of the tuberculosis bacteria and hence it can be considered as a drug target.”. So even the structure based inhibitors specific for M. tuberculosis NAD+ synthetase, can be tried and tested for the tuberculosis activity.

Even the experts are really happy over the outcome of the research and following are the lines of appreciation from Clifton E. Barry, Chief of the Tuberculosis Research Section of the Intramural Research Division of the National Institute of Allergy and Infectious Diseases “NadE [NAD+ synthetase] represents one of a small handful of TB drug targets that has iron-clad validation, the lack of a crystal structure was the only serious impediment to drug development and this study represents a hugely important step forward. Inhibiting NadE even kills non-replicating cells, so this discovery may well benefit the one-third of the human population that carries latent bacteria.".

Most interesting part of the research is the fact that “there are only two pathways involved in producing NAD+ in the tuberculosis bacterium and both depend on the activity of NAD+ synthetase to obtain NAD+ (unlike in human beings, where in several different complex pathways..). One can target these two pathways and get good drugs, those are essential and there by one can overcome the drawbacks of the present drugs (current treatment of tuberculosis targets the active tuberculosis bacterium and has little effect on the non-replicating bacterium). Once again congrats for the research group……

Broccoli sprouts may help prevent stomach cancer !

Pict., of Broccoli (Structures of DIM & Sulforaphane respectively)

We knew that Broccoli has anticancer activity due to the presence Diindolylmethane, DIM (Str-1). DIM is a natural compound formed during the autolytic breakdown of glucobrassicin present in food plants of the Brassica genus, including broccoli, cabbage, Brussels sprouts, cauliflower and kale. The autolytic breakdown of glucobrassicin requires the catalytic reaction of the enzyme myrosinase which is endogenous to these plants and released upon rupture of the cell wall

(the same compound, has been tested for viral nfections,bacterial infections and immune deficiency diseases also). And boiling the Broccoli, will lead to the loss of this compound has been also established

Now more interestingly, Dr. Jed Fahey has come out with something different and this time they have mentioned about a phytochemical from broccoli, i.e., sulforaphane. Though the cancer protective effects of sulforaphane is known two decades ago, but this is the first study to show an effect of broccoli in humans on the bacterial infection that leads to stomach cancer. In this study, researchers enrolled 48 Helicobacter-infected Japanese men and women and randomly assigned them to eat 70 grams of fresh broccoli sprouts daily for eight weeks or an equivalent amount of alfalfa sprouts.

Researchers assessed the severity of H. pylori infection at enrollment, and again at four and eight weeks using standard breath, serum and stool tests. H. pylori levels were significantly lower at eight weeks on all three measures among those patients who had eaten broccoli sprouts, while they remained the same for patients who had eaten alfalfa sprouts.

A reduction in H. pylori is expected to lead to a reduction in stomach cancer due to their well-established cause-and-effect link. Stomach cancer has a grim prognosis and is the second most common and the second deadliest cancer worldwide. Congrats Dr. Jed Fahey and group...

Niacin as one of the best and cheapest ways to manage cholesterol !

Niacin (nicotinic acid or vitamin B3), has long been regarded as one of the most effective weapons in managing cholesterol. It can lower levels of triglycerides, fatty acids and to a lesser extent, the "bad" kind of cholesterol (LDL) while at the same time powerfully increasing the "good" kind (HDL). But because of its side effect (it causes embarrassing, uncontrollable intense flushing, a rush of blood to the face and other skin surfaces accompanied by a prickling sensation) its not being used. Now thanks to the researchers lead by Dr. Robert Walters, who have come up with a novel explanation (allergy). The following is the explanation of the researchers :

Niacin stimulates production of a vasodilator that dramatically increases blood flow to the face, causing the flush and the hot, prickly sensation - and beta-arrestin1 is the culprit that enables that to happen. However, beta-arrestin1 plays no role whatsoever in niacin's ability to lower cholesterol and fatty acids.

The finding reinforces some of Lefkowitz's (who has jointly worked with this group) recent research (that demonstrated that beta-arrestins which oftenly work in tandem with G proteins) can sometimes work independently of them and there by initiating their own signals.

The discovery opens the door to the possibility of developing a "biased ligand," a drug that would trigger GP109A, but not the beta-arrestins. Though further studies are essential in this regard, its a good beginning, as the research has achieved the first target i.e., to keep all the lipid-modifying benefits of niacin, but isolate its downside. Congrats Dr. Robert Walters et. al.,

Visualization of single ribonucleic acid in living cell achieved?

Yes says a research group lead by Philip Santangelo, an Asst., Professor in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University. This finding is of importance because of the fact that, this tool will help scientists learn more about how RNA operates within living cells. And more over the researchers have overcome some of the drawbacks of the earlier method like “the need for synthetic RNA or a large number of fluorescent molecules”.

In the study, the probes - produced by attaching a few small fluorescent molecules called fluorophores to a modified nucleic acid sequence and combining the sequences with a protein - exhibited single-molecule sensitivity and allowed the researchers to target and follow native RNA and non-engineered viral RNA in living cells.

The significance of the research lies in the fact that the probes recognize RNA sequences and bind to them using the same base pairing most of us are familiar in regards to DNA, For their experiments, the team used a bacterial toxin to transport the probes into living cells - a delivery technique that when combined with the high affinity of the probes for their targets, required significantly fewer probes than existing techniques. The toxin created several tiny holes in the cell membrane that allowed the probes to enter the cell's cytoplasm and later testing the sensitivity by the conventional fluorescence microscopy to image individual probes inside a cell. More interestingly, they were able to overcome the draw back of earlier method like “accumulation of probes inside a cell”.

With single-molecule sensitivity accomplished, the researchers investigated whether they could visualize individual RNA molecules using the probes. To do this, they simultaneously delivered probes designed to target a human messenger RNA (mRNA) sequence region and a probe designed with no target in the human genome. They were able to image unbound probes of both types as well as individual RNA molecules that had attached to the former probes.

With this the researchers also were, able to observe a process called dynamic RNA-protein co-localization (joining of RNA molecules and RNA binding proteins in a single cell). Congratulations for the group and wish them further success in their endeavor…More..

Successful clinical results for plant-produced insulin....

          On Jan 25th, 2009  I did write a blog on "Insulin from Plants ?".  It has come true now and SemBioSys Genetics  has come up with clinical results for the plant-produced insulin, congrats once again.  The results are of great importance because of the fact that SBS-1000 (produced by SemBioSys, from plant) was bioequivalent to Eli Lilly's Humulin R, a widely-used human insulin in North America, meeting all four of the endpoints outlined below and also SBS-1000 in humans showed pharmacokinetics and pharmacodynamics indistinguishable from Eli Lilly's Humulin R, as SemBioSys had previously shown in animals.

        Though  final analyses regarding safety data are not yet available, the adverse events observed were typical for a study involving recombinant human insulins (Humulin R and Humulin S) . The most common events were insulin injection site reactions, pain at the site of glucose infusion, headache and dizziness, with all similar rates of occurrence for both Humulins and SBS-1000. There were no serious adverse events and there were no events indicative of a systemic allergic response to any of the insulins.  Best of luck for ur further efforts. More....  

Improved synthetic biology for Artemisinin....

We know that Artemision, is a drug to treat multi-drug resistant strains of falciparum malaria. And also fermenting artemisinin via engineered microbes, such as yeast, can be done at far lower costs than extracting the drug from Artemsisia annua , the sweet wormwood tree, making microbial-based artemisinin a much cheaper but equally effective treatment. However the cost of extracting artemisinin from wormwood trees, which only produce the drug under a narrow set of agricultural and climatological conditions or manufacturing it entirely through chemical synthesis is too high. This encouraged Dr. Keasling and his group to undertake this research and are succesful in achieving an improved method, where in the cost will drastically down. And this research is also of great important by the fact that, the same method can be elaborated to make biofuels.

In 2003, they reported their first success. By transplanting genes from yeast and from the sweet wormwood tree into E. coli bacteria and then bypassing the E. coli's metabolic pathway and engineering a new one based on the mevalonate pathway in yeast, they were able to induce the bacteria to produce amorphadiene, a chemical precursor to artemisinin. Even though the yields were low, they achieved one more significance by res using the re-synthesis and other techniques to improve the yield of amorphadiene in E. coli by a million fold. As the conversion of artemisinic acid to artemisinin in high yields are already known, this finding is of great importance.

The most significant part of their reserach is creating a new metabolic pathway in the yeast, similar to the one created in E. coli, then introduced bacterial and wormwood genes into the yeast's DNA that interacted with the yeast's own genes to produce amorphadiene. Finally, they cloned the gene from the wormwood tree that produces the enzyme P450, which the plant uses to convert amorphadiene to artemisinic acid, and expressed it in the amorphadiene-producing yeast strain. And the group wants to use the same technology to make biofuels.... Congrats Dr.Jay D. Keasling...

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...

Mode of action of curcumin establlished ?

In India, turmeric (Haldi-in Hindi, Arishin-in Kannada) has been used in food preparation. Curcumin (see the structure left side, is the principal curcuminoid). We used to read about its many properties like antitumour, antioxidant, antimyloid, antiarthritic and many others. Though scientific explanations were not established, still then our forefathers used turmeric for many centuries. Even it has been used in home remedies for cold, cough and as an antiseptic etc. But so for a little was known about the mode of action or how actually it works inside the body. Thanks to Dr.Rammoorthy, a professor of chemistry and biophysics at University of Michigan, has come up with explanation for this.

The authors claims that "curcumin acts as a disciplinarian, inserting itself into cell membranes and making them more orderly, a move that improves cells' resistance to infection and malignancy. More interesting is the technique they use is solid-state NMR spectroscopy(two-dimensional solid-state NMR technique). This technique which is unique helps to reveal atom-level details of these important molecules and the membranous milieu in which they operate.

In a related line of research, Ramamoorthy's team is using the same methods to investigate the effects of curcumin on the formation of amyloids---clumps of fibrous protein believed to be involved in type 2 diabetes, Alzheimer's disease, Parkinson's disease, and many other maladies. Congrats, Dr.Rammoorthy, for this achievement. If proven further details, hope something intersting and useful info for mankind. More..

Biomarkers for Chikungunya fever .......

Though as we Indians (and more in Karnatak), we might have seen in the last 1-2 years lots of news on Chikungunya. Like raids on many bogus doctors and bogus drugs claiming to treat the disease 100%. Many of us don't even pronounce it correctly, following are the few lines regarding Chikungunya....

Chikungunya (in the Makonde language "that which bends up") virus (CHIKV) is an insect borne virus, of the genus, Alphavirus that is transmitted to humans by virus-carrying Aedes Mosquitoes Originally from Australia, there have been recent outbreaks of CHIKV associated with severe morbidity. CHIKV causes an illness with symptoms similar to dengue fever. CHIKV manifests itself with an acute febrile phase of the illness lasts only two to five days, followed by a prolonged arthralgic disease that affects the joints of the extremities. The pain associated with CHIKV infection of the joints persists for weeks or months.

And also we knew that common laboratory tests for chikungunya include RT-PCR, virus isolation, and serological tests but none of these use to give the severity of CHIKF. Now thanks to a research group from Singapore lead by Dr. Lisa Ng have found three biomarkers for CHIKF, this is really an achievement.

As per the claims by the authors this first comprehensive report, which examines the cellular signals produced as part of the human immune response to Chikungunya virus infection, enables us to understand the changes in molecular signals in the body when infection sets in. These biomarkers can potentially lead to the development of therapeutics to reduce the severity of the disease and halt its progression.

Dr. Ng and her colleagues discovered that an increase in the levels of IL-1β and IL-6, with a concomitant decrease in RANTES, was an indication of a severe form of CHIKF. This finding would allow for quicker and more accurate prognosis of infected patients.

More interestingly the authors found that the level of RANTES was lower in patients with severe CHIKF, as compared to those with dengue. This result could potentially enable physicians and scientists to distinguish quickly between CHIKF and dengue fever - two diseases that present clinically similar symptoms. One more interesting out come of this result is that "cytokines could be used as biomarkers in predicting the severity of the disease". Though further studies are essential, its a significant contribution. Congrats Dr. Ng. More..

http://www.a-star.edu.sg/press_release/attachment/628/Press_release_SIgN-CDC_Chikungunya.pdf

Beware of cell phones of hospital workers !..

I heard from one of my friend a few days back, that a patient who was admitted to a hospital for the treatment for Parkinson disease got infected thro' the medical ventilator. One can imagine the fate of the patient.

Now while reading an article, I found this something strange (but a true fact !) which I want to share with others, this time the culprit here is mobile phone(s).

A Turkey research group lead by Dr. Fatma Ulger, tested the phones of doctors and nurses in hospital operating rooms and intensive care units. They found that almost 95% were contaminated with bacteria of different types (culturing the bacteria from cell phones !), potentially causing infections ranging from relatively minor skin complaints to life-threatening illness. The results are of great importance because of he fact that 'cross-contamination of bacteria between the hands of healthcare workers and their mobile phones' and there by cell phones acting as a reservoir of infection which may facilitate patient-to-patient transmission of bacteria in a hospital setting.

Hope, at least now the concerned authorities take the necessary steps like "strict infection-control procedures, environmental disinfections hand hygiene and decontamination methods are recommended for not only the hand-held electronic devices also for CELL PHONES.....

Phenylbutyrate for treating Alzheimer's Disease !...

We know that Phenylbutyrate is adrug, used to prescribe for patients suffering from alterations in the urea cycle. Now, Ana García-Osta and co-workers have come up with something interseting, sodium phenyl butyrate can be used to treat Alzheimer disease.

Alzheimer's disease is a neurodegenerative disorder associated with age and characterized by the progressive deterioration of cognitive and intellectual abilities. "Cognitive deficit is associated with a loss of neuron connections. For the memory to develop, it is necessary for a series of cellular and molecular mechanisms to be activated. The interruption of these processes affects the capacity to assimilate and store new memories. Since this a drug already established for its toxicity, if the results claimed by Dr. Ana are established and the mechanism of action are studied, hope this research will add one more drug as serendipity and also the much needed help for those sufferings...

Lovastatin for the treatment of degenerative disc disease ?

We know that Lovastatin is a member of the drug class of statins, used for lowering cholesterol (hypolipidemic agent) in those with hypercholesterolemia and so preventing cardiovascular disease. But recentlyDr. Yang and his research group has come up with new innovative idea that Lovastatin, helps the differentiation of disc cells in vitro.

Degenerative disc disease is one of the leading sources of back and neck pain. Disc degeneration is part of the normal aging of the spine. In this condition, the spinal discs (the pillow-like pads between the bones) lose their cushioning. When this happens, it can cause persistent pain in the lower back, legs, neck or arms. Treatments for pain can include medications and physical therapy. Sometimes surgery is needed if the pain is severe and keeps a person from participating in everyday activities.

In their quest to discover ways to stop or reverse degenerative disc disease, orthopaedic researchers have been removing disc tissue from patients who are having spine surgery and extracting cells from that tissue for cultivation in vitro (a controlled environment outside of a living organism). They then transfer the cells back into the patient. Shu-Hua Yang, MD, PhD, is part of a Taiwanese research team that has discovered that Lovastatin, a cholesterol-lowering medication, helps the differentiation of disc cells in vitro.

The results are of great interest : 1. the number of nucleus pulposus cells had increased; 2. Lovastatin increased the synthesis of collagen II, a protein that makes up moveable joints, and decreased the synthesis of collagen I, a protein that is related to fibrosis and 3. Lovastatin had no cytotoxicity (the quality of being toxic) on nucleus pulposus cells..

I think if proven, one more addition to the list of serendipity.......

Though further studeis are essential to establish their claim, its a good beginning..