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

FDA's approval of Iloperidone for schizophrenia....

Iloperidone

We did know about the "azepines" for treatment of schizophrenia, but this is a benzisoxazole derivative something interesting. Iloperidone, 1-[4-[3-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1- piperidinyl]propoxy]-3-methoxyphenyl]ethanone. The advantage, the researcher claims is that, Iloperidone acts on both dopamine and serotonin receptors, making it a favorable choice against competing drugs clozapine and olanzapine. Clinical studies have shown that some patients treated with iloperidone show reduced extrapyramidal symptoms and weight gain. Phase II testing has shown that effectiveness in humans is possible with as low as 8mg per day, and is tolerable up to 32mg per day. The common side effects with this drug are dizziness, dry mouth, fatigue, nasal congestion, sudden fall in blood pressure causing light-headedness upon standing (orthostatic hypotension), drowsiness, rapid heart rate (tachycardia) and weight increase.

Ref :http://www.fda.gov/bbs/topics/NEWS/2009/NEW02009.html

Safinamide for advanced Parkinson's disease.!

Safinamide

We knew that ‘Safinamide” is a candidate drug against Alzheimer's disease. In 2007, a Phase III clinical trial, was started by Merck-Serono for Safinamide as add-on to dopamine agonist for early idiopathic Parkinson's disease. Now thanx to the same companies for having second phase III trial of Safinamide in advanced Parkinson's disease. Interestingly the same compound has been tested for restless legs syndrome (RLS) and epilepsy As of 2008^[update], they are in Phase II.

Safinamide is believed to have a novel dual mechanism of action based on the enhancement of the dopaminergic function (through reversible inhibition of monoamine oxidase-B [MAO-B] and dopamine uptake) and reduction of glutamatergic activity by inhibiting glutamate release.

The earlier trials revealed that safinamide significantly improved motor function in patients with advanced Parkinson's disease. And also the results are encouraging and suggest that safinamide could have benefits beyond motor symptoms. The earlier results not only substantiates the claims but also established something interesting factors like ability of safinamide to improve depressive symptoms are important aspects of PD in addition to the other benefits. Hope after few days safinamide as an add-on therapy to levodopa will come in the market as a boon to those who are mid-to late-stage idiopathic Parkinson's disease (more than five years of disease duration).....

Ref : http://www.merckserono.com/corp.merckserono/en/images/20090507_en_tcm112_41170.pdf

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

A best way to deal with flu pandemic......

We are aware most of the virus and baterii are getting resistance to most of the drugs. I have mentioned in my earlier blog how the virus change their structure (mutation) and become resistant to the drugs being used to treat. Scientists are scared, because many countries have started using Oseltamivir (Tamiflu) for global influenza pandemic. As per a report Tamiflu (oseltamivir) has been stockpiled by many countries anxious to be prepared should a flu pandemic strike, but the problem according to an international team of researchers, is that influenza viruses can become resistant to antiviral drugs, and the widespread use of a single drug is likely to increase the risk that a resistant strain will emerge.

The concern is that if such a strain were to spread widely, the effectiveness of antiviral drugs such as Tamiflu in treating infected patients, as well as their ability to slow the spread of a pandemic, would be greatly reduced. A research group lead by Joseph Wu (University of Hong Kong), claims that they have developed a mathematical model to arrive at a conclusion. The team found that treating just the first 1% of the population in a local epidemic with a secondary drug, rather than with oseltamivir, could substantially delay the development of resistance to oseltamivir and this reduction in resistance was predicted to benefit not only local populations, but also those in distant parts of the world where the pandemic would subsequently spread through air travel and more interesting out come of the research is "in the current emerging swine flu situation, the secondary drug could be Relenza (zanamivir), the only other approved drug to which the new H1N1 strain has been found to be susceptible". This strategy say the researchers could be as effective because it delays use of the primary stockpiled drug until a certain proportion of the local population (about 1.5% according to the model) has been infected with virus that remains susceptible to the primary drug - with drug-sensitive virus in the majority as people recover from infection and develop immunity, only a minority of further infections are likely to be resistant to the primary drug.

The researchers say technically, such a delay could be achieved by postponing the launch of any antiviral intervention, but because even a short delay would mean denying antiviral drugs to people who would benefit from them, the researchers instead propose the deployment of a small stockpile of a secondary antiviral during the early phase of the local epidemic. More.....

Pregabalin for restless legs syndrome?

We know that Pregabalin (S)-3-(aminomethyl)-5-methylhexanoic acid), is an anticonvulsant drug used for neuropathic pain and as an adjunct therapy for partial seizures with or without secondary generalization in adults. It has also been found effective for generalized anxiety disorder and is approved for this use in Europe) and the same compound has been reported as effective treatment of chronic pain in disorders such as fibromyalgia and spinal cord injury

But something new property of this product is being presented in the American Academy of Neurology's 61st Annual Meeting in Seattle (April 25 - May 2, 2009). i.e., the drug can be used as an effective treatment for restless legs syndrome (RLS) and also helps people with the disorder get a better night's sleep.

The 12 week study involved 58 people with RLS. Of the group, 30 people received the drug pregabalin and the rest received placebo. Sleep studies were performed at the beginning and end of the research. Researchers found nearly two-thirds of the people who took pregabalin had no RLS symptoms while taking the drug. For people who still had symptoms, those symptoms had improved by 66 percent while taking the drug, compared to the placebo group where symptoms worsened by 29 percent.

Sleep also improved for those taking pregabalin. The study showed the group spent more time in slow wave sleep, otherwise known as Stage 3 or deep sleep, and they spent less time in the lighter sleep stages known as Stage 1 or Stage 2 sleep compared to those taking placebo. Congrats Dr. Diego Garcia-Borreguero (Director of the Sleep Research Institute in Madrid, Spain) for this achievement. The significance of the research lies in the fact that “compared to all the drugs that are being used to treat RLS , Pregabalin is superior over the others in helping people to get more deep sleep- a main problem with RLS…

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...

Sorafenib and vitamin K combo as anticancer drug against pancreas cancer....

We know that Sorafenib, is a drug approved for the treatment of primary kidney cancer (advanced renal cell carcinoma) and advanced primary liver cancer (heptacellular carcinoma).

Sorafenib is a small molecular inhibitor of several protein kinases. (Protein kinases are overactive in many of the molecular pathways that cause cells to become cancerous. These pathways include Raf kinase, PDGF (platelet-derived growth factor), VEGF receptor and kinases and c Kit the receptor for Stem cell factor. A growing number of drugs target most of these pathways). Sorafenib is unique in targeting the Raf/Mek/Erk pathway. After the FDA (US), approval in 2005 & European Commission in 2006, the drug was used to treat both forms of cancers. Now something interesting has been achieved by Dr. Brian Carr (a professor of Medical Oncology at the Jefferson Medical College of Thomas Jefferson University). Vitamin K1 or vitamin K2, plus sorafenib (Nexavar) each have shown activity against the growth of human cancer cells by inhibiting the extracellular signal-regulated kinase (ERK) pathway. The basis for the research lies in the fact that, sorafenib has demonstrated success at extending survival in patients with hepatocellular carcinoma (HCC, or primary liver cancer), hand-foot syndrome is a common adverse effect that affects approximately 20 percent of patients who receive the drug. It typically manifests as painful sores on the soles of patients' feet that can prevent the patients from walking, Dr. Carr said. Profound tiredness and weight loss is also seen in at least 30 percent of patients.

The research is of great significance because of the fact that in the pancreas cancer study, Dr. Carr and his colleagues tested each K vitamin in combination with sorafenib in pancreatic cell lines. Each combination inhibited cell growth, induced cell death and decreased the expression of ERK. They found that when combining vitamin K and sorafenib, the sorafenib dose required for inhibiting cancer cell growth decreased by more than 50 percent. The conclusions are really great 1. The dose required is reduced to half; 2. reduced side effects and 3. vitamin an established drug, no need of toxicological studies.... Congrats, Dr. Dr. Brian Carr and group..

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......

Synthesis of Serratezomine A (an alkaloid)...

As synthetic chemists we are aware that, how difficult is to syntheize the natural products with lots of stereochemistry involved. Congrats Dr. Jeffrey N. Johnston et.al., for their achievement in synthesising Serratezomine A. Serratezomine A is the natural compound (alkaloid), found in Lycopodium serratum(flowerless plant used in homeopathic medicine to treat a wide variety of ailments).

The longest linear sequence in the Serratezomine A synthesis is 15 steps and it has an overall yield of 1.7 percent, Johnston says. That is an average yield of 77 percent per step. The chemists kept the sequence this short by using a strategy called convergence. They prepared one of the key fragments in the synthesis in parallel to the main sequence.

It took six years to develop the process because the researchers had to invent some entirely new chemical methods to complete the synthesis. These methods should make it easier to synthesize other Lycopodium alkaloids as well as other natural compounds with therapeutic potential. The same compound is being tested for its anticancer activity. Congrats Dr. Jeffrey.. The resarch finds its importance because of its synthetic novelty....

Source:http://www.vanderbilt.edu/exploration/text/index.php?action=view_section&id=1487&story_id=367&images=

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 ....

Oral Etoricoxib as post surgery drug?

Developed as an alternative to conventional non-steroidal anti-inflammatory drugs (NSAIDs), which can cause intestinal bleeding, "coxibs" are licensed for chronic and acute pain.

Single dose oral etoricoxib produces high levels of good quality pain relief after surgery, says lead researcher Andrew Moore, of the Pain Research and Nuffield Department of Anaesthetics at the University of Oxford.Moore adds that the long lasting action of etoricoxib makes it qualitatively different from other coxibs and ibuprofen. A longer time before remedication is likely to benefit patients by providing long-lasting pain relief. More...