Thursday, April 30, 2009

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....

Sunday, April 26, 2009

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..

Friday, April 24, 2009

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......

Wednesday, April 22, 2009

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=

Tuesday, April 21, 2009

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 ....

Sunday, April 19, 2009

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...

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……