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

Chloroquine as antiviral agent !

We all knew that chloroquine derivatives are better known as antimalarials, but something new chloroquine can be used as antiviral agent? yes says a group of researchers lead by Dr. Moscona and that too against the two lethal viruses Hendra and Nipah.

The research is significant because of the fact that the two henipaviruses that are the subject of the study are Hendra Virus (HeV) and Nipah Virus (NiV) emerged during the 1990s in Australia and Southeast Asia. (Spread via fruit bats, and they did cause potentially fatal encephalitis and respiratory disease in humans, with a devastating 75 percent fatality rate.) More recently, NiV outbreaks in Bangladesh involving human-to-human transmission have focused attention on NiV as a global health concern. One more interesting fact of this research is chloroquine is already an established drug for malaria and its the cheap drug too.

Like the avian flu, SARS, and Ebola viruses Hendra and Nipah are zoonotic pathogens (originating in certain animals but can jump between animal species and between animals and humans). There are currently no vaccines or treatments against the two henipaviruses, which are listed by the U.S. government as possible bioterror agents.

The aproach of this research group is interesting and also of greater importance because the mode of action of chloroquine is (as explained by the authors) it block the action of a key enzyme, called cathepsin L, which is essential to the virus's growth and maturation. Without this enzyme, newly formed Hendra or Nipah viruses cannot process the protein that permits the viruses to fuse with the host cell. Newly formed viruses then cannot spread the infection; in other words, they can invade, but cannot cause disease.

The authors also claim the fact that "several other zoonotic viruses depend on cathepsin L - most notably, Ebola. Our findings, and our methods, could easily be applied to the study of Ebola and other emerging diseases" .

Congrats Dr. Moscona and group for this acheivement. ...

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..

Omega-3 Fatty Acids for protecting the liver from damage caused by obesity and the insulin resistance it provoke...

(1)--alpha-linolenic acid (ALA),


(2)-eicosapentaenoic acid (EPA)





(3)-docosahexaenoic acid (DHA)

According to a recent study by Dr. Joan Claria and co workers, diets rich in omega-3 fatty acids (1, 2 & 3) protect the liver from damage caused by obesity and the insulin resistance it provokes. This research should give doctors and nutritionists valuable information when recommending and formulating weight-loss diets and help explain why some obese patients are more likely to suffer some complications associated with obesity. Omega-3 fatty acids can be found in canola oil and fish.

The researchers found that lipids called protectins and resolvins derived from omega-3 fatty acids can actually reduce the instance of liver complications, such as hepatic steatosis and insulin resistance, in obese people. The group claims that, two types of lipids in omega-3 fatty acids—protectins and resolvins—were the cause of the protective effect. These results are based on animal models of testing and hope this info will help dieticin to prepare list of diets to reduce the obesity, with reduced complications to the liver. More....

Two step chemical process for Biofuel.!..

In one of my earlier blog article, have written about how a modified e-coli is used to make biofuel, but this time by chemical reaction that too in only two steps!. Something interesting, the key to the new process is the first step, in which cellulose is converted into the "platform" chemical 5-hydroxymethylfurfural (HMF), from which a variety of valuable commodity chemicals can be made. The significance of this research is in the fact that most of the groups have tried to either fructose/glucose, but this group lead by Dr. Ronald Raines, have tried to it starting from cellulose itself. The researchers have developed a unique solvent system, that makes this conversion possible. The special mix of solvents and additives, for which a patent is pending, has an extraordinary capacity to dissolve cellulose, the long chains of energy-rich sugar molecules found in plant material. Because cellulose is one of the most abundant organic substances on the planet, it is widely seen as a promising alternative to fossil fuels.

This solvent system can dissolve cotton balls, which are pure cellulose," says Raines. "And it's a simple system—not corrosive, dangerous, expensive or stinky.

This approach simultaneously bypasses another vexing problem: lignin, the glue that holds plant cell walls together. Often described as intractable, lignin molecules act like a cage protecting the cellulose they surround. However, Raines and Binder used chemicals small enough to slip between the lignin molecules, where they work to dissolve the cellulose, cleave it into its component pieces and then convert those pieces into HMF. In step two, Raines and Binder subsequently converted HMF into the promising biofuel 2,5-dimethylfuran (DMF). Though the over all yield is still to be improved, its a good beginning. Congrats Dr. Raines. More....

Vitamin B12 as an effective 'Canker Sore Therapy' ..

I used to wonder why, the medical practitioners recommend Vitamin B12 for canker sores, now thanks to the research group lead by Dr. Ilia Volkov, have confirmed the fact that a nightly dose of vitamin B12 is a simple, effective and low risk therapy to prevent Recurrent Aphthous Stomatitis (RAS), better known as "canker sores." In India vitamin B12, is available as OTC.

The researchers tested the effect of vitamin B12 on 58 randomly selected RAS patients who received either a dose of 1,000 mcg of B12 by mouth at bedtime or a placebo, and were tested monthly for six months. Approximately three quarters (74 percent) of the patients of the treated group and only a third (32 percent) of the control group achieved remission at the end of the study.

The results are of important by the fact that the average outbreak duration and the average number of ulcers per month decreased in both groups during the first four months of the trial. However, the duration of outbreaks, the number of ulcers, and the level of pain were reduced significantly at five and six months of treatment with vitamin B12, regardless of initial vitamin B12 levels in the blood. During the last month of treatment a significant number of participants in the intervention group reached 'no aphthous ulcers status' (74.1% vs 32.0%; P < .01) and not only becoz., of the statistical significance and also this treatment is simple and inexpensive and has no known significant toxic effects. More....

New Electrode Material for (Lithium-Ion Batteries) Better Performance ......

Everything nanotech.....its really interesting, now its the turn of Lithium-Ion batteries. Rice University researchers lead by Pulickel Ajayan, have achieved this significant milestone. With increasing demand for battery technology high on the list of priorities in a world demanding electric cars and gadgets that last longer between charges, such innovations are key to the future. This research wherein 'nanotubes were grown to look – and act – like the coaxial conducting lines used in cables. The coax tubes consisted of a manganese oxide shell and a highly conductive nanotube core.

The researchers put in two materials – the nanotube, which is highly electrically conducting and can also absorb lithium, and the manganese oxide, which has very high capacity but poor electrical conductivity, but combined together one get something interesting. And there by one can enhance the number of charge/discharge cycles, with a larger capacity.

The most significance of this research, is the coaxial cable design of these materials that offers improved performance as electrodes for lithium batteries over the other combination. Though further study is essential to substantiate the claim. Its a good beginning..

Ref : http://pubs.acs.org/doi/full/10.1021/nl803081j.

Oncostatin M- as antiviral (viral Hepatitis) and anti cancer agent ?

Oncostatin M, is a pleitropic cytokine that belongs to the Interleukin 6 group of cytokines. Of these cytokines it most closely resembles Leukemia inhibitory factor (LIF) in both structure and function. And this has been establisehd now Dr. Jesús Prieto. And not only Oncostatin M, has anticancer activity, it has got antiviral (Viral Hepatitis) activity also.

Explaination given by the researcher is interesting and has significant too.

When organisms suffer a viral infection, dendritic cells (natural proteins produced as a response of the immune system to foreign agents) release type I interferon. The researchers of the CIMA observed that dendritic cells also produced Oncostatin M. "What was remarkable was the evidence that Oncostatin improved the effect of interferon in inhibiting the replication of viruses as well as noticeably increasing the antiviral response of the immune system.

These findings suggest that the combination of both molecules may be useful for treating viral diseases that do not respond to isolated treatment with interferon, something which occurs in patients with viral B or C chronic hepatitis. "In addition, it is possible that this combination could be effective for designing strategies against different tumor processes in which conventional therapy is unsuccessful.

Source : http://www.basqueresearch.com/berria_irakurri.asp?hizk=I&Berri_Kod=2072

An additional tool to improve Drug Design !...

Gone are those days, when we used to kill so many albino mice/rats or guinea pigs for testing compounds for their pharmacological properties. Thanks for the innovative ideas of molecular modeling and their by knowing the mechanism of actions. So now if we know the structures of enzymes or protiens, we can test the activities by photometric analysers. Even in this type of the discovery, the methods were trial and error methods only. Its really interesting, now like a tailor measures up a person for a suit, its possible to measure accurate dimensions of proteins called membrane receptors, which makes this research more significant and hope this will go a long way in the history of drug discovery and for rational drug design with broader life sciences applications.

The method, called Differential Aberration Correction (DAC) microscopy, measures distances at the molecular level in two and three dimensions using conventional fluorescence microscopy. The special feature of this method is that one can measure proteins in solution, which is how they exist in nature, instead of using coated or crystallised proteins as other techniques do.

Proteins sit on cell boundaries, acting as gate-keepers, and they represent a class of biomolecules targetted by over 50 per cent of pharmaceuticals and hope this discovery of understanding the complex structures of these molecules and how new drugs affect their structure will help drug companies design more effective pharmaceuticals.

DAC microscopy is an improvement on an older technology, called FRET, which can measure distances from 1-10 nanometres. DAC can measure 1-250 nanometres, giving a more complete picture of drug-membrane receptor interactions. It will complement other techniques like X-ray crystallography and there by further substantiating the concclusions. As per Dr Vallotton, the DAC software was tested using fluorescent polystyrene microspheres only 100 nm across – about one thousandth the width of a hair. Hats off, to the group for this achivement. More detials with video demo .....

Vigabatrin to treat infantile spasm ?

We know that Vigabatrin, is an antiepiletic agent. Epilepsy can be repressed if the serum level of -Aminobutyric Acid, (GABA) is increased. Vigabatrin is an irreversible inhibitor of GABA transminase (GABA-T), the enzyme responsible for the catabolism of GABA. The mechanism of the Vigabatrin, is attributed to an irreversible inhibition of GABA-T and consequently increased level of GABA.

Its use, has been limited in many countries because it has been shown to cause a permanent narrowing of visual fields in approximately 40 percent of adults who have been exposed at school age or later.

However a new study has showed this drug can be used to treat infantile spasm.

The findings show that the risk of permanent visual field defects caused by VGB may be lower for treatments in infants than in adults. The cumulative VGB doses and treatment durations in the study were, on average, lower than in previous studies, which correspond to the much younger age and weight of the tested patients. Hope these results may encourage doctors to use vigabatrin to treat infantile spasms as the risk for visual field damage may be relatively low in many children compared to the risks caused by continuous seizures. Congarts Dr. Eija Gaily and co workers.....

Genetic basis of psoriasis revealed.....

As we know psoriasis, an autoimmune disease that occurs when the body's immune cells mistakenly attack the skin, is becoming more problematic with nearly 10 to 30 percent of patients (an estimated 7 million people suffer from psoriasis in US) with psoriasis develop psoriatic arthritis. which occurs when inflammation attacks the joints, causing pain and disability. Thanks to Dr. Anne Bowcock, a professor of genetics at Washington University School of Medicine in St. Louisand and his group have made significant gains in understanding the genetic basis of psoriasis, a chronic skin condition that can be debilitating in some patients.

This basic understanding of psoriasis is of significance becoz of the fact that, now one will be able target treatments to psoriasis patients based on the genetic alterations that have contributed to their disease. The two groups (Bowcock and her colleagues in Spain) found that the absence of two skin genes - LCE3B and LCE3C - increases the risk of psoriasis.

Both genes normally are activated after an injury to the skin. The researches suspect the absence of the genes could lead to an inappropriate immune response, which may cause the inflammation that is a hallmark of the disease. Until now, all of the genes linked to psoriasis have been involved in the immune system. But psoriasis is a disease of the immune system and the skin, and it makes sense that we would eventually find genes in the skin that are involved in the disease.

Though the new variants uncovered by the researchers each make only a small contribution to the overall genetic risk of the psoriasis, its a good beginning. This finding is important, because newly discovered variants have been associated with other inflammatory diseases such as Crohn's disease and autoimmune diseases like rheumatoid arthritis and lupus. Hope additional studies will help to tease apart the ways in which these diseases are connected at the level of DNA and this information will also aid in the search for more targeted drugs that can zero in on particular genetic defects that cause the diseases. More....

For Psoriasis picture, see the slide no., 4 of slide show of skin problems.