New TB vaccine ?

         On March 11, I did mention about the improvement for the existing BCG vaccine for tuberculosis. But this is something really interesting a new vaccine (AdAg85A vaccine) for TB, has been developed using a genetically modified adenovirus by a group of researchers lead by Prof. Zhou Xing of McMaster University. 
 

     As we are aware TB ranks second only to HIV among infectious killers worldwide, claiming nearly two million lives annually. The disease is evolving faster than therapies with the emergence in recent years of strains that are resistant to every last one of the antibiotic defences. This reserach is of great importance because of the fact that  new TB vaccine using a genetically modified adenovirus - a virus responsible for the common cold. After removing a small portion of the gene, they inserted part of the TB gene responsible for immunity. It is natural ways of making the body use its own immune machinery.

 

   And going by the claims that (based on all pre-clinical studies carried out on animals, including mice, guinea pigs -who are very prone to TB  and cattle), this vaccine appears to be a very promising candidate vaccine.

  Once they will be able to conlcude (may be after mid April/May), about the safety of the vaccine, this research will go a long way in the history of TB research... Congrats Prof. Xing and group.  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

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.....