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……

Broccoli sprouts may help prevent stomach cancer !

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

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

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

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

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

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

New hope for patients suffering from Parkinson’s Disease ?

A novel method for the treatment of patients suffering from parkinson's disease (and probably will be the first of its kind in the history of the treatment of Parkinson's disease- if established) has been achieved by Dr. Miguel Nicolelis, Deane Professor of Neuroscience at Duke. The research is of great importance becoz., of the fact that the researchers have developed a prosthetic device that applies electrical stimulation to the dorsal column in the spinal cord (which is a main sensory pathway carrying tactile information from the body to the brain). The device was attached to the surface of the spinal cord in mice and rats with depleted levels of the chemical dopamine - mimicking the biologic characteristics of someone with Parkinson's disease along with the impaired motor skills seen in advanced stages of the disease. When the device was turned on, the dopamine-depleted animals' slow, stiff movements were replaced with the active behaviors of healthy mice and rats. Improved movement was typically observed within 3.35 seconds after stimulation.

More interesting about this research is the fact, when the device was used without additional medication, Parkinsonian animals were 26 times more active. When stimulation was coupled with medication, only two L-DOPA doses were needed to produce movement compared to five doses when the medication was used by itself. When I talked to a Physiotherapist, he was also unaware of the basis behind this invention. But the explaination given by the authors is something interesting and justifies it i.e., the rhythmic brain activity in the animals with Parkinson's disease resembled the mild, continuous, low-frequency seizures that are seen in those with epilepsy. One effective therapy for treating epilepsy involves stimulating the peripheral nerves, which facilitate communication between the spinal cord and the body. Researchers took that concept and developed a modified approach for a Parkinson's disease model. The low frequency seizures, or oscillations, seen in the animal model of Parkinson's disease have been observed in humans with the condition. Stimulating the dorsal column of the spinal cord reduces these oscillations, which researchers believe creates the ability to produce motor function. Congrats Dr. Nicole, and hope with more studies this method becomes a ray of hope for those sufferers..

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..

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. ...

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....

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....

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.....

Nano-insulin pill ?

In my earlier blog, I wrote about the use of nanoparticles in the field of Pharmaceutical will happen in the near future. But I didn’t expect it to happen so fast. Thanks to Dr.Chandra Sharma (of Sree Chitra Tirunal Institute for Medical Science & Technology, Kerala, India) for his success in achieving this fete so fast. Its something interesting, becoz, he has chosen the field of diabetic treatment. I think this research, will be a boon to the number of insulin dependent patients (40% of 135 million people) once established in human trials. Hope this research, will lead to other drugs with nanoparticle coating for more efficacy and reduced side effects.

The minute nanoparticles are smaller than 100 nanometres across and attract water on the inside and are water-repelling on the outside - when they reach the bloodstream they break down in response to the pH of blood and then release the insulin.

The animal experiments demonstrated that the nanoparticles enter the bloodstream and end up in organs such as the liver and kidney and in diabetic pigs showed the pill containing the nanoparticles led to control of blood glucose after eating. Though the results are encouraging in the animal models, have to be established in human beings and also most importantly the impact of nanoparticles in human beings has to be studied thoroughly, so that a concrete and conclusive evidence will happen in the coming days. I hope this will research will open flood gate for other drugs with nanoparticles coating. More....

Diverse use of Nucleic acids.....

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. The design of nucleic acids, particularly oligonucleotides, for in vivo delivery requires consideration of various factors including binding strength, target specificity, serum stability, resistance to nucleases and cellular uptake. A number of approaches have been proposed in order to produce oligonucleotides that have characteristics suitable for in vivo use, such as modified backbone chemistry, formulation in delivery vehicles and conjugation to various other moieties. Therapeutic oligonucleotides with characteristics suitable for systemic delivery would be particularly beneficial.

There are many oligonucleotides with modified chemical backbones, like peptide nucleic acids (PNAs), locked nucleic acids (LNAs), methylphosphonates, phosphoramidates and thiophosphoramidates. Each of these types of oligonucleotides has reported advantages and disadvantages. For example, peptide nucleic acids (PNAs) display good nuclease resistance and binding strength, but have reduced cellular uptake in test cultures; phosphorothioates display good nuclease resistance and solubility, but are typically synthesized as P-chiral mixtures and display several sequence- non-specific biological effects; methylphosphonates display good nuclease resistance and cellular uptake, but are also typically synthesized as P-chiral mixtures and have reduced duplex stability.

The N3'-P5'phosphoramidate internucleoside linkages are reported to display favorable binding properties, nuclease resistance, and solubility (I did work for quite some time in this field and I had opportunity to interact with Dr. Sergei Gryaznov and group). Though this field is getting wider and wider with many companies trying with some innovative ideas, the real concern in this field is that the polyanionic nature of oligonucleotides reduces the ability of the compound to cross lipid membranes, limiting the efficiency of cellular uptake.But thanks to many other groups they are trying to concentrating on this issue and hope there will be may drugs in the days to come. There are many drugs already in the market by ISIS and Geron corporation has many patents to its credit in the many patents for its novel work (Dr.Sergei, Dr.Cristzina Pongracz and many others have lot of work in this field) N3'-P5'phosphoramidate internucleoside linkages. Though there were a few players in this field of nucleic acids(5-6 years' back), now a days when ever I read any medicinal chemistry news, I do find lot many companies contributing to this field of nucleic acids. Hope there will be many drugs from this field with reduced side effects....

An abondoned anticancer drug's rebirth...

α-Difluoromethylornithine or DFMO, which was developed as a cancer therapy and later shelved because of toxicity concerns, has been around since the 1970s. But over the past five years, it has undergone a rebirth as a chemoprevention agent, first showing efficacy in animal models of human cancer and more recently in human prostate and colon cancer. A recent study shows that it likely works in a large cast of tumors, even those having poor prognosis, like high-risk neuroblastoma (a childhood malignancy of the sympathetic nervous system, that accounts for accounts for nearly eight percent of all childhood cancers and 15 percent of pediatric cancer-related deaths. Its solid tumors arise from developing nerve cells, most commonly in the adrenal gland, but also in the abdomen, neck, and chest. Neuroblastoma usually occurs in infants and young children, appearing twice as frequently during the first year of life than in the second.

The best-known genetic alteration involved in neuroblastoma is the amplification of the proto-oncogene—a molecule that when overexpressed can cause cancer—called MYCN. Amplification of MYCN occurs in about 20 percent of all neuroblastoma and is associated with the high-risk form of the disease. Targeting this and related genes directly might be therapeutically tempting, the study noted, but highly problematic because the oncoproteins they produce are also required for the growth of most normal cell types. And that is why Dr. John Cleveland and colleagues focused on inhibiting ornithine decarboxylase (Odc), a protein that contributes to cancer cell growth and that is a target of the proto-oncogene MYCN. Increased levels of Odc are common in cancer, and forced Odc expression in animal models has been shown to lead to increased tumor incidence. Recent findings have shown that Odc overexpression is also an indication of poor prognosis in neuroblastoma. DFMO, the drug used by the Cleveland team, inhibits the activity of Odc. One mor interesting is at lower dose the drug is specific and it has impact on Odc only. Though the toxicity ealrier reported has to be still ascertained, it may be time to revisit the issue as the study showed that transient treatment with DFMO is sufficient to provide chemoprevention and may show benefit for this otherwise lethal malignancy. Hope the detailed study will have something inthe near future....