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Docking application on aspirin derivatives development
Posted on July 14th, 2010 No commentsDocking analysis is usually used to improve drugable molecules or develop new derivatives from old drugs. Based on this application of docking analysis, scientists from the Department of Bioinformatics at the Bharathiar University in India, generated and validated a series of aspirin analogues that act on prostaglandin H1 enzyme.
Aspirin is a common drug used to treat pain during inflammation. Its properties on platelet aggregation allow its use on thrombosis prevention. Through the analysis of interactions between the small molecule to the active site of the enzyme, they identified the pentanoate group as a possible good binder Thus, they proposed this group as a new type of non- steroidal anti- inflammatory drugs with higher precision on target and fewer side effects. The work has been published on Nature Precedings and it seems really promising. Indeed, COX-1 inhibitors are largely used and their side effects still are quite dangerous. Thus, it should be important to develop safer small molecules. TO this purpose, the molecular docking is a method well validated and it has been previously used to develop several other drugs or improve the existing ones. -
Cyclosporine A and squamous cell carcinoma
Posted on June 23rd, 2010 No commentsCyclosporine A is an immunosuppressive drug currently used after transplantation in order to reduce the risk of rejection. It has been noted that numerous patients who received transplants have been affected by squamous cell carcinomas, with a higher frequency than normal population. The molecular explanation for this so negative side effect of Cyclosporine A has been recently published on Nature journal.
Cyclosporine A seems to block the calcineurin signaling in keratinocytes and such as a block generates in animal model tumors similar to those produced through the injection of squamous cell carcinomas. Scientists demonstrated that chemical block of calcineurin or cyclosporine A treatment has the same effect on cells, both reduce the p53 expression levels, by controlling the activity of ATF3 transcriptional factor. This complex network alters the mechanism of senescence- normally regulated by p53 activity- and impairs apoptosis of too old cells. Thus, the final result is the arising of poorly differentiated tumors, with high proliferative activity. Further research is necessary to better understand the entire process and to find a solution for this side effects of ciclosporin A. It could be possible to block ATF3 and restore the expression of p53, preserving in this way the possibility to use cyclosporine A as an immunosuppressive drug. -
Benefic effects of Thalidomide on vessel maturation
Posted on May 4th, 2010 No commentsThalidomide is an antiemetic drug sadly famous for its dangerous effects during pregnancy. This drug was not tested on right animal model and generated a long series of congenital malformations in babies born from mother that had used it. For several years thalidomide has been forgotten, up to date when it has been studied to treat leprosy and cancer. This month Nature Medicine publishes an interesting paper concerning thalidomide effects on vessel maturation. Scientists from the College de la Santè in Paris and the Curie Institute demonstrated that thalidomide contributed to reduce epistaxis in individuals affected by hereditary hemorrhagic telangiectasia.
This disease is characterized by vessel malformation that leads to frequent hemorrhages and nosebleeds, seriously altering the quality of life. Thalidomide reduced the frequency of nosebleed and increased hemoglobin level. Furthermore, in mice thalidomide induced vessel wall repairing. Molecular mechanism of this process seemed to involve PDGF-B that stimulated mural cells to the activation. Indeed, pharmacological blocking of PDGF signaling pathway reverted the positive effect of thalidomide. In summary, this paper shows a new application of an old drug. Pharmacological research may use this approach to identify new therapies by further investigating old drugs that have been previously approved and tested on humans. -
Acute gastroenteritis in children
Posted on March 29th, 2010 No commentsAcute gastroenteritis affects numerous children at least one time in their infancy and childhood. This disease is usually due to viral infection and none treatment is suggested to treat the infection self. In contrast, more concerns are due to dehydration associated with vomiting and diarrhoea.
Dehydration is treated with oral or intravenous intake of fluid, but generally intravenous treatment is preferred because the high likelihood of emesis may reduce benefits. Anti- emetic drugs are not suggested for children for their important adverse effects. Anyway, several studies have been reported in literature that show the effectiveness of ondansetron, an antagonist of serotonin receptor. This drug has been initially developed to treat nausea following chemotherapy in cancer patients; up to date ondansetron seems also promising to care emesis in children during acute gastroenteritis. The major benefit is the reduction of vomiting episodes that make possible to use also oral rehydration treatment. Furthermore, duration of hospital staying or admission rate are also reduced after ondansetron treatment, showing a financial advantage in comparison to traditional approaches. In conclusion, these studies are very important to demonstrate and ascertain the effectiveness of drugs in children in well structured trials. It’s auspicial that other drugs will be analysed at the same manner. -
Automation in High-throughput screening
Posted on February 5th, 2010 No commentsDrug discovery uses the major amount of its resources for the high throughput screening. Based on specific probabilistic calculation, large experiments in HTS are performed by pharmaceutical and biotech companies to identify some molecules that could become drug after further long analyses. Robots are usually used in this complex process. It’s important that all data are generated in reliable and accurate manner in order to obtain useful results.
Robots can execute some passages: from serial dilution to reaction buffer disposal. In each of these steps, errors could be generated and, giving the small volumes in which HTS is usually performed, robots must be well calibrated in order to exclude the possibility to have this kind of problems. A lot of data arises from an HTS. Data management and statistical analyses are other key- steps for the high throughput screening. Thus, IT systems have not only to control robots to correctly work, but also help scientists to produce meaningful results from raw data. This kind of experiments are highly expensive and can be repeated only strictly necessary times. However, it’s really important to plan the experiment in the correct way and set up robot ant other IT systems involved into the process to obtain more data as possible. -
Pharmacological profile of Marijuana
Posted on November 16th, 2009 No commentsAncient Romains knew some pharmacological effect of Marijuana and have used it in their medicine. In the last time other positive effects have been identified for this plant. Unfortunately cannabis is often used out of medical control and is considered as a drug.
Specially young people prefers Marijuana to other drug, because the most recognized effect on central nervous system is an unusual happiness and appreciation of music, art and in general pleasure; furthermore it gives a relaxing sensation. The pharmacological reason for these effects is the distribution of cannabioidis receptors that are located in brain area involved in tension control, movement control and in the nucleus accumbens that is the pleasure centre of the brain. Marijuana is usually smoked and through this way it’s almost impossible to reach dangerous or lethal dosed from a pharmacological point of view. Of course the abuse of this substance causes a decreased attention that could be really dangerous if you drive. Other collateral effects are nausea and cardiovascular problems specially if it is assumed in presence of other drugs, such as cocaine. No correlation between marijuana and the use of other drugs has been identified, thus marijuana can not be considered as a passage- drug.
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