Current pharmaceutical design
-
The DNA mismatch repair system maintains genomic stability by correcting DNA sequence errors generated during DNA replication, during genetic exchanges between chromosomes i.e., recombination, and by correcting DNA lesions caused by mutagenic agents such as cis-platinum. Post-synthesis mismatch repair improves almost 1000-fold the fidelity of DNA replication; however, the functions of mismatch repair proteins extend well beyond DNA repair. ⋯ Hence, mismatch repair proteins regulate the survival threshold to DNA damage, and this function provides a novel platform for understanding the role of mismatch repair in B cells, in tumor formation, as well as in resistance to chemotherapy. In this communication, we review how mismatch repair may contribute to the physiology of cells and may be regulated by the intracellular trafficking of mismatch repair proteins.
-
Propofol (2, 6-diisopropylphenol) is a potent intravenous hypnotic agent which is widely used for the induction and maintenance of anesthesia and for sedation in the intensive care unit. Propofol is an oil at room temperature and insoluble in aqueous solution. Present formulations consists of 1% or 2% (w/v) propofol, 10% soybean oil, 2.25% glycerol, and 1.2% egg phosphatide. ⋯ In addition, this formulation has been demonstrated to result in the generation of oxygen free radicals. High dose propofol infusions have been associated with the "propofol syndrome"; this is a potentially fatal complication characterized by severe metabolic acidosis and circulatory collapse. This is a rare complication first reported in pediatric patients and believed to be due to decreased transmembrane electrical potential and alteration of electron transport across the inner mitochondrial membrane.
-
Direct visualization of the composition of the atherosclerotic plaque during its natural history and after therapeutic intervention may be helpful in detecting lesions with high risk of acute events and in understanding progression and regression of the disease. A wide variety of invasive and non-invasive imaging techniques is available to detect clue aspects of atherosclerosis from the early stage to the clinical evidence appearance. ⋯ Afterward, we will discuss in detail the use of high-resolution, multi-contrast magnetic resonance imaging for non-invasive imaging of the plaque and its characterization in terms of its various components (i.e., thickness, lipid, fibrous, calcium, or thrombus). Finally, we will describe the potential of quantitative analysis in describing of plaque constituents with improved reproducibility.
-
Several clinical trials have attempted to treat sepsis by blocking certain aspects of the inflammatory response. Tumor necrosis factor and interleukin 1 have been specific targets for inhibition but none of the trials have been successful. These trials were started on the basis of preclinical trials that suggested these would be effective. ⋯ However, before new clinical trials are started there must be careful consideration of why previous interventions were not effective. The concept of blocking a single elevated cytokine may be too simple to deal with the complex problem of sepsis. As patients move through different phases of the septic response, there may be intervals when it is appropriate to inhibit multiple cytokines while at other times it may be appropriate to augment the immune response.
-
The hypertensive disorders of pregnancy complicate 5-10% of pregnancies. Of these disorders 70% are pregnancy related (preeclampsia-eclampsia and gestation hypertension) and 30 % are a pre-existing hypertensive condition (chronic hypertension). These disorders are associated with maternal and fetal complications and have a substantial economic impact. ⋯ The choice of the antihypertensive agents depends on individual clinician preference, the specified maternal and foetal benefits and the reproductive complications (teratogenisity, fetotoxicity and neonatal toxicity) of each particular agent. There are unequivocal evidences that Magnesium sulphate is superior to other agents in reducing recurrent eclamptic seizures. There is a strong recent evidence recommended that magnesium sulphate should be considered for women with pre-eclampsia for whom there is concern about the risk of eclampsia.