Anti-IgE in allergic asthma and rhinitis: an update

Allergic asthma and rhinitis imposes a huge burden in terms of treatment costs, productivity loss and hospital admissions. IgE plays a significant role in the manifestation of these conditions and the identification of a monoclonal antibody that binds to IgE provides clinicians another therapeutic strategy in the management of these conditions. Blocking the effects of IgE by omalizumab, a recombinant humanized monoclonal antibody that selectively binds to IgE has been shown to be a useful adjunct in the treatment of allergic asthma and rhinitis. Omalizumab is effective as a steroid reducing agent in patients with severe asthma and is successful in decreasing asthma exacerbations. Omalizumab was well tolerated in clinical trials, however, the potential long-term side effects need careful monitoring. The high cost of the molecule could make this a therapeutic option in a small proportion of patients in whom there is a large unmet need.     

Effects of methotrexate on folates in Krebs ascites and L1210 murine leukemia cells

Changes in reduced folates upon exposure of Krebs ascites cells and L1210 murine leukemia cells to methotrexate (MTX) have been measured by stoichiometric entrapment of tissue methylenetetrahydrofolate into a stable ternary complex with thymidylate synthase and tritiated 5-fluoro-2'-deoxy-uridine-5'-monophosphate. Tetrahydrofolate and 5-methyltetrahydrofolate were determined after conversion to methylenetetrahydrofolate. In both tumor cell lines, treatment with methotrexate at levels which had little effect on methylenetetrahydrofolate and tetrahydrofolate concentrations resulted in nearly complete elimination of the methyltetrahydrofolate pool. Thus, an initial effect of methotrexate on folate metabolism appears to be on methyltetrahydrofolate.     

Mechanisms of tissue damage resulting from the use of oral water irrigation devices

Oral water irrigation devices (WIDs) are widely used for oral physiotherapy in homes and dental clinics throughout the world. A major area of concern in the use of WIDs has been the possibility of injury to the sulcular epithelium and underlying tissue. There are several documented clinical cases of tissue injury with the use of WIDs. The existing WIDs exert excessive pressures on the sulcular epithelium. Although it is known that the high jet impact pressures exerted by the WIDs cause the tissue damage, the underlying damage mechanisms are poorly understood. The damage to the sulcular epithelium and underlying tissue is mediated through several physiological and micromechanical processes and includes, among others, the following damage mechanisms: pressure-induced, diffusion-mediated, deposition of bacteria and toxins into the underlying tissue, damage to the collagen network integrity in the tissue, damage to the blood and lymphatic microcirculation, especially damage to the anchoring filaments attached to the terminal lymphatic wall, and direct mechanical damage due to abnormal shear forces induced by the jet. All these damage processes could lead to tissue necrosis.     

Allele and genotype frequency of MDR1 C3435T in Tamilian population

The allele and genotype frequencies of MDR1 C3435T polymorphism were determined in 185 unrelated healthy Tamilians. The genomic DNA was extracted from peripheral leucocytes using phenol chloroform method and genotyped by PCR-RFLP method. The frequencies of MDR1 C3435 and T3435 alleles in Tamilian population were 0.46 and 0.54 respectively. The distribution of T3435 in this population was found to be greater than Africans and almost similar to Caucasians and Orientals. The distribution of CC, CT and TT genotypes was 0.18, 0.56 and 0.26 respectively. The frequency distribution of the CC genotype was lower in them when compared with Chinese and Africans whereas CT genotype was higher in comparison with all the major ethnic groups.     

Influence of CYP2C9 and CYP2C19 genetic polymorphisms on phenytoin-induced neurological toxicity in Indian epileptic patients

Objective  

Cytochrome P450 2C9 and 2C19 (CYP2C9 and CYP2C19, respectively) genetic polymorphisms play an important role in phenytoin (PHT) metabolism. We have evaluated whether these genetic polymorphisms have an effect on PHT-induced neurological toxicity in Tamilian (ethnic group native to southern India) patients with epilepsy.