Metronidazole (MNZ), a widely used therapeutic drug, was administered to male and female Swiss mice intragastrically at a dose of 2 mg MNZ/mouse per day, 5 days a week, every alternate week, throughout their life span to test its carcinogenicity. The treatment induced a significant increase in the overall incidence of tumors in female mice but not in male mice. At the same dose, no teratogenic effect was observed. Perinatal carcinogenicity was studied by following up animals till the end of the F2 generation. Though different groups of animals were considered, a significant increase in tumor incidence was observed only in F1 mice which received MNZ treatment during gestation as compared to the corresponding control mice which received distilled water. The F1 mice which received MNZ during gestation, lactation, and subsequently in adulthood, and the F2 progeny had a tumor incidence comparable to that observed in control mice.
The role of host genetic factors in the pathogenesis and outcome of hepatitis B virus (HBV) infection is not well known.We assessed the association of HLA and TNF (rs361525, rs1800629, rs1799724, rs1800630 and rs1799964) polymorphisms with HBV outcome in the South Indian population. Association of HLA polymorphism was analyzed in 90 individuals from each group, that is, spontaneous recovery (SR) and chronic-HBV (C-HBV) infection. The role of TNF polymorphisms was evaluated in 150 subjects with SR and 137 patients with C-HBV infection. After adjusting for age and sex, HLA-DRB1*07:01 was strongly associated with chronicity (corrected P-value (pc) o0.005, odds ratio (OR) 3.76, 95% confidence interval (CI) 1.84-7.68). The rs1800630 genotype was associated with HBV outcome in codominant (pco0.01, OR ¼ 1.99, 95% CI 1.30-3.05) and dominant (pco0.01, OR ¼ 2.28, 95% CI 1.35-3.84) analyzing models after adjusting for age and sex. Similarly, the rs1799964 genotype was associated with HBV outcome in codominant (pc ¼ 0.01, OR ¼ 1.57, 95% CI 1.09-2.27) and dominant (pco0.01, OR ¼ 2.21, 95% CI 1.27-3.83) analyzing models. Haplotype analysis (rs1799964/rs1800630/rs1799724/rs1800629/rs361525) revealed that the CACGG haplotype was strongly associated with C-HBV infection (P ¼ 0.0004). Our study suggests that inheritance of HLA and TNF polymorphisms might explain the outcome of HBV infection in the South Indian population.
Two cases are described of previously unreported false positivity on the Luminex crossmatch assay due to non HLA specific antibodies directed against the beads. In both cases the Luminex crossmatch indicated the presence of donor specific antibodies to class II HLA antigens, which was not substantiated by the clinical scenario or other assays. We could demonstrate the non specificity of these antibodies through using the same assay in a modified form where beads were unexposed to cell lysate and therefore did not carry HLA antigens at all. These cases further serve to emphasize the absolute necessity of correlating positive results with the priming history, and confirming their relevance using other platforms.
Our findings suggest that non-response to HBV vaccine is not a major impediment to prevent HAHI. Robust seroprotection rates can be achieved using this indigenous HBV vaccine. However, gender and BMI might influence the level of anti-HBs titers. We recommend the use of this cost effective HBV vaccine as well as postvaccination anti-HBs testing to prevent HAHI among HCWs.
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