Strain differences in histopathological features of lymphoid tissues of SD and F344 rats in a T cell-dependent antibody response assay of cyclophosphamide.

When conducting histopathological evaluation of lymphoid tissues, it is necessary to know the variability and strain differences in histological features of different sites of lymphoid tissues. To investigate in detail the variability of lymphoid tissues and strain differences of control rats as well as those of immune reactivity and sensitivity to immunosuppression, we performed a histopathological analysis of various lymphoid tissues in conjunction with the evaluation of immune function in a T cell-dependent antibody response (TDAR) assay with cyclophosphamide (CP) in Sprague Dawley (SD) and F344 rats. Six-week-old male SD and F344 rats were orally treated with CP at 0 (control) or 4 mg/kg/day for 28 days; keyhole limpet hemocyanin (KLH) was introduced intravenously on Days 14 and 23, and the serum concentrations of anti-KLH antibodies were measured.

Influence of the estrus cycle on the evaluation of a vaginal irritation study in intact and ovariectomized rats.

When conducting vaginal irritation studies, ovariectomized rats or rabbits are typically used according to practical reports. In the present study, we evaluated the influence of the estrus cycle in a vaginal irritation study using intact rats and ovariectomized rats, which exhibit a late diestrus-like condition, to determine whether intact rats can be useful for evaluating vaginal irritancy. Rats were divided into 4 groups: proestrus, estrus, and metestrus or diestrus in intact rats and ovariectomized rats.

Multi-step virtual screening to develop selective DYRK1A inhibitors.

Developing selective inhibitors for a particular kinase remains a major challenge in kinase-targeted drug discovery. Here we performed a multi-step virtual screening for dual-specificity tyrosine-phosphorylation-regulated kinase 1A (DYRK1A) inhibitors by focusing on the selectivity for DYRK1A over cyclin-dependent kinase 5 (CDK5). To examine the key factors contributing to the selectivity, we constructed logistic regression models to discriminate between actives and inactives for DYRK1A and CDK5, respectively, using residue-based binding free energies.

Superoxide dismutase deficiency enhances superoxide levels in brain tissues during oxygenation and hypoxia-reoxygenation.

To determine whether the mitochondria or cytoplasm produces superoxide during ischemia-reperfusion of the brain, we analyzed lucigenine-enhanced chemiluminescence emission in slices of brain tissue prepared from manganese-superoxide dismutase (Mn-SOD)-deficient (Sod2-deficient) and copper and zinc-superoxide dismutase (Cu,Zn-SOD)-deficient (Sod1-deficient) mice during oxygenation and hypoxia-reoxygenation. The steady-state level of chemiluminescence under oxygenated conditions was significantly enhanced by a lack of either Sod. We hypothesize that the enhanced chemiluminescence produced by Sod2 and Sod1 deficiency reflects in situ superoxide generation in the mitochondria and cytoplasm, respectively.