Histoplasmosis is a systemic fungal disease caused by dimorphic fungus Histoplasma capsulatum and is more common in immunocompromised patients. We report two cases of disseminated histoplasmosis in immunocompetent individuals from a non-endemic zone in Western India. Rapid diagnostic tests like urinary antigen detection and molecular assays comprise the need of the hour as early initiation of antifungal therapy can be life-saving. Clinicians need to be aware of this entity to prevent misdiagnosis and initiate prompt effective management.

The incidence of type 2 diabetes mellitus (non-insulin-dependent diabetes mellitus) is growing worldwide and poses a serious public health problem in a current paradigm of changing life style and food habits. Tolbutamide (sulfonylurea) is among the commonly used anti-diabetic drugs worldwide for treating type 2 diabetes and is known to cause congenital malformations in animals. In this study, the effect of tolbutamide on major organogenesis period and the possible involvement of apoptosis in mediating congenital malformations have been carried out. In the present study design, post-implantation rat embryos of day 11 were cultured for 24 h with various concentrations of tolbutamide, i.e., 10, 100, and 1000 μg/mL cultures, respectively. The growth and developmental of each embryo was evaluated and compared with control ones for the presence of any malformations. The tolbutamide decreased all growth and developmental parameters in a concentration-dependent manner, when compared with control. However, exposure to tolbutamide at 10 μg/mL culture did not show any significant effect on embryonic growth and development in vitro. In parallel to this, flow cytometric analysis (cell cycle and annexin V binding) and DNA fragmentation assay were carried out followed by quantitation by 3'-OH labeling of cultured rat embryos to examine the role of apoptosis in bringing about tolbutamide-induced teratogenesis. All results were found to be dose dependent and an increase in apoptosis in embryonic tissues may be related to the increased risk of congenital malformations. The outcome of the research suggested that apoptosis might be involved in mediating teratogenesis of tolbutamide in vitro. Further research is warranted to fully understand this mechanism.

Administration of drugs during pregnancy is always done with immense caution, however multiple neurological ailments including epilepsy and depression warrant medical treatments even during pregnancy. This exposes the unborn fetus to killer teratogenic effects, thus warranting intense studies towards finding potential anti-teratogenic agents. We employed a valproic acid (VPA) induced model of fetotoxicity and teratogenicity in rats towards assessing the antiteratogenic activity of curcumin, an antioxidant well known for attenuating oxidative stress by increasing the content of glutathione and reducing the level of lipid hydroperoxide. We studied the level of GSH, catalase, SOD, ROS, TBARS and the activities of CYP2C9 and determined that VPA at a dose of 300 mg kg À1 body wt significantly decreased the levels of GSH, SOD and catalase and increased the levels of ROS, TBARS, mRNA expression and the levels of the CYP2C9 enzyme which is involved in the formation of the toxic metabolite (E)-2,4-diene-VPA. Upon co-administration of curcumin (100 150 and 200 mg kg À1 body wt) along with VPA the levels of GSH, SOD and catalase exhibited a significant increase and ROS, TBARS, mRNA expression and the level of CYP2C9 enzyme were found to be significantly decreased with respect to VPA. We conclude that the toxic metabolite (E)-2,4-diene-VPA is involved in the generation of oxidative stress subsequently contributing in the induction of malformations and anomalies and that curcumin affords dose dependent amelioration of the anomalies exerted by VPA. Our studies are suggestive of the fact that curcumin has antioxidant activity and can curtail the formation of toxic (E)-2,4-diene-VPA by inhibiting the CYP2C9 enzyme and finally protecting fetuses in a dose dependent manner.

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