Clinical oxidative stress during leprosy multidrug therapy:impact of dapsone oxidation

This study aims to assess the oxidative stress in leprosy patients under multidrug therapy (MDT; dapsone, clofazimine and rifampicin), evaluating the nitric oxide (NO) concentration, catalase (CAT) and superoxide dismutase (SOD) activities, glutathione (GSH) levels, total antioxidant capacity, lipid peroxidation, and methemoglobin formation. For this, we analyzed 23 leprosy patients and 20 healthy individuals from the Amazon region, Brazil, aged between 20 and 45 years. Blood sampling enabled the evaluation of leprosy patients prior to starting multidrug therapy (called MDT 0) and until the third month of multidrug therapy (MDT 3). With regard to dapsone (DDS) plasma levels, we showed that there was no statistical difference in drug plasma levels between multibacillary (0.518±0.029 μg/mL) and paucibacillary (0.662±0.123 μg/mL) patients. The methemoglobin levels and numbers of Heinz bodies were significantly enhanced after the third MDTsupervised dose, but this treatment did not significantly change the lipid peroxidation and NO levels in these leprosy patients. In addition, CAT activity was significantly reduced in MDT-treated leprosy patients, while GSH content was increased in these patients. However, SOD and Trolox equivalent antioxidant capacity levels were similar in patients with and without treatment. These data suggest that MDT can reduce the activity of some antioxidant enzyme and influence ROS accumulation, which may induce hematological changes, such as methemoglobinemia in patients with leprosy. We also explored some redox mechanisms associated with DDS and its main oxidative metabolite DDS-NHOH and we explored the possible binding of DDS to the active site of CYP2C19 with the aid of molecular modeling software

SELECTED FOOD-INTAKE AND RISK OF VULVAR CANCER

Background. A case-control study was conducted to analyze the association between body mass, selected indicator food intake, and vulvar cancer risk. Methods. The patients included in this report were 125 women aged 80 years or younger with histologically confirmed diagnosis of invasive vulvar cancer who were admitted to a network of general and teaching hospitals in the greater Milan area. Control subjects were 541 patients admitted to teaching and general hospitals in Milan for acute conditions. Results. The risk of vulvar cancer was inversely related to green vegetable and carrot consumption, the corresponding multivariate relative risks for lowest versus highest levels of intake being 2.0 (95% confidence interval [CI], 1.2-3.4) and 1.4 (95% CI, 0.9-2.2). The trend in risk was significant for green vegetables. No consistent association emerged between milk, meat, liver, alcohol and coffee consumption and risk of vulvar cancer. In comparison with leaner women, the relative risks of vulvar cancer were 1.8, 1.9, 2.8, and 2.9 in progressively higher quintiles of the body mass index, and the trend in risk was significant. Conclusions. These data indicate that the risk of vulvar cancer is related to a number of nutritional and dietary factors. This is of particular interest, because vulvar cancer is a relatively rare neoplasm, whose etiology is still poorly understood, and on which only a few epidemiologic studies have been conducted