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

Neuromyelitis Optica With Onset in Childhood and Adolescence

BACKGROUND: Neuromyelitis optica with onset before the age of 18 years is a relatively rare, yet potentially devastating condition. the objective of the present study was to contribute to the study of early-onset neuromyelitis optica with a case series. PATIENTS: Data were collected from medical records of Brazilian neurologists caring for patients with neuromyelitis optica occurring in childhood and adolescence. RESULTS: Twenty-nine patients with neuromyelitis optica occurring before the age of 18 years and fulfilling the diagnostic criteria were identified. the average age at disease onset was 13 years and the patients had had an average disease duration of 6 years. the expanded disability scale score at the latest consultation was, on average, 4.7, and one patient had died from the disease. the 29 patients had had an average 4.5 relapses during the disease, accounting for 0.75 relapses per year, irrespective of the medication used. All patients were using one or more of the following medications: azathioprine, prednisone, immunoglobulin, and glatiramer acetate. CONCLUSIONS: Neuromyelitis optica with onset in childhood and adolescence is a poorly understood condition that is often disabling and difficult to manage.Univ Metropolitana Santos, Santos, BrazilHosp Restauracao, Recife, PE, BrazilUniv Fed Estado São Paulo, São Paulo, BrazilSanta Casa Vitoria, Fac Ciencias Saude, Vitoria, BrazilUniv Fed Goias, Goiania, Go, BrazilUniv Fed Santa Catarina, Florianopolis, SC, BrazilUniv Fed Rio de Janeiro, Macae, BrazilHosp Beneficencia Portuguesa, São Paulo, BrazilHosp Paulistano, São Paulo, BrazilHosp Sirio Libanes, São Paulo, BrazilUniv Fed Estado São Paulo, São Paulo, BrazilWeb of Scienc