DETC Induces Leishmania Parasite Killing in Human In Vitro and Murine In Vivo Models: A Promising Therapeutic Alternative in Leishmaniasis

Background: Chemotherapy remains the primary tool for treatment and control of human leishmaniasis. However, currently available drugs present serious problems regarding side-effects, variable efficacy, and cost. Affordable and less toxic drugs are urgently needed for leishmaniasis. Methodology/Principal Findings: We demonstrate, by microscopy and viability assays, that superoxide dismutase inhibitor diethyldithiocarbamate (DETC) dose-dependently induces parasite killing (p,0.001) and is able to ??????sterilize?????? Leishmania amazonensis infection at 2 mM in human macrophages in vitro. We also show that DETC-induced superoxide production (p,0.001) and parasite destruction (p,0.05) were reverted by the addition of the antioxidant N-acetylcysteine, indicating that DETC-induced killing occurs through oxidative damage. Furthermore, ultrastructural analysis by electron microscopy demonstrates a rapid and highly selective destruction of amastigotes in the phagosome upon DETC treatment, without any apparent damage to the host cell, including its mitochondria. In addition, DETC significantly induced parasite killing in Leishmania promastigotes in axenic culture. In murine macrophages infected with Leishmania braziliensis, DETC significantly induced in vitro superoxide production (p = 0.0049) and parasite killing (p = 0.0043). In vivo treatment with DETC in BALB/C mice infected with Leishmania braziliensis caused a significant decrease in lesion size (p,0.0001), paralleled by a 100-fold decrease (p = 0.0087) in parasite burden. Conclusions/Significance: Due to its strong leishmanicidal effect in human macrophages in vitro, its in vivo effectiveness in a murine model, and its previously demonstrated in vivo safety profile in HIV treatment, DETC treatment might be considered as a valuable therapeutic option in human leishmaniasis, including HIV/Leishmania co-infection

Metabolismo de nitrogênio em dois sistemas de cultivo de café sob veranico da estação úmida

Com o objetivo de avaliar o efeito do veranico ocorrido na estação úmida sobre o metabolismo de nitrogênio em cafeeiros em sistema a pleno sol e associados com abacateiro (Persea americana Mill.) e ingazeiro (Inga edulis Mart.), foi realizado este experimento. O estudo foi conduzido em propriedade situada no município de Barra do Choça, BA, composto por plantas de café (Coffea arabica L.), variedade Catuaí, sendo caracterizados dois campos experimentais (sistema sombreado x sistema a pleno sol). As avaliações foram realizadas em janeiro (período de veranico) e março (final da estação úmida), em cinco repetições por campo experimental. Os dados foram submetidos ao teste t por meio do programa SAEG, versão 9.1. Maior teor de NO3 - foi verificado no sistema a pleno sol, tanto no período de veranico como no final da estação úmida. Em março foi observado maior acúmulo de N-orgânico no terço superior do cafeeiro a pleno sol e no terço médio do cafeeiro sombreado. Maiores teores de nitrogênio total e a tendência de maior atividade enzimática da redutase do nitrato foram verificados nos sistemas arborizados, quando avaliados dentro do mesmo terço do cafeeiro nas duas estações

Thirty distinct CACNA1F mutations in 33 families with incomplete type of XLCSNB and Cacna1f expression profiling in mouse retina

X-linked CSNB patients may exhibit myopia, nystagmus, strabismus and ERG abnormalities of the Schubert-Bornschein type. We recently identified the retina-specific L-type calcium channel alpha1 subunit gene CACNA1F localised to the Xp11.23 region, which is mutated in families showing the incomplete type (CSNB2). Here, we report comprehensive mutation analyses in the 48 CACNA1F exons in 36 families, most of them from Germany. All families were initially diagnosed as having the incomplete type of CSNB, except for two which have been designated as Åland Island eye disease (ÅIED)-like. Out of 33 families, a total of 30 different mutations were identified, of which 24 appear to be unique for the German population. The mutations, 20 of which are published here for the first time, were found to be equally distributed over the entire gene sequence. No mutation could be found in a classic ÅIED family previously shown to map to the CSNB2 interval. Cacna1f expression in photoreceptor-negative mice strains indicate that the gene is expressed in the outer nuclear, the inner nuclear, and the ganglion cell layer. Such a distribution points to the central role of calcium regulation in the interaction of retinal cells that mediate signal transmission