In vitro and in vivo anti-Trypanosoma cruzi activity of a novel nitro-derivative

Nitroarylidenemalononitriles and their cyanoacetamide derivatives with remarkable anti-epimastigote properties, were synthesized attempting to obtain new 3,5-diamino-4-(5'-nitroarylidene)-4H-thiadiazine 1,1-dioxide derivatives, which in previous reports had shown anti-Trypanosoma cruzi activity. Tests to evaluate the cytotoxicity of compounds were performed on J774 macrophages. 5-nitro-2-thienyl-malononitrile (5NO2TM), was the only product which maintained a high anti-epimastigote activity at concentrations in which it was no longer cytotoxic, thus it was assayed against intracellular amastigotes. Its anti-amastigote activity was similar to that of nifurtimox. Afterwards in vivo toxicity and anti-chagasic activity were determined. A reduction in parasitemia was observed

In vitro and in vivo assays of 3, 5-disubstituted-tetrahydro-2H-1,3,5-thiadiazin-2-thione derivatives against Trypanosoma cruzi

Cytotoxicity assays of 24 new 3,5-disubstituted-tetrahydro-2H-1,3,5-thiadiazin-2-thione derivatives were performed. The 17 compounds with higher anti-epimastigote activity and lower cytotoxicity were, thereafter, screened against amastigote of Trypanosoma cruzi. Out of these 17 derivatives S-2d was selected to be assayed in vivo, because of its remarkable trypanocidal properties. To determine toxicity against J774 macrophages, a method based on quantification of cell damage, after 24 h, was used. Cell respiration, an indicator of cell viability, was assessed by the reduction of MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] to formazan. Anti-amastigote activity was estimated after 48 h by microscopic counts of May Grünwald-Giemsa-stained monolayers. Nifurtimox and benznidazole were used as reference drugs. For the in vivo experiences, mice were infected with 10(4) blood trypomastigotes and then treated during 15 days with S-2d or nifurtimox by oral route. All of the compounds were highly toxic at 100 µg/ml for macrophages and a few of them maintained this cytotoxicity even at 10 µg/ml. Of the derivatives assayed against amastigotes 3k and S-2d showed an interesting activity, that was held even at 1µg/ml. It is demonstrated that the high anti-epimastigote activity previously reported is mainly due to the non-specific toxicity of these compounds. In vivo assays assessed a reduction of parasitemia after administration of S-2d to infected mice

Heridas penetrantes de colon. estudio comparativo de técnicas de reparación primaria en un solo plano con polipropileno y la convencional en dos planos en un modelo experimental / Wounds penetrating of colon: comparative study of first technics reparation in plane with propylene and the two plane in experimental model

El objetivo de este trabajo, es demostrar que la reparación primaria en un solo plano con polipropileno, es efectiva y segura, para el manejo de las lesiones penetrantes de colon cuando se compara con la técnica convencional en dos planos; para esto se utilizaron, animales de experimentación , alos cuales se le practicó perforación en un segmento del colon y fueron reparados con dichas técnicas. Se evaluó el tiempo empleado para la realización de cada una de las técnicas, el cual fue menor en un solo plano, la respuesta a la tolerancia de la vía oral y la restitución del tránsito intestinal fue similar en ambas técnicas. No hubo lugar de línea de sutura en ninguno de los grupos experimentales y en cuanto a la estenosis de la luz intestinal se observó una mayor proporción no significativa, en el grupo reparado con la técnica convencional. En los estudios histopatológicos se observó mayor fibrosis, presencia de úlcera, respuesta inflamatoria, y por ende mayor disrupción de al capa muscular, cuando se utiliza la técnica convencional. Se concluye que la técnica en un plano con polipropileno es efectiva y segura para las reparaciones de las heridas penetrantes de colon , al compararlas con la técnica convencional