Hematological and parasitological effect of cyctein protease inhibitor on murine schistosomiasis

Cysteine protease enzyme [CP] is crucial for parasitic disease propagation, and inhibitors of such proteases are emerging with promising therapeutic uses in the treatment. This study was designed to evaluate the hematological and parasitological efficacy of one of the cysteine protease inhibitors [Sodium nitroprusside] that was administered alone as chemotherapy for murine schistosomiasis manosni in different schistosomal stages [shistosomula and mature worm]. Thirty mice were infected with 80 S. mansoni cercariae/mouse and were divided into 3 groups [10 mice each]. Group I: Infected untreated mice Group II and III. Mice were intraperitoneally treated with 100 mg/kg of cysteine protease inhibitor for 10 consecutive days three and six weeks post infection. Eight weeks post infection all animals were sacrificed and subjected for assessment of cysteine protease protein expression in liver tissue samples using immunoblotting technique [Western blotting], parasitological criteria and EM examination of buffy coat bone marrow and worms. Expression of cysteine protease protein was detected at the expected molecular weight [28 kDa] in 9 of the 10 [90%] infected untreated mice. After treatment protein expression returned negative in the treated groups. A highly significant reduction in worm burden was observed in all groups treated with inhibitor in comparison to infected control group [p<0.001]. However the greatest reduction in the worm burden was observed in treated group 6 weeks post infection in comparison to 3 weeks post infection [P<0.05]. Also, treatment could reduce egg count when given early in infection or significantly decreased egg burden when given late in infection. As regards EM examination sodium nitroprusside treated mice 3 and 6 weeks post the infection revealed degenerated tegument with completely implanted and degenerated spines. In addition 6 weeks post infection treated Schistosoma mansoni male worms showed vaculation and necrosis of spermatocytes. Buffy coat examination of Schistosoma mansoni infected untreated mice showed the inability of the eosinophil to be degranulated, while both treated groups revealed degranulation. In addition the group treated six weeks post infection showed hypodense eosinophils with large number of cytoplasmic vacuoles which represent an activated phenotype. Also in latter group activated lymphocytes were detected with marked dilatation of the endoplasmic reticulum. Bone marrow examination of Schistosoma mansoni - treated mice revealed degranulated eosinophils and eosinophilic myelocytes with activated phenotype in addition to degranulated platelets. Our findings indicate that the cysteine protease secreted by the different stages S. mansoni plays a crucial role in attenuating effector functions of eosinophils as it decreases the eosinophil's responses and inhibit its activation to the parasite resulting in diminished degranulation and reduced generation of superoxide. So, it is preferable to give CPI at any time post infection, with frequent observation of platelets function and different coagulation tests

Aspectos terapêuticos da DHEG na Maternidade do Hospital Universitário Lauro Wanderley / Therapeutics aspects of DHEG in Lauro Wanderley University Hospital

Os autores fazem um estudo retrospectivo nos prontuários de 100 pacientes portadores de DHEG que foram internadas na Maternidade do Hospital Universitário Lauro Wanderley no período compreendido entre outubro de 1991 e março de 1993. O estudo das pacientes foi realizado levando em consideraçåo: idade, idade gestacional, pressåo arterial sistólica e distólica na admissåo, edema, proteinúria e convulsöes, tendo sido excluídas das observaçöes as pacientes portadoras de hipertensåo crônica, diabetes mellitus, cardiopatias e nefropatias. Foram analisados os resultados das drogas utilizadas em administraçåo única, no serviço, e em associaçöes, para controle da hipertensåo arterial, tendo sido a metildopa administrada com maior frequência em dosagem única, como também a mais utilizada em associaçåo com a nifedipina e fenobarbital, atingindo 46 por cento. O sulfato de magnésio foi utilizadado em 4 por cento das pacientes para controlar e prevenir crises consulvisas. Face às propriedades dos benzodiazepínicos no controle primário e na prevençåo das crises consulsivas recorrentes, foi o mesmo administrado em 4 por cento das pacientes, tendo sido utilizado o diazepan associado aos hipotensores. O nitroprussiato de sódio foi usado em 3 por cento das pacientes encaminhadas ao CTI, ocasiäo em que se pôde observar o efeito tóxico da droga para o feto, já que ocasionou óbito fetal intra-uterino em todas as pacientes que fizeram uso do medicamento