Schistosome serine protease inhibitors: parasite defense or homeostasis?

Serpins are a structurally conserved family of macromolecular inhibitors found in numerous biological systems. The completion and annotation of the genomes of Schistosoma mansoni and Schistosoma japonicum has enabled the identification by phylogenetic analysis of two major serpin clades. S. mansoni shows a greater multiplicity of serpin genes, perhaps reflecting adaptation to infection of a human host. Putative targets of schistosome serpins can be predicted from the sequence of the reactive center loop (RCL). Schistosome serpins may play important roles in both post-translational regulation of schistosome-derived proteases, as well as parasite defense mechanisms against the action of host proteases.

Serpinas são uma família de inibidores macromoleculares estruturalmente conservados encontrados em inúmeros sistemas biológicos. O término e a anotação dos genomas de Schistosoma mansoni e de Schistosoma japonicum permitiram a identificação por análise filogenética de dois principais clados de serpinas. S. mansoni mostra uma multiplicidade maior de genes de serpinas, talvez refletindo uma adaptação à infecção de um hospedeiro humano. Alvos putativos das serpinas de esquistossomos podem ser preditos a partir da sequência do "loop" do centro reativo. Serpinas de esquistossomos podem ter importantes papeis tanto na regulação pós-traducional de proteases derivadas do esquistossoma, quanto nos mecanismos de defesa contra a ação de proteases do hospedeiro.

Antithrombin III activity in cerebrovascular accidents.

Cerebrovascular accidents are commonly due to occlusive or haemorrhagic lesions. The present prospective study was planned to find out role of antithrombin in possible etiopathological process, which might predispose an individual for stroke. METHOD: Biological activity of antithrombin III was done by the method as described by Innerfield et al (1976). Immunological estimation of an antithrombin III was done by single radial immunodiffusion by the technique of Mancini et al modified by Fahey and Mckelvey. RESULTS: The biological and immunological activity of antithrombin III was measured in 98 patient of occlusive and 56 patients of haemorrhagic strokes. Significant depression in biological as well as immunological activity (p<0.001) was observed in occlusive stroke. In haemorrhagic stroke both, biological and immunological activity was increased. In follow up study, there was progressive normalization of both, biological as well as of immunological activity in both group. CONCLUSION: Decrease of antithrombin III in occlusive and increase in haemorrhagic stroke indicates that these changes have at least an additive role in the pathogenesis of stroke.

Cofactor II de la heparina (HCII), un inhibidor de trombina cuyo rol fisiologico no esta completamente esclarecido / Heparin cofactor II, a thrombin inhibitor with a still unclarified physiologic role

El Cofactor II de la Heparina (HCII) es una proteína perteneciente al sistema de coagulación que inhibe específicamente trombina, processo que es potenciado por acción de los glicosaminoglicanos dermatán sulfato y heparina. Hasta el momento las deficiencias congénitas de HCII encontradas en forma aislada no están asociadas con eventos trombóticos, sí desarollan eventos trombóticos cuando están asociadas a otros factores predisponentes. Se observó disminución en los niveles de HCII en hepatopatías, coagulación intravascular diseminada, en anemia drepanocítica, encontrándose niveles elevados en embarazo a término y por el uso de contraceptivos orales. En el laboratorio realizamos el dosaje del HCII en la población normal de la ciudad de Buenos Aires, en diversas patologías como sepsis, quemados , anticoagulados con dicumarínicos y con heparina, diabéticos, hiperhomocisteinemia, observándose valores disminuidos principalmente en sepsis y pacientes diabéticos. El HCII es una glicoproteína que participa en la inhibición de trombina pero cuyo rol fisiológico no está completamente esclarecido. Es probable que el HCII inhiba trombina en el espacio extravascular, y está relacionado con la regulación de procesos inflamatorios y de reparación tisular.