Pathogenesis of schistosomal 'pipestem' fibrosis: a low-protein diet inhibits the development of 'pipesten' fibrosis in mice

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2016-02-25T13:33:21Z No. of bitstreams: 1 Coutinho E Pathogenesis....pdf: 218245 bytes, checksum: 6c20ad21b6a34e86e7af82b8734a3cba (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2016-02-25T14:00:51Z (GMT) No. of bitstreams: 1 Coutinho E Pathogenesis....pdf: 218245 bytes, checksum: 6c20ad21b6a34e86e7af82b8734a3cba (MD5)Made available in DSpace on 2016-02-25T14:00:51Z (GMT). No. of bitstreams: 1 Coutinho E Pathogenesis....pdf: 218245 bytes, checksum: 6c20ad21b6a34e86e7af82b8734a3cba (MD5) Previous issue date: 1997Fundação Oswaldo Cruz, Centro de Pesquisas Aggeu Magalhães. Recide, Pe, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilFundação Oswaldo Cruz, Centro de Pesquisas Aggeu Magalhães. Recide, Pe, BrasilFundação Oswaldo Cruz, Centro de Pesquisas Aggeu Magalhães. Recide, Pe, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilMice maintained on a low protein diet for 30 days and then infected with Schistosoma mansoni for 16 weeks-completely failed to develop 'pipestem fibrosis' of the liver, whereas 50% of well nourished controls did. Usually mice with relatively mild and prolonged S. mansoni infection develop two diferente pathological pictures: one consisting of disseminated portal fibrosis caused by periovular granulomas concentrated at the portal spaces (pipestem fibrosis), the other represented by scattered hepatic granulomas. The reason for this dual response is poorley understood. Combined results from parasitological, histopathological, biochemical and morphometric data revealed that peri-ovular granulomas of undermourished mice were smaller, inflammation was less intense and there was minimal fibrosisi in comparison with those of controls, which suggest that a vigorou host response is necessary for the pathogenesis of schistosomal portal fibrosi

Repeated infections with Schistosoma mansoni and liver fibrosis in undernourished mice.

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2016-03-03T16:16:58Z No. of bitstreams: 1 Coutinho EM Repeated....pdf: 1268343 bytes, checksum: 8dae269706eea05e354f1ebb379ea87e (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2016-03-03T16:33:47Z (GMT) No. of bitstreams: 1 Coutinho EM Repeated....pdf: 1268343 bytes, checksum: 8dae269706eea05e354f1ebb379ea87e (MD5)Made available in DSpace on 2016-03-03T16:33:47Z (GMT). No. of bitstreams: 1 Coutinho EM Repeated....pdf: 1268343 bytes, checksum: 8dae269706eea05e354f1ebb379ea87e (MD5) Previous issue date: 2007Fundação Oswaldo Cruz, Centro de Pesquisas Aggeu Magalhães. Laboratório de Imunopatolologia, Departamento de Imunologia. Recife, PE, BrasilFundação Oswaldo Cruz, Centro de Pesquisas Aggeu Magalhães. Laboratório de Imunopatolologia, Departamento de Imunologia. Recife, PE, BrasilFundação Oswaldo Cruz, Centro de Pesquisas Aggeu Magalhães. Laboratório de Imunopatolologia, Departamento de Imunologia. Recife, PE, BrasilFundação Oswaldo Cruz, Centro de Pesquisas Aggeu Magalhães. Laboratório de Imunopatolologia, Departamento de Imunologia. Recife, PE, BrasilFundação Oswaldo Cruz, Centro de Pesquisas Aggeu Magalhães. Laboratório de Imunopatolologia, Departamento de Imunologia. Recife, PE, BrasilFundação Oswaldo Cruz, Centro de Pesquisas Aggeu Magalhães. Laboratório de Imunopatolologia, Departamento de Imunologia. Recife, PE, BrasilFundação Oswaldo Cruz, Centro de Pesquisas Gonçalo Moniz. Laboratório de Patologia Experimental. Salvador, BA, BrasilFundação Oswaldo Cruz, Centro de Pesquisas Gonçalo Moniz. Laboratório de Patologia Experimental. Salvador, BA, BrasilThe mouse model of schistosomal periportal fibrosis (Symmers’ “pipestem” fibrosis), that develops in 30–50% of the infected animals, is not reproduced in undernourished mice. Host nutritional status is likely to be a variable that may influence the outcome and progression of infection, since it interferes with the dynamics of connective tissue changes occurring in chronic hepatic schistosomiasis. Re-infections increase the occurrence of periportal liver fibrosis in well-nourished animals, but it is not known how undernourished mice would behave being repeatedly re-infected. So, 21-day-old male albino Swiss mice were individually exposed to 30 cercariae (percutaneous route) of the BH strain of Schistosoma mansoni, 4 weeks after being on a low-protein diet. Control animals were fed on a commercial balanced chow for mice. The nutritional status was evaluated by body weight gain and measurement of food intake. Mice were divided into four groups: A1 (undernourished, single infected), A2 (well-nourished, single infected), B1 (undernourished, re-infected), B2 (well-nourished, re-infected). The primary infection was performed 4 weeks after ingesting the respective diet. Re-infections started 45 days later, with exposure to 15 cercariae, at 15 day intervals. Mice were sacrificed 18 weeks after the primary exposure. The livers were submitted to morphological (gross and microscopic pathology), morphometric (percentage of fibrosis; granuloma size; volume and numerical densities) by using semi-automatic morphometry, and biochemical (quantification of collagen as hydroxyproline) studies. Worm burdens and hepatic egg counting were also recorded. Values for body weight gains were always lower in undernourished mice, the effects of re-infection being minimal on this regard. Liver and spleen weights were higher in well-nourished mice (either single infected or re-infected) and mainly related to the type of ingested diet. A greater number of re-infected well-nourished mice developed periportal fibrosis, but undernourished re-infected animals did not reproduce this lesion. The percentage of fibrosis and hepatic collagen content were higher in well-nourished mice, but differences between single infected and re-infected groups were not statistically significan

Low transformation growth factor-β1 production and collagen synthesis correlate with the lack of hepatic periportal fibrosis development in undernourished mice infected with Schistosoma mansoni

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2014-05-06T19:12:07Z No. of bitstreams: 1 Barros AF Low tranformation....pdf: 1467776 bytes, checksum: 0d1f3ebc02c562613386285d81b68bb9 (MD5)Made available in DSpace on 2014-05-06T19:12:07Z (GMT). No. of bitstreams: 1 Barros AF Low tranformation....pdf: 1467776 bytes, checksum: 0d1f3ebc02c562613386285d81b68bb9 (MD5) Previous issue date: 2014Fundação Oswaldo Cruz. Centro de Pesquisa Aggeu Magalhães. Laboratório de Imunologia e Biologia Molecular. Recife, PE, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisa Aggeu Magalhães. Laboratório de Imunologia e Biologia Molecular. Recife, PE, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisa Aggeu Magalhães. Laboratório de Imunologia e Biologia Molecular. Recife, PE, Brasil.Universidade Federal de Pernambuco. Departamento de Medicina Tropical. Centro de Ciências da Saúde. Recife, PE, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisa Aggeu Magalhães. Laboratório de Imunologia e Biologia Molecular. Recife, PE, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisa Aggeu Magalhães. Laboratório de Imunologia e Biologia Molecular. Recife, PE, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisa Aggeu Magalhães. Laboratório de Imunologia e Biologia Molecular. Recife, PE, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Laboratório de Engenharia Tecidual e Imunofarmacologia. Salvador, BA, Brasil / Centro de Biotecnologia e Terapia Celular. Hospital São Rafael. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Laboratório de Engenharia Tecidual e Imunofarmacologia. Salvador, BA, Brasil / Centro de Biotecnologia e Terapia Celular. Hospital São Rafael. Salvador, BA, Brasil.Universidade Federal de Pernambuco. Departamento de Medicina Tropical. Centro de Ciências da Saúde. Recife, PE, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisa Aggeu Magalhães. Laboratório de Imunologia e Biologia Molecular. Recife, PE, Brasil.Undernourished mice infected (UI) submitted to low and long-lasting infections by Schistosoma mansoni are unable to develop the hepatic periportal fibrosis that is equivalent to Symmers’ fibrosis in humans. In this report, the effects of the host’s nutritional status on parasite (worm load, egg viability and maturation) and host (growth curves, biology, collagen synthesis and characteristics of the immunological response) were studied and these are considered as interdependent factors influencing the amount and distribution of fibrous tissue in hepatic periovular granulomas and portal spaces. The nutritional status of the host influenced the low body weight and low parasite burden detected in UI mice as well as the number, viability and maturation of released eggs. The reduced oviposition and increased number of degenerated or dead eggs were associated with low protein synthesis detected in deficient hosts, which likely induced the observed decrease in transformation growth factor (TGF)-β1 and liver collagen. Despite the reduced number of mature eggs in UI mice, the activation of TGF-β1 and hepatic stellate cells occurred regardless of the unviability of most miracidia, due to stimulation by fibrogenic proteins and eggshell glycoproteins. However, changes in the repair mechanisms influenced by the nutritional status in deficient animals may account for the decreased liver collagen detected in the present study