Angiogenesis and experimental hepatic fibrosis

Angiogenesis is a basic change occurring during repair by granulation tissue. This process seems to precede fibrosis formation in most types of chronic liver disease. To examine its presence and significance in different types of hepatic insults, this paper sought to identify the presence, evolution and peculiarities of angiogenesis in the most common experimental models of hepatic fibrosis. The characterization of cells, vessels and extracellular matrix and the identification of factors associated with endothelium (factor VIII RA), vascular basement membrane, other components of the vascular walls (actin, elastin) and the presence of the vascular-endothelial growth factor were investigated. The models examined included Capillaria hepatica septal fibrosis, whole pig serum injections, carbon tetrachloride administration, main bile duct ligation and Schistosoma mansoni infection. The first four models were performed in rats, while the last used mice. All models studied exhibited prominent angiogenesis. The most evident relationship between angiogenesis and fibrosis occurred with the C. hepatica model due to circumstances to be discussed. Special attention was paid to the presence of pericytes and to their tendency to become detached from the vascular wall and be transformed into myofibroblasts, which is a sequence of events that explains the decisive role angiogenesis plays in fibrosis.

Angiogênese e fibrose hepática experimental / Angiogenesis and experimental hepatic fibrosis

Na cicatrização dos ferimentos a fase de intensa proliferação vascular (tecido de granulação) constitui um aspecto crucial indicativo da formação do tecido fibroso do reparo. Vários trabalhos recentes têm chamado a atenção para a semelhança deste processo com a patogênese da fibrose hepática. De fato, tem sido demonstrado que a proliferação vascular (angiogênese) ocorre como uma alteração proeminente em várias doenças crônicas fibrosantes do fígado. Os modelos experimentais de fibrose septal induzida pela infecção por Capillaria hepatica no rato, por ligadura do ducto biliar do rato, e pela esquistossomose no camundongo foram recentemente utilizados para demonstrar a estreita relação entre angiogênese e fibrose hepática. O presente trabalho procura investigar, comparativamente, a presença de angiogênese, suas características evolutivas, intensidade e peculiaridades nos modelos experimentais de fibrose hepática mais comumente utilizados. Para tal, cinco modelos diferentes e bem padronizados de fibrose hepática foram escolhidos: a) Fibrose septal induzida pela infecção com o helminto Capillaria hepatica no rato; b) Fibrose septal induzida pelo tratamento repetido com soro de porco em ratos; c) Fibrose com cirrose, provocada pelo tratamento crônico com o tetracloreto de carbono (CCI4); d) fibrose biliar provocada pela ligadura total do colédoco de ratos; e e) fibrose granulomatosa e periportal produzida em camundongos pela infecção crônica pelo Schistosoma mansoni. A primeira etapa do trabalho consistiu na produção experimental de cada tipo de fibrose hepática. A segunda etapa consistiu na avaliação dos resultados através do estudo qualitativo com técnicas histológicas e imuno-histoquímicas, tendo sido avaliadas: as carcaterísticas dos elementos celulares, matriciais e vasculares. Além da atenção dada ao comportamento do endotélio (fator VIII), da membrana basal vascular (lamina, fibronectina, colágeno tipo IV), paredes vasculares (actina, elastina)...

Sequential histological changes in Biomphalaria glabrata during the course of Schistosoma mansoni infection

Biomphalaria glabrata, highly susceptible to Schistosoma mansoni, were seen to shed less and less cercariae along the time of infection. Histological examination kept a close correlation with this changing pattern of cercarial shedding, turning an initial picture of no-reaction (tolerance) gradually into one of hemocyte proliferation with formation of focal encapsulating lesions around disintegrating sporocysts and cercariae, a change that became disseminated toward the 142nd day post miracidial exposure. Findings were suggestive of a gradual installation of acquired immunity in snails infected with S. mansoni

Contribution to the histology of Biomphalaria glabrata / Contribuiçäo à histologia da Biomphalaria glabrata

A combination of histological techniques applied to the study of Biomphalaria glabrata yielded some interesting new data about the histology of this snail, a major intermediate host of Schistosoma mansoni in Brazil. Three kinds of pigments were identified: a ark pigment which bleached following oxidation with potassium permanganate; a lipofuchsin like, diastase-resistant PAS-positive pigment and an iron-containing pigment, probably related to hemosiderin. Calcium was detected in small deposits within the connective tissue and forming a dense core inside the chitinous radular teeth. The presence of fibrils, staining with sirius-red and birefringence under polarized light strongly suggest primitive collagen tissue. The radular apparatus appeared as a storing site for glycogen, while abundant Alcian-blue positive material (proteoglycans) was extremely concentrated in the radular sac