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1.
Gene Ther ; 22(1): 9-19, 2015 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-25410742

RESUMEN

Secreted protein, acidic and rich in cysteine (SPARC) is involved in many biological process including liver fibrogenesis, but its role in acute liver damage is unknown. To examine the role of SPARC in acute liver injury, we used SPARC knock-out (SPARC(-/-)) mice. Two models of acute liver damage were used: concanavalin A (Con A) and the agonistic anti-CD95 antibody Jo2. SPARC expression levels were analyzed in liver samples from patients with acute-on-chronic alcoholic hepatitis (AH). SPARC expression is increased on acute-on-chronic AH patients. Knockdown of SPARC decreased hepatic damage in the two models of liver injury. SPARC(-/-) mice showed a marked reduction in Con A-induced necroinflammation. Infiltration by CD4+ T cells, expression of tumor necrosis factor-α and interleukin-6 and apoptosis were attenuated in SPARC(-/-) mice. Sinusoidal endothelial cell monolayer was preserved and was less activated in Con A-treated SPARC(-/-) mice. SPARC knockdown reduced Con A-induced autophagy of cultured human microvascular endothelial cells (HMEC-1). Hepatic transcriptome analysis revealed several gene networks that may have a role in the attenuated liver damaged found in Con A-treated SPARC(-/-) mice. SPARC has a significant role in the development of Con A-induced severe liver injury. These results suggest that SPARC could represent a therapeutic target in acute liver injury.


Asunto(s)
Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Células Endoteliales/fisiología , Osteonectina/genética , Animales , Enfermedad Hepática Inducida por Sustancias y Drogas/inmunología , Concanavalina A , Endotelio Vascular/patología , Técnicas de Silenciamiento del Gen , Lipopolisacáridos/farmacología , Hígado , Masculino , Ratones de la Cepa 129 , Ratones Endogámicos C57BL , Ratones Noqueados , Osteonectina/metabolismo , Transcriptoma
2.
Arq Gastroenterol ; 23(4): 242-5, 1986.
Artículo en Portugués | MEDLINE | ID: mdl-2831862

RESUMEN

Seventy infants and children with age from 2 months to 4 years old were admitted to "Hospital Infantil Menino Jesus", in São Paulo, Brazil, in the period from March 1983 to June 1984 with acute diarrhea. Feces from these patients were analysed in the search of rotavirus and enteropathogenic bacteria (Shigella, Salmonella and E. coli), for the purpose of defining the role of rotavirus as an agent of acute diarrhea in infants and young children in this country. ELISA (Enzyme-linked Immuno Sorbent Assay) was the method of choice for the search of rotavirus, because of its simplicity of management and the high sensitivity of the results. Rotavirus alone was imputed as the cause of acute diarrhea in 12 patients (17.7%), with ages from 2 months to 3 years old and in 2 patients in association with Shigella. All but one of the patients with rotavirus were undernourished and none of the infants had been breast fed before the disease.


Asunto(s)
Diarrea Infantil/microbiología , Infecciones por Rotavirus/diagnóstico , Rotavirus/aislamiento & purificación , Brasil , Preescolar , Diarrea/microbiología , Ensayo de Inmunoadsorción Enzimática , Heces/microbiología , Humanos , Lactante
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