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1.
J Cell Mol Med ; 20(4): 632-43, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-26828859

RESUMEN

Intra-abdominal adhesions are major post-operative complications for which no effective means of prevention is available. We aimed to evaluate the efficacy of exogenous pulmonary surfactant administration in the prevention of post-operative abdominal adhesions. Rats were randomly assigned to undergo laparotomy (L) or gastroenterostomy (GE) and then treated with surfactant (groups L-S and GE-S, respectively). Intra-abdominal adhesions, collagen fibre content, metalloproteinase (MMP)-9, expression of growth factors (TGF-ß, KGF and VEGF), type III procollagen (PCIII) and pro-caspase 3, as well as isolectin B4 and ED1-positive cells expressing MMP-9, were evaluated. Groups treated with surfactant (GE-S and L-S) exhibited fewer adhesions. A significant reduction in collagen fibre content was observed in GE-S compared to GE animals (P < 0.001). In situ and gelatin zymography analysis showed higher MMP-9 expression and activity in the GE-S group compared to the GE group (P < 0.05). ED1-positive cell counts were significantly higher in the GE-S group (P < 0.001) than in the GE group. Virtually all cells positive for ED1 were MMP-9+. Double-labelling of MMP-9 with IB4 showed no significant differences between GE-S and GE groups. TGF-ß, KGF, PCIII and pro-caspase-3 mRNA expression decreased significantly in GE-S compared to GE animals (P < 0.05). Surfactant administration also reduced apoptosis in the GE-S group. These findings suggest that surfactant reduces the intra-abdominal adhesions triggered by laparotomy and gastrointestinal anastomosis, thus preventing fibrosis formation at the peritoneal surfaces. This preclinical study suggests an innovative treatment strategy for intra-abdominal adhesions with surfactant and to endorse its putative mechanism of action.


Asunto(s)
Peritoneo/cirugía , Surfactantes Pulmonares/farmacología , Adherencias Tisulares/prevención & control , Animales , Caspasa 3/genética , Caspasa 3/metabolismo , Colágeno Tipo III/genética , Colágeno Tipo III/metabolismo , Gastroenterostomía , Regulación de la Expresión Génica , Laparotomía , Lectinas/genética , Lectinas/metabolismo , Masculino , Metaloproteinasa 9 de la Matriz/genética , Metaloproteinasa 9 de la Matriz/metabolismo , Peritoneo/metabolismo , Ratas , Ratas Wistar , Transducción de Señal , Adherencias Tisulares/genética , Adherencias Tisulares/metabolismo , Adherencias Tisulares/patología , Factor de Crecimiento Transformador beta/genética , Factor de Crecimiento Transformador beta/metabolismo , Factor A de Crecimiento Endotelial Vascular/genética , Factor A de Crecimiento Endotelial Vascular/metabolismo
2.
Liver Int ; 31(5): 700-6, 2011 May.
Artículo en Inglés | MEDLINE | ID: mdl-21457442

RESUMEN

BACKGROUND/AIMS: Nonalcoholic fatty liver disease (NAFLD) is highly prevalent in type 2 diabetes mellitus (T2DM). However, data regarding the prevalence and correlates of its histopathological stages are scarce. The aim was to investigate the prevalence and correlates of the more severe histopathological features of NAFLD, nonalcoholic steatohepatitis (NASH) and advanced fibrosis, in T2DM. METHODS: From 125 patients with ultrasonographic evidence of NAFLD, 98 patients underwent liver biopsies, which were examined by two independent pathologists regarding the presence of NASH and graded according to the NASH Clinical Research Network scoring system. Agreement between pathologists was assessed by weighted κ coefficients and independent correlates of NASH and advanced fibrosis (grade ≥ 2) by multivariate logistic regression. RESULTS: Ninety-two (94%) patients presented histological NAFLD. Interobserver agreement was substantial to excellent for NASH diagnosis (κ=0.82) and steatosis grading (κ=0.76), and moderate for the NAFLD activity score (κ=0.58) and fibrosis grading (κ=0.52). The prevalence of NASH was 78%, and its independent correlates were hypertriglyceridaemia (P=0.034), high alanine aminotranferase level (P=0.044) and low serum high-density lipoprotein-cholesterol (P=0.079). The prevalence of advanced fibrosis ranged from 34% in the best scenario (lowest fibrosis score) to 60% in the worst scenario (highest score). Its independent correlates were a high serum γ-glutamyl transferase (P=0.002), older age (P=0.022) and male gender (P=0.064). No diabetes-related clinical characteristic was associated with NASH or advanced liver fibrosis. CONCLUSIONS: The prevalence of the severe features of NAFLD is high in T2DM patients. Liver biopsy shall be considered in all diabetic patients with ultrasonographic evidence of NAFLD.


Asunto(s)
Diabetes Mellitus Tipo 2/epidemiología , Cirrosis Hepática/patología , Hígado/patología , Biopsia , Brasil/epidemiología , Distribución de Chi-Cuadrado , Estudios Transversales , Hígado Graso/epidemiología , Hígado Graso/patología , Femenino , Humanos , Hígado/diagnóstico por imagen , Cirrosis Hepática/epidemiología , Modelos Logísticos , Masculino , Persona de Mediana Edad , Enfermedad del Hígado Graso no Alcohólico , Variaciones Dependientes del Observador , Valor Predictivo de las Pruebas , Prevalencia , Reproducibilidad de los Resultados , Medición de Riesgo , Factores de Riesgo , Índice de Severidad de la Enfermedad , Ultrasonografía
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