ABSTRACT
Crohn's disease (CD) is a chronic inflammatory disorder, characterized by cytokine imbalance and transcription signaling pathways activation. In addition, the increase of mesenteric adipose tissue (MAT) near the affected intestinal area is a hallmark of CD. Therefore, we evaluated the transcription signaling pathways and cytokines expression in intestinal mucosa and MAT of active CD patients. Ten patients with ileocecal CD and eight with noninflammatory diseases were studied. The biopsies of intestinal mucosa and MAT were snap-frozen and protein expression was determined by immunoblotting. RNA levels were measured by qPCR. The pIkB/IkB ratio and TNFα level were significantly higher in intestinal mucosa of CD when compared to controls. However, STAT1 expression was similar between intestinal mucosa of CD and controls. Considering the MAT, the pIkB/IkB ratio was significantly lower and the anti-inflammatory cytokine IL10 was significantly higher in CD when compared to controls. Finally, the protein content of pSTAT1 was higher in MAT of CD compared to controls. These findings reinforce the predominance of the proinflammatory NF-kB pathway in CD intestinal mucosa. For the first time, we showed the activation of STAT1 pathway in MAT of CD patients, which may help to understand the physiopathology of this immune mediated disease.
ABSTRACT
BACKGROUND: Crohn's disease (CD) is associated with complex pathogenic pathways involving defects in apoptosis mechanisms. Recently, mesenteric adipose tissue (MAT) has been associated with CD ethiopathology, since adipose thickening is detected close to the affected intestinal area. However, the potential role of altered apoptosis in MAT of CD has not been addressed. AIMS: To evaluate apoptosis in the intestinal mucosa and MAT of patients with CD. METHODS: Samples of intestinal mucosa and MAT from patients with ileocecal CD and from non-inflammatory bowel diseases patients (controls) were studied. Apoptosis was assessed by TUNEL assay and correlated with the adipocytes histological morphometric analysis. The transcriptional and protein analysis of selected genes and proteins related to apoptosis were determined. RESULTS: TUNEL assay showed fewer apoptotic cells in CD, when compared to the control groups, both in the intestinal mucosa and in MAT. In addition, the number of apoptotic cells (TUNEL) correlated significantly with the area and perimeter of the adipose cells in MAT. Transcriptomic and proteomic analysis reveal a significantly lower transcript and protein levels of Bax in the intestinal mucosa of CD, compared to the controls; low protein levels of Bax were found localized in the lamina propria and not in the epithelium of this tissue. Furthermore, higher level of Bcl-2 and low level of Caspase 3 were seen in the MAT of CD patients. CONCLUSION: The defective apoptosis in MAT may explain the singular morphological characteristics of this tissue in CD, which may be implicated in the pathophysiology of the disease.
Subject(s)
Adipose Tissue/pathology , Apoptosis , Crohn Disease/pathology , Intestines/pathology , Mesentery/pathology , Case-Control Studies , Humans , In Situ Nick-End LabelingABSTRACT
Fundamentos: Acidente vascular encefálico (AVE) é uma doença cerebrovascular frequente em adultos, e uma das maiores causas de morbimortalidade no mundo. Entreos principais fatores de risco para as doenças cardiocerebrovasculares está o consumo alimentar. Objetivo: Analisar o consumo alimentar, a inter-relaçãoentre macro e micronutrientes e seus riscos clínicos em pacientes pós-AVE.Métodos: Estudo de coorte transversal realizado nos ambulatórios de Otorrinolaringologia/Disfagia eNeurologia/Vascular, de hospital terciário, em pacientes com diagnóstico de AVE. A coleta de dados realizou-sede junho a agosto 2010. Inquérito dietético, recordatório 24 horas e anamnese foram utilizados para traçar oconsumo alimentar. Foram calculadas as necessidades nutricionais. Realizou-se análise estatística, adotando-sesignificância de 5%. Resultados: Amostra constituida por 38 pacientes com média de idade de 59,5 anos; destes, 34 pacientes eram hipertensos e 19 diabéticos. Verificou-se alto consumo de macronutrientes (carboidratos, lipídios e proteínas) e baixo consumo de micronutrientes (vitaminas, saisminerais). A presença da DM apresentou associação estatisticamente significativa pela análise de Mann-Whitney com a ingestão excessiva de calorias (p=0,006),carboidratos (p=0,006) e lipídios (p=0,029). Além disso, o diabetes foi confirmado como fator que favorece o AVE recorrente pela análise de regressão logística (p=0,025).Conclusão: Os pacientes pós-AVE apresentam hábitos alimentares inadequados, porém a limentação desbalanceada dessa população não se mostrou significativa como fator de risco para o aumento das chances da ocorrência de novos eventoscardiocerebrovasculares. No entanto, o DM isoladamente se mostrou como fator de risco para a recorrência de AVE.
