|Budget Amount *help
¥2,900,000 (Direct Cost : ¥2,900,000)
Fiscal Year 1999 : ¥700,000 (Direct Cost : ¥700,000)
Fiscal Year 1998 : ¥800,000 (Direct Cost : ¥800,000)
Fiscal Year 1997 : ¥1,400,000 (Direct Cost : ¥1,400,000)
Bacterial translocation is a major concern as a cause developing sepsis or multiple organ failure. However the relationship between intestinal mucosal integrity and systemic inflammatory response syndrome (SIRS) or hypercytokinemia has not been evaluated after abdominal surgery. In this study, pathophysiology of decreased intestinal integrity and potential therapeutic modality was evaluated in clinical and experimental studies.
1)Postheparin plasma diamine oxidase (DAO) activity (PHD activity), indicator of intestinal mucosal integrity, decreased in patients shortly after major abdominal surgery (esophagectomy, pancreatectomy, total gastrectomy). Negative correlation between decreased PHD activity and elevated blood pro-inflammatory cytokine, interleukin 6 (IL-6), level or SIRS suggested the relationship between them. 2)In an in vitro study using Caco-2 monolayer cells, a model of intestinal mucosal epithelium, addition of IL-6 in the medium directly decreased DAO activity and stimulate
d E. coli passage across cells by transcellular route with intact nuclear and cytoplasmic structure. The results suggest the direct mechanism of decreased intestinal integrity under surgical stress and to develop bacterial translocation. 3)Enteral feeding, supplemented with dietary fiber and branched chain amino acids, in comparison without EN facilitated recovery of decreased PHD activity after surgery indicating the effectiveness to improve intestinal mucosal integrity. 4)As a nutritional substrate of enteral feeding, two different nutritional substrate were evaluated. The importance of dietary nucleotide to keep adhesional molecule (Mac-1, LFA-1) and oxidative burst in blood neutrophil function in mice was shown. Eicosapentaenoic acid, one of omega 3 polyunsatureted fatty acid, changed on tight junction permeability using Caco-2 monolayer cells in comparison with omega 6 or 9 polyunsaturated fatty acid. These results would provide new insights of pathophysiology and future immunonutrition to keep intestinal integrity. Less