Reserch of Clinical

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By oral intake of microsphere containing tacrolimus, tacrolimus can be distributed specifically in Peyer patches of small intestine. In this drug delivery system, high concentration of immunosuppressive agent can be achieved in local intestinal wall. Microsphere at the dose of 0.04 mg of tacrolimus was administered orally to small bowel transplant porcine. Survival was dramatically prolonged without rejection or infection in spite of low blood concentration of tacrolimus (10.5 ng/ml). One living donor small bowel transplantation (the 3rd case in Japan) and one cadaveric small bowel transplantation ( the 1st case in Japan) were performed. Monitoring of rejection was instituted by high-power zoom endoscopy and immunohistochemical staining. High-power zoom endoscopy demonstrated blunting of villi and decreased number of villi as an early stage of rejevtion, which could not be observed by ordinal endoscopy examination. III immunohistochemical staining of biopsy specimen, increase of apopstosis induced keratine fragments, FasL-staining lymphocytes, positive finding of perforin and granzymeB, decrease of Ki67-staining enterocytes were useful for detecting very early stage of rejection. The rejection was controlled well in the above clinical 2 cases by those new monitoring. Intestinal grafts functioned well, and both of them were weaned from parenteral nutrition completely. The new immunosuppresive agent (FTY720) was used for prevention of chronic rejection in small bowel transplant rats. This research is co-operative study in foreign institute. Chronic rejection model in small intestine transplantation was achieved, in which thickning of internal wall of artery was demonstrated in intestinal grafts. Combined immunosuppression with FTY720 and cyclosporine inhibited completely development of internal wall of thichning of artery.