Essential role for nuclear factor kappaB in ischemic preconditioning for ischemia-reperfusion injury of the mouse liver.

BACKGROUND: Ischemic preconditioning protects various organs from subsequent ischemic insult, but the precise mechanisms underlying this phenomenon remain undefined. To investigate the molecular mechanism by which ischemic preconditioning exerts its protective effect, we examined the activity of the transcription factor nuclear factor (NF)-kappaB and subsequent inflammatory gene expression. METHODS: Mice were used for total hepatic ischemia-reperfusion experiments after subcutaneous transposition of the spleen. Mouse liver was subjected to ischemia for 70 min followed by reperfusion for defined times. Ischemic preconditioning that consisted of 15 min of ischemia and 20 min of reperfusion was performed before 70 min of ischemia. NF-kappaB activity was analyzed by electrophoretic mobility shift assay, and the protein and tyrosine phosphorylation levels of inhibitor kappaB-alpha were assessed by Western blot analysis. Semiquantitative reverse-transcriptase polymerase chain reaction was used to analyze tumor necrosis factor (TNF)-alpha and intercellular adhesion molecule 1 mRNA levels. RESULTS: NF-kappaB was activated within 30 min after initiation of reperfusion and remained activated for 4 hr. Ischemic preconditioning attenuated NF-kappaB activation after subsequent prolonged ischemia and reperfusion and simultaneously decreased the expression of TNF-alpha and intercellular adhesion molecule 1 mRNA, the former statistically significantly (P <0.05). Tyrosine phosphorylation of inhibitor kappaB-alpha was decreased in ischemic preconditioned liver. CONCLUSIONS: These results indicate that attenuation of NF-kappaB activation and subsequent reduction in TNF-alpha mRNA expression after sustained ischemia play important roles in the protective mechanism of ischemic preconditioning against hepatic ischemia-reperfusion injury.

[Significance of peritonectomy for peritonitis carcinomatosis].

We analyzed patients who underwent multimodal treatment with peritonectomy as an aggressive treatment for peritonitis carcinomatosis. Peritonectomy was treated in eighteen cases (eleven gastric cancer, seven colon cancer). Out of these eighteen cases, nine were initial operation, six were recurrence after first operation and three were for relief after palliative operation for peritoneal dissemination. Five cases of recurrence included ileus. Of all eighteen patients, ten had received preoperative chemotherapies. Peritonectomy made complete resection possible principle, and the procedure included resection of the primary lesion, subtotal colectomy and peritonectomy. An intestinal stoma was needed in nine cases, consequently. All patients cases underwent continuous hyperthermic peritoneal perfusion (CHPP). Early postoperative peritoneal chemotherapy was given in five cases. By peritonectomy for a first time operation, macroscopically complete resection was possible in six cases. In relief and recurrence cases few tumor cells remained in five cases. Ileus due to peritoneal carcinomatosia was eliminated in all cases, and caloric intake became possible. Fourteen cases had postoperative complication (morbidity 78%), and treatment-related death occurred in three cases (mortality 17%). It became possible to resect even the peritoneal dissemination that was inoperable by conventional surgery, and improvement of QOL was achieved by peritonectomy in cases of carcinomatous peritonitis. However, postoperative care is important since aggression becomes more intense.