Therapeutic effect and the mechanism of the action of human urinary trypsin inhibitor (MTI) on experimental acute pancreatitis were studied. MTI significantly increased survival rate of animals with experimental acute pancreatitis induced by the infusion of trypsin or phospholipase A2 into pancreas or by a closed duodenal loop. The efficacy of MTI on these types of pancreatitis were higher than those of aprotinin. Pancreatic enzymes were released from pancreatic slice by trypsin or phospholipase A2, and this release was inhibited by MTI. Further, these pancreatic enzymes caused a secondary release of enzymes from other pancreatic slice, suggesting that these enzymes injured pancreatic tissue and that a chain reaction of pancreatic enzyme activation may play an important role in the pathogenesis of acute pancreatitis. MTI suppressed the secondary enzyme-induced pancreatic injury more strongly than aprotinin. These results suggest that MTI may suppress pathogenesis and development of pancreatitis by inhibiting the chain reaction of pancreatic enzyme activation.
The changes in the cellular concentrations of ATP, ADP, and AMP and in oxidative phosphorylation of mitochondria were investigated in the remaining liver of partially hepatectomized rabbits. The energy charge (defined as half of the average number of anhydride-bonded phosphate groups per adenosine moiety) of the liver remnant decreased from 0.866 to 0.767 (p less than 0.01) within 24 hr after hepatectomy, and then increased to a substantially higher level than normal within 7 days. On the other hand, the mitochondrial phosphyorylative activity increased rapidly to 170 per cent of the control within 12 hr and then retruned to normal within 7 days. The mitochondrial phosphorylative activity was inversely correlated with energy charge of the liver remnant (r = -0.75, p less less than 0.01). The maximal enhancement of mitochondrial phosphorylative activity was found in mitochondria obtained from the liver remnant with the lowest level of energy charge, suggesting a response of mitochondria in vivo involving enhanced biosynthetic ATP-utilizing reactions at an early stage of the regenerating process. The enhancement of phosphorylative activity was accompanied by a rise in the respiratory control ratio, P/O ratio and state 3 respiration. The adenylate kinase [EC 2.7.4.3] activity in the liver remnant increased to more than 160% of the control within 2 days after partial hepatectomy, while the pyruvate kinase [EC 2.7.1.40] activity decreased remarkably. However, the changes in the two enzyme activities did not correlate with those of mitochondrial phosphorylative activity or the energy charge of the liver remnant.
In this study the experiences with carcinomas of the pancreas, ampulla of Vater, terminal comma bile duct, and duodenum found in a series of 3,610 patients collected from 57 major Japanese institutions was compiled over a 26 year period. The results were analyzed as to the success of resectional and palliative surgery for the various lesions. The most common lesion was carcinoma of the head of the pancreas. Unifortunately, only 18.3% of these patients were resectable with a 25.3% mortality. Carcinoma of the body and the tail was the second most frequent lesion, and it also exhibited a low resection rate. Carcinomas of the ampulla and the terminal common bile duct and duodenal regions were the most favorable for resection; usually pancreatoduodenectomy with an overall mortality of 20.8%. As a result of the large number of pancreatectomies performed, there was also a large number of postoperative complications, the most frequent being leakage at an anastomotic line. Hemorrhage also occurred frequently. Distal pancreatectomies were reserved for carcinoma of the body and the tail of the pancreas, and the most common postoperative complication of this procedure was hemorrhage. There were only 45 total pancreatectomies among the 973 resections being performed most frequently in patients with carcinoma of the head of the pancreas. Again, the most frequent postoperative complication was hemorrhage, followed by anastomotic leakage. The long term survivals following resection for these lesions were each poor. The best mean survival time was 22.7 months for carcinoma of the ampulla of Vater. Patients having resections for carcinoma of the head of the pancreas had a mean survival time of 12.3 months. At 5 years there were few survivors and most of them were patients who had undergone resections for carcinoma of the ampulla of Vater.
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