Eiichi Shiohara

Effects of leukocyte and platelet depletion on ischemia--reperfusion injury to dog pancreas.

BACKGROUND/AIMS Ischemia-reperfusion injury has been studied in various organs. Effects of leukocyte and platelet depletion on ischemia-reperfusion injury were evaluated using the isolated, perfused dog pancreas in vivo. METHODS Pancreatic exocrine and endocrine functions were stimulated by an intra-arterial injection of cholecystokinin (10(-12) mol) and intravenous injection of glucose and arginine (1 g/kg body wt), respectively. The functions before and after 60 minutes of ischemia were evaluated in the no treatment and in the leukocyte and platelet depletion groups. RESULTS Cholecystokinin increased prostaglandin I2 and thromboxane A2 production and stimulated exocrine pancreatic secretion. Glucose and arginine stimulated insulin and glucagon release from the pancreas. Sixty minutes of ischemia followed by 60 minutes of reperfusion damaged the pancreatic acinar and ductular cells. Ischemia of 60 minutes followed by 90 minutes of reperfusion damaged beta cells. Removal of leukocytes (97.6%) and platelets (99.4%) by using a filter throughout the experiment prevented the ischemia-reperfusion injury, reduced plasma lipid peroxide and thromboxane A2, and increased prostaglandin I2 levels. CONCLUSIONS Leukocytes and platelets seem to damage the pancreas during ischemia-reperfusion by increasing the peroxidation of structurally important cell membrane lipids and reduced the thromboxane A2 prostaglandin I2 ratio, a predictor of cellular injury.

Complete disappearance of recurrent hepatocellular carcinoma with peritoneal dissemination and splenic metastasis : A unique clinical course after surgery

Spontaneous regression of hepatocellular carcinoma (HCC) is a rare phenomenon. We report a case of complete disappearance of intrahepatic, peritoneal and splenic metastases in HCC after hepatectomy using treatment with tegafur and uracil (UFT). The effect of UFT alone was not likely to have caused the disappearance of this tumour because HCC recurrence advance markedly within 5 months of surgery despite oral administration of UFT. This case demonstrates a unique postoperative clinical course that suggests spontaneous regression of HCC. This is the first case of complete disappearance of unresectable HCC with peritoneal seeding and splenic metastasis.

Gas-forming liver abscess after transcatheter arterial embolization for hepatocellular carcinoma: Report of a case

A case of a gas-forming liver abscess developing after transcatheter arterial embolization for recurrent hepatocellular carcinoma (HCC) in a 65-year-old man is presented herein. He was admitted to hospital with fever and jaundice, following which ultrasonography (US) and computed tomography revealed a gas-containing abscess in the posterior segment of the hepatic lobe with multiple HCC. Percutaneous transhepatic drainage was performed using US. Antibiotics which were sensitive to theEscherichia coli bacteria detected in the abscess were administered both intravenously and through the drainage tube into the abscess. Four months later, the abscess had diminished and the patient was discharged after receiving percutaneous ultrasonographically guided ethanol injection therapy for the recurrent HCC.

The effect of a thromboxane A2 receptor antagonist (ONO 3708) on ischemia-reperfusion injury of the dog pancreas

The effects of a thromboxane A2 receptor antagonist, ONO 3708, on ischemia-reperfusion injury of the pancreas were evaluated using an isolated in-vivo-perfused dog pancreas model. Pancreatic endocrine and exocrine function were stimulated with cholecystokinin octapeptide (10(-12) mol). This dose significantly increased endogenous prostaglandin I2 and thromboxane A2 production by the pancreas (both P < 0.001). A period of 60 min of ischemia and subsequent reperfusion induced an increase of pancreatic amylase release (P < 0.01) and a decrease of insulin release (P < 0.01). There was also a decrease of pancreatic juice and pancreatic bicarbonate and amylase output (au P < 0.01), suggesting damage to the acinar, ductular, and beta cells. Intravenous administration of ONO 3708 (200 micrograms/kg/min) throughout the experiment prevented these abnormalities of pancreatic secretion. It also reduced the plasma lipid peroxide level in the venous drainage (P < 0.01) and elevated the prostaglandin I2 level (P < 0.01) without changing thromboxane A2 levels. ONO 3708 thus appeared to protect the pancreas from ischemia-reperfusion injury by reducing the peroxidation of cell membrane lipids and by decreasing the thromboxane A2/prostaglandin I2 ratio, which is a predictor of cellular injury.

Effects of parathyroid hormone on pancreatic exocrine secretion.

The role of parathyroid hormone (PTH) and calcium on pancreatic exocrine secretion were observed using sham-operated and parathyroidectomized dogs. First, exocrine secretion of the pancreas stimulated with secretin and cholecystokinin octapeptide (CCK-8) was examined in vivo 3 weeks after parathyroidectomy. Secondly, perfusion experiments of isolated pancreas in the sham-operated and parathyroidectomized dogs were examined. In one experiment, volume of pancreatic juice and bicarbonate output, but not amylase output, was decreased in the parathyroidectornized dogs compared with those in the sham-operated dogs; no participation of calcium in exocrine secretion was revealed. In another experiment, high doses of PTH evoked increases of pancreatic juice and bicarbonate output without changing amylase output; as before, no participation of calcium in the exocrine secretion was observed. We conclude that (a) FTH increases volume of pancreatic juice and bicarbonate output, and (b) pancreatic exocrine secretion is modified by direct effect of PTH, and the pancreatic ductular cells, not the acinar cells, are the target for PTH.

Metabolism of insulin and glucagon in liver and pancreas in dogs with obstructive jaundice.

Insulin and glucagon metabolism in the pancreas with obstructive jaundice caused by complete ligation of the common bile duct and in the cholestatic liver caused by hepatic duct ligation was evaluated experimentally using dogs. The isolated perfused pancreas in obstructive jaundiced dogs, which showed a low insulin response in the peripheral blood after intravenous glucose administration, revealed depression of insulin production and no change of glucagon production in response to cholecystokinin octapeptide. The extraction of insulin in the cholestatic lobe of the liver was decreased compared with that in the noncholestatic lobe. The extraction of glucagon, on the other hand, in the cholestatic lobe and in the noncholestatic lobe showed no significant difference. So the imbalance of glucose metabolism in obstructive jaundice does not depend on the enhanced extraction of insulin in the liver, but on the depression of insulin production in the pancreas.

Prostaglandin E1 protects dog pancreas from ischemia-reperfusion injury

Effects of prostaglandin (PG) El on ischemia-reperfusion (I-R) injury to the pancreas was evaluated using isolated in vivo perfused dog pancreas. Pancreatic endocrine and exocrine functions were stimulated with 10−12 M cholecystokinin octapeptide (CCK-8). This amount of CCK-8 promoted production of insulin, glucagon, PGI2, and thromboxane (Tx) A2 in the pancreas. Sixty minutes of ischemia and subsequent reperfusion induced damage to pancreatic ductular, acinar, and β cells. Intra-arterial administration of PGE, at a dose of 0.5 pg/kg/min throughout the experiment prevented the I-R injury, reducing plasma lipid peroxides, and elevating PGI, without changing TxA2 in the pancreas. PGE2 thus appears to protect pancreatic function from I-R injury both by depressing the effect of free-radicals and by decreasing TxA2PGI2which predicts cell injury.

Enhanced sensitivity of pancreatic cells to cholecystokinin octapeptide in obstructive jaundice

Exocrine function of the pancreas in obstructive jaundice was examined using dogs. Jaundice induced by choledochal ligation over 3 weeks showed pancreatic hypersecretion in response to cholecystokinin octapeptide (CCK-8) stimulation. To clarify the mechanism of pancreatic hypersecretion in obstructive jaundice, three experiments were undertaken. In a perfusion experiment performed on isolated pancreas, hypersecretion in obstructive jaundice was observed in response to CCK-8 stimulation. An incubation experiment showed an increase in secretion in response to CCK-8 stimulation in a dose-dependent manner, producing a greater increase in dogs with obstructive jaundice than in controls, despite the fact that basal secretion in both groups was the same. This would suggest that at least one of the mechanisms of pancreatic hypersecretion in obstructive jaundice may be related to the degree of sensitivity of acinar cells to CCK- 8. In morphological observation of acinar cells by electron microscopy, the average number of zymogen granules and total granular area per unit of cytoplasm in both groups before and after stimulation with CCK-8 were compared. There was no difference between the groups before stimulation. Following stimulation, values for the control group decreased but appeared to increase in the jaundiced pancreas. These results strongly suggest that pancreatic acinar cells in obstructive jaundice may retain their secretory potential after stimulation for 60 min, though the potential in nonjaundiced pancreatic acinar cells may decrease after stimulation.Exocrine function of the pancreas in obstructive jaundice was examined using dogs. Jaundice induced by choledochal ligation over 3 weeks showed pancreatic hypersecretion in response to cholecystokinin octapeptide (CCK-8) stimulation. To clarify the mechanism of pancreatic hypersecretion in obstructive jaundice, three experiments were undertaken. In a perfusion experiment performed on isolated pancreas, hypersecretion in obstructive jaundice was observed in response to CCK-8 stimulation. An incubation experiment showed an increase in secretion in response to CCK-8 stimulation in a dose-dependent manner, producing a greater increase in dogs with obstructive jaundice than in controls, despite the fact that basal secretion in both groups was the same. This would suggest that at least one of the mechanisms of pancreatic hypersecretion in obstructive jaundice may be related to the degree of sensitivity of acinar cells to CCK-8. In morphological observation of acinar cells by electron microscopy, the average number of zymogen granules and total granular area per unit of cytoplasm in both groups before and after stimulation with CCK-8 were compared. There was no difference between the groups before stimulation. Following stimulation, values for the control group decreased but appeared to increase in the jaundiced pancreas. These results strongly suggest that pancreatic acinar cells in obstructive jaundice may retain their secretory potential after stimulation for 60 min, though the potential in nonjaundiced pancreatic acinar cells may decrease after stimulation.