Masayoshi Goto

Protective effect of nitric oxide on development of acute pancreatitis in rats

Nitric oxide (NO) has been implicated to regulate pancreatic circulation, promote capillary integrity, and inhibit leukocyte adhesion. We investigated the role of NO in the development of pancreatitis. Nitro-l-arginine, an inhibitor of NO synthase, in total dose of 35 mg/kg body wt was infused in the rats with edematous pancreatitis induced by two intraperitoneal injections of cerulein (20 μg/kg).l-Arginine (125 or 250 mg/kg), a NO donor was intravenously administered twice in the rats with hemorrhagic pancreatitis induced by waterimmersion stress plus two intraperitoneal injections of cerulein (40 μg/kg). The degree of pancreas edema, serum amylase levels, and histologic alterations were investigated. Nitro-l-arginine exacerbated cerulein-induced pancreatitis and caused a decrease in pancreatic blood flow.l-Arginine ameliorated the severity of hemorrhagic pancreatitis dose dependently and improved the pancreatic blood flow. These findings suggest that NO could confer protection against the development of hemorrhagic pancreatitis, probably through improvement of the pancreatic microcirculation.

New chronic pancreatitis model with diabetes induced by cerulein plus stress in rats

To establish a new experimental model of chronic pancreatitis (CP) with diabetes, we investigated pancreatic endocrine function, blood flow, and histopathology in CP induced by repetition of cerulein injection plus water immersion stress in rats. CP rats were treated with water immersion stress for 5 hr and two intraperitoneal injections of 20μg/kg body weight of cerulein once a week for 16 weeks. In the CP group, pancreatic contents of protein, amylase, elastase, and lipase significantly decreased to 64, 38, 23, and 68% of the control group, respectively. In oral glucose tolerance test (glucose 2 g/kg body wt), blood glucose level in the CP group was 212.1±97.8 mg/dl (mean±sd) at 30 min and was significantly higher than the control group (126.3±15.4 mg/dl) (P<0.05). Two of seven rats in the CP group showed an obvious diabetic pattern with a blood glucose level over 200 mg/dl at 120 min. The basal level of serum insulin in the CP group was 640.1±148.7 pM, significantly lower than in the control group (1133.4±242.0 pM) (P<0.001). However, insulin content in the pancreas was 12.37±1.72 nmol/pancreas and was preserved compared with the control group (10.24±1.94 nmol/pancreas). In CP rats, winding and dilatation of surface blood vessels and gland atrophy were evident. Marked fibrosis, fatty changes, and destruction of lobular architecture were also demonstrated microscopically, although the structure of each pancreatic islet was preserved and each islet was fully stained with anti-insulin antibody. In the CP group, pancreatic blood flow by the hydrogen gas-clearance method was 197.6±33.0 ml/min/100 g, which was significantly less than the control group (276.2±19.1 ml/min/100 g) (P<0.001). Thus, we conclude that the CP model induced by cerulein plus stress is a new CP model with diabetes in rats, in which the glucose tolerance was impaired without loss of insulin reserve.

Protective effects of gabexate mesilate on acute pancreatitis induced by tacrolimus (FK-506) in rats in which the pancreas was stimulated by caerulein

We investigated the acute effects of the immunosuppressive agent, tacrolimus (FK-506), on the exocrine pancreas, in rats with or without stimulation of the pancreas, in rats with or without stimulation of the pancreas, and evaluated the protective effects exerted by gabexate mesilate (FOY). While an intravenous injection of FK-506 did not change serum amylase levels during the 5-h observation period, this agent increased pancreatic amylase and protein content, and decreased the content of pancreatic DNA. Histologically, we observed intra-acinar vacuolization and individual cell necrosis. When the pancreas was stimulated by two intraperitoneal injections of caerulein (5 μg/kg) at 1-h intervals, however, which treatment did not induce any evident pancreatic change, FK-506 significantly increased serum amylase, pancreatic wet weight, and pancreatic amylase and protein, and decreased pancreatic DNA. Histologically, there were significant dose-related differences in the severity of intra-acinar vacuolization, interstitial edema, neutrophil infiltration, individual cell necrosis, and hemorrhage. Levels of intrapancreatic elastase were elevated and local pancreatic blood flow was reduced. Treatment with FOY improved the FK-506-induced acute pancreatitis, but did not increase the pancreatic blood flow. These findings indicate that FK-506 enhances abnormal pancreatic enzyme secretion and suggest that therapeutic doses of this agent can induce acute pancreatitis when the pancreas is stimulated. A protease inhibitor may protect the exocrine pancreas in patients who receive FK-506 after organ transplantation.

Morphological study of pancreatic endocrine in an experimental chronic pancreatitis with diabetes induced by stress and cerulein.

The purpose of this study was to investigate the morphological changes in the islets observed in a new chronic pancreatitis model with diabetes induced by repetition of cerulein injection plus water-immersion stress in rats. The rats of this model were treated with water-immersion stress for 5 h and two intraperitoneal injections of 20 micrograms/kg body weight of cerulein once a week for 16 weeks. In the stress and cerulein group, 62% of the islets exhibited infiltration of mononucleated cells, and/or peri- and intrainsular fibrosis. On immunohistochemical study, some islets showed reduced density of the insulin immunoreactivity. The glucagon-producing cells decreased in number. With electron microscopy, various endocrine changes were observed, mainly in the B cells. The changes included scattered debris damage with reduction of secretary granules, and vesiculation of the endoplasmic reticulum. Numerous fibroblasts clustered around the islets, and proliferating collagen fibers invaded the islets. The microvascular changes consisted of bleeding and damage to the endothels. In the pancreas treated with stress alone or cerulein alone, significant endocrine damage was not observed. In conclusion, chronic repetitive treatment with stress and cerulein, together with poor islet circulation due to fibrosis and vascular changes, resulted in the endocrine cellular damage.

Effect of pancreastatin on cerulein‐stimulated pancreatic blood flow and exocrine secretion in anaesthetized rats

Background : Pancreastatin (PST) is an inhibitor of pancreatic exocrine secretion in vivo but not in vitro, which suggests that the inhibitory effect of PST is indirect, that is, not mediated by a specific receptor on pancreatic acinar cells. In this study, we investigated the effects of PST on pancreatic exocrine secretion and local pancreatic blood flow in anaesthetized rats to elucidate the participation of PST in indirect regulation of pancreatic exocrine function through blood supply.

Measurement of Pancreatic Blood Flow with the Intraductal Electrode Method of the Hydrogen Clearance Technique in Acute Pancreatitis in Rats

Measurement of local pancreatic blood flow during acute pancreatitis is thought of as being technically difficult in smaller animals. In this study, we first employed an intraductal electrode method of the hydrogen clearance technique for measurement of changes in local pancreatic blood flow in two types of acute pancreatitis in rats, then compared this method with an interstitial electrode method that has been used in rats. There was a very close correlation between these methods (r = 0.998, p < 0.001). The intraductal electrode method was easily performed and caused minimal tissue damage.

Case Report: Mucin-producing cystic neoplasm of the pancreas with onset in childhood

Mucin‐producing tumours of the pancreas have been recently reported with increasing frequency and most cases have occurred in middle‐aged and elderly people. In the present report, a case of a 21‐year‐old man with mucinous cystadenoma of the pancreas is reported. He had a long history of recurrent pancreatitis from the age of 8. When he was aged 10, the first branch of the main pancreatic duct was shown to be enlarged on endoscopic retrograde pancreaticography (ERP). A series of ERP studies and computed tomography scans performed over a period of 11 years demonstrated continuing growth of this enlargement of the pancreatic duct. Pancreaticoduodenectomy was performed and the patient has been well without further episodes of acute pancreatitis and has been free of recurrent tumour for 1 year.

A further study on the membrane currents related to Ba-induced pacemaker in the bullfrog atrium.

In the SR-poor frog atrial muscle, the presence of transient inward current (ITI) was demonstrated in Ba (0.2-0.3 mM) Ringer after treatment with isoproterenol. A peculiar slow inward current (IU) superposing on the tail of the delayed outward current (IX) was also elucidated at the maximum diastolic potential level, which may enhance the pacemaker depolarization.