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Biomedical subjects

T Takebe

Publications and source records attributed to T Takebe.

At least 37 records · Page 2Linked to original sources

[The effect of oral synthetic protease inhibitor (FOY 305) on endocrine pancreas and carbohydrate and lipid metabolism in normal and streptozotocin-induced diabetic rats].

The effect of long-term oral synthetic protease inhibitor (FOY 305) administration on fasting blood sugar (FBS), body weight, glucose tolerance, plasma insulin and glucagon levels, pancreatic insulin and glucagon contents, hepatic enzyme activities, and plasma lipids in normal and streptozotocin (STZ)-induced diabetic rats was studied. Normal rats treated with oral FOY 305 for 9 weeks were found to have pancreatic hypertrophy and decreased body weight gain as compared with the untreated normal controls. FBS, glucose tolerance, plasma insulin and glucagon levels, pancreatic insulin and glucagon contents, and plasma lipids were uninfluenced in FOY 305 treated normal rats. STZ-induced diabetic rats treated with oral FOY 305 were found to have decreased FBS for 5 weeks after the beginning of FOY 305 administration as compared with the untreated diabetic controls, whereas at the 7th and 9th week after treatment there was no difference in FBS between FOY 305 treated and untreated diabetic rats. In the metabolic balance observed at the 4th week after treatment, a slight improvement of the diabetic state was found in FOY 305 treated diabetic rats. There was no apparent difference in the blood sugar curve and insulin response following oral glucose load between diabetic rats treated for 7 weeks and untreated diabetic rats. All the rats were sacrificed after 9 weeks of treatment. Diabetic rats treated with oral FOY 305 for 9 weeks showed pancreatic hypertrophy and decreased plasma glucagon level and decreased pancreatic glucagon content as compared with the untreated diabetic controls, whereas there was no difference in body weight, plasma insulin level and pancreatic insulin content between FOY 305 treated and untreated diabetic rats. Furthermore, oral FOY 305 treatment improved hyperlipidemia in STZ-induced diabetic rats and also significantly improved the hepatic pyruvate kinase and phosphoenlpyruvate carboxykinase activities of diabetic rats. These improvements might partly be due to a decreased pancreatic content and secretion of glucagon and/or a direct action of the synthetic PI, FOY 305 to tissues.

Animals↗

Elevation of plasma high density lipoprotein-cholesterol in spontaneously diabetic Chinese hamsters.

The aim of this study is to define the change of plasma high density lipoprotein-cholesterol (HDL-C) in the spontaneously diabetic Chinese hamsters in the Asahikawa colony (CHA). These animals were divided into two groups according to fasting plasma glucose level; non-diabetic group and diabetic group. Plasma HDL-C was measured by a microliters-scale ultracentrifugal method using an RPL-42T rotor (Hitachi Koki Co.). The diabetic hamsters had hypoinsulinemia and hyperlipidemia. Plasma HDL-C in the diabetic group was significantly elevated as compared with the non-diabetic group. A significant positive correlation was observed in both groups between plasma HDL-C and total cholesterol. The male hamsters tended to have higher plasma HDL-C and total cholesterol levels than the female hamsters in either group. Moreover, an electrophoretic analysis showed that there was some relative increase in plasma very low density lipoprotein, low density lipoprotein and high density lipoprotein (HDL) in the diabetic hamsters. An ultracentrifugal analysis showed that plasma chylomicron appeared only in the diabetic hamsters. The heterogeneity of particle size of HDL was found by gradient gel electrophoresis. The apparent average molecular weight of HDL was approximately 265,000 in either group. It is concluded that plasma HDL-C increased with the advance of hyperglycemia and hyperlipidemia in insulin-deficient diabetic hamsters and that there was sex difference in the hamsters for plasma HDL-C and total cholesterol.

Animals↗

[Acute necrotizing pancreatitis caused by the injection of lysolecithin into the pancreatic duct in the rat. Its natural course and effect of drugs on rate of survival].

Acute experimental pancreatitis was induced by retrograde injection of 0.15 ml of 0.8% lysolecithin into the pancreatic duct of Wistar rats. This procedure was always followed by severe necrosis of pancreatic parenchyma, bloody ascites and numerous fat necroses in the abdominal cavity. Histologically, at the 30th minutes after the induction of pancreatitis, spotty necrosis of pancreatic tissues and marked edema of interstitium were observed. The necrosis gradually expanded accompanying bleeding and inflammatory cell infiltration till the 60th hours. At the 72nd hours after the induction there were the replacement of the necrotic tissue with the fibroblasts, the neogenesis of the ductular epithelium and the formation of acinus-like structure. Among the changes of extrapancreatic organs those of the lung were pronounced. Macroscopically, from the 12th hours stiff and reddish lung frequently occurred. Histologically, micro-macroatelectasis, edema and cell infiltration of the alveolar wall, and the stricture of the bronchioles were observed. In this experimental pancreatitis, the rate of survival was about 50% within 48 hours and about 30% within 72 hours, respectively. Continuous intravenous infusion of cytidine diphosphate choline at a dose of 300 mg/kg/day and intravenous injection of methylprednisolone at a dose of 60 mg/kg/day significantly improved the rate of survival within 24 hours and within 30 hours, respectively.

Acute Disease↗

[Antineoplastic effect of UFT therapy (uracil-FT-207 combination therapy) on experimental pancreatic cancer transplanted in the pancreas and subcutaneous region].

The pancreatic duct cell adenocarcinoma induced by di-isopropanol nitrosamine could be easily and repeatedly transplanted into the subcutaneous or pancreatic tissues of the homologous animals. We established a tumor bearing animal design in which tumor tissues were transplanted simultaneously into subcutaneous and pancreatic tissues. At the first week after the transplantation, the animals were divided into three groups: In FT group FT-207 was given at a dose of 15 mg/kg/day, in UFT group FT-207 and uracil were given at a dose of 3 mg/kg/day and; 6.7 mg/kg/day (molar ratio; 1:4), respectively and in control group a solvent of FT-207 was given. In all groups the drugs were administrated orally for ten days. The size of tumors transplanted in subcutaneous and pancreatic tissues increased more slowly in FT and UFT groups, as compared with that of control group. The inhibitory effect on tumor growth observed in UFT group was more striking than that in FT group. No major side effects were observed in all groups. At the fourth weeks after subcutaneous and intrapancreatic transplantation, the animals were divided into two groups: In FT group FT-207 was given at a dose of 30 mg/kg and in UFT group FT-207 and uracil were given at a dose of 30 mg/kg and 67.2 mg/kg, respectively. In both groups the drugs were given orally, and at one hour after the administration all the animals were killed to determine 5-FU concentration in various tissues. The 5-FU concentrations of subcutaneous and intrapancreatic transplanted tumor tissues were significantly higher in UFT group than those in FT group. UFT therapy, therefore, seems to be hopeful for the treatment of human pancreatic cancer.

Animals↗

Effect of long term alcohol feeding on the pancreas in rat.

To elucidate the pathophysiological process of alcoholic pancreatitis, chronic alcohol intoxication was made in Wistar rats on balanced diet giving 20% ethanol freely for 60 weeks. The control rats received water. Histological picture of the pancreas, hormonal activity in the mucosa of upper digestive tract and the nature of pancreatic juice were examined in every 15th week. The results were as follows. 1) No histological changes were noted in the pancreas of control group. In the ethanol group, morphological abnormalities of the pancreas appeared after 30 weeks. Of the histological findings, the changes on the ductal system such as dilatation of pancreatic duct, plug formation in the ductal lumen and periductal fibrosis were significant. 2) The long term ethanol administration tended to decrease the amounts of gastrin, secretin and cholecystokinin contained in the gastrointestinal mucosa. 3) Regardless of the histological changes of the pancreas, almost no changes were noted in the bicarbonate and protein concentration during the experimental period of 60 weeks. From the above results, a mechanism obstructing pancreatic ductal system is considered to be important in the pancreatic lesions by alcohol rather than a mechanism of stimulating pancreatic exocrine secretion.

Alcoholism↗

Reserve capacity of bicarbonate secretion in chronic pancreatitis.

When secretin was given by continuous intravenous infusion in the control subjects, the dose of secretin inducing maximal bicarbonate output was found to be around 6.0 CHR U/kg/hr. Then the pancreatic exocrine secretory response to sequential standard (1.2 CHR U/kg/hr) and augmented (6.0 CHR U/kg/hr) dose of secretin was studied in the controls, in patients with chronic pancreatitis and in its suspected cases. This new method for exocrine pancreatic function did not offer advantage for the diagnosis of well established chronic pancreatitis. But from the results obtained in suspected chronic pancreatitis it was supposed that the decline of increasing rate of bicarbonate output with augmentation of dose and the decrease of response to augmented dose of secretin might be one of functional disorders occurred in the early stage of chronic pancreatitis.

Adolescent↗

The significance of the sweat test in chronic pancreatitis.

In order to study the disposition which is thought to be latent in chronic pancreatitis, we investigated the sweat chloride concentration of 95 normal subjects, 43 cases of chronic pancreatitis, 12 cases of cholelithiasis, 15 cases of peptic ulcers, 16 cases of hepatic diseases and 23 cases of diabetes mellitus with the sweat test, using the method of pilocarpine iontophoresis. We obtained the following results. (1) In normal subjects, the sweat chloride concentration was inclined to rise gradually with age from childhood to adulthood; the mean value of sweat chloride concentration was 30.0 mEq/liter in adults from 20 years old, and the upper limit was about 60 mEq/liter. (2) The mean value of sweat chloride concentration was 60.0 mEq/liter in chronic calcifying pancreatitis; this value was markedly higher than that of control subjects of the same age (p is less than 0.001). (3) The mean value of sweat chloride concentration in cholelithiasis, peptic ulcer and hepatic diseases did not differ significantly from control subjects. The mean value of sweat chloride concentration in diabetes mellitus was significantly higher than that of control subjects (p is less than 0.01), but was significantly lower than that in chronic pancreatitis (p is less than 0.01). (4) It was supposed that some cases of chronic pancreatitis have a congenital disposition toward abnormal secretion of sweat glands and epithelium in the pancreatic duct, resembling cystic fibrosis, and this disposition leads easily to pancreatic disorders when the individual is exposed to various external factors.

Adolescent↗

Secretin-like bioactivity in the duodenal mucosa in patients with peptic ulcer and chronic pancreatitis.

Biopsy specimens of the duodenal mucosa were assayed to determine their secretin-like activity in 9 controls, 9 patients with gastric ulcer, 19 patients with duodenal ulcer, 4 patients with gastric and duodenal ulcer, and 13 patients with chronic pancreatitis. The bioassay of secretin was done on the pancreatic secretion in anesthetized rats. The sensitivity was in the orcer of 0.0625 CHR unit/rat (4 ng/rat). In the range between 0.0625 and 0.5 CHR units a satisfactory dose dependency was recognized. The following results were obtained. 1) The level of duodenal mucosal secretin-like activity in patients with gastric ulcer was the same as that in the controls, but was elevated in 32% of the patients with duodenal ulcer, 50% of those with gastric and duodenal ulcer, and 8% of those with chronic pancreatitis. 2) The high level of secretin-like activity noted in patients with duodenal ulcer was suspected to be related to the hypersecretion of gastric acid which is characteristic of this disease, but there was no correlation between gastric acid secretion and secretin-like activity in the duodenal mucosa.

Adolescent↗

Clinical evaluation of iron metabolism in pancreatic disease.

In order to estimate the possible influence of pancreatic disease upon iron absorption, fecal analysis was carried out after administration of 5 mg iron labeled with 59Fe. Twelve cases of pancreatic calcification, 7 cases of chronic pancreatitis, 3 cases each of pancreatectomy and miscellaneous diseases, and 52 cases for control were studied. Significant elevation of iron absorption was observed in 4 or 21 patients with pancreatic diseases. Two of the 4 cases were also found to have low transferrin saturation and the other two have had a long history of heavy alcoholic intake. There was no definite correlation between the iron absorption rate and the total bicarbonate secretion, and duration of the diseases. Three cases treated with pancreatectomy failed to show increased iron absorption. The alternative administration of 59Fe and 55Fe for consecutive 4 days either alone or together with pancreatin or secretin was done to see the effect of these preparations on iron absorption. No significant inhibitory effect of these preparations on the iron absorption was noticed. These observations suggest that exocrine pancreatic function seldom appears to influence directly iron absorption, and that iron deficiency and ingestion of alcoholic beverages can be important factors affecting the iron absorption in pancreatic diseases.

Acute Disease↗

Continuous secretin infusion with pancreozymin pretreatment as a pancreatic function test.

This paper deals with a pancreatic function test with the submaximal dose of secretin given by continuous infusion after injection of cholecystokinin-pancreozymin (CCK-PZ) in the submaximal dose. The active elimination of bladder bile by CCK-PZ pretreatment decreased the influence of biliary contamination, and the volume output and the bicarbonate concentration were stabilized by the continuous infusion of secretin. As a result, the coefficients of variation in the volume output and the bicarbonate concentration were calculated to be about 15 and about 5%, respectively. These variations were considerably smaller than those obtained in the standard secretin test. Therefore, the present study is expected to improve the diagnostic means for pancreatic excretory dysfunction.

Amylases↗

Secretin-like activity in duodenal mucosa and peptic ulcer.

The secretin-like activity contained in bioptic specimens of duodenal mucosa was measured by means of bioassay in healthy controls and patients of peptic ulcer. It was found that the activity tended to be increased in duodenal ulcer in comparison with gastric ulcer which did not differ from healthy controls. Possibilities of impaired release and/or increased production of secretin-like substance in duodenal ulcer were discussed.

Animals↗