Gastric emptying controls food delivery into small intestine, thus postprandial blood sugar level is supposed to be controlled by gastric emptying. In this study we compared gastric emptying state and postprandial insulin requirement by artificial pancreas (Biostator®) in diabetic patients. The ratio of posprandial/total daily insulin requirement of patients with delayed gastric emptying is significantly lower than that of patients with normal gastric emptying. There were highly significant correlation between gastic emptying and postprandial insulin requirement by artificial pancreas in diabetic patients. This suggests that gastric emptying has important role in blood sugar level control in diabetics. Thus, the pattern of insulin demand by artificial pancreas during feedback control of constant blood sugar level is supposed to show the gastric emptying state.
The effect of hyperammonemia on the gastric mucosa were studied by light and electron microscope in the rat with portacaval shunt (PCS) in this paper. Blood ammonia level was 120±46.7μg/dl in the rats with only PCS shunt operation. Transmission electron microscopic observation demonstrated slight edematous change under the surface mucous cells in the rats with only PCS, and severe edematous change under and between surface mucous cells in the PCS rats 30 minutes after intra-peritoneal injection of ammonium acetate. In the group with ammonium loading, the edematous change improved according to the decrease of blood ammonia. Obvious disruption of mucosal epithelial cells and deterioration of the fine vessels under the surface mucous cells, suggesting erosive change, were observed by electron microscopy in the rats with PCS 120 minutes after ammonium loading. The results of this experiment may suggest that hyperammonemia is one of the important factors in the etiology of gastric mucosal injury in the rats with PCS.
We investigated the cases who were positive both HBsAg and anti-HBs in the sera clinically and immunologically. 1) 36 cases in 191 HBsAg positive subjects (18.8%) had anti-HBs in the sera simultaneously, although the anti-HBs of those were not detected by passive hemmaglutination method. 2) In HBs-Ag carriers, the case with chronic liver disease had higher rate of co-occurrence of HBsAg and anti-HBs (27 in 70, 38.6%) than that of asymptomatic carriers (9 in 117, 7.7%, p<0.005). 3) In co-occurrent cases, the titer of anti-HBs of chronic liver disease was significantly higher than that of asymptomatic carriers. 4) No differences were obtained from the analysis of the co-occurrent cases and another group about age, sex and the frequency of HBeAg and anti-HBe. 5) There was no differences in non-specific immune complexes between the co-occurent cases and another. HBsAg specific immune complex was detected more in co-occurrent cases than another (p<0.005). The cases with chronic liver disease had more non-specific and HBsAg specific immune complexes than asymptomatic carriers. According to these facts, immune complex seemed to be related to the pathogenesis or the consequences of viral hepatitis and the high incidence of liver disease in co-occurrent cases.
Rat livers in obstructive jaundice or cirrhosis were investigated for glucose utilization, hepatic blood flow, oxygen consumption and mitochondrial function. In these livers there were noted a markedly diminished glycogensynthesizing capacity, decreased reponsiveness to glucagon and cyclic-AMP, and impairment notonly of liver cell membrane but also of that portion of the second messenger. Mitochondrial function was flund diminished before any changes in the hepatic mitochondrial concent of cytochromes became noticeable and, as a consequence, a decrease in mitochondrial concent of adenine nucleotides was observed. Rat livers in obstructive jaundice or cirrhosis also showed decreased effective hapatic blood flow and diminished oxygen consumption. Cytothromes in liver tissues of obstructive jaundice or cirrhosis were converted more readily to their reduced from in the presence of oxygen deficiency than those of a normal liver.
To estimate vascular changes in chronic liver disease, we quantitated intrahepatic arterio-venous and portal-systemic shunts in 12 patients with cirrhosis and arterio-venous shunts alone in 4 patients with cirrhosis. Intrahepatic arterio-venous shunts were measured by instilling 99mTc-macroaggregated albumin into the proper hepatic artery and portal-systemic shunts by the same procedure done in the portal trunk near the portal hepatis on different days. Counts were taken over the liver and both lungs in the anterior as well as the posterior view for calculation of the shunts: lungs/(liver+lungs) counts per min×100%. In the 12 patients with cirrhosis in whom both shunts were measured, intrahepatic arterio-venous shunting was significantly lower compared with intrahepatic portal-systemic shunting (1.4%±1.1% vs. 36.0%±29.0%, p<0.001). Thus, it seems that in patients with cirrhosis, the development of intrahepatic arterio-venous shunts is not as significant as portal-systemic shunts which were found in this study to be considerable and variable in degree.
We developed a new approach of intra-arterial infusion with chemoembolization for hepatocellular carcinoma (HCC) using lipiodol (LPD), cisplatin (CDDP) and gelfoam cube. The method is as follows: the mixture of LPD and CDDP was infused before and after the massive infusion of CDDP into the hepatic artery, fullowed by embolization by gelatin cube. From November 1984 to March 1986 we performed this therapy to 63 patients with HCC and 27 patients out of 63 received hepatic resection after this therapy. Therapeutic effect could be seen in all cases. In 36 cases without hepatic resection, one and two-year cumulative survival rate were 82.3% and 42.2%, respectively. These survival rate were statistically better than in cases treated by chemoembolization using. Adriamycin, LPD and gelfoam cube in which one- and two year cumulative survival rate were 50.0% and 30.0%, respectively. Better cumulative survival rate could be seen in group with 0 or 1 of performance status (p<0.01), male (p<0.05), serum AFP levels less than 400ng/ml (p<0.05) and without tumor invasion to portal vein. Side effect were not so severe and were transient in all cases.
Fasting serum squalene (FSS) level was determined in patients with gallstones and hyperlipidemia. FSS and the lithogenic index of some gallstone patients were also determined before and during CDCA or UDCA administration. It was then discussed whether the measurement of FSS well reflects the synthesis rate of cholesterol in human subjects. Significant elevation of FSS was found in patients with cholesterol gallstone and type IV hyperlipidemia and this was accompanied by a high lithogenic index. The reason for the high incidence of gallstone in type IV may have been due to elevated synthesis of cholesterol and a situation of imminent gallstone formation is present in type IV. FSS was significantly decreased during CDCA administration, suggesting that CDCA inhibits cholesterol synthesis. FSS, which was high before medication, was also decreased during UDCA, although there was no statistically significant difference. It was concluded from the above results that the determination of FSS is clinically useful for the screening and treatment of gallstones and that FSS well reflects cholestrol synthesis in man.
In order to elucidate the relationship between the duodenal motor activity and the pancreatic exocrine function in chronic liver diseases, the intra-luminal pressure of the duodenum, the flow of pancreaticobiliary juice and plasma motilin levels were measured simultaneously during the pancreozymin-secretin test in 29 patients with chronic liver diseases and 8 patients without liver disease who served as a control. In patients with liver cirrhosis, gastroscopy was performed and the presence of gastric mucosal lesions were studied. The incidence of phase III activity induced by seretin was lower in the patients with chronic liver diseases than in the control group. Pancreatic exocrine volume was increased in the patients with chronic hepatitis and compensated liver cirrhosis, but decreased in the patients with decompensated liver cirrhosis. The incidence of gastric mucosal lesions was higher in cases with the abscence of secretin induced phase III activity than in cases with the presence of it. Regarding motilin, the changes of the plasma motilin levels were dependent on the phase III activity induced by secretin, therefore motilin was not considered to be the initiator of phase III activity. In conclusion, an imbalance between the duodenal motility and the flow of pancreaticobiliary juice existed in patients with chronic liver diseases, suggesting that it might be one of the etiology of the gastric mucosal lesions in this disorder.
The mechanism of production and secretion of CA19-9 was studied on cultured human gastric cancer cell lines. Among several cell lines, KATO-III had relatively high ability to produce CA19-9 and also secreted large amounts of CEA at the same time. Distinct difference between CA19-9 and CEA, however, was found in both their kinetics of secretion into the medium and their subcellular distribution. It was revealed that CA19-9 was present in the cell surface of KATO-III by using indirect immunofluorescence technique and that CA19-9 existed as large molecular weight glycoproteins (mucin) based on gel chromatography of the spent medium and cell lysates on Sepharose CL-4B. On the other hand, CA19-9 could not be detected in glycolipids (gangliosides) fraction from KATO-III cell membranes. These findings suggest that KATO-III produces and secretes CA19-9 as glycoproteins (mucin) but not as glycolipids.
Action of galanin on insulin and pancreatic glucagon secretion was investigated with synthetic galanin at the basal and stimulated secretion by low-dose glucose infusion. 1) Galanin infusion caused rapid and reversible inhibition of the basal insulin secretion in a dose-dependent manner. Plasma glucose levels gradually increased by galanin administration with dose-dependency, and the maximal hyperglycemic action was observed when galanin was infused at a rate of 4μg/kg/hr. Cortisol, growth hormone, adrenalin or noradrenalin, which was considered to contribute to the plasma glucose regulation, was not affected by galanin infusion. 2) During continuous infusion of low-dose glucose, galanin caused no significant changes in plasma glucose levels at a rate of 4μg/kg/hr. Infused at a rate of 16μg/kg/hr, galanin caused significant hyperglycemia similar to that seen at 4μg/kg/hr in the basal secretion. 3) Pancreatic glucagon levels were not affected by galanin administration both at the basal state and duing low-dose glucose infusion. These results indicate that galanin may play a role in the plasma glucose regulation through the inhitory action on the basal insulin secretion.
To evaluate the effects of upper abdominal autonomic denervation on the regulation of glucagon secretion 10 control dogs, 10 vagotomized dogs, 10 upper abdominal autonomic denervation dogs were investigated by intraduodenal glucose administration. In vagotomized group, responses of glucagon were not significantly different from control group. In upper abdominal autonomic denervation group, glucose, insulin, and glucagon levels were significantly higher than those in control group after glucose loading. By gel filtration analysis, the essential cause of high glucagon response after glucose loading was the increase in MW8000-12000 glucagon. These findings suggested that upper abdominal autonomic denervation augmented the responses of glucagon like immunoreactivity after intraduodenal glucose loading.
The effects of bile-pancreatic juice diversion on pancreatic secretion and changes in plasma CCK-8 equivalents were determined in conscious rats. Rats were prepared with cannulae, draining pure pancreatic juice and bile separately. Plasma CCK-8 equivalents were bioassayed, based on their ability to stimulate amylase release from isolated rat pancreatic acini. Diversion of bile-pancreatic juice resulted in an extreme increase in pancreatic protein output. Plasma CCK bioactivity also increased by BPJ diversion, peaked at 2 hours after the begining of BPJ diversion, then slightly declined and continued for 24 hours. The changes in plasma CCK concentraions almost paralleled with the change in protein output. These results indicate that the feedback regulation of pancreatic secretion in the consious rat is mediated by the release of chlecystokinin.