We have reported in the previous paper that perfusion of the canine duodenal lumen with the perfusates of pH levels either 1.0 or 3.0 could elicite active release of gastrin into the duodenal lumen from the duodenal mucosa, and gastrin thus liberated was not derived from the mesenteric blood floor. Basing upon the data mentioned above, we have conducted a series of experiments to check the following points: (1) the molecular components of duodenal luminal gastrin thus obtained and its physiological effectiveness in inducing gastric acid secretion, (2) whether the release of duodenal luminal gastrin being caused by active function of G-cells stimulated by those specific pH levels or merely by destruction of the cells, (3) effectiveness of acetylcholine in inducing duodenal luminal gastrin secretion at various pH levels, and finally (4) effectiveness of the physiological stimuly of ingested food in eliciting duodenal luminal gastrin secretion. The data and conclusions subsecuently obtained are as the following. 1) The molecular components of duodenal luminal gastrin thus obtained were composed of G-34, G-17, G-14 and the one bigger than G-34, the composition being quite different from the features of plasma gastrin, suggesting the luminal gastrin was directly derived from the duodenal mucosal G-cells. The samples were fully active in inducing gastric acid secretion. 2) The release of duodenal luminal gastrin at active pH levels was reproducible, alternating the pH levels of perfusate from the acidic to neutral then to acidic again. This finding does support the presumption that the release of gastrin at the acidic pH levels is due to the active function of G-cells and not to the destruction of them. 3) Intraluminal application of acetylcholine could release luminal gastrin only at the acidic pH levels, the molecular components thus obtained showed more prominent peaks of big big gastrin and component-I than the samples obtained without the chemical. 4) Perfusing the duodenal lumen with the test meal, we could demonstrate the active release of luminal gastrin even at the more neutral pH levels. The molecular components of luminal gastrin thus obtained were composed of G-34, G-17 and G-14, again different from the features of plasma gastrin.
To assess the effect of cimetidine and gefarnate on endogenous prostaglandins (PGs) and thromboxane (TX) in rat gastric mucosa in vivo, the animals were repeatedly given those agents for 7 days and mucosal 6-keto-PGF1α (as PGI2), PGE2 and TXB2 (as TXA2) were determined by radioimmunoassay. Cimetidine (20mg/kg i.p. twice a day for 7 days) reduced mucosal PGI2 and PGE2, not TXA2. Gefarnate (100mg/kg s.c. twice a day for 7 days) inhibited cimetidine-induced reduction of mucosal those PGs, while the agent failed to increase mucosal PGI2, PGE2 or TXA2 in untreated control rats.
We investigated the effects of exogenous and endogenous glucagon on gastric emptying, small bowel transit time and plasma motilin concentration. An exogenous administration of glucagon and an intravenous administration of arginine caused a significantly slow gastric emptying, a significantly delayed small bowel transit and a significant decrease in plasma motilin concentration. An integrated incremental response of plasma glucagon during arginine infusion was highly correlated with a delayed gastric emptying and with a prologation of small bowel transit time, which suggested that endogenous glucagon also inhibited gastric emptying and small bowel transit. An increased blood glucose during glucagon or arginine infusion was considered to be little involved in a decrease in plasma motilin concentration and in a slow gastric emptying and a delayed small bowel transit.
A new technique is introduced for the evaluation of the capacity of the gastrointestinal tract to assimilate foods by using a stable isotope of nitrogen (15N) as a tracer. Four groups of male Wistar rats were fed 15N-labeled rice for one day following a basal diet, composed of 87% poudered rice. Then, 15N-labeled rice was switched to basal diet again for the next seven days. The four groups of rats consisted of: Group A-three pancreatic duct-ligated rats; Group B-four sham operated rats; Group C-five control rats and Group D-seven Streptozotocin-treated (20mg/kg) rats. The 15N contents were measured in the stool, urine and sera collected before feeding of 15N-labeled rice and one, three and seven days thereafter. In group A, the rate of 15N excretion into the stools, i.e., the amount of 15N in the stools against the total amount of 15N consumed, was higher as compared to the control group throughout the period of the study. On the contrary, the rate of urinary excretion of 15N as well as the contents of 15N in the urine and sera were apparently lower. In group D, the rate of 15N excretion into the stools as well as the contents of 15N in the sera and urine showed no difference as compared to the control group. The rate of 15N excretion into the urine, however, was apparently higher than that of the control group throughout the period of the study. These results indicate that this stable isotope of nitrogen (15N), which clearly reveals the existence of malabsorption of pancreatic origin, is valuable as a tracer for assimilation studies and technically applicable for clinical use. We have found no evidence of malassimilation in rats with Streptozotocin-induced diabetes in spite of the presence of previous reports that assert the existence of pancreatic exocrine dysfunction in these animals.
In the obstetric records of 119, 004 from 1966-1980 in Okayama city, eight patients of severe liver injury with hepatic encephalopathy were retrospectively reviewed for studying the cause and appropriate management. The incidence of severe liver injury was 0.007 per cent and all of eight cases were primigravida. In seven of eight cases, severe liver injury occurred in the latter stages of pregnancy (3rd trimester) and its mortality rate amounted to 75 per cent. In most of them, encephalopathy occurred immediately after delivery with severe bleeding tendency, and the interval from the onset to encephalopathy and also death were 3 to 10 days and 4 to 45 days, respectively. Liver histology revealed a case of acute fatty liver of pregnancy, 5 cases of acute hepatitis (severe type) with massive or submassive hepatic necrosis and two cases of toxic fatty liver. Seven of eight patients were clinically diagnosed as fulminant hepatitis acording to the recent criteria of fulminant hepatitis. However, fulminant hepatic failure would be better in two cases with severe fatty metamorphosis, because pathological findings as hepatitis were deficient. A great attention should be paid to severe liver injury during the latter stage of pregnancy and delivery.
A nutritional survey was carried out in Tomié-Town, Goto Islands, Nagasaki Prefecture where the incidence of both liver cirrhosis and hepatocellular carcinoma has been the highest in Japan. Analysis on 143 inhabitants of Tomié-Town revealed that their daily intake of total calories, protein, fat, calcium, vitamin A, B1, B2 and C was lower than the averages of nutritional intake in whole Japanese population. Furthermore, constitution of their food was different from that of average Japanese population and was the nutritionally disproportional pattern. When the results in these inhabitants were compared between patients with clinical and/or biochemical liver damage and healthy controls, or between hepatitis B antigen carriers and the others, low nutritional intake and abnormal food constitution correlated closely with liver diseases. These results suggest that although it is not clear whether the undernutrition causes the high incidence of chronic liver diseases or chronic liver diseases are the cause of the undernutrition, nutritional intake is inadequate and unbalanced in the patients with chronic liver diseases even when they are spending normal life without any complaints.
CT and US were carried out on 81 patients with hepatocellular carcinoma, 20 patients with cholangiocellular carcinoma and 94 patients with metastatic liver cancer. 1) Cystic degeneration was observed in one with hepatocellular carcinoma (1.2%), one with cholangiocellular carcinoma (5.0%) and 12 with metastatic liver cancer (12.8%) by US, but this change was observed in only 5 by CT (1, 0, 4, respectively). Metastatic liver cancer showed the highest incidence among these tumors. 2) The characteristics of cystic degeneration of the liver tumors were thickened wall and irregularity of the inner surface of the wall. 3) Judging from macroscopic and histopathological findings, liquefactive necrosis in the tumors was shown as "echoluent" area. We concluded that cystic degeneration was one of the important findings in metastatic liver cancer and that careful observation by US and CT avoided the confusion with other hepatic cystic diseases.
Serum glutamic dehydrogenase (GLDH) activity remained unchanged in abstinence except for the hepatic encephalopathy stage in patients with liver cirrhosis, while it was increased when the patients were complicated with hepatocellular carcinoma (HCC). The increased activities of serum GLDH were also recognized in the patients with carcinoma who were complicated with liver metastasis (LM). Among several biochemical parameters in serum, the GLDH activity appeared to be the most valuable diagnostic one to test the complication of HCC in patients with liver cirrhosis, and that of LM in patients with carcinoma. When chemotherapeutic agents were infused intraarterially to patients with HCC or LM, the GLDH activity changed in reflecting on the clinical effects. Therefore, it was suggested that the measurement of serum GLDH activity in abstinence was a useful screening test for the diagnosis of HCC and LM and for the estimation of the chemotherapy effects.
To determine whether standard liver function tests reflect histological severity of alcoholic liver diseases, 93 patients were evaluated with liver biopsy and the results by a multiple regression analysis of standard liver function tests were compared with liver histology. The best combination of standard liver function tests to distinguish between various types of alcoholic liver diseases was the combination of γ-globulin, GOT/GPT ratio, GPT and total alcohol intake. Using these parameters, the probability to discriminate liver cirrhosis and alcoholic hepatitis from various types of alcoholic liver diseases was 64% and 75%, respectively. The best combination to distinguish liver cirrhosis from liver fibrosis was the combination of γ-globulin, total alcohol intake and Al-P. The probability of the discrimination between liver cirrhosis and liver fibrosis was 76%-79%.
Ultrasonically guided percutaneous drainage of the gallbladder was performed in eleven patients with severe acute suppurative cholecystitis. By the drainage, a general condition was recovered soon in all cases. No hazardous complications were seen in the technique. Seven of the eleven patients underwent cholecystectomy after disappearans of acute inflammatory signs and symptoms of the gallbladder. The 4 remainder having concomittantly severe disorders of heart, kidney or liver were discharged after a complete discovery from acute attacks by the drainage.
In order to clarify the role of the acidic mucopolysaccharides in pancreatic stone formation, secretion of hexosamine and calcium was examined experimentally in normal dogs and in dogs whose main pancreatic duct had been ligated. In normal dogs the output of hexosamine and calcium increased with the administration of pancreozymin. The degree of response showed a close correlation to the dosage of pancreozymin. On the other hand, output of these components decreased gradually and finally showed no response to pancreozymin in those dogs who had had their main pancreatic ducts ligated. But the concentration of these components stagnant in the pancreatic duct markedly increased. As the acidic mucopolysaccharides have a specific affinity for calcium in vivo, these results appear to indicate that the stagnation of pancreatic juice and the existence of the acinar cells which can continuously excrete acidic mucopolysaccharides are absolutely necessary in calcium carbonate pancreatic stone formation.
The relationship between the severity of diabetes mellitus and pancreatic exocrine dysfunction was studied in streptozotocin-induced diabetic rats. Diabetic rats with different severity were made by intravenous injection of three different doses of streptozotocin; 30, 45, or 60mg/kg. Control rats were injected with only citrate buffer. On the 7th day, oral glucose tolerance test was performed after 16-18h fast. Plasma glucose levels were elevated, while insulin response were reduced depending upon the injected dose of streptozotocin. After 12 days, the diabetic animals were used for the experiment. Body and pancreas weight were decreased in diabetics compared with control rats, whereas pancreas weight per body weight was similar in four groups. Insulin content in the pancreas was decreased significantly in diabetic animals in proportion to the injected dose of streptozotocin. Amylase content in the pancreas from the diabetic rats was similarly decreased, while amylase per insulin ratio was not different in all groups. Therefore, the decrease in pancreatic amylase content of diabetes was closely related to the severity of diabetes mellitus.
Pancreatic exocrine function and morphologic changes were investigated in groups of rats receiving solutions of ethanol by oral or intravenous route, or equicaloric doses of glucose solution by intravenous route daily for a period of 4 weeks. Comparable degrees of exocrine dysfunction and morphologic changes in the pancreas at the ultrastructural level were observed in the groups given ethanol orally and in those receiving i.v. injections of ethanol, suggesting that neither intragastric ingestion nor high blood levels of alcohol is required for alcohol to exert its pancreatotoxic effects. All groups of rats receiving ethanol or glucose showed signs and pathologic findings of nutritional disorder, and at 4 weeks of treatment, electron microscopic abnormalities in the pancreas were more pronounced and higher in incidence in the groups given ethanol p.o. or i.v. than in the groups given i.v. doses of glucose. There was no microscopic evidence of protein plug or other changes in the region of origin of the pancreatic duct system in rats after 18 months of oral administration of ethanol. The present findings indicate that the cytotoxic effect of alcohol on acinar cells and nutritional disorder associated with alcohol ingestion constitute important factors in the pathogenesis of chronic alcoholic pancreatitis.