We induced gastric mucosal lesions in fasting rats with 0.8N HCl and studied the effect of cimetidine on prostaglandin E2 and cyclic AMP to examine the mechanisms underlying the rebound phenomenon after cimetidine withdrawal. Prostaglandin levels in the fundic and antral mucosa of control rats were 1.05±0.23 and 2.53±0.44μg/g, respectively; they were significantly lower (0.30±0.08 and 0.41±0.13μg/g, respectively; p<0.01) in cimetidine treated rats (100mg/kg, i. p.). Cyclic AMP levels in the fundic and antral mucosa were also decreased by cimetidine administration. The ulcer index (total mm length of all ulcer lesions in the fundus and the pyloric antrum) of HCl-treated controls was 42.3±6.7; it was enhanced to 76.3±5.7 by cimetidine. HCl-treated rats received simultaneous administrations of cimetidine and prostaglandin E2 (100μg/kg, p. o.) did not develop gastric mucosal lesions. The results suggest that in rats, cimetidine enhances the development of HCl-induced gastric mucosal lesions by reducing intramucosal prostaglandin E2 and that the rebound phenomenon may occur when the antisecretory effect of cimetidine ceases prior to recovery of the premedication intramucosal prostaglandin E2 level.
Fibrinolytic activity in biopsied colonic mucosa was examined in patients with ulcerative colitis and most cases were found to have increased tissue fibrinolysis, mainly due to tissue plasminogen activator, in the affected mucosa. Five cases were treated with an antifibrinolytic agent, tranexamic acid (t-AMCHA), by enema to inhibit fibrinolysis of the affected mucosa directly. Four cases with elevated mucosal fibrinolysis had responded well to the therapy while one with decreased fibrinolysis did not, indicating that tranexamic acid may show a therapeutic effect in ulcerative colitis with elevated mucosal fibrinolysis when it is given by enema which allows direct contact of the drug with the affected mucosa.
A synthetic amino acid solution (GO-80) originally prescribed by Fischer was used to improve hepatic encephalopathy (HE). The solution containing 40g of amino acids was infused in 7 patients: 1 with fulminant hepatitis, 3 with subacute hepatitis and 3 with liver cirrhosis with HE. The ratio of val+Leu+Ile/Tyr+Phe (BCAA/AAA) Was elevated to normal level in all the patients, immediately after the infusion, however, the improvement of HE was observed in only 3 patients: 1 with subacute hepatitis and 2 with liver cirrhosis. The improvement of HE was correlation with neither the extent nor the duration of the elevation of the ratio. Likewise, in 17 patients with liver cirrhosis including 3 with HE, a temporal normalization of the ratio BCAA/AAA was observed after an infusion of GO-80. The elevation of the ratio was due to a significant increase of the BCAA and a significant decrease of the AAA. The levels of the AAA were lowered further by the elevation of plasma insulin levels after administration of GO-80 and glucose. In the 3 patients with HE, the urinary excretion of urea increased by GO-80 plus glucose.
Prognosis of chronic hepatitis has been evaluated clinically as well as histologically in 97 patients with a mean age of 41.0±11.5, classified on initial biopsy as chronic inactive hepatitis (CIH-39 cases), chronic active hepatitis (CAH-39 cases), chronic active hapatitis with sublobular necrosis (CAHcSN 18 cases) and chronic active hepatitis with lobular disorganization (CAHcLD-23 cases). The particular emphasis was made on the incidence of cirrhosis of the liver (LC) and clinical factors to progress to LC in these patients. The following results were obtained. 1) over-all incidence of progress to LC was 10.3% in CAH, 27.8% in CAH c SN and 52.2% in CAHcLD. There was no single case of LC from CIH. 2) Mean duration (months) progressing to LC was 86.6±21.6 in CAH, 36.6±18.7 in CAH c SN and 41.4±23.2 in CAHcLD. 3) The incidence of progress to LC was higher in patients over 40-year-old and with alcoholic history. 4) Corticosteroid therapy did not influence on the prognosis. 5) Unfavourable findings observed at the time of initial evaluation to progress to LC include the presence of vascular spider, red palm, GOT/GPT ratio>1.0, R15ICG>20%, γ-globulin>2.0g/dl and cholinesterase<0.6ΔpH. 6) Cholinesterase activity was most correlated to the pathological progress to LC.
Cell kinetics of hyperplastic lesions, normal liver cells and hepatomas in rats were investigated at different time intervals during carcinogenesis with dietylnitrosamine (DEN) administration by employing 3H-thymidine autoradiography. Furthermore, the reactive proliferative activity of the above menthoned cell populations was examined by 67% hepatectomy during the experimental course. At 12 weeks after DEN administration, hyperplastic lesions had been classified histologically into two types, the one being the nodule of large liver cells, the another the area of large liver cells. Increased labeling indices were observed in both the hyperplastic lesions and normal liver cells during DEN feeding. The labeling indices of the area of large liver cells were from 12% to 16%, and those of nodule of large liver cells and normal liver cells were about 2%. After the partial hepatectomy, both the hyperplastic lesions and normal liver cells showed considerably elevated labeling indices, indicating the reactive proliferative activity. On the other hand, hepatomas showed much higher proliferative activity than the other cell populations, but there was no change observed in the labeling index between before and after the partial hepatectomy. The hyperplastic lesions and normal liver cells were apparently reactive to partial hepatectomy, whereas the hepatomas showed almost no such response. From these results, it is concluded that the hyperplastic lesions maintained the control of cell proliferation, so that those lesions were distinct from hepatomas in the kinetics of the cell proliferation.
For the past six years, small hepatocellular carcinoma which are smaller than 5cm in diameter have been diagnosed in 15 cases. Diagnostic rates of respective examinations made were as follows: 1) ultrasonography 14/15 (93.3%), 2) angiography 7/14 (50.0%), 3) scintigraphy 4/11(36.4%), 4) AFP 20ng/ml or over 13/15 (86.7%). Ultrasonogram of small hepatocellular carcinoma with liver cirrhosis has been classified into following four type: Type I is defined as low level echo with even internal echoes. Type II is defined as uneven internal echoes and/or with same level of echo. Type III is defined as high level echo with uneven internal echoes. Type IV is defined as low and high level echo area mixed. As a fact, much of ultrasonogram of small hepatocellular carcinoma with liver cirrhosis range in Type I (50.0%) and II (25.0%), but histopathologically, none or very few of fibrous tissue in the Tumor has been found. In Type III (12.5%), numerous septum have been seen macroscopically and also numerous fibrous tissues have been histopathologically seen accordingly. Type IV (12.5%), substantial amount of necrosis has been recongnized macroscopically.
A specific radioimmunoassay has been developed for the quantification of human muscle type aldolase (M-ALD) in the sera of patients with digestive diseases. The amount of M-ALD in the sera of normal subjects were 171±39 (mean±2 SD) ng/ml. Ninety-nine percent of 102 patients with non-cancerous diseases showed normal values. In contrast, eighty-two percent of 121 patients with cancer showed increased M-ALD values. Serum M-ALD values in the four progressive stages of gastric cancer (set by the Japanese Research Society for gastric cancer) increased as follows: 29% in stage I, 67% in stage II, 93% in stage III, and all in stage IV. Serum M-ALD values correlated with serum ALD activities in patients with cancer, but serum M-ALD values showed normal ranges when serum ALD activities increased in patients with liver diseases. These results suggest the determination of M-ALD using radioimmunoassay is a useful laboratory test in the diagnosis of digestive cancer patients.
In order to obtain information concerning the mechanism of hepatic uptake and biliary excretion of 99mTc-labeled hepatobiliary imaging agents, the effect of simultaneous administration of sulfobromophthalein (BSP) in rats was studied for 6 different 99mTc-labeled preparations with regard to their plasma clearances and tissue distributions of intravenously administered radioactive preparations. The biliary excretion as assessed by the small intestinal distribution of radioactivity 30 min after iv injection of materials was higher for BIDA and PIPIDA (70-75 percent of the administered dose) compared with that of HIDA and PI (50-60%), and conversely the urinary excretion was lower for the former drugs than the latter two. The inhibitory effects of BSP loading on the hepatic uptake and subsequent biliary excretion of materials were observed for all 6 materials tested, but the BSP effect was more prominent for BIDA & EHIDA in plasma clearance and for BIDA & PIPIDA in tissue distribution of 99mTc-activity. These new 99mTc-labeled compounds not only were useful clinically but also suggested their possible contribution to the further understandings of physiology of hepatobiliary system.
In chronic pancreatic fistula dogs with Thiry's fistula made up of the upper jejunal loop, a study was made of changes in the exocrine and endocrine function of the pancreas occurring following the perfusion of hypertonic glucose solution, 12% amino acids solution, oleic acid and pancreatic enzymes into Thiry's fistula under stimulation with pancreozymin and secretin. The results obtained are summarized as follows: 1) the perfusion into Thiry's fistula of 12% amino acids solution, oleic acid and amylase failed to stimulate the exocrine secretion of the pancreas to a significant extent. 2) the perfusion of pancreatic enzyme complex resulted in a significant diminution of pancreatic secretion and bicarbonate output. 3) hypertonic glucose solution and trypsin, when perfused into the fistula, gave rise to a significant increase in pancreatic secretion and bicarbonate output, which suggests the release of secretin or a secretin-like substance. 4) IRG in peripheral venous blood did not change to any appreciable extent on perfusion of any of the substances into the fistula. IRI showed an upward tendency on perfusion of hypertonic glucose and amino acid solutions. However, these substances were considered not to affect the endocrine function of the pancreas to a significant degree when administered at the dosage level and by the method employed in this experiment.