Digestion

Walker, S.; Stiehl, A.; Raedsch, R.; Klöters, P.; Kommerell, B.

doi: 10.1159/000199268pmid: 3940233

Absorption of sulfated and nonsulfated chenodeoxycholic and glycochenodeoxycholic acid was studied in the colon and the data were compared with the absorption rates in the ileum. Absorption of nonsulfated chenodeoxycholic acid in the colon was in the same range of magnitude as in the ileum. Glycochenodeoxycholic acid absorption in the colon was lower than in the terminal ileum. Sulfated bile acids were not absorbed in the colon. In the ileum, absorption of sulfated bile acids was significantly (p < 0.01) lower than the absorption of nonsulfated bile acids. Little absorption of sulfated bile acids in the ileum and lack of absorption in the colon both contribute to the rapid turnover and excretion of bile acid sulfates.

Scarpignato, Carmelo; Tangwa, Martin; Tramacere, Roberto; Del Soldato, Piero

doi: 10.1159/000199269pmid: 2866139

The new H₂-receptor antagonist mifentidine (DA 4577) was tested for its antisecretory and gastric motor effects in comparison with cimetidine and ranitidine. The Shay rat preparation (5 h) was used for studying gastric secretion; the gastric emptying of a liquid meal was chosen for studying gastric motility. All the three compounds inhibited acid secretion in a dose-dependent fashion. Calculated ED_50s were 2.3, 12.2 and 92.8 mg·kg^-1 for mifentidine, ranitidine and cimetidine, respectively. Therefore, in this animal model, mifentidine was about 40 times more potent than cimetidine and 5 times more potent than ranitidine. As far as gastric emptying is concerned, the effect of equiactive antisecretory doses (i.e. the respective ED_50s calculated from the previously established dose-response curves) of all the three antagonists was completely different. Cimetidine delayed emptying rate, whereas ranitidine accelerated it and mifentidine was completely ineffective. However, at higher doses, also this compound affected emptying rate by reducing it dose-dependently. Gastric and duodenal ulcers were induced in the rat by dimaprit (100 mg·kg^-1 intravenously) and cysteamine (250 mg· kg^-1 subcutaneously), respectively. As far as gastric ulcer is concerned, the ED_50s (the effective dose which protected 50% of the animals from lesions) were 0.23, 4.40 and 9.70 mg·kg^-1 for mifentidine, ranitidine and cimetidine, respectively. As regards duodenal ulcer, the ED₅₀ was 4.48 for mifentidine and 150.00 mg·kg^-1 for ranitidine. In this animal model, the efficacy of cimetidine was very low. Therefore an ED₅₀ could not be determined. In conclusion, results of the present investigation demonstrated that mifentidine is a potent antisecretory compound and an effective anti-ulcer agent in the rat.

Pap, Akos; Sarles, Henri

doi: 10.1159/000199270pmid: 3940234

The effect of atropine on exocrine pancreatic secretion was investigated in conscious rats. Intravenous atropine infusion decreased nonstimulated protein secretion during recirculation of pancreatic juice into the duodenum D₅₀ = 15–20 μg/kg/h. The maximum inhibition from protein secretion (-89%) was obtained with 600 μg/kg/h. With larger doses, the inhibition was less. The response to secretin and cholecystokinin-pancreozymin was not significantly modified by atropine. When pancreatic juice was diverted during the course of an intravenous atropine infusion, the first 1-hour peak of protein output was significantly decreased, but the following 2-hour period was increased, the sum of these 2 periods being similar in both conditions. The response to soybean trypsin inhibitor during recirculation was decreased as well as the first peak after diversion. During atropine infusion fluid secretion decreased more powerfully after 1 h diversion and after soybean trypsin inhibitor than during recirculation of pancreatic juice. It is suggested that during recirculation of pancreatic juice nonstimulated protein secretion is mostly (89%), and water secretion is partially controlled by cholinergic mechanisms. After soybean trypsin inhibitor stimulus and during the early phase following juice diversion protein secretion seems to be partly under the control of cholinergic mechanisms. However, during the latter phase following diversion, it is not so. Parasympathetic stimulation appears also to play a significant, although less important, role in fluid secretion.

Andriulli, A.; Gindro, T.; Piantino, P.; Farini, R.; Cavallini, G.; Piazzi, L.; Naccarato, R.; Dobrilla, G.; Verme, G.; Scuro, L.A.

doi: 10.1159/000199271pmid: 3940235

Levels of a new carbohydrate antigen, CA 19–9, which is a monosialoganglioside identified by a monoclonal antibody raised against colorectal carcinoma cells, were compared to conventional CEA assays in 615 sera from healthy controls, patients with benign gastrointestinal disorders, and patients with cancers of gastrointestinal or extragastrointestinal origin. Whereas CEA levels were higher in smokers, CA 19–9 values were independent of the smoking history. CA 19–9 was undetectable in lymphoma and myeloma patients, but some patients with extraintestinal epithelial cancers expressed this antigen in serum. For benign and malignant gastrointestinal diseases, CA 19–9 displayed higher sensitivity, specificity, and predictive values than CEA. CA 19–9 was elevated as frequently as CEA in patients with metastatic pancreatic cancer, but in patients with localized disease, CA 19–9 was elevated more often than was CEA. In colorectal cancer, patients with and without metastases were detected at similar rates by both assays. It is concluded that CA 19–9 is a marker of epithelial cancers, does not vary with the smoking status, and is superior to CEA in detecting gastrointestinal malignancies, especially those arising from the pancreatic gland.

Takeuchi, K.; Ohtsuki, H.; Nobuhara, Y.; Okabe, S.

doi: 10.1159/000199272pmid: 3940236

A single intraperitoneal injection of compound 48/80 (48/80) (0.5–3 mg/kg) into anesthetized rats caused a dose-dependent reduction of the transmucosal potential difference (PD) and intraluminal pH (pH), and induced gastric lesions within 2 h. These same changes were seen with an intraperitoneal injection of histamine, but not with serotonin. There was a significant correlation between the lesion index and the PD reduction, although the integrity of the resting gastric mucosal barrier remained unaltered. The PD reduction caused by 48/80 was dose-dependently inhibited by tripelennamine (H₁-antagonist) and FPL-52694 (mast cell stabilizer) and partially suppressed by methysergide (serotonin antagonist), but the changes in pH were prevented by FPL-52964 and cimetidine (H₂-antagonist). The reduction of PD and pH induced by histamine was inhibited by tripelennamine or cimetidine, respectively, but these responses were not inhibited by FPL-52694 or methysergide. Gastric lesions induced by 48/80 were potently inhibited by tripelennamine and FPL-52694, and partially by cimetidine, whereas those induced by histamine were significantly prevented by tripelennamine and cimetidine, but not by FPL-52694. Methysergide had no effect on the development of gastric lesions in response to 48/80 or histamine. These results suggest that a single injection of 48/80 reduced the PD and stimulated acid secretion, thereby producing gastric lesions. These effects of 48/80 may be due to activation of H₁ and H₂-receptors by acutely released endogenous histamine.

Müller, M.K.; Scheck, T.; Demol, P.; Goebell, H.

doi: 10.1159/000199273pmid: 2415417

Exocrine pancreatic secretion is under partial control of endocrine pancreatic hormones. We studied the interaction of three doses of acetylcholine (Ach), a stimulator of exocrine and endocrine pancreatic secretion, with one dose of gastric inhibitory polypeptide (GIP) which is strongly insulinotropic, but has no effect on exocrine pancreatic secretion. The effects of Ach and GIP on insulin secretion from the rat pancreas were additive at 0.05 × 10^-6M Ach and slightly, but not significantly less than additive at 0.25 or 2.5 × 10^-6M Ach. GIP had an augmenting effect on amylase and volume secretion from the pancreas, when pancreatic secretion was stimulated by 2.5 × 10^-6M Ach, but not by 0.05 or 0.25 × 10^-6M. Exogenous rat insulin could exert an effect similar to that of GIP, although a higher dose was required. Atropine inhibited the effect of Ach on exocrine and endocrine pancreatic secretion, but not the insulinotropic action of GIP. It is hypothesized that GIP could play a role in regulating exocrine pancreatic secretion by its insulinotropic action.

Poralla, T.; Manns, M.; Hütteroth, T.H.; Hess, G.; Dormeyer, H.H.; Meyer zum Büschenfelde, K.-H.

doi: 10.1159/000199274pmid: 3940237

During a period of 3 years we observed 5 patients with chronic active hepatitis B and 2 with hepatitis B virus-induced liver cirrhosis who cleared HBsAg from their sera after 2–14 years of HBsAg carriership. 4 of them developed anti-HBs. After HBsAg clearance there was no evidence of persisting inflammatory activity within their livers. 5 of the 7 patients had been treated for 1–39 months with prednisolone, sometimes in combination with azathioprine. This therapy, however, had been stopped more than 3 years before these patients terminated their HBsAg carriership. Our observations indicate that even after long-standing chronic active hepatitis B or hepatitis B virus-induced liver cirrhosis HBsAg may be eliminated in a considerable number of patients.