摘要:

In this study, the effect of ranitidine treatment on the activation and proliferahion of rat gastric enterochromaffin-like (ECL) cells was investigated. The drug was given in a high dose in the food (1.7–1.8 g/kg/day) for 20 weeks. This dose corresponds to the high dose given in the ranitidine oncogenicity study performed by Glaxo. With this dose regimen ranitidine induced hypergastrinaemia for 10 h of the day. The duration and the extent of the hypergastrinaemia closely followed the occurrence of ranitidine in plasma, strongly suggesting that the hypergastrinaemia was secondary to inhibition of acid secretion. Following 20 weeks treatment with ranitidine, both the relative weight of the stomach and that of the oxyntic mucosa were increased. The oxyntic histamine concentration and ECL-cell density were also increased significantly. These results show that when ranitidine is given in the diet the resulting hypergastrinaemia, which had a duration of 10 h each day, leads to a general increase in the oxyntic mucosal weight and a proliferation and activation of the ECL cells, indicating that sustained hypergastrinaemia is not a necessary requirement for development of ECL-cell hyperplasi

ISSN:0012-2823    

DOI:10.1159/000200244

出版商:S. Karger AG    

年代:1990

数据来源: Karger

摘要:

Long-term administration of some long-acting inhibitors of gastric acid secretion has been associated with the development of gastric enterochromaffin-like (ECL)-cell carcinoids in the rat. It has been argued that short-acting, surmountable histamine H2receptor blockers such as ranitidine do not cause carcinoids. In this study, female rats (n = 100) were treated for 2 years with the histamine H2-receptor blocker ranitidine, 2 g/kg/day in the diet. Specimens from the stomachs of all rats, including 50 controls, were stained for argyrophil cells. Plasma gastrin and ranitidine levels were measured in separate groups of rats at different times during the study. The mean plasma level of ranitidine was 37.5 μmol/l, measured at midnight when the maximal level after food intake was expected. The resulting acid inhibition was associated with an approximately 3-fold increase in plasma gastrin which persisted throughout the whole period of the study. The ranitidine treatment resulted in a pronounced hyperplasia of gastric ECL cells. In 19 rats carcinoids were found, 4 of which were micro-invasive. No carcinoids were found in the control animals. The results provide further support for the gastrin mechanism, i.e. that the development of ECL-cell carcinoids in the rat gastric mucosa is a consequence of prolonged hypergastrinaemia and is not a unique effect of any individual acid-inhibiting drug

ISSN:0012-2823    

DOI:10.1159/000200245

出版商:S. Karger AG    

年代:1990

数据来源: Karger

摘要:

The existence of 5 different mammalian subtypes of muscarinic receptors, named M1 to M5 has been established. This study was designed to characterize the subtypes of muscarinic receptors occurring in smooth muscle of the upper gastrointestinal tract. Displacement studies of [3H]N-methylscopolamine by the highly M2-selective ligand methoctramine revealed the presence of M2-receptors. The remaining sites had characteristics of M3-receptors. The ratio of M2- to M3-receptors varied from a predominance of M3-receptors in antral tissue over a predominance of M2-receptors in gastric corpus and ileal smooth muscle to the almost exclusive presence of M2-receptors in duodenal smooth muscle. Mucosa from all areas showed characteristics of M3-receptors without evidence for the occurrence of M2-receptors.

ISSN:0012-2823    

DOI:10.1159/000200246

出版商:S. Karger AG    

年代:1990

数据来源: Karger

摘要:

Epidermal growth factor (EGF) is widely distributed in the gastrointestinal tissues and released into the gut lumen but its physiological role is questionable because of the postulated high uptake and degradation of this peptide in the liver. This study was designed to examine the action of EGF administered intraduodenally (i.d.), intravenously (i.v.) or intraportally (i.p.) on pentagastrin-stimulated gastric and pancreatic secretion and to determine the role of liver in the EGF uptake. In conscious dogs with gastric and pancreatic fistulas, EGF infused i.v. or i.p. in graded doses (0.12–1.0 μg/kg•h) caused a dose-dependent inhibition of pentagastrin-induced gastric H+ secretion without alteration in pancreatic protein secretion. EGF infused i.v. and i.p. raised significantly plasma levels of the peptide but these increments were significantly lower with i.p. than with i.v. infusion. EGF given i.d. did not affect gastric or pancreatic secretion and failed to raise significantly plasma EGF level. In anesthetized dogs, no difference was found in the basal plasma EGF levels between arterial and portal or hepatic blood, during i.v. infusion of EGF, plasma EGF level in hepatic venous blood was about 40% lower and that in the portal blood was about 30% lower than that in arterial blood indicating a marked uptake of peptide during the passage through the liver and the intestines, respectively. EGF was present in negligible amounts in gastric secretion but appeared in nanogram concentrations in the pancreatic secretion and increased after pentagastrin stimulation. We conclude that (1) the liver and the intestines are almost equally involved in partial degradation of EGF and that the kidneys may also contribute to the elimination of circulating EGF; (2) the uptake of EGF by these organs is limited and can be overcome by increasing doses of infused EGF, and (3) absorption of EGF from the intestinal lumen does not contribute to its circulating concentrat

ISSN:0012-2823    

DOI:10.1159/000200247

出版商:S. Karger AG    

年代:1990

数据来源: Karger

摘要:

Dogs were given an oral dose of 300 μg/kg/day of the prostaglandin E1 analogue, misoprostol for 11 weeks. The relative areas of the main components of the fundus and antrum per unit area of serosa were quantified. While the volume occupied by the muscle layers did not change, there was an increase in mucosal volume in both sites. The relative volume fraction of the main mucosal cell types was then determined by a point counting technique. Misoprostol very highly significantly increased the fraction of mucosal volume occupied by surface mucus cells, and also significantly decreased the volume fraction of the parietal cells

ISSN:0012-2823    

DOI:10.1159/000200248

出版商:S. Karger AG    

年代:1990

数据来源: Karger

摘要:

Thirty-nine critically ill patients with actively bleeding peptic ulcerations – Forrest lb – in the stomach or duodenum were randomly allocated to intravenous therapy with 400 mg ranitidine per day or 80 mg omeprazole per day (120 mg on the 1st day) for 5 days. Successful therapy was proven by control endoscopy on day 6 if less than 2.5 liters of blood had to be transfused from the start of therapy to maintain a hemoglobin value of 10 g/l or above. Treatment failure meant that more than 2.5 liters of blood were necessary to maintain a hemoglobin level above 10 g/l. Of 20 patients in the ranitidine group bleeding stopped in only 3 patients (15%). Of 17 patients who continued bleeding under ranitidine therapy the bleeding could be controlled in 13 patients after changing to omeprazole treatment. Of 19 patients in the omeprazole group bleeding stopped in 16 patients (84%). These results demonstrate that the significantly more effective reduction of acidity by omeprazole is promising for the therapy of bleeding peptic ulcerations and may reduce the need for invasive therapy or operat

ISSN:0012-2823    

DOI:10.1159/000200249

出版商:S. Karger AG    

年代:1990

数据来源: Karger

ISSN:0012-2823    

DOI:10.1159/000200250

出版商:S. Karger AG    

年代:1990

数据来源: Karger

ISSN:0012-2823    

DOI:10.1159/000200251

出版商:S. Karger AG    

年代:1990

数据来源: Karger

ISSN:0012-2823    

DOI:10.1159/000200243

出版商:S. Karger AG    

年代:1990

数据来源: Karger