Selective action of a CCK-B/gastrin receptor antagonist, S-0509, on pentagastrin-, peptone meal- and beer-stimulated gastric acid secretion in dogs.
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BACKGROUND: The pharmacological effects of a novel CCK-B/gastrin receptor antagonist, S-0509, on gastric acid secretion in dogs remain unknown. AIM: To evaluate the antisecretory effects of S-0509 on gastric acid secretion and to compare such effects with famotidine or atropine in dogs stimulated with various gastric stimulants. METHODS: Ten beagle dogs with a denervated Heidenhain pouch and three beagle dogs with an innervated gastric fistula were used. Gastric acid secretion was stimulated by either continuous intravenous administration of pentagastrin, carbachol or histamine, or oral administration of a peptone meal or beer. RESULTS: In the Heidenhain pouch model, both intravenously administered and orally administered S-0509 significantly inhibited the gastric acid secretion stimulated by pentagastrin, peptone meal and beer. Nonetheless, the drug had little or no effect on carbachol-stimulated or histamine-stimulated acid secretion. Famotidine extensively inhibited all gastric acid secretion stimulated by the above stimulants in a non-selective manner. Atropine also significantly inhibited the acid secretion stimulated by pentagastrin, peptone meal, beer or carbachol, but was not able to inhibit stimulation due to histamine. Oral administration of peptone meal or beer significantly increased the plasma gastrin level. Similarly to the Heidenhain pouch model, even in the gastric fistula (GF) model, S-0509 significantly inhibited pentagastrin-stimulated gastric acid secretion, yet the drug had no effect on carbachol-stimulated secretion. CONCLUSIONS: S-0509 is a selective CCK-B/gastrin receptor antagonist in dogs that inhibits gastric acid secretion stimulated by pentagastrin and gastrin-releasing substances, but does not inhibit histamine-stimulated and carbachol-stimulated acid secretion. (+info)
Anaesthetic agents inhibit gastrin-stimulated but not basal histamine release from rat stomach ECL cells.
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By mobilizing histamine in response to gastrin, the ECL cells in the oxyntic mucosa play a key role in the control of the parietal cells and hence of gastric acid secretion. General anaesthesia suppresses basal and gastrin- and histamine-stimulated acid secretion. The present study examines if the effect of anaesthesia on basal and gastrin-stimulated acid secretion is associated with suppressed ECL-cell histamine secretion. A microdialysis probe was implanted in the submucosa of the ventral aspect of the acid-producing part of the stomach (32 rats). Three days later, ECL-cell histamine mobilization was monitored 2 h before and 4 h after the start of intravenous infusion of gastrin (5 nmol kg(-1) h(-1)). The rats were either conscious or anaesthetized. Four commonly used anaesthetic agents were given 1 h before the start of the experiments by intraperitoneal injection: chloral hydrate (300 mg kg(-1)), pentobarbitone (40 mg kg(-1)), urethane (1.5 g kg(-1)) and a mixture of fluanisone/fentanyl/midazolam (15/0.5/7.5 mg kg(-1)). In a parallel series of experiments, basal- and gastrin-induced acid secretion was monitored in six conscious and 25 anaesthetized (see above) chronic gastric fistula rats. All anaesthetic agents lowered gastrin-stimulated acid secretion; also the basal acid output was reduced (fluanisone/fentanyl/midazolam was an exception). Anaesthesia reduced gastrin-stimulated but not basal histamine release by 55 - 80%. The reduction in gastrin-induced acid response (70 - 95%) was strongly correlated to the reduction in gastrin-induced histamine mobilization. The correlation is in line with the view that the reduced acid response to gastrin reflects impaired histamine mobilization. Rat stomach ECL cells were purified by counter-flow elutriation. Gastrin-evoked histamine mobilization from the isolated ECL cells was determined in the absence or presence of anaesthetic agents in the medium. With the exception of urethane, they inhibited gastrin-evoked histamine secretion dose-dependently, indicating a direct effect on the ECL cells. Anaesthetized rats are widely used to study acid secretion and ECL-cell histamine release. The present results illustrate the short-comings of such an approach in that a number of anaesthetic agents were found to impair not only acid secretion but also the secretion of ECL-cell histamine - some acting in a direct manner. (+info)
Review of 404 patients with gastrointestinal fistulas. Impact of parenteral nutrition.
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This paper represents an extensive review, spanning 30 years of experience with 404 patients with gastrointestinal fistulas. It includes the first period (1945-1960) during the introduction of antibiotics, the second period (1960-1970) which saw rapid improvements in parasurgical care including, respiratory support, perfection of antibiotics, some introduction of nutritional support and improved monitoring, and the third period which saw the introduction of parenteral nutrition specifically central venous hyperalimentation using hypertonic glucose and amino acids (1970-1975) in the treatment of patients with fistulas. The principal causes for mortality in the historical sense were malnutrition, sepsis and electrolyte imbalance. Mortality among patients with gastrointestinal cutaneous fistulas decreased between the first and second periods from approximately 48 to 15%. Surprisingly, mortality did not decrease further in the "hyperalimentation period" although spontaneous closure of gastrointestinal fistulase increased. The results suggest that the improvement in mortality in patients with gastrointestinal cutaneous fistulas is mostly due to the introduction of improved parasurgical care. It is acknowledged that nutritional support was practiced in the 1960's although this was generally not in the form of hyperalimentation. The addition of hyperalimentation in large scale to the treatment of gastrointestinal cutaneous fistulas has improved spontaneous closure and is a valuable part of the armamentarium. The decrease in mortality however, cannot be attributed to parenteral nutrition. (+info)
Gastrocolic and gastrojejunocolic fistulae: report of twelve cases and review of the literature.
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Seven gastrocolic and five gastrojejunocolic fistulae were recorded at Charity Hospital between 1940 and 1970. Such fistulae occurred in males more often than females. In this series, as in others, the most common cause was gastric surgery for peptic ulcer disease. Pain, diarrhea, and weight loss were clinical findings in half the patients; anemia, leukocytosis, electrolyte disturbances and hypoalbuminemia were common laboratory findings. A fistula was demonstrated radiologically in nine of the twelve patients, management of these patients included no operation (3); two-stage procedure (2); and one-stage procedure (7); with a recent trend toward the one-stage procedure. A case report of a fistula resulting from postoperative complications of perforative appendicitis in which a successful combination of hyperalimentation and diverting colostomy was used is presented. (+info)
The vagus, the duodenal brake, and gastric emptying.
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It has been suggested that an intact vagal supply is essential for the normal function of the recptors in the duodenum and proximal small bowel, which influence the rate of gastric emptying. This paper reports the effect of vagal denervation on gastric emptying and also examines the site and mode of action of receptors in the proximal small bowel. It has been demonstrated in the dog that most, if not all, the receptors controlling gastric emptying lie in the proximal 50 cm of the small bowel. Following truncal vagotomy the emptying time of each instillation increased significantly and the differential rate of emptying of different instillations remained unchanged. The proximal 50 cm of small bowel was capable to differentiating between different instillates even after selective extragastric vagotomy, in which the duodenum was vagally denervated and, therefore, duodenal braking receptors function independently of vagal innervation. (+info)
Gastric necrosis and perforation as a complication of splenectomy. Case report and related references.
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Necrosis of the stomach after isolated splenectomy with the formation of gastrocutaneous fistula is a rare event that occurs in less than 1% of splenectomies. It is more frequent when the removal of the spleen is done because of hematological diseases. Its mortality index can reach 60% and its pathogenesis is controversial, as it may be attributed both to direct trauma of the gastric wall and to ischemic phenomena. Although the stomach may exhibit exuberant arterial blood irrigation, anatomical variations can cause a predisposition towards the appearance of potentially ischemic areas, especially after ligation of the short gastric vessels around the major curvature of the stomach. Once this is diagnosed in the immediate postoperative period, it becomes imperative to reoperate. The surgical procedure will depend on the conditions of the peritoneal cavity and patient's clinic status. The objective of this study was to report on the case of a patient submitted to splenectomy because of closed abdominal traumatism, who then presented peritonitis and percutaneous gastric fistula in the post-operative period. During the second operation, perforations were identified in anterior gastric wall where there had been signs of vascular stress. The lesion was sutured after revival of its borders, and the patient had good evolution. Prompt diagnosis and immediate treatment of this unusual complication are needed to reduce its high mortality rate. (+info)
The effects of intra-ruminal loading with cold water on thermoregulatory behaviour in sheep.
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1. Shorn sheep exposed to ambient termperatures of 5 degrees C soon learned to turn on infra-red heaters by placing their muzzles through a photoelectric beam, although before shearing they did not operate the heaters. 2. The duration of infra-red heating obtained decreased at higher ambient temperatures and at 25 degrees C very little heat was obtained. 3. When infra-red heaters totalling 900 or 1800 W were suspended above the sheep they turned on the 900 W heaters for almost exactly twice as long as they did the 1800 W heaters when exposed to 10 degrees C for 24 hr periods. 4. Loading the rumen with 1 l. water at 0-1 degree C produced an increment in the duration of infra-red heating obtained in a 1 hr period. At ambient temperatures of 0, 10 and 20 degrees C the increment observed after intraruminal loading with 2 l. water at 0-1 degree C was almost exactly double that obtained with a 1 l. loading. 5. Loading the rumen with 1 l. water at 0-1 degree C did not result in the sheep increasing the duration of infra-red heating obtained at ambient temperatures of 30 degrees C but a 2 l. loading was effective. At an ambient temperature of 40 degrees C the 2 l. load was ineffective. (+info)
PACAP stimulates gastric acid secretion in the rat by inducing histamine release.
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Previous studies have shown that pituitary adenylate cyclase-activating peptide (PACAP) stimulates enterochromaffin-like (ECL) cell histamine release, but its role in the regulation of gastric acid secretion is disputed. This work examines the effect of PACAP-38 on aminopyrine uptake in enriched rat parietal cells and on histamine release and acid secretion in the isolated vascularly perfused rat stomach and the role of PACAP in vagally (2-deoxyglucose) stimulated acid secretion in the awake rat. PACAP has no direct effect on the isolated parietal cell as assessed by aminopyrine uptake. PACAP induces a concentration-dependent histamine release and acid secretion in the isolated stomach, and its effect on histamine release is additive to gastrin. The histamine H2 antagonist ranitidine potently inhibits PACAP-stimulated acid secretion without affecting histamine release. Vagally stimulated acid secretion is partially inhibited by a PACAP antagonist. The results from the present study strongly suggest that PACAP plays an important role in the neurohumoral regulation of gastric acid secretion. Its effect seems to be mediated by the release of ECL cell histamine. (+info)