Impact of experimental endogenous gram-negative peritonitis on the pancreas of the rat as evaluated by cationic trypsin-like immunoreactivity in peritoneal fluid and serum and by electron microscopy of pancreatic tissue

Endogenous gram-negative peritonitis leading to septic shock was induced in rats by a defined perforation of the coecum. Cationic trypsin-like immunoreactivity (CTLI) was measured in peritoneal fluid and serum by a radioimmunoassay method. Five, 10, and 15 h after the coecal perforation, CTLI in peritoneal fluid was significantly higher than before the coecal perforation and also higher than in the corresponding control rats. Moreover, CTLI in serum was under the same conditions significantly higher 10 and 15 h after the induction of peritonitis. Gel chromatography of peritoneal fluid and serum during peritonitis showed free CTLI and CTLI bound to both alpha-1-antitrypsin and alpha-2-macroglobulin, whereas only free CTLI could be detected in serum from control rats. These findings were accompanied by local ultrastructural changes in the acinar cells as evaluated by electron microscopy. The pathophysiologic implications of the findings are discussed.     

Effect of a new synthetic serum replacement on insulin and somatostatin secretion from isolated rat pancreatic islets in long-term culture

Summary Serum contains insulin degrading components. We have evaluated the insulin and somatostatin secretion from isolated rat pancreatic islets during a 2-wk culture period using three different serum-containing media, and one serum-free medium with a synthetic serum replacement. Islets incubated in serum-free medium elicited significantly higher daily insulin and somatostatin secretions than islets incubated in the serum-containing media. After a 2-wk culture period, islets from the serum-free medium secreted significantly more insulin and somatostatin than islets cultured in other media when stimulated with 25 mmol/liter glucose together with 15 mmol/liter theophylline. We conclude that the serum-free medium is superior for long-term culture of rat pancreatic islets.     

The interaction between cAMP-dependent and cAMP-independent mechanisms in mediating the somatostatin inhibition of insulin secretion in isolated rat pancreatic islets.

To characterize the intracellular mechanisms by which somatostatin modulates the insulin secretion, studies were performed with isolated rat pancreatic islets at 12 mmol l-1 glucose. Somatostatin (0.1-1000 nmol l-1) inhibited the glucose-induced insulin secretion concentration-dependently. Increasing intracellular cAMP concentration either with dibutyryl-cAMP (1 mmol l-1) or by the adenylate cyclase activator forskolin (20 mumol l-1) partly reversed the inhibition by somatostatin (100 nmol l-1). Neither somatostatin (100 nmol l-1) nor dibutyryl-cAMP (1 mmol l-1 were able to affect the low insulin secretion observed in the absence of extracellular Ca2+. To study cAMP-independent mechanisms of somatostatin, the experiments were performed with and without dibutyryl-cAMP (1 mmol l-1) present. Both somatostatin (100 nmol l-1) and the Ca(2+)-channel blocker verapamil (25 mumol l-1) inhibited the insulin secretion both with and without dibutyryl-cAMP present. An additional inhibition of the insulin secretion was observed when somatostatin was combined with verapamil in the absence, but not in the presence of dibutyryl-cAMP. We conclude that somatostatin inhibits the glucose-induced insulin secretion both by cAMP-dependent mechanism which requires extracellular Ca2+, and by cAMP-independent/verapamil-sensitive Ca(2+)-channel-dependent mechanism.     

Effects of a Gastric Partitioning Operation for Morbid Obesity on the Secretion of Gastric Inhibitory Polypeptide and Pancreatic Polypeptide

Nine morbidly obese subjects were studied with a test meal before and 3 months after a gastric partitioning operation. After the operation the postprandial release of plasma gastric inhibitory polypeptide was significantly increased, the plasma pancreatic polypeptide release was similar, and the serum insulin release significantly reduced as compared with the preoperative values.     

The effect of graded doses of secretin on serum trypsin, serum pancreatic amylase, serum insulin, plasma somatostatin, and plasma pancreatic polypeptide in man

Six healthy men were studied with intravenous infusions of 0.3, 1.0, and 3.0 CU/kg-h of pure porcine secretin on separate days. The secretin elimination followed a first-order kinetics. Low pharmacological doses of secretin had no significant effects on blood levels of trypsin, pancreatic amylase, insulin, somatostatin, or pancreatic polypeptide (PP), whereas high pharmacological doses significantly elevated the blood levels of trypsin, pancreatic amylase, insulin, and somatostatin but were without effect on PP.     

The effects of secretin on prolactin, estradiol, vasoactive intestinal polypeptide, and somatostatin levels in women

The effect of graded doses of intravenous secretin (0.5, 1.0, and 2.0 CU.kg-1.h-1) on serum prolactin and estradiol levels, as well as plasma vasoactive intestinal polypeptide and somatostatin levels was studied in 6 normally cycling and healthy women, and compared with the hormone levels obtained by a control infusion with physiologic saline (0.15 mol/l). A significant decrease in serum prolactin concentrations was found with increasing doses of secretin at steady-state levels of plasma secretin (+30 to +60 min). A significant negative correlation (p less than 0.007, r = -0.2764) existed between serum prolactin and plasma secretin concentrations at steady-state conditions. No effect of graded doses of secretin was observed on serum estradiol levels and plasma concentrations of vasoactive intestinal polypeptide and somatostatin. The results suggest a dose-related inhibitory effect of secretin on prolactin release in women.     

A single-centre study of gastric ulcer healing with 300 mg ranitidine at night versus 150 mg ranitidine twice daily

In a single-centre study 59 patients with gastric ulcer were treated either with 300 mg ranitidine at night or with 150 mg ranitidine twice daily. After 4 and 8 weeks 73% and 97%, respectively, of those treated with 300 mg at night and 59% and 86% of those treated with 150 mg twice daily had complete ulcer healing. These differences between the two groups were not statistically significant. No serious side effects were seen. Ranitidine, 300 mg at night, appears to be at least as effective as the standard 150 mg twice daily regimen in the treatment of gastric ulcer.     

Morphine effects on the release of glucagon,insulin and somatostatin from the isolated,perfused rat pancreas

The pancreatic glands from six male Wistar rats weighing between 200 and 250 g were isolated and perfused. After 30-min equilibration and 20-min basal periods, perfusion with 0.2 mg/ml of morphine for 20 min resulted in a significant (P<0.05) increase in insulin release, with no changes in release of gucagon or somatostatin. After a recovery period of 20 min, a higher morphine concentration of 2 mg/ml was introduced for another 20-min period. With this morphine dose there were significant increases in release of insulin (P<0.05), glucagon (P<0.01) and somatostatin (P<0.05). This shows that morphine induces the release of insulin, glucagon and somatostatin from pancreas in a dose-dependent way, and that release of insulin and glucagon is not primarily affected by regulation of somatostatin levels.     

Erosive prepyloric changes in dyspeptics and non-dyspeptics in a defined population. The S?rreisa Gastrointestinal Disorder Study.

In this population-based endoscopic survey we found erosive prepyloric changes (EPC) in 38.5% of dyspeptics and 35.1% of non-dyspeptics. EPC were observed more frequently in men than in women in both groups. Occurrence of Helicobacter pylori was not associated with EPC. No common gastrointestinal symptoms were found to be associated with EPC. Endoscopic duodenitis of the duodenal bulb was found more frequently in subjects with EPC of the two highest grades than in subjects without EPC. Only the highest grade of EPC was associated with chronic gastritis. EPC were associated with cigarette smoking and, among women, also use of alcohol. We conclude that EPC constitute an endoscopic finding without relation to specific symptoms. These changes therefore do not represent a clinical entity, and it is doubtful whether this finding will give the clinician a better understanding of dyspepsia.     

Aetiology of peptic ulcer: a prospective population study in Norway.

STUDY OBJECTIVE--To analyse simultaneously the effect of several risk factors for peptic ulcer. DESIGN--Cohort study where all patients with new or incident peptic ulcers in a well defined population were registered for a seven year period. The follow up started with a comprehensive health survey including a questionnaire on diet, lifestyle, psychological and social conditions, and health. Relative risks, both sex specific and separate, for gastric and duodenal ulcers were estimated from proportional hazard regression analysis. SETTING--A population based survey conducted in the municipality of Tromsø, northern Norway. PARTICIPANTS--In 1980, a total of 21,440 men and women, aged 20 to 54 years and 20 to 49 years respectively, were invited to participate. A total of 14,667 people attended and returned the questionnaire. MAIN RESULTS--A total of 328 people had their first peptic ulcer in the follow up period. Age, cigarette smoking, first degree relatives with peptic ulcer, and low educational level were shared risk factors for peptic ulcer in both men and women. In men, frequent upper respiratory infections increased the risk of gastric ulcer and drinking a great deal of milk increased the risk of duodenal ulcer. None of the other dietary variables, including coffee and alcohol consumption, contributed significantly to the risk. Use of analgesics was not a risk factor, and none of the psychological indicators analysed carried any significant risk. CONCLUSIONS--Age, inheritance, and cigarette smoking are all important risk factors for peptic ulcer. The increased risk associated with low educational background indicate that social strains, comprising lifestyle and diet habits, are part of the multifactorial aetiology of peptic ulcer. No support was found for the assumption that peptic ulcer disease is a psychosomatic disorder. This study did not support the view that duodenal and gastric ulcers have different aetiologies-rather it showed a similarity in risk patterns.