Biomedical subjects

I Koop

Publications and source records attributed to I Koop.

53 records · Page 3Linked to original sources

PubMed1989

Irradiation-induced duodenal ulcer disease refractory to ranitidine: healing by omeprazole.

In two patients duodenal ulcer refractory to high dose H2-blocker treatment started several months after irradiation therapy following right nephrectomy because of renal adenocarcinoma. Established antiulcer drugs like ranitidine, famotidine, sucralfate, pirenzepine, and antacids alone or in combination were unable to control ulcer pain and failed to induce ulcer healing. Initiation of omeprazole treatment at dosages to produce complete achlorhydria were necessary for ulcer healing and maintenance therapy. We suggest that (a) irradiation may cause duodenal ulcer disease indistinguishable from idiopathic duodenal ulcer; (b) radiation-induced ulcers in the duodenal bulb are refractory to various antiulcer drugs but may heal after administration of omeprazole in dosages that completely suppress acid secretion.

Aged↗

PubMed1989

Do bile acids exert a negative feedback control of cholecystokinin release?

The influence of intraduodenal bile deficiency due to chronic bile duct obstruction and acute exogenous administration of bile acids on plasma cholecystokinin (CCK) and pancreatic polypeptide (PP) was investigated. Fourteen patients with tumor-induced bile duct stenosis and five healthy volunteers were given a liquid test meal. Four of the patients had a simultaneous pancreatic duct stenosis. On another day 4 g chenodeoxycholic acid were administered concomitantly with the liquid test meal in six of the patients and all controls. Basal and meal-stimulated plasma CCK did not differ between patients and controls. A pancreatic duct stenosis, which was associated with diminished plasma PP concentrations, had no influence on plasma CCK release. Exogenous bile acids significantly reduced the postprandial CCK response in both groups. Bile-induced inhibition was significantly greater in patients than in controls (75 +/- 7% and 44 +/- 11%, respectively; p less than 0.05). It is concluded that intraduodenal bile is an important modulator of the postprandial secretory activity of the CCK cell. Although chronic intraduodenal bile acid reduction in tumor-induced biliary duct stenosis did not influence plasma CCK levels, a negative feedback control of plasma CCK by acute bile acid administration could be demonstrated.

Adult↗

PubMed1988

Plasma CCK levels in patients with pancreatic insufficiency.

After stimulation with a Lundh test meal, plasma concentrations of cholecystokinin (CCK) and pancreatic polypeptide (PP) and output of pancreatic enzymes were measured in 33 patients with exocrine pancreatic insufficiency and 26 healthy subjects. Patients with impairment of pancreatic function were subdivided into those with moderate and severe insufficiency. Plasma CCK and PP were measured by radioimmunoassay. Fasting plasma CCK in patients with pancreatic insufficiency (5.8 +/- 1.1 pmol/liter) did not differ significantly from controls (4.2 +/- 0.6 pmol/liter). After endogenous stimulation with a Lundh meal, plasma CCK increased in both groups without significant differences over 2 hr. Basal and stimulated plasma levels of pancreatic polypeptide (PP) were markedly decreased only in patients with severe pancreatic insufficiency. Our results demonstrate that basal and meal-stimulated CCK levels in patients with pancreatic insufficiency do not differ from controls. Furthermore the extent of functional impairment of the exocrine pancreas did not influence basal and postprandial CCK release.

Adult↗

PubMed1988

Effect of cholestyramine on plasma cholecystokinin and pancreatic polypeptide levels, and exocrine pancreatic secretion.

The effect of acute and long-term administration of cholestyramine, a non-absorbable bile salt binding resin, on exocrine pancreatic secretion, plasma-cholecystokinin (CCK) and plasma-pancreatic polypeptide (PP) was investigated in 10 healthy volunteers. Oral ingestion of 12 g cholestyramine augmented the stimulatory effect of a liquid test meal on plasma-CCK (3.5-fold) and plasma-PP (2-fold). During prolonged treatment with 3 x 12 g cholestyramine daily for 4 weeks, the most pronounced increase in basal hormone levels was observed after 1 day, but progressively decreased during treatment and had normalized after 4 weeks. However, the stimulated plasma-CCK output was still significantly elevated after cessation of treatment, compared with pretreatment values. After acute and chronic cholestyramine administration only stimulated lipase secretion was elevated, whereas trypsin and amylase remained unchanged. It is suggested that removal of bile salts enhances CCK and thereby PP release and pancreatic lipase secretion.

Adult↗

PubMed1988

Stimulation of pancreatic secretion in man by a protease inhibitor (camostate).

Pancreatic secretion and plasma cholecystokinin (CCK) and secretin levels were measured in 10 healthy volunteers after application of a serine protease inhibitor (camostate) to study the mechanism of feedback regulation. Camostate produced a strong inhibition of trypsin and chymotrypsin activity in duodenal juice for 1 h. This was accompanied by an increase in duodenal aspirate volume and pancreatic enzyme secretion under both basal and secretin-stimulated conditions. Due to inhibition of tryptic activity, survival of lipase activity in duodenal juice was prolonged. In control experiments we ruled out that the volume and the pH of the solution were responsible for stimulation of pancreatic secretion. The protease inhibitor did not alter pancreatic secretion, which was stimulated by a test meal. Plasma levels of CCK and secretin were not changed after duodenal perfusion of camostate. These observations suggest that trypsin and chymotrypsin are involved in feedback regulation of pancreatic secretion in man which is, however, not mediated by CCK or secretin.

Cholecystokinin↗

PubMed1988

Effect of atropine on intestinal phase of pancreatic secretion in man.

The effect of atropine on prestimulatory and Lundh-meal-stimulated pancreatic secretion and on plasma cholecystokinin (CCK) levels has been studied in 20 human volunteers. Prestimulatory secretion was lowered by infusion of atropine. From 10 to 30 min after ingestion of the Lundh meal, atropine had no effect on secretion. From 30 to 120 min, the stimulated enzyme secretion was reduced by 90% during infusion of atropine. Plasma CCK levels were not altered by atropine. Similar results were obtained when the test meal was instilled into the duodenum to exclude a delay of gastric emptying caused by atropine. These data show that cholinergic blockade does not interfere with CCK-mediated stimulation of pancreatic secretion during the first 30 min after ingestion of a meal, and that afterwards the intestinal phase is mainly under cholinergic control.

Adult↗

PubMed1988

Comparison of the effect of single and repeated administrations of a protease inhibitor (Camostate) on pancreatic secretion in man.

In the present study pancreatic secretion and plasma cholecystokinin (CCK) levels were analyzed in eight volunteers after daily ingestion of the serine protease inhibitor camostate for 5 days. This was compared with the effect of a single intraduodenal dose of camostate. Prolonged administration of camostate for 5 days had no effect on basal and stimulated pancreatic secretion and plasma CCK. A single dose of camostate completely inhibited enzymatic activity of trypsin and chymotrypsin and stimulated volume, amylase, and lipase secretion but induced an only slight and insignificant increase in plasma CCK. After the ingestion of a test meal, camostate did not influence stimulated enzyme secretion and increased plasma CCK. We concluded that the intraduodenal perfusion of camostate stimulated pancreatic secretion by a feedback mechanism that is not mediated by CCK. The repeated oral administration of camostate did not induce adaptive changes in pancreatic secretion.

Cholecystokinin↗

PubMed1987

Effect of somatostatin analogue (SMS 201-995, Sandostatin) on pancreatic secretion in humans.

The effect of the long-acting somatostatin analogue SMS 201-995 on exocrine pancreatic function and hormone release was investigated in a double-blind, placebo-controlled study in healthy subjects. SMS 201-995 was administered subcutaneously at a dose of 25 micrograms twice daily, and all tests were performed 30 minutes after the morning injection. Pancreatic enzyme secretion, gall bladder contraction, and cholecystokinin response after a Lundh meal were completely inhibited by SMS, while pancreatic enzyme secretion elicited by intravenous injection of secretin and pancreozymin was suppressed by 80 percent. The inhibitory effect of SMS on endogenous cholecystokinin release was fully operative on the sixth day of injection treatment, whereas the inhibitory effect on exogenous cholecystokinin injection significantly decreased after SMS administration for seven days, indicating desensitization of the end organ by somatostatin. The release of pancreatic polypeptide by a solid test meal is abolished by administration of 25 micrograms of SMS, the release of gastric inhibitory polypeptide is nearly completely suppressed, the response of insulin and C-peptide are significantly lowered, and the gastrin response is only slightly reduced.

Adult↗

PubMed1987

Stimulation of pancreatic secretory process in the rat by low-molecular weight proteinase inhibitor. I. Dose-response study on enzyme content and secretion, cholecystokinin release and pancreatic fine structure.

Application of a single dose of a new type of proteinase inhibitor camostate (FOY-305) via orogastric tube was used in rats to study the dose-response relationship of resulting pancreatic stimulation. Doses up to 10 mg/kg failed to elicit any response, while significant decrease in enzyme content and increase in serum CCK-levels were observed with doses ranging from 25 to 400 mg/kg. A single dose of 100 mg/kg was selected for a time-sequence analysis, which revealed a 60 to 70% depletion of enzyme stores persisting over 6 h and reverting to control levels by 12 h. Peak increases in serum CCK-levels (15-fold above the elevation observed after regular food intake) were found after 30 min and persisted as an 8- to 10-fold elevation for at least 3 h, then declined to control levels by 9 h. This prolonged endogenous hormone release and resulting pancreatic stimulation were also verified in a separate group of animals in which volume, protein, and enzyme output were measured after cannulation of the pancreatic duct. While volume secretion was not altered by feeding a single dose of 100 mg/kg FOY-305, protein and enzyme output increased 2- to 3-fold over a period of 7 h. Fine-structural analysis of the pancreas demonstrated efficient depletion of zymogen granules from acinar cells with all doses between 50 and 400 mg/kg, accompanied by the appearance of membrane material in the acinar lumina at 3 and 6 h. The same transient increase in the number of lysosomal bodies predominantly containing mitochondria with all doses above 50 mg/kg was interpreted as increased organelle turnover due to persisting hormonal stimulation.

Amylases↗

PubMed1987

Effect of the somatostatin analogue sandostatin (SMS 201-995) on gastrointestinal, pancreatic and biliary function and hormone release in normal men.

The effect of the long-acting somatostatin analogue Sandostatin (SMS 201-995) on intestinal absorption and propagation (mouth-to-caecum transit time; MCTT), on pancreatic secretion and on gall bladder contraction after direct (secretin-pancreozymin test) and indirect stimulation (Lundh meal), and on meal-induced responses of seven gastrointestinal regulatory peptides has been investigated. In a double-blind cross-over study, 9 healthy volunteers completed two 7-day periods with subcutaneous injections of either placebo or 25 micrograms SMS 201-995 twice daily. Mean faecal fat excretion was increased to 19.2 g/day and MCTT was three times longer during the SMS period. After duodenal infusion of a mixture containing D-galactose, D-xylose and triglycerides, SMS 201-995 significantly reduced the serum concentrations of D-galactose but increased serum levels of D-xylose. After 6 days of pretreatment, SMS 201-995 completely suppressed duodenal trypsin, lipase and bilirubin increases in response to endogenous stimulation by a Lundh meal. Concomitantly, cholecystokinin (CCK) release and gall bladder contraction were almost abolished. Compared with placebo, SMS 201-995 significantly diminished pancreatic amylase, trypsin and lipase output after stimulation with CCK, while the secretion of fluid and bicarbonate in response to secretin was unchanged. This inhibition of enzyme response was significantly more marked after a single injection of the analogue than after pretreatment for 7 days and did not reach the level of exocrine pancreatic insufficiency. CCK-induced gall bladder contraction was significantly inhibited by a single dose of 25 micrograms SMS 201-995 but not after 7 days of pretreatment with the somatostatin analogue.

Adult↗

PubMed1987

Effect of food deprivation on the function of the intestinal cholecystokinin-producing cell in the rat.

The influence of fasting and refeeding on storage and secretion of cholecystokinin (CCK) was investigated in the rat. Groups of rats deprived of food for 12 and 96 h were studied. Animals of each group received 0.75 g of long-chain triglycerides or water via an orogastric tube after the fasting period 15 min prior to exsanguination. Rats fed ad libitum served as controls. Duodenal, jejunal and ileal segments were dissected for tissue extraction and immunohistochemical staining of CCK-containing cells. Fasting over 96 h resulted in a significant reduction of plasma CCK, duodenal CCK concentrations and number of duodenal CCK-containing cells. Changes were less pronounced in the more distal parts of the small bowel. Refeeding caused an increase in plasma and tissue CCK concentrations, thus abolishing all significant differences that occurred during fasting. Gel chromatography of tissue extracts showed a shift towards the bigger molecular forms after 96 h of fasting. We conclude that storage and secretion of gut CCK are reduced during food deprivation in rats. The reduction of tissue CCK appeared at the expense of the lower molecular forms. However, the functional responsiveness of the CCK cell as indicated by the postprandial rise in plasma CCK seems to be maintained after a 4-day fast.

Animals↗

PubMed1987

Plasma cholecystokinin and pancreatic enzyme secretion in patients with coeliac sprue.

The aim of this study was to investigate simultaneously the endogenously stimulated exocrine pancreatic secretion and the cholecystokinin (CCK) response in patients suffering from coeliac sprue. A Lundh-test was performed in nine patients and twenty-six healthy volunteers. Basal plasma-CCK levels (3.4 +/- 0.5 pmol/l in sprue patients vs. 4.1 +/- 0.5 pmol/l in controls) and the integrated 120 min postprandial CCK values showed no differences in both groups. However, in controls the peak CCK value of 27.5 +/- 5.6 pmol/l appeared after 15 minutes whereas in sprue patients the peak of 18.9 +/- 4.5 pmol/l appeared after 60 minutes. CCK concentrations in duodenal biopsies of patients with coeliac sprue revealed significantly lower values compared to controls (123.4 +/- 37.4 versus 240.0 +/- 11.3 pmol/g wet weight). The stimulated lipase output was significantly lower throughout the whole sampling period in coeliac sprue patients whereas amylase output showed an inconstant reduction. The trypsin output was not altered. These results suggest that other mediators than CCK are responsible for the maintenance of trypsin output and for the reduction of lipase output in patients with coeliac sprue.

Adult↗

PubMed1986

Exocrine pancreatic function in oleic acid-induced pancreatic insufficiency in rats.

Pancreatic insufficiency was induced in rats by a single injection of 50 microliter oleic acid into the pancreatic duct over a period of 3 min. Exocrine tissue was destroyed within 3-6 days, and after 6 weeks the remaining pancreas equaled 2.7% of the original organ. The rats showed retardation of body weight in spite of normal food intake. After 7 weeks the fecal weight increased by 23%, and the fecal chymotrypsin activity decreased by 90% compared to controls. At this time plasma cholecystokinin (CCK) concentrations were significantly elevated. The amylase content in the remaining pancreas was reduced by 99%, and trypsin content was reduced by 93%. Unstimulated protein discharge from the remnant pancreas in vitro was threefold higher compared to secretion from control tissue. Thus a simple, reproducible model for inducing persistent pancreatic insufficiency was developed. To compensate for the loss of exocrine tissue, the remaining acinar cells adapt by a CCK-mediated increase in protein secretion.

Adaptation, Physiological↗

PubMed1986

Endogenous CCK release and pancreatic growth in rats after feeding a proteinase inhibitor (camostate).

The serine proteinase inhibitor camostate was fed to rats in single, daily doses of 100 mg/kg, 200 mg/kg, and 400 mg/kg for 5, 10, or 15 days. Within 5 days, pancreatic size and protein, DNA, and enzyme content increased significantly. After prolonged administration, this trophic effect was more pronounced, and anticoordinate regulation of the synthetic rate of individual secretory proteins was observed. While enzyme content and protein synthesis of trypsinogen and chymotrypsinogen were increased, respective values for amylase were drastically reduced. Plasma levels of cholecystokinin (CCK) did not differ from controls when measured 24 h after administration of camostate. Immediately after oral feeding of camostate, CCK levels increased 10-fold above controls, reached a maximum after 90 min, and remained elevated for more than 6 h. Proglumide, a CCK-receptor antagonist, only slightly reduced the trophic action of the proteinase inhibitor. The data indicate that endogenous CCK release by a proteinase inhibitor is as potent in the modulation of pancreatic growth and individual enzyme synthesis as exogenous hormone application.

Animals↗

PubMed1986

Effect of the prokinetic drug cisapride on gastrointestinal hormone release.

The influence of the prokinetic drug cisapride on the release of gastrointestinal hormones was studied in volunteers. First, acute effects of single doses of cisapride compared with saline were investigated. Cisapride at doses of 8 mg and 20 mg intravenously significantly increased plasma concentrations of pancreatic polypeptide (hPP) by 145% and 146%, respectively. Cholecystokinin (CCK) levels were increased by 176% at 8 mg cisapride, whereas gastrin and insulin levels remained unchanged. Enhancement of PP and CCK secretion was almost completely abolished by pretreatment with 1 mg atropine. Carbachol (250 micrograms subcutaneously) increased PP release by 62% but did not affect the other hormones. Second, the influence of a 1-week treatment (10 mg three times daily, given orally) on plasma hormone levels was studied. After 1 week the postprandial CCK release was diminished by 58%. Basal levels and postprandial responses of gastrin, PP, and insulin were not altered by prolonged cisapride administration. It is concluded that acute application of cisapride stimulates secretion of PP and CCK via atropine-sensitive mechanisms and that chronic treatment with cisapride diminishes CCK release by an unknown mechanism.

Adult↗

PubMed1985

Role of endogenous prostaglandins in somatostatin-induced inhibition of gastrointestinal hormone secretion.

Endogenous prostaglandins have been reported to be essential for the inhibitory effect of somatostatin on acid secretion. From these results it could be suggested that the effect of somatostatin on the secretion of gastroentero-pancreatic hormones may also be medulated by prostaglandins. This hypothesis was investigated in man and in the rat. Somatostatin-induced inhibition of postprandial gastrin, cholecystokinin, pancreatic polypeptide, and insulin release was not influenced by indomethacin pretreatment in healthy subjects. Using the isolated perfused rat stomach preparation, inhibition of acetylcholine-stimulated gastrin secretion by somatostatin was found to be unchanged by indomethacin treatment. It is concluded that endogenous prostaglandins are unlikely to be indispensable for the inhibitory effect of somatostatin on gastroentero-pancreatic endocrine cells.

Adult↗

PubMed1984

[Bezafibrate-induced myolysis and myoglobinuria in patients with impaired renal function].

A muscular syndrome has been described in patients on clofibrate and fenofibrate therapy. The present paper describes four patients with impaired renal function in whom symptoms and signs of skeletal muscle damage developed during treatment with another clofibrinic acid derivative, bezafibrate. The syndrome was characterized by variable degrees of muscular cramps and paresis, excessive elevation of muscle enzymes in serum, myoglobinemia and myoglobinuria. Transient deterioration of renal function was also common. All patients had been overdosed with bezafibrate with regard to their renal function. It is concluded that bezafibrate like other lipid lowering agents of the clofibrate type may induce muscle damage, at least if doses are not adjusted to renal function. Extreme caution is warranted when treating patients with renal impairment with bezafibrate and strict dose adjustment to kidney function is necessary to avoid muscle damage.

Aged↗