Biomedical subjects

C Beglinger

Publications and source records attributed to C Beglinger.

At least 163 records · Page 9Linked to original sources

PubMed1992

Evidence for hormonal inhibition of exocrine pancreatic function by somatostatin 28 in humans.

Somatostatin 28 (S-28), originating in gastrointestinal cells, is secreted into the circulation and increases in humans after ingestion of a mixed meal. To evaluate the possibility that the increased levels of S-28 post cibum might modulate the release of enzymes and bicarbonate from the exocrine pancreas, S-28 was infused intravenously into healthy volunteers to levels seen after food intake. During S-28 infusion, the output of lipase, trypsin, amylase, and bicarbonate stimulated by either exogenous cholecystokinin octapeptide or endogenous signals from intraduodenal administration of tryptophan or a mixture of amino acids was significantly reduced. It is concluded that S-28 released from the gut during food intake modulates pancreatic exocrine function in humans.

Adult↗

PubMed1992

Role of circulating cholecystokinin in control of fat-induced inhibition of food intake in humans.

Cholecystokinin (CCK) has been proposed to serve as a satiety signal in animals and humans. To further explore the role of CCK in humans, the effect on satiety and eating behavior of a specific CCK-receptor antagonist, loxiglumide, that preferentially inhibits peripheral (CCK-A) receptors was investigated. In a randomized, blind, four-period latin square design, 10 subjects received intravenous saline (placebo) or loxiglumide (10 mg/kg per hour) with concomitant intrajejunal perfusions of isotonic saline or fat (containing 50% corn oil and 3% albumin). Food intake and plasma CCK concentrations were assessed, and subjects scored their feelings of hunger and fullness in paired experiments. In placebo-treated subjects, the duration of the meal was shorter during fat perfusion (30 +/- 2 minutes vs. 35 +/- 2 minutes; P less than 0.01; mean +/- SEM). The amount of food intake was reduced (361 +/- 31 g vs. 454 +/- 35 g; P less than 0.05), and fluid ingestion was inhibited (490 +/- 31 mL vs. 625 +/- 38 mL; P less than 0.01). Loxiglumide did not affect any parameter and did not change the pattern of responses. In loxiglumide-treated subjects there was a 4-5-fold elevation in plasma CCK levels. These results confirm that jejunal infusion of lipid reduces the size of the meal and stimulates early satiety. The data imply that these effects are not mediated through peripheral endogenous CCK under these conditions.

Adult↗

PubMed1992

Tolerability and absorption enhancement of intranasally administered octreotide by sodium taurodihydrofusidate in healthy subjects.

Nasal sprays containing different concentrations of the somatostatin analogue octreotide and sodium tauro-24,25-dihydrofusidate (STDHF) as an absorption promoter were evaluated in two consecutive pharmacokinetic studies in healthy volunteers to characterize their bioavailability and local tolerability. The concentrations of STDHF were selected on the basis of a phase diagram generated by a dynamic laser light-scattering technique to ensure that the mixture was above the critical micellar concentrations. Compared to a 50-micrograms subcutaneous injection, the nasal spray formulation without STDHF had a mean relative bioavailability of 17.9%. For nasal formulations containing 3 and 1.65% (w/v) of STDHF, the bioavailability increased to 29.0 and 25.7%, respectively. The enhancement of nasal absorption was dependent on the STDHF concentrations as shown by decreasing the amounts to 1.2 and 0.8% (w/v) for tolerability reasons; the bioavailability was reduced to 15.3 and 20.5% in these cases, respectively. The local tolerability of all STDHF-containing sprays was poor, leading to stinging sensations and lacrimation. The poor local tolerability of the octreotide nasal spray containing different concentrations of STDHF required for effective nasal absorption enhancement appears to be impractical for further clinical development. These findings clearly stress the necessity to investigate tolerability and safety issues of new drug delivery systems in early developmental phases.

Administration, Intranasal↗

PubMed1992

The absorption site of cyclosporin in the human gastrointestinal tract.

1. An emulsion preparation of cyclosporin was administered locally to different parts of the small and large intestine by gavage: to the duodenum (opposite to the papilla of Vater), jejunum (150 cm distal to the teeth), ileum (300 cm distal to the teeth), and to the colon descendens (30 cm proximal to the anus). 2. The bioavailability of cyclosporin after these instillations was compared with that after oral administration of a hard gelatine capsule formulation. 3. Cyclosporin was found to be absorbed predominantly in the small intestine. This may have implications for dosage in patients with reduced absorptive surface area.

Adult↗

PubMed1992

Postprandial control of gallbladder contraction and exocrine pancreatic secretion in man.

To explore the interactions between cholecystokinin (CCK) and the cholinergic system, we compared the effect of cholinergic or peptidergic CCK blockade on gallbladder contraction and pancreatic enzyme secretion using atropine and loxiglumide (a specific CCK antagonist) as pharmacological tools. Gallbladder contraction was measured by sonography and pancreatic secretion by a marker perfusion and aspiration technique. Graded doses of exogenous CCK8 induced dose-dependent contractions of the gallbladder and increasing enzyme outputs. Loxiglumide (10 mg kg-1 h-1) abolished the gallbladder response and prevented an increase in pancreatic enzyme secretion to CCK8. Atropine (5 micrograms kg-1 h-1), however, only reduced gallbladder contraction and enzyme output to CCK8. Gallbladder volumes decreased maximally to 12 +/- 4% after oral food, whereas enzyme output and plasma CCK levels increased 6- to 8-fold. Loxiglumide completely abolished gallbladder contraction and inhibited enzyme secretion by 30%. Atropine caused a small reduction in gallbladder volumes, but essentially blocked postprandial enzyme secretion. The results indicate that CCK is the major regulator of gallbladder contraction with the cholinergic system modulating the response, while the exocrine pancreas is crucially dependent on a cholinergic background with CCK modulating the secretory response.

Adult↗

PubMed1992

Enteral absorption of octreotide.

1. The somatostatin octapeptide-analogue, octreotide, is absorbed as intact peptide from the gastrointestinal (GI) tract. 2. In situ absorption experiments in rats confirmed our recent intubation studies in human volunteers demonstrating that the peptide has preferential absorption sites in the small intestine. Absorption of octreotide was higher in the jejunum than in the duodenum or the ileum. 3. Experiments with bile-duct cannulated rats demonstrated that the absorption of octreotide decreased in the presence of bile, reflecting a negative influence of biliary components on the absorption of the peptide. 4. Uptake experiments using rat jejunal brush border membranes were performed to analyse the absorption mechanisms. The transport of octreotide into jejunal brush border membranes was significantly higher than the uptake into membrane vesicles isolated from rat ileum. When initial uptake (0-15s) rates into the membrane vesicles were calculated as a function of the peptide concentration, a saturable component could be observed, indicative of transport mechanisms different from simple diffusion.

Animals↗

PubMed1992

Intestinal phase of superior mesenteric artery blood flow in man.

Duplex ultrasound was used to investigate superior mesenteric artery haemodynamics in humans in order to study the contribution of the small intestine to the postprandial splanchnic hyperaemia, and to determine the relative potencies of the major food components in the postprandial mesenteric flow response. Duplex parameters of vessel diameter, mean velocity, and volume flow were determined serially in the basal state and after stimulation. Flow parameters were significantly (p less than 0.05) increased after liquid and solid oral meals. Modified sham feeding did not alter mesenteric blood flow. Intestinal perfusion of an isocaloric liquid test meal induced flow increases comparable with oral intake. Superior mesenteric artery blood flow also significantly (p less than 0.05) increased after isocaloric and iso-osmolar loads of intraduodenal carbohydrate, fat, and protein meals. Responses were similar after the test meal, fat, and protein, but were significantly (p less than 0.05) less for carbohydrates. Different osmolar loads of saline did not affect flow responses. We conclude that the intestinal phase is the major regulator of the postprandial mesenteric blood flow response in healthy humans and that the chemical nature of food determines the mesenteric response pattern.

Adult↗

PubMed1992

Non-invasive assessment of gastrointestinal motility disorders in diabetic patients with and without cardiovascular signs of autonomic neuropathy.

Twenty six patients with insulin dependent diabetes mellitus underwent a gastric emptying test, a gall bladder contraction test, an orocaecal transit study, and a colon transit test. Eleven patients had signs of cardiovascular autonomic neuropathy, 15 patients were without signs of cardiovascular autonomic neuropathy. Mean gastric clearance of radioopaque markers ingested with a meal averaged 29.5 (2.3) markers per six hours in subjects without cardiovascular autonomic neuropathy compared with 17.8 (2.3) markers per six hours in patients with cardiovascular autonomic neuropathy (p < 0.02). Gall bladder emptying in response to graded CCK8 stimulation was impaired in five of 11 patients with cardiovascular autonomic neuropathy, whereas it was normal in the patients without cardiovascular autonomic neuropathy (p < 0.01). Oral caecal transit times were not significantly different in the two patient groups, whereas colonic transit was slower in the patients with cardiovascular autonomic neuropathy compared with the group without cardiovascular autonomic neuropathy (p < 0.02). There was no correlation between disturbed gastric clearance, impaired gall bladder contraction, and prolonged colonic transit time in the patients with cardiovascular autonomic neuropathy nor was there a correlation between any disturbed motor function and age or duration of diabetes. It is concluded that autonomic neuropathy can affect motor functions throughout the gastro-intestinal tract. Any disturbed motor function in the gut could therefore be one of the numerous expressions of diabetic neuropathy affecting the cardiovascular, the endocrine or the gastrointestinal system.

Adult↗

PubMed1992

Relevant aspects of physiology in chronic pancreatitis.

Specific points of physiology which are relevant for the understanding and management of chronic pancreatitis are focussed on. First, the regulatory factors of exocrine pancreatic secretion are described, discussing the role of the cholinergic system and of the classical gut hormones cholecystokinin and secretin. The association of upper gastrointestinal dysfunctions with a disturbed exocrine pancreatic response is also dealt with. Lastly, these changes are related to clinical consequences such as maldigestion or malabsorption.

Chronic Disease↗

PubMed1992

Diagnosis of bacterial overgrowth after culturing proximal small-bowel aspirate obtained during routine upper gastrointestinal endoscopy.

The purpose of this study was to evaluate the method of obtaining aspirated fluid for culture from the small intestine through a fiberoptic gastrointestinal endoscope for diagnosing small-bowel overgrowth. The study population consisted of 10 healthy volunteers and 26 patients with various gastrointestinal problems referred for routine endoscopic examination. The material to be cultured was obtained under direct visualization approximately 25 to 30 cm distal to the pylorus or from the afferent loop (in Billroth-II patients) with a sterilized sheathed wash pipe passed through the suction channel of the endoscope. Cultures were considered positive for bacterial overgrowth if total counts of organisms were 10(5)/ml or more. All healthy volunteers and 16 of 21 unoperated patients had sterile or insignificant growth, whereas all 5 patients who had Billroth-II operations had positive overgrowth. The endoscopic method for collection of proximal gastrointestinal fluid for culture is simple and can be performed during routine endoscopy.

Adult↗

PubMed1992

[Pathophysiology of ulcer disease].

The pathogenesis of ulcer disease is complex. The present outline focuses on four main aspects: 1) The mechanisms governing acid production and the role of acid in ulcer disease. 2) The mechanisms regulating mucosal resistance to injury. 3) The association of ulcer disease with antral gastritis and Helicobacter pylori infection. 4) Ulcer disease and non-steroidal antiinflammatory drugs (NSAIDs). The complex mechanisms underlying maintenance of mucosal integrity in the normal state and in ulcer disease are discussed. Acid/peptic activity as permissive factors are related to impaired mucosal resistance due to Helicobacter infection or NSAID intake.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed1991

Human gastrin-releasing peptide: biological potency in humans.

Gastrin-releasing peptide (GRP) was infused in graded doses (1-27 pmol/kg per h) to healthy human volunteers to study the effects on gastric, pancreatic and gallbladder functions as well as on gastrin, CCK and PP release. The results were compared to equimolar doses of synthetic bombesin. GRP significantly (P less than 0.05) stimulated gastric and pancreatic secretory responses, gallbladder contraction and gastro-enteropancreatic hormone release in a dose-dependent manner. GRP was found to be equipotent to bombesin with respect to gastric acid secretion, pancreatic enzyme output, gallbladder contraction and plasma hormone release. We conclude (a) that human GRP has similar biologic effects as synthetic bombesin; (b) as GRP is localized exclusively in nerve tissue and has potent effects on different organs, it is a likely candidate for peptidergic control of human gastric, pancreatic and gallbladder functions.

Adult↗

PubMed1991

[Sensitivity and specificity of a simplified, standardized 13C-urea breath test for the demonstration of Helicobacter pylori].

A simplified 13C-urea breath test (UBT) for detection of Helicobacter pylori (Hp) infection was evaluated in 50 patients. Following upper gastrointestinal endoscopy the patients received 100 ml of a liquid test meal with 100 mg 13C-urea. Breath samples were obtained at baseline and 30 minutes respectively. The UBT was positive (difference of 13CO2 enrichment exceeding 5%) in 33/35 patients with culture-proven Hp infection and negative in 14/15 patients in whom microbiological culture, histology and a urease test (CLO-test) were negative. We conclude that in view of its high sensitivity (94%) and specificity (93%) the UBT is useful for rapid, non-invasive diagnosis of Hp infection.

Adult↗

PubMed1991

Diagnostic relevance of the amino-terminal cleavage peptide of procalcitonin (PAS-57), calcitonin and calcitonin gene-related peptide in medullary thyroid carcinoma patients.

We have identified the amino-terminal cleavage peptide of procalcitonin (PAS-57) in the plasma of normal human subjects and of medullary thyroid carcinoma (MTC) patients together with calcitonin (CT) and CT gene-related peptide (CGRP). Major components on reversed-phase high-pressure liquid chromatography had the retention times of synthetic PAS-57, CT and CGRP as well as of precursor proteins. Plasma levels of PAS-57 (290 +/- 50 pgeq/ml; mean +/- S.E.M.), CT (27 +/- 8 pgeq/ml) and CGRP (8.4 +/- 0.8 pgeq/ml) were respectively 2.3-, 1.6- and 1.5-fold higher in normal men (n = 10) than in women (n = 8). In response to 1 min intravenous calcium infusions (2 mg per kilogram body weight) PAS-57 and CT were increased 3.5- and 2.7-fold (P less than 0.001), respectively, but CGRP remained unchanged. In MTC patients (n = 57) with raised levels of PAS-57 and CT, the molar ratio between PAS-57 and CT was 1.7-times higher than in normal subjects (P less than 0.01). We have found that PAS-57 is a predominant CT/CGRP gene derived product in the circulation of normal subjects and of MTC patients and a potential new MTC tumor marker.

Adult↗

PubMed1991

[Should gallstones be crushed?].

Explore the source record for details and available documents.

Cholelithiasis↗

PubMed1991

Relevance of pH dependency on in vitro release of bromocriptine from a modified-release formulation.

Since pH profiles of the dissolution rate are thought to be predictive for the in vivo performance of oral modified-release formulations with respect to bioavailability and dose dumping with food, these pH profiles were established for a new modified-release (MR) formulation for bromocriptine (Parlodel SRO). The results show a marked decrease of bromocriptine dissolution with increasing pH of the dissolution medium. However, when measured in native human duodenal juice (pH 8.1), dissolution was significantly higher than when measured in buffer of comparable pH. In a human pharmacokinetic study, this MR formulation showed good bioavailability and no food effect on the pharmacokinetic profile. Therefore, pH profiles alone seem to have only a limited predictive power for the in vivo performance of this MR formulation for bromocriptine.

Bromocriptine↗

PubMed1991

Physiological role of cholecystokinin on postprandial insulin secretion and gastric meal emptying in man. Studies with the cholecystokinin receptor antagonist loxiglumide.

Cholecystokinin was previously proposed to play an important role in the regulation of postprandial insulin secretion either indirectly, by inhibiting gastric meal emptying, or directly, by acting as an incretin promoting the release of insulin. The aim of this investigation was therefore to clarify the role of endogenous cholecystokinin in the regulation of insulin release and gastric emptying applying the highly potent and specific cholecystokinin receptor antagonist loxiglumide. Five healthy volunteers were examined after an overnight fast. Gastric meal emptying was measured by the double indicator technique using a multiple lumen tube in the duodenum and 99mTc-diethylenetriamine pentaacetate as a meal marker and polyethylene glycol 4000 as a duodenal perfusion marker. Postprandial insulin, C-peptide, cholecystokinin and glucose levels were measured after ingestion of two isocaloric meals of a) Ensure (containing fat, protein and glucose), and b) a pure glucose meal (1.11 mol/l). The meals were given either with an intravenous infusion of loxiglumide (22 mumol.kg-1.h-1) or placebo. The infusion of loxiglumide markedly accelerated the gastric emptying of the mixed meal (area under curve, 5576 +/- 352 min vs 3498 +/- 109 min; p less than 0.001) and the pure glucose meal (area under curve 5662 +/- 537 min vs 3551 +/- 534 min; p less than 0.05). Simultaneously, loxiglumide induced a more rapid rise in postprandial insulin levels after both meals resulting in significantly higher (p less than 0.05) insulin levels during the first postprandial hour, but similar insulin levels in the second postprandial hour. Accordingly, we found a close correlation between meal emptying and insulin release (r = 0.748, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1991

Dissociation of cholecystokinin and pancreaticobiliary response to intraduodenal bile acids and cholestyramine in humans.

The role of intraduodenal bile acids in the regulation of cholecystokinin (CCK), pancreatic polypeptide (PP), and secretin as well as exocrine pancreatic and biliary secretion was investigated by means of a duodenal marker perfusion technique in volunteers. The following solutions were perfused: (1) liquid test meal, (2) test meal with 6 g cholestyramine, (3) test meal with 2 g chenodeoxycholic acid (CDC), (4) test meal with 6 g cholestyramine and 2 g CDC, (5) 6 g cholestyramine alone, and (6) 2 g CDC alone. The test meal caused an immediate increase in CCK and PP plasma levels, whereas secretin was not significantly altered. CCK release was further enhanced by addition of cholestyramine, whereas CDC inhibited release. The stimulatory effect of cholestyramine was abolished by CDC. CDC alone and in combination with the test meal stimulated secretin release. The response of PP to the test meal was not altered by addition of either compound. Cholestyramine and CDC alone caused only a very small increase in CCK levels, whereas PP was stimulated to nearly postprandial values. Meal-stimulated pancreatic and biliary secretion was significantly enhanced by cholestyramine, CDC, and the combination of both. CDC and cholestyramine alone each stimulated enzyme and bile secretion to a greater extent than the test meal. We conclude that intraduodenal bile salts are a modulator of postprandial CCK release. Changes in exocrine pancreatic and biliary and PP secretion do not necessarily parallel CCK concentrations, suggesting that different mediators are involved in the observed bile acid-induced changes in humans.

Adult↗