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Biomedical subjects

G Adler

Publications and source records attributed to G Adler.

At least 397 records · Page 22Linked to original sources
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

Stimulation of pancreatic secretory process in the rat by low-molecular weight proteinase inhibitor. II. Regulation of total protein and individual enzyme biosynthesis.

Oral application of a single dose of a new synthetic proteinase inhibitor Camostate (Foy-305) in male Wistar rats was carried out together with studies of in vitro amino acid incorporation followed by separation of proteins by two-dimensional gel electrophoresis. The aim of this experiment was to analyze changes produced by the inhibitor in total protein and individual enzyme biosynthesis. Administration of 100 mg/kg Foy-305 resulted in significant inhibition of total pancreatic protein synthesis, without changes in fractional rates for individual enzymes. 50 mg/kg Foy-305 induced a 10-fold elevation of cholecystokinin (CCK) levels in serum; this persisted for 3 h and led to a significant increase in the total rate of protein synthesis with peak values at 6 and 9 h (78% and 84% above control levels, respectively), returning to control by 15 h. Changes in fractional rates of synthesis occurred with a latency of 6 h and were restricted to amylase and the anionic form of trypsinogen and chymotrypsinogen. Amylase biosynthesis decreased by about 40% from control levels at 9 h to return to control levels by 15 h. Increased synthesis of trypsinogen and chymotrypsinogen was observed; this was also phasic. The results show similar enzyme-specific regulation as previously described for exogenous CCK stimulation and for the adaptation of the pancreas to diets enriched in protein. They demonstrate the effectiveness of pulsatory endogenous hormone release in the regulation of protein synthesis.

Amylases↗
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

Exocytosis occurs at the lateral plasma membrane of the pancreatic acinar cell during supramaximal secretagogue stimulation.

In vitro and in vivo studies indicate that the secretory response to both caerulein and carbamylcholine stimulation is biphasic. Over the range of submaximal to maximal concentrations of secretagogues, discharge of exocrine proteins in vitro into the incubation medium and in vivo into the pancreatic duct increased and morphologic analysis indicated that exocytosis of zymogen granules occurred exclusively at the luminal membrane. Under in vivo conditions, supramaximal stimulation with caerulein or carbamylcholine resulted in a dose-dependent decrease in amylase release into the pancreatic duct and increase in the appearance of amylase in the blood circulation. Under in vitro or in vivo conditions, supramaximal secretagogue stimulation resulted in marked inhibition of exocytotic activity at the luminal plasma membrane, the appearance of intergranule contacts and fusions within the cytoplasm, and the appearance of exocytotic activity at the lateral plasma membrane. Lateral exocytotic images were observed with individual and fused zymogen granules and autophagic vacuoles. This redirection in the final step of the secretory pathway provides in part the biological basis for the increased appearance of pancreatic (pro)enzymes in the interstitial fluid and serum during supramaximal secretagogue stimulation.

Animals↗
PubMed1987

Tubular complexes in cerulein- and oleic acid-induced pancreatitis in rats: glycoconjugate pattern, immunocytochemical, and ultrastructural findings.

Ductlike tubular complexes in cerulein-induced pancreatitis and oleic acid-induced pancreatic insufficiency were studied to analyze further their origin and development. Immunocytochemistry for pancreatic enzymes, lectin-binding studies, and ultrastructural investigations were combined with autoradiographic quantitation of labeling indices of ductlike cells in tubular complexes. In one group of rats, pancreatitis was induced by infusion of cerulein (10 micrograms kg-1 h-1). In a second group, pancreatic insufficiency was induced by intraductal injection of oleic acid (50 microliters). The investigations were carried out at distinct intervals following induction of pancreatic injury. In both groups of animals, after 3 days, a significant widening of acinar lumina was paralleled by a decreasing height of acinar cells, which showed pronounced retrogressive changes. At this time, acinar cells bound all of the lectins used and retained their immunoreactivity for amylase, trypsinogen, chymotrypsinogen, and lipase. At further intervals, acinar structures formed typical ductlike complexes, with a progressive loss of immunoreactivity for pancreatic enzymes and a reduced lectin-binding for L-fucose and N-acetylgalactosamine. Autoradiographic quantitation demonstrated no significant labeling of acinar cells undergoing tubular dedifferentiation. In both models, tubular complexes were removed by macrophages. It is concluded that lining cells in tubular complexes represent degenerating acinar cells that have no regenerative potency and have lost their secretory and membrane characteristics.

Animals↗
PubMed1987

Effect of pancreatic atrophy and hypertrophy on the small intestine.

Intestinal enzyme activities were investigated in mice with spontaneously occurring exocrine pancreatic insufficiency (EPI), in rats after induction of pancreatic insufficiency by intraductal injection of oleic acid, and in rats after feeding a proteinase inhibitor (Camostate) which induced a marked pancreatic hypertrophy. An increase in saccharase activity and in vitro uptake of L-phenylalanine was found in EPI mice, while activities of alkaline phosphatase and lactase were not altered. In oleic acid induced pancreatic insufficiency and in pancreatic hypertrophy no alterations in enzyme activities were observed. Morphometric analysis revealed no alterations in mucosal surface of EPI mice. It was suggested that the small intestine adapts fuctionally to severe and long lasting pancreatic insufficiency, but not to pancreatic hypertrophy.

Adaptation, Physiological↗
PubMed1987

Endocrine pancreatic morphology and function in exocrine insufficiency in rats.

Exocrine pancreatic insufficiency was induced in rats by injection of oleic acid into the pancreatic duct. Six weeks after a single injection of 50 microliters oleic acid, the exocrine tissue was reduced by 98%. The islets of Langerhans remained intact and showed no changes in the relative distribution of beta-, alpha-, D-, and PP-cells. In rats fed ad libitum, plasma insulin levels and pancreatic insulin content did not differ between oleic acid-treated animals and controls. The dynamic insulin response was evaluated in the isolated perfused pancreas. The biphasic pattern of insulin release after stimulation by glucose was preserved. The half-maximal (10 mM) glucose-induced insulin release was reduced to 49% after onset of exocrine atrophy. After stimulation of insulin secretion by a maximal glucose load (20 mM), the insulin output from the perfused pancreas was reduced to 56%. A reduction in insulin release to 24% occurred with respect to the arginine (15 + 10 mM glucose)-stimulated secretion. To evaluate the significance of these findings in intact animals, glucose tolerance tests were performed. There were no differences between oleic acid-, saline-, or untreated animals with respect to serum glucose or plasma insulin levels during the oral glucose tolerance test. The insulin response after intravenous glucose in oleic acid-treated rats was not statistically different from controls. Nevertheless, the serum glucose levels in rats with exocrine atrophy were above controls, indicating a slight impairment of glucose tolerance.

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↗
PubMed1987

Cardiac anti-ischemic effect of metoprolol: role of beta-blockade within the ischemic region.

The distribution of metoprolol and atenolol into ischemic and nonischemic myocardium was studied in anesthetized dogs, pigs, and cats. The beta-blockers were administered intravenously after coronary artery occlusion. Metoprolol was found to be significantly more efficiently distributed to the ischemic myocardium than atenolol in all three species. To investigate the functional implications of this difference in tissue distribution, the anti-ischemic effects of the two beta-blockers were studied in the 2-h period following coronary artery occlusion in anesthetized cats, in which heart rate was kept at a constant level. In this model, metoprolol (0.3 mg.kg-1 + 0.15 mg.kg-1.h-1) was found to attenuate or delay the developing ischemic process. This is shown by its significant reduction of (a) the decline of CK activity in ischemic myocardium, (b) the ST elevation in a precordial ECG lead, and (c) the decrease of arterial pressure and cardiac output. In contrast to metoprolol, atenolol (0.3 mg.kg-1 + 0.15 mg.kg-1.h-1) caused no significant anti-ischemic effect in this cat model. The difference in the effectiveness of the two drugs can most probably be explained by their differential distribution in the ischemic heart. Furthermore, the anti-ischemic effect of metoprolol shows that the presence of a beta-blocker in ischemic left ventricular myocardium can favorably affect the early phase of developing infarction.

Adrenergic beta-Antagonists↗
PubMed1986

Karyotype and ultrastructure of a colony stimulating factor (CSF) producing cell line (5637) originated from a carcinoma of the human urinary bladder.

The cell line 5637 which originated from a human urinary bladder carcinoma is known to produce GM-CSF and Multi-CSF ectopically. Determination of cell surface antigens defined by monoclonal antibodies was recently reported. Here we report on the ultrastructure and karyology of this CSF secreting cell line. At the ultrastructural level the monolayer in vitro culture and the solid tumors formed in nude mice showed all characteristics consistent with a well-differentiated transitional cell carcinoma (TCC). A subclone was found to grow in suspension and did not secrete any CSF activity. High resolution chromosome analysis revealed chromosomal abnormalities which agreed only in few particulars with nonrandom chromosomal aberrations usually found in TCC. Analysis of the cytogenetic results showed that nearly all structural abnormalities present are known to be associated with acute or chronic human leukemia. The possibility that the ectopic production of CSF in this cell line may be correlated to one or more of the described chromosomal aberrations is discussed.

Animals↗
PubMed1986

Human acute pancreatitis: its pathogenesis in the light of immunocytochemical and ultrastructural findings in acinar cells.

Human acute pancreatitis results from an autodigestive process frequently associated with alcohol abuse, gall stone disease and shock. Peripancreatic fat necrosis was identified as one of the earliest visible lesions, whereas acinar cell necrosis and haemorrhage were regarded as secondary changes. To examine the alterations in acinar cells in more detail, their enzyme content and fine structural features were studied immunocytochemically using antisera against alpha-amylase, lipase, trypsin, chymotrypsin and pancreatic stone protein, and electronmicroscopically in pancreatic tissues from patients with severe acute pancreatitis. Peripheral acinar cells in the immediate vicinity of fat necrosis were found to be heavily degranulated, while acinar cells at some distance of necrosis fully retained their enzyme content. Other frequent changes of the acinar cells included cuboidal transformation, loss of microvilli, increased occurrence of autophagosomes, and formation of enlarged acinar lumina. As there was no apparent cell membrane leakage or rupture of duct lumina, it is concluded that the acinar cells adjacent to fat necrosis release their granules by undirected basolateral extrusion. The findings thus suggest that one of the basic defects in acute pancreatitis is the uncontrolled release of enzymes from peripheral acinar cells into the interstitial space which, in turn, presumably by the action of lipase, leads to autodigestive fat necrosis.

Acute Disease↗
PubMed1986

Effects of oral agents on pancreatic duct permeability. A model of acute alcoholic pancreatitis.

The main pancreatic duct can be made permeable to molecules of up to 20,000 daltons by oral pretreatment with aspirin and ethanol. Because pancreatic enzymes have similar molecular weights, we hypothesized that activated pancreatic enzymes would leak from a permeable duct and produce pancreatitis. Four groups of cats were pretreated with either milk, aspirin, ethanol, or aspirin and ethanol for 48 hr. Then pancreatic juice (either activated by enterokinase or nonactivated) was perfused along the duct from tail to duodenum. Twenty-four hours later the animals were examined. Animals pretreated with aspirin, ethanol, or both, and in which ducts were perfused with activated juice, developed acute edematous pancreatitis. Animals that had perfusion with nonactivated enzymes had pancreases indistinguishable from control animals. Morphological studies on ductal permeability in animals pretreated with ethanol and aspirin showed electron-dense material (believed to be dextran) between the basal plasma membrane and basal lamina, and in the basal intercellular space.

Acute Disease↗
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↗