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H Koop

Publications and source records attributed to H Koop.

At least 37 records · Page 2Linked to original sources
PubMed1994

A new CCK-B/gastrin receptor antagonist acts as an agonist on the rat pancreas.

The new CCK-B/gastrin receptor antagonist PD 136450 is of potential value in treating neurologic and psychiatric disorders. We investigated possible side effects on the rat pancreas using acute and chronic administration schedules. In chronic experiments, four groups of rats were given either PD 136450, the proton pump inhibitor BY 308 (in order to induce hypergastrinemia), a combination of both, or control solutions over 14 d. Pancreatic growth, DNA, and protein content were significantly increased in rats given PD 136450 irrespective of circulating gastrin levels. Furthermore, an anticoordinate shift in pancreatic enzyme content in favor of trypsin and chymotrypsin at the expense of amylase and lipase was observed. Plasma CCK levels remained unchanged in this group making a role of circulating hormone unlikely. In order to investigate a possible direct agonist effect of the CCK-B/gastrin receptor antagonist, we studied amylase release from isolated rat pancreatic acini in response to PD 136450 and sulfated CCK8 alone and in combination with the specific CCK-A receptor antagonist MK 329. Increasing concentrations of PD 136450 caused a monophasic dose-response curve in contrast to the well-known biphasic amylase release in response to CCK8. Addition of increasing doses of PD 136450 to a concentration of CCK causing maximal stimulation of amylase release (0.1 nM) further enhanced amylase release from pancreatic acini. The specific CCK-A receptor antagonist MK 329 dose-dependently inhibited CCK8- and PD 136450-induced amylase release. In conclusion, the new CCK-B/gastrin receptor antagonist PD 136450 exhibited profound agonist actions on the rat pancreas mediated via CCK-A receptors.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1994

Rat gastric somatostatin and gastrin release: interactions of exendin-4 and truncated glucagon-like peptide-1 (GLP-1) amide.

The effect of exendin-4, a peptide of the secretin-glucagon family with high homology of amino acid sequence with glucagon-like peptide-1 (GLP-1), on gastric hormone release was investigated in the isolated perfused rat stomach. Exendin-4 dose dependently stimulated somatostatin release up to 9-fold at a concentration of 10(-7) M whereas gastrin release was inversely inhibited by up to 63%. These effects could partially be reduced by concomitant perfusion of truncated exendin-4, exendin(9-39)amide. Similarly, stimulation of somatostatin secretion and inhibition of gastrin release induced by GLP-1(7-36)amide was partially reversed by exendin-4 (9-39)amide. These data are consistent with the assumption that exendin-4 and truncated GLP-1amide exert their effects on gastric D and G cell by interaction with the same receptor.

Animals↗
PubMed1994

Expression of the gastric H+/K(+)-ATPase and histidine decarboxylase during omeprazole treatment.

The gastric proton pump H+/K(+)-ATPase in the parietal cell is central to acid secretion into the stomach. We performed the following experiment to examine the pattern of expression of the alpha- and beta-subunits of the H+/K(+)-ATPase at the transcriptional level during 7 days' application of the proton pump inhibitor omeprazole, in relation to the expression of gastrin and histamine, two stimuli of gastric acid secretion. Serum gastrin concentrations and mRNA levels of antral gastrin, fundic histidine decarboxylase (HDC) and H+/K(+)-ATPase alpha- and beta-subunits were determined after 8 h, 1, 3 and 7 days. Omeprazole treatment rapidly caused an increase in the serum gastrin concentration and the antral gastrin mRNA level after 3 days. HDC mRNA expression showed a steady increase with a 5-fold induction after 1 week. However, mRNA levels of the alpha- and beta-subunits of the H+/K(+)-ATPase were unchanged during the course of omeprazole treatment. These results suggest that omeprazole inhibition of the gastric proton pump does not result in feedback activation of H+/K(+)-ATPase gene expression despite adaptive changes of the endocrine stomach.

Animals↗
PubMed1994

[Results of selective kidney DSA in suspicious computerized tomography findings--retrospective evaluation of 122 cases].

The superiority of computer tomography in the detection and staging of renal malignomas has been proven in numerous studies. In this retrospective analysis, the significance of the pre-surgically still widely and routinely performed, selective kidney angiography was investigated. The written computer tomographical and angiographic findings of 122 patients were classified according to malignancy stage urgency. They were then compared to progression, and surgical finding respectively. Angiography had the greatest influence on the therapeutic procedure in those patients having only a slight computer-tomographical suspicion of tumor. An operation was waived by 12 patients. A small hypernephroma (pT 2 showing typical tumor vessels was found in two patients. Inoperability excepted, a surgical denudation was performed in all patients with computer tomographical tumor typical, or suspicious finding, irrespective of the angiographic result. The diagnosis was surgically confirmed in all patients having a tumor-specific angiogram. Yet besides benign tumors, 4 hypernephromas and 5 other malignomas were found in those patients showing an angiographically classified, vessel-free formation.

Adult↗
PubMed1993

Gastric argyrophil (enterochromaffin-like), gastrin, and somatostatin cells after proximal selective vagotomy in man.

The number, size, and volume density of endocrine cells was determined in biopsies obtained endoscopically in patients after proximal selective vagotomy (PSV; N = 31), antrectomy (N = 9), untreated duodenal ulcer (DU) disease (N = 11), and in controls (N = 15). Serum gastrin was significantly elevated after PSV (mean 60 pg/ml) compared to DU patients (29 pg/ml), controls (26 pg/ml), and after antrectomy (11 pg/ml). Volume density of fundic argyrophil (largely enterochromaffin-like) cells after PSV (0.74%) and in DU disease (0.63%) were significantly (P < 0.001) higher when compared with controls (0.37%) but lower after antrectomy (0.24%; P < 0.02). The density of argyrophil cells was not influenced by the interval following PSV or the magnitude of hypergastrinemia. Antral gastrin cells were increased after vagotomy, whereas the antral and fundic somatostatin cell numbers were reduced after PSV. It is concluded that: (1) a major role of the vagal nerve as a trophic factor for enterochromaffin-like cells could not be demonstrated after PSV, and (2) moderate hypergastrinemia after PSV did not induce proliferation of ECL cells.

Adult↗
PubMed1993

[A combination of conventional single contrast arthrography with arthro-CT of the shoulder--an evaluation of 78 cases].

For the diagnosis of traumatic shoulder lesions, 78 patients have been examined by conventional single contrast arthrography with subsequent CT. For 26 patients, it was possible to compare the radiological diagnosis with the arthroscopic or surgical findings. The combination of both diagnostic methods provided a high sensitivity (94%) and specificity (100%) for lesions of the ventral or dorsal limbus. Ruptures of the rotator cuff showed a sensitivity of 60% and a specificity of 89%. An unsatisfying sensitivity (60%) with high specificity (95.6%) was observed in the diagnosis of the ventral capsula. A retrospective screening of the roentgenography showed a good detectable leak of contrast medium, which was misinterpreted as being an artefact. All in all, the combination of conventional arthrography in mono-contrast and CT in daily routine should be recommended the diagnosis of traumatic shoulder lesions since it is easy to use, is of low inconvenience for the patient, and provides a high level of information.

Adolescent↗
PubMed1992

[Current pathogenetic principles in peptic ulcer].

New concepts in the pathophysiology of peptic ulcers must acknowledge 1. the close association of ulcers and Helicobacter pylori infection, 2. the protective role of endogenous prostaglandins, 3. the scarcity of new data on the importance of acidity (though presence of gastric acid remains indispensible for ulcer development). The different pathophysiologically relevant factors closely interact with each other. However, many not of actual concepts are still experimental and--apart from Helicobacter pylori--have not yet led to new therapeutical approaches.

Gastric Acid↗
PubMed1992

Low hepatic clearance of peptide YY (PYY) in the perfused rat liver.

The hepatic clearance rate and secretion rate mainly determine peripheral plasma concentrations of regulatory peptides released from the gastrointestinal tract. In the present study hepatic extraction of peptide YY (PYY) during a single passage was investigated in the in situ perfused rat liver excluding modulating actions of circulating hormones. During perfusion of low amounts of PYY (50, 100, 500 pmol l-1), peptide concentrations in the portal vein (5.1 +/- 4.6, 98.1 +/- 2.6, 558 +/- 13.6 pmol l-1) and in the hepatic vein (50.2 +/- 1.4, 88.6 +/- 2.2, 503 +/- 18.1 pmol l-1 was only 22.1%. PYY had no influence on hepatic glucose and lactate production, portal flow as well as bile flow and bile acid secretion at these concentrations. PYY seems to traverse the liver almost intact and reaches the target organs without any significant hepatic extraction. Concomitant studies on metabolic and excretory functions of the liver showed no effect of PYY.

Animals↗
PubMed1992

Cephalic stimulation of gastrointestinal secretory and motor responses in humans.

The present study was designed (a) to investigate the cephalic phase of gastropancreatic secretion, antroduodenal motility, and regulatory peptide release in six healthy young men and (b) to assess its regulation by the cholinergic system and endogenous cholecystokinin. Sham feeding performed for 15 minutes induced a concurrent stimulation of gastropancreatic secretion, antroduodenal motility, and pancreatic polypeptide release that lasted for 30 minutes. Reappearance of interdigestive phases III was retarded in the post-sham-fed state. Atropine abolished secretory, motor, and pancreatic polypeptide responses to sham feeding and enhanced gastrin release. The cholecystokinin receptor antagonist loxiglumide did not attenuate pancreatic enzyme response but diminished antral motor response by 72% (P less than 0.05) and release of pancreatic polypeptide by 91% (P less than 0.05); it enhanced gastrin release and abolished retardation of reappearance of phase III with sham feeding. It is concluded that (a) there is a distinct cephalic phase of gastropancreatic secretion, antroduodenal motility, and pancreatic polypeptide release in humans that is primarily under cholinergic control and that (b) endogenous cholecystokinin is involved in antral motor, gastrin, and pancreatic polypeptide responses to sham feeding.

Adult↗
PubMed1992

Effect of gastrin receptor blockade on endocrine cells in rats during achlorhydria.

Hyperplasia of the oxyntic enterochromaffinlike cells in response to long-lasting blockade of acid secretion is closely related to hypergastrinemia. In the present study, the effect of a specific gastrin receptor antagonist on proton pump inhibitor-induced changes on serum gastrin levels, mucosal height, as well as gastrin- and enterochromaffin-like cells was investigated in rats. The proton pump inhibitor BY 308 or the vehicle methylcellulose [Methocel (controls)] was administered for 2 weeks in the presence and absence of the gastrin receptor antagonist PD 136450 (CAM 1189). BY 308 significantly increased serum gastrin levels, gastrin cell density, and antral gastrin concentration. Concomitant application of PD 136450 did not alter this response. In the oxyntic stomach, mucosal height, enterochromaffinlike cell density, labeling index of enterochromaffinlike cells, and histamine concentration were elevated after treatment with BY 308. These increases were almost completely abolished by PD 136450. Even in normogastrinemic control rats, PD 136450 significantly decreased mucosal height of the oxyntic part of the stomach and the labeling index of enterochromaffinlike cells. The results show that (a) trophic effects of drug-induced achlorhydria are mediated by gastrin; (b) even in control rats (normogastrinemic), gastrin is a trophic factor for the oxyntic mucosa; and (c) antral gastrin cell hyperplasia in states of chronic achlorhydria is not mediated by gastrin itself.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1992

Serum iron, ferritin, and vitamin B12 during prolonged omeprazole therapy.

Since gastric acid plays an important role in the absorption process of iron and vitamin B12, we determined levels of iron, ferritin, vitamin B12, and folic acid in 75 serum samples obtained during continuous omeprazole therapy (6-48 months after start of therapy) from 34 patients with peptic diseases (primarily reflux esophagitis). Serum iron and ferritin levels were decreased in two and three patients, respectively, but there is little evidence that omeprazole administration was causally related to these findings. Serum vitamin B12 and folic acid levels were normal in all cases. We conclude that iron, vitamin B12, and folic acid malabsorption is unlikely to occur, at least within the initial 3-4 years of continuous omeprazole therapy.

Esophagitis, Peptic↗
PubMed1992

Healing and relapse of duodenal ulcer during ranitidine therapy in the elderly. The RUDER Study Group.

A total of 2,109 outpatients with active duodenal ulcer (DU) entered an open, prospective study in order to investigate factors influencing healing and relapse during 2 years of ranitidine therapy (300 mg daily for healing, 150 mg as maintenance treatment). In a retrospective analysis, we evaluated the influence of age. Symptoms related to DU in 1,899 evaluable cases in patients over 65 years of age (n = 185) were identical to those of DU patients younger than 65 years old (n = 1,714). Rapid healing within 2 weeks of ranitidine therapy was less frequent in the elderly (32.5%) than in younger patients (40.7%) though identical healing rates (94.1%) in each group were achieved by continuation of ranitidine therapy for 8 weeks. Cumulative recurrence rates during the 2 years of long-term therapy were lower (17.3%) in old age than in patients under 65 years of age (23.3%). Adverse events were rare in both age groups. We conclude that DU healing during ranitidine is delayed in old age. Additional differences in relapse rates in favor of the elderly suggest that DU disease has a different course in the elderly.

Adult↗
PubMed1992

Review article: metabolic consequences of long-term inhibition of acid secretion by omeprazole.

Metabolic sequelae of profound and long-lasting inhibition of gastric acid secretion by omeprazole have largely been neglected. Data from long-term studies suggest that vitamin B12 stores decrease slightly over several years, although this was not clinically relevant within the first 4 years of therapy. Additionally, it cannot be completely ruled out that patients with an increased iron demand may develop iron deficiency, but data available at present do not provide any evidence that iron malabsorption is to be expected under normal conditions. Protein homeostasis and calcium metabolism seem to be unaffected by long-term omeprazole therapy. Based upon present experience, serum cobalamin concentration should be monitored in patients undergoing omeprazole therapy for several years.

Absorption↗
PubMed1992

Effect of gastrin receptor antagonists on gastric acid secretion and gastrin and somatostatin release in the rat stomach.

The effects of two recently developed gastrin receptor antagonists, PD 136450 and L-365,260, on pentagastrin-stimulated acid secretion were investigated in rats. PD 136450 at a dose of 6 mg/kg s.c. (9.6 mumol) completely abolished acid secretion induced by pentagastrin. The inhibition of 18 mg/kg PD 136450 s.c. lasted for at least 8 h and was still effective after 14 days of treatment (18 mg/kg s.c. every 8 h). Acute application of L-365,260 at a dose of 3.8 mg/kg, which is equimolar (9.6 mumol) to 6 mg/kg PD 136450 reduced acid responses slightly. However, when L-365,260 was administered intravenously at a dose of 3 mg/kg, this antagonist completely abolished the pentagastrin-stimulated acid secretion. Furthermore, the effect of PD 136450 on endogenous gastric somatostatin and gastrin releases was tested in the isolated, vascularly perfused rat stomach. PD 136450 perfused at a concentration of 1 microM slightly increased somatostatin secretion after stimulation with a high dose of isoproterenol (10(-7) M). There was no effect of PD 136450 on basal or acetylcholine-stimulated gastrin secretion.

Animals↗
PubMed1992

Adaptation and renewal of the endocrine stomach.

At present at least seven different endocrine cell types have been identified in the stomach. According to their relative frequency and secretion products the antral gastrin producing G cell and somatostatin producing D cell and the fundic histamine producing ECL cell are the best characterized cell types. Total endocrine cell mass is controlled by various factors from inside and outside the stomach. Density of antral G and D cells depends on the presence and absence of food, on the antral pH and on additional humoral and/or neural factors. Gastrin and not gastric pH has been identified as the most important factor regulating the density of fundic ECL cells. Adaptation of gastric endocrine cells to gastric pH and to the presence, abundance or absence of humoral and neural regulators are well known phenomena though only partially understood. Antral G cells increase and antral D cells decrease during long-term achlorhydria which as a consequence leads to hypergastrinaemia. Examples are pernicious anaemia in man and drug-induced acid suppression under experimental conditions. Interestingly, achlorhydria-induced G cell hyperplasia never progresses to gastrinomas. Fundic ECL cell density increases markedly in the presence of long-lasting hypergastrinaemia independently of gastric pH. In contrast to G cells ECL cell hyperplasia may progress to rarely occurring ECLomas. However, this depends on additional conditioning factors as the presence of severe atrophic gastritis as in pernicious anaemia or a specific genetic trait present in patients with gastrinomas associated with the MEN I syndrome.

Adaptation, Physiological↗