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C von Ritter

Publications and source records attributed to C von Ritter.

35 records · Page 2Linked to original sources
PubMed1992

[Drug prevention and therapy of acute gastroduodenal lesions (stress ulcers)].

The incidence of acute lesions of the gastroduodenal mucosa is high in intensive care patients. A disturbed balance between aggressive and defensive factors is the cause of the mucosal damage. H2-receptor antagonists reduce gastric acidity, the most important aggressive agent, and are, therefore, still the drugs of choice for the prevention of stress ulcerations. Bleeding from mucosal lesions is the most common complication of stress ulcers. In addition to endoscopic and surgical techniques to stop bleeding, and prevent rebleeding, medical treatment with drugs like omeprazole have gained importance in recent years.

Acute Disease↗
PubMed1991

Role of high total protein in gallbladder bile in the formation of cholesterol gallstones.

While it is generally accepted that cholesterol supersaturation of bile is of key importance in the rapid formation of cholesterol crystals, the role of total biliary protein and pH in the pathogenesis of cholesterol gallstones is less well understood. The relation of cholesterol saturation, total protein, and pH was studied in 73 gallbladder bile samples with and 35 gallbladder bile samples without cholesterol crystals. In samples containing crystals, a trend to higher values of cholesterol and to a higher cholesterol saturation index was observed. However, significantly (P = 0.02) higher concentrations of total protein were found in samples with crystals [0.80 +/- 0.40 g/dL (8.0 +/- 4.0 g/L)] than in samples without crystals [0.63 +/- 0.26 g/dL (6.3 +/- 2.6 g/L)]. Moreover, of 22 bile samples with total protein concentrations greater than 10.0 g/L, cholesterol crystals were detected in all but 2. Total lipids, bile acids, phospholipids, and pH values were not significantly different in the two groups of bile samples. It was concluded that high biliary protein concentrations are frequently associated with cholesterol crystals and may, therefore, be a possible risk factor in the pathogenesis of cholesterol gallstones.

Bile↗
PubMed1990

Effects of neutrophil-derived oxidants on intestinal permeability, electrolyte transport, and epithelial cell viability.

There are several pathophysiologic conditions in which intestinal inflammation is associated with enhanced mucosal permeability, fluid loss, and epithelial cell injury. The objective of this study was to determine the effects of polymorphonuclear leukocyte (PMN)-derived oxidants on ileal mucosal permeability in vivo as well as electrolyte transport and epithelial cell viability in vitro. Using blood-to-lumen clearance of [51Cr]EDTA as a measure of mucosal permeability, we found that luminal perfusion with hydrogen peroxide (H2O2), hypochlorous acid (HOCl), or monochloramine (NH2Cl) produced a dose-dependent increase in mucosal permeability. Perfusion with 0.1 mM, 0.5 mM, and 1.0 mM oxidant produced a 2 +/- 1, 5 +/- 2, and 11 +/- 5-fold increase in mucosal permeability for H2O2, a 2 +/- 1, 8 +/- 3, and 36 +/- 12-fold increase for HOCl, and a 3 +/- 1, 11 +/- 2, and 30 +/- 7-fold increase for NH2Cl. Taurine monochloramine (TauNHCl) was ineffective in enhancing the blood-to-lumen clearance of [51Cr]EDTA. Furthermore, 0.01 mM and 0.1 mM NH2Cl and H2O2 produced significant increases in short-circuit current across rat ileum in vitro, whereas HOCl and TauNHCl were without effect. Tissue resistance and potential difference were not altered, suggesting that NH2Cl, HOCl, and H2O2 were not cytotoxic under these conditions. Cultured intestinal epithelial cells exposed to NH2Cl and HOCl were injured in a dose-dependent manner in vitro, whereas H2O2 and Tau NHCl were nontoxic. Taken together, our data suggest that PMN-derived oxidants may mediate the enhanced mucosal permeability, electrolyte transport, and epithelial cell injury associated with acute inflammation of the bowel.

Animals↗
PubMed1989

Neutrophilic proteases: mediators of formyl-methionyl-leucyl-phenylalanine-induced ileitis in rats.

N-formyl-methionyl-leucyl-phenylalanine (FMLP), a tripeptide of bacterial origin that activates and attracts neutrophils, increases mucosal permeability when placed in the lumen of rat ileum. Although studies using neutropenic animals demonstrate the essential role of neutrophils in FMLP-induced mucosal injury, the neutrophil-derived chemical mediator of this injury process remains undefined. The objective of this study was to determine whether neutrophilic proteases mediate FMLP-induced increases in mucosal permeability. The blood-to-lumen clearance of 51Cr-ethylenediaminetetraacetate was used to monitor mucosal permeability in the terminal ileum of Sprague-Dawley rats. In control (untreated) animals luminal perfusion with 10(-5) M FMLP resulted in twofold and fourfold increases in 51Cr-ethylenediaminetetraacetate clearance after 1 and 2 h of FMLP exposure, respectively. Pretreatment with the nonspecific serine protease inhibitor, soybean trypsin inhibitor (15 mg/kg), significantly attenuated the clearance responses normally observed during luminal perfusion with FMLP. The specific elastase inhibitors MeOSuc-Ala-Ala-Pro-Val-CH2Cl (10 mg/kg) and Eglin c (8 mg/kg) significantly attenuated the FMLP-induced increases in ethylenediaminetetraacetate clearance observed after both 1 and 2 h of exposure. The results of this study indicate that neutrophilic proteases mediate at least part of the increased mucosal permeability induced by luminal exposure to FMLP.

Animals↗
PubMed1989

Neutrophil-derived oxidants mediate formyl-methionyl-leucyl-phenylalanine-induced increases in mucosal permeability in rats.

The effects of several free radical scavengers and antioxidant enzymes on neutrophil-mediated changes in mucosal permeability (measured using blood-to-lumen clearance of 51Cr-labeled ethylene-diaminetetraactate) were assessed using ileal loops perfused with N-formyl-methionyl-leucyl-phenylalanine (FMLP). Neither superoxide dismutase nor catalase reduced the FMLP-induced increase in mucosal permeability. However, manganese-loaded desferrioxamine (a superoxide dismutase mimetic), PZ51 (a glutathione peroxidase analogue), desferrioxamine (an iron chelator), or dimethylsulfoxide (a hydroxyl radical scavenger) significantly attenuated FMLP-induced mucosal damage. The results of our experiments indicate that neutrophilic oxidants are responsible for a major portion of the mucosal permeability changes induced by FMLP.

Animals↗
PubMed1989

Effects of hCGRP I and II on gastric blood flow and acid secretion in anesthetized rabbits.

Effects of intravenously administered human calcitonin gene-related peptides (hCGRP) I and II on regional blood flow and gastric acid secretion were examined in barbiturate-anesthetized rabbits. Blood flow was measured by injection of radioactively labeled microspheres at 0, 10, 20, 30, and 60 min. hCGRP I and II and vehicle were infused intravenously in five rabbits in rising doses of 0.01 (0-10th min), 0.03 (11-20th min), and 0.1 microgram.kg-1.min-1 (21-30th min). hCGRP I and II increased gastric blood flow dose dependently. Moreover, hCGRP I raised regional conductance (inverse of vascular resistance) in the stomach, duodenum, heart, brain, and skeletal muscle. As a result of the increased total peripheral conductance the mean arterial pressure was reduced, but the cardiac output remained unchanged. hCGRP II increased blood flow and conductance selectively in the stomach and the pancreas. The total peripheral conductance and mean arterial pressure remained unchanged. Apparently, hCGRP II exerts a more localized effect on the stomach than hCGRP I. hCGRP I and II did not affect basal gastric acid secretion. Pentagastrin-stimulated acid secretion was increased by 28% with hCGRP I (0.025 micrograms.kg-1.min-1) and decreased by 27% with hCGRP II (0.025 micrograms.kg-1.min-1). The inverse effect of hCGRP I and II and the parallel stimulation of blood flow brought about with hCGRP I and II indicate a different mode of action of the peptides on gastric blood flow and gastric acid secretion.

Animals↗
PubMed1989

Sulfasalazine metabolites and dapsone attenuate formyl-methionyl-leucyl-phenylalanine-induced mucosal injury in rat ileum.

The effects of 5-aminosalicylic acid (5-ASA), 4-ASA, N-acetyl-5-ASA, and sulfapyridine on mucosal permeability were determined in an experimental model of acute ileitis. In addition, the antiinflammatory drug dapsone was tested. The distal 10 cm of rat ileum was perfused with formyl-methionyl-leucyl-phenylalanine (FMLP) (10(-5) M), a bacterial peptide that activates and attracts neutrophils. Changes in mucosal permeability were assessed using the blood-to-lumen clearance of 51Cr-ethylene-diamineacetate. Luminal FMLP increased 51Cr-labeled ethylenediamineacetate clearance twofold and fourfold in the first and second hour, respectively. Addition of 5-ASA (10 mM), 4-ASA (10 mM), or dapsone (4 mM) to the luminal perfusate after 60 min of FMLP perfusion greatly attenuated the increased mucosal permeability observed after 120 min of FMLP perfusion. Neither N-acetyl-5-ASA (10 mM) nor sulfapyridine (5 mM) had an effect on the FMLP-induced increase in mucosal permeability. We characterized the inhibitory effect of these drugs on the catalytic activity of myeloperoxidase and tested their ability to scavenge hypochlorous acid in vitro. 5-Aminosalicylic acid, 4-ASA, and dapsone demonstrated a powerful inhibitory effect on the catalytic activity of myeloperoxidase, whereas all drugs were equally effective in scavenging HOCl. In additional in vitro experiments we were unable to demonstrate an inhibitory effect of either of the drugs on the catalytic activity of neutrophilic elastase. Our results indicate that inhibition of neutrophilic myeloperoxidase may be an important mechanism by which 5-ASA, 4-ASA, and dapsone attenuate FMLP-induced mucosal injury.

Aminosalicylic Acid↗
PubMed1988

Gastric mucosal lesions induced by hemorrhagic shock in baboons. Role of oxygen-derived free radicals.

In this study we sought to define the role of oxygen-derived free radicals during ischemia and reperfusion in the production of acute damage to the gastric mucosa of baboons. The protective effect of the xanthine oxidase inhibitor, allopurinol, the superoxide scavenger, superoxide dismutase (SOD), and a long-acting SOD-albumin was determined. Mucosal damage was evaluated using light and scanning electron microscopy. Evidence for oxidative insult to the gastric mucosa was sought by measuring tissue concentrations of reduced (GSH) and oxidized (GSSG) glutathione. Gastric mucosal blood flow was estimated using the microsphere technique. A similar pattern of tissue damage was found at the end of ischemia in all three groups. Thirty minutes after reperfusion, severe mucosal damage (grade 3) increased only in the untreated control. In the two treated groups, grade 3 damage remained unchanged during reperfusion and a decrease in the percentage of moderate damage (grade 2) was seen. Both GSH and GSSG tissue concentrations were lower in the untreated controls as compared to the scavenger-treated groups, making it questionable whether GSH/GSSG tissue levels adequately reflect oxidative stress. We conclude that in our ischemia-reperfusion model the generation of oxygen-derived free radicals produces mucosal damage and prevents the restitution of moderate mucosal damage during reperfusion. In ischemia, factors other than free radicals seem to be responsible for mucosal damage. The protective effect of allopurinol and SOD was not mediated by changes in gastric mucosal blood flow.

Allopurinol↗
PubMed1988

Stimulation of gastric acid secretion increases mucosal blood flow in immediate vicinity of parietal cells in baboons.

In acute experiments carried out in 27 baboons under general anesthesia, the regional gastric mucosal and muscle layer blood flow and gastric acid secretion were measured during 4 hr. Baboons were allocated to each of the following six groups: control, gastric acid stimulation with histamine 40 micrograms/kg/hr intravenous, inhibition of basal or stimulated acid secretion with either ranitidine 50 mg intravenous or omeprazole 1 microgram/kg/hr. There were no significant cardiovascular alterations during the experiments. Histamine stimulation produced a concomitant rise in acid secretion and increase in blood flow only to the mucosal layer of the parietal-cell-bearing area of the stomach. Neither the underlying muscle layer nor the non-parietal-cell-bearing fundic or antral mucosa took part in this response, suggesting that a mechanism controlling blood flow is present in close proximity to the parietal cells. It was also established that the increase in blood flow occurs in response to parietal cell activity and not as a result of the action of histamine on the vascular system. Suppression of both basal and stimulated acid secretion did not cause a fall of mucosal blood flow below basal levels in any part of the stomach, indicating that drugs that inhibit parietal cell activity can be used in conditions where gastric mucosal ischemia should be avoided.

Animals↗
PubMed1988

The chemotactic peptide N-formyl methionyl-leucyl-phenylalanine increases mucosal permeability in the distal ileum of the rat.

Activation of granulocytes within the lamina propria by luminally derived bacterial products may represent an important mechanism in the pathogenesis of inflammatory bowel disease. The objective of this study was to determine the effects of luminal perfusion with N-formyl methionyl-leucyl-phenylalanine (FMLP), a bacterial product that attracts and activates granulocytes, on mucosal permeability in different regions of the rat small intestine and colon. Mucosal permeability was measured using blood-to-lumen clearance of 51Cr-ethylenediamine-tetraacetate during luminal perfusion with FMLP (10(-3) to 10(-8) M) dissolved in Tyrode's solution. Of the bowel segments studied, mucosal permeability was significantly increased by FMLP only in the distal 10 cm of ileum. The minimal FMLP concentration required to increase mucosal permeability was 10(-6) M. The increased mucosal permeability induced by FMLP could be prevented by depletion of circulating granulocytes with antineutrophil serum. The greater sensitivity of the distal ileum to FMLP did not correlate with a higher tissue myeloperoxidase activity, but it was associated with a higher basal ethylenediaminetetraacetate clearance. These observations indicate that a high basal mucosal permeability to solutes the size of FMLP (5-6 A radius), rather than a greater number of resident granulocytes in the lamina propria, predisposes the terminal ileum to the inflammatory actions of FMLP.

Animals↗
PubMed1988

Microsphere estimates of blood flow: methodological considerations.

The microsphere technique is a standard method for measuring blood flow in experimental animals. Sporadic reports have appeared outlining the limitations of this method. In this study we have systematically assessed the effect of blood withdrawals for reference sampling, microsphere numbers, and anesthesia on blood flow estimates using radioactive microspheres in dogs. Experiments were performed on 18 conscious and 12 anesthetized dogs. Four blood flow estimates were performed over 120 min using 1 X 10(6) microspheres (15 microns) each time. The effects of excessive numbers of microspheres (13 million), pentobarbital sodium anesthesia (30 mg/kg), and replacement of volume loss for reference samples with dextran 70 were assessed. In both conscious and anesthetized dogs a progressive decrease in gastric mucosal blood flow and cardiac output was observed over 120 min. This was also observed in the pancreas in conscious dogs. The major factor responsible for these changes was the volume loss due to reference sample withdrawals. Replacement of the withdrawn blood with dextran 70 led to stable blood flows to all organs. The injection of excessive numbers of microspheres did not modify hemodynamics to a greater extent than did the injection of 4 million microspheres. Anesthesia exerted no influence on blood flow other than raising coronary flow. We conclude that although blood flow to the gastric mucosa and the pancreas is sensitive to the minor hemodynamic changes associated with the microsphere technique, replacement of volume loss for reference samples ensures stable blood flow to all organs over a 120-min period.

Animals↗
PubMed1987

Does smoking interfere with the effect of histamine H2-receptor antagonists on intragastric acidity in man?

The interaction between smoking and the effect of histamine H2-antagonists on intragastric acidity was examined in a double blind double dummy placebo controlled study. Healthy volunteers, 11 smokers and 10 non-smokers, were given, on four separate days at least one week apart, either placebo or cimetidine 800 mg nocte or ranitidine 2 X 150 mg per day or ranitidine 300 mg nocte. Tablets were taken at 2115 and 0900 h. Smokers smoked a cigarette hourly from 0700 to 2300 h. Breakfast, lunch, and dinner were standardised. Intragastric acidity was measured with a combined intragastric glass electrode and a solid state recorder. The subjects were fully ambulatory. The three histamine H2-receptor antagonist regimens were less effective (p = 0.04) in smokers than in non-smokers, but the difference between acidity of smokers and non-smokers was small. Means of medians of pH during a 24-h period with placebo, cimetidine 800 mg, ranitidine 2 X 150 mg and ranitidine 300 mg were 1.6, 2.3, 3.1, and 2.7 in smokers and 1.5, 2.7, 3.2, and 3.1 in non-smokers, respectively. In a second part of the study seven chronic smokers were reexamined after acutely stopping smoking: inhibition of gastric acidity by histamine H2-receptor antagonists was similar before and after withdrawal. Smoking does not affect intragastric acidity in untreated volunteers and only slightly decreases the effectiveness of histamine H2-receptor antagonists on intragastric acidity. This effect best in part explains the unfavourable effect of smoking on healing of peptic ulcer in patients treated with these drugs.

Adult↗
PubMed1985

Long-term ambulatory gastric pH monitoring: validation of a new method and effect of H2-antagonists.

A new ambulatory monitoring system was evaluated for long-term measurements of gastric acidity. A close correlation was observed between values indicated by the pH electrode of the system and the pH of simultaneously aspirated gastric juice, suggesting that the electrode signaled the pH of the gastric fluid content. When the pH electrode was passed via an endoscope, and its bulb was placed against the corpus mucosa, a higher acidity was recorded as compared with gastric juice. To test whether the electrodes measured mucosal pH during ordinary test conditions, the readings of pH probes with mechanically shielded bulbs that did not come into direct contact with the mucosa were compared with those of nonshielded probes in identical positions. Similar results were observed, supporting the hypothesis that nonshielded probes measured the pH of gastric contents rather than that of the mucosa. The importance of a standardized electrode position and a fixed meal schedule was demonstrated in simultaneous recordings of antral and fundic pH. Under fasting conditions, acidity was similar in both regions. After ingestion of a meal, gastric contents were more alkaline in the fundus than in the antrum. A wide range of 24-h acidity (19-83 mmol/L) was detected in 25 healthy subjects. The day-to-day reproducibility of the method as revealed in two consecutive 24-h tests was good. The effect of cimetidine and ranitidine on gastric acidity was evaluated in 9 subjects in a double-blind, double-dummy trial. Mean 24-h H+ activity was 37.4 +/- 4.6 mmol/L under placebo medication. It was lower with cimetidine, two doses of 400 mg (23.8 +/- 4.0); cimetidine, four doses of 400 mg (10.2 +/- 3.0); ranitidine, two doses of 150 mg (10.3 +/- 3.6), and two doses of 300 mg (10.0 +/- 3.5), respectively. In conclusion, ambulatory long-term pH monitoring is a suitable method to assess the physiologic pattern of gastric acidity and the effect of antisecretory drugs.

Adolescent↗
PubMed1985

Measurement of monoamines and their metabolites in the interstitial fluid of the gut.

Bundles of hollow dialysis fibers were surgically implanted into the submucosa of the stomach and intestine allowing collection of an interstitial fluid (ISF) dialysate. Measurement of monoamines and their metabolites in ISF was performed using high-performance liquid chromatography with electrochemical detection. The local concentration of L-5-hydroxy-tryptophan (5-HTP) in ISF from the antrum was determined in conscious rats after intraperitoneal loading with 5-HTP. The metabolite was similarly evaluated after the administration of levodopa (L-DOPA). Validation of ISF dialysis as a method for determining changes of biogenic amine concentration in the extracellular fluid was determined for the antrum, duodenum, and colon in dogs after the oral or subcutaneous administration of 5-HTP as a precursor of serotonin and 5-hydroxyindole acetyl acetic acid. The proposed procedure provides a novel approach in pharmacologic studies, where a direct correlation between the distribution of a drug and its metabolites (pharmacokinetics) and their effects (pharmacodynamics) has to be measured.

5-Hydroxytryptophan↗
PubMedDate not supplied

Biliary mucin secreted by cultured human gallbladder epithelial cells carries the epitope of CA 19-9.

Serum CA 19-9 is increased in patients with different gastrointestinal malignancies. Unfortunately, CA 19-9 is also detected in high concentrations in normal bile causing unspecific serum elevations during inflammatory disease of the biliary tract and cholestasis. In order to identify the source of CA 19-9 in bile, the capacity of cultured human gallbladder epithelial cells (HGBEC) to secrete CA 19-9 was investigated. Cells were harvested from gallbladders removed by cholecystectomy and cultured for up to 14 days in collagen I coated 24-well culture dishes. CA 19-9 was measured in the culture medium by a solid-phase CA 19-9 EIA (Boehringer). In addition, culture medium was separated by Sepharose 4B-Cl, Concanavalin-A (Con-A) and CA 19-9 affinity chromatography. Significant CA 19-9 activity was measured in the culture medium after a 24 hour incubation period. Following separation of the culture medium by Sepharose 4B-Cl and Con-A affinity chromatography, 90% of the CA 19-9 activity was recovered in the exclusion volume (> 2000 kDa) from which 90% were identified as Con-A negative. A close correlation was found between CA 19-9 and concentrations of mucin purified from human gallbladder bile. Furthermore, CA 19-9 affinity chromatography selectively extracted mucins from the culture medium of HGBEC. Finally, addition of the mucin secretagogue bethanechol (6 mM) to the culture medium increased CA 19-9 activity in the medium. In conclusion, normal HGBEC secrete mucins carrying the epitope of CA 19-9. During inflammatory biliary disease unspecific elevation of CA 19-9 in serum may reflect both inflammatory hypersecretion and leakage of biliary mucins into serum.

Bethanechol↗