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Biomedical subjects

S Szabo

Publications and source records attributed to S Szabo.

At least 163 records · Page 9Linked to original sources
PubMed1983

Duodenal ulcerogens cysteamine and propionitrile decrease duodenal neutralization of acid in the rat.

Neutralization of acid was evaluated in rat proximal duodenal segments isolated from biliary and pancreatic secretions. Duodenal ulcerogenic doses of cysteamine produced a significant decrease in acid disposal 0.5-2 hr after treatment. Oral or subcutaneous administration of the duodenal ulcerogen was effective. The potent ulcerogen cysteamine produced a more pronounced decrease than propionitrile (a weak duodenal ulcerogen). The failure of ethanolamine, a nonulcerogenic structural analog of cysteamine to significantly alter acid disposal suggests that the effect is not due to the toxic properties of the duodenal ulcerogen. The results reinforce the concept that the duodenum is able to dispose of significant quantities of acid. The decrease in acid-handling may contribute to duodenal susceptibility to acid after treatment with ulcerogens and possibly reflects pathophysiologic changes early in duodenal ulceration.

Animals↗
PubMed1983

The effect of the duodenal ulcerogen cysteamine on somatostatin and gastrin cells in the rat.

Previous studies showed a rapid decrease of somatostatin concentration in the gut and an increase in serum gastrin levels after a single dose of the duodenal ulcerogen cysteamine. An attempt was made to identify morphologic changes that would correlate with these functional changes. Rats were killed 1, 4, 8, or 24 hr after a single dose of cysteamine and sections of gastric mucosa and pancreas were processed for electron and light microscopy. Subtle ultrastructural alterations were seen in D cells of the stomach (e.g., dilation of mitochondrial cristae and endoplasmic reticulum, and apparent increase in electron density of secretory granules) after cysteamine administration. The number of somatostatin-positive cells visualized by the immunoperoxidase technique using light microscopy was decreased in 1-4 hr but returned to normal by 24 hr. The alterations observed in the G cells after cysteamine administration are consistent with release of gastrin from mature granules and increased synthesis of the hormone. The lack of major morphologic changes in the D cells suggests that cysteamine affects somatostatin without causing cell necrosis or alteration in lysosome formation. The effect of the drug may thus be mediated at the biochemical level without marked morphologic alterations.

Animals↗
PubMed1983

Role of lipid peroxidation in tissue injury after hepatic ischemia.

Ischemia and anoxia are associated with decreased concentrations of cellular antioxidants. The hypothesis that recirculation of oxygenated blood to previously ischemic tissue may result in enhanced free-radical reactions leading to lipid peroxidation and tissue damage was investigated. Elevated hepatic conjugated diene concentrations were detected 60 min after treatment of rats with carbon tetrachloride, a positive control, but were not found after 90 min ischemia or at 5 or 60 min after reperfusion of ischemic tissue. These findings suggest that lipid peroxidation may not be an early event in ischemia-induced necrosis but do not rule out a role of other free-radical reactions in the pathogenesis of ischemic necrosis.

Alanine Transaminase↗
PubMed1983

Potentiation of duodenal ulcerogenic action of acrylonitrile by PCB or phenobarbital in the rat.

Pretreatment of rats with the polychlorinated biphenyl (PCB) Aroclor 1254 or phenobarbital markedly increased the duodenal ulcerogenic action of acrylonitrile. The extent of forestomach and hepatic lesions in these rats, on the other hand, was not modified. The duodenal ulcers produced by Aroclor 1254 and acrylonitrile morphologically resembled the ulcers induced in other animal models of the human duodenal ulcer disease. The possible mechanisms of this potentiation of acrylonitrile action are discussed.

Acrylonitrile↗
PubMed1983

Somatostatin depletion of the gut and pancreas induced by cysteamine is not prevented by vagotomy or by dopamine agonists.

The role of endogenous somatostatin in the pathogenesis of duodenal was investigated in the present study by using the cysteamine animal model of the disease. Our previous studies showed a rapid and multiorgan depletion of somatostatin immunoreactivity (SIR) in rats given a single dose of duodenal ulcerogen cysteamine. We now determined whether acetylcholinergic and dopaminergic modulation (both known to influence the development of duodenal ulcer) are accompanied by modification of cysteamine-induced SIR depletion in rat organs. Vagotomy performed either 1 or 18 h before cysteamine administration did not interfere with the chemically induced SIR decrease in pancreas, gastric and duodenal mucosa. Vagal denervation alone had no marked influence on SIR levels but if combined with cysteamine, the SIR depletion in the stomach was significantly more pronounced than after the duodenal ulcerogen alone. Pretreatment with the dopamine agonists bromocriptine or lergotrile (known to prevent the chemically induced duodenal ulcers) did not influence the SIR depletion by cysteamine. Thus cysteamine depletes endogenous somatostatin in peripheral organs (e.g., stomach, duodenum, pancreas) by mechanisms independent of both vagus nerve and dopamine agonists. A role of central somatostatin depletion leading to disinhibition of vagus is also considered in the pathogenesis of experimental duodenal ulcer.

Animals↗
PubMed1983

The protective effect of sulfur-containing steroids against nephrocalcinosis induced by mercuric chloride in rats.

1. Experiments were conducted on rats and structure-activity correlations were performed using sulfur-containing steroids against nephrocalcinosis induced by mercuric chloride (HgCl2). 2. The protective effect of spironolactone has been described previously and we have now demonstrated the activity of 7-mercapto-17-hydroxy-3-oxo-4-androsten-17-propionic acid-lactone. 3. The activity of the sulfhydryl radical present in this molecule has been shown to be slightly lower than that of the thioacetyl radical present in spironolactone. 4. The importance of the steroid structure to which a specific radical is attached has become evident during these experiments with the inactivity of 7-mercapto-3,20-dioxo-4-pregnene-16-carbothiamineacetate which possesses a thioacetyl group in the same position as spironolactone (i.e. only the two lateral chains in position 16 and 17 are different between these two steroids). 5. Thus, both the composition of the sulfur-containing radical and the steroid moiety are important for protection against inorganic mercury poisoning.

Animals↗
PubMed1983

Cysteamine and prostaglandin F2 beta stimulate rat gastric mucin release.

Gastric mucin glycoproteins form an adherent gel over the surface epithelium that is thought to protect the stomach against chemical and physical damage. The purpose of this study was to measure the release of mucin glycoproteins from rat stomach after treatment with cysteamine and prostaglandin F2 beta, two structurally unrelated drugs that have been shown to protect the stomach against the noxious effects of alcohol and other damaging agents. Gastric mucin was separated into soluble (washout) and insoluble (adherent) phases before colorimetric quantitation of total mucin, protein-bound hexose, and sialic acid. Cysteamine produced a dose-dependent increase in release of soluble and gel mucin. Prostaglandin F2 beta caused a dose-dependent release of hexose-containing mucin but had no effect on sialic acid-containing glycoproteins. Sepharose 4B chromatography of both the soluble and adherent mucus revealed that greater than 90% was a high molecular weight glycoprotein fraction. N-Ethylmaleimide, a known inhibitor of cytoprotection by cysteamine, had no effect on mucin secretion. Similarly, indomethacin inhibited mucin secretion by cysteamine but did not significantly influence cytoprotection. Thus the secretion of mucin by cytoprotective agents is unlikely by itself to explain the ability of the stomach to resist chemical or physical damage.

Animals↗
PubMed1983

Gastric cytoprotection by agents altering gastric mucosal sulfhydryl compounds: role of endogenous prostaglandins.

Intragastric administration of cysteamine or diethyl maleate caused a dose-dependent reduction in the mean area of gastric lesions induced by absolute ethanol but failed to affect gastric ulcerations produced by acidified aspirin. Mucosal levels of glutathione were increased with cysteamine and reduced with diethyl maleate and did not correlate with the protective action of these agents on ethanol-induced mucosal lesions. The protective effects of these agents probably involved mucosal generation of prostaglandins, because pretreatment with indomethacin or aspirin, potent inhibitors of cyclooxygenase, partially prevented this protection. This study indicates that the mucosal generation of prostaglandins contributed, at least in part, to the gastric cytoprotection by agents altering mucosal contents of sulfhydryl compounds.

Animals↗
PubMed1983

Role of the adrenal cortex in gastric mucosal protection by prostaglandins, sulfhydryls, and cimetidine in the rat.

To investigate the possible role of hormones in gastric mucosal protection, the effect of prostaglandin F2 beta, dimercaprol, or cysteamine on ethanol-induced gastric erosions, and of cimetidine on gastric erosions caused by aspirin was studied in intact, adrenalectomized, medullectomized, ovariectomized, or thyroidectomized rats. Cimetidine was administered at a low dose that did not inhibit hydrogen ion secretion. Adrenalectomized animals failed to exhibit the usual mucosal protective response to prostaglandin F2 beta, sulfhydryls, or cimetidine. Ovariectomy or thyroidectomy did not influence mucosal protection with these agents. The inhibition by total adrenalectomy of mucosal protection was not reversed by large intragastric doses or by parenteral administration of prostaglandin F2 beta. Adrenal medullectomy alone significantly diminished (by approximately one-third) ethanol-induced gastric mucosal injury; prostaglandin F2 beta or sulfhydryl drugs produced significant additional protection. Replacement therapy with glucocorticoids (triamcinolone, corticosterone) but not with mineralocorticoids (deoxycorticosterone, 9 alpha-fluorocortisol) restored the cytoprotective effect of prostaglandin F2 beta and sulfhydryls in adrenalectomized rats. The generation of prostaglandin E2- and prostaglandin I2-like activity in the gastric mucosa was unaltered by adrenalectomy. These studies suggest a permissive role for glucocorticoids in gastric mucosal protection induced by prostaglandins, sulfhydryls, and cimetidine.

Adrenal Cortex↗
PubMed1982

Cytoprotection - organoprotection by somatostatin: gastric and hepatic lesions.

In rats, the hemorrhagic gastric erosions produced by ethanol, and the fatal hemorrhagic hepatic necrosis induced by phalloidin, were significantly reduced by regular somatostatin, but not by derivatives devoid of -SH containing cysteines. These effects of the hormone were abolished in animals which received, in addition, the sulfhydryl blocker n-ethylmaleimide before the toxic chemicals. Thus, somatostatin exhibits organoprotection dependent on endogenous sulfhydryls.

Animals↗
PubMed1982

Possible role of lipid peroxidation in the actions of acrylonitrile on the adrenals, liver and gastrointestinal tract.

Acrylonitrile-induced adrenal necrosis is associated with the early depletion of adrenal glutathione and elevation of adrenal dopamine. These biochemical events could result in increased susceptibility to free radical-mediated lipid peroxidation which may play a role in the pathogenesis of adrenal injury caused by acrylonitrile. In the studies reported here we found no elevation in malonaldehyde or conjugated diene concentrations of adrenal glands (or of glandular stomach and duodenal mucosa which may be other targets of acrylonitrile action) from rats given acrylonitrile. Conjugated diene concentrations in liver microsomes were significantly elevated (132%) 60 min after administration of carbon tetrachloride or 15 (38%), 30 (58%), and 60 (46%) min after injection of acrylonitrile whereas mitochondrial conjugated diene concentrations were not significantly altered by acrylonitrile. Our results suggest that while lipid peroxidation may not be involved in the pathogenesis of acrylonitrile adrenal injury it may occur in other tissues after acrylonitrile administration.

Acrylonitrile↗
PubMed1982

Structure-activity relations between alkyl nucleophilic chemicals causing duodenal ulcer and adrenocortical necrosis.

Structure-activity relationships were qualitatively and quantitatively examined for 56 chemicals (e.g., derivatives of propionitrile, acrylonitrile and cysteamine) which caused duodenal ulcer and/or adrenocortical necrosis in rats. For the first time the duodenal ulcerogenic property of numerous chemicals has been studied in a rational and predictive manner. Ulcerogenic activity was most intense in the carbonitriles attached to two or three carbon backbones and diminished by shortening, lengthening, branching, unsaturating, halogenating or hydroxylating the carbon chains. Different modes of action are implied. Adrenocorticolytic potency was associated with unsaturation of the carbon chain and substitution of the nitrile by thiol or amine radicals. An action of these chemicals on the central nervous system has been suggested.

Adrenal Cortex↗
PubMed1981

Sulfhydryl compounds may mediate gastric cytoprotection.

Ethanol induces hemorrhagic gastric erosions and causes a dose-dependent decrease in the concentration of nonprotein sulfhydryl compounds in rat gastric mucosa. Sulfhydryl-containing drugs protect rats from ethanol-induced gastric erosions, whereas sulfhydryl blocking agents counteract the mucosal cytoprotective effect of prostaglandin F2 beta. These observations suggest that endogenous nonprotein sulfhydryls may mediate prostaglandin-induced gastric cytoprotection and that sulfhydryl drugs may have potential for preventing or treating hemorrhagic gastric erosions.

Animals↗
PubMed1981

Somatostatin in rat tissues is depleted by cysteamine administration.

Administration of cysteamine (mercaptoethylamine) induces in rats severe perforating duodenal ulcers. Because the ulcerogenic properties of cysteamine are markedly reduced by treatment with somatostatin, we considered the possibility that cysteamine-induced duodenal ulcer might be mediated by depletion of tissue somatostatin, and thereby of its paracrine influences on gastrin and gastric acid secretion. To test this hypothesis, we measured the concentration of immunoreactive somatostatin (IR-somatostatin) in stomach and duodenal mucosa at intervals after administration of a single ulcerogenic dose (30 mg/kg by stomach tube). IR-somatostatin in these tissues fell rapidly to reach a minimum at 4 h (stomach 31%, duodenum 60% of control respectively). IR-somatostatin in hypothalamus and pancreas decreased gradually to a minimum at 7 h. Another duodenal ulcerogen, propionitrile (10 mg/100 g bw, s.c.) which is more toxic than cysteamine, and several stressful procedures including ether anesthesia, restraint and s.c. formalin did not lower stomach or duodenal IR-somatostatin. Gut, pancreas and hypothalamic VIP levels were not influenced by cysteamine. These findings suggest that cysteamine is a relatively specific depletor of tissue somatostatin. Because blood levels of somatostatin fell, and only trivial amounts of the peptide were found in the stomach lumen after cysteamine administration, it appears likely that this agent acts at the cellular level to cause breakdown of preformed somatostatin and/or to acutely reduce its synthesis.

Animals↗