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Biomedical subjects

S Szabo

Publications and source records attributed to S Szabo.

At least 145 records · Page 8Linked to original sources
PubMed1985

Duodenal ulcerogens cysteamine and propionitrile induce gastroduodenal motility alterations in the rat.

The effects of the duodenal ulcerogens cysteamine and propionitrile on gastroduodenal myoelectric activity and intraluminal pressure in the fasted rat as well as on contractility of isolated gut muscle strips were investigated. Duodenal ulcerogens, unlike the nonulcerogen but toxic analogue ethanolamine, caused an early disruption of the myoelectric migrating complex, a marked increase in the spiking activity, and a decrease in the frequency of the slow waves in the duodenum. Both the increased spiking activity and the decreased slow wave frequency were dose dependent for cysteamine. Manometrically recorded contractions at the stomach corpus, midantrum, and antropyloric region as well as in the proximal duodenum of the conscious rat showed decreased contractions at the corpus and midantrum and an increase at the pyloric and duodenal sites during an intravenous infusion of cysteamine. In vitro studies demonstrated that circularly or longitudinally cut muscle strips taken from different regions of the stomach and duodenum responded to cysteamine with increased contractility. In summary, the duodenal ulcerogens cysteamine and propionitrile rapidly induce motor abnormalities in the stomach and duodenum of the rat. In vitro studies suggest that a cholinergic mechanism may be involved. It is possible that motor changes play a role in the pathogenesis of the experimentally induced duodenal ulcers.

Acetylcholine↗
PubMed1985

Early vascular injury and increased vascular permeability in gastric mucosal injury caused by ethanol in the rat.

The hypothesis that vascular injury contributes to the development of hemorrhagic erosions after intragastric administration of ethanol has been examined in the rat using vascular tracers. Extravasation of intravenously injected Evans blue into the gastric wall and into gastric contents was used as an indicator of vascular permeability. India ink and monastral blue, which label damaged blood vessels, were used to demonstrate vascular injury morphologically. Intragastric instillation of 75% and 100% ethanol induced increased vascular permeability within 1-3 min and resulted in monastral blue labeling of vessels in 13% and 17%, respectively, of the glandular mucosa within 1 min. After 1 h of 100% ethanol exposure, the areal density of monastral blue-stained blood vessels did not increase compared with that seen at 1 min, but the areal density of grossly visible hemorrhagic lesions increased strikingly and approximated that of vessel staining. The hemorrhagic erosions consistently occurred in regions of glandular mucosa where vessels were stained with monastral blue. Pretreatment with prostaglandin F2 beta or cysteamine reduced ethanol-induced Evans blue extravasation and monastral blue staining of mucosal blood vessels but did not reduce histologic evidence of gastric surface cell damage in the glandular mucosa. As increased vascular permeability and morphologically detectable vascular lesions consistently preceded the development of grossly visible hemorrhagic erosions in the glandular mucosa, we suggest that vascular injury is an early pathogenetic factor in the development of ethanol-induced gastric hemorrhagic erosions. The data also indicate that the degree of vascular damage, unlike the injury to surface epithelial cells, is reduced by pretreatment with prostaglandin F2 beta or the sulfhydryl cysteamine.

Animals↗
PubMed1985

Duodenal ulcer induced by MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine).

Experiments in rats revealed that the parkinsonian drug 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) given in multiple daily doses either per os (p.o.) or subcutaneously (s.c.) induced in a dose-dependent manner solitary or double ("kissing") duodenal ulcers in the rat. MPTP also diminished cerebral concentrations of DOPAC and the duodenal ulcers were prevented by pretreatment with dopamine agonists (e.g., bromocriptine, lergotrile) or monoamine oxidase inhibitors (e.g., pargyline, 1-deprenyl). High doses of MPTP also caused gastric erosions and motility changes resembling parkinsonism (e.g., akinesia, rigidity, forward bending of trunk). This chemical decreased gastric secretion of acid and pepsin, as well as pancreatic bicarbonate, trypsin and amylase. Thus, MPTP causes duodenal ulcers that are possibly associated with impaired defense in the duodenal bulb (e.g., decreased availability of duodenal and pancreatic bicarbonate).

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1985

Somatostatin depletion by cysteamine: mechanism and implication for duodenal ulceration.

Cysteamine (CSH) and its close derivatives deplete immunoreactive somatostatin (SS) in rat organs. The effect of CSH is dose and time dependent and reversible. Structural requirements of the analogs are the presence of either -SH or -NH2 on a two- or three-carbon alkyl molecule; both radicals together increase, whereas insertion of carboxyl abolishes potency. The duodenal ulcerogenic potency of CSH derivatives is correlated significantly with their SS-depleting activity in the gastric mucosa. The mechanism of this action of CSH is poorly understood, but it is not caused by increased release, enhanced degradation of the peptide, or selective necrosis of SS cells. It is likely that in the intracellular environment CSH causes a conformational change in the peptide that affects the antigenic and functional properties of SS.

Animals↗
PubMed1985

Effects of cysteamine on the hypothalamic-pituitary axis in the rat.

The effects of cysteamine (CSH) on hypothalamic concentrations of neuropeptides were reviewed and correlated with available information on changes in pituitary hormone content and circulating pituitary hormone levels. In our study, we found notable changes in the morphology of lactotropes from female Long-Evans rats treated for 7 days with CSH (300 mg/(kg X day) per os). Forming granules increased in number, and crinophagy, which is the augmented incorporation of these granules into lysosomes, was evident. Storage granules were reduced in number. These changes were not suppressed by simultaneous administration of 17 beta-estradiol (50 micrograms/day s.c.) for 7 days. CSH administration failed to prevent estrogen-induced lactotrope hyperplasia. Serum prolactin levels were unaffected by CSH treatment. The morphological changes in the adenohypophysis did not resemble those observed when rats were treated with bromocriptine. The rough endoplasmic reticulum luminal density was reduced in gonadotropes from intact CSH-treated rats after 1 wk. CSH treatment suppressed the development of castration cells and significantly reduced serum luteinizing hormone levels in ovariectomized rats. The morphological effects of CSH appeared to be confined to lactotropes and gonadotropes.

Animals↗
PubMed1985

Cysteamine-induced duodenal ulcer is not site-specific: effect of local modulating factors.

In cysteamine-induced duodenal ulcer, an animal model for the clinical disease, lesions are characteristically produced on the anterior and posterior walls of the proximal duodenum. Using this model, we investigated factors that may affect duodenal ulcer localization and intensity. Mobilization of the gastroduodenum by severing its ligaments; circumscribed application of acetic acid to the serosa of the lateral wall of the duodenum; or placement of materials (e.g., gelfoam, parafilm) on the proximal duodenum, each decreased the intensity of anterior-posterior ulcers and resulted in formation of atypical, mostly distal duodenal ulcers. The effect of these manipulations on acid secretion suggests that their influence on the development of duodenal ulcer is not entirely due to modulation of gastric secretion. The data indicate that the localization of induced duodenal ulcer can be shifted distally and is therefore not site specific. This study provides new clues and techniques for the study of the pathogenesis of duodenal ulcer disease.

Acetates↗
PubMed1984

Subacute and chronic action of acrylonitrile on adrenals and gastrointestinal tract: biochemical, functional and ultrastructural studies in the rat.

A single dose of acrylonitrile can produce fatal adrenal apoplexy within approximately 2 h. Our previous studies also indicate that multiple injections of the chemical cause acute hemorrhagic and occasional nonperforating duodenal ulcers. Other authors have reported increase in gut and lung neoplasia after chronic exposure. The present study was designed to elucidate the subacute and chronic actions of acrylonitrile on the adrenals, stomach and duodenum by correlating biochemical, functional and morphologic investigations, as well as to gain insight into the mechanisms of action of acrylonitrile. Rats were exposed to 0, 0.0001% (1 ppm), 0.002%, 0.01%, 0.05% or 0.2% acrylonitrile in drinking water, or to the same amount of the chemical given through daily gavage, for 7, 21 or 60 days. Acrylonitrile caused a time- and dose-dependent decrease in plasma corticosterone levels; aldosterone was affected only by the 'high' dose and prolonged time of exposure. Young rats were more susceptible than adults to this action of acrylonitrile. The adrenal cortex, especially the zona fasciculata, was atrophic in rats that had ingested the nitrile through drinking water. At 0.05% and 0.2%, it also caused decreased food intake and body weight gain. The adrenals were enlarged with a hyperplastic zona fasciculata after daily doses of a bolus of acrylonitrile. Ingestion of the chemical did not interfere with compensatory enlargement of the adrenal gland following unilateral adrenalectomy. On the other hand, the ACTH-induced elevation of corticosterone plasma concentration was significantly attenuated by acrylonitrile in drinking water. Electron microscopy of the adrenal glands revealed no consistent changes in the steroid-producing cells. We thus postulate that accelerated turnover of circulating corticoids and/or interference with the secretion or action of ACTH may primarily be responsible for the decreased plasma levels of corticosterone and aldosterone in rats that ingest acrylonitrile. The mucosa in the stomach at the junction of the forestomach and glandular region of animals that had ingested acrylonitrile was hyperplastic. The corpus also showed regional mucosal hyperplasia with the appearance of 'cobble-stoning'. These changes were preceded and associated with an elevated concentration of non-protein sulfhydryls mostly in the mucosa of the glandular stomach. A similar, less prominent elevation also occurred in the proximal duodenum. These alterations may resemble the preneoplastic combination of elevated glutathione and focal hyperplasia described in the liver with hepatocarcinogens.(ABSTRACT TRUNCATED AT 400 WORDS)

Acrylonitrile↗
PubMed1984

Morphologic effects of cysteamine on the rat adenohypophysis.

In pituitary lactotrophs of female Sprague-Dawley rats given cysteamine (300 mg/kg, per os/day) for 7 days, forming granules were increased in number and contained many separate electron-dense structures suggesting crinophagy. Compared to control values, cysteamine treatment caused no change in blood prolactin (PRL) levels, measured by radioimmunoassay (RIA). 17 beta-Estradiol (50 micrograms, sc/day) for 7 days, induced lactotroph hyperplasia and increased blood PRL levels which were unaffected by simultaneous cysteamine administration. The ultrastructural changes did not reflect those due to bromocriptine suppression of secretory activity, and supported the concept that cysteamine altered lactotroph morphology by an unknown mechanism. In pituitary gonadotrophs following cysteamine treatment, increased electron lucency of luminal contents of dilated rough endoplasmic reticulum was noted; however, blood luteinizing hormone (LH) levels did not differ from those of control values. In ovariectomized rats, cysteamine suppressed castration cell formation and reduced blood LH levels, suggesting an interference with the cell's ability to respond to GnRH stimulation. The morphologic effects of cysteamine appeared to be selective to lactotrophs and gonadotrophs, and were not secondary to vascular impairment, as capillary endothelial cells were undamaged.

Animals↗
PubMed1984

Tyrosine increases tissue dopamine concentration in the rat.

Dopamine and norepinephrine concentrations in the stomach, duodenum, and brain were measured after subcutaneous injection of tyrosine methyl ester in the rat. Tyrosine significantly increased dopamine concentrations in each tissue without altering norepinephrine levels. The increase in dopamine concentration in the stomach or duodenum was observed 1 h after tyrosine methyl ester injection, but it returned to normal 4 h after the administration of the chemical.

Adrenal Glands↗
PubMed1984

Direct measurement of duodenal acid-pepsin exposure at site of ulceration in rats.

A new technique for the preparation of a chronic duodenal fistula in the rat is described. The effect of cysteamine and propionitrile on the acidity of duodenal contents was studied, and the degree of acidity correlated with the respective duodenal ulcerogenicity of these two compounds. After subcutaneous administration of cysteamine, reduced duodenal acid was seen for 2-4 h, followed by large increases continuing up to 12 h and declining thereafter. Oral cysteamine administration produced acid increases of rapid onset and shorter duration, accompanied by increased pepsin activity. The weak duodenal ulcerogen propionitrile did not affect duodenal acidity. Cimetidine markedly reduced the duodenal acidification induced by cysteamine, whereas the dopamine agonist bromocriptine did not affect acid delivery to the duodenum but reduced the pepsin activity in the duodenal contents by 50%. The duodenal fistula rat provides a new model system for studies on the pathogenesis of experimental duodenal ulcer.

Animals↗
PubMed1984

Secretory changes associated with chemically-induced duodenal ulceration: simultaneous measurements of acid, pepsin, base and pancreatic enzymes in rats with chronic gastric fistula.

Rats with chronic gastric fistula were used to study gastric and duodenal/pancreatic secretory changes evoked by chemical duodenal ulcerogens. Although the data demonstrate stimulation of gastric output of acid and pepsin by certain doses of cysteamine or propionitrile, cysteamine produced dose-response increases in acid secretion only during the 1st hour following administration. The base output was also elevated at most of the time intervals after cysteamine. Decreased alkaline secretion was only seen following propionitrile injection. Although hyperacidity at the ulcer site may occur during duodenal ulcerogenesis, these results suggest that direct stimulation of acid-pepsin secretion or depression of pancreatic alkaline output are not the primary mechanisms explaining the ulcerogenic action of cysteamine and propionitrile.

Amylases↗
PubMed1984

Role of local secretory and motility changes in the pathogenesis of experimental duodenal ulcer.

Changes in gastric acid and pepsin secretions do not fully account for the duodenal ulcerogenic effect of cysteamine or propionitrile in the rat. We investigated the role of pancreatic and biliary secretions as well as motility changes in the duodenum. Bypass of bile to the jejunum and/or ablation of pancreatic secretion or drainage of these secretions through chronic duodenal fistula aggravated the cysteamine-induced duodenal ulcers. Biliary bypass to the proximal duodenum, on the other hand, decreased the incidence and intensity of experimental duodenal ulcers. An increased and dopamine-sensitive myoelectric activity caused by cysteamine or propionitrile was recorded in the proximal duodenum, indicating a state of hypermotility. Indeed, a decreased quantity of bilirubin was recovered through the chronic fistula in the proximal duodenum, suggesting an impaired delivery of bile to the ulcer area after cysteamine administration. Thus, duodenal hypermotility probably prevents the proper mix and neutralization of gastric acid and duodenal (mucosal, biliary and pancreatic) secretions, predisposing to ulceration in the proximal duodenum.

Animals↗
PubMed1983

Somatostatin stimulates clearance and hepatic uptake of colloidal carbon in the rat.

Somatostatin exerts hormonal and neuroendocrine effects. Since it prevents several organ injuries and systemic intoxications, we tested the hypothesis that activation of Kupffer cells might be one mechanism of the beneficial actions of this peptide. The data presented here demonstrate that somatostatin given i.v. in rats dose- and time-dependently accelerated the clearance of colloidal carbon from the blood and enhanced the uptake of carbon in the liver. On a weight basis, somatostatin was more potent than the RES stimulant zymosan or RES blocker gadolinium chloride. Thus, somatostatin might modulate Kupffer cells and possibly other macrophages, and these effects may have a role in the physiologic or pharmacologic actions of this peptide.

Animals↗
PubMed1983

Occupational stress: understanding, recognition and prevention.

Occupational stress occurs in the working environment where the stressors may be physical, chemical, biologic or psychosocial in nature. This review especially emphasizes the most novel and probably most prevalent type of work-related factors and response to them: psychologic stress. A brief historical introduction concerning the development of the (biologic) stress concept underlines the duality of stressors (i.e., extremely unpleasant and pleasant events, too much work and work stagnation) equally cause stress. A section on 'Recognition and manifestation' emphasizes the need for understanding the origins and nature of occupational stress before considering its manifestations (e.g., nonspecific behavioral changes and specific hormone level measurements). Under 'Prevention and treatment' reduction or avoidance of psychosocial stressors coupled with minimizing predisposing and promoting protective intervening variables are discussed. Thus, although occupational stress might be a major complication at the workplace, understanding this stress could lead to its partial or complete prevention.

Adrenal Cortex↗