YOU ARE NOW CONNECTED TO THE TOXLINE (1981 FORWARD, NON-ROYALTY) FILE. ==GASTRIC DYSMOBILITY== 7 AUTHOR Hendel L AUTHOR Svejgaard E AUTHOR Walsoe I AUTHOR Kieffer M AUTHOR Stenderup A TITLE Esophageal candidosis in progressive systemic sclerosis: occurrence, significance, and treatment with fluconazole. SOURCE Scand J Gastroenterol; VOL 23, ISS 10, 1988, P1182-6 ABSTRACT Esophageal mucosal brushings from 51 consecutive patients with progressive systemic sclerosis (PSS) (group I), 18 PSS patients continuously treated with high-dose ranitidine or omeprazole (group II), 34 controls referred to the outpatient clinic for endoscopy (group III), and 10 patients receiving long-term potent antireflux therapy for idiopathic gastroesophageal reflux (group IV) were cultured for Candida albicans. There were 44%, 89%, 9%, and 0% Candida albicans culture-positive patients in groups I through IV, respectively. Fifteen patients with candida esophagitis from group II were treated with fluconazole systemically. Eleven and 14 patients became culture-negative after 2 and 4 weeks' treatment, respectively. Three months after fluconazole withdrawal the recurrence rate was 100%. It is concluded that esophageal dysmotility predisposes for candidosis. Adding gastric acid inhibitory treatment to dysmotility enhances the risk significantly (p less than 0.01). The efficiency of fluconazole treatment was close to 100%, but so was the recurrence rate within a short period. 6 AUTHOR Scarpignato C TITLE Nonsteroidal anti-inflammatory drugs: how do they damage gastroduodenal mucosa? SOURCE Dig Dis; VOL 13 Suppl 1, 1995, P9-39 (REF: 205) ABSTRACT Gastroduodenal mucosa possesses an array of defensive mechanisms and nonsteroidal anti-inflammatory drugs (NSAIDs) have a deleterious effect on most of them. This results in a mucosa less able to cope with even a reduced acid load. The presence of acid appears to be a conditio sine qua non for NSAIDs injury. Acid not only injures the mucosa by back-diffusing from the lumen to cause tissue acidosis but also serves to increase drug absorption. Although much of the experimental work has been done using salicylates, it is now well accepted that almost all the NSAIDs are capable of causing mucosal damage. These compounds appear to cause gastro-duodenal damage, by two main mechanisms: a physiochemical disruption of the gastric mucosal barrier and a systemic inhibition of gastric mucosal protection, through inhibition of cyclo-oxygenase activity of gastro-intestinal (GI) mucosa. A reduced synthesis and secretion of mucus and bicarbonate, an impairment of mucosal blood flow and an increase of acid secretion represent the main consequences of NSAID-induced prostaglandin (PG) deficiency. Additional mechanisms which may add to the damage have been demonstrated. These include uncoupling of oxidative phosphorylation, reduced mucosal cell proliferation and DNA synthesis as well as neutrophil activation. Recent work has demonstrated that, after administration of NSAIDs, neutrophil adherence to the vascular endothelium occurs, with consequent reduced mucosal perfusion and release of tissue-damaging mediators. Since PGs are well-established modulators of inflammatory response, it is evident that NSAIDs induce damage to GI tract via a mechanism identical to that by which they exert their anti-inflammatory action. In this context, it is very difficult to imagine an effective NSAID completely devoid of gastrointestinal side effects. Although NSAIDs with tissue-selective effects on cyclo-oxygenase are available and compounds with reduced topical irritancy have been developed, gastroduodenal damage still represents an important effect of this class of drugs, because no NSAID is completely devoid of GI side effects. 10 AUTHOR Tache Y AUTHOR Maeda-Hagiwara M AUTHOR Goto Y AUTHOR Garrick T TITLE Central nervous system action of TRH to stimulate gastric function and ulceration. SOURCE Peptides; VOL 9 Suppl 1, 1988, P9-13 (REF: 54) ABSTRACT Intracisternal or intracerebroventricular injection of TRH (0.1-10 micrograms) in rats stimulated the secretion of gastric acid and pepsin secretion, increased gastric mucosal blood flow and gastric contractility and emptying, induced gastric hemorrhagic lesions and aggravated experimental ulcers elicited by aspirin, serotonin or indomethacin. TRH action was dose-dependent, rapid in onset and central nervous system-mediated by activation of the parasympathetic outflow to the stomach and cholinergic receptors. The stable TRH analog, RX 77368, was more potent and longer lasting than TRH. TRH and its stable analog appear as new chemical probes to produce centrally-mediated vagal-dependent stimulation of gastric function and experimental ulcers. The physiologic role of endogenous TRH in the central regulation of gastric function and ulceration remains to be established. 11 AUTHOR Guslandi M TITLE Gastric effects of leukotrienes. SOURCE Prostaglandins Leukot Med; VOL 26, ISS 3, 1987, P203-8 (REF: 21) ABSTRACT The effects of leukotrienes on gastric functions have been outlined by recent experimental and clinical studies. Leukotrienes were found to stimulate pepsin secretion, to reduce mucosal blood flow and to interfere with gastric emptying. Lipoxygenase products appear to impair gastric mucosal integrity and to exacerbate the damaging effects of noxious agents such as absolute ethanol. Drugs acting as leukotriene inhibitors may have a place in the future as anti-ulcer agents.