dinoprost and Stomach-Ulcer

Aspirin causes peptic ulcers predominately by reducing gastric mucosal cyclooxygenase (COX) activity and prostaglandin synthesis. Because aspirin circulates for only a few hours, we hypothesized that aspirin's inhibitory effect on gastric COX activity must be prolonged. We performed a placebo-controlled experiment in healthy humans to determine the duration of inhibition of aspirin on gastric mucosal COX activity (PGE(2) and PGF(2alpha) synthesis rates). Recovery of gastric COX activity after stopping aspirin was slow and linear. Seventy-two hours after 325-mg aspirin, gastric COX activity was still reduced by 57% (P < 0.001). Duration of inhibition of gastric COX activity was estimated to be 7-8 days after 325-mg aspirin and 5 days after 81-mg aspirin. Recovery of gastric prostaglandin synthesis after 325-mg but not after 81-mg aspirin occurred at slower rates in subjects with Helicobacter pylori-associated gastritis than in those with normal histology. In conclusion, aspirin inhibits gastric COX activity for much longer than predicted from its pharmacokinetic profile, explaining why aspirin at widely spaced intervals is ulcerogenic.

Topics: Adolescent; Adult; Aspirin; Blood Platelets; Cyclooxygenase Inhibitors; Dinoprost; Dinoprostone; Female; Gastric Mucosa; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Prostaglandin-Endoperoxide Synthases; Regression Analysis; Stomach Ulcer; Thromboxane A2; Time Factors

This study investigated the mechanisms involved in the protective actions exerted by lansoprazole against experimental gastric injury. Following the intraluminal injection of ethanol-HCl, the histomorphometric analysis of rat gastric sections demonstrated a pattern of mucosal lesions associated with a significant increase in the mucosal contents of malondialdehyde and 8-iso-prostaglandin F(2alpha) (indices of lipid peroxidation), as well as a decrease in the levels of mucosal sulfhydryl compounds, assayed as reduced glutathione (GSH). Pretreatment with lansoprazole 90 micromol/kg, given intraduodenally as single dose or once daily by intragastric route for 8 days, significantly prevented ethanol-HCl-induced gastric damage. The concomitant changes in the mucosal levels of malondialdehyde, 8-iso-prostaglandin F(2alpha) and GSH elicited by ethanol-HCl were also counteracted by lansoprazole. In separate experiments, performed on animals undergoing 2-h pylorus ligation, lansoprazole did not enhance the concentration of prostaglandin E(2), bicyclo-prostaglandin E(2), or nitric oxide (NO) metabolites into gastric juice. Western blot analysis revealed the expression of both type 1 and 2 cyclooxygenase (COX) isoforms in the gastric mucosa of pylorus-ligated rats. These expression patterns were not significantly modified by single-dose or repeated treatment with lansoprazole. Lansoprazole also exhibited direct antioxidant properties by reducing 8-iso-prostaglandin F(2alpha) generation in an in vitro system where human native low-density lipoproteins were subjected to oxidation upon exposure to CuSO(4). The present results suggest that the protective effects of lansoprazole can be ascribed to a reduction of gastric oxidative injury, resulting in an increased bioavailability of mucosal sulfhydryl compounds. It is also proposed that lansoprazole does not exert modulator effects on the gastric expression of COX isoforms as well as on the activity of NO pathways.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Animals; Anti-Ulcer Agents; Cyclooxygenase 1; Cyclooxygenase 2; Dinoprost; Ethanol; Gastric Juice; Gastric Mucosa; Hydrochloric Acid; Isoenzymes; Lansoprazole; Male; Malondialdehyde; Membrane Proteins; Necrosis; Omeprazole; Oxidative Stress; Prostaglandin-Endoperoxide Synthases; Rats; Rats, Wistar; Stomach Ulcer; Sulfhydryl Compounds

Taking rats and mice as subjects, observation had been made on the protecting action of acupuncture to prevent the gastric mucosa from experimental injury. The pH value (by accurate test paper), gastric acid output (by titration), the secretion of PG in gastric mucosa (by radioimmunoassay) were observed altogether at 1-3h, 5-7h, 9-11h, 13-15h, 17-19h and 21-23h. All of the above indices were changed along with the alternation of day and night. And the effects of acupuncture on these indices were different when giving acupuncture at different times. The action of acupuncture to prevent experimental gastric ulcer was also different at different times. It is the general regularity that puncturing at the acrophase of circadian rhythm, the effect was mainly inhibitory, while puncturing at the valleyphase, the effect was mostly excitatory. Therefore, utilizing the influence of the various phases of circadian rhythm on the acupuncture effect, to choose the optimum time giving acupuncture could be one way to promote the acupuncture curative effect.

Topics: Acupuncture Therapy; Alprostadil; Animals; Circadian Rhythm; Dinoprost; Gastric Mucosa; Indomethacin; Mice; Rats; Rats, Wistar; Stomach Ulcer; Time Factors

Topics: Acetates; Acetic Acid; Animals; Dinoprost; Dinoprostone; Female; Gastric Mucosa; Male; Moxibustion; Rats; Rats, Sprague-Dawley; Stomach Ulcer

Infusion of endothelin-1 reduced vascular flow in the isolated perfused rat stomach. Concurrent infusion of iloprost and capsaicin, respectively, did not counteract the flow-reduction caused by endothelin-1. Infusion of prostaglandin (PG)F2 alpha caused vasoconstriction and significantly augmented the endothelin-1-induced flow reduction. In vivo, i.v. infusion of endothelin-1 (50 pmol/kg//min for 10 min) did not cause gastric mucosal damage, but enhanced injury produced by intragastric instillation of 20% ethanol. Intragastric administration of iloprost or PGF2 alpha prevented the pro-ulcerogenic effect of endothelin-1. Similarly, stimulation of afferent sensory neurons by intragastric capsaicin (0.5 mg/kg) protected against damage caused by endothelin-1 and 20% ethanol. Functional ablation of afferent sensory neurons by s.c. administration of 125 mg/kg capsaicin markedly enhanced gastric mucosal damage by intraluminal 20% ethanol. This damage was, however, not further increased by infusion of endothelin-1. These findings show that protection against the proulcerogenic effect of endothelin-1 can occur without antagonism of vasoconstriction. The findings also show that parameters involved in protection such as afferent sensory neurons do not contribute to the pro-ulcerogenic effects of endothelin-1 suggesting that protection against and potentiation of damage rely on different mechanisms.

Topics: Animals; Capsaicin; Dinoprost; Endothelins; Gastric Mucosa; Iloprost; In Vitro Techniques; Neurons, Afferent; Prostaglandins; Rats; Regional Blood Flow; Stomach; Stomach Ulcer; Vasoconstriction

We measured gastric and duodenal mucosal prostaglandin concentrations in 69 patients with active or inactive duodenal or gastric ulcer disease and 26 non-ulcer controls. Each underwent endoscopy enabling us to obtain multiple biopsies from the gastric body and antrum and from the duodenal bulb and postbulbar duodenum for measurement of mucosal prostaglandin concentrations, as well as a single biopsy from each region for mucosal histology. Using a multivariate linear regression model, we found that neither gastric nor duodenal ulcer disease significantly affected gastric or duodenal mucosal prostaglandin concentrations. Mucosal prostaglandin concentrations were similar at the edge of the ulcer and in the adjacent non-ulcerated mucosa. Neither gender symptoms, smoking, use of H2-receptor antagonists, disease activity, nor Helicobacter pylori infection had an independent effect on mucosal prostaglandins in any region. Gastritis in the body of the stomach was associated with significantly higher prostaglandins, while older age was associated with significantly lower gastric and duodenal prostaglandins. Gastroduodenal mucosal prostaglandins are thus not altered in patients with active or inactive peptic ulcer disease, even when multiple demographic and histologic variables are taken into consideration.

Topics: Age Factors; Dinoprost; Dinoprostone; Duodenal Ulcer; Female; Gastric Mucosa; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Male; Metaplasia; Middle Aged; Prevalence; Prospective Studies; Stomach Ulcer

The amount of prostaglandins (PD) E, F2 alpha and I2 (measured as 6-keto-Pg F1 alpha) in endoscopic biopsy specimens of gastric corpus' mucosa also as the concentration of Pg E and F2 in gastric juice of cirrhotic patients without or with gastric and duodenal ulcer were measured by radioimmunoassay. Release of Pgs with gastric juice (in the basal state and after histamine stimulation) was also significantly less in these patients. It was concluded that the severe disturbance of endogenous biosynthesis Pgs in gastroduodenal mucus of cirrhotic patients may play an important role in the development of ulcer disease in these patients.

Topics: Biopsy; Chronic Disease; Dinoprost; Duodenal Ulcer; Gastric Juice; Gastric Mucosa; Humans; Liver Cirrhosis; Peptic Ulcer; Prostaglandins; Prostaglandins E; Radioimmunoassay; Stomach Ulcer

A study was made of the effect of copper laser therapy on the content of PGE and PGF2 alpha and on the adenylate cyclase system (cAMP, cGMP and adenylate cyclase content) in patients with gastric ulcer. Seventy patients with indolent (from 3 months to 2 years) gastric ulcers were examined. The patients were assigned into 2 groups: group I received drug therapy combined with the influence of laser on copper vapours on the ulcerous surface (a single radiation dose 10 to 15 J). As compared to group I, the patients of group II manifested a considerable rise of the content of cAMP and prostaglandins, as well as adenylate cyclase activation in the gastric mucosa. Nonspecific biostimulating action of laser radiation exercised via the influence on the dysregenerative processes in the epitheliocytes of long nonhealing ulcer edges is under discussion.

Topics: Adenylyl Cyclases; Adult; Chronic Disease; Combined Modality Therapy; Dinoprost; Dinoprostone; Drug Therapy, Combination; Female; Gastric Mucosa; Gastroscopy; Humans; Laser Therapy; Male; Middle Aged; Stomach Ulcer; Wound Healing

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Arachidonate Lipoxygenases; Arthritis, Experimental; Carrageenan; Cyclooxygenase Inhibitors; Dinoprost; Edema; Inflammation; Leukemia, Basophilic, Acute; Leukotriene B4; Lipoxygenase Inhibitors; Mycobacterium; Phenols; Pyrazoles; Rats; Stomach Ulcer; Tumor Cells, Cultured; Zymosan

The aim of the study was to evaluate the influence of atropine, PGF2 alpha and cimetidine on the gastric cytoprotective effect of beta-carotene. Mucosal damage was produced by intragastric (i.g.) addition of 96% ethanol in CFY-strain rats of both sexes weighing 180-220 g. Gastric cytoprotection caused by i. g. pretreatment with 1.0 mg/kg beta-carotene 30 minutes before ethanol administration, was observed after 1 hour. Atropine (0.5 mg/kg), cimetidine (50 mg/kg) and PGF2 alpha (200 micrograms/kg) were given intraperitoneally (i.p.) 30 minutes before ethanol administration with and without beta-carotene and the changes in the number and severity of the gastric ulcers were detected. PGF2 alpha did not influence the gastric cytoprotective effect of beta-carotene meanwhile it was inhibited by atropine and markedly by cimetidine. Deleterious effect of cimetidine on the beta-carotene-induced cytoprotection may be explained perhaps by the adverse effect of the two compounds on ATP-cAMP transformation hereby counteracting one another, but more data are needed to the better understanding of drug interactions relating to mucosal cytoprotection.

Topics: Animals; Atropine; beta Carotene; Carotenoids; Cimetidine; Dinoprost; Ethanol; Female; Gastric Mucosa; Male; Rats; Rats, Inbred Strains; Stomach Ulcer

During Shay-ulcer formation damages to the barrier of the gastric mucosa develop even before the appearance of macroscopic ulceration. Proximal selective vagotomy prevents these damages. Following pyloric ligation the prostaglandin content of the mucosa changes in parallel with the injuries of the mucosal barrier: TXB2 content of the forestomach increases, while PGF2 alpha content of both the forestomach and the antrum decreases. Following PSV operation the 6-keto-PGF1 alpha content of the mucosa decreases, whereas PGF2 alpha and TXB2 contents exhibit no alteration. As a combined effect of proximal selective vagotomy pretreatment and pyloric ligation the 6-keto-PGF1 alpha and PGF2 alpha contents of the mucosa remain low and the TXB2 increase, otherwise detectable after pyloric ligation, does not take place.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Dinoprost; Disease Models, Animal; Gastric Mucosa; Prostaglandins; Pyloric Antrum; Radioimmunoassay; Rats; Stomach Ulcer; Thromboxane B2; Vagotomy, Proximal Gastric

Mucosa damage, these appear in the Shay ulcer model before the macroscopic ulceration, can be prevented by the selective proximal vagotomy. Changes of the potential difference and the prostaglandin content were discovered after pylorus ligation, and Thromboxane was increased, PGF2 alpha and TXB2 were nearly constant, whereas 6-keto-PGF1 alpha increased clearly in the rumen. The 6-keto-PGF1 alpha and the PGF2 alpha content and Thromboxane remained unchanged and the potential difference was normalized in case of selective proximal vagotomy and pylorus ligation. The SPV is significant as you know for the secretion of H+ion and bicarbonate, but also for the normalization of increased TXB2 on the basis of our investigation results.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Dinoprost; Disease Models, Animal; Gastric Mucosa; Male; Prostaglandins; Rats; Stomach Ulcer; Thromboxane B2; Thromboxanes; Vagotomy, Proximal Gastric

Topics: Animals; Cold Temperature; Dinoprost; Dinoprostone; Female; Male; Rats; Restraint, Physical; Stomach Ulcer; Stress, Physiological

Topics: Adolescent; Adult; Dinoprost; Female; Gastric Mucosa; Humans; Male; Middle Aged; Nucleotides, Cyclic; Prostaglandins E; Prostaglandins F; Stomach Ulcer

We have observed that the contents of prostaglandin (PG) D2 and 6-keto-PGF1 alpha were five times higher than those of PGE2 and PGF2 alpha in rat gastric mucosa. In order to elucidate the role of PGs in the function of gastric mucosa, we studied the effect of hypoxia on the levels of PGs in relation to the degree of gastric mucosal lesions. 6-Keto-PGF1 alpha levels were significantly decreased only by severe and long-term hypoxia (10% O2, 18 hours) when severe ulcerative lesions were observed. PGE2 levels were significantly decreased even by mild and short-term hypoxia (13% O2, 4 hours) when slight ulcerative lesions were observed. PGF2 alpha and PGD2 levels were significantly decreased by mild and short-term hypoxia; however, there was no significant difference from the control group under severe and long-term hypoxia. These results suggest that each of the PGs plays a different role in the pathogenesis of acute gastric mucosal lesions induced by hypoxia.

Topics: Animals; Dinoprost; Dinoprostone; Epoprostenol; Gastric Mucosa; Hypoxia; Male; Prostaglandin D2; Prostaglandins D; Prostaglandins E; Prostaglandins F; Rats; Rats, Inbred Strains; Stomach Ulcer

Sucralfate promotes the healing of peptic ulcers and, in large doses, increases gastric mucosal prostaglandins. The present study was designed to further elucidate the protective effect of sucralfate and to evaluate the role of prostaglandins in this action. Eight chair-adapted rhesus monkeys received a subcutaneous injection of either 150 mg/kg of aspirin or vehicle in combination with either a therapeutic oral dose of sucralfate (50 mg/kg X day) or water. Gastric soluble mucus concentration was determined in samples of gastric juice by Alcian blue dye binding of acidic glycoproteins, and mucus output was determined using a technetium 99m-diethylenetriaminepentaacetic acid dilution technique. Monkeys underwent endoscopy to assess gastric mucosal damage, which was ranked blindly on a scale of 0-5, and to obtain biopsy specimens for determination of mucosal prostaglandin E2, prostaglandin F2 alpha, and 6-keto-prostaglandin F1 alpha. Aspirin did not alter soluble mucus but did significantly increase gastric mucosal damage and suppress tissue levels of all prostaglandins. Sucralfate significantly increased the output of soluble mucus, even after aspirin treatment, and protected against aspirin-induced damage, although it did not modify aspirin-induced suppression of prostaglandins. These results suggest that the gastric protection afforded by sucralfate is related to a prostaglandin-independent increase in mucus production.

Topics: 6-Ketoprostaglandin F1 alpha; Aluminum; Animals; Anti-Ulcer Agents; Aspirin; Dinoprost; Dinoprostone; Macaca mulatta; Mucus; Prostaglandins; Prostaglandins E; Prostaglandins F; Stomach Ulcer; Sucralfate

PGF2 alpha, 100 micrograms/kg intraperitoneally, applied 30 min before 1.0 ml intragastric ethanol (96%) exerts cytoprotective effect on the gastric mucosal membrane. After a week long pretreatment of the animals with 0.25; 0.5 and 1.0 mg/day PGF2 alpha resulted in a diminishing cytoprotective effect. The gastric tissue cAMP level raised simultaneously and after the PGF2 alpha pretreatment with the taming cytoprotection the cAMP level diminished parallel in a dose dependent manner. It is assumed that after PGF2 alpha pretreatment the density of the cellular PGF2 alpha receptors decreases, according to the observed phenomenon.

Topics: Animals; Cyclic AMP; Dinoprost; Dose-Response Relationship, Drug; Drug Tolerance; Ethanol; Female; Gastric Mucosa; Male; Premedication; Prostaglandins F; Rats; Receptors, Prostaglandin; Stomach Ulcer

The purpose of the present study was to determine whether feeding stimulates prostaglandin (PG) synthesis in the gastric mucosa and whether this might play a role in the defensive mechanism of the gastric mucosa. The effect of refeeding on the formation of gastric lesions induced by nonsteroidal antiinflammatory drugs and on the generation of prostaglandin in the gastric mucosa was investigated. In the fasted rat aspirin and indomethacin produced many lesions in the corpus, but few or no lesions in the antrum. Refeeding of chow pellets before aspirin or indomethacin significantly decreased the corpus lesions, but provoked lesions in the antrum. When each drug was given before the refeeding, the protection against corpus lesions by refeeding was reduced and the lesions in the antrum were significantly increased. Mucosal generation of 6-keto-PGF 1 alpha (a stable metabolite of PGI2) and PGF2 alpha was measured ex vivo by the method of Whittle. The generation of 6-keto-PGF1 alpha and PGF2 alpha in the fasted rat deprived of food for 24 hr was 1761 +/- 170 and 217 +/- 7 ng/min/g tissue in the corpus mucosa, and 2958 +/- 217 and 453 +/- 33 ng/min/g tissue in the antral mucosa, respectively. Refeeding of chow pellets significantly increased the generation of both prostaglandins in the antral mucosa and of PGF2 alpha in the corpus mucosa, but did not affect the generation of PGI2 in the corpus mucosa.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Aspirin; Dinoprost; Eating; Epoprostenol; Evaluation Studies as Topic; Female; Gastric Mucosa; Indomethacin; Prostaglandins F; Pyloric Antrum; Rats; Rats, Inbred Strains; Stomach Ulcer; Time Factors

Structurally modified prostaglandins have been synthesized, PGF2 alpha skeleton being substituted at the 13 and 17 position. The prostacyclin analogues were modified at the 3,13 or 17 positions of the prostacyclin skeleton. The effect of these compounds was studied on the development of gastric mucosal damage produced by the intragastric administration of 96% ethanol. The different compounds were given intraperitoneally 30 min before the administration of ethanol. The number and severity of gastric mucosal lesions (ulcers) were recorded without and with the use of different compounds. The prostanoids and prostacyclin analogues were given in doses of 1, 5, 25 or 126 micrograms/kg. Among the tested compounds several fairly active molecules could be found. The significance and practical usefulness of these modifications of prostaglandins and prostacyclins are discussed with special respect to the stereochemistry of molecules.

Topics: Animals; Dinoprost; Dose-Response Relationship, Drug; Epoprostenol; Ethanol; Gastric Mucosa; Prostaglandins F; Prostaglandins, Synthetic; Rats; Stomach Ulcer; Structure-Activity Relationship

Topics: Adrenalectomy; Cysteamine; Dinoprost; Humans; Mucus; Prostaglandins F; Stomach Ulcer

Gastric mucosal damage was provoked by the topical application of 96% ethanol (1 ml) or 0.6 M HCl, (1 ml) by the method of Robert et al. [11]. Different doses of PGF2 alpha 100, 200 and 400 micrograms/kg) were given ip 30 min before the administration of the necrotizing agents. The animals were killed 1 hr after the application of the necrotizing agents. The number and severity of gastric lesions (ulcers) were recorded. Gastric mucosal superoxide dismutase (SOD) activity was measured by the method of Misra and Fridovich [8]. It was found that: PGF2 alpha dose-dependently decreased the number and severity of gastric lesions produced by 96% ethanol or 0.6 M HCl: gastric mucosal superoxide dismutase activity could be increased significantly by PGF2 alpha in the HCl-model: gastric mucosal superoxide dismutase activity could be significantly decreased by PGF2 alpha administration in the ethanol-model: no significant difference was obtained between the ulcer preventive effect of PGF2 alpha and the changes in the gastric mucosal SOD activity. It was concluded that: the ulcer preventive effect of PGF2 alpha partly depends on the scavanger mechanism (in the ethanol-model): the cytoprotective (100 micrograms/kg) and by antisecretory (400 micrograms/kg) doses of PGF2 alpha; exert similar effects on the changes of gastric mucosal SOD activity.

Topics: Animals; Dinoprost; Dose-Response Relationship, Drug; Ethanol; Female; Gastric Acid; Gastric Mucosa; Hydrochloric Acid; Male; Prostaglandins F; Rats; Stomach Ulcer; Superoxide Dismutase

To assess how endogenous prostaglandin (PG) in gastric mucosa acts against ulcer formation, we determined the mucosal prostacyclin (PGI2), PGE2, PGF2 alpha, and thromboxane A2(TXA2) concentrations before and after polypectomy in 6 patients in whom gastric ulcers were produced by electric burning resection of gastric polyps. These artificially induced ulcers all healed within short periods (25.7 +/- 7.4 days, mean +/- SE). Of the PGs assayed, the level of PGI2 was highest. The pG levels were increased at 4 and 7 days post-polypectomy; the most remarkable increase took place in the mucosa along the ulcer margin rather than the mucosa far from the ulcer site. We suggest that the observed increase in endogenous PGs represents a physiological response against polypectomy-induced ulcer formation.

Topics: Alprostadil; Dinoprost; Dinoprostone; Electrocoagulation; Epoprostenol; Female; Gastric Mucosa; Gastroscopy; Humans; Intestinal Polyps; Male; Middle Aged; Prostaglandins; Prostaglandins E; Prostaglandins F; Stomach Neoplasms; Stomach Ulcer; Thromboxane A2