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At least 181 records · Page 10Linked to original sources
PubMed1992

[Role of ACE in the gastric cytoprotection. Dopaminergic and peripheral alpha 2 adrenergic mechanisms].

In Wistar rats, four experiments were carried out, studying specific inhibitors for ACE (angiotensin-converting enzyme), such as captopril, enalapril, lisinopril, ramipril and cilazapril, in presence of 20% and 95% ethanol induced gastric lesions. The effect of lisinopril and angiotensin I on the same injury was also studied. Subsequently, drugs with known role in gastric mucosa cytoprotection, such as enprostil, paracetamol, ketotiphen, levamisole, diazepam, bromocriptine, dopamine and clonidine, before and after absolute ethanol gastric injury were also studied. Finally, to examine the potential role of ACE in gastric cytoprotection, pretreatment with enalapril, followed by cytoprotective drugs, was carried out. We conclude that all ACE blockers aggravate the gastric lesion induced by 20% and 95% ethanol and are similar to the findings with angiotensin I. The gastric ACE probably plays an important role in the gastric mucosa defense. On the other hand, gastric ACE, as a physiologic regulator of microcirculation, acts by a double mechanism. a) converting the vasopressor amine, angiotensin I in angiotensin II. b) activating vasoactive peripheric receptors such as DA 2 dopaminergic and alfa 2 adrenoreceptors.

Angiotensin I↗
PubMed2004

[The role of mucoprotective drugs in gastric ulcer treatment: with specifical reference to their effects on gastritis mucosa].

A study group supported by Ministry of Health, Labor and Welfare recently reported the Japanese guideline for gastric ulcer treatment which suggests that gastric ulcer can be cured by either H. pylori eradication or acid suppression therapy by proton pump inhibitors(PPI) and H2-receptor antagonists(H2RA). It also suggests that all mucoprotective drugs except sucrafate, misoprostol and enprostil can't be recommended for gastric ulcer treatment. However, some mucoprotective drugs have been shown to possess anti-inflammatory action, leading to the inhibition of leucocyte infiltration in H. pylori gastritis, while long-term usage of PPI and H2RA might worsen gastritis. Thus, mucoprotective drugs should be investigated in terms of long-term effects on H. pylori-gastritis rather than the effects on gastric ulceration.

Gastric Mucosa↗
PubMed1990

[Campylobacter pylori and the reparative processes in peptic ulcer].

The paper deals with reparative potential of gastric and duodenal mucosa in ulcer in connection with the presence and quantity of Campylobacter pylori (CP) which is found practically in all patients not only with duodenal localization of ulcer but with mediogastric and pyloroantral localization as well. No correlation between the CP presence and CP mucosa colonization on the one hand and the type of reparative processes in the mucosa is found. The presence or the absence of CP as well as the degree of CP mucosal dissemination have no influence on the clinical course of the ulcer. Antiulcer treatment aiming at aggression factors (histamine H2-receptors blockers) and protective factors (enprostil) and lacking antibacterial activity improves the reparative processes but does not influence CP. Thus, CP is not etiological and probably is not a main pathogenetic factor in ulcer development. Its participation in the genesis of ulcer is possibly brought about under conditions of suppression of local protective mechanisms.

Adult↗
PubMed1989

[Prostaglandin analogues in the treatment of peptic ulcer disease].

The cytoprotective properties of native prostaglandins have been exploited for ulcer therapy through the development of analogous molecules, which are characterized by longer duration of action, more potent acid inhibitory effect and higher pharmacologic specificity. The therapeutic efficacy of prostaglandin analogues has been evaluated in a variety of controlled clinical trials, which are summarized briefly. The experience with arbaprostil, enprostil, misoprostol, rioprostil and trimoprostil shows that their effect on ulcer healing is superior to that of a placebo in acid inhibitory doses, which are also cytoprotective. Nevertheless, prostaglandin analogues are inferior to H2-receptor antagonists as regards their effects on ulcer healing, pain relief, and relapse prevention and less effective than expected from their acid inhibitory action. Placebo controlled trials of arbaprostil in acute upper gastrointestinal haemorrhage have failed to demonstrate any reduction in numbers of patients whose bleeding stopped, numbers with rebleeding or transfusion requirement. Diarrhoea occurs in 4%-34% of all patients and prostaglandin analogues are contraindicated in pregnant women. Although these drugs will probably not be marketed in Denmark for ulcer therapy, they may prove useful as replacement therapy in patients requiring nonsteroidal antiinflammatory drugs.

Humans↗
PubMed1986

Current concepts in clinical therapeutics: peptic ulcer disease.

The epidemiology, pathophysiology, diagnosis, clinical presentation, and treatment of peptic ulcer disease (PUD) are reviewed. PUD occurs commonly, with about 4 million Americans affected in a year. Cigarette smoking, aspirin use, and prolonged corticosteroid use are associated with PUD. The disease's etiology is multifactorial; the long-held assumption that ulcers develop solely because of increased gastric acid secretion is no longer valid. Although duodenal ulcer patients are frequently hypersecretors of acid, gastric ulcer patients more commonly have defective mechanisms for protecting the mucosal lining from acid, pepsin, and other agents. PUD is best diagnosed using an upper gastrointestinal roentgenographic series or using endoscopy. The clinical presentations, which involve epigastric abdominal pain that is relieved by food, milk, or antacids, may aid in diagnosis but are not usually definitive. Treatment is designed to relieve symptoms, heal the ulcer, prevent recurrences, and prevent complications. Of the four currently available drug treatments (cimetidine, ranitidine, antacids, and sucralfate), the treatment of first choice is cimetidine or ranitidine for four or six weeks, respectively, for duodenal and gastric ulcer patients. Antacids should be used as needed for pain, and the patient should be reassessed at the end of this period. For most patients, neither cimetidine nor ranitidine is demonstrably superior to one another. Several agents are under investigation in the U.S., including other H2-receptor antagonists (famotidine and nizatidine), proton-pump inhibitors (omeprazole), prostaglandins (misoprostol, arbasprostil, enprostil, and trimoprostil), antimuscarinic agents (pirenzepine), and tricyclic antidepressants (doxepin and trimipramine). peptic ulcer disease is an important disease. It is best treated with H2-receptor antagonists supplemented with antacids as needed for pain.

Adenosine Triphosphatases↗
PubMed1986

Anti-ulcer drugs in antisecretory doses for "cytoprotection" in arthritic patients?

Gastric injury and dyspepsia are major side-effects of acetylsalicylic acid (ASA) or most non-steroidal anti-inflammatory drugs (NSADs) which cause either gastric ulcerations or gastroduodenal erosions. There is only a limited number of trials in which the possibility of preventing or treating gastric lesions due to those drugs have been studied in man. This paper reviews trials in which H2-receptor antagonists, pirenzepine and prostaglandins have been investigated. - Pirenzepine given in antisecretory doses seems to improve gastrointestinal symptoms induced by ASA or NSADs. Cimetidine and misoprostol might prevent fecal blood loss. Gastroduodenal lesions might be prevented by pirenzepine, misoprostol and enprostil. It might be possible that cimetidine or ranitidine heal NSAD-induced peptic ulcers better than placebo in arthritic patients who stop the ingestion of NSADs. - All over the results of the cited trials are inconclusive, since the number of patients studied were too small and the design of almost all trials was incomparable. Furthermore, all cited studies do not correspond to Robert's concept of "cytoprotection", since H2-blockers, pirenzepine and prostaglandins have been applied in antisecretory doses in man.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1987

Prostaglandins for duodenal ulcer.

Studies to date indicate that certain synthetic prostaglandin E derivatives, notably misoprostol and enprostil, possess duodenal ulcer healing efficacy that is equivalent to that of the existing H2-receptor antagonists. Whether healing is achieved by virtue of their antisecretory action alone or in combination with their cytoprotective properties cannot be ascertained. Earlier reports that non-antisecretory prostaglandin E2 was effective for duodenal-ulcer healing suggested that cytoprotective mechanisms may contribute to ulcer healing, but this needs be confirmed. Chronic cigarette smoking adversely affects duodenal ulcer healing despite treatment with potent acid-reducing regimens. Evidence is available that cigarette smoking reduces luminal prostaglandins in the stomach, and that misoprostol, a prostaglandin E1 is able to overcome the adverse effect of smoking on duodenal ulcer healing, further suggesting that cytoprotective mechanisms may contribute to ulcer healing. Furthermore, misoprostol has been shown to be the first therapeutic agent capable of improving active chronic antral gastritis, which has recently been found to be almost invariably associated with active duodenal ulcer.

Anti-Ulcer Agents↗
PubMed1998

Pharmacological characterization of an FP prostaglandin receptor on rat vascular smooth muscle cells (A7r5) coupled to phosphoinositide turnover and intracellular calcium mobilization.

An FP prostaglandin (PG) receptor on the A7r5 rat aorta smooth muscle cell line has been characterized by assays of phosphoinositide (PI) turnover and intracellular calcium mobilization stimulated by structurally diverse PGs. In the PI turnover assay, cloprostenol was the most potent PG tested, with a potency (EC50) of 0.84 +/- 0.06 nM (mean +/- S.E.M., n = 34), and was a full agonist. Other known FP receptor agonists tested in this assay had efficacies > or = 85% of the cloprostenol value and high potencies: 16-phenoxy PGF2 alpha (2.05 +/- 0.19 nM), 17-phenyl PGF2 alpha (2.80 +/- 0.59 nM), fluprostenol (4.45 +/- 0.19 nM), PGF2 alpha (30.9 +/- 2.82 nM) and PhXA85 (43.5 +/- 11.4 nM). Other classes of PGs evaluated (PGD2, enprostil, 17-phenyl PGE2, PGE2, sulprostone and U-46619) were less potent and less efficacious than the FP receptor agonists, or were inactive. For a large group of standard PGs evaluated in the PI turnover assay, both potencies and efficacies correlated well with those reported for the FP receptor of Swiss mouse 3T3 fibroblasts. The potencies of fluprostenol and PGF2 alpha as stimuli of intracellular calcium mobilization matched well their potencies in the PI turnover assay, but fluprostenol had twice the efficacy of PGF2 alpha. Both signaling responses stimulated by fluprostenol were significantly inhibited by U73122, a selective inhibitor of phosphoinositide turnover (IC50 = 1.25 +/- 0.16 microM for PI turnover), and by chelation of calcium in the medium. Together with the PI turnover data, these studies of intracellular calcium mobilization linked to activation of the FP receptor, provide additional characterization of the pharmacological properties of this receptor.

Animals↗
PubMed1998

Pharmacology of [3H]prostaglandin E1/[3H]prostaglandin E2 and [3H]prostaglandin F2alpha binding to EP3 and FP prostaglandin receptor binding sites in bovine corpus luteum: characterization and correlation with functional data.

Specific binding of [3H]prostaglandin (PG) E1, [3H]PGE2 and [3H]PGF2alpha to washed total particulate homogenates of bovine corpus luteum comprised 60 to 82% of total binding. Scatchard analysis of competition data revealed the presence of an apparent single population of binding sites for [3H]PGE1 and [3H]PGE2 with dissociation constants (Kds) of 2.76 to 3.39 nM and apparent receptor density (Bmax) of 1.5 to 1.56 pmol/g wet weight (n = 3-4). However, [3H]PGF2alpha appeared to interact with two classes/states of binding sites (Kd1 = 6.51 +/- 0.65 nM, Bmax1 = 2.33 +/- 0.26 pmol/g wet weight; Kd2 = 986 +/- 269 nM; Bmax2 = 44.8 +/- 11.3 pmol/g wet weight, n = 11). Specific [3H]PGE1 and [3H]PGE2 binding was most potently (nanomolar affinity) inhibited by PGs with high selectivity for the EP3 receptor subtype (e.g., GR63799, sulprostone, enprostil) but was weakly (Kis > 1 microM) influenced by EP1-selective (SC-19220), FP-selective (fluprostenol, PHXA85), DP-selective (BWA868C; ZK118182), IP-selective (iloprost) and TP-selective (U46619) PGs. Specific [3H]PGF2alpha binding was potently displaced by FP-selective agents such as fluprostenol, PHXA85 and cloprostenol with nanomolar affinities (n = 3-25), but weakly (Kis > 1 microM) by other PGs showing high selectivity for other PG receptor subtypes mentioned above. The relative specificities and potencies of EP3- and FP-selective PGs tested in the binding assays were confirmed using various functional assays. These studies have provided strong pharmacological evidence for the similarity of [3H]PGE1 and [3H]PGE2 binding to EP3 receptors and for [3H]PGF2alpha binding to FP receptors in washed bovine corpus luteum homogenates.

Alprostadil↗
PubMed1995

Effect of a synthetic prostaglandin E2 analogue, RS-86505-007, on plasma lipids and lipoproteins in patients with moderate hypercholesterolaemia: efficacy and tolerance of treatment and response in different apolipoprotein polymorphism groups.

A double-blind, placebo-controlled ascending dose trial was carried out to evaluate the hypocholesterolaemic efficacy and tolerance of RS-86505-007, a prostaglandin E2 analogue, in moderately hypercholesterolaemic patients. Twenty-four patients received an oral dose of RS-86505-007 3 micrograms t.i.d. and a separate group of 26 patients 6 micrograms t.i.d. for 6 weeks. Plasma total and low-density lipoprotein (LDL) cholesterol concentrations decreased after 2 weeks of treatment, and the reductions were dose dependent. After 6 weeks of treatment (6 micrograms t.i.d.), the reductions from baseline in total and LDL cholesterol concentration were 14.6% and 18.5%, respectively. No changes in the plasma concentration of triglycerides or high-density lipoprotein (HDL) cholesterol were observed. RS-86505-007 tended to reduce total and LDL cholesterol concentrations less in patients with the epsilon 4 allele of the apolipoprotein E than in those with epsilon 3 allele. In contrast, the XbaI or EcoRI polymorphisms of the apolipoprotein B gene seemed to have no effect on the hypocholesterolaemic efficacy of the drug. The drug had no effect on the lipoprotein (a) concentration. Sixty-three percent of patients receiving 3 micrograms t.i.d. and 81% receiving 6 micrograms t.i.d. had adverse events, two-thirds of which related to the gastrointestinal tract. One patient in the 3-micrograms group and three patients in the 6-micrograms group terminated the study prematurely due to adverse effects.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1997

Distribution of prostaglandin E receptors in the rat gastrointestinal tract.

AIMS: In order to study the role of prostaglandin in the regulation of the gastrointestinal functions, gene expression of prostaglandin receptors along the rat gastrointestinal tracts were investigated. METHODS: Rats were used for the study. The combination of counterflow elutriation separation of mucosal cells and Northern blot analysis was used to detect the gene expression of prostaglandin receptors in gastrointestinal tracts. RESULTS: In small intestine and colon, prostaglandin E2 EP1 and EP3 receptor mRNAs were mainly localized in the deeper intestinal wall containing muscle layers. EP4 receptor gene expression, on the other hand, was detected in the intestinal mucosal layer. In the stomach, EP1 mRNA was detected in gastric muscle layers, whereas EP3 and EP4 receptor gene expression was mainly present in the gastric mucosal layer containing epithelial cells. In gastric epithelial cells, parietal cells were found to have both EP3 and EP4 receptors. At lower concentrations, prostaglandin E2 inhibited gastric acid secretion by parietal cells probably through EP4 receptors. At higher concentrations, however, it stimulated it. On the other hand, mucous cells possessed only EP4 receptor mRNA. CONCLUSIONS: Thus, it is suggested that prostaglandin E2 modulates gastrointestinal functions through at least three different prostaglandin receptors (EP1, EP3, and EP4), each of which has a distinct contribution in the gastrointestinal tract.

Aminopyrine↗
PubMed1986

Strategies for preventing aspirin-induced gastric bleeding.

Prostaglandins protect the gastric mucosa in animals, but the evidence of an effect independent of pH changes in man is not overwhelming. Gastrointestinal bleeding because of non-steroidal anti-inflammatory drugs is a major clinical problem, which we have investigated in a model system measuring bleeding rates caused by short-term administration of aspirin. Of the various strategies tested, only those that elevated intra-gastric pH reduced aspirin-induced bleeding.

Animals↗
PubMed1988

Prostaglandin treatment for peptic ulcer.

Prostaglandin analogues have been expected to outperform other antisecretory drugs as ulcer healing agents. This expectation arises from their ability to combine 'cytoprotection' with gastric secretory inhibition. Evidence of the existence of these two separate functions abounds in animals and in humans, but a clinical advantage has not evolved. Whereas most clinical trials show no difference between prostaglandin analogues and H2-receptor antagonists, some studies have shown the prostaglandins to be significantly less effective or no better than placebo. The role of cytoprotection in ulcer healing (as opposed to prevention) may be questioned and the present clinical role for these agents is unclear.

Alprostadil↗
PubMed1990

Prostaglandins and peptic ulcer therapy.

The expectation that prostaglandin analogues would improve the ulcer healing abilities of other agents by combining mucosal protection with decreased acid secretion has been proved unwarranted. The ulcer healing capabilities of these drugs reflect their antisecretory potency. A role for these drugs in ulcer healing is questionable but their use has been advocated most strongly to prevent ulceration developing during treatment with non-steroidal anti-inflammatory drugs. While some evidence supports this role, an important clinical benefit of reducing complication rates has yet to be demonstrated.

Alprostadil↗