salicylates and Stomach-Ulcer

Topics: Anti-Inflammatory Agents; Arthritis; Aspirin; Child; Drug Tolerance; Female; Gastric Mucosa; Gastritis; Humans; Indomethacin; Infant, Newborn; Inflammation; Kidney; Kinetics; Liver; Maternal-Fetal Exchange; Pregnancy; Prostaglandins; Salicylates; Stomach Ulcer

Topics: Adolescent; Adult; Aged; Carbenoxolone; Child; Female; Glycyrrhiza; Humans; Male; Middle Aged; Peptic Ulcer Hemorrhage; Peptic Ulcer Perforation; Plants, Medicinal; Salicylates; Sex Factors; Stomach Ulcer; Triterpenes

Topics: Adrenal Cortex Hormones; Duodenal Ulcer; Gastric Juice; Gastric Mucosa; Peptic Ulcer; Salicylates; Stomach; Stomach Ulcer

A review of the literature on the gastrointestinal side effects of the analgesic drugs has disclosed a disparity between generally held views and the scientific evidence. This is largely due to the paucity of large long term controlled trials since the cost of these is very high. The problems in mounting a large observational study with population controls are discussed against a backgrwound of exploratory work in Australia and New Zealand and the conclusion is reached that a comprehensive survey is needed. The difficulties in mounting such a survey are discussed.

Topics: Adrenal Cortex Hormones; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Female; Humans; Indomethacin; Male; Oxyphenbutazone; Peptic Ulcer; Phenylbutazone; Rheumatic Diseases; Salicylates; Stomach Diseases; Stomach Ulcer

Topics: Age Factors; Alcohol Drinking; Animals; Anti-Inflammatory Agents; Ascorbic Acid Deficiency; Aspirin; Blood Group Antigens; Female; Food; Gastric Mucosa; Gastrointestinal Hemorrhage; Humans; Hydrogen-Ion Concentration; Male; Nutritional Physiological Phenomena; Particle Size; Permeability; Prostaglandins; Regional Blood Flow; Salicylates; Sex Factors; Stomach Diseases; Stomach Ulcer; Structure-Activity Relationship

Topics: Adrenocorticotropic Hormone; Aged; Aminopyrine; Animals; Anti-Inflammatory Agents; Arthritis, Rheumatoid; Aspirin; Dogs; Drug Hypersensitivity; Duodenal Ulcer; Esophageal Diseases; Female; Gastric Mucosa; Gastrointestinal Hemorrhage; Glucocorticoids; Humans; Hydrocortisone; Indomethacin; Intestinal Mucosa; Osteoarthritis; Penicillins; Phenylbutazone; Prednisolone; Rats; Rheumatic Diseases; Salicylates; Sodium Salicylate; Stomach Diseases; Stomach Ulcer; Streptomycin

Helicobacter pylori infection is associated with gastric ulcer disease in about 75% of cases.. The aim of this study was to determine whether H. pylori eradication reduces gastric ulcer relapse rates.. The study was randomized, controlled, multicentric and investigator blinded, and was conducted at three university hospitals, two teaching hospitals, and by six practising gastroenterologists.. During a period of 1 year 152 patients with gastric ulcers were randomly assigned to one of two treatment regimens: omeprazole 20 mg daily in the morning for 8 weeks (74 patients), or bismuth subsalicylate 600 mg three times daily for 8 weeks combined with 500 mg amoxicillin twice daily and 1000 mg tinidazole twice daily for the first 10 days (triple therapy) (78 patients). Follow-up examinations were performed 6, 12 and 18 months after treatment and whenever ulcer symptoms occurred.. Of the 152 randomized patients five were excluded because of gastric cancer, 10 missed follow-up examinations and seven receiving triple therapy terminated treatment because of side effects. Of the remaining 130 patients, five of 69 (7.2%) in the omeprazole and six of 61 (9.8%) in the triple group were H. pylori negative. After 8 weeks' therapy, the gastric ulcer was healed in 85.9% (omeprazole) and in 81.8% triple) in H. pylori-positive patients, and in 80% (omeprazole) and 16.7% (triple) in H. pylori-negatives. H. pylori was eradicated in 8.1% of the patients who received omeprazole monotherapy and in 78.2% receiving triple therapy, and in 8.1% and 69.4% in an intention-to-treat analysis. The subsequent relapse rates during a follow-up period of 12 months were 50% in the omeprazole group and 4% in the triple group. Gastric ulcer relapse was observed in 49% of patients who were H. pylori positive and in 2% who were H. pylori negative after treatment.. The data show that the presence of H. pylori is an important predictor of gastric ulcer relapse and that eradication of H. pylori may heal gastric ulcer disease.

Topics: Adult; Aged; Amoxicillin; Anti-Ulcer Agents; Biopsy; Bismuth; Drug Administration Schedule; Drug Therapy, Combination; Female; Follow-Up Studies; Gastric Mucosa; Helicobacter Infections; Helicobacter pylori; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Omeprazole; Organometallic Compounds; Penicillins; Recurrence; Salicylates; Stomach Ulcer; Time Factors; Tinidazole

Triple therapies using bismuth, metronidazole and tetracycline or amoxicillin were the first truly successful anti-H. pylori therapies. Metronidazole resistance has become an increasing problem that has severely limited the usefulness of the original triple therapy. Resistance to tetracycline or amoxicillin has not been reported and both are effective against H. pylori. We therefore tested a new triple therapy consisting of 500 mg tetracycline, 500 mg amoxicillin, and 2 tablets of bismuth subsalicylate each administered four times daily (with meals and at bedtime) for 14 days during treatment with ranitidine 300 mg daily. H. pylori eradication was defined as no evidence of H. pylori one or more months after stopping therapy. H. pylori status was evaluated by a combination of urea breath test and histology. Sixteen patients with H. pylori infection and active peptic ulcers were enrolled. The new triple therapy was successful in only 7 individuals (43%). Metronidazole appears to be critical for the effectiveness of the original triple therapy. An alternative to metronidazole will be required for a new successful triple therapy.

Topics: Adult; Aged; Amoxicillin; Bismuth; Drug Therapy, Combination; Duodenal Ulcer; Helicobacter Infections; Helicobacter pylori; Humans; Male; Metronidazole; Middle Aged; Organometallic Compounds; Salicylates; Stomach Ulcer; Tetracycline

To determine the effect of treating Helicobacter pylori infection on the recurrence of gastric and duodenal ulcer disease.. Follow-up of up to 2 years in patients with healed ulcers who had participated in randomized, controlled trials.. A Veterans Affairs hospital.. A total of 109 patients infected with H. pylori who had a recently healed duodenal (83 patients) or gastric ulcer (26 patients) as confirmed by endoscopy.. Patients received ranitidine, 300 mg, or ranitidine plus triple therapy. Triple therapy consisted of tetracycline, 2 g; metronidazole, 750 mg; and bismuth subsalicylate, 5 or 8 tablets (151 mg bismuth per tablet) and was administered for the first 2 weeks of treatment; ranitidine therapy was continued until the ulcer had healed or 16 weeks had elapsed. After ulcer healing, no maintenance antiulcer therapy was given.. Endoscopy to assess ulcer recurrence was done at 3-month intervals or when a patient developed symptoms, for a maximum of 2 years.. The probability of recurrence for patients who received triple therapy plus ranitidine was significantly lower than that for patients who received ranitidine alone: for patients with duodenal ulcer, 12% (95% CI, 1% to 24%) compared with 95% (CI, 84% to 100%); for patients with gastric ulcer, 13% (CI, 4% to 31%) compared with 74% (44% to 100%). Fifty percent of patients who received ranitidine alone for healing of duodenal or gastric ulcer had a relapse within 12 weeks of healing. Ulcer recurrence in the triple therapy group was related to the failure to eradicate H. pylori and to the use of nonsteroidal anti-inflammatory drugs.. Eradication of H. pylori infection markedly changes the natural history of peptic ulcer in patients with duodenal or gastric ulcer. Most peptic ulcers associated with H. pylori infection are curable.

Topics: Adult; Aged; Aged, 80 and over; Bismuth; Drug Therapy, Combination; Duodenal Ulcer; Female; Helicobacter Infections; Helicobacter pylori; Humans; Male; Metronidazole; Middle Aged; Organometallic Compounds; Ranitidine; Recurrence; Risk Factors; Salicylates; Stomach Ulcer; Tetracycline

Enprostil is a synthetic dehydro-prostaglandin E2 with gastroduodenal ulcer-healing and mucosal-protective properties. One hundred and three healthy volunteers were randomized to receive capsules of enprostil 35 micrograms b.d. (the clinically recommended dose), enprostil 70 micrograms b.d., or placebo b.d. All underwent endoscopic assessment of the gastroduodenal mucosa, scored using a 0-4 scale, at baseline and on Days 3, 7, 14, 21 and 28 of dosing. Mean and median maximum scores demonstrated a dose response, and the mean maximum scores were statistically significantly higher for both enprostil groups on each endoscopy day when compared with placebo. The majority of enprostil-treated subjects had petechial haemorrhages. The proportion of volunteers with small white-based mucosal breaks (erosions) was significantly higher for the fundus in the enprostil 70-microgram group on Days 21 and 28 when compared with placebo, but there were no significant differences between treatment groups for any area on the other study days. The 70-microgram dose was associated with significantly more gastrointestinal adverse events than the 35-microgram dose, which was similar to placebo. There were no significant differences between groups for large white-based mucosal breaks (ulcers). We conclude that oral enprostil produced gastric mucosal petechial haemorrhages, primarily in the fundus of the stomach. Gastric mucosal petechial haemorrhages are probably without clinical significance because they are very common in the general population (10-15%) and do not progress to erosions and ulcers.

Topics: Double-Blind Method; Duodenum; Enprostil; Female; Gastric Mucosa; Gastrointestinal Hemorrhage; Humans; Intestinal Mucosa; Male; Reference Values; Salicylates; Salicylic Acid; Stomach Ulcer

This randomized, investigator-blinded, parallel group endoscopic study evaluated the effects of salsalate and naproxen on the gastroduodenal mucosa over a 3-month period in patients with RA. Using therapeutic doses of the drugs, 8 of 21 patients (38%) in the naproxen group had endoscopically shown active ulcers (seven patients) or diffuse erosions (one patient), whereas none of the 18 patients treated with salsalate (0%) had such lesions (P = .003). Five of the eight naproxen-treated patients with evidence of GI damage were asymptomatic at the time of endoscopic verification of their lesions. The most significant disadvantage of salsalate was its higher incidence of otologic problems accounting for six of the nine discontinuations with salsalate. However, the findings of this study suggest that patients receiving salsalate are at lower risk for developing significant gastropathy than those treated with naproxen. The relative benefit-to-risk ratio of salsalate indicates that this drug should be considered as a significant alternative NSAID therapy.

Topics: Adolescent; Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Double-Blind Method; Duodenal Ulcer; Female; Gastric Mucosa; Gastroscopy; Humans; Intestinal Mucosa; Linear Models; Male; Middle Aged; Multicenter Studies as Topic; Naproxen; Prospective Studies; Randomized Controlled Trials as Topic; Salicylates; Stomach Ulcer

Topics: Adult; Aged; Bismuth; Campylobacter; Campylobacter Infections; Cimetidine; Clinical Trials as Topic; Duodenal Ulcer; Female; Humans; Male; Middle Aged; Organometallic Compounds; Random Allocation; Recurrence; Salicylates; Stomach Ulcer; Wound Healing

Topics: Aspirin; Clinical Trials as Topic; Esterases; Ethanol; Female; Gastric Mucosa; Humans; Male; Methods; Salicylates; Stomach Ulcer

Topics: Adult; Aged; Antacids; Female; Glycopyrrolate; Hospitalization; Humans; Male; Middle Aged; Parasympatholytics; Recurrence; Rest; Salicylates; Smoking; Stomach Ulcer; Time Factors

The study of pharmacological interactions between herbal remedies and conventional drugs is important because consuming traditional herbal remedies as supplements or alternative medicine is fairly common and their concomitant administration with prescribed drugs could either have a favorable or unfavorable effect. Therefore, this work aims to determine the pharmacological interactions of a turmeric acetone extract (TAE) and its main metabolite (curcumin) with common anti-ulcer drugs (ranitidine and bismuth subsalicylate), using an ethanol-induced ulcer model in Wistar rats. The analysis of the interactions was carried out via the Combination Index-Isobologram Equation method. The combination index (CI) calculated at 0.5 of the affected fraction (fa) indicated that the TAE or curcumin in combination with ranitidine had a subadditive interaction. The results suggest that this antagonistic mechanism is associated to the mucoadhesion of curcumin and the TAE, determined by rheological measurements. Contrastingly, both the TAE and curcumin combined with bismuth subsalicylate had an additive relationship, which means that there is no pharmacological interaction. This agrees with the normalized isobolograms obtained for each combination. The results of this study suggest that mucoadhesion of curcumin and the TAE could interfere in the effectiveness of ranitidine, and even other drugs.

Topics: Animals; Anti-Ulcer Agents; Bismuth; Curcuma; Curcumin; Disease Models, Animal; Drug Interactions; Ethanol; Gastric Mucosa; Herb-Drug Interactions; Male; Organometallic Compounds; Plant Extracts; Ranitidine; Rats; Rats, Wistar; Salicylates; Stomach Ulcer

One of the major factors limiting the use of non-steroidal anti-inflammatory drugs is gastrointestinal toxicity. Gaultherin, 2-[(6-O-beta-D-Xylopyranosyl-beta-D-glucopyranosyl)oxy] benzoic acid methyl ester, a natural salicylate derivative extracted from Gaultheria yunnanensis, has been shown to have analgesic and anti-inflammatory effects and lack gastric ulcerogenic effect compared to aspirin in our primary study. The aim of this study was to investigate the mechanism of action of gaultherin, which may rely on its active metabolite, and the mechanism responsible for the non-ulcerogenic property. The results showed that gaultherin (200 mg/kg) significantly inhibited the abdominal contractions in the acetic acid-induced writhing test in mice. The anti-inflammatory effect of gaultherin was demonstrated in the croton oil-induced ear edema model in mice. The results showed that gaultherin and equimolar dose of aspirin produced comparable inhibitory effects. The study of the metabolism characters of gaultherin in mice and rats indicated that gaultherin could be metabolically converted to salicylate, which produced the pharmacological effects, and provided effective concentrations for an extended period. In vitro metabolism experiment showed that gaultherin was metabolized by beta-glycosidase produced by human intestinal bacteria and esterases in intestine, blood and liver successively to release salicylate finally. The study suggested gaultherin did not cause gastric ulcer for the reason that it released salicylate in intestine slowly, not in stomach and it left the cyclooxygenase-1 unaffected, which was the source of cytoprotective prostaglandins in gastric epithelium.

Topics: Abdominal Pain; Acetic Acid; Administration, Oral; Animals; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Chromatography, High Pressure Liquid; Croton Oil; Disaccharides; Disease Models, Animal; Ear Diseases; Esterases; Gastric Mucosa; Gaultheria; Glycoside Hydrolases; Humans; Immersion; Inflammation; Intestines; Male; Mice; Plant Leaves; Plant Stems; Rats; Rats, Wistar; Restraint, Physical; Salicylates; Stomach Ulcer; Stress, Psychological; Water

This work includes the synthesis of 15 final compounds (6a-h and 7b-h) as prodrugs of 5-ASA in the form of the acid itself, esters and amides linked by an amide linkage through a spacer to the endocyclic ring N of nicotinamide. Also, 15 new intermediate compounds were prepared. The target compounds (6b, 6f, 7b, and 7e-h) revealed potent analgesic and anti-inflammatory activities in comparison to sulfasalazine and 5-ASA. In addition, ulcerogenicity, LD50, in vivo and in vitro metabolism of compound 7f were determined.

Topics: Analgesics; Animals; Anti-Inflammatory Agents, Non-Steroidal; Carrageenan; Drug Stability; Edema; Feces; Gastrointestinal Contents; Hydrogen-Ion Concentration; Lethal Dose 50; Magnetic Resonance Spectroscopy; Male; Mesalamine; Mice; Pain; Prodrugs; Rats; Salicylamides; Salicylates; Stomach Ulcer; Streptococcus pyogenes; Structure-Activity Relationship

The gastric toxic effects of aspirin (ASA) and NCX-4016, a nitric oxide (NO)-releasing ASA, were compared in normal, cirrhotic, and arthritic rats. Oral administration of ASA (100 mg/kg) produced hemorrhagic lesions on the gastric mucosa in normal rats. The gastric ulcerogenic response to ASA was significantly worsened in both cirrhotic rats induced by N-nitrosodiethylamine and in arthritic rats induced by Freund's complete adjuvant. By contrast, NCX-4016 at 190 mg/kg (a dose equimolar to 100 mg/kg of ASA) did not induce damage in normal rat stomachs but caused slight lesions in the gastric mucosa of both cirrhotic and arthritic rats. Plasma salicylate levels following administration of ASA or NCX-4016 were not different between normal, cirrhotic, and arthritic rats, although the latter drug gave significantly lower values in any group of rats as compared to the former. Acid secretion was significantly increased in both cirrhotic and arthritic rats. ASA with 150 mM HCl caused severe gastric lesions in normal rats, the degree of damage being significantly greater than that induced by ASA alone. Coadministration of NOR-3, a NO donor, significantly prevented the development of gastric lesions induced by ASA, irrespective of whether or not ASA was given together with HCl. Gastric mucosal application of ASA (100 mg/kg) for 30 min caused a marked reduction of transmucosal potential difference (PD) with a minimal effect on gastric mucosal blood flow in both normal and cirrhotic rats, while that of NCX-4016 did not cause a PD reduction and produced a marked increase in the mucosal blood flow in both groups of rats. These results suggest that gastric mucosal susceptibility to ASA-induced damage is increased in both cirrhotic and arthritic rats (the process being partly accounted for by acid hypersecretion in these animals), NCX-4016 has even less gastric toxicity in both cirrhotic and arthritic rats, and the gastric-sparing effect of NCX-4016 is due, at least partly, to an increase of gastric mucosal blood flow, mediated by NO released from this drug.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Experimental; Aspirin; Blood Flow Velocity; Gastric Acid; Gastric Mucosa; Hydrochloric Acid; Liver Cirrhosis; Male; Membrane Potentials; Nitric Oxide Donors; Nitro Compounds; Rats; Rats, Sprague-Dawley; Salicylates; Stomach Ulcer

Among patients with peptic ulcer disease, the prevalence of Helicobacter pylori has been reported to range from 80% to 90%. Thus empirical cost-effective therapy has been suggested. We surveyed patients with peptic ulcer disease in Rochester, NY.. From two teaching hospitals all patients who had duodenal ulcers (DU) and/or gastric ulcers (GU) on esophagogastroduodenoscopy (EGD) with antral biopsy for histology for H. pylori and for rapid urease (CLO) test were included in the study. We examined a total of 160 patients with DU and 145 patients with GU, age range 18-92 yr, obtaining clinical data, race, medication profile, and history of use of nonsteroidal antiinflammatory drugs (NSAIDs). An ulcer was defined if the lesion with loss of mucosal integrity was > or = 0.5 cm, with apparent depth. H. pylori was considered present if CLO test and/or histology were positive for H. pylori. To confirm the reliability of nonuse of NSAIDs, we randomly checked blood samples of 90 such patients from the ambulatory clinic for the presence of salicylates. To identify the sensitivity of the CLO test, we performed a serology test for H. pylori antibody in 100 subjects to compare the CLO test results. Also, 500 CLO test results were compared to the histology results for H. pylori.. Among 160 DU patients, 16 were NSAID users with negative H. pylori and excluded from the prevalence study. Of the remaining 144 patients with DU, H. pylori was present in 88 patients (61%). When these data were analyzed according to race, H. pylori was present in 54 (52%) of 104 whites compared to 34 of 40 (85%) nonwhites (blacks, Hispanics, Asians) (p < 0.01). Among 145 GU patients 18 were NSAID users with negative H. pylori and excluded from the prevalence analysis. Of the remaining 127 patients with GU, H. pylori was present in 87 patients (61%). Among them, H. pylori was present in 46 of 87 (53%) whites, whereas 31 of 40 nonwhites (78%) were H. pylori-positive (p < 0.01). Antral histology and CLO test for H. pylori were in agreement in 92% of cases. Serology and CLO test for H. pylori were in agreement in 87% of cases. None of the randomly screened patients, including 16 ulcer patients with negative H. pylori, showed presence of salicylate in blood.. In greater Rochester, NY, where the majority of our patients with EGD were whites, the prevalence of H. pylori among ulcer patients was lower compared to other regions, particularly among whites. This suggests that an additional causative factor or factors for peptic ulcers may be present. Hence, empirical antibiotic therapy of ulcer patients without confirming the presence of H. pylori may not be justified.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Anti-Inflammatory Agents, Non-Steroidal; Drug Therapy, Combination; Duodenal Ulcer; Endoscopy, Digestive System; Helicobacter Infections; Helicobacter pylori; Humans; Middle Aged; New York; Peptic Ulcer; Pyloric Antrum; Retrospective Studies; Salicylates; Stomach Ulcer; Urease; White People

To study the mechanism for the low ulcerogenicity of the antithrombotic agent aspalatone ([3-[2-methyl-4-pyronyl)]-2-acetyloxybenzoate, CAS 147249-33-0), the metabolism and disposition of aspalatone were compared with those of acetylsalicylic acid (ASA) in the gut wall in relation to the salicylate level in the stomach tissues following oral administration in pyrolus-ligated rats. Both aspalatone and ASA were essentially stable in gastric juice and were absorbed in stomach unchanged. In glandular portion of the stomach, salicylate level found at 10 min post-dose in aspalatone (80 mg/kg)-and in ASA (50 mg/kg)-treated group was 67 +/- 43 nmol/g tissue and 2000 +/- 250 nmol/g tissue, respectively. In non-glandular (rumen) tissue, salicylate was not detected in the aspalatone group, whereas it reached a concentration of up to 1100 +/- 130 nmol/g tissue in the ASA group. As a result of the relative stability of the ester bond connecting the salicylic acid and maltol groups towards hydrolysis in the stomach and entrapment of ASA due to ion trapping, a lower salicylate level was observed in the stomach after oral aspalatone administration, and this may, at least in part, be the underlying mechanism for the low ulcerogenicity of aspalatone.

Topics: Animals; Aspirin; Gastric Mucosa; Male; Platelet Aggregation Inhibitors; Rats; Rats, Sprague-Dawley; Salicylates; Stomach Ulcer

Topics: Anti-Bacterial Agents; Anti-Ulcer Agents; Bismuth; Drug Therapy, Combination; Helicobacter Infections; Helicobacter pylori; Humans; Organometallic Compounds; Recurrence; Salicylates; Stomach Ulcer

Cure of H. pylori infection in peptic ulcer patients significantly reduces the risk of ulcer recurrence. Since data on the rate of H. pylori reinfection in patients undergoing successful anti-H. pylori therapy are sparse, this study was conducted with the aim of determining the H. pylori reinfection rate in peptic ulcer patients receiving antibacterial treatment to heal their ulcer and cure H. pylori infection.. A total of 217 patients with H. pylori-associated duodenal or gastric ulcer were followed up after treatment with various antibacterial regimens resulting in histologically documented cure of H. pylori infection. Endoscopic and histological examinations were performed 4 weeks after completion of treatment and after 1, 2 and 5 years, or whenever dyspeptic symptoms occurred. To assess the H. pylori status two antral and two corpus biopsies were obtained for histological examination.. Out of 217 patients with initially cured H. pylori infection 175 were available for endoscopic follow-up. At the time of analysis, 44 patients were re-examined after 1 year, 113 patients after 2 years and 18 patients after 5 years, giving a total of 360 patient years of follow-up. The mean duration of follow-up was 24.7 months. H. pylori reinfection was confirmed histologically in eight patients, three of whom becoming H. pylori-positive again within the first year of follow-up. Six of the eight patients with H. pylori reinfection also suffered an ulcer relapse. Eight cases of reinfection in 360 patient years represents an overall reinfection rate of 2.2%. Within the first 2 years of follow-up the reinfection rate was 0.8% per year.. Our data suggest that H. pylori reinfection is rare in peptic ulcer patients receiving successful anti-H. pylori therapy. H. pylori reinfection frequently coincides with ulcer recurrence. Cure of H. pylori infection results in cure of peptic ulcer disease, provided H. pylori reinfection does not occur.

Topics: Amoxicillin; Anti-Ulcer Agents; Bismuth; Drug Therapy, Combination; Duodenal Ulcer; Female; Follow-Up Studies; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Omeprazole; Organometallic Compounds; Penicillins; Recurrence; Salicylates; Stomach Ulcer; Time Factors; Tinidazole

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Arginine; Aspirin; Detergents; Gastric Mucosa; Gastrointestinal Hemorrhage; Gels; Intestinal Mucosa; Mucus; NG-Nitroarginine Methyl Ester; Nitric Oxide; Nitric Oxide Synthase; Phospholipids; Rats; Salicylates; Stomach Ulcer

To determine the role of Helicobacter pylori infection in children with recurrent abdominal pain and the usefulness of serologic tests in screening H pylori infection and monitoring treatment of H pylori-associated gastritis.. During a 3 year period, we investigated the presence of serum immunoglobulin G (IgG) antibody to H pylori in 456 children using the high-molecular-weight cell-associated protein H pylori enzyme immunoassay kit. Among the 456 children studied, 218 (age range, 3 to 18 years; mean age, 9.5 years) had symptoms of recurrent abdominal pain (RAP syndrome) with or without vomiting, and the remaining 238 (age range, 3 to 18 years; mean age, 9.8 years) had no RAP (non-RAP syndrome). We performed upper gastrointestinal endoscopy on 111 consecutive children of the 218 with RAP syndrome and obtained mucosal biopsies for culture, histologic analysis, CLO test (Delta West, Perth, Australia), and H pylori detection by polymerase chain reaction.. Thirty-eight (17.4%) of 218 children in the RAP group and 25 (10.5%) of 238 children in the non-RAP group were seropositive for H pylori. Of the 111 children endoscoped, 95 were found to be negative, and 12 were positive by all five assays. Specimens from 2 children were negative by culture and the CLO test but positive by the other three assays. Specimens from 1 child were negative by histologic analysis but positive by all other tests. The remaining child was positive for anti-H pylori IgG but negative by all of the other four assays. Upper gastrointestinal endoscopy detected 14 children with peptic ulcer disease (9 duodenal ulcer and 5 gastric ulcer) and 12 with antral nodular gastritis. Only 4 of the 14 diagnosed with peptic ulcer were H pylori positive by all five assays, whereas all 12 children with antral nodular gastritis were H pylori positive. Nine of the 12 H pylori-positive children were treated with a combination of bismuth subsalicylate, amoxicillin, and metronidazole for 2 weeks. Sera obtained at 2, 4, and 6 months after treatment from all 9 children showed a decrease in anti-H pylori IgG titer. Three H pylori-infected children who did not receive any treatment served as control children, and their IgG levels remained elevated or increased over time.. The results from our study indicate that screening for the serum IgG antibody to H pylori is a practical method for diagnosing H pylori infection in children, and that serial measurements of the H pylori IgG antibody are useful for monitoring treatment of H pylori because of its high sensitivity and ease of performance. Only 4 of the 14 children diagnosed with peptic ulcer disease were confirmed to be infected with H pylori, whereas all 12 children with antral nodular gastritis were found to be infected by H pylori. These observations suggest that H pylori infection is more frequently associated with gastritis than with peptic ulcer disease in children, and that H pylori gastritis is a cause of RAP syndrome in children.

Topics: Abdominal Pain; Adolescent; Amoxicillin; Antibodies, Bacterial; Bismuth; Child; Child, Preschool; Duodenal Ulcer; Endoscopy, Gastrointestinal; Enzyme-Linked Immunosorbent Assay; Female; Follow-Up Studies; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Immunoglobulin G; Male; Metronidazole; Organometallic Compounds; Polymerase Chain Reaction; Recurrence; Salicylates; Stomach Ulcer

The effects of nonsteroidal antiinflammatory drugs on ulcerogenesis and gastric secretion were evaluated in a pylorus-ligated rat model. Oral administration of salicylate (50 mg/kg), aspirin (50 mg/kg), and indomethacin (3.5 mg/kg) significantly increased ulcerogenesis over the basal value by six- to sevenfold, but ibuprofen's (10 mg/kg) fourfold increase was not significant. Aspirin in conjunction with histamine (0.5 mg/kg subcutaneously) significantly increased ulcerogenesis by 2.7-fold compared to histamine alone. Basal acid secretion was increased significantly by 156% after indomethacin, but not by other nonsteroidal antiinflammatory drugs. In contrast, all nonsteroidal antiinflammatory drugs, except indomethacin, significantly decreased histamine-stimulated acid secretion. Non-steroidal antiinflammatory drugs had no effect on pepsinogen secretion. Ranitidine pretreatment (25 mg/kg intraperitoneally) significantly decreased basal acid and pepsinogen secretion in all treatment groups by > 85% and > 40%, respectively, and ulcerations induced by salicylate, aspirin, and indomethacin were also inhibited by 90%, 60%, and 60%, respectively. The observed inhibition of prostaglandin E2 generation by nonsteroidal antiinflammatory drugs under basal secretory conditions appeared to correlate with the extent of ulcerogenesis. Our data support the concept that acid, in addition to inhibition of prostaglandin E2 synthesis, plays an important role in the pathogenesis of nonsteroidal antiinflammatory drug-induced gastropathy.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Dinoprostone; Gastric Acid; Gastric Mucosa; Histamine; Ibuprofen; Indomethacin; Ligation; Male; Pepsinogens; Pylorus; Ranitidine; Rats; Rats, Sprague-Dawley; Salicylates; Stomach Ulcer

The objective of the present work was to determine the effect of treating Helicobacter pylori infection on the recurrence of peptic ulcer bleeding. We prospectively followed 66 out of 70 consecutive H. pylori-positive (histology and/or culture) patients with conservatively and endoscopically managed peptic ulcer bleeding (duodenal ulcer; n = 39, gastric ulcer: n = 25, gastroduodenal double ulcer: n = 2) for a median period of 17 months (range 6-33 months). Patients were treated in seven different clinical protocols, each of which included the attempt to eradicate H. pylori infection. Patients with (n = 42) and without (n = 24) bacterial eradication had similar demographic and clinical characteristics. Eradication of H. pylori was associated with a statistically significant reduction of ulcer recurrences (2.4 vs. 62.5%; p < 0.001) and bleeding relapses (0 vs. 37.5%; p = 0.01). We conclude that H. pylori eradication markedly changes the natural history in patients with complicated duodenal and gastric ulcer disease. Thus, treatment aimed at bacterial eradication should be considered in all patients with conservatively managed bleeding from H. pylori-positive ulcers.

Topics: Adult; Aged; Aged, 80 and over; Amoxicillin; Bismuth; Drug Therapy, Combination; Duodenal Ulcer; Female; Helicobacter Infections; Helicobacter pylori; Humans; Male; Metronidazole; Middle Aged; Omeprazole; Organometallic Compounds; Peptic Ulcer; Peptic Ulcer Hemorrhage; Prospective Studies; Ranitidine; Recurrence; Salicylates; Stomach Ulcer

Helicobacter pylori infection has been associated with gastritis, duodenal ulcer, gastric ulcer, and the epidemic form of gastric carcinoma. Eradication of H. pylori infection has proven to be difficult. Recently, combinations of antimicrobial drugs have been shown to eradicate greater than 50% of infections; however, the results have proven variable, and the factors influencing effectiveness of therapy are unclear. In the present study, the effectiveness of a triple therapy for eradication of H. pylori infection was evaluated. Triple therapy consisted of 2 g tetracycline, 750 mg metronidazole, and five or eight tablets of bismuth subsalicylate daily in 93 patients (70 with duodenal ulcer, 17 with gastric ulcer, and 6 with simple H. pylori gastritis). Combinations of a sensitive urea breath test, serology, culture, and histology were used to confirm the presence of infection, eradication, or relapse. Eradication was defined as inability to show H. pylori greater than or equal to 1 month after ending therapy. The overall eradication rate was 87%. The factors evaluated for their effect on predicting eradication included age, gender, type of disease, duration of therapy, amount of bismuth subsalicylate [five or eight Pepto-Bismol tablets daily (Procter & Gamble, Cincinnati, OH)], and compliance with the prescribed medications. Stepwise regression showed that compliance was the most important factor predicting success; the success rate was 96% for patients who took greater than 60% of the prescribed medications and 69% for patients who took less. For those taking greater than 60% of the prescribed therapy, the eradication rates were similar (a) for patients receiving therapy for 14 days or when tetracycline and bismuth subsalicylate were taken for an additional 14 days; (b) for patients with duodenal ulcer, gastric ulcer, and simple H. pylori gastritis; and (c) whether five or eight bismuth subsalicylate tablets were taken. It is concluded that triple therapy is effective for eradication of H. pylori and that future studies need to take compliance into account for comparisons between regimens.

Topics: Adult; Aged; Aged, 80 and over; Bismuth; Drug Therapy, Combination; Duodenal Ulcer; Female; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Male; Metronidazole; Middle Aged; Organometallic Compounds; Patient Compliance; Regression Analysis; Salicylates; Stomach Ulcer; Tetracycline

Topics: Biological Availability; Female; Fluorescent Antibody Technique; Humans; Male; Protein Binding; Salicylates; Stomach Ulcer

Topics: Administration, Oral; Bismuth; Campylobacter Infections; Dose-Response Relationship, Drug; Gastritis; Humans; Organometallic Compounds; Salicylates; Stomach Ulcer

Aspirin and other non-steroidal anti-inflammatory drugs are associated with gastritis and mucosal injury. The present study examined the efficacy of the synthetic prostanoid, Ro 22-1327, as a mucosal protectant against aspirin. Dogs were orally administered either vehicle followed by 650 mg of aspirin, or Ro 22-1327 followed one hour later by 650 mg of aspirin. Two hours later the dogs were endoscoped and lesions were scored. In separate dogs, with gastric pouches, acid secretion stimulated by food was monitored in the absence and presence of Ro 22-1327 for four hours. There were no gastric lesions in the dogs treated with the vehicle (polyethylene glycol 400; PEG) for Ro 22-1327 followed by vehicle (carboxymethylcellulose) for aspirin. Dogs dosed with PEG followed by aspirin had gastric lesions: mean (+/- S.E.) scores were 2.16 +/- 0.24 and 2.75 +/- 0.18 for the antrum and body, respectively. Ro 22-1327 provided protection from aspirin-induced injury. Significant (P less than 0.01) protection occurred at 1.0 mcg/kg of Ro 22-1327 in the antrum (0.60 +/- 0.40) and body (1.60 +/- 0.40). An oral dose of 10 mcg/kg did not inhibit peak or total food-stimulated gastric acid output. Ro 22-1327 is a potent mucosal protectant against aspirin-induced mucosal injury and this activity is not dependent upon inhibition of gastric acid secretion.

Topics: Animals; Anti-Ulcer Agents; Aspirin; Dogs; Female; Gastric Acid; Gastric Mucosa; Gastroscopy; Male; Prostaglandins E; Salicylates; Stomach Ulcer

Cu(II) complexes with salicylates or aminopyrine were administered to rats with local inflammation (acute paw oedema elicited with carrageenan) to determine their anti-inflammatory activity and ulcerogenic effects following oral administration. The complexes were more effective than the parent ligands or appropriate mixtures of these ligands with Cu(II) as anti-inflammatory agents. All complexes indicated low ulcerogenity. The differences in pharmacologic activity between the complexes and mixtures in question are discussed.

Topics: Administration, Oral; Animals; Anti-Inflammatory Agents, Non-Steroidal; Carrageenan; Copper; Edema; Inflammation; Male; Organometallic Compounds; Rats; Rats, Inbred Strains; Salicylates; Stomach Ulcer

Three pilot studies were performed to evaluate the efficacy of bismuth subsalicylate (BSS) and nitrofurantoin to eradicate Campylobacter pylori colonization in man. Nitrofurantoin 3 x 100 mg capsules for 10 days did not clear C. pylori in any of 13 patients, and neither did the combination of BSS and nitrofurantoin suspension (0/6 patients). Immediately after high dose BSS therapy 3 x 900 mg for 28 days, 8/17 patients (47%) had negative cultures and rapid urease tests. There was recrudescence in 5 out of 6 patients so far submitted to follow-up investigations, giving a best possible outcome estimate of 18% and a worst possible eradication rate of 6% in this study. Preliminary data indicate that triple therapy may be a more effective option, but doubts remain as to whether the puristic therapeutic goal of complete bacterial eradication can be safely and effectively achieved with presently available drugs.

Topics: Adult; Biopsy; Bismuth; Campylobacter Infections; Drug Therapy, Combination; Duodenal Ulcer; Dyspepsia; Female; Humans; Male; Middle Aged; Nitrofurantoin; Organometallic Compounds; Pilot Projects; Pyloric Antrum; Salicylates; Stomach Ulcer; Urease

The acetyl moiety in aspirin (acetyl salicylic acid: ASA) is considered to play a major part in the pathogenesis of ASA-induced mucosal injury. At equivalent salicylate doses and pH values, the induction of acute gastric mucosal haemorrhagic erosions in rats by ASA and choline magnesium trisalicylate (CMT), a new non-acetylated salicylate, with and without the potentiating damaging effect of taurodeoxycholic acid (TDCA) were compared. Test solutions were administered by per oral intubation to five groups of fasting Sprague-Dawley rats (n = 24). Gastric mucosa were examined after 4 hours and mucosal injury assessed by a lesion-scoring system. The incidence and severity (median lesion scores with quartiles) of the lesions were 83% and 13 (7:20) respectively for ASA (128 mg kg-1) compared with 17% and 0 (0:0) for CMT (128 mg kg-1) (P less than 0.001 and P less than 0.001). TDCA increased mucosal damage to 100% and 29 (20:34) for ASA compared with 30% and 0 (0:4) for CMT (P less than 0.001) and P less than 0.001). Serum salicylate levels (median values of 1.4 for ASA and 1.5 mmol litre-1 for CMT) were not significantly different. It is concluded that replacing the acetyl moiety in ASA with choline and magnesium moieties reduces the ASA-induced mucosal injury, without affecting blood salicylate concentrations.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Choline; Gastric Mucosa; Male; Rats; Rats, Inbred Strains; Salicylates; Stomach Ulcer

The course of 177 consecutive patients with severe salicylate self-poisoning treated in an intensive care unit (ICU) during a period of 15 years is presented. On admission, cerebral depression was observed in 61% respiratory failure was present in 47%, acidosis in 36% and cardiovascular function was impaired in 14%. A mortality rate of 15% was observed, which was proportionally higher in patients more than 40 years old and in patients with delayed diagnosis. Twenty-seven patients died and an autopsy was performed on 26 patients. The main autopsy diagnosis was ulcers of the gastrointestinal tract in 46%, pulmonary oedema in 46%, cerebral oedema in 31% and cerebral haemorrhage in 23%.

Topics: Acute Disease; Adolescent; Adult; Aged; Aged, 80 and over; Brain Edema; Cerebral Hemorrhage; Child; Child, Preschool; Duodenal Ulcer; Female; Humans; Infant; Intensive Care Units; Male; Middle Aged; Pulmonary Edema; Respiratory Distress Syndrome; Retrospective Studies; Salicylates; Salicylic Acid; Stomach Ulcer; Suicide, Attempted

Colloidal bismuth subcitrate (CBS) precipitates in an acid environment, adheres to mucus, blocks pepsin activity, retards hydrogen-ion back diffusion and stimulates prostaglandin synthesis. The average healing rate after 4 weeks' treatment with CBS is 78% in duodenal ulcer versus 67% with cimetidine. A direct comparison with ranitidine gives healing rates of 78% (CBS) as opposed to 78% with ranitidine. The corresponding figures in gastric ulcer are 68% (CBS) and 54% (cimetidine). The percentage of relapse-free patients is substantially higher after CBS ulcer healing than after H2-blockers. Bismuth subsalicylate eliminates Campylobacter pylori in 71% after 4-weeks' therapy. Parallel to this elimination a decrease and normalization of the acute inflammatory process can be seen in antral mucosa.

Topics: Anti-Ulcer Agents; Bismuth; Campylobacter Infections; Chronic Disease; Duodenal Ulcer; Gastritis; Humans; Organometallic Compounds; Peptic Ulcer; Salicylates; Stomach Ulcer

"Mild irritants" have been shown to protect rat gastric mucosa from damage induced by noxious topical agents, supposedly by induction of mucosal prostaglandin (PG) biosynthesis. The protective effect of NaCl 5%, ethanol 20%, NaOH 0.075 N, HCl 0.35 N, salicylic acid 100 mg/kg and paracetamol 200 mg/kg was investigated in rats treated with an ulcerogenic dose (25 mg/kg) of indomethacin; mucosal PG synthesis was simultaneously determined. Significant protection was achieved only with NaCl 5%, salicylic acid and paracetamol. Salicylic acid and paracetamol significantly decreased acid secretion and enhanced PGE2 or 6-keto PGF1 alpha generation in control rats, while a small but significant change in the indomethacin-inhibited PG synthesis was observed after treatment with NaCl 5% or salicylic acid. We conclude that protection by "mild irritants" against indomethacin-induced mucosal damage may involve increased cytoprotective PG generation, as shown for paracetamol and salicylic acid, or partial blocking of indomethacin binding at the cyclooxygenase receptor site, as shown for NaCl 5% and salicylic acid.

Topics: 6-Ketoprostaglandin F1 alpha; Acetaminophen; Animals; Dinoprostone; Ethanol; Gastric Acid; Gastric Mucosa; Indomethacin; Irritants; Male; Prostaglandin-Endoperoxide Synthases; Prostaglandins; Prostaglandins E; Rats; Salicylates; Salicylic Acid; Saline Solution, Hypertonic; Sodium Hydroxide; Stomach Ulcer

Salicylic acid has been shown to decrease gastric mucosal lesions induced by indomethacin in the rat. In vitro, it has also been shown to counteract the inhibitory effect of indomethacin and aspirin on the cyclooxygenase enzyme system in seminal vesicle microsomes and in platelets and vascular tissue. The hypothesis that the mechanism of salicylic acid "protection" against indomethacin-induced gastric lesions involves interference with indomethacin-induced mucosal cyclooxygenase inhibition was tested. Male, fasted rats were treated with intragastric salicylic acid in doses of 50, 100, 200, 300, or 400 mg/kg concomitantly with a sc injection of 20 mg/kg of indomethacin. Gastric mucosal lesions and mucosal cyclooxygenase activity (as measured by ex vivo prostaglandin F2 alpha synthesis) were examined 3 hr later. Intragastric salicylic acid, 200-400 mg/kg, significantly reduced indomethacin-induced lesion formation, while counteracting significantly indomethacin inhibition of prostaglandin synthesis. Salicylic acid alone did not significantly change cyclooxygenase activity. It is concluded that topical salicylic acid can decrease indomethacin-induced gastric mucosal lesion in the rat, in part, by counteracting the inhibitory effect of indomethacin at the cyclooxygenase level.

Topics: Animals; Anti-Inflammatory Agents; Cyclooxygenase Inhibitors; Gastric Mucosa; Humans; Indomethacin; Male; Prostaglandin-Endoperoxide Synthases; Rats; Rats, Inbred Strains; Salicylates; Salicylic Acid; Stomach Ulcer

The ulcerogenic actions of aspirin and sodium salicylate in cat gastric antrum following intravenous injection, and their effects on the synthesis of two major cyclo-oxygenase products by antral mucosa have been determined. Near-maximal rates of gastric acid secretion were stimulated by histamine, infused i.v. for 1 h prior to bolus injection of aspirin or salicylate and throughout the subsequent 4 h. The area of lesions in the cat gastric antrum were then assessed macroscopically and the generation of both 6-oxo-PGF1 alpha and PGE2 from strips of antral mucosal tissue following 1 min vortex-incubation was determined by radioimmunoassay. The plasma and mucosal-tissue levels of both aspirin and salicylate were determined using HPLC techniques. Aspirin (0.2 mmol. kg-1 i.v.) induced substantial deep antral ulceration during the 4 h histamine infusion, whereas sodium salicylate (0.2 mmol. kg-1 i.v.) caused no significant macroscopic damage. Sodium salicylate likewise caused no significant inhibition in the ex vivo generation of either 6-oxo-PGF1 alpha or PGE2, whereas aspirin induced 92 +/- 3 and 97 +/- 1% inhibition of generation of these prostanoids respectively. The levels of total salicylate in plasma and mucosal tissue were comparable following bolus i.v. injection of aspirin or sodium salicylate. These observations support the concept that cyclo-oxygenase inhibition is an important mechanism underlying deep gastric ulceration induced by aspirin, when administered parenterally in the cat.

Topics: Animals; Aspirin; Cats; Cyclooxygenase Inhibitors; Dinoprostone; Epoprostenol; Female; Histamine; Infusions, Parenteral; Male; Prostaglandins E; Salicylates; Salicylic Acid; Stomach Ulcer

We have examined the effects of seven different "barrier breakers" (including ethanol, aspirin, salicylic acid, isobutyric acid, Na taurocholate, thermal injury, and hyperosmotic glucose) on chambered gastric mucosae of rats in an attempt to identify variations in accepted indicators of mucosal barrier integrity which would accurately predict the extent of subsequent hemorrhagic erosion. When results from all experimental groups were considered, only the initial decrease in transmucosal potential difference (PD) showed significant correlation with final damage (lesion area). When the results were analyzed as separate subgroups, significant correlations were also found between net K+ efflux during the first 10 min after luminal infusion and final lesion area. Only in the subgroup containing ethanol, salicylates, and thermal injury was there a correlation between net loss of luminal H+ (back-diffusion) and lesion area. These results are considered in terms of their implications for the ulcerogenic actions of each group of agents.

Topics: Animals; Aspirin; Ethanol; Female; Gastric Mucosa; Gastrointestinal Hemorrhage; Mannitol; Prognosis; Rats; Rats, Inbred Strains; Salicylates; Salicylic Acid; Stomach Ulcer; Taurocholic Acid

The effect of 16,16-dimethyl prostaglandin E2 (DmPGE2), in doses subthreshold for antisecretory activity, were examined in female rats. The aims were to determine if DmPGE2 alters the disposition of acetylsalicylic acid (ASA) within the gastric mucosa and if DmPGE2 could attenuate the ulcerogenic effect of oral ASA. Gastric lesions occurred after an oral, but not an intravenous dose of 150 mg/kg ASA. Lesions could be prevented by pretreatment with 5 micrograms/kg DmPGE2 orally 30 min prior to ASA. DmPGE2 elevated fundic concentrations of both ASA and salicylic acid (SA) within the first hour when ASA was given orally. The ratio of the concentration of ASA/SA in fundus was not changed, indicating that DmPGE2 did not depress the fundic esterase activity. It is concluded that the cytoprotective effect of DmPGE2 is not related to a change in mucosal concentration or elimination of ASA or SA.

Topics: Administration, Oral; Animals; Aspirin; Chromatography, High Pressure Liquid; Female; Gastric Mucosa; Injections, Intravenous; Prostaglandins E, Synthetic; Rats; Rats, Inbred Strains; Salicylates; Salicylic Acid; Stomach Ulcer

Topics: Animals; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Central Nervous System; Death, Sudden; Imidazoles; In Vitro Techniques; Kinetics; Male; Mice; Platelet Aggregation; Rabbits; Rats; Rats, Inbred Strains; Salicylates; Salicylic Acid; Stomach Ulcer; Thromboxane A2; Thromboxanes

Side effects of non-steroidal antirheumatic drugs (NSAD) may occur in any organ system, since the prostaglandins, the synthesis of which is inhibited by NSAD, play a role in numerous adverse cellular processes throughout the body. Besides these physiologic regulations there are adverse effects of NSAD, such as bone marrow aplasia, of unexplained etiology. The interactions of NSAD are of clinical relevance in drug types such as the salicylates, pyrazolons and fenamic acids (e.g. interactions with cumarin derivatives). The clinically relevant interactions of NSAD are discussed in detail.

Topics: Anemia, Aplastic; Anti-Inflammatory Agents, Non-Steroidal; Coumarins; Drug Interactions; Gastrointestinal Diseases; Humans; Indomethacin; Naproxen; ortho-Aminobenzoates; Phenylbutazone; Prostaglandins; Rheumatic Diseases; Salicylates; Stomach Ulcer

Copper salicylate has been shown to be an inhibitor of gastric lesions in rats induced by aspirin, indomethacin and cold stress whereas cimetidine was only effective against those produced by cold stress. The results are in line with those reported earlier for the anti-ulcer activity of sodium salicylate and metiamide respectively. On this basis, it appears that the animal model of stress-induced gastric lesions in the rat is the most suitable for testing the activity of new-antiulcer drugs.

Topics: Animals; Anti-Ulcer Agents; Aspirin; Cimetidine; Cold Temperature; Copper; Indomethacin; Mucus; Organometallic Compounds; Rats; Rats, Inbred Strains; Receptors, Histamine H2; Salicylates; Stomach Ulcer; Stress, Physiological

Evidence is presented to show that nonsteroidal antiinflammatory drugs react with two sites on the cyclooxygenase (8,11,14-eicosatrienoate, hydrogen-donor:oxygen oxidoreductase, EC 1.14.99.1). Although the degree of interaction with the catalytic site determines the potency of such compounds, interaction with the supplementary site is also obligatory for efficacy as cyclooxygenase inhibitors and may explain the selectivity of such drugs in inhibiting the cyclooxygenase but not the lipoxygenase pathway. Drugs that interact more effectively with the supplementary site than with the catalytic site--i.e., those of weak to moderate activity as cyclooxygenase inhibitors--are shown to prevent inhibition of the enzyme by indomethacin. Compounds in this class are also capable of blocking the ulcerogenic action of indomethacin, which suggests that this antiulcerogenic property stems from a direct action at the level of the cyclooxygenase in the stomach.

Topics: Acetaminophen; Animals; Anti-Inflammatory Agents; Cyclooxygenase Inhibitors; Diflunisal; Indomethacin; Ketoprofen; Male; Rats; Salicylates; Stomach Ulcer; Structure-Activity Relationship

To evaluate the effect of anti-inflammatory drug therapy on ulcer healing, we studied retrospectively patient records listing the dual diagnoses of rheumatoid arthritis and peptic ulcer (1953-1975). Forty-three ulcers (23 gastric and 20 duodenal) occurred in 41 subjects. Evaluation of ulcer healing was possible in 35 patients, 27 of whom had continued on anti-inflammatory drug therapy while being treated for ulcer disease and eight who did not. In 21 of the 27 patients the ulcer healed; in six the ulcer failed to heal, including one who died from gastric carcinoma. Fourteen of the 21 patients whose ulcer healed were taking both aspirin and corticosteroids; in all eight patients who stopped taking anti-inflammatory drugs, the ulcers (eight gastric, one duodenal) healed. In six patients no evaluating was possible because the outcome of ulcer therapy was unknown. The numbers of patients not studied, unlisted or unretrieved are unknown, though probably small, and while no data are available on controls drawn from the same population or on the rates of spontaneous ulcer healing and recurrence in this population, our study nevertheless establishes that ulcer healing does occur in many patients with rheumatoid arthritis despite continued treatment with salicylate, corticosteroid, or other anti-inflammatory drugs.

Topics: Anti-Inflammatory Agents; Arthritis, Rheumatoid; Humans; Peptic Ulcer; Salicylates; Stomach Ulcer; Wound Healing

Sodium salicylate (SA), contrary to acetylsalicylic acid (ASA, aspirin), was not ulcerogenic in rats. SA was also found to be cytoprotective: it prevented formation of gastric mucosal necrosis produced by either absolute ethanol or 0.6 M HCl, and formation of gastric ulcers produced by acidified ASA. The degree of protection was dose dependent. The mechanism of this cytoprotection is unknown, but unlike cytoprotection elicited by mild irritants, e.g., 20% ethanol or 0.35 M HCl, whose effects appear to be due to endogenous formation of PG by the stomach, SA acts through a different mechanisms, since its protective effect was not blocked by indomethacin.

Topics: Animals; Aspirin; Ethanol; Gastric Mucosa; Indomethacin; Male; Rats; Salicylates; Salicylic Acid; Stomach Ulcer; Structure-Activity Relationship

Topics: 3',5'-Cyclic-AMP Phosphodiesterases; Analgesics; Animals; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Hemolysis; Male; Mice; Organophosphates; Organophosphorus Compounds; Platelet Aggregation; Prostaglandins; Rats; Salicylates; Stomach Ulcer

Topics: Animals; Anti-Inflammatory Agents; Benzoxazines; Biotransformation; Fenoprofen; Ibuprofen; Indomethacin; Male; Naproxen; Oxazines; Peptic Ulcer Hemorrhage; Phenylbutazone; Rats; Salicylates; Stomach Ulcer; Time Factors; Tolmetin

Topics: Animals; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Biological Availability; Buffers; Female; Rats; Salicylates; Stomach Ulcer; Therapeutic Equivalency

The methyl and some other esters of acetylsalicylic and salicylic acids and their derivatives were found to have much lower gastric ulcerogenic activity (when assayed in the stress-sensitized rat) compared with their corresponding acids. There was little or no loss in therapeutic potencies of these salicylate esters as determined by assessment of anti-inflammatory activity (against the carrageenan-induced oedema) and antipyretic activity (against yeast-induced fever in rats. The methyl ester of acetylsalicylic acid (=AME) was almost devoid of gastric irritancy/ulcerogenicity (as observed with acetylsalicylic acid) when given orally to pigs for 10 days. AME had appreciable anti-inflammatory activity in the adjuvant-arthritis model and at high doses (200 mg/kg t.i.d.) was without the lethal effects seen with acetylsalicylic acid. Moreover, no toxic effects were seen after long-term administration of 100-1000 mg/kg/day AME for 3-4 months. The results provide further evidence for the hypothesis that the carboxylic acid moiety of salicylates is a major factor in the gastric ulcerogenic activity of these drugs. The methyl esters of these salicylates may be considered as models for the development of pro-drugs and in some cases may be therapeutic alternatives to acetylsalicylic acid or salicylate.

Topics: Animals; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Drug Evaluation, Preclinical; Female; Male; Rats; Salicylates; Stomach Ulcer; Structure-Activity Relationship; Swine

The distribution of three radioactively labelled salicylate derivatives with low ulcerogenic activity was compared with that of acetylsalicylic acid (ASA) and salicylic acid using whole body autoradiography and liquid scintillation counting techniques in rats. The methyl ester of ASA (AME) was distributed in vivo very similarly to that observed with ASA and salicylic acid. AME is rapidly demethylated following absorption from the stomach and is subsequently converted to ASA and salicylate. Salicylate is the main metabolite produced from both AME and ASA, which specifically accumulates in inflamed tissues. The 3-methyl- and 6-methyl-substituted salicylic acids are not as rapidly absorbed as either ASA or salicylic acid and do not pass readily into the brain or bone marrow. These results show that the methyl (ester) group of AME (which adequately protects the gastric mucosa from damage caused by ASA itself) does not impair the quantity of pharmacologically active form of drug (salicylate and ASA) generated in vivo. However, insertion of the methyl group at the 3- and 6-position of salicylic acid markedly affects both absorption, distribution and pharmaco-activity of these acids.

Topics: Animals; Aspirin; Male; Rats; Salicylates; Stomach Ulcer; Tissue Distribution

In 7 subjects, 100-ml successive portions of buffered acid (pH between 3.5 and 2.9) solutions of aspirin (1 g/liter) were instilled into the stomach and recovered after 10 min. Blood in the recoveries was estimated chemically. After there had been three successive increases in the rate of blood loss into the gastric lumen, typically rising from about 0.1 to 1 ml/day after about 80 min, buffered neutral solution of aspirin was instilled and recovered after 10 min. This was followed by a fall in the rate of blood loss into the gastric lumen which occurred despite a rise in the concentration of salicylate in the plasma from a mean of 55 mg/liter to 74 mg/liter. Under these conditions, salicylate in the plasma and acetylsalicylate in the gastric contents did not prevent gastric mucosal bleeding from falling to control levels within 50 min.

Topics: Aspirin; Female; Gastric Mucosa; Humans; Kinetics; Male; Salicylates; Stomach Ulcer

A series of 1,3-dialkanoyl-2-(2-methyl-4-oxo-1,3-benzodioxan-2-yl)glycerides ("cyclic aspirin triglycerides") was synthesized. They demonstrated essentially all the systemic antiinflammatory activity associated with aspirin in the carrageenin-induced rat paw edema test. Examination of the rat stomachs showed that the 1,3-didecanoyl derivative did not cause gastric lesions.

Topics: Animals; Anti-Inflammatory Agents; Aspirin; Carrageenan; Edema; Male; Rats; Salicylates; Stomach Ulcer; Triglycerides

Topics: Animals; Aspirin; Cats; Female; Histamine; Infusions, Parenteral; Male; Prostaglandins; Pyloric Antrum; Salicylates; Stomach Ulcer

A combination of indomethacin and diflunisal, a new salicylic acid derivative, when given to rats, gave a greater reduction in the size of permanganate induced granulomas and less gastric irritation, than either drug given alone.

Topics: Animals; Diflunisal; Drug Therapy, Combination; Granuloma; Indomethacin; Male; Rats; Salicylates; Stomach Diseases; Stomach Ulcer

In this work, the authors are concerned with the study of the effects of non-steroidal antiinflammatory drugs in the gastric mucosa of the rat after induced chronic inflammation with potassium permanganate.

Topics: Animals; Diflunisal; Drug Interactions; Gastric Mucosa; Indomethacin; Male; Potassium Permanganate; Rats; Salicylates; Stomach Ulcer

Topics: Aged; Anti-Inflammatory Agents, Non-Steroidal; Female; Humans; Peptic Ulcer Hemorrhage; Salicylates; Stomach Ulcer

Topics: Aged; Anti-Inflammatory Agents, Non-Steroidal; Female; Humans; Peptic Ulcer Hemorrhage; Salicylates; Stomach Ulcer

A series of 1,3-bis(alkanoyl)-2-(O-acetylsalicyloyl)glycerides (aspirin triglycerides) having aspirin at the 2 position of glycerol and fatty acids at the 1 and 3 positions was prepared. The compounds were administered orally and tested for efficacy in the rat paw edema test, and the stomachs were examined for the presence of lesions. The results showed that the members of this series in which the fatty acids are of intermediate chain length (C4-C12) do not cause gastric lesions and have essentially all the systemic activity associated with aspirin.

Topics: Animals; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Carrageenan; Dose-Response Relationship, Drug; Edema; Male; Rats; Salicylates; Stomach Ulcer; Structure-Activity Relationship; Time Factors; Triglycerides

While some salicylates (salicyclic acid and salicylaldehyde, especially) are as potent as aspirin as acute, orally-active anti-flammatory drugs in the rat, they are either inactive or far less potent as PG synthesis inhibitors when added directly to isolated platelets or when given orally. Although PGE1 and PGE2 produce anti-ulcerogenic effects when given to rats in the presence of selected non-steroidal anti-flammatory drugs, they fail to inhibit the acute anti-flammatory and anti-nociceptive effects of these drugs. They are anti-flammatory and anti-nociceptive under certain experimental conditions. PGE1 and PGE2 can also behave as hypothermic agents when given subcutaneously. Related studies, using PG synthesis stimulators in vivo and in vitro (substituted phenylureas), also cause anti-nociception and hypothermia. All of these indirect studies, when taken together, infer that PG synthesis inhibition per se fails to explain, entirely, the pharmacologic effects of non-steroidal anti-inflammatory drugs. They also suggest that the precise role of certain PGs in toxicopharmacology is far from simple and straightforward.

Topics: Analgesics; Animals; Blood Platelets; Body Temperature; Carrageenan; Edema; In Vitro Techniques; Inflammation; Male; Prostaglandins; Prostaglandins E; Rats; Salicylates; Stomach Ulcer

The interaction of salicylates and other non-steroidal anti-inflammatory drugs was studied in rats. Concurrent oral administration of sodium salicylate (SS) or salicylic acid (SA) and indomethacin (IND) significantly reduced the gastro-ulcerogenicity and the plasma concentrations of IND. Acetylsalicylic acid (ASA) failed to do so. IND had no significant influence on plasma concentrations of SA. Simultaneous administration of SS and IND intraperitoneally or subcutaneously showed the same pattern of interaction as for oral administration. Concurrent oral administration of SS and IND exerted similar anti-inflammatory activity as the single drugs. SS significantly antagonized the ulcerogenicity of ibuprofen and tended to antagonize the ulcerogenic activity of ASA, phenylbutazone, tolfenamic acid and naproxen. The results suggest that in rats SS and SA (but not ASA) interact with IND concerning both gastro-ulcerogenicity and plasma concentrations of IND (but not of SA) and that the interaction is systemic in nature. We propose that the ulcerogenic interaction might be explained partly by the reduced IND plasma concentrations and partly by a weaker inhibition by SS of the prostaglandin system in the rat stomach.

Topics: Administration, Oral; Animals; Anti-Inflammatory Agents; Drug Interactions; Gastric Mucosa; Indomethacin; Injections, Intraperitoneal; Injections, Subcutaneous; Male; Rats; Salicylates; Sodium Salicylate; Stomach Ulcer

The production by stress of gastric lesions in rats was inhibited by metiamide and by mepyramine. Lesions induced by indomethacin treatment were inhibited by mepyramine but not by metiamide. Those induced by aspirin treatment in pylorus-ligated rats were not affected by either antihistamine drug. Oral glutamine inhibited lesion production in all three systems whereas aspirin orally markedly potentiated it. Sodium salicylate inhibited both indomethacin-induced lesions and those produced by aspirin in pylorus-ligated rats. On the other hand, copper salicylate inhibited stress-induced lesions and it, like copper aspirinate, also markedly reduced the extent of lesions produced by aspirin. On the basis of these results, stress-induced lesion production offers a suitable animal model for testing anti-ulcer drugs as it is, like most human gastric ulcers, inhibited by H2-receptor inhibitors like metiamide.

Topics: Animals; Aspirin; Disease Models, Animal; Female; Glutamine; Histamine Antagonists; Indomethacin; Ligation; Pylorus; Rats; Salicylates; Stomach Ulcer; Stress, Physiological

Triglycerides containing aspirin in place of one or more fatty acid residues of the molecule have been synthesized. Metabolism of the compound with the labelled (14C) drug residue introduced specifically into the 2-position of the triglyceride is reported. Plasma salicylate concentrations with this synthetic glyceride were determined and compared with those obtained with commercially available aspirin labelled with the 14C-isotope. Both compounds gave a therapeutic concentration of salicylate in the plasma after ingestion. The 1,3-di-fatty acyl-2-aspirin glyceride was absorbed through the intestine as 2-aspirin monoglyceride, some 20% of which was transported through the thoracic-duct chyle and about 30% through the portal system. Whereas pronounced ulceration of the rat stomach occurred with free aspirin, the above fatty acyl glyceride of aspirin produced no ulceration.

Topics: Animals; Aspirin; Chyle; Male; Rats; Salicylates; Stomach Ulcer; Time Factors; Triglycerides

Topics: Acetanilides; Acute Disease; Animals; Anti-Inflammatory Agents; Aspirin; Drug Evaluation, Preclinical; Gastric Mucosa; Lethal Dose 50; Mice; Salicylates; Stomach Ulcer; Time Factors

Topics: Acetates; Animals; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Gastric Mucosa; Glycoproteins; Intestinal Mucosa; Male; Rats; Salicylates; Stomach Ulcer; Threonine; Time Factors

In unanesthetized cats, continuous intravenous infusion of aspirin for 36 hr did not produce gastric ulcers when given alone but did when combined with 160 microgram kg-1 hr-1 of histamine-2HCl intravenously. The ulcers were mainly antral in location. The incidence and severity of ulcers increased with duration of the infusion up to 36 hr and with dose of aspirin up to 4 mg kg-1 hr-1. With the highest doses and longest durations some of the antral ulcers perforated. Antral ulcers occurred in more than half of the cats getting 0.25 mg kg-1 hr-1 or more of aspirin for 36 hr or getting 4 mg kg-1 hr-1 of aspirin for 6 or more hr. Intravenous aspirin plus intragastric infusion of 40 ml hr-1 of 150 mM HCl for 16 hr also produced gastric ulcers. Plasma salicylate concentrations were less than 350 microgram ml-1 with all doses and durations of aspirin used (400 microgram ml-1 is regarded as the upper limit of the therapeutic range in man). These studies show that when the stomach is acidified by giving histamine intravenously or HCl intragastrically, intravenous aspirin produces large deep gastric ulcers. The mechanism of the ulcerogenic action of intravenous aspirin is not known.

Topics: Animals; Aspirin; Cats; Dose-Response Relationship, Drug; Drug Combinations; Drug Synergism; Female; Gastric Mucosa; Histamine; Hydrochloric Acid; Male; Salicylates; Stomach Ulcer

We found that there are strain differences in aspirin-induced ulceration in pylorus-ligated rats; the ulcer indices varied, from high to low, in the following order: Donryu greater than Sprague-Dawley greater than Wistar. Several experiments including analysis of gastric contents or ionic flux, determination of serum aspirin esterase activity, absorption of aspirin from the stomach, prothrombin time and hexosamine content in gastric mucosa and juice were performed to elucidate the origin of the differences. A significantly higher acid output in Donryu rats, and higher hexosamine content in the gastric mucosa of Wistar rats were noted. However, it appears unlikely that these factors only contribute to the marked strain difference in aspirin-induced ulcers. The possible different sensitivity of gastric mucosal cell itself to aspirin must be considered.

Topics: Animals; Aspirin; Esterases; Gastric Juice; Gastric Mucosa; Hexosamines; Ions; Male; Prothrombin Time; Rats; Salicylates; Species Specificity; Stomach Ulcer

Topics: Animals; Anti-Inflammatory Agents; Chemical Phenomena; Chemistry, Physical; Female; Heterocyclic Compounds; Lasers; Male; Methods; Phenylacetates; Rats; Salicylates; Spectrum Analysis, Raman; Stomach Ulcer; Structure-Activity Relationship

An analysis of 246 cases of perforated peptic ulcer, treated at the Royal Newcastle Hospital from 1964 to 1974, is presented. The incidence has fallen considerably over that period. The rising proportion of women has reached a plateau. A perforated peptic ulcer in an Australian women is still just as likely to be located in the stomach as in the duodenum. In men, however, 84% of perforations are pyloroduodenal. A perforated gastric ulcer is closely associated with the use of salicylate preparations. The mortality rate has remained steady at 15% over the last 30 years. It is significantly higher in women. There is a highly significant relationship between the mortality and (a) the duration of perforation; and (b) the size of the perforation, particularly if it is located in the stomach.

Topics: Adult; Aged; Analgesics; Australia; Duodenal Ulcer; Female; Humans; Male; Middle Aged; Peptic Ulcer Perforation; Salicylates; Sex Factors; Stomach Ulcer

Topics: Adrenal Cortex Hormones; Duodenal Ulcer; Gastrointestinal Hemorrhage; Hematemesis; Humans; Mallory-Weiss Syndrome; Melena; Middle Aged; Pancreatic Diseases; Peptic Ulcer Hemorrhage; Prognosis; Salicylates; Shock, Hemorrhagic; Stomach Ulcer

A multifactorial basis has been shown to exist in the development of gastric damage induced by aspirin and related N.S.A.I. drugs. Aspirin-induced gastric damage is characterized by a variety of physical and biochemical changes induced in the gastric mucosa which occur at different stages after administration of the drug. Aspirin only causes gastric ulceration and massive haemorrhage in the stomach when the stomach has been sensitized by the prior exposure to moderate stress conditions (which may resemble anxiety or psychologic stress). A model of ulcer development in which aspirin or other N.S.A.I. drugs are given to rats or pigs exposed to brief periods of stress has been described. Using this more sensitive assay procedures can be explored for reducing the gastric damaging effects of N.S.A.I. drugs. One such procedure involves chemical modification of the carboxylic acid moiety of aspirin.

Topics: Animals; Aspirin; Female; Gastric Mucosa; Gastrointestinal Hemorrhage; Guinea Pigs; Humans; Pregnancy; Prostaglandins E; Rats; Salicylates; Stomach; Stomach Ulcer; Stress, Psychological; Structure-Activity Relationship; Swine

Topics: Animals; Aspirin; Enterobacter; Escherichia coli; Female; Inflammation; Male; Mice; Platelet Aggregation; Rats; Salicylates; Stomach Ulcer; Swine

Topics: Acacia; Adjuvants, Pharmaceutic; Animals; Aspartic Acid; Aspirin; Carrageenan; Diclofenac; Drug Evaluation, Preclinical; Edema; Female; Glucose; Glycyrrhiza; Male; Phenylacetates; Plants, Medicinal; Pyrroles; Rats; Salicylates; Stomach Ulcer; Tolmetin

Aspirin was given by continuous intravenous infusion to 35 intact cats for 7 days in doses ranging from 25 to 200 mg kg-1 day-1. Gastric mucosal lesions occurred in 50 to 70% of the animals in the various dosage groups, including deep ulcers in 20%. All of the ulcers were in antral mucosa near its border with oxyntic mucosa. The incidence of lesions, including ulcers, showed no apparent relation to the dose of aspirin. With all but the highest dose, plasma salicylate levels were within or below what is regarded as the therapeutic range for man. Asprin, 100 mg kg-1 day-1, was given for 7 days to 4 cats with pouches containing all of the antral mucosa plus some oxyntic mucosa. One or more deep ulcers occurred in the antral mucosa of the pouches in each of these 4 cats. The electrical potential difference across the mucosa did not decrease, and net fluxes of hydrogen ions out of the pouch and of sodium ions into the pouch did not increase during the 7 days of aspirin administration despite the occurrence of ulcers in the pouches. It is concluded that intravenous aspirin, in doses giving plasma levels within or below the therapeutic range for man, causes gastric mucosal lesions including deep ulcers within 7 days in cats. These lesions occur without the changes in electrical potential difference and hydrogen and sodium fluxes that are regarded as characteristic of the "broken barrier."

Topics: Animals; Aspirin; Body Weight; Cats; Dose-Response Relationship, Drug; Female; Gastric Mucosa; Hydrogen-Ion Concentration; Infusions, Parenteral; Ions; Male; Membrane Potentials; Salicylates; Stomach Ulcer

Four hundred consecutive patients, in a representative Southern California population, hospitalized for upper gastrointestinal hemorrhage, had endoscopic examinations performed within 24 hours of arrival in the emergency room. Seventy-four (18.5 percent) of these were found to have the typical lesions of acute hemorrhagic erosive gastritis. The clinical spectrum of this group is examined and a comparison made with a Veterans Hospital population reported previously.

Topics: Adult; Aged; Duodenal Ulcer; Esophageal and Gastric Varices; Esophagitis; Ethanol; Female; Gastritis; Gastrointestinal Hemorrhage; Gastroscopy; Humans; Male; Middle Aged; Peptic Ulcer Hemorrhage; Salicylates; Sex Ratio; Stomach Ulcer

Evidence is presented which indicates that 7-chloro-3,3a-dihydro-2-methyl-2H,9H-isoxazolo-(3,2-b) (1,3)-benzoxazin-9-one (I) and 5-chlorosalicylic acid, its major metabolic end-product, are equally effective as anti-inflammatory and antipyretic agents, while the former is a somewhat more effective analgesic than its metabolite in the rat. However, at the equimolar doses used in this study, I is not ulcerogenic, while 5-chlorosalicylic acid does possess this untoward effect in the fasted rat. Moreover, the LD50 for 5-chlorosalicylic acid (261.0 mg/kg) is approximately 6.5 times less than that of I (1710.0 mg/kg) in the nonfasted rat. These results support the postulation that 5-chlorosalicylic acid is most likely responsible for the pharmacological activity displayed by I; i.e., the latter acts as a carrier or delivery system, allowing attenuation of the toxic properties of its active metabolite.

Topics: Analgesics; Animals; Anti-Inflammatory Agents; Arthritis; Body Temperature; Edema; Isoxazoles; Male; Oxazines; Oxazoles; Rats; Salicylates; Stomach Ulcer

Topics: Adrenal Cortex Hormones; Animals; Cold Temperature; Female; Metiamide; Rats; Salicylates; Stomach Ulcer; Stress, Physiological

Topics: Alcoholic Beverages; Diet; Duodenal Ulcer; Gastric Juice; Gastrins; Gastrointestinal Hormones; Histamine Release; Humans; Indomethacin; Peptic Ulcer; Salicylates; Secretin; Smoking; Stomach Ulcer; Stress, Psychological; Vagus Nerve

Topics: Acetates; Animals; Anti-Inflammatory Agents; Body Weight; Cortisone; Gastric Mucosa; Hexosamines; Hydroxyproline; Male; Phenylbutazone; Prednisone; Rats; Rats, Inbred Strains; Salicylates; Staining and Labeling; Stomach; Stomach Ulcer; Time Factors

Topics: Analgesics; Anti-Inflammatory Agents; Antimalarials; Aspirin; Digestive System; Duodenal Ulcer; Esophagoscopy; Gastritis; Gastrointestinal Diseases; Gastrointestinal Hemorrhage; Gastroscopy; Glycols; Humans; Indomethacin; ortho-Aminobenzoates; Phenylbutazone; Pyrazoles; Quinolines; Salicylates; Stomach Ulcer

Topics: Aspirin; Electric Conductivity; Fatty Acids, Unsaturated; Gastric Acidity Determination; Gastric Mucosa; Gastritis; Glycyrrhiza; Humans; Hydrogen-Ion Concentration; Plants, Medicinal; Salicylates; Sesquiterpenes; Stomach Ulcer; Succinates; Triterpenes

Topics: Adult; Aged; Alcohol Drinking; Gastroscopy; Humans; Indomethacin; Male; Middle Aged; Peptic Ulcer Hemorrhage; Phenylbutazone; Plants, Medicinal; Radiography; Rauwolfia; Salicylates; Stomach Ulcer; Time Factors; Wound Healing

Topics: Animals; Aspirin; Bile; Blood Proteins; Digestion; Dogs; Gastric Mucosa; Histamine Release; History, 19th Century; History, 20th Century; Humans; Hydrogen-Ion Concentration; Radiology; Receptors, Cholinergic; Salicylates; Societies, Medical; Stomach Ulcer; United States

Topics: Administration, Oral; Animals; Aspirin; Autopsy; Autoradiography; Biopsy; Body Weight; Dogs; Epithelial Cells; Gastric Mucosa; Gastrointestinal Hemorrhage; Histocytochemistry; Mucins; Salicylates; Stomach; Stomach Ulcer; Time Factors

Topics: Acute Disease; Child; Humans; Hypersensitivity; Male; Rheumatic Fever; Salicylates; Stomach Ulcer; Urticaria

Topics: Adult; Aged; Arthritis, Rheumatoid; Female; Humans; Indomethacin; Male; Middle Aged; Peptic Ulcer Hemorrhage; Peptic Ulcer Perforation; Prednisone; Salicylates; Stomach Ulcer

Topics: Animals; Gastric Mucosa; Glycosaminoglycans; Male; Phenylbutazone; Rats; Salicylates; Stomach Ulcer; Sulfur Isotopes

Topics: Biliary Tract Diseases; Duodenal Ulcer; Gastric Acidity Determination; Gastric Juice; Gastritis; Glycoproteins; Humans; Hydrochloric Acid; Mucoproteins; Neuraminic Acids; Salicylates; Stomach Ulcer; Tannins

Topics: Adrenalectomy; Animals; Fasting; Female; Gastric Mucosa; Histamine; Hypophysectomy; Phenylbutazone; Pyrazoles; Rats; Salicylates; Stomach; Stomach Ulcer; Thyroidectomy; Vagotomy

Topics: Adrenal Cortex Hormones; Antitubercular Agents; Duodenal Ulcer; Humans; Peptic Ulcer; Reserpine; Salicylates; Stomach Ulcer

Topics: Adult; Aged; Analgesics; Blood Chemical Analysis; Blood Pressure Determination; Duodenal Ulcer; Female; Humans; Kidney Function Tests; Kidney Papillary Necrosis; Male; Mental Disorders; Middle Aged; Phenacetin; Pyelonephritis; Salicylates; Stomach Ulcer; Urography

Topics: Adrenal Cortex Hormones; Cortisone; Duodenal Ulcer; Fluorouracil; Geriatrics; Oxyphenbutazone; Salicylates; Stomach Ulcer; Toxicology