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Biomedical subjects

R Sáinz

Publications and source records attributed to R Sáinz.

At least 19 recordsLinked to original sources
PubMed2002

Helicobacter pylori increases the risk of upper gastrointestinal bleeding in patients taking low-dose aspirin.

AIM: To evaluate the role of Helicobacter pylori infection and other clinical factors in the risk of upper gastrointestinal bleeding in patients taking low-dose aspirin. SUBJECTS AND METHODS: A case-control study was carried out of consecutive current users of low-dose aspirin admitted because of upper gastrointestinal bleeding. Within a cohort of 695 patients with upper gastrointestinal bleeding, 98 patients had taken low-dose aspirin and no other non-steroidal anti-inflammatory drug. Controls were 147 low-dose aspirin users without upper gastrointestinal bleeding of similar age, sex and extent of aspirin use as cases. H. pylori infection was determined by CagA/VacA serology and 13C-urea breath test in all cases and controls. Adjusted odds ratios (OR) are provided. RESULTS: H. pylori infection was identified as an independent risk factor of upper gastrointestinal bleeding in this population (OR, 4.7; 95% confidence interval (95% CI), 2.0-10.9), but the presence of CagA-positive serology was not. Other risk factors identified were a previous ulcer history (OR, 15.2; 95% CI, 3.8-60.1), alcohol use (OR, 4.2; 95% CI, 1.7-10.4) and use of calcium channel blockers (OR, 2.54; 95% CI, 1.25-5.14). Antisecretory therapy (OR, 0.1; 95% CI, 0.02-0.3) and nitrovasodilators (OR, 0.2; 95% CI, 0.1-0.6) decreased the risk of bleeding. CONCLUSIONS: H. pylori infection is a risk factor for upper gastrointestinal bleeding in low-dose aspirin users, which might have therapeutic implications in high-risk patients.

Aged↗
PubMed2001

[CagA and VacA cytotoxin antibodies and risk for peptic ulcer disease in patients with Helicobacter pylori infection].

BACKGROUND: The presence of cagA antibodies constitutes a serum marker of infection caused by virulent strains of Helicobacter pylori. The objective of this study was to determine the risk of peptic ulcer in patients with H. pylori infection, in relation to the detection of CagA and VacA antibodies. PATIENTS AND METHOD: Prospective case-control study including 104 peptic ulcer patients with active H. pylori infection (positive urease test and/or histology, or positive urea breath test) and 104 age- and sex-matched controls, without peptic ulcer history, with active H. pylori infection (positive urea breath test). Serum CagA and VacA antibodies were determined by Western blot. Non-steroidal antiinflamatory drugs (NSAID) use was determined by structured data collection. A multivariate analysis (logistic regression) was carried out to determine the odds ratio (OR). RESULTS: Presence of serum antibodies against CagA was higher in peptic ulcer patients (74%) than in controls (46.2%) (OR = 5.7; 95% CI = 2.1-15.6). However, presence of serum antibodies against VacA in patients (46.2%) was similar to that in controls (36.5%). NSAID use was also more frequent in patients (51.9%) than in controls (21,2%) (OR = 6.5; 95% CI = 2.2-19,5). CONCLUSIONS: Serum antibodies against CagA and use of NSAID are the most important risk factors for peptic ulcer disease.

Aged↗
PubMed2000

Nitrovasodilators, low-dose aspirin, other nonsteroidal antiinflammatory drugs, and the risk of upper gastrointestinal bleeding.

UNLABELLED: BACKGROUND The relation between medications that release nitric oxide, such as nitroglycerin and other nitrovasodilators, and upper gastrointestinal bleeding is uncertain. In animals, these medications reduce the gastric damage induced by nonsteroidal antiinflammatory drugs. Nitric oxide, however, inhibits platelet aggregation and may contribute to bleeding from an ulcer. METHODS: We performed a case-control study to determine the risk of bleeding in patients taking nitrovasodilators, low-dose aspirin, or other nonsteroidal antiinflammatory drugs. The case group was made up of 1122 consecutive patients admitted to one of four hospitals with bleeding from a peptic lesion. The 2231 control subjects were 1109 patients hospitalized for other reasons and 1122 outpatients from the same geographic area. RESULTS: In the week before admission, 520 (46.3 percent) of the patients with bleeding had taken a nonsteroidal antiinflammatory drug other than low-dose aspirin, 120 (10.7 percent) had taken low-dose aspirin (< or = 300 mg per day), 60 (5.3 percent) a nitrovasodilator, and 135 (12.0 percent) an antisecretory agent such as a histamine H2-receptor antagonist or a proton-pump inhibitor. In multivariate models that adjusted for age, sex, and clinical risk factors, the use of a nonsteroidal antiinflammatory drug other than low-dose aspirin was independently associated with an increased risk of bleeding from a peptic ulcer (odds ratio, 7.4; 95 percent confidence interval, 4.5 to 12.0), as was the use of low-dose aspirin alone (odds ratio, 2.4; 95 percent confidence interval, 1.8 to 3.3). The use of a nitrovasodilator was associated with a decreased risk of bleeding (odds ratio, 0.6; 95 percent confidence interval, 0.4 to 0.9), as was antisecretory therapy (odds ratio, 0.6; 95 percent confidence interval, 0.4 to 0.8). In patients taking any type of nonsteroidai antiinflammatory drug, the use of a nitrovasodilator or antisecretory therapy was independently associated with a decreased risk of bleeding. CONCLUSIONS: The use of nitrovasodilator drugs is independently associated with a decreased risk of upper gastrointestinal bleeding.

Aged↗
PubMed2000

Prevention and healing of experimental indomethacin-induced gastric lesions: effects of ebrotidine, omeprazole and ranitidine.

BACKGROUND: Ebrotidine is a new H2 receptor antagonist that potentiates the gastric mucosal barrier. AIM: To compare ebrotidine with other anti-secretory drugs in the prevention and healing of indomethacin-induced gastric lesions. METHODS: Three different models of indomethacin-induced gastric lesions were used. (1) Fasted rat model: indomethacin was intra-gastrically administered in rats pre-treated with different doses of the anti-secretory drugs. (2) Re-fed rat model: rats orally treated with different doses of anti-secretory drugs had free access to chow pellets and were then treated with parenteral indomethacin. (3) Healing model: either oral or parenteral anti-secretory drugs were given after indomethacin administration. Computer-assisted analysis of the area of damage was expressed as ulcer index. Gastric secretion was evaluated in the pylorus-ligated rat model. RESULTS: Inhibition of acid secretion was in the order omeprazole > ebrotidine = ranitidine. Ebrotidine at the highest dose used (100 mg/kg) and omeprazole, but not ranitidine, significantly prevented indomethacin-induced corpus (fasted rat) and antrum (re-fed rat) gastric lesions. In the ulcer healing model, oral administration of omeprazole and both ranitidine and ebrotidine at the highest dose used improved the ulcer index. The parenteral administration of these drugs had a lesser effect than the oral route and was in the order ebrotidine > omeprazole > ranitidine. CONCLUSIONS: Ebrotidine is effective in both the prevention and healing of indomethacin-induced experimental gastric lesions. In these models, the effect of ebrotidine is comparable to omeprazole and more effective than ranitidine.

Animals↗
PubMed2000

Study of outcome after targeted intervention for peptic ulcer resistant to acid suppression therapy.

OBJECTIVE: Different factors might affect outcome in ulcers resistant to antisecretory therapy. The aim of the study was to define the odds of resistant ulcers being associated with NSAID use, and/or Helicobacter pylori (H. pylori) infection, or neither. METHODS: A total of 80 patients with resistant peptic ulcers were prospectively followed after targeted intervention for a mean follow-up of 39.5+/-6.9 months. RESULTS: NSAID use was involved in 24 cases (14 with and 10 without concomitant H. pylori infection), H. pylori alone was involved in 44, and 12 patients had neither factor present. Of the NSAID group, resistant ulcers healed in patients who stopped taking NSAIDs. Those continuing to use NSAIDs (10 of 24; 41.6%) had either persistent ulceration or ulcer complications despite H. pylori eradication and omeprazole therapy. Of the H. pylori group, infection eradication induced ulcer remission in most patients, but those with persistent infection and a small subset of H. pylori eradicated patients (16.6%) had persistent/recurrent ulceration. Of the 12 refractory patients with neither NSAID use nor H. pylori infection, three had persistent ulceration but nine were controlled with antisecretory agents. Other factors (e.g., smoking or acid hypersecretion) were not associated with final outcome after targeted intervention of H. pylori infection and NSAID use. CONCLUSIONS: With current antiulcer therapies, NSAID use is the main, but not the exclusive, factor leading to intractability and complications in refractory ulcers. In a subset of resistant ulcers, neither the presence of H. pylori nor use of NSAIDs are involved. In this study, despite specific therapeutic intervention, 22.5% of patients with resistant ulcers had continuing ulcer problems.

Adult↗
PubMed1999

Experimental esophagitis induced by acid and pepsin in rabbits mimicking human reflux esophagitis.

BACKGROUND & AIMS: The lack of appropriate animal models might explain the paucity of information on the mechanisms of mucosal damage and defense in reflux esophagitis. The aim of this study was to develop a model of esophagitis in rabbits mimicking human reflux esophagitis. METHODS: New Zealand white rabbits underwent surgery for placement of a plastic tube into the cervical esophagus. Acidified pepsin (AP) was intermittently perfused for different periods. Esophageal injury was assessed by macroscopic and microscopic examination, including the cell proliferation immunohistochemical parameter mib1. RESULTS: Rabbit losses (20%) were attributable mostly to postsurgical mortality and tube displacement. Perfusion of AP for 60 min/12 h or 45 min/12 h induced high-grade esophagitis by days 3 and 5, respectively, characterized by diffuse erosion/ulceration, inflammation, bleeding, and reactive epithelial changes. Perfusion of acidified pepsin for 60 min/day, especially at 30 min/12 h, induced low-grade esophagitis characterized by superficial epithelial loss, mild/absent inflammation, and epithelial reactive changes including increased cell proliferation, basal hyperplasia, and papillomatosis, which reached maximal expression by day 7. This perfusion regimen induced mucosal adaptation to damage. CONCLUSIONS: Different and highly reproducible esophageal mucosal lesions mimicking human reflux esophagitis can be induced in rabbits with repetitive acid and pepsin exposure.

Acute Disease↗
PubMed1999

Sebaceous carcinoma of the vulva.

Extraocular sebaceous carcinoma is an uncommon neoplasm usually localized on the head and neck. Sebaceous glands are abundant on the vulva, but vulvar sebaceous carcinoma is an uncommon neoplasm. To our knowledge, there are only five previously reported cases of sebaceous carcinoma on this location. We report an additional case of vulvar sebaceous carcinoma associated with Bowen's disease in the overlying epidermis. The patient also had bowenoid papulosis involving the skin of labia majora. We analyzed by immunohistochemistry, Southern blot hybridization, and polymerase chain reaction (PCR) techniques for the presence of DNA of human papilloma viruses (HPVs) in the specimen of sebaceous carcinoma and in lesions of bowenoid papulosis. Immunohistochemistry, Southern blot hybridization, and PCR studies in specimens of bowenoid papulosis lesions and sebaceous carcinoma did not detect DNA of HPVs. A significant increase in intranuclear p53 staining was demonstrated in several areas of neoplastic aggregations of sebaceous carcinoma.

Adult↗
PubMed1998

Esophageal motility and intraesophageal pH patterns in patients with esophagitis and chronic nonsteroidal anti-inflammatory drug use.

Clinical reports suggest that nonsteroidal anti-inflammatory drugs (NSAIDs) use might induce esophageal symptoms and damage, including esophagitis, but experimental data are conflicting, and some indicate that NSAIDs improve mucosal damage. It is not known whether patients with endoscopically diagnosed esophagitis during NSAID use have different baseline reflux patterns from patients with reflux esophagitis and no NSAID use. Two groups of patients with and without chronic NSAID use and esophagitis were prospectively studied. Twenty-four-hour pH monitoring and esophageal manometry were performed in all patients who were free of NSAID and any other drug use during tests. Esophageal motility and reflux patterns did not differ in patients with esophagitis regardless of the presence or absence of NSAID use. However, the subgroup of patients with grades II and III esophagitis and chronic NSAID use had a significantly greater lower esophageal sphincter (LES) pressure and a less severe intraesophageal pH profile than patients without NSAID use. In agreement with clinical reports, these results suggest that NSAID use may aggravate an otherwise milder acid-related esophageal disease in a subgroup of patients.

Adult↗
PubMed1997

Adaptation of esophageal mucosa to acid- and pepsin-induced damage: role of nitric oxide and epidermal growth factor.

To study whether the esophageal mucosa was able to elicit mucosal adaptation, we induced esophageal damage by perfusing acidified pepsin in rabbits. Mucosal adaptation was induced by preexposing the esophageal mucosa to a mild irritant (acidified saline) for 60 min prior to acidified pepsin (strong irritant). Macroscopic and microscopic esophageal injury, cell proliferation, and mucosal barrier function (H+, K+, hemoglobin flux rates) were studied. Preexposure of the esophageal mucosa to acidified saline significantly decreased both the mucosal damage and the mucosal barrier dysfunction induced by acidified pepsin. The development of this phenomenon was nondependent on cell proliferation. Concomitant treatment with either the nitric oxide synthase inhibitor, N(G)-nitro-L-arginine, or the perfusion of immunospecific EGF-receptor antibodies or tyrphostin-25, an inhibitor of the tyrosine kinase activities ligated to the intracytoplasmatic domain of the EGF receptor, during the preexposure period completely reversed the protection induced by acid. We conclude that the rabbit esophageal mucosa shows mucosal adaptation to acid and pepsin. The development of this phenomenon is fast, not dependent on cell proliferation, and dependent, at least in part, on nitric oxide and EGF-receptor-mediated mechanisms.

Adaptation, Physiological↗
PubMed1997

Evidence of aspirin use in both upper and lower gastrointestinal perforation.

BACKGROUND & AIMS: Current studies lack appropriate data on aspirin and other risk factors for gastrointestinal perforation. The aim of this study was to obtain the best estimate on aspirin and nonaspirin nonsteroidal anti-inflammatory drug (NSAID) use in these patients. METHODS: In 76 consecutive patients with gastrointestinal perforation and 152 matched controls, a detailed clinical history supplemented with an objective test of current aspirin use (platelet cyclooxygenase activity) was obtained. RESULTS: Of the 76 cases, 78.9% were upper and 21% lower gastrointestinal perforations. Evidence of NSAID use was found in 71% of cases (70% upper, 75% lower) vs. 26.9% of controls (odds ratio, 6.64; 95% confidence interval, 3.6-12.2; P < 0.0001). The objective test showed 12.7% more aspirin users than clinical history alone. NSAID use was aspirin (alone or combined) in 66.6% of cases, and 59.25% was nonprescription. Other independent risk factors were smoking, alcohol, and a history of arthritis or peptic ulcer but not a positive Helicobacter pylori serology. Age, but not NSAID use, affected perforation-associated mortality. CONCLUSIONS: NSAID use is strongly associated with an increased risk of both upper and lower gastrointestinal perforation. The high prevalence of aspirin (over-the-counter) use suggests that future introduction of new NSAIDs may not have a major impact on decreasing gastrointestinal complications if other measures are not taken. Concomitant NSAID use, smoking, and alcohol use is a pervasive association.

Aged↗
PubMed1997

Cytokine effects on pepsinogen secretion from human peptic cells.

BACKGROUND: Different cytokines, including epidermal growth factor (EGF) and interleukin 1 beta (IL 1 beta), participate in the pathogenesis of gastric mucosal damage and repair by means of different mechanisms that are either paracrine or autocrine in nature. AIMS: To study whether EGF and IL 1 beta affect pepsinogen secretion in vitro. METHODS: Dispersed human peptic cells were prepared from endoscopically obtained biopsy specimens after collagenase digestion, mechanical disruption, and density gradient centrifugation. RESULTS: EGF dose dependently increased basal pepsinogen secretion and mitogenic concentrations (0.1 nM) of EGF induced submaximal stimulation. Similar effects were observed with transforming growth factor alpha. EGF effects on pepsinogen secretion were in addition to that induced by CCK-OP and db-cAMP stimulated pepsinogen secretion. EGF stimulated pepsinogen secretion was completely inhibited by a human immunospecific EGF receptor antibody and reduced by both genistein and tyrphostin-25, two different tyrosine kinase inhibitors. IL 1 beta does not affect basal, CCK-OP or acetylcholine stimulated pepsinogen secretion. However, IL 1 beta dose dependently inhibited db-cAMP and histamine stimulated pepsinogen secretion. CONCLUSIONS: These results show that both EGF and IL 1 beta modulate human pepsinogen secretion in vitro and suggest that the paracrine effects of these cytokines on pepsinogen secretion might be involved in some pathological conditions of damage and inflammation of the gastric mucosa.

Adult↗
PubMed1997

Platelet-derived growth factor reverses the effects induced by NSAIDs on ulcer healing.

BACKGROUND: It is known that non-steroidal anti-inflammatory drug (NSAID) use delays the healing of peptic ulcers and that growth factors play an important role in the ulcer healing process. AIM: To evaluate the effect of platelet-derived growth factor (PDGF) in healing chronic gastric ulcers in rats treated with NSAIDs. METHODS: Chronic gastric ulcers were induced with acetic acid in male Wistar rats and then treated with either aspirin (100 mg/kg/day), indomethacin (2 mg/kg/day), PDGF-BB (0.1 nM/kg/day) or combinations. Gastric secretion and ulcer size, wound contraction, mucosal regeneration and cell proliferation were assessed in histological specimens. RESULTS: Both aspirin and indomethacin delayed the healing rate of gastric ulcers and reduced ulcer contraction, mucosal regeneration and cell proliferation. All these effects were completely reversed by oral treatment with PDGF-BB without affecting gastric acid secretion. CONCLUSION: Oral administration of PDGF accelerates ulcer healing and reverses the effects induced by NSAIDs on ulcer healing without affecting gastric secretion.

Animals↗
PubMed1996

Aspirin related gastrointestinal bleeders have an exaggerated bleeding time response due to aspirin use.

BACKGROUND: Gastrointestinal bleeding is related to non-steroidal anti-inflammatory drug (NSAID) use, especially aspirin, but only a small subset of users bleed. AIM: To look for risk factors or mechanisms whereby aspirin may promote gastrointestinal bleeding. PATIENTS: Sixty one patients with previous aspirin related upper gastrointestinal bleeding and 61 matched controls. METHODS: Patients and controls were given 375 mg of aspirin and sequential skin bleeding time and blood aspirin levels were measured. Additional studies included platelet lumiaggregation, von Willebrand factor, Factor VIII, and coagulation studies. RESULTS: Baseline skin bleeding time was similar in bleeders and controls, but bleeders had a more prolonged skin bleeding time after aspirin use. Hyper-response was more frequent in bleeders (30% v 9.3%; p < 0.01) and was associated with more than one previous separate bleeding event and a lower packed cell volume during the preceding bleeding episode. No differences were found in other factors studied. Logistic regression analysis identified prolonged skin bleeding time after aspirin use as an independent factor contributing to aspirin related gastrointestinal bleeding (RR = 5.4; 95% CI: 1.8 to 17.1). CONCLUSIONS: 30% of patients with a history of aspirin related gastrointestinal bleeding have an exaggerated prolongation of skin bleeding time in response to aspirin, which may be a risk factor for bleeding. This intrinsic defect or to subclinical von Willebrand disease or different aspirin metabolism.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1995

Risk factors associated with refractory peptic ulcers.

BACKGROUND & AIMS: The risk factors associated with refractory peptic ulcers are still undefined. The purpose of this study was to identify these factors in a multivariate context. METHODS: Clinical and endoscopic findings as well as Helicobacter pylori status, gastric secretion analysis, serum gastrin levels, nonsteroidal anti-inflammatory drug (NSAID) use, and objective testing of aspirin use by platelet cyclooxygenase activity were studied in 60 consecutive refractory patients with peptic ulcer and 54 matched nonrefractory controls. RESULTS: Refractory patients had a longer history of symptomatic ulcer, had an earlier onset, had more frequent relapses, and smoked more during the episode of refractoriness. H. pylori status was similar in both groups, but H. pylori eradication in a subset of refractory patients (23 of 26) was highly effective in healing these ulcers (14 of 23). Globally, NSAID-analgesic abuse (including > 1500 mg/day paracetamol) was present in 40% of refractory patients (P < 0.006). Objective testing showed that 43.7% of NSAID use was surreptitious. Multivariate logistic regression analysis identified only NSAID and analgesic abuse and the number of relapses as individually affecting refractoriness. CONCLUSIONS: NSAID and analgesic abuse is the single most important exogenous factor associated with refractoriness. H. pylori infection emerges as an important intrinsic factor, but almost a quarter of refractory patients cannot be linked to either NSAID use or H. pylori infection.

Alcohol Drinking↗
PubMed1995

Effect of parenteral omeprazole and ranitidine on gastric pH and the outcome of bleeding peptic ulcer.

The pharmacotherapy of bleeding peptic ulcer is directed at attempting to keep the gastric pH above the proteolytic range for pepsin. In this randomized, prospective, open clinical trial we have compared the effects and outcome of omeprazole versus ranitidine in patients with bleeding peptic ulcer. Of 219 consecutive patients with upper gastrointestinal bleeding, 51 (23.2%) had an ulcer with endoscopic predictors of rebleeding at the time of diagnosis. These 51 patients were selected at random to receive either omeprazole (80 mg bolus and 40 mg/12 h i.v.) or ranitidine (50 mg/4 h i.v.). No endoscopic therapy was performed at the time of diagnosis. Twenty of these patients with duodenal ulcer (n = 10 omeprazole, n = 10 ranitidine) underwent 24-h gastric pH monitoring. Both groups were homogeneous in all clinical and endoscopic parameters. No differences in blood transfusion units, time of hospitalization, the lowest hematocrit measured, and mortality rates were observed between the groups. However, omeprazole reduced the number of rebleeding episodes (p = 0.1) and the need for surgery (3.8% vs. 22.7%; p = 0.05). Omeprazole also reduced the amount of time the gastric pH was < 6 (15.3 +/- 5.9% vs. 61.8 +/- 5.6%, p < 0.0001). We conclude that parenteral omeprazole is much more effective than ranitidine in keeping the gastric pH above the proteolytic range for pepsin in bleeders and that this might explain a better outcome in a subset of patients with bleeding peptic ulcers treated with parenteral omeprazole.

Adult↗
PubMed1995

Aspirin renders the oesophageal mucosa more permeable to acid and pepsin.

OBJECTIVE: To examine the effects of aspirin on the oesophageal mucosa and on acid- and pepsin-induced oesophagitis. DESIGN AND METHODS: The effects both of intraluminal (18 mg/ml) and of parenteral (100 mg/kg per h) aspirin on an in-vivo rabbit model of oesophagitis induced by acidified pepsin (pH 2) were studied. Oesophageal injury was assessed by macroscopic and microscopic scoring including the cell proliferation immunohistochemical parameter mib1. The mucosal barrier function was determined by hydrogen, potassium and haemoglobin flux rates. RESULTS: Acidified saline alone caused no damage, but the addition of aspirin induced mucosal barrier damage (P < 0.05). The exposure of the oesophageal mucosa to acidified aspirin and then acidified pepsin significantly increased mucosal injury and mucosal barrier dysfunction compared with control experiments (exposure to acidified saline and acidified pepsin). This damage was significantly (P < 0.05) reduced (> 40%) by prostaglandin cotherapy (prostaglandin E2) administered before acidified aspirin exposure. Mucosal damage was less severe (P < 0.05) when the oesophageal mucosa was exposed to a pH 6 aspirin solution. Parenterally administered aspirin also increased the oesophageal damage induced by acidified pepsin compared with control experiments, but the damage was 23% lower than that obtained with intraluminal aspirin. Cell proliferation studies showed a significant increase in the number of positive cells in those experiments with a higher degree of damage and in those treated with prostaglandins. CONCLUSION: Aspirin renders the oesophageal mucosa more permeable to acid and pepsin. These effects are in part pH-dependent and might be partially reversed by prostaglandin E2 cotherapy.

Acids↗
PubMed1995

Non-steroidal anti-inflammatory drugs and prostaglandin effects on pepsinogen secretion by dispersed human peptic cells.

The effects of aspirin and ibuprofen on pepsinogen secretion were studied in isolated human peptic cells prepared from endoscopically obtained biopsy specimens after collagenase digestion, mechanical disruption, and percoll gradient centrifugation. Pharmacological concentrations of aspirin and ibuprofen (10(-8)-10(-4) M), potentiated histamine (10(-6)-10(-4)M) and forskolin (10(-5)M) stimulated pepsinogen secretion without affecting basal secretion, acetylcholine (10(-6)M) stimulated pepsinogen secretion or cell vitality. Augmentation of secretagogue stimulated pepsinogen secretion was dependent on extracellular calcium because potentiation was abolished by calcium depletion of the medium. Cimetidine inhibited the potentiation effect on histamine but not on forskolin stimulated pepsinogen secretion, thus suggesting that this augmentation was independent of histamine H2 receptors. Of interest, potentiation was also independent of endogenous prostaglandin inhibition because exogenous addition of prostaglandin E2 and D2 increased both basal and acetylcholine stimulated pepsinogen secretion in a dose dependent way, but they did not modify histamine or histamine plus aspirin or ibuprofen stimulated pepsinogen secretion. In conclusion, aspirin and ibuprofen potentiate secretagogue stimulated pepsinogen secretion by dispersed human peptic cells and this might be an additional mechanism of non-steroidal anti-inflammatory drug (NSAID) induced gastric injury. This potentiation effect is regulated by calcium, independent of endogenous prostaglandin inhibition and seems to act on pepsinogen secretion at a post-receptor site.

Acetylcholine↗