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Biomedical subjects

A Lanas

Publications and source records attributed to A Lanas.

At least 55 records · Page 3Linked to original sources
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↗
PubMed2000

Platelet-derived growth factor and epidermal growth factor play a major role in human colonic fibroblast repair activities.

BACKGROUND AND AIMS: Ulceration is a common feature of inflammatory bowel diseases, where subepithelial cell growth is frequently necessary for resolution. In order to further understand the role of colonic fibroblasts in this process, we have used an in vitro model of wound repair to study the response of human colonic fibroblasts to several growth factors expressed in colonic tissues. METHODS: Proliferation was determined by [(3)H]thymidine incorporation into DNA in subconfluent fibroblast cultures. In vitro wound repair was determined in confluent fibroblast monolayers after mechanical denudation. The presence of growth factors secreted by fibroblasts was studied in conditioned medium by heparin affinity chromatography and immunodetection with specific antibodies. RESULTS: Serum and platelet-derived growth factor (PDGF-BB) induced a dramatic increase in both colonic fibroblast proliferation and closure of wounded cell monolayers. Epidermal growth factor (EGF) stimulated both fibroblast activities, but the effect was less potent. However, colonic fibroblasts did not respond to transforming growth factor-beta(1). Conditioned medium stimulated fibroblast proliferation and wound repair activity, which was reverted by the addition of suramin. Furthermore, a PDGF-like factor was isolated from colonic fibroblast-conditioned medium. CONCLUSIONS: EGF and PDGF-BB promote human colonic fibroblast-dependent wound repair activities. Human colonic fibroblasts may exert an autocrine regulation via the production of growth factors.

Cell Division↗
PubMed2000

[Antisecretory drugs and prophylaxis of secondary gastrointestinal effects associated with the consumption of non steroid anti-inflammatory drugs].

BACKGROUND: To evaluate the available evidence on the efficacy of antisecretory drugs in the prevention of serious upper gastrointestinal adverse events associated with the use of nonsteroidal antiinflammatory drugs (NSAID). METHODS: All studies published and abstracted in the MEDLINE from 1970 to 1999 were reviewed. Only randomized, double-blind and placebo-controlled studies with a follow-up longer than 4 weeks were selected. The variables upper gastrointestinal complications, gastric ulcer, duodenal ulcer and side effects in both primary and secondary prophylaxis were analyzed by meta-analysis techniques. RESULTS: No studies were available regarding the effects of antisecretory drugs in the prevention of upper gastrointestinal bleeding associated with NSAID use. Ten studies were identified in the prevention of both gastric and duodenal ulcers. The effect of these agents was found to be especially useful in the prevention of duodenal ulcers, in secondary prophylaxis and in the long-term use of NSAID. The most consistent effect was seen with omeprazole for both duodenal ulcer prevention (OR [95% CI] = 0.12 [0.06-0.23]) and gastric ulcer prevention (OR = 0.20 [0.13-0.31)]. However, H2-receptor, antagonists were not significantly associated with gastric ulcer prevention in all the scenarios analyzed. CONCLUSIONS: Prescription of antisecretory drugs are justified in the prevention of both gastric and duodenal ulcers in patients taking NSAID. The best benefit is achieved with omeprazole.

Adolescent↗
PubMed2000

[Cost stratification of nonsteroidal anti-inflammatory drug-associated gastrointestinal side effects].

BACKGROUND: Nonsteroidal anti-inflammatory drugs induce gastrointestinal side effects. In this study we have analyzed the economic impact of these side effects on the National Health System. MATERIAL AND METHODS: Costs were calculated based on actual data obtained from a General Hospital attending a population of 256,000 people with similar demographic distribution to the country 39 million people. The number of prescriptions of NSAID issued in the area during a 12 month period (1998), the attributable risks obtained from different epidemiological studies of this area and the rate and type of co-prescribing of gastroprotective agents were obtained from different local and national surveys and specialized agencies. Costs of complication and dyspepsia treatments were obtained from actual cost charged by the Spanish National Institute of Health. Sensitivity analyses were also performed to estimate maximal and minimum costs. RESULTS: Costs per 100,000 people/year were: a) hospitalization = 24,100,983 pesetas; b) gastroprotective agents = 81,759,255 pesetas; c) management of dyspepsia = 31,527,895 pesetas. Estimates showed that global costs per 100,000 people/year were nor higher than 31,353 million and nor lower than 71,312 million pesetas. It was also estimated that gastroprotective therapy was inadequately prescribed in 80% of cases (25,720 million pesetas), and that 8,312 million pesetas per 100,000 patient/year of the global cost was due to OTC NSAID use. Globally, GI side effects increased 86% the actual cost of NSAID in 1998. Almost half of that increase was due to inadequate prescription of gastroprotective therapy and only 5.4% of that was due to OTC NSAID use. CONCLUSIONS: Gastrointestinal side effects due to NSAID use have an enormous economic impact on the National Health System. Any new therapeutic strategy in the management of rheumatic conditions which decrease the rate of complications and the need of coprescription of gastroprotective agents will decrease these costs.

Anti-Inflammatory Agents, Non-Steroidal↗
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

Effects of extracellular pH on restitution and proliferation of rabbit oesophageal epithelial cells.

BACKGROUND AND AIMS: Exposure to luminal acid induces mucosal damage in the oesophagus. The extent and degree of interaction of acid with wound repair mechanisms of the oesophagus have not been explored. METHODS: Rabbit oesophageal cells were isolated, cultured and exposed to different extracellular pHs for several periods of time. Cell mortality was studied in both isolated and primary cultures of these cells by cell flow cytometry using fluorochrome propidium iodide and LDH release. Subconfluent cell cultures were used to study proliferative responses determined by [3H]-thymidine incorporation into DNA. Restitution was studied in confluent monolayers wounded by mechanical denudation. RESULTS: Isolated cells were resistant to acid when exposed to pH > 2 for 15 min. Cell proliferation increased with small pH decreases (7-6.5) if the period of exposure was less than 6 h, but was inhibited with lower pHs and/or longer periods of acid exposure. However, restitution was gradually inhibited with further pH decreases (6.5-3) and time of acid exposure (0.5-24 h). CONCLUSIONS: The wound repair activities of oesophageal epithelial cells are deeply affected by even small decreases in pH. These findings may help to explain the need for profound acid inhibition in acid-related reflux oesophagitis.

Animals↗
PubMed1999

Helicobacter pylori infection is a protective factor for bleeding gastric ulcers but not for bleeding duodenal ulcers in NSAID users.

BACKGROUND: The effect of Helicobacter pylori infection on NSAID-induced gastroduodenal damage is unclear. AIM: To determine the role of H. pylori and NSAID use in complicated peptic ulcers. METHODS: A total of 185 consecutive patients with bleeding peptic ulcers and 185 hospitalized matched controls were studied prospectively. Additionally, 75 consecutive uncomplicated peptic ulcers and 75 community controls were also studied. Active H. pylori infection was determined by urea breath test and/or both urease test and histology. Serum CagA and VacA status were determined at random in 135 infected patients and 82 controls. NSAID use was determined by structured data collection. RESULTS: H. pylori (odds ratio [OR]=5. 98; 2.9-12.3) and NSAID use (OR=5.74; 3.4-9.7) were independent risk factors for duodenal ulcer bleeding, whereas NSAID use was the main risk factor for bleeding gastric ulcers (OR=12.4; 5.5-27.9). Interaction of both factors was associated with reduced risk for bleeding gastric ulcers (OR=0.19; 0.04-0.88) but not for bleeding duodenal ulcers, which showed a similar risk to any one factor alone. This was observed for all types of NSAID use, including low-dose aspirin, and infection by CagA positive strains. H. pylori was the only factor involved in common uncomplicated duodenal ulcers. CONCLUSION: Interaction of both H. pylori infection and NSAID use decreases the risk of bleeding due to gastric ulcers, but not that due to duodenal ulcers.

Duodenal Ulcer↗
PubMed1999

Toxicity of NSAIDs in the stomach and duodenum.

NSAIDs are widely used for analgesic, anti-inflammatory and anti-thrombotic indications. Such use carries the risk of gastrointestinal complications (1% over 6 months) which NSAIDs may promote from both ulcerous and nonulcerous lesions. Symptoms are poor predictors of serious lesions and complications, which may occur without previous symptoms. NSAIDs also delay healing of peptic ulcers, even to the extent of intractability, and may cause recurrence after gastric surgery. Prophylactic therapy is indicated in high-risk patients (age > 60 years, previous ulcer history, high dose, concomitant use of corticosteroids or anticoagulants). Misoprostol, omeprazole and high-dose famotidine have been shown to reduce the occurrence of both gastric and duodenal ulcers in NSAID users. At present, the role of Helicobacter pylori in NSAID-induced gastroduodenal lesions is controversial and there is no agreement in considering the organism as a risk factor and indicating its eradication in NSAID users.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1999

Non-steroidal anti-inflammatory drugs and gastrointestinal bleeding.

Non-steroidal anti-inflammatory drug use carries the risk of gastrointestinal complications (1% over 6 months) which is increased by a factor of 4 to 5, although strong differences are observed between different non-steroidal anti-inflammatory drugs. This risk is present in both the upper and lower gastrointestinal tract which indicates that non-steroidal anti-inflammatory drugs induces bleeding from both peptic ulcer and non-peptic ulcer sources. Symptoms are poor predictors of serious lesions and complications, which may occur without previous symptoms. At present, risk factors for non-steroidal anti-inflammatory drug-associated upper gastrointestinal bleeding are well defined and include ulcer or complication history, age, high non-steroidal anti-inflammatory drug dose, combination with corticosteroid and warfarin. Helicobacter pylori infection is not considered a risk factor for complications in non-steroidal anti-inflammatory drug users. There is a high prevalence of over-the-counter non-steroidal anti-inflammatory drug (especially aspirin) use among those presenting with gastrointestinal complications. Prophylactic aspirin regimens increase the risk of gastrointestinal bleeding. The potential beneficial effect of nitrate treatments (nitric oxide donors) in low dose aspirin users deserves further study. The mechanisms involved in the induction of gastrointestinal bleeding by non-steroidal anti-inflammatory drugs are poorly understood. Platelet activity inhibition associated with an abnormal, but reversible, prolongation of the bleeding time in susceptible individuals using aspirin might be a mechanism affecting no more than a third of patients with gastrointestinal bleeding.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1998

Randomised controlled trial of Helicobacter pylori eradication in patients on non-steroidal anti-inflammatory drugs: HELP NSAIDs study. Helicobacter Eradication for Lesion Prevention.

BACKGROUND: The effect of Helicobacter pylori in patients receiving non-steroidal anti-inflammatory drugs (NSAIDs) is unclear. We investigated the effects of H. pylori eradication in patients with current or previous peptic ulceration, dyspepsia, or both who continued to use NSAIDs. METHODS: 285 patients were randomly assigned omeprazole 20 mg, amoxycillin 1000 mg, and clarithromycin 500 mg, twice daily (n=142, H. pylori eradication treatment), or omeprazole with placebo antibiotics (n=143, controls) for 1 week. All patients received omeprazole 20 mg once daily for 3 weeks until endoscopy, and, if the ulcer was not healed, 40 mg once daily until repeat endoscopy at 8 weeks. Ulcer-free patients with mild dyspepsia continued NSAIDs but not antiulcer treatment. We investigated ulcers with endoscopy at 1, 3, and 6 months and with carbon-13-labelled urea breath test at 3 months. FINDINGS: The estimated probability of being ulcer-free at 6 months was 0.56 (95% CI 0.47-0.65) on eradication treatment and 0.53 (0.44-0.62) on on control treatment (p=0.80). Time to treatment failure did not differ between groups for ulcers or dyspepsia alone, per-protocol analysis, or final H. pylori status. 66% (58-74) of the eradication group compared with 14% (8-20) of the control group had a final negative H. pylori result (p<0.001). Fewer baseline gastric ulcers healed among eradication-treatment patients than among controls (72 vs 100% at 8 weeks, p=0.006). INTERPRETATION: H. pylori eradication in long-term users of NSAIDs with past or current peptic ulcer or troublesome dyspepsia led to impaired healing of gastric ulcers and did not affect the rate of peptic ulcers or dyspepsia over 6 months.

Adolescent↗
PubMed1998

Intractable upper gastrointestinal ulceration due to aspirin in patients who have undergone surgery for peptic ulcer.

BACKGROUND & AIMS: Postsurgical ulcer recurrence is a challenging problem. The aim of this study was to define the role of aspirin in postsurgical ulcers. METHODS: We studied 30 patients with postsurgical ulcer and aspirin abuse. Preoperatively 13 had stenosis, 7 bleeding, and 7 perforation or penetration; 18 had undergone vagotomy and 11 gastrectomy. RESULTS: Of 30 patients, 15 admitted long-term aspirin use (1-4 g/day), whereas 15 denied use but had positive salicylate blood levels (15.1 +/- 2.25 mg/100 mL; >1 mmol/L). Gastrin or gastric secretion was normal in the 24 patients tested. On follow-up, 3 (10%) healed after surgery (all stopped taking aspirin), whereas 27 continued and had new ulcers; 12 (44%) developed stenosis, and 6 (23%) developed bleeding. A second operation was required in 16 patients who had continued aspirin abuse, which was surreptitious in 10 (63%). Thirteen of these 16 had recurrent ulceration (7 [43%] with stenosis and 1 with bleeding); 1 died and 2 stopped taking aspirin and healed. A third operation was required in 8 patients. All had continued aspirin abuse (75% surreptitiously), and all again had relapses (3 with stenosis); 1 underwent an unsuccessful fourth operation, and 3 died. CONCLUSIONS: With continued aspirin abuse, recurrent ulceration is the rule, and complications, especially stenosis, are common. Surreptitious aspirin abuse, if discovered, is a clear contraindication to elective ulcer surgery, because aspirin-abuse ulceration is incurable by gastric surgery.

Aspirin↗
PubMed1998

In vitro wound repair by human gastric fibroblasts: implications for ulcer healing.

Fibroblasts modulate epithelial biological activities and play a key role in the ulcer healing process. There is no information regarding the biological response of human gastric fibroblasts to regulatory compounds. The aim of this study was to assess the effects of growth factors and prostaglandins on an in vitro model of human gastric fibroblast wound repair. Subconfluent fibroblast cultures were used to study proliferative responses, determined by [3H]thymidine incorporation into DNA. In vitro wound repair was determined in confluent fibroblast monolayers after mechanical denudation. The presence of putative growth factors secreted by fibroblasts was studied in conditioned medium by heparin-affinity chromatography and immunodetection with specific antibodies. Serum and platelet-derived growth factor (PDGF) -BB induced a dramatic increase in both gastric fibroblast proliferation and closure of wounded cell monolayers, whereas these activities were inhibited by both transforming growth factor (TGF) -beta1 and prostaglandin E1. Basal activities in unstimulated gastric fibroblasts were lower than those obtained in skin fibroblasts. Conditioned medium stimulated fibroblast proliferation and wound repair activity, which was inhibited by the addition of suramin, and was partially dependent on the presence of PDGF-like factor. PDGF is a major, autocrine promotor of human gastric fibroblast-dependent wound repair activities, which are inhibited by prostaglandins and TGF-beta. These findings might be important for future therapeutic ulcer healing approaches.

Adult↗
PubMed1998

Effect of growth factors and prostaglandin E2 on restitution and proliferation of rabbit esophageal epithelial cells.

Factors and mechanisms involved in esophageal mucosal injury and repair are not well known. The aim of this study was to assess the effects of growth factors and prostaglandins on esophageal mucosal cell repair activities. Rabbit esophageal cells were isolated, cultured, and exposed to different growth factors and prostaglandin E2. Subconfluent cell cultures were used to study proliferative responses determined by [3H]thymidine incorporation into DNA. Restitution was studied in confluent monolayers wounded by mechanical denudation. Restitution was the main mechanism involved in wound repair within the first 24 hr. HGF, IGF-I, and EGF dose-dependently stimulated cell proliferation but did not affect restitution. TGF-beta1 inhibited both proliferation and restitution while PDGF-BB and prostaglandin E2 had no effect. Esophageal epithelial cell restitution and proliferation are affected by growth factors. HGF, IGF-I, EGF (stimulation), and TGF-beta1 (inhibition) are major growth factors affecting in vitro esophageal wound repair activities, which, unlike those of other areas of the digestive tract, are not affected by prostaglandins.

Animals↗
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↗
PubMed1998

Collagen secretion by human gastric and skin fibroblasts: implications for ulcer healing.

Fibroblasts (FIB) play an important role in the wound-healing process. It is not known whether human skin and gastric FIB show different responses to regulatory compounds. In this study, we have examined the collagen production by these FIB after different stimuli. In vitro release of collagen into the medium by steady-state confluent human FIB cultures was assessed over a 24-hour period by 3H-proline incorporation into collageneous protein. Serum and epidermal growth factor increased collagen secretion in both types of FIB, but gastric FIB produced less collagen than skin FIB. Prostaglandin E1 inhibited collagen production in both types of FIB, but nonsteroidal anti-inflammatory drugs and interleukin-1beta, a cytokine involved in the wound-healing process, had opposite effects on gastric and skin FIB. The effects of lipoxygenase metabolites on collagen secretion was small, but different in both types of FIB. We conclude that, when compared to skin FIB, human gastric FIB produce less collagen and show pronounced different responses to different agents, which might be relevant to explain (in part) their clinical effects on ulcer healing. These data provide new insights into the wound-healing process.

Adult↗
PubMed1997

Prostaglandin E2 is the major arachidonic acid metabolite secreted by esophageal mucosal cells in rabbits.

Unlike gastric mucosa, it has been considered that lipoxygenase metabolites protect the esophageal mucosa and that prostaglandins are only secreted in the presence of esophageal inflammation. The aim of this study was to determine the profile of arachidonic acid metabolites and their response to regulatory compounds in rabbit esophageal mucosal cells in culture. Eicosanoids secreted into the medium were extracted and identified by HPLC and RIA. Esophageal mucosal cells in culture metabolized arachidonic acid mainly through the cycloxygenase pathway and PGE2 was the major arachidonic acid metabolite secreted. The addition of IL-1 beta and A23187 (calcium ionophore) stimulated PGE2 synthesis. In basal conditions neither leukotrienes nor HETEs were detected. However, the addition of the NDGA induced the secretion of lipoxygenase metabolites identified as 12-15 HETEs. In conclusion, rabbit esophageal epithelial cells in culture metabolize arachidonic acid via both cycloxygenase and lipoxygenase pathways. In our system, PGE2 was the main arachidonic acid metabolite.

6-Ketoprostaglandin F1 alpha↗