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Biomedical subjects

A Lanas

Publications and source records attributed to A Lanas.

At least 37 records · Page 2Linked to original sources
PubMed2003

COX-2 inhibition in esophagitis, Barrett's esophagus and esophageal cancer.

There is extensive evidence that cyclooxygenase-2 (COX-2) plays a significant role in the process of carcinogenesis in different tumors. Although most of these evidences derive from studies in colorectal cancer, data obtained from recent studies strongly suggest that COX-2 might play an important role in the neoplastic transformation of esophageal epithelium. NSAIDs use is associated with a reduction of the risk of developing esophageal cancer, including adenocarcinoma. Up-regulation of COX-2 has been reported in different stages of the carcinogenic sequence leading to esophageal adenocarcinoma. Treatment with selective COX-2 inhibitors has been shown to reduce the damage induced by acid and pepsin in the esophageal mucosa of rabbits, the incidence of tumors in an animal model of esophageal adenocarcinoma and to decrease proliferation and induce apoptosis in both Barrett's epithelial and adenocarcinoma cells. The first clinical study has shown that selective inhibition of COX-2 is followed by a significant decrease of cell proliferation in human Barrett's metaplasia. Clinical trials have begun in order to assess the efficacy of selective COX-2 inhibitors to prevent the progression of Barrett's esophagus to adenocarcinoma. Bile salts and acid are likely to early induce COX-2 in this sequence, although other factors, such as proinflammatory cytokines, inducible nitric oxide synthase and growth factors such as TGF-beta, are potential COX-2 inducers in the esophagus. Further studies are necessary in order to better understand factors involved in COX-2 up-regulation and mechanisms of COX-2 associated tumorigenesis in the esophagus.

Animals↗
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↗
PubMed2002

Risk of upper gastrointestinal bleeding in patients taking low-dose aspirin for the prevention of cardiovascular diseases.

BACKGROUND: Most patients with vascular-occlusive diseases benefit from low-dose aspirin (75-325 mg/day). However, they have an increased risk of upper gastrointestinal bleeding (UGIB). AIMS: To analyse the incidence and factors influencing the occurrence of UGIB in patients taking low-dose aspirin for the prevention of cardiovascular diseases outside clinical trials. METHODS: We studied 903 consecutive patients discharged on low-dose aspirin from the Cardiology Department of a general hospital. Data were collected from medical charts and structured telephone interviews. RESULTS: Forty-one patients (4.5%) presented with UGIB requiring hospitalization during follow-up (45 +/- 22 months). The incidence of UGIB was uniform during follow-up (1.2 UGIB per 100 patient years). Multivariate analysis showed that a history of peptic ulcer or UGIB [risk ratio: 3.1, 95% CI: (1.5-6.5)] and aspirin dose (per 100 mg/day) [1.8 (1.5-2.9)] was associated with higher risk of UGIB. On the other hand, antisecretory [0.22 (0.07-0.75)] and nitrovasodilator drugs [0.73 (0.55-0.96)] were associated with a decreased risk. CONCLUSIONS: Cardiovascular patients on long-term low-dose aspirin have a stable risk of major UGIB, which is higher than published controlled clinical trials. Antisecretory and nitrovasodilator drugs protect from UGIB, whereas previous peptic ulcer or UGIB and higher doses of aspirin increase the risk.

Aged↗
PubMed2002

Helicobacter pylori stimulates pepsinogen secretion from isolated human peptic cells.

BACKGROUND: Different acid and peptic related gastroduodenal diseases are associated with both increased gastric secretion and Helicobacter pylori infection. Patients with H pylori associated gastritis or duodenal ulcer have increased serum pepsinogen levels which decrease after eradication. The mechanisms of H pylori induced gastric mucosal damage are not completely understood. AIM: To determine the effects of H pylori on pepsinogen secretion from isolated human peptic cells. METHODS: Dispersed human peptic cells were prepared from endoscopically obtained biopsy specimens after collagenase digestion, mechanical disruption, and density gradient centrifugation. H pylori was obtained from gastric biopsies (antrum and body), and cultured in non-selective and selective media. Isolates of H pylori were used at different concentrations (1 - 20 x 10(6) colony forming units (cfu)). RESULTS: H pylori (10(6) - 2 x 10(7) cfu) increased basal pepsinogen secretion in a concentration dependent manner. This stimulus was not observed with Escherichia coli. The increased secretion was in addition to that observed with 0.1 mM histamine and 0.1 mM dibutyryl-cyclic adenosine monophosphate. However, H pylori did not affect either carbamylcholine (0.1-10 microM) or cholecystokinin (1 microM) stimulated pepsinogen secretion. Addition of the nitric oxide synthase inhibitor N(w)-monomethyl-L-arginine (1 mM) inhibited H pylori induced cGMP generation and pepsinogen secretion, which were also reduced in the absence of extracellular calcium. H pylori induced pepsinogen secretion was not affected by the absence/presence of the cagA gene. CONCLUSIONS: H pylori increases pepsinogen secretion from human peptic cells through a calcium and nitric oxide mediated intracellular pathway. This effect is independent of the H pylori virulent cagA gene, and may be a mechanism of H pylori induced gastric mucosal damage.

Adult↗
PubMed2002

Clinical experience with cyclooxygenase-2 inhibitors.

Rheumatoid arthritis (RA) and osteoarthritis (OA) are chronic conditions requiring long-term therapy for pain relief. Currently prescribed non-steroidal anti-inflammatory drugs (NSAIDs) provide symptomatic efficacy, but are frequently associated with gastrointestinal (GI) toxicities such as dyspepsia and ulcerations. In a small but significant number of cases, complications including perforations and massive bleeding develop and these may be fatal. A desirable therapeutic strategy would maintain efficacy while minimizing gastric intolerance. Two potential approaches have been suggested: (i) administration of NSAIDs in combination with gastroprotective compounds; or (ii) administration of potentially safer anti-inflammatory compounds which act via selective inhibition of cyclooxygenase-2 (COX-2). The selective COX-2 inhibitors rofecoxib and celecoxib consistently demonstrate efficacy comparable to conventional NSAIDs in patients with RA and OA, but have a significantly reduced propensity to cause GI toxicity. In many cases, the gastric effects of therapeutically active doses of COX-2 inhibitors are indistinguishable from placebo. The safety benefits of COX-2 inhibitors given alone appear similar to combined therapy with conventional NSAIDs and gastroprotective agents. Findings warrant the consideration of COX-2 inhibitors as first-line therapy in patients requiring long-term pain relief.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2001

[Helicobacter pylori and immunogenetic factors of the host: relevance of the HLADQA1 *0102 and *0301 alleles in peptic ulcer].

AIM: To investigate the potential contribution of the *0102 and *0301 alleles of the HLADQA1 gene in Helicobacter pylori infection and peptic ulcer disease in a Spanish Caucasian population. PATIENTS AND METHODS: We studied 163 patients with peptic ulcer (117 duodenal ulcers and 46 gastric ulcers; 111 with recent upper gastrointestinal hemorrhage) and 90 controls. The *0102 and *0301 alleles of the HLADQA1 gene were typed by polymerase chain reaction using genomic DNA. H. pylori infection were determined by breath test and/or serology. The cytotoxins CagA and VacA were investigated using serology (Western-blot) in 98 patients and 48 controls with H. pylori infection. RESULTS: H. pylori infection was found in 94.6% of patients with duodenal ulcer, in 84.4% of those with gastric ulcer and in 67.4% of controls (p < 0.001). The distribution of the *0102 allele of the HLADQA1 gene was similar in patients (31.9%) and in controls (36.7%). The *0301 was more frequent in patients with gastric ulcer (32.6%) than in those with duodenal ulcer (16.2%) (p < 0.05) but no differences were found on comparison with the control group (24.4%). No differences were found when the groups were analyzed according to H. pylori infection, CagA- and VacA-positive strains, consumption of non-steroidal antiinflammatory drugs or previous history of ulcer or hemorrhage. CONCLUSION: The *0102 and *0301 alleles of the HLADQA1 gene did not alter susceptibility to H. pylori infection or the evolution of peptic ulcer disease in a Caucasian population in Spain.

Alleles↗
PubMed2001

Cyclo-oxygenase-1/cyclo-oxygenase-2 non selective non-steroidal anti-inflammatory drugs: epidemiology of gastrointestinal events.

Non-steroidal anti-inflammatory drug use is associated with gastrointestinal side-effects including complications such as bleeding and perforation, which occur in 1-2% of patients after 6-12 months of therapy. A high level of non-prescription non-steroidal anti-inflammatory drug use is observed among those presenting complications. More common side-effects are symptomatic gastro-duodenal ulcers (annual incidence of 4-8%) and dyspepsia (25-50%). Low-dose aspirin use is also associated with an increased risk of upper gastrointestinal bleeding, but the increase is about 3 times lower than that found with common non-steroidal anti-inflammatory drugs. Recent studies suggest that the risk of bleeding in patients taking preferential cyclooxygenase-II inhibitors (e.g. nimesulide) is similar to that in patients taking non-selective non-steroidal anti-inflammatory drugs. Epidemiological studies have also shown that nitric oxide donors and antisecretory drugs reduce the risk of upper gastrointestinal bleeding both in non-steroidal anti-inflammatory drug and low-dose aspirin users.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2001

Superoxide anion and nitric oxide in high-grade esophagitis induced by acid and pepsin in rabbits.

It has been proposed that free radicals are involved in the pathogenesis of esophageal mucosal damage induced by acid and pepsin. Recent data have suggested that nitric oxide (NO) is involved in the mucosal defense of the esophagus and that superoxide anion plays a minor role in low-grade esophagitis. To study the role and potential interaction of NO and superoxide anion in an experimental model of high-grade esophagitis, acidified pepsin was perfused (45 min/12 hr) for five days in rabbits with different agents to modulate the generation of these radicals. Measurements included both macroscopic and microscopic mucosal damage, superoxide anion generation, NO synthase mucosal activity, and peroxynitrite formation. High-grade esophagitis was associated with mucosal superoxide anion generation. Treatment with exogenous superoxide dismutase completely prevented mucosal damage. The perfusion of acidified pepsin in the lumen of the esophagus was initially associated with increased NO synthase mucosal activity but decreased with the progression of damage. Generation of peroxynitrites was present in those cases with severe damage. Treatment with NO-modifying agents did not induce consistent modification of mucosal damage. It is concluded that superoxide anion is involved in the induction of high-grade esophagitis and that it interacts with nitric oxide to generate peroxynitrite radicals in this model. Superoxide dismutase but not NO-donor-modifying agents might have a therapeutic role in preventing severe esophageal mucosal damage induced by acid and pepsin.

Animals↗
PubMed2001

TNF and LTA gene polymorphisms reveal different risk in gastric and duodenal ulcer patients.

A small proportion of patients infected with Helicobacter pylori or using non-steroidal anti-inflammatory drugs (NSAIDs) develops peptic ulcer disease. Since family studies have shown the importance of the genetic background of the host in the development of gastric and duodenal ulcers, immunogenetic factors involved in the regulation of inflammation deserve further study. Polymorphisms in the genes encoding tumour necrosis factor (TNF) and lymphotoxin-alpha (LTA) have been shown to contribute to the severity of infectious disease. Our aim was to study four bi-allelic polymorphisms in the TNF and LTA genes, which occur as five haplotypes, in patients with peptic ulcer disease. A total of 130 patients with duodenal ulcer, 50 with gastric ulcer and 102 ethnically-matched Spanish Caucasian healthy controls were studied. H. pylori infection was determined by invasive and non-invasive tests. Odds ratios were obtained by logistic regression analysis. H. pylori was detected in 91.8% of peptic ulcer patients and in 73.3% of controls (P < 0.001). Patients with gastric ulcer had a lower frequency of the TNF-308 allele 2 and a higher frequency of the LTANcoI 2.2 genotype when compared with duodenal ulcer patients (P < 0.01 and P = 0.03, respectively). Carriers of haplotype TNF-I were more frequent in gastric ulcer patients (49%) than in controls (28%) (P < 0.05) and the haplotype TNF-E was significantly more frequent in duodenal ulcers than in gastric ulcers (27% vs 8.2%; P < 0.01). Logistic regression analysis identified haplotype TNF-I carrier status as an independent risk factor for peptic ulceration in H. pylori-infected patients (OR: 4.2; 95%CI: 1.7-10.2). These results suggest that TNF and LTA gene polymorphisms are related to the development of gastric and duodenal ulcer and may determine disease outcome in H. pylori infection.

Adolescent↗
PubMed2001

The polymorphic IL-1B and IL-1RN genes in the aetiopathogenesis of peptic ulcer.

Besides environmental factors, the genetic background of an individual may contribute to the development and final outcome of peptic ulcer disease. Interleukin-1beta (IL-1beta) and the interleukin-1 receptor antagonist (IL-1ra) are cytokines that play a key role in modulating the inflammatory response in the gastrointestinal mucosa. This study aimed to investigate whether polymorphisms in the IL-1B and IL-RN genes are involved in the susceptibility to and final outcome of peptic ulcer disease. DNA from 179 unrelated Spanish Caucasian patients with peptic ulcer diseases and 99 ethnically matched healthy controls was typed for the TaqI polymorphism at position + 3954 in the IL-1B gene and the variable number of tandem repeats polymorphism in intron 2 of the IL-1RN gene. The determination of Helicobacter pylori status and non-steroidal anti-inflammatory drug (NSAIDs) use was studied in all patients and in controls. H. pylori infection and NSAID use were more frequent in ulcer patients than in controls. There were no significant differences in carriage rate, genotype and allele frequencies of the IL-1RN and the IL-1B(+3954) gene polymorphisms between peptic ulcer patients and controls. However, a strong allelic association between IL-1B and IL-1RN genes was found in duodenal ulcer patients (P < 0.0006). Logistic regression identified H. pylori infection and NSAIDs use as independent risk factors for peptic ulcer diseases whereas the simultaneous carriage of IL-1B(+3954) allele 2 and IL-1RN allele 2 was associated with reduced risk for duodenal ulcer disease (OR: 0.37, 95% CI = 0.14-0.9). Our data suggest that IL-1B and IL-1RN genes in addition to bacterial and environmental factors play a key role in determining the final outcome of peptic ulcer disease.

Adult↗
PubMed2001

Diaphragm disease of the small bowel: a case without apparent nonsteroidal antiinflammatory drug use.

BACKGROUND: Diaphragm-like strictures of the small bowel are an infrequent complication of the treatment of patients with nonsteroidal antiinflammatory drugs (NSAIDs). STUDY: We report a patient with this condition in whom the use of NSAIDs was ruled out by both clinical history and objective blood testing of current aspirin use. RESULTS: He reported a history of recurrent episodes of colic abdominal pain during the past 25 years; he underwent three surgical operations for this condition. Before these symptoms, he had an undefined abdominal process with diarrhea, weight loss, and diffuse edema, which resolved spontaneously without reaching a diagnosis. CONCLUSIONS: We suggest that diaphragm-like strictures might be developed as a nonspecific response to different damaging insults to the intestine and are not necessarily associated with NSAID use.

Constriction, Pathologic↗
PubMed2001

Nonsteroidal anti-inflammatory drugs, low-dose aspirin, and potential ways of reducing the risk of complications.

Use of nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with an annual incidence of 1-2% of gastrointestinal (GI) complications, which may be fatal in some cases. Low-dose aspirin is also associated with an increased risk of upper GI bleeding, but the increase is about three times lower than that found with common NSAIDs. Misoprostol (600-800 microg/day) reduces the incidence of complications in non-aspirin NSAID users. Co-therapy with antisecretory drugs (proton pump inhibitors, PPIs) also reduces the risk of GI bleeding in high-risk patients taking NSAIDs and/or low-dose aspirin. Another way of reducing the incidence of GI complications is to use the highly selective cyclo-oxygenase 2 (COX-2) inhibitors. The GI safety of nitric oxide NSAIDs (NO-NSAIDs) has been demonstrated extensively in experimental conditions and preliminary clinical studies. Epidemiological studies have also shown that nitric oxide donor drugs reduce the risk of upper GI bleeding, which might be important in patients receiving low-dose aspirin.

Animals↗
PubMed2001

Gastroesophageal reflux disease (GERD): current agents and future perspective.

The objectives of medical treatment of patients with gastroesophageal reflux disease (GERD) are relief of symptoms and healing of esophagitis, which can be achieved, at least in part, by drugs which suppress acid secretion. In patients with GERD symptoms and/or mild esophagitis, the best and most cost-effective therapeutic strategy is to start with a proton pump inhibitor with subsequent trial of step down of the intensity of therapy (e.g. H2-receptor antagonists). In patients with moderate or severe esophagitis, proton pump inhibitors are the mainstay of treatment and the most effective in preventing symptoms and esophagitis. In patients with mild disease, the recurrence of symptoms is less frequent and many patients may not need continuous maintenance therapy or may require treatment with either low dose proton pump inhibitors, H2-receptor antagonists or cisapride only. H. pylori eradication might be needed in GERD patients on long-term treatment with proton pump inhibitors, but the benefit of this strategy has not yet been adequately demonstrated. Antireflux surgery is a maintenance option for the young patient on long-term medical therapy. Improved medical therapy for GERD might depend on future agents with different therapeutic targets, including GABA inhibitors and nitric oxide modulating drugs in the control of the lower sphincter esophagus and in motility disorders, free radical scavengers in the prevention of mucosal damage and COX-2 specific inhibitors in the prevention of the progression of Barret's esophagus to adenocarcinoma. Finally, the modulation of some growth factors might have a potential role in delayed esophageal ulcer healing, refractory esophagitis and in Barrett's esophagus.

Animals↗
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

Nitric oxide and superoxide anion in low-grade esophagitis induced by acid and pepsin in rabbits.

It has been suggested that free radicals are involved in esophagitis. To study the role and potential interaction of superoxide anion and nitric oxide (NO) in low-grade esophagitis, we perfused acidified pepsin (30 min every 12 hr) for seven days in rabbits treated with different agents to modulate the generation of these radicals. Measurements included macroscopic and microscopic damage, superoxide anion generation, mucosal nitric oxide synthase activity, and peroxynitrite formation. Low-grade esophagitis was associated with increased nitric oxide synthase mucosal activity and mucosal damage was dose-dependently increased by treatment with the NO synthase inhibitor NG-nitro-L-arginine. Superoxide anion was scarcely generated in the mucosa, but this was not accompanied by any change in the activity of mucosal superoxide dismutase. Treatment with superoxide dismutase did not improve mucosal damage. Generation of peroxynitrites was not detected. In conclusion, nitric oxide is involved in the mucosal defense of the esophagus against acid- and pepsin-induced damage. Superoxide anion generation seems irrelevant in the induction of low-grade esophagitis and not sufficient to interact with nitric oxide to generate measurable mucosal peroxynitrite radicals.

Animals↗
PubMed2000

Omeprazole does not interfere with the antiplatelet effect of low-dose aspirin in man.

BACKGROUND: Experimental studies have shown that omeprazole and other anti-inflammatory agents compromise the therapeutic activity of nonsteroidal anti-inflammatory drugs and aspirin in rats. It is not known whether this effect will occur in humans. Our aim was to determine whether omeprazole affects the antiplatelet effects of low-dose aspirin in humans. METHODS: Platelet lumiaggregation, skin bleeding time, plasma levels of aspirin and salicylic acid, and serum gastrin levels were determined in 14 healthy men before and after the ingestion of 125 mg aspirin with or without previous treatment with 20 mg/day of omeprazole for 4 days before testing. RESULTS: Omeprazole increased serum gastrin levels from 64 (median; range, 52-91) pg/ml to 80.5 (median; range, 56-455) pg/ml (P < 0.05) but did not significantly affect the plasma concentration of aspirin or salicylic acid. Aspirin increased skin bleeding time in all subjects, and the increase was similar with and without previous omeprazole treatment. Aspirin inhibited platelet aggregation in response to both collagen and arachidonic acid regardless of omeprazole treatment. CONCLUSION: A single dose of 20 mg omeprazole daily does not interfere with the biologic activity of 125 mg aspirin on platelets in humans.

Adult↗