bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pioglitazone, a specific PPAR‐γ ligand, inhibits aspirin‐induced gastric mucosal injury in rats
Authors: Naito Y. , Takagi T. , Matsuyama K. , Yoshida N. , Yoshikawa T. 
Published: March 2003

Background:Neutrophils activation and tumour necrosis factor‐α (TNF‐α) induction play a critical role in aspirin‐induced gastric mucosal injury. Peroxisome proliferator‐activated receptor‐γ (PPAR‐γ), a member of the nuclear hormone receptor superfamily, has recently been implicated as a regulator of inflammatory responses. The aim of the present study was to determine whether pioglitazone, a specific PPAR‐γ ligand, can ameliorate aspirin‐induced gastric mucosal injury in rats, and whether the agent can inhibit the increase in neutrophil accumulation associated with TNF‐α expression.Methods:Aspirin‐induced injury was produced by the intragastric administration of aspirin (200 mg/kg) and HCl (0.15 N, 8.0 mL/kg). Pioglitazone was given to the rats by gastric intubation 1 h before the aspirin administration. Thiobarbituric acid‐reactive substances and tissue‐associated myeloperoxidase activity were measured in gastric mucosa as indices of lipid peroxidation and neutrophil infiltration. The gastric concentration of TNF‐α and the expression of TNF‐α mRNA was determined by ELISA and reverse transcriptase‐polymerase chain reaction.Results:The intragastric administration of acidified aspirin induced hyperemia and haemorrhagic erosions in rat stomachs. The increase in the total gastric erosive area after aspirin administration was significantly inhibited by treatment with pioglitazone in a dose‐dependent manner. The increases in thiobarbituric acid‐reactive substances and myeloperoxidase activity after aspirin administration were both significantly inhibited by pre‐treatment with pioglitazone (10 mg/kg). The gastric content of TNF‐α increased and the expression of TNF‐α mRNA was up‐regulated after aspirin treatment. However, the peak TNF‐α mRNA expression 1 h after aspirin administration was inhibited by pioglitazone.Conclusion:Based on these data, the beneficial effects of pioglitazone on aspirin‐induced gastric mucosal injury may be attributed to its anti‐inflammatory properties.
Guidelines for adults on self‐medication for the treatment of acute diarrhoea
Authors: Wingate D. , Phillips S. F. , Lewis S. J. , Malagelada J.‐R. , Speelman P. , Steffen R. , Tytgat G. N. J. 
Published: March 2003

Acute uncomplicated diarrhoea is commonly treated by self‐medication. Guidelines for treatment exist, but are inconsistent, sometimes contradictory, and often owe more to dogma than evidence. Anad hocmultidisciplinary group has reviewed the literature to determine best practice.In general it is recognized that treatment of acute episodes relieves discomfort and social dysfunction. There is no evidence that it prolongs the illness. Self‐medication in otherwise healthy adults is safe.Oral loperamide is the treatment of choice. Older anti‐diarrhoeal drugs are also effective in the relief of symptoms but carry the risk of unwanted adverse effects. Oral rehydration solutions do not relieve diarrhoea, and confer no added benefit for adults who can maintain their fluid intake. Probiotic agents are, at present, limited in efficacy and availability. Antimicrobial drugs, available without prescription in some countries, are not generally appropriate for self‐medication, except for travellers on the basis of medical advice prior to departure.Medical intervention is recommended for the management of acute diarrhoea in the frail, the elderly (> 75 years), persons with concurrent chronic disease, and children. Medical intervention is also required when there is no abatement of the symptoms after 48 h, or when there is evidence of deterioration such as dehydration, abdominal distension, or the onset of dysentery (pyrexia > 38.5 °C and/or bloody stools).
Influence of risk factors on endoscopic and clinical ulcers in patients taking rofecoxib or ibuprofen in two randomized controlled trials
Authors: Hawkey C. J. , Laine L. , Harper S. E. , Quan H. U. I. , Bolognese J. A. , Mortensen E. ,   For The Rofecoxib Osteoarthritis Endoscopy Multinational Study Group
Published: March 2003

Background:Highly selective inhibitors of the inducible cyclooxygenase‐2 enzyme (coxibs) have been associated with less gastrotoxicity than nonselective NSAIDs in clinical studies.Aim:To evaluate the influence of risk factors for NSAID‐induced gastrotoxicity on endoscopic and clinical ulcers in patients taking rofecoxib or ibuprofen.Methods:We analysed pooled data from two identical double‐blind, randomized, 12‐week endoscopy studies which compared the gastroduodenal toxicity of placebo (n=371), rofecoxib 25 mg (n=390), rofecoxib 50 mg (n=379), and ibuprofen 2400 mg daily (n=376) in patients with osteoarthritis. The potential risk factors evaluated were: age (< 65, ≥ 65 years), sex, race (white, nonwhite), Helicobacter pylori status, presence of gastroduodenal erosions at baseline, a history of upper gastrointestinal disease, prior NSAID use within 30 days of study entry, and smoking. We also evaluated these factors for possible association with the development of clinically‐evident gastrointestinal perforations, ulcers or bleeds over 12 weeks.Results:Across all treatment groups, the likelihood of detecting endoscopic ulcers, or of clinical presentation with a bleed, over 12 weeks was increased approximately 4–5‐fold in patients with previous upper gastrointestinal disease (relative risk [95% confidence interval] of 4.2 [2.5, 7.1] for endoscopic ulcers; 3.8 [1.4, 10.6] for bleeds), or those with gastroduodenal erosions at baseline endoscopy (relative risk of 4.4 [2.6, 7.5] for endoscopic ulcers; 5.0 [1.9, 13.5] for bleeds). H. pylori infection did not increase the risk of endoscopic ulcers or bleeds (relative risk of 1.1 [0.8, 1.6] for endoscopic ulcers; 0.3 [0.1, 0.9] for bleeds). The risk factor sub‐group effects were constant across all treatment groups, and the significantly higher incidence of ulcers with ibuprofen as compared to rofecoxib and placebo was maintained in all risk factor subgroups.Conclusions:Gastroduodenal erosions at baseline and a clinical history of upper gastrointestinal disease, but not H. pylori colonization, increased the risk for endoscopically‐detected ulcers and clinical bleeds. Rofecoxib did not magnify the risk in any of the patient subgroups studied.
In vivo and in vitro permeability in coeliac disease
Authors: Vogelsang H. , Schwarzenhofer M. , Steiner B. , Wyatt J. , Oberhuber G. 
Published: March 2003

Background:An increased permeability to sugars is found in the intestine of untreated patients with coeliac disease after oral ingestion.Aim:To test whether in vitro permeability resembles in vivo permeability tests and whether an in vitro gliadin gluten challenge could be performed by an in vitro permeability test.Methods:We measured in vivo (urinary excretion after sucrose–lactulose–mannitol ingestion) and in vitro permeability (by mini‐Ussing chambers) in 25 healthy controls, 12 relatives of coeliac disease patients, 19 treated, eight partly treated and 16 untreated patients with coeliac disease.Results: In vivo sugar permeability was increased in nearly all coeliac patients. Additionally, in vitro permeability to lactulose (P=0.0007), mannitol (P=0.004) and sucrose (P=0.042) was higher in untreated patients with coeliac disease. It correlated with in vivo permeability (sucrose τ=0.61, P=0.006; lactulose τ=0.41, P < 0.0001; mannitol τ=– 0.56, P=0.62) and was dependent on mucosal damage. An in vitro gliadin challenge over 24 h could not significantly change in vitro permeability in treated patients with coeliac disease.Conclusions:An in vitro permeability test capable of measuring elevated permeability in coeliac mucosa was described, but this test cannot replace oral gluten challenge by in vitro gliadin incubation.
Apoptosis and proliferation in Helicobacter pylori‐associated gastric intestinal metaplasia
Authors: Leung W. K. , Yu J. , To K. F. , Go M. Y. Y. , Ma P. K. , Chan F. K. L. , Sung J. J. Y. 
Published: March 2003

Background:Imbalance between apoptosis and proliferation may be one of the mechanisms underlying H. pylori associated gastric carcinogenesis.Aim:To examine the cell kinetics of gastric intestinal metaplasia and the effect of H. pylori eradication.Methods:Endoscopic gastric biopsies were obtained from 100 H. pylori‐infected patients. Apoptosis was determined by triphosphate nick‐end labelling (TUNEL) and apoptotic nuclei counting, whereas proliferation was assessed by Ki67 immunostaining. Gastric biopsies were repeated in a sub‐group of intestinal metaplasia patients after H. pylori eradication.Results:Antral apoptotic index was significantly lower in intestinal metaplasia than in non‐intestinal metaplasia (0.19% vs. 0.51%; P < 0.0001) whereas the level of proliferation was comparable (28% vs. 22%, P=0.15). Serial antral biopsies taken from 14 intestinal metaplasia patients before and 1 year after H. pylori eradication showed a significant drop in proliferation in both intestinal metaplasia (50% vs. 12%, P < 0.001) and non‐intestinal metaplasia area (47% vs. 9%, P < 0.001). A similar fall in apoptosis was detected in non‐metaplastic region (0.58% vs. 0.38%, P < 0.001) but not in intestinal metaplasia (0.24% vs. 0.27%, P=0.56), resulting in a significant increase in the apoptosis/proliferation ratio (0.005–0.021; P=0.03).Conclusions:Dysregulation in apoptosis control of gastric intestinal metaplasia may contribute to gastric carcinogenesis, which may be retarded by clearance of H. pylori.
Efficacy of triple therapy with rabeprazole for Helicobacter pylori infection and CYP2C19 genetic polymorphism
Authors: Hokari K. , Sugiyama T. , Kato M. , Saito M. , Miyagishima T. , Kudo M. , Nishikawa K. , Ishizuka J. , Komatsu Y. , Mizushima T. , Kagaya H. , Hige S. , Takeda H. , Asaka M. 
Published: March 2003

Background:Rabeprazole is a new, potent, proton pump inhibitor. The metabolism of rabeprazole is less dependent on CYP2C19 genetic polymorphism.Methods:A total of 102 Helicobacter pylori‐positive patients with gastric ulcer were randomly allocated to three groups: rabeprazole 10 mg (RAC10), rabeprazole 20 mg (RAC20) or rabeprazole 40 mg (RAC40) plus amoxicillin 750 mg and clarithromycin 200 mg twice daily for 7 days. CYP2C19 genotype was determined by the polymerase chain reaction‐restriction fragment length polymorphism method.Results:All‐patients‐treated‐based eradication rates in patients treated with RAC10, RAC20 and RAC40 were 83%, 77% and 90%, respectively, and per protocol‐based eradication rates were 83%, 80% and 90%, respectively. The eradication rates in the three groups were not significantly different. There was also no significant difference between the all‐patients‐treated‐based eradication rate in CYP2C19 extensive metabolizers and that in poor metabolizers (86% vs. 77%). Adverse events were 12% in extensive metabolizers and 23% in poor metabolizers, and the difference in these incidence rates was also not statistically significant.Conclusions:Triple therapy with 10 mg of rabeprazole combined with amoxicillin/clarithromycin is effective for Japanese patients with H. pylori infection, and the H. pylori eradication rate is not affected by CYP2C19 genetic polymorphism.
Effects of CYP2C19 genotypic differences in the metabolism of omeprazole and rabeprazole on intragastric pH
Authors: Shirai N. , Furuta T. , Moriyama Y. , Okochi H. , Kobayashi K. , Takashima M. , Xiao F. , Kosuge K. , Nakagawa K. , Hanai H. , Chiba K. , Ohashi K. , Ishizaki T. 
Published: March 2003

Background:Omeprazole is mainly metabolized in the liver by CYP2C19, a genetically determined enzyme, whereas rabeprazole is mainly reduced non‐enzymatically and partially metabolized by CYP2C19. The therapeutic effects of rabeprazole are therefore assumed to be less affected by an individual’s CYP2C19 status.Aim:To investigate the acid inhibitory effects and plasma levels of omeprazole and rabeprazole with reference to different CYP2C19 genotypes.Methods:Fifteen healthy volunteers took a daily dose of 20 mg of omeprazole or rabeprazole for 8 days. On post‐dose days 1 and 8, 24‐h profiles of intragastric pH were recorded and plasma concentrations of omeprazole, rabeprazole and their metabolites were determined.Results:After single and repeated doses of omeprazole, the intragastric pH values and plasma concentrations of omeprazole and its metabolites were significantly dependent on the CYP2C19 genotype. Significant differences in the same kinetic and dynamic parameters were also observed after single doses of rabeprazole. Although the plasma levels of rabeprazole differed among the different CYP2C19 genotype groups after repeated doses, no significant differences in intragastric pH values were observed.Conclusions:The acid inhibitory effects of omeprazole and rabeprazole are significantly dependent on the CYP2C19 genotype status, as well as on their intrinsic pharmacokinetic and pharmacodynamic characteristics and dosing schemes.
Lansoprazole vs. omeprazole for gastro‐oesophageal reflux disease: a pH‐metric comparison
Authors: Frazzoni M. , De Micheli E. , Grisendi A. , Savarino V. 
Published: March 2003

Background:Lansoprazole and omeprazole are widely used proton pump inhibitors for the management of gastro‐oesophageal reflux. Normalization of oesophageal acid exposure is an important goal in the management of complicated and atypical gastro‐oesophageal reflux disease.Aim:To compare the efficacy of lansoprazole and omeprazole in the abolition of abnormal reflux as assessed by oesophageal pH monitoring.Methods:Seventy patients with complicated or atypical gastro‐oesophageal reflux disease were randomly assigned to receive 30 mg lansoprazole or 20 mg omeprazole once daily. Three to four weeks after the start of treatment, patients underwent oesophageal pH monitoring while on therapy. If the results were still abnormal, the proton pump inhibitor dosage was doubled and 24‐h pH‐metry was repeated after 20–30 days.Results:Thirty‐six patients were randomized to receive lansoprazole and 34 patients to receive omeprazole. Ten of the 36 (29%) patients treated with 30 mg lansoprazole once daily and 23 of the 34 (68%) patients treated with 20 mg omeprazole once daily had persistently abnormal reflux at oesophageal pH monitoring (P < 0.001). In all such cases, repeat pH monitoring after doubling the proton pump inhibitor dosage gave normal results.Conclusions:At the currently marketed dosages of lansoprazole and omeprazole, normalization of oesophageal acid exposure in patients is accomplished more easily with lansoprazole.
A double‐blind comparison of balsalazide, 6.75 g daily, and sulfasalazine, 3 g daily, in patients with newly diagnosed or relapsed active ulcerative colitis
Authors: Green J. R. B. , Mansfield J. C. , Gibson J. A. , Kerr G. D. , Thornton P. C. 
Published: March 2003

Background:Sulfasalazine is well established in the treatment of active ulcerative colitis. Intolerance to sulfasalazine, however, is a common problem. Balsalazide has been designed to deliver 5‐aminosalicylic acid to the colon without the poor tolerability of sulfasalazine.Aim:To compare the safety and efficacy of balsalazide, 6.75 g daily, with sulfasalazine, 3 g daily, in the treatment of active ulcerative colitis of all grades of severity.Methods:Balsalazide and sulfasalazine were compared in a multicentre, double‐blind, parallel group study over 12 weeks. Patients were stratified for disease severity and topical and/or oral steroids were co‐administered where clinically necessary.Results:Fifty‐seven patients were randomized: 28 to receive balsalazide and 29 to receive sulfasalazine. Significantly fewer patients withdrew from the balsalazide group due to adverse events (2/28 vs. 9/29, P=0.041). These data confirm that balsalazide is better tolerated than sulfasalazine. In patients able to tolerate the treatment, similar improvements were recorded in clinical, sigmoidoscopic and histological assessments in both treatment groups.Conclusions:This study confirms the better tolerability of balsalazide compared to sulfasalazine, and supports the use of balsalazide in ulcerative colitis of all grades of severity.
Lectins can reverse the distal intestinal atrophy associated with elemental diets in mice
Authors: Sasaki M. , Fitzgerald A. J. , Grant G. , Ghatei M. A. , Wright N. A. , Goodlad R. A. 
Published: March 2003

Background:Elemental diets cause intestinal atrophy and reduced intestinal integrity, which can lead to significant increases in intestinal permeability and bacterial translocation. Recently, several lectins have been shown to have trophic effects on the intestine.Aims:We examined the effects of concanavalin‐A and phytohaemagglutinin on cell proliferation and crypt fission throughout the intestine of mice fed on elemental diets.Methods:Mice were randomized to chow fed, elemental diet, elemental diet plus concanavalin‐A and elemental diet plus phytohaemagglutinin groups. Cell proliferation and crypt fission were estimated in microdissected crypts. Plasma gastrin and enteroglucagon levels were measured by radioimmunoassay.Results:Elemental diet feeding significantly decreased cell proliferation and crypt fission of the middle and distal small intestine and throughout the colon. Phytohaemagglutinin significantly increased the weight of the intestine, but concanavalin‐A had little effect. Cell proliferation in the small intestine was significantly increased by both lectins. However, in the stomach and colon, only phytohaemagglutinin increased proliferation. Crypt fission in the colon was dramatically increased by phytohaemagglutinin. Phytohaemagglutinin increased the plasma gastrin level, but not the enteroglucagon level.Conclusions:Lectins have significant trophic effects on the small intestine and colon of mice fed elemental diets, and these actions vary between different sites in the gastrointestinal tract.
Sulphide‐induced energy deficiency in colonic cells is prevented by glucose but not by butyrate
Authors: Hulin S. J. , Singh S. , Chapman M. A. S. , Allan A. , Langman M. J. S. , Eggo M. C. 
Published: March 2003

Background:In ulcerative colitis, hydrogen sulphide is postulated to impair colonocyte butyrate metabolism, leading to cellular energy deficiency and dysfunction.Aims:To determine the effects of sulphide exposure on butyrate metabolism and adenosine triphosphate levels of HT29 colonic epithelial cancer cells, and to establish whether energy deficiency can be prevented by increased butyrate concentrations or the presence of glucose.Methods:HT29 cells were maintained in medium containing 3 mM butyrate, 5 mM glucose, or both substrates. Oxidation rates were measured by 14CO2 release from 14C‐labelled substrates. Cellular adenosine triphosphate was assayed using the luciferin/luciferase chemiluminescent method. The effects of sulphide (0–5 mM) on substrate oxidation and adenosine triphosphate levels and of increasing butyrate concentration (0–30 mM) with sulphide were observed.Results:HT29 cells showed similar energy substrate usage to primary colonocyte cultures. Sulphide exposure inhibited butyrate oxidation and led to a reduction in cellular adenosine triphosphate. This fall was prevented by co‐incubation with glucose, but not by increasing concentrations of butyrate.Conclusions:HT29 cells utilize butyrate as an energy substrate and represent a useful in vitro model of the effects of sulphide on colonocytes. Sulphide inhibits butyrate oxidation and leads to demonstrable energy deficiency, prevented by the presence of glucose but not by increased butyrate concentrations.
Randomized, controlled trial of recombinant human interleukin‐11 in patients with active Crohn's disease
Authors: Sands B. E. , Winston B. D. , Salzberg B. , Safdi M. , Barish C. , Wruble L. , Wilkins R. , Shapiro M. , Schwertschlag U. S. ,   THE RHIL‐11 CROHN'S STUDY GROUP
Published: March 2003

Background:Interleukin‐11 is a mesenchymally derived cytokine with pleiotropic activities. A pilot study suggested therapeutic benefit of recombinant human interleukin‐11 (rhIL‐11) in patients with Crohn's disease.Aim:To determine the safety and preliminary estimate of efficacy of rhIL‐11 in treating active Crohn's disease.Methods:Patients with mild to moderately active Crohn's disease, defined as a Crohn's disease activity index (CDAI) ≥ 220 and ≤ 450, were enrolled in a multicentre trial. Stable doses of 5‐aminosalicylates, antibiotics, 6‐mercaptopurine or azathioprine were permitted with appropriate wash‐in periods. Oral, intravenous or rectally administered corticosteroids were not allowed. Patients were randomized to 6 weeks of subcutaneous injection with rhIL‐11 15 μg/kg or placebo weekly, or rhIL‐11 7.5 μg/kg or placebo twice weekly. The primary end‐point was per cent change in CDAI at week 6; the major secondary end‐point was the proportion of patients in remission, defined as a 100 point decrease in CDAI and absolute CDAI ≤ 150.Results:Baseline characteristics were similar among the 148 evaluated patients (49 placebo, 49 rhIL‐11 15 μg/kg once weekly, 50 rhIL‐11 7.5 μg/kg twice weekly). Treatment was well‐tolerated, with mild injection site reactions occurring more frequently among patients treated with rhIL‐11. Headache, oedema, and increased platelet count occurred significantly more often in the rhIL‐11 7.5 μg/kg twice weekly group, but not the 15 μg/kg once weekly group. There was a trend toward decreased mean per cent change in CDAI in the rhIL‐11 15 μg/kg once weekly group vs. placebo (–31.5% vs. – 18.5%, 95% confidence interval for the difference – 27.9–1.6%). A significantly greater proportion of patients receiving rhIL‐11 15 μg/kg once weekly achieved remission compared to placebo (36.7% vs. 16.3%, 95% confidence interval for the difference 3.4–37.4%; 16.4% for rhIL‐11 7.5 μg/kg, N.S.).Conclusions:Weekly subcutaneous injection with rhIL‐11 15 μg/kg is safe and effective in inducing remission in a subset of patients with active Crohn's disease.
Effect of acute and chronic levosulpiride administration on gastric tone and perception in functional dyspepsia
Authors: Distrutti E. , Fiorucci S. , Hauer S. K. , Pensi M. O. , Vanasia M. , Morelli A. 
Published: March 2003

Background:Altered visceral perception is common in functional dyspepsia (FD). Dopaminergic pathways control gastrointestinal motility, but whether they modulate visceral sensitivity is unknown.Aim:To investigate whether levosulpiride, a D2 antagonist, modulates gastric sensitivity and compliance in dyspeptic patients.Methods:Eight healthy subjects and 16 dyspeptic patients underwent graded gastric distensions using a tensostat. In dyspeptic patients the same isotonic distensions were repeated during either levosulpiride or saline administration. Eight FD patients were evaluated after 4‐week treatment with oral levosulpiride. Gastrointestinal symptoms were evaluated using a 100 mm visual analogue score. Perception was scored on a scale of 0 to 6.Results:Although healthy subjects and FD patients had similar gastric compliance, FD patients tolerated lower tension levels. At the same distending tension levels, levosulpiride decreased gastric compliance and perception score (14 ± 6% and 38 ± 10% change, respectively; P < 0.05 vs. saline) only in FD patients. Isotonic distensions exhibited very reproducible perception. Chronic levosulpiride administration significantly reduced dyspeptic symptoms and increased discomfort threshold.Conclusions:Compared with healthy subjects, FD patients show marked gastric hypersensitivity. In FD patients levosulpiride decreased the perception of gastric distension with an action unrelated to change of gastric tone. Chronic levosulpiride administration significantly ameliorates gastrointestinal symptoms and increases the discomfort threshold.