bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bioavailability of four ursodeoxycholic acid preparations
Authors: Williams  , Al‐Knawy  , Blanchard  
Published: March 2003

Background:Ursodeoxycholic acid (UDCA) is the drug of choice for treating primary biliary cirrhosis and dissolving cholesterol gallstones.Objectives:The objective of this study was to compare the bioavailability of four commercially available ursodeoxycholic acid formulations in standardized doses.Methods:Twenty‐four healthy subjects were studied in groups of four, and received each of the different UDCA preparations in random order, with a 1‐week washout or more in‐between. Serum UDCA levels were determined for a 6‐h period. The mean area under the curve (AUC), Cmax and Tmax were determined for each drug formulation, and the results compared. Dose proportionality was determined using the Canadian Ursofalk tablet using either 250 mg, 500 mg or 750 mg dosing. The intraparticipant variability was assessed by asking each participant to repeat the last drug that they took the second time, 1 week later.Results:The mean AUC was 68.99 μmol/1.6 h−1 for the USA UDCA tablet, 59.34 μmol/1.6 h−1 for the Canadian UDCA tablet, 55.55 μmol/1.6 h−1 for Ursolvan capsules, and 46.66 μmol/1.6 h−1 for Actigall capsules. The mean Cmax values were 24.29, 17.85, 16.63 and 413.32 nmol/mL, respectively. The mean Tmax was 1.82, 2.3, 2.79 and 3.39 h, respectively. Linear aggression analysis assessing the direct proportionality of AUC on the dose for the Canadian UDCA tablet gave an estimate of 0.063 + 0.0164 (standard error, P‐value=0.0117), e.g. if the dose increases from 250 mg to 500 mg, the serum ursodeoxycholic acid increases by 250 × 0.063=15.75. There was excellent reproducibility for the AUC for the North American tablets (0.97, 0.88) compared to the two capsules (0.32, 0.15).Conclusions:The significantly higher AUC and Cmax and shorter Tmax for the Canadian Ursofalk tablets compared to the UDCA capsule preparations supports better bioavailability.
The effect of unfiltered coffee on potential biomarkers for colonic cancer risk in healthy volunteers: a randomized trial
Authors: Grubben  , Van Den Braak  , Broekhuizen  , De Jong  , Van Rijt  , De Ruijter  , Peters  , Katan  , Nagengast  
Published: March 2003

Background:Epidemiologic studies suggest that coffee use might protect against colorectal cancer. Inconsistencies as to the effect of coffee use and colorectal cancer between epidemiologic studies might be related to the type of coffee brew.Objective:We studied the effect of unfiltered coffee consumption on putative biomarkers for colonic cancer risk.Design:A total of 64 healthy volunteers (31 men and 33 women), with a mean age of 43 ± 11 years were randomly assigned to two groups in a crossover design, with two intervention periods of 2 weeks separated by a washout period of 8 weeks. Treatments were 1 L of cafetière (French press) coffee daily or no coffee. At the end of each intervention period, fasting blood samples, colorectal biopsies and 48 h faeces were collected.Results:No effect of coffee on colorectal cell proliferation, assayed by estimating the Proliferating Cell Nuclear Antigen labelling index, was seen. Additionally, no effects were seen on the concentrations of faecal soluble bile acids and colorectal mucosal glutathione S‐transferase activity. However, unfiltered coffee significantly increased the glutathione content in the colorectal mucosa by 8% and in plasma by 15%. Other aminothiols in plasma also increased on coffee.Conclusion:Unfiltered coffee does not influence the colorectal mucosal proliferation rate, but might increase the detoxification capacity and anti‐mutagenic properties in the colorectal mucosa through an increase in glutathione concentration. Whether this effect indeed contributes to a lower colon cancer risk remains to be established.
Drug‐induced symptoms of functional dyspepsia and nausea. A symmetry analysis of one million prescriptions
Authors: Bytzer P. , Hallas J. 
Published: March 2003

Background:A large variety of drugs have been implicated in causing dyspepsia. Due to the high background incidence of dyspepsia it is impossible to distinguish between spontaneous and truly drug‐related symptoms. Most patients with dyspeptic symptoms are treated empirically. Drug‐induced dyspepsia might therefore be reflected in the sequencing of prokinetics relative to other medications.Aim:To screen a large prescription database for signs of drug‐induced functional dyspepsia, applying a symmetry principle.Methods:Prescription data on all incident users of cisapride and metoclopramide were used to identify individuals who had started their first therapies with a prokinetic drug and an index drug within a 100‐day span. A dyspepsia‐provoking effect of the index drug would manifest as an excess of persons with the prokinetic drug prescribed last in this selected population. Relative to conventional analyses based on case–control or cohort design, this principle is robust to confounders that are stable over time.Results:In the cisapride analysis (1825 persons) no single drug had adjusted rate ratios significantly above unity. An inverse signal for antidepressants (rate ratio 0.57; 95% CI: 0.39–0.84) suggests that these drugs may have a therapeutic effect against functional dyspepsia. In the metoclopramide analysis (6126 persons) positive signals were found for 14 drugs, all well‐known for causing nausea as a side‐effect, with the exception of insulin (rate ratio 2.91, 95% CI: 1.40–8.11).Conclusions:Drug‐induced symptoms of functional dyspepsia are rare and do not contribute to the use of cisapride. The start of insulin treatment may induce nausea.
Pantoprazole, azithromycin and tinidazole: short duration triple therapy for eradication of Helicobacter pylori infection
Authors: Calabrese C. , Di Febo G. , Areni A. , Scialpi C. , Biasco G. , Miglioli M. 
Published: March 2003

Background:Azithromycin is an acid‐stable macrolide that achieves remarkably high concentrations in gastric tissue, persisting above the MIC90 for Helicobacter pylori over a period of 5‐days, after a single 500 mg oral dose.Aim:To evaluate and compare the efficacy, safety, and tolerability of two eradicating regimens of pantoprazole, azithromycin and tinidazole.Methods:A total of 100 consecutive symptomatic H. pylori‐positive patients received pantoprazole 40 mg b.d. for 1 week, and were randomly assigned to either azithromycin 500 mg o.m. and tinidazole 500 mg b.d. during the first 3 days (early group, n=50) or during the last 3 days of therapy with pantoprazole (late group, n=50). H. pylori status was assessed by histology and rapid urease test at entry and by histology and 13C‐urea breath test 1 month after the end of the therapy.Results:Ninety‐nine patients completed the study. H. pylori was eradicated in 86% of patients in the early group (intention‐to‐treat 86%) and in 88% of patients in the late group (intention‐to‐treat 88%).Conclusions:This short triple therapy is effective for H. pylori eradication. The compliance was excellent and side‐effects negligible. Moreover, the pantoprazole pre‐treatment did not modify the efficacy of the therapy.
A double‐blind, randomized, dose response study testing the pharmacological efficacy of synthetic porcine secretin
Authors: Jowell P. S. , Robuck‐Mangum G. , Mergener K. , Branch M. S. , Purich E. D. , Fein S. H. 
Published: March 2003

Background:Biologically derived porcine secretin has been used as a diagnostic agent in clinical gastrointestinal practice for many years. Pure synthetic porcine secretin is now available for investigational clinical use.Aim:To compare the pharmacology of synthetic porcine secretin and biologically derived porcine secretin in healthy volunteers.Methods:Secretin stimulation tests were performed in 12 volunteer subjects in a double‐blind, randomized, Latin square crossover design study comparing three doses of synthetic porcine secretin (0.05, 0.2, and 0.4 μg/kg) with a standard dose of biologically derived porcine secretin (1 CU/kg). Duodenal aspirates were analysed for total volume and for bicarbonate concentration. Total bicarbonate output was calculated.Results:Twelve subjects completed four dosing regimens. A multiple comparison test was used to compare dosing regimens. The 0.2 and 0.4 μg/kg doses of synthetic porcine secretin were not different from the 1 CU/kg dose of biologically derived porcine secretin for volume, bicarbonate concentration and total output from 0 to 60 min. Only one patient had an adverse event, which was mild, transient flushing after the 0.2 and 0.4 μg/kg doses of synthetic porcine secretin and after the 1 CU/kg dose of biologically derived porcine secretin.Conclusions:Synthetic porcine secretin has identical pharmacologic effects to biologically derived porcine secretin in normal subjects. Both drugs were safe and well‐tolerated. This study validates synthetic porcine secretin as a substitute for biologically derived porcine secretin.
The roles of nitric oxide and prostaglandins in alterations of ulcerogenic and healing responses in adjuvant‐induced arthritic rat stomachs
Authors: Kato S. , Tanaka A. , Kunikata T. , Mizoguchi H. , Takeuchi K. 
Published: March 2003

Summary Aim: To examine alterations of gastric ulcerogenic and healing responses in adjuvant‐induced arthritic rats. Methods: Arthritis was induced in male Dark Agouti rats by injection of Freund's complete adjuvant into the right hind paw. Results: The gastric ulcerogenic response to indomethacin was markedly increased in AA rats, depending on the degree of arthritic change. By contrast, HCl/ethanol‐induced gastric lesions were significantly suppressed in arthritic rats when compared with normal rats. The increased ulcerogenic response to indomethacin was significantly prevented by L‐NAME and antineutrophil serum but not by FR167653, while the reduced ulcerogenic response to HCl/ethanol was significantly prevented by L‐NAME and partly by indomethacin or NS‐398. On the other hand, the healing of chronic gastric ulcers induced by thermal cauterization was also significantly delayed in arthritic rats when compared with normal rats. This delayed healing of gastric ulcers was affected by neither L‐NAME, indomethacin nor FR167653. The gastric mucosa of arthritic rats showed a significant increase in both inducible nitric oxide synthase (iNOS) activity and prostaglandin (PG) E2 contents. Conclusions: Gastric ulcerogenic and healing responses were altered in arthritic rats. The ulcerogenic response to indomethacin was increased while that to HCl/ethanol was decreased. These changes in ulcerogenic responses may both be accounted for by increased production of NO/iNOS, with the latter also being partially related to elevated production of PGs/COX‐2. Moreover, the healing of gastric ulcers was also delayed in arthritic rats, but the mechanism was related to neither NO nor PGs.
Matrix metalloproteinase expression in cultured human gastric wall fibroblasts – interactions with Helicobacter pylori isolated from patients with ulcers
Authors: Yokoyama T. , Otani Y. , Kurihara N. , Sakurai Y. , Kameyama K. , Suzuki H. , Igarashi N. , Kimata M. , Wada N. , Kubota T. , Kumai K. , Kitajima M. 
Published: March 2003

Summary Background: Matrix metalloproteinases (MMPs), enzymes capable of degrading collagens and other extracellular matrix components, have been implicated in gastric ulcer formation. However, the effect on MMP expression of Helicobacter pylori, also implicated in these lesions, has not been studied to our knowledge. Aim: To seek links between H. pylori and MMP expression likely to affect gastric ulcer formation. After fibroblasts from human gastric wall were cocultured with H. pylori, concentrations of MMP‐1 and ‐2 in the medium were determined by enzyme‐linked immuno‐sorbent assays. Results: Whereas MMP‐1 was not detected in media from fibroblasts or H. pylori culture alone, MMP‐1 was detected in cocultures (P < 0.01). Similar amounts of MMP‐2 were detected in medium from fibroblasts cultured alone and with H. pylori. No MMP‐2 production by H. pylori cultured alone was detected. Conclusions: MMP‐1 appears to be important in gastric ulcer pathogenesis, and MMP‐1 induction by H. pylori may impede gastric ulcer healing.
Is Helicobacter pylori relevant in the management of reflux disease?
Authors: Dent J. 
Published: March 2003

Data on the interaction of reflux disease and Helicobacter pylori infection are limited in scope and rigour, controversial and difficult to interpret. Despite this, a framework of understanding is emerging, which is consistent with known effects on gastric acid secretion.In patients with moderate to severe H. pylori‐induced corpus gastritis, eradication can increase substantially impaired gastric acid secretion sufficiently to precipitate reflux disease in people with pre‐existing sub‐clinical defective gastro‐oesophageal competence. By contrast, reflux disease in duodenal ulcer patients probably benefits from eradication of H. pylori. There appears to be no significant impact on reflux disease from eradication in healthy subjects or individuals whose primary problem is reflux disease. Helicobacter pylori‐infected reflux disease patients respond slightly better to proton pump inhibitors. These agents cause a topographic alteration of gastritis from antrum to corpus, the clinical significance of which is controversial.Many practitioners misjudge the risks and benefits of the effects of H. pylori eradication on reflux disease. Regardless of patient diagnosis, the balance is in favour of H. pylori eradication. For those in whom reflux oesophagitis development is a defined possibility, oesophagitis is mild, easily treated and most unlikely to be associated with any major risk for development of oesophageal adenocarcinoma.
Duration of effect of lansoprazole on gastric pH and acid secretion in normal male volunteers
Authors: Bell N. , Karol M. D. , Sachs G. , Greski‐Rose P. , Jennings D. E. , Hunt R. H. 
Published: March 2003

Aim:A double‐blind, placebo‐controlled study to assess the duration of effect of lansoprazole 30 mg o.m. on intragastric pH, acid secretion, gastrin levels, the potential for rebound acidity, and the relationship between gastric acid and drug pharmacokinetic parameters.Methods:Sixteen subjects were treated with lansoprazole 30 mg daily or placebo for 14 days, followed by a 7‐day post‐dosing period and a post‐study evaluation on day 28. Ambulatory 24‐h pH was recorded and pentagastrin‐stimulated acid secretion measured. Plasma kinetics of lansoprazole were determined.Results:Mean intragastric pH in the lansoprazole group increased significantly (P < 0.05) from baseline to day 14 compared to placebo. After cessation of treatment, secretory activity, as measured by intragastric pH, basal acid output and stimulated acid output, returned to baseline in 2 to 4 days without any overshoot, indicating the absence of acid rebound. Lansoprazole’s terminal disposition half‐life was 1.11 h. Mean pH and serum gastrin returned to baseline with half‐lives of 22 and 19 h, respectively.Conclusions:Lansoprazole 30 mg daily significantly increases mean intragastric pH without producing acid rebound. Regeneration of acid production depends primarily on de novo synthesis of the acid pump.
Lack of small intestinal ulcerogenecity of nitric oxide‐releasing indomethacin, NCX‐530, in rats
Authors: Mizoguchi H. , Hase S. , Tanaka A. , Takeuchi K. 
Published: March 2003

Aim:To evaluate the intestinal ulcerogenic property of nitric oxide‐releasing indomethacin (NCX‐530) in the rat, in comparison with indomethacin.Methods:Animals were given indomethacin or NCX‐530 subcutaneously and killed 24 h later for macroscopic examination of the small intestine.Results:A single administration of indomethacin (10 mg/kg) provoked damage, mainly in the jejunum and ileum, accompanied by an increase in myeloperoxidase and inducible nitric oxide synthase activities as well as bacterial translocation. NCX‐530 at an equimolar dose (14.2 mg/kg) caused no gross damage in the small intestine, nor any significant change in inducible nitric oxide synthase and myeloperoxidase activities or bacterial translocation. NOR‐3, the nitric oxide donor (6.0 mg/kg), when administered subcutaneously together with indomethacin, significantly prevented the occurrence of intestinal lesions and other mucosal changes. Indomethacin reduced mucus and fluid secretions in the small intestine, while both NCX‐530 and NOR‐3 enhanced these secretions. NCX‐530 reduced the mucosal prostaglandin E2 contents and exhibited an anti‐inflammatory action against carrageenan‐induced paw oedema, with equal effectiveness to indomethacin.Conclusion:NCX‐530 does not cause intestinal damage, despite inhibiting cyclooxygenase activity. The reduced intestinal toxicity of NCX‐530 may be attributable to inhibition of enterobacterial translocation, partly by increasing the mucus and fluid secretions mediated by nitric oxide released from this compound.
Minimal renal dysfunction in inflammatory bowel disease is related to disease activity but not to 5‐ASA use
Authors: Herrlinger K. R. , Noftz M. K. , Fellermann K. , Schmidt K. , Steinhoff J. , Stange E. F. 
Published: March 2003

Background:Conflicting data exist about proteinuria in inflammatory bowel diseases. It is still unclear whether the occurrence of proteinuria in inflammatory bowel disease patients is an extra‐intestinal manifestation of disease or the result of adverse effects to medication, especially to aminosalicylates (ASA).Methods:A total of 95 patients (51 with Crohn’s disease and 44 with ulcerative colitis) were enrolled in the study. Disease activity was assessed by Crohn’s Disease Activity Index (CDAI) or the Truelove index, respectively. Urine was collected over 24 h and protein excretion of specific marker proteins for tubular (α1‐microglobulin‐α1‐MG) and glomerular (albumin‐Alb, Immunoglobulin G‐IgG) dysfunction was measured using a highly sensitive immunoluminometric assay.Results:Out of 51 Crohn’s disease patients, 20 showed elevated urinary α1‐MG. The amount of α1‐MGuria was strongly correlated to the CDAI (r=0.6, P < 0.001). Only four Crohn’s disease patients showed slightly elevated values for glomerular proteins in urine. Similar results were obtained for ulcerative colitis: whereas only two ulcerative colitis patients showed albuminuria, tubular proteinuria was detected in 28 out of 44 ulcerative colitis patients. Proteinuria was strongly dependent on disease activity (P < 0.01) but was not related to ASA treatment.Conclusions:Proteinuria of tubular marker proteins occurs in the majority of inflammatory bowel disease patients and is related to disease activity rather than to ASA treatment. Tubular proteinuria seems to reflect a renal extra‐intestinal manifestation of inflammatory bowel disease and may serve as a new relevant marker of disease activity.
The new proton pump inhibitor esomeprazole is effective as a maintenance therapy in GERD patients with healed erosive oesophagitis: a 6‐month, randomized, double‐blind, placebo‐controlled study of efficacy and safety
Authors: Vakil N. B. , Shaker R. , Johnson D. A. , Kovacs T. , Baerg R. D. , Hwang C. , D'Amico D. , Hamelin B. 
Published: March 2003

Background:Esomeprazole, the S‐isomer of omeprazole, is the first proton pump inhibitor to be developed as an optical isomer. In patients with erosive oesophagitis, esomeprazole has produced significantly greater healing rates and improved symptom resolution vs. omeprazole.Aim:This study assesses the efficacy of esomeprazole for preventing relapse in patients with healed oesophagitis.Methods:In this 6‐month US multicentre randomized double‐blind placebo‐controlled trial, 375 Helicobacter pylori‐negative patients with endoscopically healed oesophagitis received esomeprazole 40 mg, 20 mg, 10 mg, or placebo once daily. The primary efficacy end‐point was maintenance of healing at 6 months. Secondary end‐points assessed changes in symptoms, and long‐term safety and tolerability.Results:Significantly (P < 0.001) more patients remained healed with esomeprazole 40 mg (87.9%), 20 mg (78.7%), or 10 mg (54.2%), than with placebo (29.1%). Relapse, when it occurred, was later with esomeprazole. Sustained resolution of heartburn was observed in the 40 mg and 20 mg groups; there was a high correlation between absence of heartburn and maintenance of healing. Adverse effects were mild, infrequent and not significantly different between groups.Conclusions:Esomeprazole is effective and well‐tolerated in the maintenance of healing of erosive oesophagitis. Esomeprazole 40 mg and 20 mg offer significant clinical benefit to patients.
Probiotic impact on microbial flora, inflammation and tumour development in IL‐10 knockout mice
Authors: O'Mahony L. , Feeney M. , O'Halloran S. , Murphy L. , Kiely B. , Fitzgibbon J. , Lee G. , O'Sullivan G. , Shanahan F. , Collins J. K. 
Published: March 2003

Background:The enteric bacterial flora has been implicated in the pathogenesis of enterocolitis and colon cancer in C57BL/6 IL‐10 knockout mice. Probiotic Lactobacilli modify the enteric flora and are thought to have a beneficial effect on enterocolitis. We conducted a controlled feeding trial in IL‐10 knockout mice using the probiotic Lactobacillus salivarius ssp. salivarius UCC118.Aim:To determine the effect of probiotic consumption on the gastrointestinal microflora, tumour development and colitis in IL‐10 knockout mice.Methods:Twenty IL‐10 knockout mice were studied (10 consumed probiotic organisms in milk and 10 consumed unmodified milk) for 16 weeks. Faecal microbial analysis was performed weekly to enumerate excretion of the probiotic UCC118, total lactobacilli, Clostridium perfringens, bacteroides, coliforms, bifidobacteria and enterococci. At sacrifice, the small and large bowel were microbiologically and histologically assessed.Results: L. salivarius UCC118 was detected in faeces from all mice in the probiotic fed group, but not the control group. Faecal coliform and enterococci levels were significantly reduced in probiotic fed animals compared to the controls (P < 0.05). At sacrifice, a significant reduction in C. perfringens numbers was observed in the test mice (P < 0.05). There were no fatalities in the test group compared to two deaths from fulminant colitis in the control group. Only one test mouse developed colonic adenocarcinoma compared to five in the control group. Test animal mucosal inflammation consistently scored lower than that of the control mice.Conclusion:In this placebo controlled trial, modification of enteric flora in IL‐10 knockout mice by probiotic lactobacilli was associated with reduced prevalence of colon cancer and mucosal inflammatory activity.