bluuebunny/crossref_metadata_2025_split huggingface dataset:
Review article: the hypersensitive gut—peripheral kappa agonists as a new pharmacological approach
Authors: JUNIEN J. L. , RIVIERE P. 
Published: July 2010

SUMMARYHypersensitivity to pain is a common component of functional bowel disorders. Hyperalgesia may be induced by various stimuli which produce a cocktail of inflammatory mediators that decrease the pain threshold. Drugs able to block these peripheral events within the gut may offer a new pharmacological approach for treating functional bowel disorders. Kappa opioids have been shown to inhibit somatic pain through a peripheral mechanism of action, acting directly on receptors located on peripheral sensory endings. They can block both the nociceptive messages as well as the release of sensory peptides. This paper reviews the effects of opioid agonists on gut visceral pain and motility anomalies induced by visceral pain. Kappa opioids have strong effects on all models tested, with a peripheral mechanism of action allowing the design of drugs acting only in the periphery and having no central nervous system side‐effects. This contrasts with mu agonists which are centrally active on pain and worsen the subsequent transit and motility anomalies.
factors protecting the oesophagus against acid‐mediated injury
Authors: BROWN C. M. , REES W. D. W. 
Published: July 2010

SUMMARYReflux of gastric acid and pepsins into the lower oesophagus causes symptoms such as heartburn and nausea, and tissue injury leading to erosive oesophagitis and stricture formation. This article reviews the mechanisms involved in protecting the oesophagus against acid‐mediated injury, including the role of the lower oesophageal sphincter, secondary oesophageal peristalsis and swallowed saliva. The oesophageal mucosa has inherent abilities to resist acid damage, and recent data from three laboratories suggest a secretory function with local production of bicarbonate and mucus responsive to local acidification. The evidence for these putative oesophageal defence mechanisms is discussed.
Ranitidine maintenance therapy in the prevention of duodenal ulceration; a comparison of 150 mg at night with 300 mg at night
Authors: McDOUGLE A. M. A. , LANCASTER‐SMITH† M. J. , HIGSON D. L. 
Published: July 2010

SUMMARY Background: The purpose of this study was to investigate if the use of a higher night time dose of ranitidine (300 mg) could keep significantly more duodenal ulcer patients in remission than the usual maintenance dose (150 mg). Methods: Double‐blind, multi‐centre, parallel group study of patients with proven healed duodenal ulcer randomized to ranitidine 150 mg or 300 mg daily for 1 year. The primary study end‐point was symptomatic, endoscopically proven ulcer relapse. Results: A total of 489 patients were recruited into the study. The endoscopically proven relapse rates were 6.1% of ranitidine 150 mg daily (n= 250) and 6.9% on 300 mg daily (n= 239). These differences were not statistically significant. Conclusion: This study provides further evidence that maintenance therapy with ranitidine 150 mg daily is highly effective at preventing duodenal ulcer relapse. The use of the higher dose of 300 mg daily does not appear to keep significantly more patients in remission.
A double‐blind study of pantoprazole and omeprazole in the treatment of reflux oesophagitis : a multicentre trial
Authors: MÖSSNER J. , HÖLSCHER† A. H. , HERZ R. , SCHNEIDER A. 
Published: July 2010

SUMMARYBackground: Pantoprazole is a new substituted benzimidazole which is a potent inhibitor of gastric acid secretion by its action upon H+,K+‐ATPase.Aim:To compare pantoprazole 40 mg with omeprazol 20 mg as once daily dosing in the treatment of reflux oesophagitis (grades II and III).Methods: This double‐blind, randomized, multicentre study included 286 patients. Patients were reendoscoped after 4 weeks, and continued to receive a further 4 weeks of treatment if they were not healed a this time.Results: After 4 weeks of treatment, complete healing occurred in 126/170 (74%) patients in the pantoprazole group and in 67/86 (78%) patients in the omeprazole group (per‐protocol analysis). At 8 weeks, the corresponding healing rates were 153/170 (90%) and 81/86 (94%). The differences between the treatment groups were not significant (P= 0.57 and 0.34). Improvement in the principal symptoms of reflux oesophagitis was also very similar between the treatment groups, with 59% and 69% at 2 weeks, and 83% and 86% at 4 weeks, respectively, being free from any individual symptom. Both treatments were well tolerated.Conclusions: This study has shown pantoprazole and omeprazole to be similarly effective and well tolerated in the treatment of mild to moderate reflux oesophagitis.
Intestinal site‐dependent susceptibility to chronic indomethacin in the rat: a morphological and biochemical study
Authors: NYGÅRD G. , ANTHONY A. , KHAN K. , BOUNDS S. V. J. , CALDWELL J. , DHILLON A. P. , POUNDER R. E. , WAKEFIELD A. J. 
Published: July 2010

SUMMARY Background: The cyclo‐oxygenase inhibitor indomethacin induces a pattern of gastrointestinal injury in the rat that is site‐dependent. This study compared the extent of injury to different regions of the rat intestine (small intestine, caecum and colon) with the corresponding changes in arachidonic acid metabolism in these areas, following long‐term, low‐dose indomethachin. Methods: Rats (eight per group) received either indomethacin (3 mg.kg/day) or control diet for either 6 or 12 weeks. At termination animals were bled, examined both macroscopically and microscopically for ulcers, and assayed for blood thromboxane B2, intestinal tissue prostaglandin E2 content and production of leukotriene B4. In a further eight animals luminal indomethacin concentrations from the small intestine, caecum and colon were measured following 6 weeks of chronic drug ingestion. Results: At 6 weeks, macroscopic ulcers were observed in 2/8 (small intestine), 3/8 (caecum) and 1/8 (colon) animals. The corresponding ratios at 12 weeks were 5/8, 8/8 and 0/8. In control animals, a site‐dependent gradient of the prostaglandin E2 concentration was found. In indomethacin‐dosed animals the intestinal prostaglandin E2 content was reduced significantly in the caecum at 6 weeks, and in all tissues at 12 weeks. An increased leukotriene B4 production was observed in the caecum only, at 12 weeks (P < 0.01), and the blood thromboxane B2 was reduced at both time points (P < 0.05). Conclusion: There is a site‐dependent gradient of the prostaglandin E2 concentration in the rat intestine. The rat caecum is particularly sensitive to long‐term low‐dose indomethacin, both in terms of chronic intestinal inflammation and changes in prostanoid metabolism. This site‐dependent degree of injury may be associated with a local cyclo‐oxygenase inhibition.
Comparison of pantoprazole versus omeprazole in the treatment of acute duodenal ulceration—a multicentre study
Authors: REHNER M. , ROHNER H. G. , SCHEPP W. 
Published: July 2010

SUMMARY Methods: In this randomized, double‐blind, multicentre study, the proton pump inhibitors pantoprazole and omeprazole were compared in patients with active duodenal ulcers. Two hundred and seventy‐six protocol‐correct patients received either pantoprazole 40 mg (n= 185) or omeprazole 20 mg (n= 91), once daily for 2 or 4 weeks, depending on the progress of ulcer healing. Results: Rates of complete ulcer healing after 2 weeks were 71% in patients given pantoprazole and 74% in patients given omeprazole. After 4 weeks the figures were 96% and 91%, respectively. These differences were not significant. There was no significant difference in ulcer pain prior to treatment, and 85% of the pantoprazole group and 86% on omeprazole were pain‐free after 2 weeks (not significant). The time until complete pain relief with pantoprazole or omeprazole, based on data from diary cards, was not significantly different (P < 0.05, Uleman's U‐test). Both treatments were equally well tolerated. Changes in routine laboratory parameters were minimal in both groups. Conclusion: Pantoprazole was shown to be a highly‐effective and well‐tolerated treatment for acute duodenal ulcer. Pantoprazole 40 mg and omeprazole 20 mg were equally effective with respect to ulcer healing and pain relief, and have similar adverse event profiles.
Pain and quality of life in patients with acute duodenal ulcer treated with ranitidine
Authors: RAMPAL P. , RUSZNIEWSKI P. , BOUREAU F. , RICHARD A. , SLAMA A. 
Published: July 2010

SUMMARY Background: The various components of pain and quality of life in duodenal ulcer patients receiving antisecretory drugs have not been studied to date. Methods: Ninety‐five patients with epigastric pain and duodenal ulcer at endoscopy completed this prospective, multicenter, open‐study. All were treated with effervescent ranitidine 300 mg daily for 4 weeks. The following parameters were assessed: (a) disappearance of duodenal ulcer pain by self‐evaluation and on a weekly visual analogue scale (VAS) from 0 to 100; (b) evolution of sensory and affective components of ulcer pain by the Validated French Version of the McGill Pain Questionnaire (Questionnaire Douleur de Saint‐Antoine, QDSA); (c) quality of life by the Nottingham Health Profile (NHP) which includes six criteria: pain, mobility, energy, emotions, sleep and social isolation. Results: Forty‐nine, 66 and 87% of the patients were pain‐free during the day‐time after 7, 14 and 28 days, respectively. Corresponding figures for the night‐time were 80%, 88% and 97% respectively. Median time to disappearance of ulcer pain was 8 days. VAS self‐assessment showed a significant decrease each week throughout the treatment period (P= 0.001). Sensory and affective QDSA scores were significantly improved after the second day and at each assessment during the 28 days of treatment (P= 0.001). Physical as well as affective aspects of quality of life were significantly improved after 28 days for each of the six criteria explored (P= 0.001). The duodenal ulcer healing rate was 86% after 4 weeks of treatment. Conclusions: Using complementary scales measuring different aspects of ulcer pain, sensory and affective components improved significantly from the second day of treatment with ranitidine 300 mg. A significant improvement in quality of life is observed after a 4‐week treatment.QDSA and NHP appear to be useful evaluation tools of duodenal ulcer pain and quality of life.
Loperamide oxide in acute diarrhoea: a double‐blind, placebo‐controlled trial
Authors: DREVERMAN J. W. M. , VAN DER POEL A. J. M. 
Published: July 2010

SUMMARYBackground: Loperamide is an established treatment of acute diarrhoea with only rare adverse reactions. The pro‐drug loperamide oxide is converted to loperamide by anaerobic bacteria in the lower alimentary tract. With the use of loperamide oxide, it was expected to obtain similar antidiarrhoeal efficacy as with loperamide, but with a lower dose and a lower plasma concentration. The incidence of adverse reactions might be reduced with the use of loperamide oxide.Methods: Loperamide oxide (0.5 and 1 mg capsules) was compared with placebo in a double‐blind treatment of acute diarrhoea of 242 patients. Relief of diarrhoea was significantly more rapid for either dose of loperamide oxide than for placebo. Both the investigators’and the patients’global assessment of the treatment significantly favoured the loperamide oxide 1 mg capsule, but not 0.5 mg, over placebo. Adverse experiences were less frequent in the drug‐treated than in the placebo‐treated group.Conclusion: These results suggest that loperamide oxide 1 mg produces effective relief of diarrhoeal symptoms.
the risks of malignancy from either immuno‐suppression or diagnostic radiation in inflammatory bowel disease
Authors: FORBES A. , READING N. G. 
Published: July 2010

SUMMARYInflammatory bowel disease is associated with an increased risk of gastrointestinal malignancy. There has been concern that either diagnostic medical radiation and long‐term drug therapy—particularly immunosuppression—might contribute to this increased cancer risk.For the major drug groups (5‐aminosalicylates, steroids and immunosuppressants) data are scant but broadly reassuring. Only azathioprine (including 6‐mercaptopurine) has been investigated at all carefully. Short‐ to medium‐term therapy probably poses a very slightly increased risk of malignancy which is easily accepted given the current limitation of this agent to second‐line use. Continuous therapy for more than two years is much less well documented, and caution should be maintained.A hypothetical model based on data from occupational radiation exposure has been constructed; this permits reasonable confidence that the medical use of ionising radiation contributes a negligibly increased risk of malignancy overall, and is particularly unlikely to add significantly to the incidence of gastrointestinal malignancy.
Pre‐ulcerative villous contraction and microvascular induced by indomethacin in the rat jejunum: a detailed morphological study
Authors: ANTHONY A. , DHILLON A. P. , THRASIVOULOU C. , POUNDER R. E. , WAKEFIELD A. J. 
Published: July 2010

SUMMARYBackground: In indomethacin‐induced jejunal ulceration in the rat, villi undergo both early microvascular injury and shortening that may involve activation of villous smooth muscle.Aim: This study sought to substantiate light microscopic observations using three‐dimensional imaging of early villous architectural changes in response to indomethacin.Methods: At both 2 and 6 h after oral indomethacin 15 mg/kg or vehicle to groups of rats, the vasculature of the small intestine was visualised by both carbon‐ink perfusion/confocal microscopy and injection casting. The mucosa was also examined for lesions by dissection microscopy and scanning electron microscopy.Results: In indomethacin‐dosed rats examined by scanning electron microscopy and histology, the mucosa at 2 h showed villous shortening and wrinkling of the surface epithelium without epithelial loss: at 6 h, the mucosa was flattened, often with epithelial loss to expose a ‘contracted’ villous core. Examination of the vasculature in carbon‐injected tissues indicated significant reductions of both mucosal height and inter‐capillary distance at both 2 and 6 h post‐indomethacin. Scanning electron microscopy of injection casts at 2 and 6 h indicated similar changes. These changes were not seen in control tissues.Conclusion: Histology, confocal microscopy and scanning electron microscopy support the proposal that villous shortening with disruption of surface capillary architecture are early changes in the ulcerative enteropathy induced by nonsteroidal anti‐inflammatory drugs.
Review article: Refractory distal colitis—explanations and options
Authors: GRIFFIN M. G. , MINER P. B. 
Published: July 2010

SUMMARYDistal colitis refractory to standard therapy is a complex and challenging problem. Physiological differences between the right and left colon may be exploited for maximum therapeutic benefit. Overreliance on oral therapy should be seen as one of the reasons for treatment failure and delivery systems should target therapy to the distribution of the disease in doses proven to be therapeutically beneficial. The clinician should also be cognizant of potential adverse effects of standard therapies, particularly colitis due to mesalazine, which may mimic worsening disease. Numerous endogenous and exogenous factors that may exacerbate the underlying inflammatory bowel disease are discussed. This review explores the potential mechanisms why distal colitis may be refractory to therapy and addresses newer therapies that, while still in the investigatory stages, offer hope for a widening armamentarium of therapeutic modalities.
Prevention of water immersion stress‐induced gastric lesions through the enhancement of nitric oxide synthase activity in rats
Authors: TACHI K. , GOTO H. , HAYAKAWA T. , SUGIYAMA S. 
Published: July 2010

SUMMARYBackground: Gastric mucosal microcirculation is an important factor in the protection of gastric mucosa, and nitric oxide (NO) plays a crucial role in the regulation of regional blood flow. This study was designed to evaluate the effect of cetraxate, an anti‐ulcer drug, on water immersion stress‐induced gastric lesions in relation to the changes in NO synthase activity.Methods: Gastric lesions were induced in rats by water immersion stress. The effects of cetraxate on NO synthase activity with or without stress was determined enzymatically. Changes in gastric mucosal prostaglandin (PG) contents with or without stress were also determined using high‐performance liquid chromatography. Gastric mucosal blood flow was measured by hydrogen gas clearance technique.Results: Water immersion stress‐induced gastric lesions. Cetraxate significantly mitigated the lesions but NG‐monomethyl‐l‐arginine (l‐NMMA), a specific inhibitor of NO synthase, exacerbated the lesions. The favourable effect of cetraxate was remarkably diminished by administration ofl‐NMMA. NO synthase activity decreased significantly by 6 h after stress. Cetraxate treatment increased NO synthase activity throughout the experiment in rats with or without stress treatment. Water immersion stress decreased all PGs detected, i.e. 6‐keto‐PGF1α, PGF2αPGE2and PGD2. Cetraxate prevented stress‐induced decreases in PG contents.l‐NMMA showed no significant effect on PG contents. Cetraxate increased gastric mucosal blood flow significantly andl‐NMMA cancelled out cetraxate‐induced increase in blood flow.Conclusions: The pharmacological efficacy of anti‐ulcer drugs such as cetraxate might be attributable to the enhancement of NO synthase activity resulting in an increase in gastric mucosal blood flow.
Metronidazole, ranitidine and clarithromycin combination for treatment of Helicobacter pylori infection (modified Bazzoli's triple therapy)
Authors: YOUSFI M. M. , EL‐ZIMAITY H. M. T. , COLE R. A. , GENTA R. M. , GRAHAM D. Y. 
Published: July 2010

SUMMARY Background: Multi‐drug regimens are generally required to reliably cure Helicobarter pylori infection. Metronidazole, clarithromycin and omeprazole has proven to be an effective combination therapy with a cure rate of 90% or greater. Methods: We evaluated a 14‐day combination regimen for H. pylori infection consisting of metronidazole 500 mg b.d., clarithromycin 250 mg b.d. and ranitidine 300 mg b.d. (MRC) instead of omeprazole. Ranitidine alone was continued for an additional 4 weeks. H. pylori status was determined by rapid urease testing. histopathology using the Genta stain, and by culture at entry and 4 weeks after completing antimicrobial therapy. Results: Twenty‐seven patients with documented peptic ulcer disease and H. pylori infection were treated. Five had previously failed macrolide‐based antimicrobial therapy: none had received metronidazole. All ulcers were healed at week 6 except one patient taking naproxen; his H. pylori infection was cured. Overall, H. pylori infection was cured in 78% (95% CI = 58–91%). In patients with clarithromycin‐sensitive isolates, the cure rate was 20 of 23 (87%, 95% C.I. = 66–97%); only one of four patients (25%) with clarithromycin‐resistant isolates was cured. In contrast, four of five patients with metronidazole‐resistant isolates were cured (80%). In patients with isolates sensitive to both antibiotics, the cure rate was 16 of 18 (89% 95% C.I. = 65–99%). Mild side effects were reported by 27%, including diarrhoea and altered taste. Compliance averaged 98%. Conclusion: These results suggest that the combination of metronidazole, ranitidine and clarithromycin results in high cure rates in patients with clarithromycin‐sensitive isolates. Omeprazole may not be required for Bazzoli's triple therapy; and large multicentre comparative trials are indicated.
Could frameshift mutations in the frxA and rdxA genes of Helicobacter pylori be a marker for metronidazole resistance?
Authors: MASAOKA T. , SUZUKI H. , KURABAYASHI K. , NOMOTO Y. , NISHIZAWA T. , MORI M. , HIBI T. 
Published: July 2010

SummaryBackgroundAlthough resistance of Helicobacter pylori to metronidazole had been reported to be associated with mutations in the rdxA or the frxA gene, recent studies have indicated that they may contribute little to metronidazole resistance.AimTo clarify the roles of these genes in metronidazole resistance, we examined them in strains that were not eradicated by first‐line eradication therapy.Patients and methodsA total of 132 patients (92 males, 40 females, average age: 53.8 years old) who underwent upper gastrointestinal endoscopy after unsuccessful first‐line H. pylori eradication were enrolled. Antibiotic susceptibility to metronidazole was investigated using the agar dilution method. The H. pylorirdxA and frxA genes were then sequenced.ResultsIn the metronidazole‐resistant strains, the sensitivity of detection of frameshift mutations in the rdxA gene was 44%. A significant association between the presence of frameshift mutations in the rdxA gene and resistance to metronidazole was observed. No significant association between frameshift mutations in the frxA gene and resistance to metronidazole was observed.ConclusionMutation in the rdxA gene was sufficient, but not necessary to confer resistance to metronidazole in H. pylori. Mutation in the frxA gene was not necessary for resistance to metronidazole in H. pylori.
Enhanced plasma ghrelin levels in patients with functional dyspepsia
Authors: NISHIZAWA T. , SUZUKI H. , NOMOTO Y. , MASAOKA T. , HOSODA H. , MORI M. , OHARA T. , MORISHITA T. , KANGAWA K. , HIBI T. 
Published: July 2010

SummaryBackgroundGhrelin, growth‐hormone‐releasing peptide, has been reported to accelerate food intake and gastrointestinal motility.AimThe present study was designed to investigate the plasma ghrelin levels in patients with functional dyspepsia (FD).Patients and MethodsNinety‐seven patients, who showed no evidence of peptic ulcer disease or gastrointestinal cancer on upper gastrointestinal endoscopy, were recruited. Seventeen patients who had no gastrointestinal symptoms were recruited as controls. Forty‐seven patients were diagnosed to be suffering from FD, based on the Rome II criteria. The FD patients were further subdivided into those with ulcer‐like FD, dysmotility‐like FD and non‐specific‐type FD, based on their Gastrointestinal Symptom Rating Scale (GSRS) scores. Fourteen patients were categorized as having gastro‐oesophageal reflux disease, and 19 patients were excluded as having the irritable bowel syndrome, based on the GSRS. The plasma ghrelin levels were measured by radioimmunoassay.ResultsThe plasma ghrelin levels were significantly higher in FD patients, especially in those with dysmotility‐like FD, as compared with those in controls. The plasma ghrelin levels were also correlated well with the indigestion scores.ConclusionPlasma ghrelin levels are significantly higher in patients with dysmotility‐like FD, suggesting that this parameter could become useful as a novel supportive marker for the diagnosis of FD.