bluuebunny/crossref_metadata_2025_split huggingface dataset:
Acid‐induced increase in duodenal mucosal alkaline secretion in the rat involves the L‐arginine/NO pathway
Authors: HOLM M. , JOHANSSON B. , BOTHMER C. VON , JÖNSON C. , PETTERSSON A. , FÄNDRIKS L. 
Published: October 2003

Duodenal mucosal alkaline secretion increases in response to hydrochloric acid exposure. The tentative role of nitric oxide (NO) in the mediation of this response was investigated. The mucosal alkaline output by a duodenal segment was recorded by in situ titration in chloralose‐anaesthetized rats. In some experiments the duodenal blood flow was estimated by laser‐Doppler flowmetry. Exposure of the duodenum to acid (0.01 M HCl, 5 min) increased the alkaline secretion by ≈85%. The NO synthase inhibitor NG‐nitro‐L‐arginine methyl ester (L‐NAME, 10 mg kg−1 intravenously or 0.3 mM intraluminally) blocked the secretory increment after mucosal acid exposure. Mean arterial pressure and basal alkaline secretion were markedly raised, whereas duodenal blood flow was decreased, when L‐NAME was given intravenously (i.v.). Intraluminal (i.l.) administration left mean arterial pressure as well as duodenal blood flow unaltered, and the duodenal mucosal alkaline secretion was only slightly elevated. The stereoisomer NG‐nitro‐D‐arginine methyl ester (D‐NAME) had no effect on either basal or acid‐induced duodenal alkaline output. In animals receiving L‐arginine (10 mg kg−1 min−1 i.v., or 3 mM i.l.) and L‐NAME, the acid exposure elicited an increase in duodenal mucosal alkaline secretion, similar to that observed in controls.The results suggest that the acid‐induced increase in duodenal mucosal alkaline secretion involves NO synthesis, which takes place close to the lumen, probably within the mucosa.
Heterogeneous blood flow response in the foot on dependency, assessed by laser Doppler perfusion imaging
Authors: GOLSTER H. , THULESIUS O. , NILSSON G. , SJÖBERG F. 
Published: October 2003

The exact nature of the decrease in foot skin blood flow seen after a change in posture remains unsettled. This mechanism has previously been examined by non‐invasive techniques such as the laser Doppler perfusion monitor (laser Doppler flowmetry). Taking into account the shortcomings of laser Doppler perfusion monitoring when applied to the determination of skin blood flow, which normally shows substantial heterogeneity, we have applied an emerging technology, the laser Doppler perfusion imager (LDPI). This technique provides a more comprehensive picture of the blood flow distribution in the skin, as it maps skin blood flow over a surface area (120×120 mm, 4096 measurement sites). It was used to examine if the reduction in tissue perfusion or the alterations in flow distributions seen after a change in posture (supine to dependency) could be fully explained by an increase in venous pressure (venous stasis of 50 mmHg) or if the data suggest a complementary mechanism.Skin blood flow of the forefoot decreased from 0.60 V (volt) (median) during rest to 0.40 and 0.38 V during venous stasis and dependency, respectively. Although almost identical median values were obtained during stasis and dependency, the flow distributions were different, with a loss of high flow values during venous stasis. Biological zero was 0.24 V.As the LDPI technique readily records skin perfusion during variations in venous stasis and posture, as well as information on flow distribution changes, it appears promising for future application in stimuli‐response studies of skin blood flow. The difference in flow distribution seen between increased venous pressure and dependency suggests an additive regulatory mechanism to the veni‐vasomotor reflex during a change in posture.
Influence of picrotoxin and strychnine on the spectral sensitivity of the turtle ERG b‐ and d‐waves: II. Light adaptation
Authors: VITANOVA L. , KUPENOVA P. , POPOVA E. , MITOVA L. 
Published: October 2003

The aim of the present work was to investigate the role of GABA and glycine, the two main inhibitory neurotransmitters in the retina, in the spectral sensitivity coding under conditions of light adaptation. To study this question, spectral sensitivity curves, based on the turtle ERG responses to stimuli of different wavelengths, were constructed. The spectral sensitivity curves, obtained before and during treatment with picrotoxin (PT), a GABAA antagonist, or with strychnine (ST), a glycine antagonist, were compared. Both PT and ST increased the b‐ and d‐wave absolute sensitivity in a wavelength‐dependent manner. PT significantly changed the shape of the b‐ and d‐wave spectral sensitivity curves and the latter lost their peaks.It is concluded that, under conditions of light adaptation, GABA and glycine took part in the formation of the b‐ and d‐wave spectral sensitivity curves, that both of them exerted an effect on the gain and that, furthermore, GABA had a well pronounced effect on the tuning of the spectral sensitivity curves.
Resistance of Helicobacter pylori to antibiotics
Authors: MÉGRAUD F. 
Published: October 2003

Resistance of Helicobacter pylori to antibiotics included in current regimens used to eradicate H. pylori is a major reason for failure. The definition of resistance is not simple, and the clinical relevance of in vitro results must be considered. The different methods of testing antibiotics cannot apply in all cases.Resistance to clarithromycin has a low prevalence rate (<10%) and its mechanism is well defined (point mutation on the 23S rRNA genes, and decreased binding of the antibiotics to the ribosome). Its clinical relevance is not questioned and, because of a clear occurrence of a bimodal strain population, the method for detecting resistance is not crucial.Resistance to nitroimidazoles is much more common, probably in the range of 30% or more in Europe. Neither the mechanism of action of metronidazole resistance nor its mechanism of is well known. The redox potential inside the cell which is important in reducing metronidazole to its active metabolite is probably a key element, but the exact metabolites involved are not yet known. Metronidazole resistance was found to be clinically relevant when standard triple therapy was used. The relevance is questioned for triple therapies including a proton pump inhibitor, clarithromycin and metronidazole. More clinical data are needed in this field and the use of agar dilutions is recommended to assess the susceptibility of H. pylori to metronidazole.The mechanism of resistance to quinolones has been described but these compounds are not currently used for H. pylori infection. No resistance has yet been described for amoxycillin but continuous surveillance is needed in order to detect new cases, as was recently the case for tetracycline resistance.
Lansoprazole, clarithromycin and metronidazole for seven days in Helicobacter pylori infection
Authors: HARRIS A. W. , PRYCE D. I. , GABE S. M. , KARIM Q. N. , WALKER M. M. , LANGWORTHY H. , BARON J. H. , MISIEWICZ J. J. 
Published: October 2003

Background: This study determines the efficacy and safety of a 1‐week triple therapy regimen of lansoprazole, clarithromycin and metronidazole in an area with a high prevalence of pre‐treatment metronidazole‐resistant strains of Helicobacter pylori. Methods: Seventy‐five H. pylori positive patients with gastritis or duodenal ulcer were entered into an open study of lansoprazole 30 mg o.m., clarithromycin 250 mg b.d. and metronidazole 400 mg b.d. H. pylori status was determined by CLOtest, histology, culture and by 13C‐urea breath test (repeated 28 days after treatment). Results: Seventy‐one patients completed the treatment and returned for follow‐up. H. pylori was eradicated in 61 of 71 (86%) patients by per‐protocol analysis, and in 61 of 75 (81%) patients by intention‐to‐treat analysis. H. pylori was eradicated in 12 of 16 (75%) patients with metronidazole‐resistant strains compared with 22 of 24 (92%) in patients with metronidazole‐sensitive strains of H. pylori (P = 0.14). Forty‐five patients reported at least one adverse event, and three patients stopped treatment due to them (two with headaches and one with diarrhoea). Conclusions: A 1‐week course of lansoprazole 30 mg o.m., clarithromycin 250 mg b.d. and metronidazole 400 mg b.d. eradicates H. pylori in up to 86% of patients. It is of proven benefit in patients with pre‐treatment metronidazole‐resistant strains of H. pylori.
Sublingual nitroglycerine: effects on contractile activity of the distal oesophagus and lower oesophageal sphincter in healthy men
Authors: STACHER G. , SCHNEIDER C. , STEINRINGER H. , SATZINGER U. , WEBER U. 
Published: October 2003

Background and Aims: Nitric oxide plays an important role in the control of gastrointestinal motility. This study assessed the effects of graded doses of the nitric oxide‐releasing agent, nitroglycerine, on distal oesophageal motor activity and lower oesophageal sphincter resting pressure. Methods: Eight healthy young men received at 1‐week intervals placebo, 0.2 mg, 0.4 mg or 0.8 mg nitroglycerine sublingually under random double‐blind conditions. Sphincter pressure was recorded using a Dent sleeve and oesophageal motility using sensors 1, 4, 7 and 10 cm orad the sleeve during two 15‐min periods before and four 15‐min periods after drug administration. In minutes 4 to 6 of each period, subjects swallowed 5 mL water at 30 s intervals. Results: After 0.2 mg and 0.4 mg nitroglycerine, amplitude, duration and area under curve of swallow‐initiated contractions were smaller than after placebo. After 0.8 mg nitroglycerine, amplitude, duration and area under curve were slightly greater than after placebo and significantly greater than after the lower nitroglycerine doses. No effects were discernible on onset latency and propagation velocity of contractions as well as on lower oesophageal sphincter resting pressure. Conclusions: Sublingual nitroglycerine had modest, dose‐dependent effects on oesophageal peristaltic amplitude and duration, but did not affect the tone of the lower oesophageal sphincter.
Time to maximum effect of lansoprazole on gastric pH in normal male volunteers
Authors: BELL N. J. V. , HUNT R. H. 
Published: October 2003

Background: The time to maximum inhibition of gastric acidity resulting from repeated oral dosing with lansoprazole 30 mg daily for 7 days was studied in nine healthy male volunteers. Methods: Twenty‐four hour intragastric pH monitoring was performed before treatment and on days 1, 3, 5 and 7 of dosing with lansoprazole. Blood samples were taken for the estimation of plasma lansoprazole concentrations. Results: Lansoprazole 30 mg increased mean 24‐h intragastric pH to 3.57 on day 1 compared with baseline mean pH of 2.11 (P<0.05). The mean intragastric pH during the morning period (08.00–13.00 h) was significantly higher on days 3, 5 and 7 than on day 1, but no consistent differences between day 1, 3, 5 and 7 were noted for subsequent periods (13.00–18.00, 18.00–21.00 and 23.00–07.00 h). There were no differences in mean pH between days 3, 5 and 7. Intragastric pH was maintained above pH 3 for 54.7, 60.1, 61.9 and 67.4% of the time on days 1, 3, 5 and 7, respectively.Lansoprazole pharmacokinetic parameters did not change with daily dosing. The area under the lansoprazole plasma concentration–time curve correlated with the intragastric pH (P<0.005). Conclusions: Lansoprazole 30 mg raised intragastric pH significantly from baseline on day 1 to a maximum effect as early as 6 h after the first dose. The degree and duration of acid suppression confirm the usefulness of lansoprazole for the treatment of acid‐related disorders.
Effect of the kappa agonist fedotozine on perception of gastric distension in healthy humans
Authors: COFFIN B. , BOUHASSIRA D. , CHOLLET R. , FRAITAG B. , DE MEYNARD C. , GENEVE J. , LEMANN M. , WILLER J.‐C. , JIAN R. 
Published: October 2003

Background and Aim: Gastric hypersensitivity to mechanical distension has been observed in functional dyspepsia, but no drug is available that specifically acts on gastric afferent pathways to decrease gastric nociception. The aim of this study was to assess the effect of fedotozine, a synthetic ligand for peripheral kappa receptors, on human gastric sensitivity. Methods: Twenty‐seven healthy volunteers were randomized to receive either fedotozine (30 mg t.d.s.) or a placebo, for 7 days. On day 7, the effects of fedotozine were tested on discomfort threshold and gastric compliance during graded isobaric and isovolumic distensions. In 16 of these subjects, the effect of this drug was tested on somatic sensitivity. In 10 other healthy volunteers the effect of fedotozine on gastric distension‐induced inhibition of the RIII reflex, a process closely related to visceral sensitivity, was also studied. Results: During isobaric distensions, the discomfort threshold was significantly higher in subjects on fedotozine than in those on placebo (14.4±0.92 vs. 12.0±1.13 mmHg; P=0.04). Compared to placebo, fedotozine did not modify gastric compliance and somatic sensitivity. Fedotozine also reduced the inhibition of the RIII reflex induced by gastric distension. Conclusion: Fedotozine decreases gastric sensitivity to distension by exerting specific action on gastric afferent pathways.
Lansoprazole versus ranitidine in the maintenance treatment of reflux oesophagitis
Authors: GOUGH A. L. , LONG R. G. , COOPER B. T. , FOSTER C. S. , GARRETT A. D. , LANGWORTHY C. H. 
Published: October 2003

Aims: To assess the relative efficacies of lansoprazole 15 mg once daily, lansoprazole 30 mg once daily and ranitidine 300 mg b.d. in the maintenance treatment of reflux oesophagitis for 12 months. Methods: Multicentre, out‐patient, double‐blind, parallel group, prospectively randomized clinical trial. Patients with grade 0, asymptomatic oesophagitis after 8 weeks of treatment with lansoprazole 30 mg once daily were randomized to receive lansoprazole 30 mg once daily (L30) (n=75), lansoprazole 15 mg once daily (L15) (n=86) or ranitidine 300 mg b.d. (R600) (n=74) for 12 months. Endoscopy was repeated at 6 and 12 months, and symptomatic assessment was made every 3 months. Efficacy was primarily assessed by the time to endoscopically confirmed relapse (oesophagitis grade1) and the proportion of patients who relapsed during the 12‐month study period. Severity of symptoms were secondary efficacy measures. Results: For all patients randomized with at least one post‐baseline endoscopy (intent‐to‐treat principle) both lansoprazole 15 mg (P<0.001) and lansoprazole 30 mg (P<0.001) were significantly superior to ranitidine 600 mg with respect to time to endoscopic relapse. There was no difference between the lansoprazole groups (P=0.11). There was evidence of relapse in 27 of 86 (31.4%), 15 of 75 (20.0%) and 50 of 74 (67.6%) of the patients treated with lansoprazole 15 mg and 30 mg and ranitidine 600 mg, respectively. Patients receiving treatment with either lansoprazole dosages experienced significantly less severe heartburn and regurgitation than those patients treated with ranitidine. There were no differences between the treatment groups with respect to the severity or incidence of adverse events. No clinically significant laboratory changes were observed in any of the treatment groups. Serum gastrin levels were elevated in all treatment groups, and most markedly in those patients receiving lansoprazole, but there was no significant difference between the treatments. Morphological and immunohistochemical examination of the gastric biopsies revealed no clinically relevant changes from baseline in any of the treatment groups. Conclusion: Both lansoprazole 15 mg and lansoprazole 30 mg once daily are significantly more effective than high‐dose ranitidine in maintaining reflux oesophagitis in remission.
One‐week triple therapy with omeprazole, amoxycillin and clarithromycin for treatment of Helicobacter pylori infection
Authors: YOUSFI M. M. , EL‐ZIMAITY H. M. T. , GENTA R. M. , GRAHAM D. Y. 
Published: October 2003

Background: Multi‐drug regimens are generally required to reliably cure H. pylori infection. We previously demonstrated that a 2‐week three‐times‐a‐day regimen of amoxycillin and clarithromycin was effective against H. pylori infection. Objectives: To evaluate the efficacy and side‐effects of a 1‐week twice‐daily dosing schedule for the treatment of H. pylori infection. Methods: We studied the efficacy of 1‐week of therapy with 20 mg of omeprazole, 1 g of amoxycillin and 250 mg of clarithromycin, all twice daily H. pylori status was determined at entry and 4 or more weeks after completing antimicrobial therapy using histology (Genta stain) and culture. Results: Thirty‐one patients with documented peptic ulcer disease and H. pylori infection were treated. The H. pylori infection was cured in 24 (77%, 95% CI= 58–90%) (intention‐to‐treat). In a per protocol analysis the cure rate was 23 of 29 patients (79%, 95% CI= 60–92%). One patient took only 43% of the study drugs and another withdrew following development of an anaphylactic reaction to study medication. Mild side‐effects were reported by 16% including diarrhoea, headache and altered taste. Compliance averaged 95%. Pretreatment clarithromycin resistance averaged 5% and had not been acquired by any strains post‐therapy. Conclusion: This combination of omeprazole, amoxycillin and low‐dose clarithromycin resulted in a relatively low cure rate even in patients with clarithromycin‐sensitive isolates. Large comparative studies will be needed to define the optimal duration, dose and dosing interval if this combination of drugs is to become competitive.
Effect of short‐ and long‐term treatment with omeprazole on the absorption and serum levels of cobalamin
Authors: SCHENK B. E. , FESTEN H. P. M. , KUIPERS E. J. , KLINKENBERG‐KNOL E. C. , MEUWISSEN S. G. M. 
Published: October 2003

Aims: To evaluate absorption of protein‐bound and unbound cyanocobalamin before and during treatment with omeprazole, and cobalamin levels in patients on long‐term treatment with omeprazole. Methods: In eight former duodenal ulcer patients absorption of unbound and protein‐bound cobalamin was determined by measuring 24‐h urinary excretion of unbound 58Co‐cyanocobalamin or protein‐bound 57Co‐cyanocobalamin during a modified Schilling test. Tests were performed before and during treatment with 20 mg and 40 mg omeprazole daily for 9 days.Serum cobalamin levels were assessed in 25 patients with gastro‐oesophageal reflux disease (GERD) before and during long‐term maintenance therapy with omeprazole. Mean treatment duration was 56 months (range 36–81 months). Results: Urinary excretion of unbound cobalamin was unchanged with both dosages of omeprazole. Excretion of 57Co‐cyanocobalamin, however, decreased significantly during treatment with both 20 mg omeprazole (mean ±S.E.M.: 1.31±0.20 vs. 0.54±0.17%; P<0.02) and 40 mg omeprazole (1.25±0.26 vs. 0.29±0.06%; P<0.02).Mean serum cobalamin levels (±S.E.M.) before and during therapy with omeprazole in GERD patients were 298±27 and 261±16 pg/mL (normal range 180–900 pg/mL), respectively (P=N.S.). Conclusions: Absorption of protein‐bound, but not unbound, cyanocobalamin is decreased when measured by a modified Schilling test during treatment with omeprazole. However, no change in serum cobalamin levels was observed in patients with GERD after treatment with omeprazole for up to 7 years.
Effects of misoprostol on healing and prevention of biopsy‐induced gastroduodenal lesions occurring during the administration of diclofenac to volunteers
Authors: DORTA G. , NICOLET M. , VOUILLAMOZ D. , MARGALITH D. , BLUM A. L. , ARMSTRONG D. 
Published: October 2003

Aim: To determine whether misoprostol promotes the healing of non‐steroidal anti‐inflammatory drug‐induced gastroduodenal lesions in a human experimental model. Methods: Mucosal damage and healing of mucosal biopsy sites were assessed endoscopically in 10 healthy, Helicobacter pylori‐negative volunteers with a normal initial endoscopy: they were enrolled in a double‐blind, double‐dummy, placebo‐controlled cross‐over study. They received 2‐week courses of misoprostol (200 μg b.d.) or placebo; a water‐soluble non‐steroidal anti‐inflammatory drug diclofenac 50 mg t.d.s., was given during the second week of each dosage regimen after three endoscopic biopsies had been taken from each of the duodenum, antrum and corpus. Results: The number of unhealed biopsy sites was not different after misoprostol or placebo, although the number of healed biopsy sites was greater in the corpus and duodenum than in the antrum. Misoprostol did not prevent the appearance of diclofenac‐induced erosions and petechiae. Epigastric discomfort was related to the intake of diclofenac and was reduced by misoprostol. Bloating and flatulence occurred more frequently with misoprostol alone and with misoprostol plus diclofenac, than with placebo alone or placebo plus diclofenac. Conclusion: Misoprostol does not prevent new mucosal lesions induced by diclofenac in healthy volunteers and it does not accelerate the healing of the biopsy sites. Misoprostol decreases the frequency of diclofenac‐induced epigastric discomfort, but it increases gas bloating and flatulence.
Selective 5‐hydroxytryptamine antagonism: a role in irritable bowel syndrome and functional dyspepsia?
Authors: MAXTON D. G. , MORRIS J. , WHORWELL P. J. 
Published: October 2003

Background: Abnormalities of gut motility and visceral pain perception are both thought to be involved in the pathogenesis of irritable bowel syndrome and may be susceptible to modulation by drugs affecting the various 5‐HT receptor subtypes. The aim of this study was to investigate the therapeutic potential of a 5‐HT3 antagonist in irritable bowel syndrome. Methods: Fifty patients with irritable bowel syndrome were treated with ondansetron, a highly selective 5‐HT3 antagonist, in a double‐blind, placebo‐controlled cross‐over study. In addition to assessing its effect on the classical symptoms of irritable bowel syndrome (abdominal pain, distension and disordered bowel habit) its effect on symptoms often seen in irritable bowel syndrome, but more commonly associated with functional dyspepsia, was also examined. Results: Ondansetron reduced bowel frequency (P=0.035) and improved stool consistency (P=0.002) in diarrhoea predominant irritable bowel syndrome and did not cause a deterioration of bowel habit in constipation predominant subjects. No statistically significant improvement was seen for abdominal pain or distension, although those patients who did respond were approximately twice as likely to be taking ondansetron than placebo. It was also found that ondansetron significantly improved the upper gastrointestinal symptoms of post‐prandial epigastric discomfort (P=0.008), flatulence (P=0.022) and heartburn (P=0.003). Conclusion: The results of this study justify evaluation of the therapeutic potential of selective 5‐HT antagonists in both functional dyspepsia and irritable bowel syndrome.