bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of photoperiod on the reproductive condition of Nile grass rats (Arvicanthis niloticus) from an equatorial population
Authors: Nunes Scott , McElhinny Teresa L. , Mahoney Megan M. , Smale Laura
Published: March 2003

We evaluated the effects of photoperiod on the reproductive condition of male and female Nile grass rats (Arvicanthis niloticus) descended from members of an equatorial population trapped 2°S of the equator. Study animals housed in 12:12 light:dark (LD) cycles were transferred either to short photoperiod (9:15) or long photoperiod (15:9) for 9 weeks (males) or 11 weeks (females), and various reproductive parameters were assessed. We observed no differences between short‐ and long‐day males with respect to plasma concentration of testosterone, testicular mass, seminal vesicle mass, or spermatogenesis. Similarly, we observed no differences between short‐ and long‐day females with respect to oestrous cycles, uterine mass, follicle size, or presence of corpora lutea. Reproductive parameters of male and female A. niloticus housed in short‐ and long photoperiods were similar to those typically observed among animals descended from the same equatorial population and housed in LD 12:12. Thus, photoperiod appears not to elicit changes in reproductive condition among A. niloticus from populations whose native habitat lies within 2° of the equator. These data contrast with the results of other studies indicating that photoperiod alters reproductive condition in A. niloticus populations living >10° from the equator.
Coastal sponge communities of the West Indian Ocean: morphological richness and diversity
Authors: Barnes David K. A. , Bell James J.
Published: March 2003

Sponges are a reasonably ubiquitous, abundant and highly morphologically plastic taxon. They are very unusual in showing considerable morphological plasticity, not only within higher taxa but within species and at macro and micro scales. In this study we determined the prevalence of sponge morphologies at four coastal study regions in the west Indian Ocean. We show that tropical and subtropical assemblages (in the present study) can be separated on the basis of morphological composition alone (by > 4% arborescent forms or presence of palmate forms in the former). Inter‐tidal sponge assemblages can also be separated from those in the subtidal to a high degree of certainty, also on prevalence of morphologies (absence of tubular or branching forms in the former). The species diversity of many sponge assemblages has been quantified in various environments but, typically, only by specialists. Rarely have equivalent measures been made of morphological diversity. Values of morphological diversity (Shannon H′) were similar, though more variable, to those measured in temperate waters. Substratum nature had a major influence on morphological diversity and evenness, in contrast to geography and bathymetry. As coral reefs were the most diverse and caves and boulders the least, we suggest that substratum heterogeneity and water‐flow complexity are probably the chief determinant of sponge assemblage morphological diversity.
Autonomic nervous activity before and after eradication of Helicobacter pylori in patients with chronic duodenal ulcer
Authors: Katoh K. , Nomura M. , Nakaya Y. , Iga A. , Nada T. , Hiasa A. , Ochi Y. , Kawaguchi R. , Uemura N. , Honda H. , Shimizu I. , Ito S.
Published: March 2003

Background:

Helicobacter pylori infection is involved in the formation of chronic peptic ulcer. However, a previously reported hypothesis concerning the involvement of central autonomic nervous disorder in this condition cannot be ruled out.

Aim:

To use spectrum analysis of heart rate viability to examine autonomic nervous activity before and after H. pylori eradication.

Methods:

Twenty patients with chronic duodenal ulcer (duodenal ulcer group) and 20 age‐matched normal adults (N group). In both groups, 24‐h Holter electrocardiograms (ECGs) were recorded and spectrum analysis of heartrate variability was performed. In the duodenal ulcer group, Holter ECG was recorded before and after H. pylori eradication.

Results:

In the N group, analysis of heart rate variability showed that high frequency (HF) power, an index of parasympathetic activity, was high at night, while the low frequency (LF)/HF ratio, an index of sympathetic function, was high during the daytime. In the duodenal ulcer group, HF power was higher at night than during the daytime, showing a similar pattern to the N group, but the power value was higher than in the N group (P < 0.05). In the duodenal ulcer group, LF/HF at night was significantly higher than that of the N group. In addition, in the duodenal ulcer group, autonomic activity after H. pylori eradication did not differ significantly from that before H. pylori eradication.

Conclusions:

In patients with chronic peptic ulcer, both sympatheticotonia and parasympatheticotonia may occur at night, and this abnormality in autonomic nervous activity may cause increased gastric acid secretion and gastric mucosal vasoconstriction. Abnormalities in autonomic activity persist even after H. pylori eradication, suggesting that they may be an independent risk factor in the formation of chronic peptic ulcer in addition to H. pylori infection.
Ubiquitin‐proteasome inhibitor enhances tumour necrosis factor‐α‐induced apoptosis in rat gastric epithelial cells
Authors: Naito Y. , Handa O. , Takagi T. , Ishikawa T. , Imamoto E. , Nakagawa S. , Yamaguchi T. , Yoshida N. , Matsui H. , Yoshikawa T.
Published: March 2003

Background:

Tumour necrosis factor (TNF‐α) is a candidate factor for involvement in inflammation‐mediated gastric mucosal injury. However, the effect of this cytokine on gastric epithelial cells has been poorly investigated. In the present study, we examined whether gastric epithelial cells are resistant to TNF‐ α‐induced apoptosis, and whether this resistance is related to ubiquitin‐proteasome‐associated nuclear factor‐κB (NF‐κB) activation.

Methods:

The rat gastric mucosal cell line RGM‐1 was grown in DMEM/F12 medium supplemented with 10% FCS. Confluent monolayers of cells were pretreated or not for 60 min with PSI, a peptide aldehyde known to specifically inhibit the chymotrypsin‐like activity of 26S proteasome. Cells were subsequently stimulated with recombinant rat TNF‐α and their viability was determined by WST‐1 assay. Apoptosis was confirmed by fluorescence microscopy after staining with Hoechst 33342 and propidium iodide, and DNA fragmentation was determined by flow cytometry using an APO‐BRDU kit. IκB‐α and the p65 binding subunit of NF‐κB were detected by Western blots.

Results:

Twenty‐four‐hour incubation with TNF‐α alone or PSI alone did not affect the cell viability of RGM‐1 cells. Pretreatment with PSI significantly enhanced the level of apoptosis induced by TNF‐α. In RGM‐1 cells treated with TNF‐α, cytoplasmic IκB‐α decreased and p65 in nuclear extracts increased markedly 30 min after cytokine stimulation. Pretreatment with PSI at 12.5 μmol/L blocked these TNF‐α‐induced changes.

Conclusion:

PSI enhances TNF‐α‐induced apoptosis through inhibition of NF‐κB activation in RGM‐1 cells.
Inhibition of CN (protein phosphatase‐2B) suppresses Ca2+‐mediated acid secretion in rats
Authors: Itoh S. , Otaka M. , Odashima M. , Zeniya A. , Okuyama A. , Jin M. , Otani S. , Iwabuchi A. , Sasahara H. , Masamune O. , Watanabe S.
Published: March 2003

Background and aim:

It has been suggested that CN (calcineurin, protein phosphatase‐2B) regulates signal transduction, particularly in various secretory cells. In this study, we examined whether CN plays a role in stimulus‐secretion coupling of gastric parietal cells.

Materials and methods:

Localization of CN in gastric epithelial cells was examined immunohistochemically. The role of CN in the acid secretion pathway of gastric parietal cells was assessed by evaluating the effect of FK506, a specific inhibitor of CN, on gastric acid secretion in pylorus‐ligated rats. In addition, the effect of FK506 on secretagogue (carbachol, tetragastrin and histamine)‐stimulated acid secretion was investigated in lumen‐perfused rats.

Results:

CN was specifically expressed in gastric parietal cells and chief cells of the gastric mucosal epithelium immunohistochemically. FK506 dose‐dependently inhibited gastric acid secretion in pylorus‐ligated rats. In lumen‐perfused rats, FK506 completely inhibited acid secretion prestimulated by carbachol and tetragastrin, agonists known to increase cytosolic Ca2+, but did not affect acid secretion prestimulated by histamine.

Conclusions:

Our findings demonstrate that FK506 has a potent antisecretory effect in parietal cells through inhibition of only Ca2+‐mediated acid secretion pathways. As FK506 is known to specifically inhibit CN, which plays an important role in signal transduction in various secretory cells, protein dephosphorylation signalling might also be crucial for gastrin and M3 muscarine receptor‐mediated stimulation of proton pump.
Dyspepsia: how to manage and how to treat?
Authors: Talley N. J.
Published: March 2003

Recent guidelines for dyspepsia, defined as pain or discomfort centred in the upper abdomen, emphasize that in younger patients with no alarm features and not taking nonsteroidal anti‐inflammatory drugs, testing for Helicobacter pylori and treatment of the infection if present is a standard of care. If H. pylori is not present, empirical management (e.g. acid suppression) is often prescribed. It is further recommended that if patients relapse or fail to respond to treatment then upper endoscopy be undertaken. However, these guidelines have become controversial for a number of reasons. Firstly, the prevalence of H. pylori infection is falling as is the incidence of peptic ulcer disease due to the infection. Idiopathic peptic ulcer disease is also being increasingly recognized. Furthermore, the cost‐effectiveness of endoscoping treatment failures has been questioned, as the yield is low and patient management is usually not altered. Finally, it remains controversial whether the treatment of H. pylori infection in functional dyspepsia is of value, and two recent high quality meta‐analyses have reached diametrically opposite conclusions. Alternative strategies, such as initially treating with acid suppression and then considering H. pylori infection in those who fail have been suggested, as has in low H. pylori prevalent regions the abandonment of a test‐and‐treat strategy. However, appropriate management trials of these alternative strategies in primary care are lacking. The management of patients with functional dyspepsia who fail initial antisecretory therapy is now difficult; prokinetics have fallen into some disrepute. Tricyclic antidepressants (at a low dose) may be useful in a subset, but adequate trials are lacking.
Esomeprazole in the treatment of Helicobacter pylori
Authors: Laine L.
Published: March 2003

Proton pump inhibitor‐based triple therapy is the most commonly used treatment for eradication of Helicobacter pylori, with pooled eradication rates of approximately 90%. In the USA, per protocol eradication rates with 10‐day proton pump inhibitor‐based triple therapy are approximately 85%. Esomeprazole, a new proton pump inhibitor that is the S‐isomer of omeprazole and produces a greater inhibition of acid secretion than omeprazole, has recently been evaluated in the treatment of H. pylori. Seven‐day twice daily triple therapy with esomeprazole 20 mg, amoxicillin 1 g and clarithromycin 500 mg provided intention‐to‐treat eradication rates of 86–90% and per protocol eradication rates of 90–91% in duodenal ulcer patients in Europe and Canada. Ten‐day triple therapy with esomeprazole 40 mg q.d.s., amoxicillin 1 g b.d. and clarithromycin 500 mg b.d. achieved intention‐to‐treat eradication rates of 77–78% and per protocol eradication rates of 84–85% in USA duodenal ulcer patients. Thus, esomeprazole triple therapy with amoxicillin and clarithromycin is effective in the treatment of H. pylori, with eradication rates comparable to previously studied proton pump inhibitor‐based triple therapies.
Review article: esomeprazole, 40 mg once daily, compared with lansoprazole, 30 mg once daily, in healing and symptom resolution of erosive oesophagitis
Authors: Vakil N.
Published: March 2003

Background : Proton pump inhibitors are the most effective agents for treating erosive oesophagitis, but their relative efficacies have not been well characterized in large clinical trials.

Aim : To compare standard doses of esomeprazole and lansoprazole in healing oesophagitis and resolving accompanying symptoms.

Methods : This was a US, multicentre, randomized, double‐blind trial and included 5241 adult patients (intention‐to‐treat) with endoscopically documented erosive oesophagitis. Patients were randomized to esomeprazole, 40 mg once daily, or lansoprazole, 30 mg once daily, for up to 8 weeks. The primary end‐point, endoscopic healing at Week 8, was assessed using life‐table analysis and a log‐rank test. Secondary endpoints included healing at Week 4, healing according to baseline severity of oesophagitis, control of heartburn and side‐effects.

Results : Healing rates were 92.6% with esomeprazole and 88.8% with lansoprazole at Week 8 (P = 0.0001, log‐rank test). A significant difference was also observed at Week 4. Sustained resolution of heartburn occurred faster and in a larger proportion of patients treated with esomeprazole. Both agents were well tolerated.

Conclusions : Esomeprazole produced significantly higher oesophagitis healing rates than lansoprazole over all grades of oesophagitis. Esomeprazole also provided better control of heartburn and was associated with a greater proportion of patients with sustained resolution of symptoms.
A comparison of omeprazole, lansoprazole and pantoprazole in the maintenance treatment of severe reflux oesophagitis
Authors: Jaspersen  , Diehl  , Schoeppner  , Geyer  , Martens
Published: March 2003

Background:

Proton pump inhibitors are effective for the healing of oesophagitis. Standard doses of omeprazole, lansoprazole or pantoprazole are sufficient for healing in mild to moderate cases of oesophagitis.

Aim:

To compare the efficacy of double the standard doses of omeprazole, lansoprazole or pantoprazole for maintenance treatment of severe oesophagitis complicated by a stricture.

Methods:

Thirty‐six patients with reflux oesophagitis and stricture confirmed by endoscopy were included in a prospective study comparing three maintenance therapies. In all cases weekly dilatation of the stenosis was performed and patients were treated with omeprazole 20 mg b.d. until healing of oesophagitis and dysphagia relief were achieved. Thirty participants responded to therapy and were then randomly assigned to 4 weeks of maintenance treatment with omeprazole (20 mg b.d.; n=10), lansoprazole (30 mg b.d.; n=10) or pantoprazole (40 mg b.d.; n=10). Subsequently, endoscopies were performed—the endoscopists were blinded to the therapy assignment. The endpoints were defined as the absence of oesophagitis, oesophageal stricture and complaints.

Results:

After 4 weeks of treatment, the number of patients remaining in remission (no oesophagitis or stricture and no symptoms) was nine out of 10 (90%) in the omeprazole group, two out of 10 (20%) in the lansoprazole group (P < 0.01) and three out of 10 (30%) in the pantoprazole group (P < 0.01).

Conclusions:

In our study omeprazole was superior to either lansoprazole or pantoprazole in the maintenance treatment of complicated gastro‐oesophageal reflux disease.
Randomized, multicentre comparison of sodium alginate and cisapride in the symptomatic treatment of uncomplicated gastro‐ oesophageal reflux
Authors: Poynard  , Vernisse  , Agostini
Published: March 2003

Aim:

To assess the efficacy and tolerance of sodium alginate compared to cisapride in patients suffering from reflux symptoms, without severe oesophagitis.

Methods:

A total of 353 patients with symptoms of reflux oesophagitis (average age 40 years, 51% men, 33% smokers, 43% consumers of alcoholic drinks) were selected at random—180 treated with sodium alginate (4 sachets per day) and 173 treated with cisapride (5 mg four times a day) for 1 month, with a consultation every 2 weeks. Patients with severe oesophagitis or with predominant symptoms of motor dyspepsia were not included. The principal assessment criterion was the change in the severity of the reflux symptoms as evaluated using a visual analogue scale (VAS) at 4 weeks (extremes 0–100). The secondary criteria were the VAS score at 2 weeks, the number of patients considered as treatment failures, the number of episodes of pain, the impact of the reflux on daily activities and on sleep, and an estimate of costs.

The statistical analyses were planned without any knowledge of the treatments allocated and on an intention‐to‐treat basis.

Results"

There was no difference between the groups at the time of randomization. There were differences in the VAS in favour of the alginate at 2 weeks (29 ± 22 vs. 35 ± 25, P = 0.01) at 4 weeks (13 ± 17 vs. 20 ± 23, P = 0.001), for the number of episodes at 4 weeks (2 ± 2 vs. 3 ± 4, P = 0.001), for pain interfering with daily activities (3% vs. 10%, P = 0.009), for pain disturbing sleep (2% vs. 9%, P = 0.004), and for the proportion of patients considered as treatment failures (11% Vs. 24%, P < 0.001).

Compliance was similar in the two groups. The average cost for 1 month was lower for alginate (130 fr.) than for cisapride (175 fr.).

Conclusion:

Sodium alginate is more effective, and costs less, than cisapride for the treatment of symptoms presented by patients suffering from reflux without severe oesophagitis.
Bismuth‐containing single‐antibiotic 1‐week triple therapy for Helicobacter pylori eradication
Authors: Scott
Published: March 2003

Background:

Although bismuth was both the first drug shown to alter the natural history of peptic ulcer disease and also a constituent of the first very effective eradication regimens, it has been excluded from the newer regimens, despite its safety and low cost, in favour of two antibiotics.

Aim:

To asses a novel 1‐week regimen consisting of bismuth, clarithromycin and a proton pump inhibitor in routine clinical practice.

Methods:

One hundred and three consecutive patients with peptic ulcer disease and antral biopsies containing Helicobacter pylori were given a 7‐day course of treatment with bismuth (tripotassium dicitrato bismuthate chelate) 120 mg q.d.s., clarithromycin 500 mg t.d.s. and lansoprazole 30 mg o.d. Completeness of eradication was assessed by a 13C‐urea breath test, in all except three patients, at least 4 months later.

Results:

Of the 100 patients who were assessed in this open treatment study 84 (84%; 95% CI: 77–91%) had a negative breath test. Minor side‐effects were reported by 14% and more troublesome side‐effects (nausea, vomiting, diarrhoea, hallucinations, nasty taste and body pains) were reported by 10%.

Conclusions:

A 1‐week course of triple therapy including bismuth, clarithromycin and a proton pump inhibitor is effective in routine clinical practice and is well tolerated.
Acid‐inhibitory effects of omeprazole and lansoprazole in Helicobacter pylori‐negative healthy subjects
Authors: Geus  , Mulder  , Nicolai  , Boomgaard D. M. Van Den , Lamers
Published: March 2003

Background:

Omeprazole 20 mg once daily (o.d.) and lansoprazole 30 mg o.d. have similar acid‐inhibitory effects in healthy Helicobacter pylori‐positive subjects. However, little is known about the acid‐inhibitory effects of the o.d. and twice daily (b.d.) doses in H. pylori‐negative subjects.

Aim:

To compare the decrease in gastric acidity of omeprazole 20 mg (o.d. and b.d.) with lansoprazole 30 mg (o.d. and b.d.) in healthy H. pylori‐negative subjects on day 6–7 of dosing.

Methods:

A randomized, investigator‐blind, crossover study design was used. Intragastric pH was measured continuously with glass electrodes positioned in the gastric corpus. Sixteen H. pylori‐negative subjects, whose intragastric acidity fell below pH 4 for 70% of a 24‐h baseline period, were entered in the study.

Results:

Both dosing regimens of omeprazole and lansoprazole significantly increased median gastric pH and percentages of time above pH 4 during the entire 24‐h period, night‐ and daytime, compared to baseline. There were no significant differences in median gastric pH values or time above pH thresholds 3, 4 and 5 between the o.d. dosing regimens. During the night the percentage of time spent above pH 3 and 4 was significantly higher with omeprazole 20 mg b.d. than with lansoprazole 30 mg b.d.

Conclusions:

This comparative study demonstrates that daily doses of omeprazole 20 mg and lansoprazole 30 mg are equally effective in raising intragastric pH in H. pylori‐negative subjects on day 6 of dosing. During the night, omeprazole 20 mg b.d. provides superior gastric acid suppression compared to lansoprazole 30 mg b.d.
Bone and joint diseases in inflammatory bowel disease
Authors: Vos M. De , Keyser F. De , Mielants  , Cuvelier  , Veys
Published: March 2003

The intestinal and articular systems are closely linked in inflammatory bowel disease. Clinical and immunological studies support an important aetio‐pathogenetic link between intestinal and articular inflammation. There is increasing evidence for a negative link between bone mass density and intestinal inflammation. This paper will focus on the prevalence, aetio‐pathogenesis and treatment of arthritis (peripheral, sacroiliitis and spondylitis) and osteoporosis in inflammatory bowel disease.
One‐week therapy for Helicobacter pylori eradication: ranitidine bismuth citrate plus medium‐dose clarithromycin and either tinidazole or amoxycillin
Authors: Cammarota  , Cannizzaro  , Tursi  , Papa  , Gasbarrini  , Cuoco  , Cianei  , Armuzzi  , Fedeli  , Fedeli  , Gasbarrini
Published: March 2003

Background:

One‐week ranitidine bismuth citrate (RBC)‐based triple regimens may be effective for the eradication of Helicobacter pylori. We evaluated the efficacy of two short‐term RBC‐based eradicating therapies including RBC plus medium‐dose clarithromycin and either tinidazole or amoxycillin.

Methods:

Seventy consecutive patients, who underwent gastroscopy for dyspeptic symptoms and were found to be H. pylori‐positive, were randomly subdivided into two groups receiving either RBC 400 mg b.d. plus clarithromycin 250 mg t.d.s. and tinidazole 500 mg b.d. (group RBCCT) or RBC 400 mg b.d. plus clarithromycin 250 mg t.d.s. plus amoxycillin 1 g b.d. (group RBCCA). H. pylori status was evaluated by means of histology and rapid urease test at entry, and by 13C‐urea breath test alone 8 weeks after treatment.

Results:

Sixty‐nine out of 70 enrolled patients completed the study: 35/35 in group RBCCT and 34/35 in group RBCCA. One patient in group RBCCA was lost to follow‐up. In group RBCCT, at the end of treatment, 32 of 35 patients were H. pylori‐negative (per protocol analysis 91%, intention‐to‐treat analysis 91%; 95% CI: 77–98%). In group RBCCA, 31 of 34 patients returned H. pylori‐negative (per protocol 91%; 95% CI: 76–98%, intention‐to‐treat 89%; 95% CI: 73–97%). Slight side‐effects occurred in 3/35 patients (9%) in group RBCCT and in 3/34 (9%) in group RBCCA.

Conclusions:

One‐week regimens consisting of RBC plus clarithromycin and either tinidazole or amoxycillin, combine high eradication rates with modest side‐effects. No substantial difference was found between the two treatment regimens tested in this trial.
Addition of bismuth subnitrate to omeprazole plus amoxycillin improves eradication of Helicobacter pylori
Authors: Carvalho  , Fiorelli  , Jorge  , Silva C. M. F. Da , Nucci  , Ferraz  , Pedrazzoli
Published: March 2003

Objective:

To evaluate whether the addition of bismuth subnitrate to a dual oral therapy regimen with omeprazole plus amoxycillin could improve Helico‐bacter pylori eradication.

Methods:

Fifty consecutive Helicobacter pylori‐positive patients were randomly enrolled to receive either (A) bismuth subnitrate (300 mg q.d.s.), omeprazole (20 mg b.d.) and amoxycillin (500 mg q.d.s.), or (B) omeprazole (20 mg b.d.) and amoxycillin (500 mg q.d.s.). Both groups (n = 25 each) received the medication for 14 days. H. pylori status was reassessed 30 days after completion of the therapy in order to evaluate eradication rates.

Results:

Six patients were lost to follow‐up and therefore excluded from the study (three patients from each group). One patient from Group B withdrew from the study because of side‐effects. The addition of bismuth subnitrate to omeprazole and amoxycillin significantly improved its efficacy in eradicating H. pylori, with 72% (18/25) eradication in Group A and 52% (13/25) in Group B (P = 0.027). The addition of bismuth subnitrate to dual oral therapy was also capable of improving the healing of peptic ulcers when compared with dual oral therapy alone (100%, 8/8 vs. 58%, 4/7; P = 0.021).

Conclusion:

Our results demonstrate that the addition of bismuth subnitrate to dual oral therapy enhances H. pylori eradication, and improves healing of peptic ulcers.
Effects of oral clarithromycin and amoxycillin on interdigestive gastrointestinal motility of patients with functional dyspepsia and Helicobacter pylori gastritis
Authors: Bortolotti  , Brunelli  , Sarti  , Miglioli C.mari M.
Published: March 2003

Background:

Clarithromycin and amoxycillin are antibiotics commonly used in association for Helicobacter pylori eradication. Because this treatment, which lasts 1–2 weeks, is frequently associated with gastrointestinal symptoms, we investigated the effects of these antibiotics on gastrointestinal motility.

Patients and methods:

Gastroduodenal motility was recorded in 14 patients with functional dyspepsia and H. pylori gastritis by means of a low‐compliance manometric system with four recording ports in the stomach and four in the duodenum. Two tablets of clarithromycin 250 mg (seven patients, clarithromycin group) or one of amoxycillin 1 g (seven patients, amoxycillin group), ground and dissolved in 20 mL of water, were given randomly and in double‐blind manner 30 min after the end of the first activity front (AF) of the migrating motor complex (MMC) or, in the absence of AFs, after at least 200 min of recording. Recording continued until an AF was observed during the subsequent 200 min.

Results:

Clarithromycin administration was followed by a typical gastroduodenal AF in a significantly higher number of patients than for amoxycillin administration. In addition, the time lag between clarithromycin administration and the appearance of AFs was 48 min ± 8.5 (mean ± s.d.), significantly shorter than after amoxycillin (121 min ± 29). The clarithromycin‐related duodenal AFs showed a duration of 6.6 min ± 1.5, significantly longer than that of the spontaneous AFs (3.6 min ± 1.2, P < 0.01), while the amoxycillin‐related AFs were not significantly different from the spontaneous ones.

Conclusion:

Clarithromycin stimulated cyclic gastroduodenal motility, while amoxycillin was ineffective. It is likely that symptoms during the eradication treatment are due to this effect of clarithromycin.
Sleep‐related gastro‐oesophageal reflux: provocation with a late evening meal and treatment with acid suppression
Authors: Orr  , Harnish
Published: March 2003

Background:

Two studies were carried out in order to investigate the issue of meal‐provoked nocturnal gastro‐oesophageal reflux.

Methods:

In Experiment 1, 20 symptomatic reflux patients underwent both pH and polysomnographic monitoring on two nights. On one night, patients ate a non‐provocative meal prior to 19.00 hours, while on the other night patients consumed a late evening meal (21.00 hours). In Experiment 2, 17 symptomatic reflux patients were studied using pH and polysomnographic monitoring on two nights subsequent to a late evening provocative meal. On one night, patients received 75 mg of the H2‐antagonist ranitidine, while on another night they received a placebo. The data from 12 of the 17 patients studied were used in the analysis.

Results:

For Experiment 1, no significant differences in the number or duration of reflux events, acid exposure (total %), or polysomnographic measures of per cent of sleep stages between the two nights were observed. The results of the second experiment demonstrated that when given ranitidine, patients experienced significant decrease in acid contact time (total %), and mean duration of reflux events. Subjective reports of discomfort and sleep disturbance were also significantly improved on the drug night. However, significant differences in polysomnographic measures were not observed.

Conclusions:

Based on these results, we conclude that in some symptomatic reflux patients a late‐night non‐provocative meal may not increase the incidence of gastro‐oesophageal reflux, and that a low dose of an H2‐antagonist is effective in decreasing oesophageal acid contact time following a late evening provocative meal.
Insulin‐like growth factor I plays a role in gastric wound healing: evidence using a zinc derivative, polaprezinc, and an in vitro rabbit wound repair model
Authors: Watanabe  , Wang  , Hirose  , Kivilioto  , Osada  , Miwa  , Oide  , Kitamura  , Yoneta  , Seto  , Sato
Published: March 2003

Background:

Although the detailed mechanism is unclear, zinc and its derivative, polaprezinc, have been reported to accelerate gastric ulcer healing in vivo.

Aim:

To investigate the detailed cellular mechanism of polaprezinc on gastric epithelial cells and fibroblasts with special attention to insulin‐like growth factor I (IGF‐I).

Methods:

Isolated rabbit gastric epithelial cells formed a complete monolayer, from which a circular artificial wound with constant size was made. The restoration process was monitored by measuring wound size up to 48 h. Either polaprezinc, IGF‐I, fibroblast conditioned medium or neutralized medium conditioned by anti‐IGF‐I antibody was added at the time of wounding. The expression of mRNA of IGF‐I, hepatocyte growth factor (HGF) and transforming growth factor α (TGF‐α) in fibroblasts with or without polaprezinc treatment was tested using reverse transcription polymerase chain reaction (RT‐PCR). Gastric epithelial cell proliferation was also examined by bromodeoxyuridine (BrdU) staining.

Results:

IGF‐I and fibroblast conditioned medium treatment accelerated gastric epithelial restoration which included cell migration and proliferation. However, polaprezinc and neutralized conditioned medium treatment did not accelerate epithelial repair. RT‐PCR for growth factor mRNA revealed the IGF‐I mRNA expression in fibroblasts was increased after treatment with polaprezinc.

Conclusion:

Polaprezinc induced IGF‐I production from mesenchymal cells, resulting in stimulation of epithelial cell restoration through a paracrine pathway. IGF‐I may play an important role in gastric wound repair.
Foetal outcome in women with inflammatory bowel disease treated during pregnancy with oral mesalazine microgranules
Authors: Marteau  , Tennenbaum  , Elefant  , Lémann  , Cosnes
Published: March 2003

Background:

Little information is available about the safety of high doses of mesalazine during pregnancy.

Aim:

To study the fate of pregnancy and foetal outcome in women taking 1–4 g/day of mesalazine microgranules for inflammatory bowel disease.

Patients and methods:

Case reports were collected from the Pharmacovigilance Department of Ferring SA, France, from a survey conducted in three gastroenterology units, and from a teratology information service. The evolution of pregnancy and foetal outcome were assessed by questionnaire.

Results:

The study covered a total of 123 pregnancies (126 foetuses). Ninety‐six women took mesalazine during the first trimester, 85 during the second and 83 during the third. The mean daily dose was 2.1 ± 0.8 g; 86 women received <3 g/day (low‐dose group), 37 women received ≥3 g/day (high‐dose group). The following abnormalities were observed in the low‐dose and high‐dose groups, respectively: ectopic pregnancy (1/0), spontaneous abortions (1/1), foetal death (0/1), premature deliveries (3/5, P < 0.05), congenital malformations (3/1) and one case of lethal oxalosis. Abnormalities were not considered to be related to mesalazine.

Conclusions:

The use of oral mesalazine microgranules during pregnancy is safe at doses ≤ 2 g/day, and probably also at a dose of 3 g/day.
Review article: clinical pharmacology models of irritable bowel syndrome
Authors: Malagelada J.‐R.
Published: March 2003

This review describes the basis for development of clinical pharmacology models of irritable bowel syndrome (IBS) and presents a critical analysis of current models. IBS is becoming a more circumscribed diagnosis by improved symptom criteria and this is perceived as helpful progress for the development of suitable models. Concepts about the aetiopathogenesis and pathophysiology of IBS are also evolving. Different models have been established to study specific derangements in motor function, visceral reflexes and conscious perception of gut stimuli. The review also focuses on specific examples of drug evaluation using appropriate and validated models.
Review article: the safety and efficacy of alosetron, a 5‐HT3 receptor antagonist, in female irritable bowel syndrome patients
Authors: Mangel A.W. , Northcutt A.R.
Published: March 2003

Irritable bowel syndrome (IBS) is one of the most common gastrointestinal‐related conditions. In this review, the safety and efficacy of alosetron, a potent and selective 5‐HT3 receptor antagonist, in the treatment of IBS are discussed.

Alosetron has been shown to produce statistically significant improvements in abdominal pain, stool consistency, stool frequency and urgency in female IBS patients. By contrast, no consistent improvement has been seen in male IBS patients treated with alosetron. The only adverse event of note with alosetron was constipation, and this represents a class effect of 5‐HT3 receptor antagonists.

In conclusion, alosetron is a safe and effective treatment for female IBS patients.
Review article: pharmacokinetic concerns in the selection of anti‐ulcer therapy
Authors: Lew
Published: March 2003

Rabeprazole is a new, highly potent proton pump inhibitor (PPI) being introduced for the treatment of disorders of gastric acid hypersecretion. Rabeprazole joins other drugs in this class, such as omeprazole, pantoprazole, and lansoprazole, which share a common mechanism of action. Each of these drugs is a substituted benzimidazole, which inhibits activity of the H+, K+‐ATPase located on the apical surface of parietal cells, thereby preventing the secretion of gastric acid. As a result of structural and functional similarities, the PPIs share many pharmacokinetic features. They have comparable rates of absorption, maximum plasma concentrations, and total drug absorptions resulting in similar bioavailability after single‐dose administration. With multiple dosing, rabeprazole differs from omeprazole in that its pharmacokinetic profile does not change significantly over the course of therapy.

All the PPIs are metabolized rapidly, resulting in short half‐lives. However, their duration of activity is much longer, due to the way in which they bind to H+, K+‐ATPase. All are metabolized by hepatic cytochrome P450 enzymes, although only omeprazole has demonstrated significant interactions with other drugs metabolized by this pathway.

Rabeprazole, which has a low potential for interacting with drugs metabolized by cytochrome P450, does interfere with the absorption of digoxin and ketoconazole because of its antisecretory effects. The pharmacokinetics of rabeprazole are altered slightly in elderly subjects and in patients with renal and moderate hepatic disease. However, the pharmacokinetic findings suggest that no dosage adjustment is required in these special populations.
Optimal duration of therapy combining ranitidine bismuth citrate with clarithromycin and metronidazole in the eradication of Helicobacter pylori infection
Authors: SAVARINO  , ZENTILIN  , BISSO  , PIVARI  , BILARDI  , BIAGINI  , MELE  , MANSI  , TERMINI  , VIGNERI  , CELLE
Published: March 2003

Background:

Ranitidine bismuth citrate (RBC) co‐prescribed with clarithromycin and metronidazole for 1 week has been shown to be an effective eradicating regimen for Helicobacter pylori.

Aim:

To determine the optimal duration of this regimen.

Methods:

A series of 165 dyspeptic patients were recruited for this randomized, open, parallel‐group study. They were subdivided into three groups receiving RBC 400 mg b.d. plus clarithromycin 250 mg b.d. and metronidazole 500 mg b.d. for three different periods (4, 7 and 10 days). H. pylori infection was assessed by the concomitant positivity of CLO‐test and histology performed at the pre‐entry endoscopy. The bacterium was considered eradicated on the basis of a negative 13C‐urea breath test performed at least 28 days after the completion of treatment.

Results:

The three subgroups were well matched and 16 patients dropped out of the study for many reasons (six in the 4‐day, five in the 7‐day and five in the 10‐day treatment regimens). Intention‐to‐treat cure rates were 60%, 84% and 85%, and the per‐protocol rates 67%, 92% and 94% in the 4‐day, 7‐day and 10‐day treatment regimens, respectively. There was a significant difference, P = 0.003−0.006 on intention‐to‐treat and P = 0.001−0.002 on per protocol analysis between the 4‐day and the 7‐day and the 4‐day and the 10‐day periods, respectively. The 7‐day and 10‐day periods did not differ from each other. Side‐effects were reported in 9%, 14% and 20% of the 4‐, 7‐ and 10‐day regimens. They led to stopping treatment in four cases (one in the 7‐day and three in the 10‐day period). There was no statistical difference among them.

Conclusions:

Reducing the duration of RBC‐based triple therapy to 4 days provides a low and unacceptable rate of H. pylori eradication. As there is no difference between 7 and 10 days of treatment, 1 week represents the optimal time period for this kind of treatment, based on RBC plus two antibiotics.
Clinical economics review: medical management of inflammatory bowel disease
Authors: WARD  , BODGER  , DALY  , HEATLEY
Published: March 2003

Inflammatory bowel diseases, although they are uncommon and rarely fatal, typically present during the period of economically productive adult life. Patients may require extensive therapeutic intervention as a result of the chronic, relapsing nature of the diseases. Their medical management includes oral and topical 5‐amino salicylic acid derivatives and corticosteroids, as well as antibiotics and immunosuppressive therapies. Assessing the cost‐effectiveness of rival treatments requires valid, reliable global assessments of outcome which consider quality of life, as well as the usual clinical end‐points. Macro‐economic studies of the overall impact of inflammatory bowel disease on health care systems have so far been largely confined to North America, where the total annual US costs, both direct and indirect, incurred by the estimated 380 000–480 000 sufferers has been put at around US2bn. Drugs were estimated to account for only 10% of total costs, whereas surgery and hospitalization account for approximately half. Studies from Europe suggest that the proportion of patients with Crohn’s disease and ulcerative colitis who are capable of full time work is 75% and 90%, respectively. However, whilst only a minority of inflammatory bowel disease patients suffer chronic ill health and their life expectancy is normal, obtaining life assurance may be problematic, suggesting a misconception that inflammatory bowel disease frequently results in a major impact on an individual’s economic productivity.
Delta‐9‐tetrahydrocannabinol delays the gastric emptying of solid food in humans: a double‐blind, randomized study
Authors: McCALLUM  , SOYKAN  , SRIDHAR  , RICCI  , LANGE  , PLANKEY
Published: March 2003

Background:

Delta‐9‐tetrahydrocannabinol (THC), the active constituent of marijuana, is an effective agent in the prevention of chemotherapy‐induced nausea and vomiting.

Aim:

To determine the effect of THC on gastric emptying of a radiolabelled solid food in humans.

Methods:

Thirteen healthy volunteers underwent gastric emptying studies after receiving THC and placebo in a randomized double‐blind fashion on 2 separate days. THC, at a dose of 10 mg/m2 of body surface area, or placebo were administered.

Results:

Gastric emptying after THC was slower than placebo in all subjects. Mean percentage of isotope remaining in the stomach was significantly greater than after placebo from 30 min (85.5 ± 4.3% vs. 94.2 ± 1.4% placebo and THC, respectively, P < 0.05) to 120 min (45.6 ± 7.2% vs. 73.9 ± 7.1% placebo and THC, respectively, P < 0.001) after the test meal. No correlation was found between plasma THC levels and the delay in gastric emptying.

Conclusions:

THC at a dose used for preventing chemotherapy‐induced nausea and vomiting significantly delays gastric emptying of solid food in humans. Therefore, the anti‐emetic property of THC may be mediated through the central nervous system.
Nitric oxide‐releasing NSAIDs inhibit interleukin‐1β converting enzyme‐like cysteine proteases and protect endothelial cells from apoptosis induced by TNFα
Authors: FIORUCCI  , SANTUCCI  , FEDERICI  , ANTONELLI  , DISTRUTTI  , MORELLI  , RENZO  , COATA  , CIRINO  , SOLDATO  , MORELLI
Published: March 2003

Background

: Nitric oxide (NO)‐releasing NSAIDs are a new class of NSAID derivatives with markedly reduced gastrointestinal toxicity. Although it has been demonstrated that NO‐NSAIDs spare gastric mucosal blood flow, molecular determinants involved in this effect are unknown.

Aim

: To investigate the effect of aspirin, naproxen and flurbiprofen, and their NO‐derivatives, on gastric apoptosis and endothelial cell damage induced by tumour necrosis factor‐α (TNFα). In other systems, TNFα‐induced apoptosis is mediated by caspases, a growing family of cysteine proteases similar to the IL‐1β converting enzyme (ICE), and so we have investigated whether NO‐NSAIDs modulate ICE‐like endopeptidases.

Methods

: Rats were treated orally with aspirin, naproxen and flurbiprofen, or their NO‐releasing derivatives in equimolar doses, and were killed 3 h later to assess mucosal damage and caspase activity. Endothelial cells (HUVECs) were obtained from human umbilical cord by enzymatic digestion. Caspase 1 and 3 activities were measured by a fluorimetric assay using selective peptides as substrates and inhibitors. Apoptosis was quantified by ELISA specific for histone‐associated DNA fragments and by the terminal transferase nick‐end translation method (TUNEL).

Results

: In vivo NSAID administration caused a time‐dependent increase in gastric mucosal damage and caspase activity. NCX‐4016, NO‐naproxen and NO‐flurbiprofen did not cause any mucosal damage and prevented cysteine protease activation. NSAIDs and NO‐NSAIDs stimulated TNFα release. Exposure to TNFα resulted in a time‐ and concentration‐dependent HUVEC apoptosis, an effect that was prevented by pretreating the cells with NCX‐4016, NO‐naproxen, NO‐flurbiprofen, SNP or Z‐VAD.FMK, a pan‐caspase inhibitor. The activation of ICE‐like cysteine proteases was required to mediate TNFα‐induced apoptosis of HUVECs. Exogenous NO donors inhibited TNFα‐induced cysteine protease activation. Inhibition of caspase activity was due to S‐nitrosylation of ICE/CPP32‐like proteases. NO‐NSAIDs prevented IL‐1β release from endotoxin‐stimulated macrophages.

Conclusions

: NO‐releasing NSAIDs are a new class of non‐peptide caspase inhibitors. Inhibition of ICE‐like cysteine proteases prevents endothelial cell damage induced by pro‐inflammatory agents and might contribute to the gastro‐protective effects of NO‐NSAIDs.
A cortisol suppression dose–response comparison of budesonide in controlled ileal release capsules with prednisolone
Authors: Edsbäcker  , Nilsson  , Larsson
Published: March 2003

Aim:

To assess the systemic effect of oral budesonide, given as Entocort controlled ileal release capsules, over a dose range of 3–15 mg/day, compared with that of a moderate dose (20 mg/day) of prednisolone.

Methods:

Twenty four healthy subjects were given 3, 9 or 15 mg budesonide or 20 mg prednisolone once daily, or 4.5 mg budesonide b.d., or placebo for 5 days in a randomized, double‐blind crossover study. The area under the curve (AUC) of plasma cortisol concentration and the amount of cortisol excreted in the urine were monitored.

Results:

Both plasma and urine cortisol suppression showed a dose‐response for the daily doses of budesonide. Prednisolone, 20 mg, suppressed plasma cortisol (AUC) statistically significantly more than 15 mg budesonide (P = 0.014), and 3 mg budesonide statistically significantly more than placebo (P = 0.010). No difference in AUC was detected between 9 mg and 4.5 mg budesonide b.d. Similar results for budesonide vs. placebo were obtained from urine cortisol excretion data. However, prednisolone affected urine cortisol less than it affected plasma cortisol.

Conclusion

After 5 days of administration, budesonide controlled ileal release capsules, in both clinical (9 mg/day) and high doses (15 mg/day), affected plasma cortisol less than a moderate (20 mg/day) dose of prednisolone.
Impact of food intake on the antisecretory effect of low‐dose ranitidine and famotidine
Authors: NETZER  , ESCHENMOSER  , HALTER  , INAUEN
Published: March 2003

Background

: Over‐the‐counter status has recently been approved for low‐dose H2‐antagonists in several countries. Insufficient information is currently available on the effect of food in low‐dose H2‐antagonist therapy.

Aim

: Compare the antisecretory efficacy of low‐dose ranitidine and famotidine in fasting and non‐fasting volunteers.

Methods

: Twenty volunteers were randomized into a double‐blind, placebo‐controlled, multiple‐step crossover study comparing the antisecretory efficacy of 75 mg ranitidine, 10 mg famotidine and placebo over 12 h using intragastric pH‐metry. Two standard meals were given after 4 h and 8 h of medication. Fifteen volunteers also participated in a second study comparing the antisecretory effect of both drugs, both with and without meals.

Results

: In non‐fasting subjects, the percentage of time with pH > 4 was similarly elevated for both drugs compared with placebo over the first 8 h: ranitidine 39.3%, famotidine 29.5%, placebo 9.5% (P < 0.001); but not for the last 4 h after the second meal (P > 0.05). Comparing the first 4‐h period with the second, the percentage of pH > 4 was significantly reduced for both drugs in the second period in the subjects given food at the end of the initial 4‐h period (ranitidine 56.9% vs. 26.6%, P = 0.005; famotidine 46.6% vs. 13.3%, P < 0.001). It remained more or less constant, however, for the second 4‐h period in fasting subjects (ranitidine 41% vs. 28.1%, P = 0.46; famotidine 52.7% vs. 52.2%, P = 0.12).

Conclusion

: In non‐fasting volunteers both low‐dose H2‐antagonists had comparable antisecretory effects and were superior to placebo over the first 8 h of therapy. Both drugs achieved a slightly higher antisecretory effect without food intake compared to with food intake.