The human migrating motor complex (MMC) and sleep cycle have a similar periodicity, and there is some contention as to whether these biorhythms are linked. In irritable bowel syndrome (IBS), episodes of intestinal dysmotility have been described almost exclusively during wakefulness, but IRS patients often complain of poor sleep, and it has been suggested that IBS patients have increased rapid eye movement (REM) sleep. This study sought to identify any associations between sleep stage and small intestinal motility and any objective sleep abnormalities in IBS. Nocturnal motility was recorded from six small intestinal sensors mounted on a fine nasoenteric catheter in eight IBS patients and 10 healthy volunteers. Polysomnography to determine sleep stage was recorded simultaneously. The proportions of time awake, in non-REM and REM sleep was similar in controls and IBS. REM latency did not differ between the two groups despite increased depression in the IBS patients (Hamilton Depression Rating of 8.3 +/- 1.7 in IBS, 3.0 +/- 0.7 in controls, P < 0.01). Nocturnal motility was similar, with phase I occupying most of the MMC cycles. There was no temporal association between MMCs and sleep stage, with no synchrony of phase III for REM episodes. The mean motility index of 4.5 +/- 0.4 during wakefulness was greater than during all sleep stages (P < 0.05). During non-REM sleep stages 1 and 2, motility index of 3.2 +/- 0.3 was greater than 2.3 +/- 0.2 during stages 3 and 4 (P < 0.05), but similar to motility index of 3.3 +/- 0.4 during REM sleep. This sleep architecture and nocturnal small intestinal motility are normal in IBS.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1995

Effect of a tricyclic antidepressant on small intestinal motility in health and diarrhea-predominant irritable bowel syndrome.

Antidepressants are used in irritable bowel syndrome (IBS) and may have effects on the gut independent of improving mood. We have investigated the actions of a tricyclic antidepressant on small intestinal motor function in eight healthy volunteers and in six patients with diarrhea-predominant IBS. Fasting ambulatory motility was recorded from six small intestinal sites for 16-18 hr while on no drug (baseline) and while taking imipramine for five days. Orocecal transit time (OCTT) was measured by lactulose hydrogen breath test, during baseline and imipramine administration. Imipramine did not alter migrating motor complex periodicity, but slowed jejunal phase III propagation velocity in controls from 7.5 +/- 1.1 to 3.6 +/- 0.5 cm/min (P < 0.01) and in IBS from 7.8 +/- 0.6 to 4.4 +/- 0.5 cm/min (P < 0.0001). Phase III duration at each site was increased, and total recorded phase III was greater during imipramine than baseline studies. Imipramine increased the amplitude of phase III contractions. There was no effect of imipramine on non-phase-III motility index or discrete clustered contractions. Imipramine, prolonged OCTT from 73 +/- 6 min to 97 +/- 8 min in controls (P < 0.05) and from 61 +/- 9 min to 89 +/- 8 min in IBS (P < 0.05). Although OCTT was shorter in the IBS group, no motility differences were seen between controls and IBS. This demonstration that a tricylic antidepressant can modify small intestinal motor function in health and in IBS supports the view that these drugs may have therapeutic actions in IBS unrelated to mood improvement.

Adult↗

PubMed1995

Characterization of bile salt uptake by Giardia lamblia.

We have shown previously that Giardia lamblia takes up conjugated bile salt in vitro, and have now investigated the mechanism by which this occurs. Uptake of sodium taurocholate (TC) and glycocholate (GC) with respect to time had an initial exponential component followed by a linear component, consistent with a combination of both active and passive transport processes. The presence of an active transport process was further supported by experiments which showed that bile salt uptake: (i) was concentration dependent (apparent Km's for TC and GC were 0.21 and 0.63 mM, respectively); (ii) was competitively inhibitable; (iii) was reduced by the metabolic inhibitor sodium fluoride (50 mM) and low temperature (4 degrees C). Bile salt was not taken up by glutaraldehyde-fixed parasites, indicating that bile salt was not merely being adsorbed on to the parasite surface. Differential centrifugation of lyzed parasites following exposure to radiolabelled GC, showed that the majority of bile salt was located in the cytosol fraction (76%) with a relatively minor component associated with cell membrane, indicating that bile salt had been internalized. Bile salt analysis of extracts of parasites and culture medium indicated that GC had not been metabolized by Giardia. Thus, like the mammalian ileum, Giardia appears to take up conjugated bile salts by active and passive transport processes. Conjugated bile salts are known to promote encystation and thus these uptake mechanisms may constitute an important survival mechanism for the parasite enabling it to complete its life cycle.

Animals↗

PubMed1995

A randomized prospective comparison of clarithromycin versus amoxycillin in combination with omeprazole for eradication of Helicobacter pylori.

AIM: To compare H. pylori eradication rates using omeprazole in conjunction with either amoxycillin or clarithromycin. BACKGROUND: Omeprazole with amoxycillin is the most widely used dual therapy regimen for eradication of H. pylori. A recent open study suggested a high eradication rate combining omeprazole with the newer macrolide, clarithromycin. METHODS: A randomized prospective trial in 54 patients was conducted to compare 2 weeks of treatment with omeprazole 40 mg once daily and either amoxycillin 500 mg three times daily or clarithromycin 500 mg three times daily. H. pylori eradication was assessed using the 13C urea breath test. RESULTS: Eradication was achieved in 18/26 (69.2%) of subjects treated with omeprazole and amoxycillin and 18/25 (72.0%) of those treated with omeprazole and clarithromycin (P = N.S.). Minor side effects, most commonly altered taste, were reported by 16% of patients and were more frequent in those randomized to clarithromycin (P = 0.01). CONCLUSIONS: These regimens are similarly effective. However, clarithromycin is more expensive, associated with a greater frequency of side effects and, unlike amoxycillin, resistance by H. pylori has been reported. This suggests that clarithromycin may be a useful alternative when there is penicillin allergy or previous treatment failure, but it should not replace amoxycillin as first choice in omeprazole-based dual therapy.

Adolescent↗

PubMed1995

Prevalence of Helicobacter pylori in acromegalic patients during treatment with octreotide.

BACKGROUND: Octreotide, a synthetic long-acting analogue of somatostatin, now has an established role in the treatment of acromegaly. In acromegalic patients treated with octreotide there is an increased incidence of gallstones and possibly gastritis. OBJECTIVES: (1) To compare the seroprevalence of Helicobacter pylori (H. pylori) infection, in acromegalic patients treated with octreotide to that in patients given other treatment modalities. (2) To study retrospectively the temporal relation between H. pylori acquisition and octreotide treatment. PATIENTS: Three groups of acromegalic patients were studied; 35 (20 M) had been treated with octreotide, 17 (10 M) with bromocriptine and 19 (12 M) had received no pharmacological intervention (untreated, surgically treated or treated with radiotherapy). DESIGN/MEASUREMENTS: The presence of H. pylori infection was assessed serologically (Bio-Rad GAP test for IgG), using stored serum, on the most recent sample from each patient and on serial samples from patients treated with octreotide. RESULTS: The prevalence of H. pylori seropositivity was similar in each treatment group, 34, 35 and 37%, respectively. Mean age and duration of acromegaly were similar in the first two groups. Patients who had never received medical treatment were slightly younger. GH levels were similar in all three groups. Patients on octreotide who were seropositive for H. pylori did not differ from those with negative serology with respect to age, duration of acromegaly, duration of octreotide treatment or serum GH level. Serial samples in octreotide treated patients showed a change in status in only one patient; 18 patients continued with negative serology during a mean period of 30 (range 4-62) months. In each of the 6 patients with persistently positive serology during octreotide treatment, stored samples predating octreotide therapy were shown to have already been positive. CONCLUSIONS: The seroprevalence of H. pylori infection in acromegalic patients does not appear to be increased in a manner dependent on the type or duration of medical treatment. In particular, octreotide therapy, while causing the development of histological gastritis in some patients, does not appear to induce the development of H. pylori infection.

Acromegaly↗

PubMed1995

Contractile activity of endothelin precursors in the isolated gallbladder of the guinea-pig: presence of an endothelin-converting enzyme.

A single addition of 3 x I0-7 M ET-1, ET-2 or ET-3 produced contractions that reached a steady state in 28.2 +/- 4.2, 21.1 +/- 1.3 and 24.0 +/- 3.8 min, respectively and took 2.7 +/- 0.4, 2.1 + 0.1 and 1.6 +/- 0.1 min to reach half of this steady-state response.4. Contractions induced by 3 x I0-7 M big ET-11-38 or big ET-11- 39 reached a plateau in 38.5 +/- 3.6 and 35.6 +/- 3.3 min, respectively, and half of these responses were attained in 12.0 +/- 2.5 and 7.1 +/- 1.1 min.Thus, these contractions developed more slowly than those induced by ET-1. Contractions induced by 3 x 10-7 M big ET-21-38 were also much slower to develop than those to ET-2, for these took 49 +/- 2 min to reach plateau and 19.4 +/- 2.1 min to attain half that response. Contractions induced by 3 x 10-7 M big ET-31-41 amide took 50.2 +/- 3.7 min to reach a plateau and 27.3 +/- 3.0 min to reach half of this response.5. Phosphoramidon (0.1, 1 and 3 x 10-4 M) inhibited contractions induced by big ET-11.39. For instance,the contractions induced by 3 x 10-7 M big ET-11-39 were inhibited by 10-4 M or 3 x 10-4 M of phosphoramidon by 62.8 +/- 6.7% or 74.5 +/- 4.6%, respectively. Similarly, contractions induced by ET-21-38 were inhibited by 91.3 +/- 5.4% and the small response induced by big ET-3l-4l amide was abolished by 3 x 10-4M phosphoramidon. Conversely, the neutral endopeptidase (EC 24.11) inhibitor DL-thiorphan(3 x 10-4 M) had no effect. Captopril (10-5 M), pepstatin A (10-5 M), phenylmethylsulphonylfluoride(PMSF, 10-3 M), aprotinin (10-5 M), E-64 (10-5 M), cystatin (10-6 M), leupeptin (10-4 M),chymostatin (10-4 M), or bestatin (10-5 M) did not inhibit but rather increased to a similar, but small degree the contractions induced by 3 to 30 x 10-9 M big ET-11-39. Only captopril (10-5 M) or leupeptin(10-4 M) increased the contraction induced by 3 x 10-7 M big ET-11-39. Phosphoramidon (10-4 M),pepstatin (10-5 M) or PMSF (10-3 M) did not affect contractions induced by ET-1.6. Removal of the epithelium increased by 70% the size of the contraction induced by 5 microM histamine(1.08 +/- 0.05 g; n = 160 to 1.84 +/- 0.14 g; n = 12) but did not affect, in absolute terms, the contraction induced by ET-1 (as a % of the response to histamine, these responses were, of course, apparently depressed). Epithelium removal did, however, increase the size of the contractions induced by 3 to 30 x 10-9 M big ET-1 -39 which was very similar to the effect of the protease inhibitors.7. In competition binding studies on membranes prepared from the guinea-pig gallbladder, 10-11 MET-1 inhibited by 76.9 +/- 3.1% the binding of [125]-ET-I while porcine big ET-11-39 caused no inhibition(0.7 +/- 3.0; n = 3). ET-1 (10-6 M) inhibited binding by 95.7 =/- 1.1% (n = 3) while at this much higher concentration, big ET-11-39 inhibited binding by only 16.8 +/- 4.2% (n = 3). This clearly suggests that big ET-11-39 does not bind directly to ET receptors.8. Thus, a phosphoramidon-sensitive endothelin-converting enzyme (ECE), different from neutral endopeptidase (NEP; EC 24.11) and not located on the epithelium, converts big ET-1 into ET-1 in the gallbladder of the guinea-pig. This ECE appears to act preferentially on big ET-1 or big ET-2 over bigET-3.

Animals↗

PubMed1995

Sequential changes in small intestinal structure and function during rotavirus infection in neonatal rats.

Rotavirus infection is the most common cause of acute diarrhoea in children worldwide. The structural and functional consequences of mammalian rotavirus infection in the small intestine have been incompletely studied and the mechanism of enterocyte damage poorly defined. This study used a neonatal rat model of group B rotavirus infection to study the natural history, clinical features, and the structural and functional consequences of infection in the small intestine. Group B rotavirus infection in eight day old neonatal rats produced diarrhoea by 24-36 hours, which was accompanied by weight loss during the early stages of infection. By seven days the diarrhoea had ceased and body weight was similar to noninfected controls. Rotavirus could be recovered in faeces from 24-72 hours. Light microscopy and morphometry confirmed reduction in villous height in both jejunum and ileum, with a reduction in total mucosal thickness indicating true flat mucosa. Increase in crypt depth followed villous shortening and continued as villous height progressively increased between 96-168 hours. Steady state perfusion of the entire small intestine with a plasma electrolyte solution confirmed the presence of a net secretory state for water between 12-48 hours, with a parallel reduction in sodium absorption. Group B rotavirus infection produces a self limiting acute diarrhoeal illness in neonatal rats similar to human rotavirus infection. Infection causes a reversible flat mucosa resulting from enterocyte loss associated with a net secretory state for water and impaired sodium absorption as a functional correlate. These findings may have relevance for the pathogenesis of human rotavirus infection.

Animals↗

PubMed1995

Role of 5-hydroxytryptamine in intestinal water and electrolyte movement during gut anaphylaxis.

Exposure of sensitised intestine to specific allergen is known to produce appreciable reduction in water and electrolyte absorption. The mediators participating in this process have not been fully characterised. The effects of the 5-hydroxytryptamine2 (5-HT2) and 5-HT3 receptor antagonists, ketanserin and granisetron, respectively, on water movement during intestinal anaphylaxis were studied. Hooded Lister rats (120-150 g) were sensitised to ovalbumen and 14 days later, intestinal water and electrolyte movement was assessed at 10 minute intervals by in situ jejunal perfusion with a plasma electrolyte solution (PES) or PES containing 20 mg/l ovalbumen. Within 20 minutes of exposure to PES+ovalbumen, net water secretion that could be completely prevented by the mast cell stabilising agent doxantrazole occurred compared with absorption with PES alone (median -20 microliters/min/g (interquartile range -43 to -5), n = 11), v (107 (86 to 113), n = 10; p < 0.01). Pre-treatment with subcutaneous ketanserin 200 micrograms/kg (n = 7) or granisetron 300 micrograms/kg (n = 8) partially inhibited the secretory response to PES+ovalbumen (18 (11 to 48) and 13 (6 to 32) respectively; both p < 0.01 compared with PES+ovalbumen control). After 40 minutes perfusion with PES+ovalbumen, the changes in water movement were less pronounced 24 (-3 to 43) and neither ketanserin or granisetron had any effect (ketanserin: 48 (28 to 87), granisetron: 41 (32 to 83); NS). In all experiments, sodium and chloride movement paralleled that of water. Thus, the profound water secretion that occurs in the early stages of intestinal anaphylaxis is partly 5-HT dependent because it can be reversed by 5-HT2 and 5-HT3 receptor antagonists. Other mediators must also be involved, especially in the late phase of anaphylaxis.

Anaphylaxis↗

PubMed1995

Ornithine decarboxylase as a marker for premalignancy in the stomach.

Assessment of mucosal ornithine decarboxylase (ODC) activity in the human large bowel may be of value as a marker of potential malignant risk. Its value as a marker of premalignancy in the upper gastrointestinal tract is less clear. Using a [14C]-ornithine bioassay, gastric mucosal ODC activity was measured in 32 normal subjects and 22 patients with confirmed gastric cancer. These results were compared with 47 patients at increased risk of upper gastrointestinal malignancy, (32 patients with partial gastric resection, 15 patients with familial adenomatous polyposis). Median ODC activity in normal subjects was 371 pmol/mg protein/h, (interquartile range (IQR), 230-617). There was no variation with age or sex and no relation to Helicobacter pylori status. Normal subjects had significantly lower ODC activity than patients with a gastric resection or confirmed gastric cancer, but similar to patients with familial adenomatous polyposis. Furthermore, no difference in activity was identified between patients with a gastric resection and established gastric cancer. ODC activity was, however, significantly increased in areas of gastric atrophy or intestinal metaplasia, regardless of the clinical group from which the samples were obtained. It is concluded that measurement of mucosal ODC activity does not provide additional predictive information of malignant risk in the stomach and investigation of other potential biomarkers of malignancy is warranted.

Adenomatous Polyposis Coli↗

PubMed1995

Role of 5-hydroxytryptamine type 3 receptors in rat intestinal fluid and electrolyte secretion induced by cholera and Escherichia coli enterotoxins.

Cholera toxin and Escherichia coli heat labile toxin (LT) induced intestinal secretion has in the past been attributed exclusively to an increase in intracellular cAMP whereas E coli heat stable toxin (ST) induced secretion is mediated through cGMP. Evidence is accumulating on the importance of 5-hydroxytryptamine (5-HT) in cholera toxin induced secretion, but its role in LT and ST is not well established. This study therefore investigated in vivo the effect of 5-HT3 receptor antagonist, granisetron, on intestinal fluid and electrolyte secretion induced by cholera toxin, LT, and ST. Granisetron (30, 75, 150, or 300 micrograms/kg) was given subcutaneously to adult male Wistar rats 90 minutes before instillation of 75 micrograms cholera toxin or 50 micrograms LT in isolated whole small intestine. In situ small intestinal perfusion was performed with an iso-osmotic plasma electrolyte solution (PES) to assess fluid movement. In a second group of animals, granisetron (300 micrograms/kg) was given subcutaneously and two hours later small intestinal perfusion with PES containing 200 micrograms/l ST was performed. Cholera toxin induced net fluid secretion (median -50.1 microliters/min/g (interquartile range -59.5 to -29.8)) was found to be dose dependently decreased or abolished by granisetron (plateau effect at 75 micrograms/kg: 18 (-7.8 to 28), p < 0.01). Granisetron in high dose (300 micrograms/kg), however, failed to prevent LT or ST induced secretion (-52 (-121 to -71) v -31 (-44 to -18), and (-39 (-49 to 17) v (-22 (-39 to -3)), respectively). Sodium and chloride movement paralleled that of fluid. In conclusion, these data show that 5-HT and 5-HT3 receptors play an important part in cholera toxin induced secretion but are not involved in E coli heat stable or heat labile toxin induced secretion.

Animals↗

PubMed1995

Attachment of Giardia lamblia trophozoites to a cultured human intestinal cell line.

Attachment of Giardia lamblia trophozoites to enterocytes is essential for colonisation of the small intestine and is considered a prerequisite for giardia induced enterocyte damage. The precise mechanisms involved are still being debated and some earlier work has been performed in models of uncertain biological relevance. In this study, co-incubation of giardia with enterocyte-like differentiated Caco-2 cells was used as a model to study the influence of physical and chemical factors on attachment. Giardia attachment was maximal between one and eight hours and stable over pH 7.2-8.2 but it was reduced by acidification. Attachment was dependent on temperature and was maximal at 37 degrees and virtually abolished at 4 degrees C. It was reduced compared with controls (p < 0.05) by EDTA 2.5 mM (mean (SEM) 32 (4)%), colchicine 12.5 microM (35 (5)%), mebendazole 10 micrograms/ml (30 (3)%), and cytochalasin B 1 microgram/ml (34 (3)%). Giardia attachment was also diminished by preincubation with mannose 50 mM or mannose-6-phosphate 35 mM (21 (4); 17 (5)%) or by preincubating Caco-2 cells with concanavalin A 100 micrograms/ml (19 (2)%). Enhanced binding was not evident after trypsinisation of trophozoites. Scanning electron microscopy showed that giardia seemed to attach to the Caco-2 monolayer predominantly by its ventral surface but dorsal orientation was also observed. No difference in attachment was observed between three different giardia isolates or a parent isolate and its clone. Attachment of giardia to Caco-2 cells is primarily by cytoskeletal mechanisms, inhibitable by interference with contractile filaments and microtubules, while attachment by mannose binding lectin also seems to mediate binding.

Animals↗

PubMed1995

Traveler's diarrhea: clinical presentation and prognosis.

Traveler's diarrhea is usually a short, self-limiting illness lasting on average 3-5 days. The illness may present either as (1) acute watery diarrhea, (2) diarrhea with blood (dysentery) or (3) chronic diarrhea, often with clinical evidence of fat or carbohydrate malabsorption. The majority of cases of traveler's diarrhea are due to intestinal infection and resolve without specific treatment. Antibiotics can reduce the severity and duration of the illness and are always indicated for dysenteric shigellosis and amoebiasis. Oral rehydration therapy is the mainstay for managing water and electrolyte depletion.

Acute Disease↗

PubMed1995

Central 5-hydroxytryptaminergic function in irritable bowel syndrome.

BACKGROUND: Psychological factors may contribute to the aetiology and exacerbation of symptoms in irritable bowel syndrome (IBS), suggesting that the central nervous system may be an important site of dysfunction in IBS. Hormonal responses after a serotonergic challenge assess the functional integrity of central 5-hydroxytryptaminergic pathways and are diminished in depression. The aim of this study was to determine whether hormonal responses in IBS after a serotonergic challenge would be decreased, as in depression, or exaggerated, as have been reported in another functional gastrointestinal disorder, nonulcer dyspepsia. METHODS: Fourteen IBS patients, 16 healthy volunteers, and 9 patients with inflammatory bowel disease were given 30 mg d-fenfluramine, a selective stimulus to central 5-hydroxytryptaminergic pathways. RESULTS: Plasma prolactin and cortisol concentrations during the following 5 h increased to a similar extent in all three subject groups, despite increased levels of anxiety and depression (as scored on the Hospital Anxiety and Depression Scale and Beck Depression Inventory) in the IBS and inflammatory bowel disease patients compared with the healthy controls. Base-line cortisol concentration correlated with the magnitude of affective disorder. CONCLUSION: In contrast to the alterations of central 5-hydroxytryptamine receptor sensitivity seen in depression and non-ulcer dyspepsia, central 5-hydroxytryptaminergic pathways function normally in IBS.

Adult↗