Biomedical subjects
Publications and source records attributed to M Delvaux.
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Isolated smooth muscle cells from the circular layer of pig and guinea-pig ileum were used to study the effect of prostaglandin E2 (PGE2) and three PGE2 receptor (EP) agonists; iloprost (EP1), butaprost (EP2) and enprostil (EP3). In pig cells, PGE2 and enprostil induced cell contraction (22.1 and 21.5% shortening of cell length, obtained at 10 nM for PGE2 and 1 nM for enprostil, respectively). Iloprost and butaprost had no contractile effect. However, the cholecystokinin octapeptide (CCK-8; 10 nM)-induced contraction was inhibited when cells were preincubated with iloprost or butaprost. In guinea-pig cells, PGE2, butaprost and iloprost induced cell contraction, whereas enprostil had no effect (23.1% for 10 nM PGE2, 22.8% for 1 nM butaprost and 22.6% for 10 nM iloprost). Preincubation with SC19220 (EP1 antagonist) inhibited the PGE2-, butaprost- and iloprost-induced contractions. When the contractile effect of PGE2, butaprost and iloprost was inhibited by addition of SC19220, these agents inhibited the cell contraction induced by CCK-8 (1 nM). Smooth muscle cells from guinea-pig and pig ileum express two PGE2 receptor subtypes that induce opposite effect. EP1 and EP3 receptors mediate cell contraction in guinea-pig and pig, respectively, whereas EP2 receptors mediate cell relaxation in both species.
This study was designed to evaluate the effect of platelet-activating factor (PAF) on isolated smooth muscle cells from guinea pig ileum circular layer, to characterize the PAF receptors involved in this effect and to determine the intracellular pathways triggered by PAF. Cells dispersed by enzymatic digestion were incubated for 30 sec in the presence of PAF and fixed by glutaraldehyde. When inhibitors or antagonists were tested, cells were preincubated with them for 1 min. Then PAF was added for 30 sec, and the cells were fixed. Contraction was assessed by measuring the length of 50 cells and was expressed as the percentage decrease in cell length from controls. The relaxing effect of inhibitors was expressed as the percentage of the maximal contraction observed in their absence. PAF induced a cell contraction in a concentration-dependent manner. Maximal contraction (24.2 +/- 4.2%) was obtained for a PAF concentration of 10 nM (EC50 = 10 pM). PAF-induced contraction was inhibited by the PAF receptor antagonists BN52021, L659.989 and SR27417. Contraction induced by 10 nM PAF was inhibited when cells were incubated in Ca(++)-free medium with or without 2 mM EGTA or in a 1 mM Ca++ medium to which 100 nM nifedipine was added. When cells were preincubated with concentrations ranging from 0.01 pM to 10 microM of relaxing agents (vasoactive intestinal polypeptide, forskolin, 8 Bromo cAMP) known to increase the intracellular level of cAMP, PAF-induced contraction was inhibited. Moreover, when cells were preincubated with pertussis toxin (200 ng/ml) or cholera toxin (8.4 ng/ml), contraction induced by PAF was also inhibited.(ABSTRACT TRUNCATED AT 250 WORDS)
Using an intraluminal probe with six pairs of annular electrodes, the myoelectric activity of the proximal jejunum was recorded during 48-hr sessions in 16 healthy volunteers receiving evening and noon meals (1000 kcal) and breakfast (400 kcal). In 10 subjects receiving no drug, the characteristics of the migrating motor complexes (period, duration of each phase, velocity of propagation of phase 3, duration of the postprandial disruption) varied markedly between subjects but were relatively constant from the first to the second day of recording. Single spike bursts propagated at a rate of 2-5 cm/sec, clusters of 3-10 spike bursts propagated at a rate of 0.5-1 cm/sec, and similar clusters recurring repetitively each 1.5-2 min were observed after the meals and very rarely in the fasted state during phase 2 of nocturnal migrating motor complexes. In six subjects, oral administration of codeine (50 mg) 1 hr before a meal induced migrating motor complexes in the postprandial state, with characteristics similar to that observed in the fasted state except a longer duration of phase 2. Single spike bursts and isolated and repetitive clusters of spike bursts were observed during phase 2 of the codeine-induced migrating motor complexes and after meals preceded by placebo, but very rarely during the phase 2 of nocturnal (fasted state) migrating motor complexes. It is concluded that the patterns of jejunal contractions consisting of propagated single spike bursts and isolated or repetitive spike bursts characterize the postprandial state in healthy humans and are dependent upon digesta flow.
The usefulness of microscopic examination of pure bile directly collected from the biliary tract during endoscopic retrograde cholangiography and without hormonal simulation was prospectively evaluated in 72 patients. According to clinical, biochemical, ultrasonographic, and radiographic data, the patients were separated into two groups: group 1, patients with proven stones (N = 50), and group 2, patients with suspected microlithiasis presenting symptoms suggestive of cholelithiasis but without evidence of macroscopic stones at echography or cholangiography (N = 22). Cholesterol crystals and/or bilirubinate granules were observed (eg, positive examination) in the bile of 41 of the 50 patients of group 1 (82%). Among patients of group 2, seven (32%) had a positive bile examination: cholecystectomy (N = 2) or endoscopic sphincterotomy (N = 5) disclosed minute stones in all cases. In the 15 patients of group 2 with a negative bile examination, cholecystectomy (N = 3), sphincterotomy (N = 2), and clinical (and/or echographic) 20-month follow-up (N = 9) revealed biliary lithiasis in only one patient, in whom recurrent cholangitis led to disclosure of one bile duct stone. According to these results, microscopic examination of bile samples collected during endoscopic retrograde cholangiography exhibited a sensitivity and a specificity for cholelithiasis recognition of 82.7% and 100%, respectively, with a positive predictive value of 88%. We conclude that the accuracy of this method makes it useful to investigate and manage patients with suspected microlithiasis.
The aim of this study was to determine the cholecystokinin (CCK) receptor subtype involved in the direct myogenic effect of CCK on pig ileum. Smooth muscle cells were dispersed from pig ileum circular muscle layer and incubated in the presence of various concentrations of CCK agonists and antagonists. Contraction was assessed by measuring the length of 50 cells and expressed as the percentage decrease in cell length from control. Maximal contraction varied between 19% +/- 3% (gastrin II, 10 nmol/L) and 26% +/- 3% [CCK octapeptide (CCK-8), 10 nmol/L]. EC50 for CCK tetrapeptide (CCK-4) was the same than for pentagastrin (30 pmol/L), which were more potent than CCK-8 (100 pmol/L) and unsulfated gastrin 17 (100 pmol/L), which in turn were more potent than unsulfated CCK heptapeptide (CCK-7; 300 pmol/L) and sulfated gastrin II (300 pmol/L). The maximal contraction induced by synthetic analogs of CCK was 22% +/- 1% for 1 nmol/L JMV 170 and 23% +/- 1% for 10 nmol/L JMV 180. EC50 was 10 pmol/L for JMV 170 and 800 pmol/L for JMV 180. Contraction induced by 10 nmol/L CCK was inhibited as follows: L 365,260 half maximal inhibition (IC50) = 1 nmol/L greater than L 364,718 (IC50 = 90 nmol/L) greater than proglumide (IC50 = 1 mumol/L). Contraction induced by 10 nmol/L unsulfated gastrin 17 was inhibited as follows: L 365,260 (IC50 = 1 pmol/L) greater than L 364,718 (IC50 = 60 nmol/L) greater than proglumide (IC50 = 4 mumol/L). Removal of Ca2+ from the extracellular medium did not alter the contraction induced by CCK-8 (10 nmol/L) but impaired the contraction induced by unsulfated gastrin 17 (10 nmol/L) -56% in Ca(2+)-free medium, -77% in Ca(2+)-free medium plus 2 mmol/L EGTA, and -70% in the presence of 1 mumol/L nifedipine. These results show that the CCK receptor of pig ileum smooth muscle cells is closely similar to the B receptor and is not dependent on an influx of extracellular Ca2+ to induce cell contraction. By contrast, gastrin could act through a specific receptor subtype, the "gastrin receptor," triggering a Ca2+ influx into the cell to induce cell contraction.
Effect of galanin and CCK8 were studied on isolated smooth muscle cells obtained from pig, guinea-pig, rat, rabbit and dog ileum circular muscle layer. Galanin as well as CCK8 induced a concentration-dependent contraction of pig, rat, rabbit and guinea-pig ileum smooth muscle cells. Maximal contraction ranged between 23.7 +/- 1.9% and 26.1 +/- 3.1% decrease in cell length from control in the presence of both peptides. This maximal contraction was obtained at 1 nM galanin in pig, rat, rabbit, 1 nM CCK8 in rat, rabbit, guinea-pig, at 10 nM galanin in guinea-pig and 10 nM CCK8 in pig. Concentrations of galanin inducing a half maximal contraction (EC50) ranged between 8 pM and 80 pM in these species. In dog, CCK8 induced a concentration-dependent contraction of ileum smooth muscle cells, with a maximal contraction (24.5 +/- 2.3%) at 1nM and an EC50 of 50 pM while galanin inhibited cell contraction induced by CCK8. The CCK-induced contraction was abolished at 10 nM galanin and 10 nM VIP. Concentrations of galanin and VIP inducing a half-maximal relaxation of contracted cells were 2 pM and 3 pM respectively. It is concluded that galanin may induce cell contraction of pig, guinea-pig, rat and rabbit ileum circular muscle layer and cell relaxation of dog ileum by a direct myogenic effect.
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1. In order to determine the intracellular mechanisms by which galanin induces contraction of isolated smooth muscle cells from pig ileum, we examined the effects of external Ca2+, relaxing agents, pertussis toxin and forskolin on the galanin-induced contraction and compared these effects to those observed on the cholecystokinin derivative CCK8-induced contraction. 2. Galanin induced a concentration-dependent cell contraction. The maximal contraction (24.5 +/- 2.1% of the length of resting cells) was observed at 1 nM of galanin. When cells were incubated in the simultaneous presence of concentrations of galanin (10 fM) and CCK8 (1 pM) which were ineffective alone, or galanin (10 fM) and acetylcholine (100 pM), a synergistic action was observed corresponding to a submaximal contraction. 3. Incubation of cells in Ca(2+)-free medium caused a significant decrease in galanin- but not in CCK-induced contraction. Nifedipine, a Ca2+ channel blocker, provoked a concentration-dependent inhibition of galanin-induced contraction while it had no effect on the contraction induced by CCK8. 4. Vasoactive intestinal polypeptide (VIP) and isoprenaline, known to induce cell relaxation through an increase in intracellular cAMP level, inhibited CCK-induced cell contraction at concentrations ranging from 1 pM to 1 microM but failed to inhibit cell contraction induced by galanin. 5. When cells were pre-incubated for 3 h in the presence of 200 ng/ml of pertussis toxin, the contraction induced by galanin was abolished while the CCK-induced contraction remained unchanged. On the contrary, 10 microM forskolin abolished the contraction induced by 10 nM CCK but had no effect on galanin-induced contraction. 6. These results indicate that galanin induces a concentration-dependent contraction of pig ileum smooth muscle by a direct myogenic effect. This effect of galanin involves the activation of a pertussis toxin-sensitive G protein, which results in an influx of Ca2+ into the cell. This intracellular pathway is insensitive to the relaxing effect of cAMP.
The effects of galanin and its interaction with cholecystokinin and acetylcholine on smooth muscle cells were studied in vitro on isolated cells obtained from pig ileum circular muscle layer. Galanin induced a concentration-dependent cell contraction with a maximal contraction (24.5% decrease in cell length from control) obtained at 1 nM. The concentration of galanin inducing a half-maximal contraction was 3 pM. Tetrodotoxin (10 microM) failed to inhibit cell contraction induced by galanin (1 nM), pentagastrin (10 nM) and acetylcholine (1 microM). Atropine abolished the contraction induced by acetylcholine (1 microM), but had no effect on galanin- and pentagastrin-induced contraction. L 364,718 inhibited the contraction induced by CCK8 but not the galanin-induced contraction. At the uneffective concentration of 10 fM, galanin had a synergistic effect with an uneffective concentration of CCK8 (1 pM). These results suggest that (i) galanin contracts smooth muscle cells from pig ileum by acting on a specific receptor; (ii) galanin and either CCK or acetylcholine may act in a synergistic way to induce cell contraction.
There are three main groups of indications of lower digestive tract endoscopy: (1) endoscopy may be performed to detect adenomatous polyps and thus prevent colorectal cancer by systematic excision of these polyps before they become invasive malignancies; (2) it may also be performed in patients whose symptoms (e.g. pain, diarrhoea or anaemia) may be due to a lesion of the colon. It usually provides evidence of such diseases as colorectal adenocarcinoma, ulcerative colitis, Crohn's disease, pseudomembranous colitis, post-irradiation colitis, collagen colitis, ischaemic colitis or colonic angiodysplasia; (3) finally, emergency endoscopy can be used in case of rectal haemorrhage, where it is often completed by haemostasis, or in case of volvulus, where it removes the occlusion.
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To study the relation between activation of the Na(+)-H+ antiporter and gastrointestinal cell proliferation, we characterized this antiporter in a pancreatic cell line (AR42J) and studied the effects of mitogenic and nonmitogenic agents as well as those of Na(+)-H+ exchange blocking agents on DNA synthesis. Characteristics of amiloride-sensitive Na+ uptake were those of the Na(+)-H+ exchanger: 1) Na+ uptake was increased by intracellular acidification and depended on external [Na+] and pH; 2) concentrations for half-maximal inhibition (IC50) of Na+ uptake (3 mM [Na+] in medium) were 40 nM 5-(N,N-hexamethylene)amiloride (HA) less than 0.1 microM 5-(N-ethyl-N-isopropyl)amiloride (EIPA) less than 1 microM 5-(N,N-dimethyl)-amiloride (DMA) less than 40 microM amiloride; 3) IC50 for amiloride and analogues to inhibit Na+ uptake depended on [Na+] in medium (in 25 mM Na+ medium, the IC50 values were higher than in 3 mM and were 1 microM EIPA less than 10 microM DMA less than 0.3 mM amiloride). Growth factors for AR42J cells (dialyzed fetal calf serum and epidermal growth factor) activated Na+ uptake in a dose-dependent manner. Bombesin, which is nonmitogenic for AR42J cells, also increased Na+ uptake, indicating that activation of the antiporter is not sufficient to initiate cell proliferation in the AR42J cell line. The effects of Na(+)-H+ exchange blocking agents were tested on serum-stimulated cell proliferation. Decreasing external Na+ dramatically decreased AR42J cell proliferation. Amiloride and analogues inhibited [3H]thymidine incorporation in the same range of concentrations as that with which they inhibited Na(+)-H+ exchange.(ABSTRACT TRUNCATED AT 250 WORDS)
To study the relationships between activation of the Na+/H+ antiporter and gastrointestinal cell proliferation, we characterized this antiporter in a pancreatic cell line (AR4-2J). In the present study, the effects of mitogenic and non-mitogenic agents and of Na+/H+ exchange blocking agents on DNA synthesis are reported. Dialyzed fetal calf serum (FCS) (0-10%) increased amiloride-sensitive 22Na+ uptake in a concentration-dependent manner. There was a linear relationship between the increase in 22Na uptake and cell number when FCS was added in the 2-10% concentration range. Amiloride and analogs inhibited 3H-thymidine incorporation in the same concentration range as that with which they inhibited the Na+/H+ exchange. IC50 values were 1 microM for 5-(N-ethy-N-isopropyl)-amiloride (EIPA), 10 microM for 5-(N,N-dimethyl)-amiloride (DMA) and 0.1 mM for amiloride, respectively, indicating that activation of the Na+/H+ antiporter is necessary to initiate cell proliferation in AR4-2J cells. Maximal CCK9-induced 22Na uptake was 3.65 times the basal rate and was obtained at 0.1 nM. Maximal 22Na uptake triggered by unsulfated gastrin 17 was 2.51 times the basal rate and was obtained at 0.1 nM. The EC50s of CCK9 and gastrin in stimulating the 22Na uptake were similar at 1 pM. Maximal carbamylcholine-induced stimulation was observed at 0.1 mM and was 2.37 times greater than the basal rate. EC50 was 1 microM. In AR4-2J cells, the activity of the Na+/H+ exchanger seems to be directly involved in the control of cell proliferation. However, stimulation of this exchanger by stimulating factors that are not growth factors suggests that intracytoplasmic alkalinization could regulate other important metabolic processes which, as yet, are unknown.
The importance of colonic motor disorders during the irritable bowel syndrome is recognized, but, paradoxically, their description has yet to be perfected. Among the fundamental questions that remain unanswered, three are of prime importance: a) are there one or more specific disturbances in basal colonic motility? b) can specific motor disorders be induced by certain situations, for instance, during stress? c) is there any real relationship between clinical symptoms and coexisting motor disorders? The answers to these questions are full of ambiguities; this may be explained by the difficulty with which methods of investigation are performed as well as the heterogeneous character of the disorders. Presently, recording colonic myoelectric activity over a 24 hour period or more might prove to be useful in increasing our knowledge on motor disorders. It is not at all certain that a specific basal abnormality exists and the results of the effects of stress vary according to the methods used. Segmental hyperactivity in painful constipation, abnormal colonic response to alimentation in the case of painful bloating, and propulsive hyperactivity with absence or decrease in the "sigmoid brake" during painless diarrhea have been noted on basal motor activity recordings during sleep and after meals. Myoelectric disorders, however, are seen in only two-thirds of patients with intestinal functional disorders. "Sensitivity", personality, or other disorders, and particularly, intestinal disorders, can contribute to explain the pathophysiology of "irritable bowels" in which the role of colonic disorders has yet to be shown.
This paper was addressed to know whether early events in mitogenesis (activation of the Na+/H+, activation of ornithine decarboxylase and formation of cyclic AMP) are involved in pancreatic cell proliferation and mediate secretory process. The AR4-2J cell line was used. Analogues of amiloride inhibited cell proliferation but had no effect on amylase release. Activation of ornithine decarboxylase was triggered via a CCK B receptor type not involved in pancreatic secretion. Inhibition of cyclic AMP was not involved in inhibition of cell proliferation caused by somatostatin. Specific effectors might be related either to the secretory or to the trophic pathway. Another possibility is that multiple receptor sub-classes are linked to specific pathways.
This multicentric, double-blind and prospective study, which involved 41 French Gastroenterology Units, was designed to evaluate the efficacy and safety of famotidine, 40 mg at bedtime, compared to single dose ranitidine, 300 mg, in promoting the healing of duodenal ulcer. Two hundred and ninety-six patients with endoscopically proven duodenal ulcer were randomly allocated to 2 treatment groups: 148 were treated with famotidine, and 148 with ranitidine. Patients were treated during 4 weeks and then controlled by endoscopy. Unhealed patients at 4 weeks were treated again by the same drug for 2 weeks and then endoscopically controlled. One hundred and nine patients were evaluable in the famotidine group and 111 in the ranitidine group. Groups were well-matched for age, sex, alcohol and smoking habits, and duration of ulcer disease. At 4 weeks of treatment, 86 of the 109 patients treated with famotidine had healed (79 percent) and 74 of the 111 patients treated with ranitidine healed (67 percent). At 6 weeks of treatment, 104 patients had healed in the famotidine group (95 percent) and 101 in the ranitidine group (91 percent). Results were significantly different between the 2 groups at 4 weeks of treatment only (p = 0.039). Among smoking patients, no statistical difference was observed between the 2 groups at 4 and 6 weeks of treatment. By contrast, in non smoking patients, famotidine appeared more effective (83 percent healed) than ranitidine (67 percent) (p = 0.014) at 4 weeks. Both treatments were well tolerated and severe adverse effects were scarcely observed.(ABSTRACT TRUNCATED AT 250 WORDS)
Surgical fragments of healthy and tumor-bearing pancreas from a patient with pancreatic tumor were studied by electron or light microscopy, histochemistry, and immunocytochemistry (human insulin, glucagon, somatostatin, gastrin, and bovine pancreatic polypeptide). Histological results were compared to those obtained by radioimmunoassay, both in tumor and serum. The tumor was identified as a glucagonoma because reactions for Grimelius' silver impregnation and immunoreaction with an antiserum against glucagon were positive and because a very high level of glucagon in the tumor was observed. Insulin, somatostatin, and gastrin levels remained normal, both in tumor and serum, but the glucagon level was normal in serum. Associated with this silent glucagonoma, an uncommon nesidioblastosis was also diagnosed with many A cells irregularly mixed with acinar cells, isolated or clustered in small groups. Acinar "intermediate" cells of "A" type were also observed. Such associative histopathological processes evoked possible development of an endocrine tumor from nesidioblastic-like tissue. Its embryogenic origin remained uncertain.