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Biomedical subjects

M Chovet

Publications and source records attributed to M Chovet.

At least 19 recordsLinked to original sources
PubMed2005

LPS-induced lung inflammation is linked to increased epithelial permeability: role of MLCK.

The respiratory system is directly exposed to low levels of lipopolysaccharide (LPS), present as a contaminant on airborne particles. In cystic fibrosis, the prevailing data identify structural changes of the airway epithelium, as well as tight junction dilatation. This study was aimed at determining the contribution of myosin light chain kinase to maintaining airway epithelium barrier integrity in the lung inflammatory response to LPS in rats. The effects of the selective myosin light chain kinase inhibitor, 5-iodonaphthalene-1-sulphonyl-homopiperazine (ML-7), were evaluated: 1) on pulmonary inflammation and airway epithelium barrier permeability alterations induced by intra-tracheal LPS from Pseudomonas aeruginosa; and 2) on levels of the phosphorylated form of the myosin light chain, which is increased in a human airway epithelial cell line (NCI-H292) and tracheal tissue after LPS exposure. The results show that LPS increased airway epithelium barrier paracellular permeability and lung inflammation, and that pre-treatment with ML-7 inhibited both effects. This effect of ML-7 was associated with the inhibition of phosphorylated myosin light chain in both NCI-H292 cells and tracheal tissue. The data, obtained using in vivo and in vitro approaches, demonstrate a key role for myosin light chain kinase in lung inflammation, and suggest that myosin light chain kinase could be a potential target for novel drugs intended for relief of lung injury.

Animals↗
PubMed2002

Antidiarrhoeal properties of a novel sigma ligand (JO 2871) on toxigenic diarrhoea in mice: mechanisms of action.

BACKGROUND AND AIMS: Sigma ligands display antisecretory activity against various secretagogues, suggesting antidiarrhoeal properties. In this study, we evaluated: (i) the antidiarrhoeal effect of JO 2871, a high affinity sigma ligand, in three models of toxigenic diarrhoea in mice; and (ii) the site and mechanism of action of this compound. METHODS: Faeces were collected after toxin or vehicle administration in male DBA2 or NMRI mice. Diarrhoea was determined by cumulative stool weight (mg) over a 120 minute period. Diarrhoea was induced by intravenous administration of Salmonella enteriditis lipopolysaccharide (LPS), or oral administration of Escherichia coli heat stable (E coli-sta) or Clostridium difficile toxins. Two sigma ligands, igmesine and JO 2871, were administered either orally or intravenously, 60 and 30 minutes before the toxins, respectively. JO 2871 was also given orally 30 minutes after E coli-sta. In addition, JO 2871 was administered intracerebroventricularly five minutes before LPS and E coli-sta. BMY 14802 (1000 microg/kg orally), a sigma receptor antagonist, or cyclosomatostatin (CSS 1 microg/kg intravenously), a somatostatin antagonist, were given five minutes prior to JO 2871 in LPS, E coli-sta, and C difficile toxin treated mice. Gastric emptying and intestinal transit were evaluated after oral JO 2871 and BMY 14802 and intravenous CSS. RESULTS: Stool weight measured 120 minutes after administration of the toxins was significantly increased. Oral JO 2871 and igmesine dose dependently inhibited toxigenic diarrhoea in all models. ED(50) values obtained using JO 2871 (1-20 microg/kg) were more than 40 times lower than those obtained with igmesine. Oral JO 2871 given after E coli-sta also inhibited diarrhoea in a dose dependent manner (ED(50) 50 microg/kg). Both sigma ligands were active by the intravenous route on LPS and E coli-sta induced stool weight increases. JO 2871 administered intracerebroventricularly failed to block this effect at any dose tested. Both BMY 14802 and CSS reversed the antidiarrhoeal effect of oral JO 2871. JO 2871, BMY 14802, and CSS did not affect transit parameters. CONCLUSIONS: JO 2871 exerts a potent oral antidiarrhoeal effect, acting peripherally through sigma sites and somatostatin release.

Animals↗
PubMed2000

Gastrointestinal functional bowel disorders: new therapies.

Present therapies for functional gastrointestinal disorders are symptomatic and mainly treat altered bowel habits. New therapies are focused on nerve-gut communication dysfunction: 5-HT3 antagonists and 5-HT4 agonists have demonstrated activity in clinical trials. Promising targets for upper gut dysmotility drugs are motilin and cholecystokinin A receptors. Tachykinins, calcitonin gene-related peptide or glutamate antagonists are the most relevant candidates for visceral pain.

Gastrointestinal Diseases↗
PubMed2000

Antinociceptive effect of pregabalin in septic shock-induced rectal hypersensitivity in rats.

Pregabalin [S-(+)-3-isobutylgaba] is a novel compound under development for its analgesic, anxiolytic, and anticonvulsant properties, and its interaction with the alpha(2)delta-subunit of voltage-dependent Ca(2+) channels. In this study, we investigate the antinociceptive activity of pregabalin in a rat model of delayed visceral hyperalgesia induced by i.p. lipopolysaccharide (LPS) administration. LPS (Escherichia coli, serotype O111:B4) leads to a delayed lowering threshold (9-12 h) of abdominal contractions in response to rectal distension (RD) in awake rats surgically prepared for electromyography of abdominal muscles. This allodynic effect of LPS was blocked by morphine (0.3 mg/kg s.c.), and the action of morphine was antagonized by naloxone (2.5 mg/kg s.c.). A single i.p. (10, 30 mg/kg) and oral (1, 3, 10 and 30 mg/kg) treatment of pregabalin dose dependently suppressed LPS-induced rectal hypersensitivity. When administered 2 h before RD (but preceded 12 h by LPS injection), the oral dose of 10 mg/kg was effective both in the allodynic response induced by LPS and in the intensity of the nociceptive response related to RD. Pretreatment by either naloxone or bicuculline (a GABA(A) antagonist, 0.5 mg/kg i.p.) did not affect the antiallodynic effect of pregabalin. We conclude that pregabalin is a therapeutic candidate in the treatment of gut hypersensitivity not acting through GABA(A) and opiate receptors.

Analgesics, Non-Narcotic↗
PubMed1995

[Mass treatment of onchocerciasis in 1996].

Mass treatment of onchocerciasis has changed radically in the last 20 years. With implementation of the Onchocerciasis Control Programme (OCP), use of insecticides to control vector larvae has been effective but has not been extended to all infected areas due to the cost. The consequences of this problem have been lessened thanks to ivermectin, an effective drug that can be administered in a single yearly dose. Although ivermectin does not appear to induce major side-effects, surveillance is necessary after administration in polyparasitized subjects living in zones where loaiasis is present and in hypermicrofilaremic subjects. To assist in the fight against onchocerciasis, ivermectin is distributed free of charge through the Mectizan Foundation by Merck Laboratories. Inexpensive community distribution programs with active participation of the populations at risk have demonstrated their usefulness. The results of mass treatment through the Mectizan Foundation have been excellent. Non-governmental organizations and in particular the Organization for the Prevention of Blindness (OPB) have become increasingly involved in the fight against onchocerciasis. The campaign conducted by the OPB in Mali, Senegal and Guinea illustrate this involvement. The role of non-governmental organizations expanded greatly with the implementation of the APOC programme supported by the World Bank.

Filaricides↗
PubMed1993

Neuropeptide Y and sigma receptor agonists act through a common pathway to stimulate duodenal alkaline secretion in rats.

Neuropeptide Y (NPY) has been shown to mimic the effects of some sigma receptor agonists in the brain and to possess the same proabsorptive effect as these agonists in the isolated mouse jejunum. The aim of present study was to investigate the effect of NPY on duodenal alkaline secretion in the rat and to define its mode of action. NPY (0.01 to 3 micrograms/kg i.v.) induced a dose-related increase in duodenal bicarbonate secretion, the maximal effect being obtained at 1 micrograms/kg. This response was significantly inhibited by the i.v. administration of haloperidol, BMY 14802, devazepide, hexamethonium, tetrodotoxin and by bilateral truncal vagotomy, but not by SCH 23390, sulpiride, prazosin or atropine, whereas i.c.v. devazepide had no effect. This pharmacological profile is identical to that reported for sigma receptor agonists. The results suggest that NPY and sigma ligands act through a common pathway to stimulate duodenal alkaline secretion in the rat.

Animals↗
PubMed1993

Effects of a new sigma ligand, JO 1784, on cysteamine ulcers and duodenal alkaline secretion in rats.

BACKGROUND: The ulceroprotective effects of JO 1784 [(+)-N-cyclopropyl-methyl-N-methyl-1,4-diphenyl-1-ethyl-but-3-en-1-yl amine, hydrochloride], a new specific and highly selective sigma ligand, were examined in rats. METHODS: Different models of gastric ulcers (4-hour restraint stress, aspirin, ethanol, and taurocholate) and cysteamine-induced duodenal ulcers were used. The gastric acid secretion (4-hour Shay rat preparation) and the duodenal bicarbonate secretion were also studied. RESULTS: JO 1784 elicited a potent protection against duodenal ulcers but had a weaker protective effect on any of the gastric ulceration models tested. It displayed no gastric antisecretory activity but induced a dose-dependent stimulation of duodenal bicarbonate secretion. Haloperidol, hexamethonium, tetrodotoxin, bivagotomy (but not atropine), and the intravenous but not intracerebroventricular administration of devazepide, a cholecystokinin A antagonist, inhibited the stimulatory effect of JO 1784. CONCLUSION: These results show that JO 1784, a selective sigma ligand, is a potent protector of the duodenal mucosa. This activity may be related to its stimulating effect on bicarbonate secretion, which is driven through a complex nervous mechanism involving muscarinic synapses, vagal afferent fibers, and peripheral cholecystokinin receptors. This drug might open a new specific way in the treatment of duodenal ulcers.

Animals↗
PubMed1990

[Ambulatory surgery of cataracts in Eastern Senegal].

The epidemiologic data and surgical results of 253 cataract extractions performed in a new department of Ophthalmology in Eastern Senegal were reviewed. 87 per cent have been operated without hospitalization, with restricted follow up. The complication rate was low, showing that this kind of surgery was suitable to local socio-economical conditions.

Ambulatory Surgical Procedures↗
PubMed1989

Central and peripheral effects of prostaglandin E2 and enprostil on exocrine pancreatic secretion in rats.

Prostaglandin E2 (PGE2) has been reported to exert some centrally mediated effects on intestinal motility and secretion and on gastric secretion, but it is not known whether such central effects exist on pancreatic secretion. The central and peripheral effects of PGE2 and enprostil, a long-acting, potent PGE2 analogue, were studied in conscious and anesthetized rats fitted with pancreatic fistulae. In chronically implanted, conscious rats, PGE2 inhibited the secretion of fluid, bicarbonate, and total protein in the pancreatic juice, both after i.v. or intracerebroventricular (icv) injections. The maximal inhibition was similar after both injection procedures (about 45% for fluid and bicarbonate and 60% for protein), but the potency of PGE2 was three to 10 times greater by the icv than the i.v. route. Enprostil also inhibited pancreatic secretion in a dose-related way. The maximal inhibition was larger than after PGE2 injection (about 70% for fluid and bicarbonate and 90% for protein). The potency of enprostil was five to 10 times lower by the icv than by the i.v. route. The diversion of gastric secretion suppressed the effect of icv PGE2 on fluid and bicarbonate output but not on protein and did not change the effect of enprostil on all the variables of pancreatic secretion. Adrenergic antagonists did not suppress the effect of icv PGE2 or enprostil on pancreatic secretion. In anesthetized rats, i.v. PGE2 inhibited hormone-stimulated protein secretion but did not change fluid and bicarbonate output, while i.v. enprostil inhibited cholecystokinin-stimulated fluid, bicarbonate, and protein output in the pancreatic juice.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1980

[Ocular lesions in lepromatous leprosy (author's transl)].

Ocular lesions observed in III cases of lepromatous or borderline leprosy are described. Tables are included which indicate the visual acuity, corneal sensitivity, and lesions noted in the appendages. Particular attention is paid to lesions in the pars plana, which include true posterior cyclitis having the appearance of "ants eggs" or "pearls" deposits on the retina, associated with vascular lesions and peripheral hyalitis. The absence of associated mucular edema is strongly emphasized. The etiopathogenicity of lesions of this type is probably directly related to leprous erythema nodosum. Detailed studies should be conducted on the chronological stages of these affections and their subsequent progression.

Adolescent↗