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Biomedical subjects

M Prouteau

Publications and source records attributed to M Prouteau.

13 recordsLinked to original sources
PubMed2000

Lentil root statoliths reach a stable state in microgravity.

The kinetics of the movement of statoliths in gravity-perceiving root cap cells of Lens culinaris L. and the force responsible for it have been analysed under 1 g and under microgravity conditions (S/MM-03 mission of Spacehab 1996). At the beginning of the experiment in space, the amyloplasts were grouped at the distal pole of the statocytes by a root-tip-directed 1-g centrifugal acceleration. The seedlings were then placed in microgravity for increasing periods of time (13, 29, 46 or 122 min) and chemically fixed. During the first 29 min of microgravity there were local displacements (mean velocity: 0.154 microm min(-1)) of some amyloplasts (first at the front of the group and then at the rear). Nevertheless, the group of amyloplasts tended to reconstitute. After 122 min in microgravity the bulk of amyloplasts had almost reached the proximal pole where further movement was blocked by the nucleus. After a longer period in microgravity (4 h; experiment carried out 1994 during the IML 2 mission) the statoliths reached a stable position due to the fact that they were stopped by the nucleus. The position was similar to that observed in roots grown continuously in microgravity. Treatment with cytochalasin D (CD) did not stop the movement of the amyloplasts but slowed down the velocity of their displacement (0.019 microm min(-1)). Initial movement patterns were the same as in control roots in water. Comparisons of mean velocities of amyloplast movements in roots in space and in inverted roots on earth showed that the force responsible for the movement in microgravity (Fc) was about 86% less (Fc = 0.016 pN) than the gravity force (Fg = 0.11 pN). Treatment with CD reduced Fc by two-thirds. The apparent viscosity of the statocyte cytoplasm was found to be 1 Pa s or 3.3 Pa s for control roots or CD treated roots, respectively. Brownian motion or elastic forces due to endoplasmic reticulum membranes do not cause the movement of the amyloplasts in microgravity. It is concluded that the force transporting the statoliths is caused by the actomyosin system.

Fabaceae↗
PubMed2000

Immunolocalization of actin in root statocytes of Lens culinaris L.

Lentil root statocytes show a strict structural polarity of their organelles with respect to the g vector. These cells are involved in the perception of gravity and are responsible for the orientation of the root. Actin filaments take part in the positioning of their organelles and could also be involved in the transduction of the gravitropic signal. A pre-embedding immunogold silver technique was carried out with a monoclonal antibody in order to study the distribution of actin cytoskeleton in the statocytes at the electron microscopic level. Some areas were never labelled (cell wall, vacuole, nucleoplasm, mitochondria, starch grains of the amyloplasts) or very slightly labelled (stroma of the amyloplasts). The labelling was scattered in the cytoplasm always close to, or on the nuclear and amyloplast envelopes and the tonoplast. Associations of 2 to 6 dots in file were observed, but these short files were not oriented in one preferential direction. They corresponded to a maximum distance of 0.9 micron. This work demonstrated that each statocyte organelle was enmeshed in an actin web of short filaments arranged in different ways. The images obtained by rhodaminephalloidin staining were in accordance with those of immunogold labelling. The diffuse fluorescence of the cytoplasm could be explained by the fact that the meshes of the web should be narrow. The vicinity of actin and of the amyloplasts envelope could account for the movement of these organelles that was observed in spatial microgravity.

Actins↗
PubMed1996

Normalization of insulin secretion by a selective alpha 2-adrenoceptor antagonist restores GLUT-4 glucose transporter expression in adipose tissue of type II diabetic rats.

Noninsulin-dependent mellitus is characterized by the coexistence of defective insulin secretion with insulin resistance in peripheral tissues. Therapeutic objectives are, therefore, to normalize glucose-induced insulin secretion and to restore normal glucose transport into insulin-sensitive tissues. In the present study we evaluate the effects of acute and subchronic administration (2 or 10 days) of the alpha 2-adrenoceptor antagonist SL 84.0418 on glucose tolerance in nondiabetic control rats and type I and type II diabetic rats and the level of the insulin-sensitive glucose transporter GLUT-4, which is exclusively expressed in white and brown adipose tissues, heart, and skeletal muscles. Glucose tolerance and insulin secretion were markedly impaired in type II diabetic rats (neonatal injection of streptozotocin) and were totally corrected by an acute i.p. injection of SL 84.0418. As a consequence of the chronic restoration of insulin secretion, GLUT-4 messenger RNA (mRNA) levels, initially decreased by 67% in white adipose tissue of type II diabetic rats, were normalized by subchronic (10 days), but not acute (2 days), treatment with SL 84.0418. The same results were obtained in brown adipose tissues of type II diabetic rats, whereas no modification of GLUT-4 mRNA levels remained very low in brown adipose tissues of type I diabetic rats (adult injection of streptozotocin) after acute or subchronic administration of SL 84.0418, suggesting that this drug acted by the restoration of insulin secretion. This study reports a decrease in GLUT-4 levels in insulin-sensitive tissues in this model of type II diabetes as well as its regulation after subchronic normalization of insulin secretion. We suggest a direct role for the alpha 2-adrenoceptor antagonist SL 84.0418 in pancreatic beta-cells that allows normalization of glucose tolerance.

Adipose Tissue↗
PubMed1995

Anti-anaphylactic activity of the novel selective histamine H1 receptor antagonist mizolastine in the rodent.

The anti-anaphylactic/anti-histamine activity of mizolastine (CAS 108612-45-9, SL 85.0324), a novel histamine H1 receptor antagonist devoid of sedative properties, has been evaluated in the rat, mouse and guinea pig. Mizolastine inhibited the passive cutaneous anaphylactic reduction caused by ovalbumin challenge in the rat (ED50 = 0.7 mg/kg i.v., 1.6 mg/kg p.o.) and effectively protected rats from the lethal shock induced by compound 48/80 (ED50 = 0.07 mg/kg p.o.). Mizolastine protected actively sensitized guinea pigs from anaphylactic mortality, bronchospasm and respiratory difficulties (increase in pulmonary resistance) preceding this event and from morphological modifications at doses from 0.05 mg/kg i.v. The pharmacological activity of mizolastine is linked to a selective blockade of histamine H1 receptors as indicated by the ability of this compound to antagonize rat paw edema induced by the subplantar injection of histamine (ED50 = 0.5 mg/kg p.o.) but not that induced by the injection of serotonin or bradykinin. Mizolastine also antagonized the increase in cutaneous capillary permeability caused by the intradermal injection of histamine (-80% at 0.3 mg/kg p.o.) and compound 48/80 (ED50 = 1.1 mg/kg p.o.) but not that induced by serotonin in the rat. In the guinea pig, mizolastine antagonized i.v. histamine-induced bronchoconstriction (ED50 = 0.03 mg/kg p.o.) and histamine-induced vascular permeability and edema in trachea and bronchi (ED50 < or = 0.05 mg/kg i.v.). Moreover, at higher doses, mizolastine antagonized the bronchospasm caused by systemic injection of platelet-activating factor (PAF) and leukotriene D4 (LTD4) (ED50's = 0.30 and 3.0 mg/kg p.o., respectively). However, mizolastine only weakly antagonized bronchospasm induced by aerosolized PAF (-67% at 50 mg/kg p.o.), failed to antagonize (up to 3 mg/kg i.v.) PAF-induced microvascular permeability of the tracheal mucosa in the guinea pig and was a weak inhibitor of PAF-induced platelet aggregation in the rabbit (IC50 = 74 mumol/l). In addition to antagonizing histamine H1 receptors, mizolastine also inhibits the release of histamine during allergic reactions in tissues. Thus, mizolastine antagonizes the antigen-induced in vivo release of histamine from mast cells in bronchoalveolar lavages of actively sensitized guinea pigs (minimal effective dose 0.3 mg/kg p.o.) and the release of histamine from mast cells in the peritoneal fluid of passively sensitized rats (ED50 = 0.9 mg/kg i.v.). In these various models, mizolastine was more potent than loratadine and terfenadine but less potent than ketotifen. The apparent half-life for the pharmacological actions of mizolastine ranged from 6 to 8 h.(ABSTRACT TRUNCATED AT 400 WORDS)

Anaphylaxis↗
PubMed1995

In vivo and in vitro interaction of the novel selective histamine H1 receptor antagonist mizolastine with H1 receptors in the rodent.

The interaction of mizolastine (CAS 108612-45-9, SL 85.0324) with histamine H1 receptors has been evaluated in the rodent. Mizolastine inhibited with high affinity (IC50 = 47 nmol/l) the binding of [3H]pyrilamine to histamine H1 receptors in guinea pig cerebellar membranes and sections. The order of potency of mizolastine and various H1 antagonists in this binding assay was the following: cyproheptadine > pyrilamine > mequitazine > mizolastine > astemizole > terfenadine > cetirizine > loratadine. Mizolastine also potently antagonized the contractile effects of histamine in the guinea pig ileum (pA2 = 8.5) and histamine-induced stimulation of phosphoinositide turnover in rat cortical slices (IC50 = 0.35 mumol/l). In contrast, this compound displayed very low affinity for serotonergic, noradrenergic and muscarinic cholinergic receptors as evidenced in both binding assays and functional tests. In guinea pig cerebellar membranes, [3H]mizolastine labelled in a saturable and reversible manner a single population of binding sites with Kd and Bmax values of 1.1 nmol/l and 635 fmol/mg protein, respectively. [3H]Mizolastine binding in guinea pig cerebellar membranes was inhibited by histamine (IC50 = 30 mumol/l) and by drugs that possess affinity for the H1 receptor such as pyrilamine (IC50 = 1 nmol/1), DL-chlorphenyramine (IC50 = 6.4 nmol/l) terfenadine (IC50 = 6 nmol/l) and loratadine (IC50 = 50 nmol/l). At concentrations lower than 10 mumol/l, the H2 receptor ligands dimaprit and cimetidine and the H3 receptor ligands burimamide and 4-methyl-histamine failed to displace [3H]mizolastine binding.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Litoxetine: a selective 5-HT uptake inhibitor with concomitant 5-HT3 receptor antagonist and antiemetic properties.

The selective 5HT uptake inhibitor, litoxetine (SL 81.0385), currently under development as an antidepressant was shown to have antiemetic properties in the ferret. Litoxetine (at 1 and 10 mg/kg i.v.) dose dependently reduced the number of retches and vomiting as well as the number of emetic episodes induced by cisplatin (10 mg/kg i.v.) and delayed the onset of emesis. Fluoxetine (at 1 or 10 mg/kg i.v.) failed to inhibit cisplatin-induced emetic responses and, in contrast, significantly increased the number of retches and vomiting and accelerated the onset of emesis. The possibility that the antiemetic effects of litoxetine may be mediated through an interaction with 5HT3 receptors was studied using [3H]quipazine or [3H]BRL 43694 to label the 5HT3 receptor. Litoxetine has moderate affinity for cerebral 5HT3 receptors (Ki = 85 nM), while fluoxetine, similar to other 5HT uptake inhibitors, has only negligible affinity for this receptor (Ki = 6.5 microM). It is proposed that litoxetine inhibits cisplatin-induced emetic responses due to its moderate 5HT3 antagonist properties. The clinical use of the majority of serotonergic antidepressants (e.g. fluoxetine, fluvoxamine etc.) is associated with gastrointestinal discomfort (particularly nausea and vomiting) as a major side-effect. If nausea and vomiting associated with the use of 5 HT uptake inhibitors are due to stimulation of 5HT3 receptors, the concomitant 5HT3 antagonism of litoxetine may limit the gastrointestinal side-effects of this novel antidepressant and thus offer an important advantage.

Animals↗
PubMed1988

Sulphasalazine and PhCL28A inhibit the formation of ethanol- and phenylbutazone-induced rat gastric ulcers: lack of involvement of endogenous prostaglandins?

1. The effects of sulphasalazine (SZP) and PhCL28A on macroscopic lesion formation and ex vivo prostaglandin inactivation were studied in the ethanol (ETOH) and phenylbutazone (PBT) models of gastric ulcers in the rat. Prostaglandin 'synthesis' during homogenisation of the stomachs was also studied in the latter model. 2. Both PhCL28A and SZP when injected i.p. prevented the formation of ETOH- and PBT-induced gastric ulcers with ED50 values of 13 and 41 mgkg-1 (vs ETOH) and 3 and 32 mgkg-1 (vs PBT) for PhCL28A and SZP respectively. However, neither compound was active orally in the dose ranges used (up to 30 mg kg-1 for PhCL28A and 100 mg kg-1 for SZP). 3. Irrespective of the route of administration, SZP (100 mg kg-1) and PhCL28A (30 mg kg-1) produced slight but statistically significant decreases in ex vivo prostaglandin inactivation by 100,000 g cytosolic supernatants prepared from stomachs not receiving ulcerogen. When tested in vitro, PhCL28A (IC50 = 230 nM) was approximatively 480 times mor potent than SZP (IC50 = 110 microM) against rat stomach cytosolic prostaglandin inactivation. 4. Both ETOH (50%, 5 ml kg-1, orally) and PBT (200 mg kg-1, orally) significantly decreased ex vivo gastric cytosolic prostaglandin inactivation. PhCL28A (30 mg kg-1, orally or i.p.) decreased prostaglandin inactivation still further after ulcerogen treatment except when given i.p. before ETOH treatment. SZP (100 mg kg-1) had a similar effect when given orally before PBT treatment. 5. When the prostaglandin content of the stomach homogenates was used as a measure of ex vivo prostaglandin synthesis in the PBT experiments, PhCL28A 30 mg kg-' orally (but not i.p.) produced an 88% increase in prostaglandin E2 (PGE2) levels, but had no effect on 6-keto-PGF,, or thromboxane B2 formation during homogenization. SZP (100mg kg' i.p. or orally) was without effect. 6. We conclude from these results that the anti gastric ulcer activity of SZP and PhCL28A is independent of prostaglandin inactivation and endogenous prostaglandin formation is probably not involved.

Animals↗
PubMed1984

Prolonged treatment with D-penicillamine: effects on adjuvant arthritis in the rat.

The effects of long term D-penicillamine treatment on adjuvant arthritis in the rat were determined in order to establish a possible approach to the laboratory evaluation of anti-rheumatic drugs. Oral pretreatment (1-3 months) followed by continued through-treatment on a daily basis (100 mg/kg p.o.) failed to modify the parameters tested: viz. (a) body weight changes; (b) primary paw lesions; (c) secondary hind paw lesions; (d) secondary forepaw, ear and tail lesions; (e) the number of 'responders'. Autopsy showed no macroscopic abnormalities in the lungs, heart, thymus, liver, spleen, adrenal glands, kidneys and gastro-intestinal tract. These results are discussed in relation to previous findings whereby rat adjuvant arthritis, in addition to other experimental immune reactions, has been suggested as an indicator for D-penicillamine activity.

Administration, Oral↗
PubMed1984

Antrafenine: anti-inflammatory activity with respect to oedema and leucocyte infiltration in the rat.

Antrafenine effectively suppressed carrageenan paw oedema in the rat (ED 40 = 24 mg/kg p.o) in the dose range of 10-40 mg/kg p.o, approximating that of phenylbutazone. Antrafenine was superior to phenylbutazone with respect to inhibition of exudate volume and total leucocyte infiltration in carrageenan and calcium pyrophosphate dihydrate crystal pleurisies. The effect of antrafenine on leucocytes was most striking, significant suppression being observed at each dose tested (10, 20, 40 mg/kg p.o), whereas phenylbutazone showed significant activity only at the relatively elevated dose of 40 mg/kg p.o. These observations suggest that antrafenine merits further investigation with respect to its anti-inflammatory effects.

Animals↗
PubMed1983

Qualitative and quantitative effects of fenfluramine and tiflorex on food consumption in trained rats offered dietary choices.

The qualitative and quantitative anorectic effects of intraperitoneally-administered fenfluramine and tiflorex were studied in male rats trained during 10 d to a reversed dark/light cycle ('night' 1100-2300 h), and to a food choice (of either a protein-rich or protein-poor meal, or of a carbohydrate-rich or carbohydrate-poor meal) available only during the first 4 h of the dark cycle. On the first day of drug treatment (2.5 mg/kg or 5.0 mg/kg i.p., administered 0.5 h before the end of the light cycle) both fenfluramine and tiflorex provoked a dose-dependent reduction in the consumption of the protein-rich diet, and a reduction in the consumption of the protein-poor diet. In the carbohydrate study, on the first day of drug treatment, there was a dose-related reduction in the consumption of the carbohydrate-rich regime, and marked reduction by both drugs of consumption of the carbohydrate-poor regime (except in the case of the lower dose of fenfluramine, 2.5 mg/kg). There was generally a rapid development of tolerance to the anorectic effects of the anti-obesity drugs, although this was delayed somewhat in the case of tiflorex. These results suggest that drugs like fenfluramine and tiflorex, which enhance central serotoninergic transmission, reduce caloric intake whether the calories are presented as protein or carbohydrate, compatible with the anti-obesity actions of these agents in omnivorous man.

Analysis of Variance↗
PubMed1979

Synthesis and analgesic activities of some (4-substituted phenyl-1-piperazinyl)alkyl 2-aminobenzoates and 2-aminonicotinates.

A series of (4-substituted phenyl-1-piperazinyl)alkyl 2-aminobenzoates and 2-aminonicotinates has been prepared and screened for analgesic and antiinflammatory properties in mice and rats. The tabulated results reveal several 2-(4-substituted phenyl-1-piperazinyl)ethyl 2-(7- or 8-substituted 4-quinolinylamino)benzoates to be six to nine times more potent analgesics than the reference compounds (glafenine and aminopyrine) and to possess minor antinflammatory activity. Compound 45, 2-[4-[3-(trifluoromethyl)phenyl]-1-piperazinyl]ethyl 2-[[7-(trifluoromethyl)-4-quinolinyl]amino]benzoate (antrafenine), showed marked analgesic activity, long duration of action, and excellent tolerance in pharmacological and toxicological studies, as well as in clinical trials.

Acetates↗