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H Allain

Publications and source records attributed to H Allain.

At least 73 records · Page 4Linked to original sources
PubMed1997

Is chlormethiazole neuroprotective in experimental global cerebral ischemia? A microdialysis and behavioral study.

Chlormethiazole, an anticonvulsive agent, has been shown to have a possible neuroprotective effect against cerebral ischemia. In addition, chlormethiazole inhibits methamphetamine-induced release of dopamine, protecting against this neurotransmitter's neurotoxicity. The aim of this work was to ascertain whether, in experimental cerebral ischemia, chlormethiazole administration attenuated the ischemia-induced rise of the extracellular concentration of aminergic neurotransmitters and whether it reduces ischemia-induced deficits in memory and learning. Histology for assessment of ischemic damage was a so included. The four-vessel occlusion rat model was used to induce global cerebral ischemia. Aminergic neurotransmitters and their metabolites in the striatal extracellular fluid obtained by microdialysis were assayed by high-performance liquid chromatography-electrochemical detection. The drug was administered either IP (50 mg/kg-1) or directly through the dialysis probe (30 microM) 80 min before ischemia. For the behavioral test and histology, the drug was given IP (100 mg/kg-1) 1 h postischemia. The results obtained did not demonstrate any statistically significant evidence that chlormethiazole has an effect on the ischemia-induced rise in extracellular dopamine and serotonin levels. There was also no variation in metabolite levels. Behavioral measures (learning, recall) were not changed appreciably by the treatment. We observed no significant cell protection in the hippocampus (CA1, CA1), striatum, and entorhinal cortex in animals treated with chlormethiazole. We conclude that, under our experimental conditions, chlormethiazole has little or no effect on the neurochemical, neurobehavioral, and histological consequences of global cerebral ischemia.

Animals↗
PubMed1997

Hypoxic contractile response in isolated rat thoracic aorta: role of endothelium, extracellular calcium and endothelin.

The effects of hypoxia on isolated arteries remain controversial, depending on the species, vascular beds and protocols. The aims of the study were to characterize the response of rat thoracic aorta to hypoxia and to examine the roles of endothelium, extracellular calcium and endothelin in this response. Hypoxia was induced by bubbling Krebs solution with 95% N2 and 5% CO2 instead of 95% O2 and 5% CO2. Experiments were performed during 1 h in norepinephrine (0.01 microM) precontracted rings. Hypoxia produced a biphasic response consisting of an initial transient partial relaxation (67% at 14 min) followed by a slow but sustained contraction (27% from 40 to 60 min). After endothelium removal, relaxation appeared faster with increased magnitude (82% at 12 min) and was followed by a weak transient contraction (16% at 25 min). In endothelium-intact rings, Ca2+ free medium (EGTA, 0.1 mM) and Ca2+ channel blockers, verapamil (0.05, 0.5 and 5 microM) or nicardipine (0.1, 1 and 10 microM), had no effect on relaxation but inhibited the contraction, the effects of both calcium antagonists being concentration-dependent. Similarly, the ETA/ETB receptor antagonist, bosentan (0.1, 10 and 1,000 nM), induced a concentration-dependent decrease in the contraction. We conclude that 1) the response of rat thoracic aorta during 1 h of hypoxia is biphasic (relaxation followed by contraction); 2) the endothelium is involved in the contraction whereas its role in the relaxation remains to be elucidated; 3) extracellular calcium is involved in the contraction; and 4) endothelin may play a role in the contraction.

Animals↗
PubMed1996

Effect of brain microdialysis on aminergic transmitter levels in repeated cerebral global transient ischemia in rat.

The effect of repeated transient global ischemia and microdialysis on changes in aminergic neurotransmitter release was investigated using the rat four-vessel occlusion model of global ischemia. To examine the possible transient or permanent changes in neurotransmitter release, ischemia was induced at varying time points in 5 groups of rats. The first ischemia occurred either 24 h (groups I, II, IV, V) or 96 h (group III) following vertebral artery electro-coagulation and guide probe implantation(s), and the second ischemia was induced either 48 h (groups I, IV, V) or 72 h (group II) following the first ischemia. To assess the consequence of repeated microdialysis on the results, one group of rats (group IV) was not dialysed during the first ischemia and another group (group V) was bilaterally dialysed during the second ischemia. Finally, amphetamine-induced neurotransmitter release was also studied in rats submitted to ischemia and compared with that in normal rats. In each case, dopamine, serotonin and their main metabolites were measured by HPLC with electrochemical detection. Monoamine release was inhibited during the second episode of transient ischemia; this non-release was linked to the repeated microdialysis and not to the repeated ischemia. Although the results of chronic studies using brain microdialysis have been widely recognized as valid, the findings presented here indicate that combined with ischemia, probe reinsertion modifies the level of neurotransmitter release.

Amphetamines↗
PubMed1996

Pharmacodynamics and pharmacokinetics of two dose regimens of befloxatone, a new reversible and selective monoamine oxidase inhibitor, at steady state in healthy volunteers.

The pharmacodynamic equipotency of 2 dose regimens (5 mg twice daily versus 10 mg once daily) of befloxatone, a new reversible and selective monoamine oxidase A (MAO-A) inhibitor, after single and multiple doses for 6 days was examined in a randomized, double-blind, three-way crossover, placebo-controlled trial of 12 healthy volunteers. Plasma levels of the deaminated metabolite 3-4 dihydroxyphenylglycol (DHPG), as measured by high-performance liquid chromatography (HPLC) with coulometric electrochemical detection, were used as an index of MAO inhibition. A single dose of befloxatone produced a significant dose-related reduction in plasma DHPG levels, as shown by the decrease in the 24-hour area under the concentration-time curve (AUC0-24) of DHPG, which peaked 2 hours after administration and persisted over 24 hours. Both dose regimens provided equipotent extent and duration of MAO-A inhibition at steady state, suggesting a once daily dosage should be sufficient for most patients. The pharmacokinetic bioavailability at steady state of both dose regimens was also similar. The concentration-time effect curve after a single dose revealed a hysteresis corresponding to the delay necessary to elicit MAO inhibition and/or elimination of DHPG. The relationship between plasma levels of DHPG and/or elimination of plasma concentrations of DHPG and befloxatone after a single dose can be modeled using the Emax model with a mean EC50 of 4.75 ng/mL, and suggests the presence of a maximal response from the single dose. This model permits prediction of steady-state levels of DHPG.

Adult↗
PubMed1996

Assessment of procedural memory in Parkinson's disease.

1. Findings in cognitive psychology and neuropsychology have led to consider the existence of several mnestic systems. This study focuses on a now clearly established distinction between the procedural and the declarative memories. 2. The aim of the present study was to try and determine which of the two acquisition steps (learning and automation) is affected by Parkinsonians' mnestic difficulties, and to verify if these difficulties are linked to the skill content (declarative or motor). 3. To answer these questions, 20 Parkinsonians under treatment underwent specific tests: the maze test and the arithmetic alphabet test. 4. Results show that, by comparison with 20 matched healthy individuals, the deficiencies observed in Parkinson's disease affect both the declarative and the motor skills. In addition, Parkinsonians suffer difficulties in both acquisition steps: learning and automation. 5. These results could account for the cognitive and motor disturbances observed in Parkinson's disease; these abnormalities should be among the pharmacological targets in future.

Adolescent↗
PubMed1996

Noninterchangeability of specific radioimmunoassay and monoclonal antibody fluorescent polarization immunoassay in cyclosporine measurements.

This study compares cyclosporine (CsA) concentrations in whole blood from patients receiving bone marrow (n = 10), renal (n = 48), heart (n = 50) or liver (n = 50) transplants, as measured by monoclonal antibody flurorescence polarization immunoassay (FPIA) and specific 125I-radioimmunoassay (RIA). The FPIA overestimated CsA by an average of 25%. Results were higher for all indications: FPIA/RIA ratios were 1.17 for bone marrow, 1.23 for renal and 1.27 for both heart and liver transplants, and these values were significantly different from 1.0. The percentage of overestimation was higher at low CsA concentrations (< or = 100 micrograms/L) than at high CsA concentrations (> or = 400 micrograms/L). In all indications, results by both methods correlated well (r > 0.96) but slopes and intercepts were different from 1.0 and 0.0, respectively, and these parameters varied greatly between the grafted populations. These findings obtained with the two methods could not be attributed to matrix effect because the mean FPIA/RIA ratio for spiked control samples was 1.0. The discrepancy between the FPIA and RIA could be explained by the lower specificity of the monoclonal antibody contained in the FPIA kit. These results suggest that FPIA is not as accurate as RIA and that the two methods are not interchangeable in CsA level measurement.

Antibodies, Monoclonal↗
PubMed1996

Study of the mechanisms involved in adenosine-5'-O-(2-thiodiphosphate) induced relaxation of rat thoracic aorta and pancreatic vascular bed.

1. The endothelium-dependent relaxation of blood vessels induced by P2Y-purinoceptor activation has often been shown to involve prostacyclin and/or nitric oxide (NO) release. In this work, we have investigated the mechanisms involved in the relaxant effect of the P2Y agonist, adenosine -5'-O-(2-thiodiphosphate) (ADP beta S) using two complementary preparations: rat pancreatic vascular bed and aortic ring. 2. On the pancreatic vascular bed, ADP beta S (1.5 and 15 microM) infused for 30 min induced a concentration-dependent vasodilatation; it was progressive during the first 10 min (first period) and sustained from 10 to 30 min (second period). Indomethacin (10 microM) delayed ADP beta S-induced vasodilatation (1.5 and 15 microM) by about 6 min. N omega-nitro-L-arginine methyl ester (L-NAME) (200 microM) suppressed the relaxation for about 5 min but thereafter ADP beta S at the two concentrations progressively induced an increase in the flow rate. Even the co-administration of L-NAME and indomethacin did not abolish the ADP beta S-induced vasorelaxation. 3. On 5-hydroxy tryptamine (5-HT) precontracted rings mounted in isometric conditions in organ baths, we observed that ADP beta S induced a concentration-dependent relaxation of rings with a functional endothelium; this effect was stable for 25 min. The ADP beta S relaxant effect was strongly inhibited by Reactive Blue 2 (30 microM) and was suppressed by pretreatment of rings with saponin (0.05 mg ml-1 for 30 min), which also abolished the acetylcholine-induced relaxation. 4. ADP beta S-induced relaxation of 5-HT precontracted rings is largely inhibited by indomethacin (100 or 10 microM) or L-NAME (100 microM). 5. We conclude that: the ADP beta S-induced relaxation is endothelium-dependent, mediated by P2Y-purinoceptors, and at least in part linked to NO and prostacyclin release, depending on the preparation used. Furthermore, on the pancreatic vascular bed, (an)other mechanism(s) than prostacyclin and NO releases may be involved in ADP beta S-induced vasodilatation.

Adenosine Diphosphate↗
PubMed1996

The dopamine agonists lisuride and piribedil protect against behavioural and histological changes following 4-vessel occlusion in the rat.

The 4-vessel occlusion model of ischaemia in the rat was used to assess the effects of two dopaminergic agonists, lisuride and piribedil, on some behavioural and histological changes. Animals were either sham-operated, subjected to 20 min 4-vessel occlusion, or administered lisuride (0.5 mg/kg i.p.) or piribedil (10 mg/kg i.p.) 1 h before 20 min 4-vessel occlusion. Both drugs attenuated deficits in neurological testing, Morris water maze and 14-unit T-maze (p < 0.05). Extensive neuronal death was observed in the CA1, CA3 and CA4 regions of the hippocampus of 4-vessel-occluded animals. Pretreatment with both lisuride and piribedil provided protection against cell death in the hippocampal regions. These findings suggest dopamine may play a role in cerebral ischaemia and dopaminergic agonists may be beneficial in preventing ischaemia-induced neurodegeneration.

Animals↗
PubMed1996

Induction of sleep.

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Antidepressive Agents↗
PubMed1996

Systemic and regional hemodynamic and biological effects of a new kappa-opioid agonist, niravoline, in healthy volunteers.

We noninvasively investigated the effects of a single 30-min i.v. infusion of a 2-mg dose of niravoline, a new selective kappa-opioid agonist, on systemic and regional (brachial artery) hemodynamics, on plasma levels of the main hormones regulating the cardiovascular system, on diuresis and on plasma and urinary osmolalities and electrolytes. This was a placebo-controlled, randomized, double-blind, crossover study performed in 12 healthy volunteers. Compared with placebo, niravoline induced a significant, early and potent diuresis, which peaked within 2 hr (urine output increased 2.4-fold) and lasted for 4 hr. Niravoline significantly decreased, between 0 and 2 hr, urine osmolality (-71%) and sodium (-38%) and potassium (-29%) excretion and significantly increased plasma osmolality and natremia, without changing kalemia. Niravoline induced a slight, but significant, increase in blood pressure (+8% at 0.5 hr), which disappeared within 2 hr. Because heart rate, stroke volume and cardiac output were not modified, this effect was due to an increase in total peripheral resistance (+22% at 0.5 hr). Niravoline did not modify brachial artery diameter and flow and corresponding vascular resistance. Niravoline tended to decrease plasma vasopressin levels and urinary excretion and significantly increased plasma levels of norepinephrine (+44% at 0.5 hr), active renin (+22% at 1.25 hr), aldosterone (+52% at 1.25 hr) and atrial natriuretic factor (+20% at 2 hr). We conclude that niravoline induces a potent aquaretic effect associated with antinatriuresis and antikaliuresis. These main effects are accompanied by a stimulation of the sympathetic and reninangiotensin systems and a slight and transient increase in blood pressure.

Adult↗
PubMed1995

Explicit and procedural memory in Parkinson's disease.

One of the aims of cognitive psychology is to breakdown complex tasks into their most basic components. The components of explicit (declarative) and implicit (procedural) memory were thus analyzed in undemented, non-depressed Parkinsonian patients under anti-Parkinsonian treatment, and compared with young and elderly healthy subjects. Three series of experiments were conducted in 61 patients in total. Statistically significant results revealed an impairment of explicit memory (verbal recall of words and drawings) with preserved recall of faces, in Parkinsonians. Implicit memory was also deficient, only in association tests (sound-form; arithmetical alphabet) and maze tests. Braille reading tests and Toronto tower tests did not discriminate between Parkinsonians and elderly subjects. Lastly, analyzing learning and automation revealed a dysfunctioning in Parkinsonian patients. All these data indicate a dysregulation of the cortical-sub-cortical systems, not essentially pre-frontal, and not necessarily dopaminergic. Cognitively, it appears that procedural and implicit memories should be dissociated conceptually.

Adult↗
PubMed1995

[Delay in the effect of antidepressive agents: pharmacologic approach].

A paradox which is not resolved in the use of antidepressants (ATD) is that in pharmacological studies of animal models of depression and in neurochemical studies, the onset of activity of all drugs is extremely rapid, whereas in human clinical practice the onset is delayed (15 days). An attempt is made to explain this in 3 ways, involving the synapse, transduction mechanisms, and cognition. Analysis of the impact of all ATDs shows that we are confronted with slow adaptive processes which are correlated with the delay observed in clinical practice. The interest of such considerations is that they may give rise to alternative therapies which are able not only to accelerate response, but also to increase it.

Affect↗