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Biomedical subjects

J M Gaillard

Publications and source records attributed to J M Gaillard.

At least 37 records · Page 2Linked to original sources

Platelet phosphoinositide signaling system: an overstimulated pathway in depression.

In order to test a possible depression-associated defect in signal transduction, platelet alpha 2-adrenergic-mediated phosphoinositide (PI) hydrolysis was measured, both in drug-free major depressed patients and in control healthy subjects. Results that express phospholipase C activity have shown significant increase in the metabolites of epinephrine-stimulated tritiated phosphatidyl-4,5-biphosphate (3H-PIP2) with respect to basal activity (saline-stimulated). Thrombin (2 units) and 10 mM sodium fluoride (NaF) also induced an increase in 3H-PIP2 metabolites. These increases were potentiated in drug-free depressed patients both in epinephrine-and thrombin-stimulated platelets. In contrast, sodium fluoride, which directly stimulates G protein without receptor interaction, did not differentiate between patients and controls with respect to PI hydrolysis. This result suggests a possible depression-associated defect in heterologous receptor-G protein interaction.

Adrenergic alpha-2 Receptor Antagonists↗

Possible involvement of alpha 2-adrenoceptor on the hypnotic action of flunitrazepam.

This study examined whether the pharmacologic manipulation of catecholaminergic systems would affect the hypnotic action of flunitrazepam in rats. Flunitrazepam, a potent hypnotic, was used alone or in combination with alpha-methyl paratyrosine (alpha MPT), an inhibitor of the synthesis of catecholamines, and clonidine (CLN), an alpha 2-adrenoceptor agonist. Flunitrazepam significantly increased the amount of slow-wave sleep and the latency of paradoxical sleep (PS) and decreased the amount of PS. Administration of flunitrazepam to alpha MPT-treated rats significantly increased the number of sleep cycles and PS episodes as compared with flunitrazepam alone. Clonidine decreased total sleep time and significantly decreased PS. The association of flunitrazepam with CLN induced a decrease in PS and waking as compared with flunitrazepam alone. The possible involvement of noradrenergic mechanisms in modulating the effect of flunitrazepam on the rat sleep-waking cycle is proposed.

Adrenergic alpha-2 Receptor Agonists↗

Effects of a D2 receptor agonist RO 41-9067 alone and with clonidine on sleep parameters in the rat.

The effects of RO 41-9067, a D2 dopamine receptors agonist, on different sleep parameters were studied in the rat. RO 41-9067 dose dependently decreased paradoxical sleep, and only at the higher dose increased waking during the light period. In contrast, the higher dose of RO 41-9067 increased paradoxical sleep and decreased waking during the dark period. Finally, the combination of RO 41-9067 and clonidine significantly prevent the decrease of total sleep time and paradoxical sleep found after clonidine alone. These results, compared with those of classical D2 dopamine receptors agonists, suggest an action for RO 41-9067 on D2 dopamine receptors depending on the cerebral structure, a different action particularly on the striatum and/or on the structures responsible for paradoxical sleep. An active role for D2 dopamine receptors and an interaction between noradrenergic and dopaminergic systems in the regulation of sleep is proposed.

Adrenergic alpha-Agonists↗

Effects of WIN 35,428 a potent antagonist of dopamine transporter on sleep and locomotor activity in rats.

The new cocaine derivative CFT naphthalene sulphonate (WIN 35,428), has been shown to have a considerably longer duration of action and greater potency than cocaine as a central stimulant and it appears to have a similar mode of action on dopamine (DA) systems. The purpose of the present study was first to investigate the effects of low doses of WIM 35,428 with particular reference to the involvement of dopaminergic system in paradoxical sleep (PS), other sleep parameters and locomotor activity in the rat. WIN 35,428 a potent ligand of dopamine transporter showed biphasic effects upon PS and locomotor activity with low doses increasing and high doses decreasing PS. These changes reflect a functional involvement probably relevant to the action of Win 35,428 on DA transporters.

Analysis of Variance↗

Relationship between erythrocyte magnesium, plasma electrolytes and cortisol, and intensity of symptoms in major depressed patients.

53 male and female drug-free major depressed patients were separated into three groups according to the severity of the depression. In the entire regrouped population, plasma and erythrocyte magnesium (Mg) were shown to increase as compared with 48 healthy controls, confirming our previous studies. The middle and highly depressed patients had higher erythrocyte and also plasma Mg levels than either lowly depressed patients or controls. Only, a few differences were noticed in plasma sodium, potassium and calcium (Ca) in the three groups of patients, except for ultrafiltrable plasma Ca, measured for the first time in affective disorders. Thus, erythrocyte and also plasma Mg are shown to be associated with the intensity of the depression. As blood hypomagnaesemia is often related to hyperexcitability, further investigations are actually in process to shown whether hypermagnesaemia might be, in contrast, associated with psychomotor retardation as observed in many depressed patients.

Adult↗

Active immunization against insulin affects sleep and feeding in rats.

The effects of active immunization against peripheral insulin on different sleep parameters and food consumption were studied in rats. Insulin coupled to thyroglobulin was used as immunogen and rats immunized with thyroglobulin alone served as controls. Active immunization against insulin is summarized as follows: (a) the number of arousals was reduced; (b) waking time decreased by about 20%; (c) slow wave sleep was increased; (d) The amount of sleep increased during the light and dark period; (e) feeding was decreased; (f) body weight was reduced; and (g) the blood glucose level rised. These results are compatible with previous studies showing positive correlation between decrease of insulin secretion, sleep disturbances and decrease of feeding. A possible association between peripheral insulin and brain noradrenergic system, sleep and feeding is suggested.

Animals↗

Effect of a new cognitive drug-enhancer S-12024-2 on EEG sleep recordings in rats.

A newly synthesized agent S-12024-2 was shown to improve some aspects of cognitive processes such as memory consolidation. The relationships between sleep and memory lead us to investigate the effects of the intraperitoneal administration of three different doses (1, 3, and 10 mg/kg) of S-12024-2 on sleep variables in the rat. The results showed that S-12024-2 (10 mg/kg) increased slow wave sleep (SWS) and decreased wakefulness during the light period of the first 24 h of sleep recording. During day 1 of sleep recording, S-12024-2 tended to increase paradoxical sleep (PS) with a maximal effect observed with 3 mg/kg. Four days after administration of S-12024-2 (3 mg/kg), PS remained significantly high. These data suggest an active role for S-12024-2 on SWS and PS, compatible with its favourable effects on memory.

Animals↗

Sodium-magnesium exchange in erythrocyte membranes from patients with affective disorders.

The Vmax of erythrocyte sodium-magnesium exchange was measured for the first time in 63 patients suffering from affective disorders and compared to that in 33 healthy subjects. Depressed patients had a significantly higher Vmax (215 +/- 13 vs. 151 +/- 14 mumol/l.cells/h; p < 0.005; mean +/- SEM). This tendency was conserved after division of the 63 patients into three clinical subgroups according to the DSM-III-R criteria. Thirty-four patients from this panel were divided into three subgroups according to the chemical class of the antidepressant drug used and were followed up during a 3-month period of drug treatment. Mood improvement over the 3-month period was associated with a slow increase in Vmax of Na/Mg exchange (delta increase approximately 25 mumol/l.cells/h), except in the subgroup of patients treated with non-tricyclic antidepressants (n = 8). These results are consistent with the previously reported link between high erythrocyte magnesium content and affective disorders. Indeed, enhanced Na/Mg exchange Vmax, which probably results from an increased number of transport units per cell, contributes to the normalization of red blood cell magnesium content correlated with mood improvement.

Adolescent↗

Effects of clonidine and alpha-methyl-p-tyrosine on the carbachol stimulation of paradoxical sleep.

Acetylcholine promotes paradoxical sleep (PS), but the role of noradrenaline in this stimulation is controversial. The relationship between cholinergic and noradrenergic systems in the production of PS was investigated in the rat implanted on a continuous basis for sleep recordings. Stimulation of PS was obtained with microinjections of carbachol (1 microgram) into the pontine reticular formation. In the presence of the alpha 2-agonist clonidine (5 micrograms/kg, IP), the carbachol activation of PS was abolished. This stimulation also disappeared when the animals were pretreated with alpha-methyl-paratyrosine (150 mg/kg, IP), an inhibitor of catecholamine synthesis. Thus, carbachol stimulation appeared inefficient when brain noradrenergic activation was decreased. This observation supports the view that the realization of PS by the cholinergic system requires a certain level of noradrenergic activity.

Animals↗

Platelet serotonin and plasma tryptophan in depressed patients: effect of drug treatment and clinical outcome.

Platelet serotonin and plasma tryptophan were studied in healthy subjects and in depressed patients before and during their antidepressant drug treatment. Before treatment, mean platelet serotonin level was normal in depressed patients compared with healthy subjects while a significant decrease in patients' plasma TRP was noted (t = 6.0, p < .001). The concentrations of platelet 5-HT level did not correlate with either plasma TRP or with clinical variables, that is, AMDP depression and AMDP anxiety scores. Antidepressant drugs treatment decreased platelet 5-HT level (ANOVA F = 8.27, p < .001) whatever the clinical outcome of the patient, whereas the changes observed in plasma TRP were positively related to the mood state change. These results suggest that platelet serotonin could be a good pharmacological model but has no relevance concerning the mood state.

Affect↗

Subjective assessment of sleep: statistical analysis in a population of healthy subjects.

A principal components analysis was carried out on subjective data obtained from the sleep questionnaire systematically used in our laboratory on the morning following a polysomnographic recording. This technique, based on 70 healthy subjects, revealed three principal axes which explore the questionnaire. The first axis reflects the subjective evaluation of the quality of sleep. The second underlines the importance of dreams and of the brief waking periods which immediately follow. Finally, the third axis brings out the subjective assessment of sleep efficiency. The third axis was the most ambiguous and the only one to show a gender difference. Women tend to better estimate general sleep events, while men tend to evaluate better the more circumstantial events. Finally, given the results, it would be interesting to apply a similar analysis to populations presenting sleep disorders in order to establish the presence of an eventual pattern specific to the disorder.

Adult↗

The estimation of age-specific breeding probabilities from recaptures or resightings in vertebrate populations: II. Longitudinal models.

We provide a statistical framework to estimate age-specific breeding probabilities in vertebrate populations, from recaptures or resightings of individuals marked as young. We consider data collected at one or possibly several points over time, when individual recapture histories are known, leading to models which we call longitudinal models. An example of resightings of black-headed gulls, Larus ridibundus, is considered.

Aging↗

New variables for defining sleep continuity.

One very synthetic way to represent a night's sleep is by way of a hypnogram: a graphical representation of the sleep stages as a function of time. The hypnogram is generally quantified by a series of variables that measure the durations and latencies of the various sleep stages including wake. These variables, however, do not fully account for all the information contained in the hypnogram, in particular information on sleep continuity. A series of variables that measure and localize disruption of this continuity are proposed and their utility validated on three groups of patients presenting sleep disorders. Utility is established if the variable is capable of differentiating between patients and healthy controls. Two sets of variables are examined: those that use the entire sleep period as unit of measurement, and those that are measured within each consecutive NREM-REM sleep cycle. The results show that the variables proposed are able to differentiate between groups and, therefore, are useful measures reflecting the hypnogram more precisely. They also show that fragmentation of REM sleep does not present a systematic trend across the night, but that fragmentation of NREM sleep goes up linearly.

Adult↗

Lack of effect of anxiety on total plasma MHPG in depressed patients.

This report was undertaken to test the noradrenergic deficiency hypothesis of depression and the postulated increase in noradrenergic activity associated to anxiety states. A possible dual effect of both depression and anxiety on total plasma MHPG levels was hypothesized and assessed in anxious and non-anxious depressed patients. The findings show a decrease in plasma MHPG levels in depressed patients whatever their degree of anxiety. There was no difference in total plasma MHPG levels either between anxious and non-anxious depressed patients or between low and high anxiety to depression ratio (ADR) depressed patients. Following antidepressant drug-treatment, a decrease in plasma MHPG was found. A positive correlation between the drug-induced decrease in NA activity and the severity of depression was observed, and suggested a relationship between the severity of depression and the instability of the NA system. No correlation between the drug-induced decrease in plasma MHPG and the degree of anxiety was found. The results do not suggest out an effect of anxiety on total plasma MHPG levels in depressed patients.

Adult↗

Adrenaline-induced platelet aggregation in depressed patients and control subjects.

We measured alpha 2-adrenoceptor-mediated platelet primary aggregation in depressed patients and healthy subjects. Both initial velocity and maximum amplitudes of platelet response to increasing concentrations of adrenaline were decreased in drug-free depressed patients as compared with controls. The EC50 of both initial slope and maximum amplitude were also increased in drug-free depressed patients. The results suggested a lowered platelet alpha 2-adrenoceptor function. Demographic factors (age and sex) and the time between blood collection and start of aggregation monitoring did not influence the results. This report is consistent with postsynaptic receptor desensitization in depressed patients. The precise molecular mechanism for this impairment remains to be elucidated.

Adolescent↗

[Classification of sleep disorders].

Abnormal sleep can be insufficient, which constitutes insomnia; it can be excessive or inappropriate, which is hypersomnia, it can be misplaced with respect to the normal sleep-wakefulness rhythm, or it can be accompanied by various phenomena which do not belong to sleep itself (i.e. parasomnia). This is the format of most traditional classifications of sleep disorders. A modern classification has been introduced in 1990 and contains the description of 88 different sleep disturbances. They are classified in the main categories of dyssomnia, parasomnia and sleep disorders associated with psychiatric, neurological or somatic conditions. This classification is an excellent tool for the practice of sleep medicine and for the study of sleep disorders.

Circadian Rhythm↗

Blood magnesium, potassium, sodium, calcium and cortisol in drug-free depressed patients.

Many biochemical variables, including plasma and erythrocyte magnesium, were simultaneously measured in drug-free depressed patients (n = 34), compared to healthy controls (n = 35). Higher plasma and erythrocyte magnesium concentrations were observed in patients than in controls (+12 per cent, P < 0.0001 and 14 per cent, P < 0.0001, respectively). In contrast, patients showed a lower plasma potassium level (-10 per cent; P < 0.007). Cortisol secretion was much higher in patients (+35 per cent; P < 0.02), particularly in females, showing overactivity of the hypothalamo-hypophyseo-adrenal axis in the patients. Except in a few cases, plasma sodium and calcium in patients did not differ from control values. Significant differences in magnesium and cortisol levels were observed between patients classified in diagnostic groups and by sex, whereas little variation in the other biochemical indices was noted. The increase in blood magnesaemia and its possible association with central hypocatecholaminergic deficiency in affective disorders are discussed.

Calcium↗