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Biomedical subjects

J M Gaillard

Publications and source records attributed to J M Gaillard.

At least 73 records · Page 4Linked to original sources

[Topographic aspects of visual and auditory evoked potentials in schizophrenics].

The EPs to bilaterally presented non-verbal and non-cognitive visual and auditory stimuli were studied in 15 schizophrenics and 15 normal subjects. Many anomalies of exogenous components of VEPs and AEPs were observed in schizophrenics in comparison with control subjects, pointing to an abnormal cerebral functioning. So, the patients presented: (1) a less interhemispheric difference in latency of P100 component of VEPs over the occipital area; (2) a decrease or a lack of left hemispheric predominance of P2 component of AEPs over the central area; (3) a lower interhemispheric waveform similarity both for VEPs and AEPs. These results suggest a lower hemispheric specialization and interhemispheric synchronization of EPs in schizophrenics.

Adult↗

The decrease of erythrocyte catechol-O-methyltransferase activity in depressed patients and its diagnostic significance.

Erythrocyte catechol-O-methyltransferase (COMT) activity was measured in normal and depressed populations before specific medication. In the groups of patients, anxiety and depression scores were evaluated by the AMDP rating scale. The authors found lower enzyme activity in patients with major depression, recurrent and bipolar disorder, depressed, but no change was found in dysthymic disorder when compared to control values. However, there was no relationship between COMT activity and age, anxiety and depression scores of patients. Furthermore, the subdivision into two subpopulations, one with normal COMT activity and another with lower COMT activity, did not make it possible to assign a role to the enzyme in the severity of depression. The enzyme could, however, be considered as a genetic marker of depressive vulnerability.

Adult↗

EEG fitting: a new method for numerical analysis of EEG.

A new method for numerical analysis of EEG is described. It consists of fitting the EEG with orthogonal polynomials in several steps to separate the different frequencies contained in the original recording (high-frequency noise, beta, sigma, alpha, theta, delta, low-frequency noise). The original EEG is separated into 5 different signals with cutoff frequencies at 40, 18, 4 and 0.6 Hz. The activity in these signals is classified into the usual EEG bands by zero-crossing. The results are given as integrated values over 1 s in the different EEG bands, or wave by wave, each wave being described by its time of occurrence, amplitude and duration. This method is designed for accurate amplitude measurement in the frequency bands of EEG, particularly for application in psychiatry and psychophysiology.

Arousal↗

In vitro effects of short-chain aliphatic alcohols, benzyl alcohol and chlorpromazine on the transport of precursors of monoamines across the human erythrocyte membrane.

In previous papers we reported a deficit of tyrosine (TYR) and tryptophan (TRP) transport across the erythrocyte membrane in depressed patients. To investigate further the transport mechanism of both monoamine precursors, we tested in healthy subjects the role played by membrane fluidity, using different fluidizing agents such as alcohols and the neuroleptic chlorpromazine. We found that the transport of both amino acids depended on the length of the chain of each alcohol tested (number of carbon atoms = C). No inhibition was observed after methanol (C1) preincubation, in contrast to benzyl alcohol (C6), which produced an inhibition of about 80% of amino acid basal transport. In a condition of incubation by suspension of cells in an artificial medium, we observed a dose response of these transports with ethanol used at doses of 0.1-1.3 M. Finally we found in this study that the effect of ethanol on membrane fluidity, and therefore on inhibition of basal amino acid transport, was totally reversible after having washed the suspended cells, suggesting a superficial, noncovalent ethanol binding on such biological membranes.

Adult↗

Is 3,4-dihydroxyphenylglycol the major route of central norepinephrine metabolism in rat brain?

Central norepinephrine (NE) metabolism was assessed by measuring 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG) and 3,4-dihydroxyphenylethyleneglycol (DHPG) in different rat brain areas after saline or probenecid (300 mg/kg) administration. Under probenecid, results showed an increased accumulation of total MHPG and DHPG, and a clear preponderance of DHPG levels over MHPG in almost all the brain areas examined. Estimation of their formation rates confirmed that in basal conditions DHPG is formed more rapidly. This study supports the notion that, without ruling out the importance of MHPG, brain DHPG may be a useful index of central NE activity.

Animals↗

Internal structure of sleep cycles in a healthy population.

A large body of data has been gathered on the sleep characteristics of normal subjects. The evolution of each sleep stage within each NREM/REM cycle is presented in detail, showing stage intensities minute by minute. There is a three-phase pattern in each stage intensity diagram: an initial phase of rapid change; a central phase of relative stability; and a terminating phase, again, of rapid change. The details of this pattern change progressively during the night. Throughout all cycles, there is a complementary relationship between the intensities of stage 2 sleep and the other stages that underlines the central role of stage 2 sleep in all stage transitions. Stage intensity diagrams for two groups, one group with and one group without stage 4 sleep, were compared. Subjects without stage 4 sleep tended to have a shorter duration and greater latency of stage 3 sleep. Surprisingly, cycles interrupted by abnormally long periods of continuous wake showed a negative correlation between the intensities of wake and slow wave sleep, and these interruptions did not appear to reset the cycle clock to zero. Sleep stage intensity diagrams may be useful to study the sleep patterns of populations of insomniac and depressive patients, as well as the effect of drugs on sleep.

Adult↗

L-tyrosine and L-tryptophan transport in red blood cells in normal subjects. Effects of other amino acids, temperature and medium of incubation.

Blood cells may be used as a model in the central transport mechanisms of amino acids, precursors of amines, implicated in some hypotheses of psychiatric diseases. In a previous paper, we showed a deficit of tyrosine transport by red cells incubated in the plasma of depressed patients. In the present study, we have investigated the interaction of these peripheral transport mechanisms for tyrosine and tryptophan with other amino acid transports, such as the L and ASC systems, and the role of sodium ions in the extracellular medium. We also describe the inhibition induced by incubation at a low temperature, and a probable role of the membrane viscosity. The interest of incubating the cells in their own plasma, in order to have physiological conditions, is also discussed.

Alanine↗

In vitro effects of ionophores and inhibitors of main sodium and calcium movements on tyrosine and tryptophan transport by human erythrocytes.

Peripheral models using blood cells might be biochemical markers in various psychiatric illnesses. In previous papers we reported a deficit of tyrosine and tryptophan transport in red cells incubated in plasma from depressed patients. In the present study we investigated the role played by sodium and calcium in these transports by using inhibitors and ionophores of the main movements of these electrolytes. We also studied the contribution of phloretin-sensitive countertransport, which has been described as low in psychiatric conditions.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

Modifications of sleep parameters in the rat by (+)- and (-)-3-PPP.

The effects of subcutaneous administration of the two enantiomers of 3-(3-hydroxyphenyl)-N-n-propylpiperidine (3-PPP), a new dopamine analogue, were studied with regard to their effects on sleep parameters in the rat. The studies with both enantiomers were carried out taking into account their different effects on central dopaminergic receptors. At low doses they act preferentially as autoreceptor agonists; at higher doses the (+)-form is also an agonist while the (-)-form acts as an antagonist at postsynaptic dopamine receptors. The results showed the following: (1) with the high dose of (+)-3-PPP there was no change in REM sleep, but a marked increase in wakefulness; (2) with the high dose of (-)-3-PPP there was a significant increase in REM sleep and in the mean duration of REM episodes; (3) with the low dose of (+)-3-PPP similar results to those described for high-dose (-)-3-PPP were obtained; (4) there was no significant alteration of sleep parameters with the low dose of (-)-3-PPP. The data are discussed in terms of an active role for dopamine in the regulation of REM sleep.

Animals↗

Statistical description and evaluation of the interrelationships of standard sleep variables for normal subjects.

This study explores the relationships between the standard sleep variables, particularly between those of NREM and REM sleep. A total of 399 nights of sleep was recorded in 147 adults who had no known pathology. This amount of data allowed for an accurate description of the generally nonnormal variable distributions and established the relative predominance of the intra- over the interindividual variability. Most correlations between variables were low, showing that there is little redundancy in the choice of variables. The relationships between stage 2 and 4 of NREM and REM sleep and between sleep stages and wakefulness were statistically significant. We found that a short latency of stage 2 predicted a sleep of poorer quality than did a longer latency and confirmed that stage 2 has a central role in transition between stages. Finally, there was an association between the variables describing sleep stability and those describing cyclic organization and sleep efficiency. However, it cannot be determined from these data whether teh relationship is causaL or permissive. In addition, these results suggest that further work on cycle structure is required and that future experiments should incorporate a larger number of observed nights per individual.

Adolescent↗

Brain noradrenergic activity in wakefulness and paradoxical sleep: the effect of clonidine.

Several experiments in which the effects of clonidine (CLN) have been studied in the rat and in man are summarized. CLN inhibits paradoxical sleep (PS) both in the rat and in man. This inhibition is followed by a rebound, but with a different time course in the two species. Wakefulness (W) is enhanced after some critical doses of CLN, and decreased after higher doses. These effects of CLN suggest that alpha 2-adrenoceptors are involved in the regulation of W and PS.

Animals↗

Neurochemical regulation of the states of alertness.

Sleep and wakefulness are two active states of the central nervous system, and sleep is further subdivided into two components: orthodox sleep (OS) and paradoxical sleep (PS). The relationships between sleep and wakefulness are asymmetrical inasmuch as wakefulness can override sleep whereas the converse occurs much more rarely. This probably indicates that sleep and wakefulness are mediated by different sorts of neurotransmitter systems. The types of neurotransmission, and the concepts of cotransmitter and neuromodulation are briefly outlined. The role of particular wiring of some neurones is also relevant in the understanding vigilance regulation. Activation of catecholamine pathways is coincident with wakefulness and deactivation is one of the conditions necessary for sleep to take place. The induction of PS is also positively related to brain catecholaminergic activity; the level of activation of these systems appears, however, to be lower during PS than during wakefulness. Serotonin, once thought to be the main transmitter in sleep, now appears to regulate the synthesis of yet unidentified sleep factors, responsible for OS and PS realization. Cholinergic mechanisms are also involved in wakefulness and in PS triggering. Such mechanisms may be part of the switch between wakefulness and PS, possibly by controlling the level of catecholaminergic activity. Gamma-aminobutyric acid also participates in the vigilance states, and benzodiazepines exert hypnogenic effects by modulating gamma-aminobutyric acid transmission. Sleep factors and hypnogenic peptides probably exist, but none of the substances so far described can yet be identified as the critical component in the subtle and still largely elusive mechanisms of vigilance regulation.

Acetylcholine↗

The effects of indalpine--a selective inhibitor of 5-HT uptake--on rat paradoxical sleep.

In order to document the role of monoamines in the reduction of paradoxical sleep by antidepressant drugs, we examined the effect of indalpine , a selective inhibitor of serotonin uptake. Indalpine dose dependently decreased paradoxical sleep and delayed its first appearance. Pretreatment with parachlorophenylalanine markedly decreased the effect of indalpine . In contrast, pretreatment with alpha-methylparatyrosine potentiated the indalpine -induced depression of paradoxical sleep. The results of the study indicate that the increase of extracellular concentration of 5-HT has an inhibitory effect on paradoxical sleep, and this effect is enlarged if catecholaminergic activity is reduced.

Animals↗

Evaluation of the levels of free and total amitriptyline and metabolites in the plasma and brain of the rat after long-term administration of doses used in receptor studies.

This study was conducted in order to investigate the level of amitriptyline (AT) and its metabolites. Three separate experiments were carried out. In two of these experiments, rats were treated over 7 days with IP doses of AT (10 mg/kg in experiment A and 2 X 20 mg/kg in experiment C). The rats were sacrificed either 2 (experiment C) or 12 h (experiments A and C) after the last dose. In experiment B, rats were sacrificed 2 or 12 h after a single dose of 20 mg/kg AT. The results of these experiments showed the following: in experiment A only AT was measurable in the brain and in the plasma, in contrast to experiments B and C, where NT and the hydroxylated metabolites AT-OH and NT-OH reached significant levels in the plasma and in the brain. The concentrations of AT-OH, NT-OH, and NT (12-h values) that were found in the brain are probably not pharmacologically relevant. The 12-h plasma values of all compounds tested were, even with the highest dose, lower than those expected to be clinically effective in man. Our results suggest that AT, at higher doses, may induce its own metabolism. The free plasma levels of this drug and its metabolites are higher in man than in the rat. The possible implications of these results in the use of antidepressants in the treatment of depression are discussed.

Amitriptyline↗

Intrinsic activity of the benzodiazepine antagonist Ro 15-1788 in man: an electrophysiological investigation.

Ten healthy volunteers were injected i.v. with 5 mg Ro 15-1788, a specific benzodiazepine antagonist, or placebo in a double-blind randomised design. In the EEG, Ro 15-1788 led--with some topographical variations--to a diminution of theta and alpha power, an increase of alpha mean frequency and a decrease of delta mean frequency. In auditory evoked potentials, the N1P2 and P2N2 amplitudes decreased. The electrophysiological changes induced by Ro 15-1788 are consistent with a central stimulant action. Ro 15-1788 induced some slight behavioural and subjective changes.

Adult↗

Effects of a benzodiazepine antagonist on the diazepam-induced electrical brain activity modifications.

Brain electrical activity changes induced by Ro 15-1788, an antagonist of central benzodiazepine effects, were investigated in 10 normal subjects. The diazepam-induced sedation, as ascertained by spontaneous EEG, was rapidly reversed after an intravenous injection of 5 mg Ro 15-1788. There appeared to be a good correlation between the EEG and evoked responses modifications; the decrease of the amplitude of the N2 wave may reflect an increase of alertness.

Adult↗

EEG asymmetry during sleep.

The ratio of integrated EEG amplitude from left and right temporal areas was analyzed during sleep in normal subjects for two consecutive nights. The results showed that the differences between the subjects were similar in both nights and were much larger than the differences between the stages of sleep. No significant variation was found between stages, although stage 1 tended to show greater relative right activation in night 1. Also, the relative right activation was greater in wakefulness in night 2 as compared to night 1. The classification of the correlation coefficients between stages corresponded to the physiological transitions between stages, suggesting that the small source of variance due to sleep stage contains relevant information.

Adult↗