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Biomedical subjects

J M Gaillard

Publications and source records attributed to J M Gaillard.

At least 55 records · Page 3Linked to original sources
PubMed1992

The EEG of the sleep onset period in insomnia: a discriminant analysis.

A period of rapid change in the wave components of the electroencephalogram (EEG) marks the transition from wake to sleep. Twenty-six insomniac and 28 control nights were studied in a discriminant analysis to determine whether this transitional state is modified in any way in subjects diagnosed for psychophysiological insomnia. A discriminant function was derived based on 20 insomniac and 22 normal nights. All 42 nights were correctly classified by this function. The sleep onset period, extending on the average over about 3 minutes, was characterized essentially by the beta and delta components of the EEG signal and by an activity index given by the ratio beta/delta, measured at the temporal lobe sites. Other variables included the subject's age and the magnitude of the changes occurring in the difference between activities in the right and left hemispheres. The variables contributing most to the discrimination were the activity index and beta, especially at the transitions from wake to stage 1 and from stage 1 to stage 2. The contribution of delta to the discrimination was less, but extended further in time to include stage 2 sleep. A test on the remaining six insomniac and six control nights gave a 75% classification accuracy, thus validating the derived discriminant function.

Adolescent↗
PubMed1992

Platelet membrane alpha 2-adrenergic receptors in depression.

The platelet membrane was used as a model system to examine alpha 2-adrenergic receptors in 30 depressed patients and 30 healthy control subjects. The number of binding sites and their affinity for 3H-UK 14304 (5-bromo-6-(2-imidazoline-2-ylamino)-quinoxaline), a potent, highly selective alpha 2-adrenergic receptor agonist, was measured. Plasma magnesium and free 3-methoxy-4-hydroxyphenylglycol (MHPG) concentrations were assayed in the same sample. A decreased agonist-receptor affinity was found in depressed patients, whereas receptor density was not significantly altered compared with that in control subjects. In bipolar depressed and dysthymic patients, there was a tendency toward a higher density of alpha 2-adrenergic receptors. This trend was not apparent in unipolar, recurrent depressed subjects. Moreover, a positive correlation between Bmax and Kd values was observed in patients but not in control subjects--a finding that suggests that a compensatory phenomenon occurs in depression. After the patients were treated with antidepressant drugs, an increased affinity (decrease in Kd) was observed, together with a decrease in binding sites. Plasma magnesium concentrations were higher in drug-free depressed patients than in control subjects. In addition, magnesium concentrations were negatively correlated with the density of alpha 2-adrenergic receptor binding sites in depressed patients, both before and during treatment. Lastly, a trend toward a negative correlation between plasma MHPG concentration and the number of binding sites was also observed. These results suggest a complex multifactorial regulation of alpha 2-adrenergic receptors, which are probably hyposensitive in depressive syndromes.

Adrenergic alpha-Agonists↗
PubMed1992

Decrease in epinephrine-induced attenuation of platelet adenylate cyclase activity in depressed patients: relation with plasma electrolytes.

We have measured the alpha 2-adrenoceptor-mediated inhibition of platelet membrane adenylate cyclase in depressed patients and control subjects. The results showed a decrease in the forskolin-stimulated adenylate cyclase inhibition of depressed patients compared to the healthy subjects. This suggests a subsensitivity of alpha 2-adrenoceptor in depression. However, this subsensitivity was not correlated to the severity of depression as both severely and moderately depressed patients exhibited the same percent of adenylate cyclase inhibition. The antidepressant drugs treatment induced an increase in the percent of adenylate cyclase inhibition with a trend towards the control values. However, this increase did not equal control value, and moreover both remitted and unremitted patients presented a similar change in their alpha 2-adrenoceptor-mediated adenylate cyclase inhibition. This result raises the question about a simple and direct relation between the clinical status of depression and the power of alpha 2-adrenoceptor-mediated adenylate cyclase inhibition. Plasma magnesium and sodium yielded correlations to this alpha 2-adrenoceptor-mediated adenylate cyclase inhibition suggesting a relation between the platelet adrenergic function and plasma electrolytes.

Adenylyl Cyclase Inhibitors↗
PubMed1992

Evolution of blood magnesium, sodium and potassium in depressed patients followed for three months.

No consensus has been obtained about blood electrolyte status, especially about magnesium, in affective disorders. This is mainly due to the lack of information about the distribution of the patients in clinical subgroups, sex, type of treatment and about the severity of their illnesses. Most of these studies concerned treated patients. We confirmed in this study that drug-free depressed patients have higher erythrocyte and plasma magnesium than controls, as shown in previous reports. Significant differences are observed in as shown in previous reports. Significant differences are observed in patients for sex and between clinical subgroups. Low plasma potassium levels are described in both male and female depressed patients. The erythrocyte magnesium level tends to normalize in parallel with clinical improvement, depending on sex and clinical subgroup, and seems then to be related to the intensity of the depression. Plasma magnesium in male and female patients, except for female unipolars, remains higher than controls in all conditions and might be related to the diagnosis of affective disorders.

Adult↗
PubMed1991

A study of the interrupted REM episode.

Brief interruptions of REM sleep are considered to be part of the REM episode. The maximum allowable duration of such an interruption, which is used to define the end of the REM episode, is currently a matter of debate. Making measurements on individual REM cycles, inter-REM interval analysis was carried out to determine whether the generally adopted 15 minute empirical rule for this maximum needs to be extended to 25 minutes as suggested by several including Kobayashi et al. Our results show that there is no reason to alter the 15 minute rule and that measurements which do not take into account the time-of-night effect may be misleading. The proportion of interrupted REM episodes observed in our population of healthy adults is high. We have therefore also examined in some detail the phenomenology of the temporal evolution of the structure and content of the interrupted REM episodes. Both showed a definite change over the night: the interruptions in the earlier episodes tend to return the system to slow wave sleep while those in the later episodes tend to return it to wake. It is hypothesized that these interruptions reflect a measure of REM sleep pressure and its interaction with both slow wave sleep and wake pressures.

Adolescent↗
PubMed1991

Hypnotic action of flunitrazepam is reversed by proglumide in rats.

1. Caerulein, an analogue of cholecystokinin (CCK-8), like CCK-8, has been shown to produce hypnotic effects similar to those of benzodiazepine (flunitrazepam). 2. Proglumide antagonizes the action of CCK-8 and of its analogue. 3. The aim of the present study was to demonstrate whether proglumide would affect the potent hypnotic action of flunitrazepam in rats. 4. The association of proglumide with flunitrazepam suppress the increase of total sleep time and slow wave sleep seen after flunitrazepam alone. Proglumide alone has no effect on sleep stages. The authors report here for the first time that the hypnotic action of flunitrazepam is antagonized by proglumide in rat.

Animals↗
PubMed1990

Effects of moclobemide on sleep in healthy human subjects.

Ten healthy, normal subjects (5 male and 5 female) aged 20-28 years participated in this experimental study of the effect of moclobemide on sleep. The design consisted of 2 sessions of 5 nights each, comprising 1 adaptation night, 2 nights on placebo and 2 inputs of moclobemide 4 mg/kg (session B). The 2 sessions were separated by at least 15 days and their order was balanced and randomized. During the last 4 nights of each session, sleep parameters were recorded throughout the night according to standard procedures. Moclobemide at a dose of 4 mg/kg induced moderate changes in the sleep-wake balance: a significant increase in stage 1 on the second drug night, a slight increase in stage 2 and a significant decrease in paradoxical sleep on the 2 drug nights. There was also a moderate reduction in the number of rapid eye movements (REM) during paradoxical sleep, but the number of cycles and latency to paradoxical sleep were unchanged, as well as all other sleep parameters measured. With 6.5 mg/kg, the changes were more pronounced: total sleep time was diminished, but this was significant only on the second and third nights. Transient awakenings increased significantly on the first drug night, and wakening latency decreased. The only modification of orthodox sleep was an increase in the percentage of stage 2 on the first drug night, whereas slow-wave sleep was unchanged. Paradoxical sleep was reduced on the first 2 drug nights, but tolerance appeared on the third night. The decrease in paradoxical sleep was exacerbated in the last part of the night. REM were decreased during paradoxical sleep.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

The intrasleep relationship between wake and stage 4 examined by transition probability analysis.

The relationship between wake and stage 4 of slow-wave sleep (SWS), in particular the previously observed deficiency in SWS accompanying sleep containing long-wake periods, is examined in this study of 147 health subjects. Stage shift comportment is compared between those NREM/REM cycles with wake periods greater than 3 minutes and those with less, using the method of transition probabilities. It is shown that these long wake interruptions occur preferentially in light sleep, and systematically disrupt the regular normal descent towards SWS, but do not significantly reduce the number of SWS episodes. There is at the same time, however, a reduction in the average duration of stage 4 periods of SWS which accounts for the observed reduction in the total amount of SWS.

Adolescent↗
PubMed1989

Differential effects of flunitrazepam on human sleep in combination with flumazenil.

The experiments reported here were designed to characterize in detail the spectrum of activity of flunitrazepam in human sleep. The direct and residual effects of flunitrazepam, as well as the antagonism by flumazenil, an antagonist of benzodiazepine receptors, were studied in 28 normal subjects recorded in the sleep laboratory. The five categories of variables--sleep-wake balance, sleep organization, orthodox sleep, phasic events in sleep, and sleep waveforms--were all modified by flunitrazepam. Some of these modifications were observed only on the drug night and were antagonized by flumazenil, whereas others persisted in the placebo postdrug night and were not antagonized by flumazenil. A few variables showed changes intermediate between these two types of reactivity. The results do not fit well with the multiple benzodiazepine receptors theory, but instead support the concept of spare receptors. Along these lines, the study of the reactivity of sleep components to ligands of benzodiazepine receptors can contribute to the better understanding of the neuronal systems involved in their control.

Adult↗
PubMed1989

The heterogeneity of 3-methoxy-4-hydroxyphenylglycol levels among depressed patients.

A previous report by our group and results published by other research groups have indicated a dichotomy in MHPG levels in depressed patients. This study attempted to characterize phenomena associated with this dichotomy in plasma MHPG levels. First, we have noted, at least in female patients, that homogeneity of MHPG levels, as tested by fitting with a normal curve, can be ruled out. In contrast, in the total population, a dichotomy was less evident in this study; the 2 subgroups, high and low levels of MHPG, partially overlap, and this results in a gaussian distribution. However, based on the hypothesis of a bimodal distribution, as shown by others and not excluded here, it was possible to find some factors associated with heterogeneity. Thus, polarity of depression, sex and age of the patients, age of disease onset and depression score affect MHPG levels. On the other hand, other elements suspected to modify MHPG values, such as the different lengths of the washout period (minimum 10 days), or some medication (chloralhydrate or levomepromazine) required during the washout period, did not show any effect. The aim of this study was to better characterize this peripheral index for its possible use in clinical application.

Adult↗
PubMed1989

Involvement of sulfhydryl groups in the transport of L-tyrosine and L-tryptophan across the human red cell membrane in vitro.

In previous papers, we reported a deficit in tyrosine (TYR) and tryptophan (TRP) transport across the erythrocyte membrane in depressed patients. To investigate further the transport mechanism of the two precursors of monoamines, we tested in healthy subjects the role played by sulfhydryl groups (SH). These groups, cysteine residues, are localized on the intrinsic domain such as the transporters of chloride or sugars. We found that all sulfhydryl reagents that inactivated the SH induced a strong inhibition of the transport of amino acid across the red cell membrane when incubated in the plasma as medium. We concluded that a relationship might exist between these neutral amino acids and D-glucose transport.

4-Chloromercuribenzenesulfonate↗
PubMed1988

Hypnotic action of flunitrazepam in the rat: does 5-HT mechanism play a role?

This study examined whether pharmacological manipulation of serotonergic (5-HT) systems would affect the hypnotic action of flunitrazepam in rats. Flunitrazepam, a potent hypnotic, was used alone or combined with parachlorophenylalanine (pCPA), an inhibitor of the synthesis of 5-HT, 8-OH-DPAT, a 5-HT1A receptor agonist and fluvoxamine, an inhibitor of the reuptake of 5-HT. Flunitrazepam increased the amount of orthodox sleep, the latency of rapid eye movement (REM) sleep and decreased the amount of REM sleep. The drug pCPA decreased the total sleep time and the amount of orthodox and REM sleep. Administration of flunitrazepam to pCPA-pretreated rats induced orthodox sleep in an identical way to that found in the controls. The drug 8-OH-DPAT increased wakefulness and the latency of REM sleep. The association of flunitrazepam with 8-OH-DPAT abolished the increase in waking seen after 8-OH-DPAT alone. In contrast, the combined treatment with flunitrazepam and 8-OH-DPAT resulted in a lengthening of the latency of REM sleep significantly greater than that observed with the same dose of each drug alone. Fluvoxamine increased the latency a decrease the amount of REM sleep. The association of fluvoxamine with flunitrazepam induced a decrease in REM sleep, equal to the sum of the effects of the two drugs alone. Fluvoxamine did not modify the other effects of flunitrazepam. The present experiments demonstrate that the association of pCPA, 8-OH-DPAT and fluvoxamine, did not alter the hypnogenic effect of flunitrazepam. The possibility of an involvement of 5-HT mechanisms in the effect of flunitrazepam on the phasic events in sleep is questionable.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1988

Sleep pharmacology of typical and atypical ligands of benzodiazepine receptors.

The effects of several benzodiazepine and non-benzodiazepine ligands of benzodiazepine receptors have been investigated in sleep of normal young adults. The spectrum of activity of each compound has been characterized using a number of sleep variables in addition to the standard sleep stages. These substances affect all the principal components of sleep, that is the sleep-wake balance, paradoxical sleep, orthodox sleep and the EEG waveforms in the different sleep stages. Some, but not all, modifications induced by flunitrazepam are antagonized by flumazenil and they recover with various time constants after a single administration of the drug. The results of these experiments indicate a heterogeneity in the mechanism of action of benzodiazepine and non-benzodiazepine ligands of benzodiazepine receptors, because they affect differently the various components of sleep. It is not necessary to invoke a heterogeneity of the central benzodiazepine receptors (the BZ1-BZ2 theory) in order to account for these differences, but they can be explained by the concept of spare receptors.

Humans↗
PubMed1988

Evolution of red blood cell membrane transport and plasma level of L-tyrosine and L-tryptophan in depressed treated patients according to clinical improvement.

The erythrocyte membrane transport (MT) of L-tyrosine (TYR) and L-tryptophan (TRP) and their plasma concentration showed abnormal mean values in 37 depressed patients compared to control subjects before treatment. The pattern of these abnormal values differed according to the clinical subgroup (DSM III criteria). In bipolar disorders the TYR values were all low and the TRP values showed little change, except a low level of plasma TRP. In major depression, MT were abnormal (MT TYR low, MT TRP high) with a very low plasma TRP. In dysthymic disorders the TYR and TRP values were normal. The normalization of the above biochemical variables was significantly correlated with the clinical improvement; however, the plasma concentration of TRP remained abnormal in some patients who had recovered. In contrast, only plasma TYR and TRP were significantly increased in patients without recovery.

Adult↗
PubMed1987

Determination of 3,4-dihydroxyphenylglycol (DHPG) by HPLC with coulometric detection, and correlation with 3-methoxy-4-hydroxyphenylglycol (MHPG) in human plasma.

A method for determining plasma 3,4-dihydroxyphenylethyleneglycol (DHPG), a central noradrenaline (NA) metabolite, is described. The method used HPLC with dual coulometric detection set in screen mode of operation. The isolation of DHPG and related catecholamines (noradrenaline, dopamine and dihydroxybenzylamine) was performed on acid washed alumina extracted with 0.2 M HCIO4 containing EDTA (0.2%), and reduced glutathione as stabilizer. A reversed phase column with an eluting system containing 0.025 M citric acid-sodium hydrogen phosphate buffer in the ratio 3:2 (v:v) and 5% methanol was used. The experimental results of plasma DHPG levels compared favourably with the results from the literature, and a positively significant correlation with plasma MHPG was found. This method could be used as an alternative in central NA assessment.

Catecholamines↗