Biomedical subjects

R Elie

Publications and source records attributed to R Elie.

At least 19 recordsLinked to original sources

PubMed2001

Effects of chronic antidepressant treatments on 5-HT and NA transporters in rat brain: an autoradiographic study.

Tricyclic antidepressants and serotonin (5-HT) uptake inhibitors rapidly block uptake sites, or transporters; however, their therapeutic effects are only seen after 2-3 weeks of treatment. Thus, direct blockade of 5-HT and noradrenaline (NA) transporters cannot account entirely for their clinical efficacy, and other long-term changes may be involved. Adult Sprague-Dawley rats were treated for 21 days with daily injections of either desipramine, trimipramine, fluoxetine, or venlafaxine; a fifth group that was used as a control, received daily saline injections. Identified cortical areas, hippocampal divisions and nuclei raphe dorsalis, raphe medialis and locus coeruleus were examined by quantitative autoradiography using either [3H]citalopram to label 5-HT transporters, or [3H]nisoxetine for NA uptake sites. Increases in [3H]nisoxetine binding were found in the cingulate, frontal, parietal, agranular insular, entorhinal and perirhinal cortices as well as in the hippocampal divisions CA1, CA3, dentate gyrus and subiculum, and in nucleus raphe dorsalis of trimipramine-treated animals compared to the control rats. Also, densities of NA transporters decreased in temporal cortex, CA2 and nucleus raphe dorsalis in fluoxetine-treated rats as compared to the controls. Also, there was a decrease in NA transporters in the locus coeruleus of the desipramine-treated animals as compared to the densities measured in the control group. Chronic treatment with desipramine or trimipramine, which do not directly inhibit 5-HT uptake, compared to fluoxetine and venlafaxine, lead to increases in 5-HT transporter densities in cingulate, agranular insular and perirhinal cortices. The present study shows differential region-specific effects of antidepressants on 5-HT and NA transporters, leading to distinct consequences in forebrain areas.

Animals↗

PubMed2001

Accuracy of the Pepin method to determine appropriate lithium dosages in healthy volunteers.

OBJECTIVE: To assess if the lithium dosage prescribed according to the Pepin method leads to therapeutic serum concentrations of lithium. METHODS: For 13 healthy volunteers, the initial daily doses of lithium were calculated according to the Pepin formula with a view to obtaining a serum lithium level of 0.8 mmol/L. Lithium was administered twice daily for 21 days, and blood samples were drawn daily, 12 hours after the last dose was taken. Dosage was adjusted if serum concentrations were below 0.6 mmol/L or above 1.0 mmol/L or if major side effects were reported. RESULTS: Daily lithium doses ranged from 1050 mg to 1950 mg (mean 1569 mg, standard deviation [SD] 291 mg), The mean serum lithium concentrations for weeks 1, 2 and 3 were 0.74 mmol/L (SD 0.19 mmol/L), 0.67 mmol/L (SD 0.22 mmol/L) and 0.69 mmol/L (SD 0.13 mmol/L), respectively. Within-subject variance was negligible. Sixty-eight percent of the serum lithium concentration measurements fell between 0.57 mmol/L and 0.83 mmol/L, and 84% fell within the recommended therapeutic range of 0.60 mmol/L and 1.20 mmol/L. CONCLUSIONS: The Pepin method is a safe but conservative method for predicting the appropriate daily dose of lithium.

Adolescent↗

PubMed2001

Effect of antidepressants on ATP-dependent calcium uptake by neuronal endoplasmic reticulum.

This study investigated the effect of tricyclic and atypical antidepressants on adenosine triphosphate (ATP) dependent calcium uptake by the endoplasmic reticulum of lysed synaptosomes from rat brain cortex. Tricyclic antidepressants (imipramine, desipramine, clomipramine, amitriptyline) exhibited no effect in the lower range (0.06 to 2 microM) of drug concentrations, and a concentration-dependent inhibition of calcium uptake in the upper range (6 to 200 microM). A concentration-dependent inhibition was observed for atypical antidepressants (mianserin, desmethylmianserin, venlafaxine, desmethylvenlafaxine, fluoxetine) in both the lower and the upper range of drug concentrations. Since no stimulation of calcium uptake was observed in either concentration range, it appears that the tricyclic and atypical antidepressants tested are not capable of normalizing, through their effect on the endoplasmic reticulum, an overactive calcium signal. which is possibly implicated in the etiology of affective disorders. Also, although only marginal inhibition of calcium uptake is expected at brain concentrations of tricyclics and mianserin-desmethylmianserin that are likely to be encountered during clinical use, a more substantial inhibition could occur with fluoxetine.

Adenosine Triphosphate↗

PubMed1999

Interaction between dopamine and glutamate receptors following treatment with NMDA receptor antagonists.

Interactions between dopamine and glutamate neurotransmission have been reported to play an important role in a number of different systems. We were interested in examining the effects of sub-chronic treatment with NMDA receptor antagonists (dizocilpine [MK-801], and 3-carboxy-piperazin-propyl phosphonic acid [CPP]) on dopamine D(1)-like, dopamine D(2)-like, as well as glutamate receptors of the NMDA and AMPA receptor subtypes in the neostriatum and substantia nigra of rats that had received a massive dopamine denervation at 3 days of age. Using quantitative ligand binding autoradiography, we demonstrated that the two NMDA receptor antagonists did not have different profiles of action. Furthermore, while we found a significant negative relationship between NMDA receptors and dopamine receptors (both dopamine D(1)-like and D(2)-like receptor subtypes) in the neostriatum, AMPA receptors were positively correlated with dopamine D(1)-like binding sites in all regions investigated. These findings suggest that the interrelationship between dopamine and glutamate receptors is highly controlled and that the nigrostriatal dopamine systems play an important role in this interaction.

Animals↗

PubMed1999

Inhibition of K+-induced Ca2+ uptake in rat hippocampus synaptosomes by mianserin enantiomers.

In order to test potential links with other stereospecific neurobiological effects of mianserin, the present study explored the stereospecificity for inhibition of depolarization-induced Ca2+ uptake by mianserin. Synaptosomes from rat hippocampus were incubated with 45Ca2+ in either resting or depolarizing (60 mM K+) choline medium, in the absence or presence (0.6-200 microM) of a mianserin enantiomer. The enantiomers were equipotent (IC50 approximating 50 microM) at inhibiting net depolarization-induced Ca2+ uptake. This finding, therefore, cannot help to explain the stereoselective enhancement of noradrenaline release by S(+)-mianserin; it is also not in keeping with the stereospecificity exhibited by mianserin in acute tests predictive of antidepressant activity, thus suggesting that the calcium-channel blocking activity of mianserin is not linked to its antidepressant effect.

Analysis of Variance↗

PubMed1999

Amantadine hydrochloride treatment in olivopontocerebellar atrophy: a long-term follow-up study.

The efficacy of amantadine, a dopamine-releasing agent and antagonist of the N-methyl-D-aspartate glutamate receptor, was evaluated in patients with olivopontocerebellar atrophy. By contrast to an untreated control group whose terminal performance deteriorated on 8 of 8 measurements of reaction time and movement time, patients treated with amantadine for a mean duration of over 40 months had improved performances in 1 of 4 reaction time measurements and in 3 of 4 movement time measurements and remained stable on the others. These results demonstrate long-term benefits of amantadine in olivopontocerebellar atrophy-induced deficits of movement initiation and movement completion.

Adult↗

PubMed1999

Occupational asthma caused by isocyanates: patterns of asthmatic reactions to increasing day-to-day doses.

Inhalation challenges to isocyanates are conducted in specialized centers to confirm occupational asthma. The pattern of asthmatic reactions due to consecutively increasing daily doses of isocyanates is unknown. We conducted a study involving 24 subjects who had undergone specific inhalation challenges to isocyanates (toluene diisocyanate [TDI], n = 8; hexamethylene diisocyanate [HDI], n = 10; and methylene diisocyanate [MDI], n = 6) on three or more consecutive days. Challenge tests were given through a closed-circuit apparatus (n = 12) or in small cubicles (n = 12), allowing assessment of the total inhaled dose (concentration x duration). The pattern of asthmatic reactions was described. In addition, dose-response curves were analyzed and tested for their linear and quadratic trends. Four patterns of response were observed: (1) linear (n = 10); (2) minimal effect followed by a brisk change (n = 7); (3) significant change followed by tachyphylaxis or a plateau (n = 4); (4) biphasic (i.e., significant change followed by a reduction in the effect and significant change on the last day of exposure [n = 3]). Subjects with a linear dose-response pattern had been exposed to isocyanates at work for a significantly shorter interval (7.2 +/- 6.7 yr) than subjects with a nonlinear pattern (20.0 +/- 13.1 yr). An analysis of variance covering a 3-d period for all subjects showed a significant linear model for the response (p < 0.0001); there was no quadratic trend. However, when the analysis was done on subjects with four or more days of challenge (n = 10), we found both linear and quadratic significant components. This analysis shows that the most common pattern of asthmatic reactions to inhaled isocyanates generated on consecutive days is linear; however, other patterns are also observed. In some individuals, particularly those in whom more days of challenge are required, we observed in addition to a strong linear component a quadratic component manifested by a brisk change on the last day of exposure.

Adult↗

PubMed1999

Sleep latency is shortened during 4 weeks of treatment with zaleplon, a novel nonbenzodiazepine hypnotic. Zaleplon Clinical Study Group.

BACKGROUND: Zaleplon is a short-acting pyrazolopyrimidine hypnotic with a rapid onset of action. This multicenter study compared the efficacy and safety of 3 doses of zaleplon with those of placebo in outpatients with DSM-III-R insomnia. Zolpidem, 10 mg, was used as an active comparator. METHOD: After a 7-night placebo (baseline) period, 615 adult patients were randomly assigned to receive, in double-blind fashion, I of 5 treatments (zaleplon, 5, 10, or 20 mg; zolpidem, 10 mg; or placebo) for 28 nights, followed by placebo treatment for 3 nights. Sleep latency, sleep maintenance, and sleep quality were determined from sleep questionnaires that patients completed each morning. The occurrence of rebound insomnia and withdrawal effects on discontinuation of treatment was also assessed. All levels of significance were p < or = .05. RESULTS: Median sleep latency was significantly lower with zaleplon, 10 and 20 mg, than with placebo during all 4 weeks of treatment and with zaleplon, 5 mg, for the first 3 weeks. Zaleplon, 20 mg, also significantly increased sleep duration compared with placebo in all but week 3 of the study. There was no evidence of rebound insomnia or withdrawal symptoms after discontinuation of 4 weeks of zaleplon treatment. Zolpidem, 10 mg, significantly decreased sleep latency, increased sleep duration, and improved sleep quality at most timepoints compared with placebo; however, after discontinuation of zolpidem treatment, the incidence of withdrawal symptoms was significantly greater than that with placebo and there was an indication of significant rebound insomnia for some patients in the zolpidem group compared with those in the placebo group. The frequency of adverse events in the active treatment groups did not differ significantly from that in the placebo group. CONCLUSION: Zaleplon is effective in the treatment of insomnia. In addition, zaleplon appears to provide a favorable safety profile, as indicated by the absence of rebound insomnia and withdrawal symptoms once treatment was discontinued.

Acetamides↗

PubMed1997

Atypical antidepressants inhibit depolarization-induced calcium uptake in rat hippocampus synaptosomes.

The effect of the atypical antidepressants mianserin, iprindole, and fluoxetine on synaptosomal calcium uptake was tested under conditions where a selective action on voltage-dependent calcium channels can be documented. Synaptosomes from rat hippocampus were incubated with 45calcium either in choline-rich medium or in depolarizing (60 mM K+) choline-rich medium, and drug effects on calcium uptake in these two conditions, as well as on the net depolarization-induced calcium uptake, were studied in the range of concentrations 0.6-200 microM. A concentration-dependent marked inhibition of uptake in depolarizing choline medium was observed for the three antidepressants, whereas only a minor degree of inhibition of uptake in resting choline medium was present at the highest drug concentration; as a result, the concentration-effect relationships exhibited a strong concentration-dependent inhibition of net depolarization-induced calcium uptake. The IC50 values, calculated by interpolation of the last three or four points of the concentration-effect relationships, were 27, 39, and 68 microM for fluoxetine, iprindole, and mianserin, respectively. Significant degrees of calcium channel inhibition are not expected at brain concentrations of mianserin and iprindole that are likely to be encountered during clinical use; however, the fluoxetine concentration-effect relationship established in the present study, coupled with the published ratio of 20:1 for brain:plasma concentrations of fluoxetine-norfluoxetine in humans, suggests that brain calcium channel function could be appreciably reduced in some patients treated with this atypical antidepressant.

Animals↗

PubMed1996

Involvement of the 12-lipoxygenase pathway of arachidonic acid metabolism in homosynaptic long-term depression of the rat hippocampus.

Low-frequency stimulation is associated with long-term depression (LTD) of synaptic efficacy in various brain structures. Like long-term potentiation (LTP), homosynaptic LTD in area CA1 of the hippocampus appears to require NMDA receptor activation, changes in postsynaptic calcium concentration and phospholipase A2 (PLA2) activation. Arachidonic acid (AA) is released after the activation of calcium-dependent phospholipases and free AA is rapidly metabolized to a family of bioactive products (the eicosanoids) which are thought to be both intracellular and extracellular messengers. In the present study, we investigated the involvement of the cyclooxygenase and lipoxygenase pathways of AA metabolism in the formation of homosynaptic LTD in the rat hippocampus. Stimulation at 1 Hz for 15 min was used to produce homosynaptic depression in area CA1 of hippocampal slices. LTD induction was partially blocked by bromophenacyl bromide (50-100 microM), a selective PLA2 inhibitor, and by the a nonselective lipoxygenase inhibitor nordihydroguaiaretic acid (NDGA; 100 microM). In contrast, the specific cyclooxygenase blocker indomethacin (100 microM) did not significantly reduce hippocampal LTD. Since NDGA interferes with LTD formation, we examined whether specific inhibitors of 5- and 12-lipoxygenases were capable of blocking LTD expression. The 12-lipoxygenase inhibitor baicalein at a concentration of 50 microM reduced LTP formation when given in the bath, an effect that was less pronounced with the 5-lipoxygenase inhibitor AA-861. These data suggest that the activation of endogenous PLA2 and the formation of 12-lipoxygenase metabolites of AA may be important factors controlling the expression of hippocampal LTD.

Acetophenones↗

PubMed1996

Amantadine hydrochloride treatment in heredodegenerative ataxias: a double blind study.

OBJECTIVE: A group of 27 patients with Friedreich's ataxia and another group of 30 patients with olivopontocerebellar atrophies were each randomly divided into two subgroups, one receiving placebo and the other amantadine hydrochloride (AH; 200 mg daily) for three to four months. METHODS: The effect of double blind treatment was evaluated by simple visual and auditory reaction time (RT) and movement time (MT) for both right and left hands. RESULTS: The subgroup with olivopontocerebellar atrophies receiving AH showed significant improvement on seven out of eight variables studied by analysis of covariance. In patients with Friedreich's ataxia, improvement was definitely less. Treatment remained contraindicated for those with cardiomyopathies or drug intolerance. CONCLUSION: The rationale of AH use in heredodegenerative ataxias can be explained by its replacement effect (dopamine release) and by direct involvement of N-methyl-D-aspartate (NMDA) in glutamate mediated neurotoxicity in cerebellar granular cells; memantine, an AH analogue, is a potent blocker of NMDA receptors.

Adult↗

PubMed1995

Differential effect of desipramine and 2-hydroxydesipramine on depolarization-induced calcium uptake in synaptosomes from rat limbic sites.

This study was conducted to investigate the inhibition of synaptosomal 45Ca uptake by desipramine and its major metabolite 2-hydroxydesipramine in the rat hippocampus and cingulate cortex, areas associated with emotional control. A concentration-dependent inhibition of net depolarization-induced 45Ca uptake was observed for desipramine (20-200 microM) in synaptosomes from both sites. However, 20 microM 2-hydroxydesipramine failed to inhibit calcium channel function in either of the two limbic sites; higher concentrations (60 or 200 microM) did produce a minor degree of inhibition in hippocampus synaptosomes. Others have shown that the clinically encountered plasma concentrations of 2-hydroxydesipramine are lower than those of desipramine, and the brain concentration of 2-hydroxydesipramine is therefore not expected to surpass or even reach 20 microM. In view of the previously observed clinical activity of 2-hydroxydesipramine, the present results indicate that calcium channel antagonism may not be the basis for the therapeutic effect of tricyclic antidepressants.

Animals↗

PubMed1994

The treatment of avoidant personality disorder by social skills training in the clinic or in real-life settings.

Twenty-eight outpatients who met DSM-III diagnostic criteria for avoidant personality disorder completed 14 one and a half hour sessions of social skills training in the clinic only or a combination of four sessions in the clinic, four sessions in real-life and six follow-up sessions in the clinic. Subjects were assessed before treatment began, after four sessions, at the end of treatment and at three month follow-up points. Training in real-life did not enhance social skills training; no significant difference between the groups at any assessment points was found. In both groups improvement in time was significant and clinically worthwhile. The treatment effects were maintained up to the three month follow-up, where available. Social skills training appears to be a useful and promising intervention for avoidant personality disorder but its long term impact remains to be investigated.

Adolescent↗

PubMed1994

Influence of affective words on lexical decision task in major depression.

In cognitive science, lexical decision task is used to investigate visual word recognition and lexical access. The issue of whether or not individuals who are depressed differ in their access to affectively laden words and specifically to words that have negative affect was examined. Based on some aspects of the Resource Allocation Model (Ellis), it was postulated that patients suffering from depression take more time to recognize items from an affective-loaded list. In order to compare their behavior in a lexical decision task, patients suffering from depression and healthy controls were studied. We hoped to find an interaction between the mood state of subjects and the categories (affective or neutral) of words. Two groups of right-handed adults served as subjects in our experiment. The first group consisted of 11 patients suffering from depression (mean age: 40.2; sd: 6.8). All of this group met the DSM-III-R and the Research Diagnostic Criteria for major depressive disorder. Severity of their disease was rated using the 24-item Hamilton Depressive Rating Scale. All patients suffering from depression were without psychotropic medication. The control group was composed of 24 subjects (mean age: 32.7; sd: 7.9). A depressive word-list and a neutral word-list were built and a computer was used for the lexical-decision task. A longer reaction time to detect the non-word stimuli (F1,33 = 11.19, p < 0.01) was observed with the patients by comparison to the normal subjects. In the analysis of the word stimuli, a group by list interaction (F1,33 = 7.18, p < 0.01) was found.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1994

Absence of stereoselectivity of some tricyclic antidepressants for the inhibition of depolarization-induced calcium uptake in rat cingulate cortex synaptosomes.

This study was conducted in order to investigate the inhibition of synaptosomal 45calcium uptake by oxaprotiline, trimipramine and doxepin stereoisomers in the rat cingulate cortex which is an associative area of the cortex that interacts with the limbic system. A concentration-dependent inhibition of net depolarization-induced 45calcium uptake was observed for all substances tested. No significant difference in potency could be established within any of the pairs of antipodes and the IC50 values obtained were in the 30 microM to 50 microM range. These results are quite similar to those previously obtained with this group of compounds in hippocampal synaptosomes where discrepancies between relative calcium channel antagonism and clinical activity of the antipodes have been identified. Therefore, the present study of stereoisomers of tricyclic antidepressants fails to resolve these discrepancies and does not provide unequivocal support for the hypothesis that calcium channel blockade is somehow responsible for the therapeutic effect of tricyclic antidepressants.

Animals↗

PubMed1994

A double-blind comparison of nefazodone, imipramine, and placebo in major depression.

BACKGROUND: Nefazodone is a 5-HT2-receptor antagonist and serotonin (5-HT) selective reuptake inhibitor. This study evaluates the safety and efficacy of nefazodone in patients with major depressive disorder (MDD) in comparison to imipramine and placebo treatments. It also compares two dose ranges of nefazodone to investigate its optimal dose range. METHOD: Nefazodone was evaluated in a 6-week, double-blind trial of novel design involving 180 patients meeting Research Diagnostic Criteria for major depressive disorder and having a minimum pretreatment score of 22 on the first 17 items of the Hamilton Rating Scale for Depression (HAM-D). Patients were randomly assigned to placebo (2-10 capsules/day), imipramine (50-250 mg/day), or nefazodone in two dose ranges (50-250 mg/day or 100-500 mg/day). RESULTS: Improvement on depression measures with nefazodone in the 100-500-mg/day dose range (endpoint mean = 460 mg/day) and imipramine (endpoint mean = 214 mg/day) exceeded that with placebo. Some benefit was also observed in the nefazodone 50-250-mg/day treatment group (endpoint mean = 242 mg/day), but it was suboptimal. Evidence of nefazodone's efficacy as an antidepressant was consistently observed on physician- (HAM-D, Clinical Global Impressions [CGI]) and patient-rated (CGI-patient rated) scales. By patient self-report, improvement of anxiety symptoms associated with depression was evident with nefazodone as early as the first week of treatment, and benefit was seen with both nefazodone dosage groups. Analyses of the physician's global assessments of therapeutic effect and side effects at end of treatment showed therapeutic benefit for both nefazodone and imipramine treatments; however, patients in the nefazodone treatment groups were significantly less troubled by adverse experiences than were imipramine-treated patients, resulting in a lower dropout rate for adverse experience. CONCLUSION: Nefazodone is a well-tolerated and effective antidepressant for the treatment of major depressive disorder.

Adult↗

PubMed1993

Effect of some stereoisomeric tricyclic antidepressants on 45Ca uptake in synaptosomes from rat hippocampus.

The present study has examined the inhibition of synaptosomal 45calcium uptake by trimipramine, oxaprotiline and doxepin, and their stereoisomers, in synaptosomes from the rat hippocampus. No significant difference in potency could be established for inhibition of net depolarization-induced 45calcium uptake for any pair of antipodes, and the IC50 values for calcium channel blockade were in the vicinity of 30 microM for this group of compounds. Trimipramine, doxepin and oxaprotiline also inhibited the 45calcium uptake mediated by Na(+)-Ca2+ exchange, with IC50 values of 71 microM, 110 microM, and 100 microM, respectively. The similar potency of doxepin isomers for inhibition of voltage-dependent calcium channels is in harmony with their reported similar potency in the clinic. A slight difference in potency is reported between the isomers of oxaprotiline in the behavioral despair test in rats, and the dextrorotatory isomer of trimipramine is reported to be a much more potent antidepressant than the levorotatory isomer: these order of potencies do not correspond perfectly with the similar potency of the antipodes against voltage-dependent calcium channels. The present study of stereoisomeric tricyclic antidepressants therefore fails to provide unequivocal support for the hypothesis that calcium channel blockade by tricyclic antidepressants is involved in their therapeutic effect.

Animals↗

PubMed1993

Radiologic correlates of reaction time measurements in olivopontocerebellar atrophy.

We measured simple visual and auditory reaction time (RT) and movement time (MT) in 32 patients with olivopontocerebellar atrophy (OPCA) in comparison to 32 control subjects. In addition, we followed 2 approaches to radiologic assessment by computed tomographic scans: subjective (by inspection of films) and objective (by measurement of 4 radiologic ratios at the level of the posterior fossa and 1 ratio at the supratentorial level). All OPCA patients had various degrees of cerebellar atrophy and lengthened RT and MT in comparison to their controls. There were no significant differences in RT and MT performances in patients with mild-moderate versus those with severe cerebellar atrophy as assessed by inspection of their films. OPCA patients with severe versus mild-moderate atrophy evaluated by 3 measures, i.e., brainstem, brachium pontis and fourth ventricle ratios, presented few significantly lengthened RT and MT performances. In contrast, patients with severe atrophy revealed by the midbrain ratio had significantly lengthened RT and MT performances compared to those with mild-moderate atrophy assessed by this ratio on 7 of 8 measures; the 8th measure showed a borderline significant difference. This could be explained by the fact that atrophy at the midbrain level is the only one which involves dopaminergic, noradrenergic and glutamatergic structures and pathways.

Adult↗