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Biomedical subjects

J C Bisserbe

Publications and source records attributed to J C Bisserbe.

At least 19 recordsLinked to original sources
PubMed1994

Moclobemide in social phobia: a pilot open study. GRP Group. Groupe de Recherche en Psychopharmacologie.

In an open-label pilot study, 35 outpatients with social phobia (DSM-III-R) received moclobemide for 12 weeks. The dosing range was 300-600 mg/day. Eighteen patients completed the study and 28 received at least 4 weeks of treatment. There was a consistent improvement in the efficacy parameters. Moclobemide was effective in both major components of social phobia (fear and avoidance). Moclobemide seems as effective as conventional irreversible monoamine oxidase inhibitors. Tolerability was good apart from one occurrence of grand mal seizure.

Adult↗
PubMed1992

Potential use of DPCPX as probe for in vivo localization of brain A1 adenosine receptors.

The suitability of (3H)DPCPX (8-cyclopentyl-1,3-dipropylxanthine), a xanthine derivative, as an vivo probe for labelling adenosine A1 receptors was studied in rats. [3H]DPCPX (nM) penetrated largely into the brain (0.8% of the injected dose per gram of brain tissue 5 min after injection). Brain concentrations stayed at a plateau level from 5 to 15 min after the injection. The distribution in the different brain regions was heterogeneous with the highest amount of [3H]DPCPX in cerebellum and hippocampus and the lowest concentrations in hypothalamus and brain stem. Displacement (45-70% of total radioactivity) was obtained by the injection of 250 nM of cold DPCPX or cyclopentylxanthine, an analog of DPCPX. The ex vivo autoradiographic distribution of [3H]DPCPX was similar to the in vitro autoradiographic distribution of tritiated A1 adenosine receptor ligand as [3H]CHA. These results suggest the potential use of DPCPX for further in vivo investigation of A1 adenosine receptors with techniques such as positron emission tomography.

Animals↗
PubMed1992

Central benzodiazepine receptors in human brain: estimation of regional Bmax and KD values with positron emission tomography.

Studies of central benzodiazepine receptors in the human brain in vivo are now possible using positron emission tomography (PET) and [11C]flumazenil. With the aim of measuring Bmax and Kd in brain regions, we used a two-injection [11C]flumazenil (at high and low specific radioactivity, respectively) pseudo-equilibrium paradigm to evaluate, in seven unmedicated healthy volunteers, the relative merits of three 'reference' structures (pons, hemispheric white matter and corpus callosum) in which the free radioligand concentration in brain tissue was estimated 15-40 min after i.v. injection of the radioligand. By means of high-resolution PET, the Bmax and Kd were calculated for each subject in 18 gray matter structures, based on a two-point Scatchard plot. We found that the use of the corpus callosum as reference often resulted in spurious Bmax and Kd values. The pons was the best reference structure because it provided satisfactory Bmax values (closest to in vitro data) and most consistent Kd values, and was the region easiest to sample on PET images. The pattern of regional Bmax was consistent with that expected from in vitro studies, with values highest in the cerebral cortex, intermediate in the cerebellum, and lowest in the striatum and the thalamus. The Kd values were uniform among regions and were consistent with earlier in vitro and in vivo data. This work documents the feasibility of estimating Bmax and Kd of central benzodiazepine receptors in multiple brain regions for clinical research.

Adult↗
PubMed1992

Regional cerebral glucose utilization in chronic organic mental disorders associated with alcoholism.

Localized cerebral utilization rates for glucose (CMRglu) were determined in 10 detoxified patients with alcoholic organic mental disorders and in 7 age-equivalent normal volunteers using [18F]2-fluoro-2-deoxyglucose positron emission tomography. Although gray and white matter CMRglu were not significantly different, normalized CMRglu was increased in the left cerebellar and parietal cortical regions and decreased in the right posterior white matter and anterior temporal regions of alcoholic patients, and the pattern of regional CMRglu differed between the two groups. The results suggest functional disruption of right-sided and frontal brain regions and hyperactivity of cerebellar-cortical connections in alcoholic chronic organic mental disorders.

Aged↗
PubMed1990

Late clinical testing of cognition enhancers: demonstration of efficacy.

The major difference between clinical trials for efficacy and Phase I trials is their duration; clinical trials of cognition enhancers, for example in senile dementia, require at least 6 months. Because no widely accepted treatment is available, the methodology for these trials is still in a the process of refinement. Double blind placebo-controlled trials are considered to be mandatory particularly by the FDA. Parallel group designs seem preferable and the so-called "enriched design" seems to possess advantages over more classical procedures. Outcome measures should include ratings by clinicians and family members. Self-reports are considered to be unreliable in Alzheimer patients but may be less problematic in AAMI. Psychometric tests of cognition and motor skill should also be included. An essential and pragmatic outcome criterion is, however, the quality of daily life.

Aging↗
PubMed1988

Autoradiographic localization of mouse brain adenosine receptors with an antagonist ([3H]xanthine amine congener) ligand probe.

A [3H]xanthine amine congener (XAC), a potent adenosine receptor antagonist, binds in a saturable and reversible fashion to high affinity binding sites in mouse brain (Bmax = 323 +/- 17 fmol/mg protein, Kd = 1.4 +/- 0.4 nM). Adenosine receptor agonists and antagonists are more potent than adenosine uptake inhibitors in displacing the binding of [3H]xanthine amine congener ([3H]XAC). The anatomical distribution of [3H]XAC binding sites is consistent with its being a ligand probe for adenosine receptors. High binding site densities were observed in the hippocampus (stratum oriens and radiatum, molecular layer), superior colliculus (superficial gray), cerebellum (molecular layer), cerebral cortex and substantia nigra. The availability of a high affinity antagonist radioligand probe like [3H]XAC for adenosine receptors allows the comparative quantitative autoradiographic analysis of agonist and antagonist binding to adenosine receptors, e.g. under varying in vitro incubation conditions (presence and absence of guanine nucleotides and cations).

Animals↗
PubMed1988

Synthesis, affinity and specificity of 18F-setoperone, a potential ligand for in-vivo imaging of cortical serotonin receptors.

Setoperone, a piperidine derivative known for its potent serotonin and moderate dopamine receptor blocking properties was labelled with the positron emitter 18F using a nucleophilic substitution on the nitro derivative. The general pattern of the in-vivo and in-vitro rat brain distribution of this new radioligand was consistent with the mapping of serotonin (5HT2) and dopamine (D2) receptors. The cortical binding of 18F-setoperone was selectively inhibited by ketanserin and not by sulpiride. The affinity of the radiofluorinated ligand for the serotonin receptors was in the nanomolar range (Kd = 0.7 nM).

Animals↗
PubMed1988

Adenosine uptake sites in brain: regional distribution of putative subtypes in relationship to adenosine A1-receptors.

Adenosine uptake sites have been characterized and localized in guinea pig and pointer dog brain by in vitro autoradiography, using as probes 3H-nitrobenzylthioinosine (3H-NBI) and the recently available 3H-dipyridamole (3H-DPR). In guinea pig brain and, to a lesser extent, in pointer dog brain, 3H-DPR was found to label more high-affinity binding sites than 3H-NBI and NBI inhibited 3H-DPR binding having pseudo-Hill coefficients smaller than 0.5. 3H-DPR and 3H-NBI labeled brain structures with different intensities in guinea pig brain, as was revealed by quantitative analysis. While the intensity of 3H-DPR binding varied about 4-fold in neuron-containing structures, 8-fold differences were observed for 3H-NBI binding with phylo- and ontogenetically older brain areas such as hypothalamus and various brain stem structures showing relatively higher densities. These findings raise the interesting possibility of adenosine uptake site heterogeneity (NBI-sensitive and insensitive) in guinea pig brain, complementing the well-established adenosine receptor heterogeneity (A1 and A2). As adenosine's neurodepressant effects are believed to be mainly mediated by adenosine A1-receptors, these were localized using 3H-cyclohexyl-adenosine (3H-CHA) as a ligand probe. In guinea pig brain, the highest receptor densities were seen in hippocampus and claustrum, while only relatively low levels were found in hypothalamus and various brain stem structures. As was previously described for rat brain, major discrepancies in the regional distribution of adenosine A1-receptors and adenosine uptake sites, as labeled by 3H-NBI, were seen in guinea pig brain. These discrepancies were only partly abolished (e.g., in cerebellum) by the use of 3H-DPR as an additional ligand probe for adenosine uptake sites. Adenosine uptake site heterogeneity, therefore, probably does not explain the previously described discrepancies in rodent brain between the distribution of adenosine A1-receptors and uptake sites. Because of the low affinity of 3H-DPR for adenosine uptake sites in rat and mouse brain, these species could not be investigated with this new radioligand probe. In pointer dog brain, as compared to guinea pig brain, a more similar distribution pattern of adenosine A1-receptors and adenosine uptake sites in the brain structures investigated (e.g., hippocampus) could be observed. The situation in guinea pig brain can, therefore, not be universalized to other species.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenosine↗
PubMed1987

Quantitative [3H]dipyridamole autoradiography: evidence for adenosine transporter heterogeneity in guinea pig brain.

[3H] Dipyridamole binding in guinea pig brain slices has been characterized. Binding of [3H] dipyridamole to guinea pig forebrain slices was found to be rapid, reversible and saturable. Saturation experiments revealed a class of high affinity binding sites with a Bmax value of 592 +/- 118 fmol/mg protein and Kd value of 10.8 nM +/- 2.1 nM in the analysed concentration range. In competition experiments, the adenosine transport inhibitors hexobendine and dipyridamole itself were the most potent displacers (inhibition constants of 4.6 nM +/- 1 nM and 11.5 nM +/- 3 nM) with "pseudo-Hill" coefficients close to 1. Competition curves with nitrobenzylthioinosine, another adenosine transport inhibitor, however, showed a biphasic profile with a "pseudo-Hill" coefficient of 0.33 +/- 0.04. Just 42% +/- 4% of [3H] dipyridamole binding were inhibited by nanomolar concentrations of nitrobenzylthionosine and only micromolar concentrations displaced the remainder. Subsequent quantitative autoradiography demonstrated regional differences in the inhibition of [3H] dipyridamole binding by submicromolar concentrations of nitrobenzylthioinosine. While in cortical areas of cerebrum and cerebellum 500 nM nitrobenzylthioinosine displaced binding of [3H] dipyridamole to only about one-third of its sites (in the Purkinje cell layer less than 10%), it showed similar potency as dipyridamole in various areas of the brainstem and hypothalamus. This biphasic and regionally heterogenous interaction of nitrobenzylthioinosine with [3H] dipyridamole binding sites in guinea pig brain slices strongly suggests heterogeneity of adenosine transporters.

Adenosine↗
PubMed1986

Autoradiographic localization of adenosine uptake sites in guinea pig brain using [3H]dipyridamole.

Tritiated dipyridamole, a specific adenosine uptake inhibitor binds in a saturable and reversible fashion to high-affinity receptor sites in guinea pig brain sections (Kd = 10 +/- 1.5 nM; Bmax = 650 +/- 100 fmol/mg prot.). The anatomical distribution of [3H]dipyridamole binding sites obtained with autoradiographic techniques shows a widespread but heterogeneous distribution of the binding sites throughout the whole guinea pig brain. Very high densities of binding sites are observed in the cerebellar cortex (molecular layer), the pyriform cortex, the superior colliculus (superficial layer), the supraoptic nucleus and the nucleus of the tractus solitarius. The anatomical characterization of the adenosine uptake site, using [3H]dipyridamole as a probe, may be useful to determine the functional role of adenosine in the brain.

Adenosine↗
PubMed1986

Evidence that the peripheral-type benzodiazepine receptor ligand Ro 5-4864 inhibits beta-endorphin release from AtT-20 cells by blockade of voltage-dependent calcium channels.

The demonstrations that Ro 5-4864, a ligand selective for the peripheral-type benzodiazepine (BZD) binding site, inhibited cellular differentiation and proliferation and that occupancy of the peripheral-type BZD binding site likely mediated the observed BZD effects on diverse endocrine tissues suggested that Ro 5-4864 disrupted a common cellular regulatory event. Using a well-characterized anterior pituitary-derived tumor cell line (AtT-20 cells), which synthesizes and secretes adrenocorticotropic hormone (ACTH), beta-lipotropin hormone (beta-LPH), and beta-endorphin (BE), we have investigated the molecular mechanism of action of Ro 5-4864's capacity to alter BE secretion. Ro 5-4864 inhibits basal and induced BE release from AtT-20 cells, through a cyclic AMP-independent mechanism. Ro 5-4864 completely blocked the corticotropin-releasing hormone and forskolin-induced release of BE without altering the concomitant production of cyclic AMP. The addition to AtT-20 cells of CGP 28392, a dihydropyridine that has been demonstrated in other systems to specifically activate voltage-dependent Ca2+ channels, resulted in a cyclic AMP-independent, dose-related increase in BE secretion. This CGP-induced BE release was blocked by increasing concentrations of Ro 5-4864. In contrast to the capacity of Ro 5-4864 to block CGP-induced BE release, Ro 5-4864 lacked the capacity to block enhanced BE secretion due to the calcium ionophore A23187, which increases intracellular Ca2+ levels independent of the voltage-dependent Ca2+ channels. Our findings suggest that Ro 5-4864 inhibits BE secretion from AtT-20 cells through a blockade of the voltage-dependent membrane Ca2+ channels and this mechanism of action may be responsible for Ro 5-4864's diverse effects observed on other cell types.

Animals↗
PubMed1985

Glucocorticoids are modulators of GABAA receptors in brain.

Modulation of binding of [3H]muscimol, a GABAA receptor agonist, by natural and synthetic glucocorticoids was investigated in crude synaptosomal membranes and in brain sections of rat. In adrenalectomized (Adx) rats, muscimol binding was reduced by 30-50% in cerebral cortex, cerebellum, thalamus and hippocampus, as compared to sham-operated controls. This decrease was due to reduced binding affinities of GABA receptors for muscimol. In contrast muscimol binding was increased by 38% in the hypothalamus and did not change in the pons-medulla after Adx. Nanomolar concentrations of corticosterone and pregnenolone-sulfate, but not dexamethasone, enhanced muscimol binding in brain regions that were characterized by reduced binding following Adx. This steroid-induced increase in muscimol binding was due to enhanced affinities of GABA receptors.

Adrenalectomy↗
PubMed1985

Autoradiographic localization of adenosine uptake sites in rat brain using [3H]nitrobenzylthioinosine.

The adenosine uptake site has been localized in rat brain by an in vitro light microscopic autoradiographic method, using [3H]nitrobenzylthioinosine ( [3H]NBI) as the probe. The binding characteristics of [3H]NBI on slide-mounted sections are comparable to those seen in studies performed on brain homogenates. A very high density of uptake sites occurs in the nucleus tractus solitarius, in the superficial layer of the superior colliculus, in several thalamic nuclei, and also in geniculate body nuclei. A high density of sites are also observed in the nucleus accumbens, the caudate putamen, the dorsal tegmentum area, the substantia nigra, and the central gray. The localization of the adenosine uptake site in brain may provide information on the functional activity of the site and suggests the involvement of the adenosine system in the central regulation of cardiovascular function.

Adenosine↗
PubMed1984

Estradiol increases dopamine turnover in intermediate and posterior pituitary lobes of ovariectomized rats.

Dopamine levels were specifically increased in the intermediate lobe of the pituitary gland of ovariectomized rats following acute 17-beta-estradiol administration. Estradiol treatment increased the dopamine turnover rate 10-fold in the intermediate lobe and 2-fold in the posterior lobe of ovariectomized rats. In contrast, estrogen treatment had no effect on the endogenous levels or the turnover rate of norepinephrine in these tissues. Our results suggest that estrogens can selectively modulate dopamine metabolism in the posterior and intermediate lobes of the rat pituitary gland.

Animals↗
PubMed1983

[Computerized quantitative topo-electroencephalography].

A method is described which has been developed to topographically display the values of spectral EEG analysis from 11 electrodes on each hemisphere and 5 electrodes on the midline. The EEG from 16 channels at a time is multiplexed and sampled at 3.2 kHz. From power spectra averaged every 10 sec for 5 min a few spectral parameters are computed among which are the spectral intensities within the delta, theta, alpha and beta bands. The whole values are then displayed on maps representing lateral views of cerebral hemispheres by means of spectral iso-intensity surfaces with extrapolation of the intermediate points. Different spectral intensities are coded by means of different gray levels. These maps clearly illustrate the topographical distribution of EEG rhythms and their peculiarities related to the side of the head recorded.

Alpha Rhythm↗
PubMedDate not supplied

[Exploration of memory disorders in anxiety states].

According to cognitive model of anxiety, memory process in anxious patients is usually tested by comparing the incidental recall of positive and negative, threatening and non threatening, self and other-referenced words. Contrary to expectation, the results indicate relatively poorer memory for threatening material in anxious patients and no bias in favour of the recall of self referent negative words. At the opposite this memory bias can be evidenced in patients with panic disorder. The bias for anxiety words is better evidenced in the subgroups with the higher arousal level or when there is a mood induction by reading first an anxiogenic text. Consistent with prediction a perceptive pre-attentional bias can be shown for the great majority of the subjects studied in recent researches.

Adult↗