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J C Bisserbe

Publications and source records attributed to J C Bisserbe.

At least 37 records · Page 2Linked to original sources

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

[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↗

Anxiolytic and hypnotic use by general hospital inpatients. The impact of psychopathology and general medical conditions.

This study explored the relative impact of general medical conditions and psychopathology on the current and lifetime use of anxiolytic and/or hypnotic drugs by general hospital inpatients. One hundred and five consecutive patients, admitted to an internal medicine department, were assessed by a structured interview about current and lifetime use of anxiolytic and/or hypnotic drugs, and with somatic and psychopathology scales. Eighty percent of patients reported using anxiolytics and/or hypnotics at least once in a lifetime, 62.9% in the last year, 55.2% in the last 3 months, and 42.9% in the last week. Correlations were found between drug use and current levels of anxiety and depression, but not somatic pathology. Psychological suffering appeared to be a major determinant for anxiolytic and/or hypnotic use by patients with general medical conditions. Consumption rates were higher than in the general population, but there was no direct link between somatic morbidity and drug use.

Adolescent↗

Economic assessment of a maintenance treatment strategy in prevention of recurrent depressive disorder.

OBJECTIVE: To compare the 12-month cost-effectiveness of milnacipran in maintenance treatment of depression to that of medical follow-up without antidepressant. METHOD: A Markov model with transition probabilities from a double blind clinical trial demonstrating the prophylactic efficacy of milnacipran was used. Other parameters were obtained from published sources. RESULTS: Base-case incremental cost for preventive treatment was 1,191 FF. It was reduced to 685 FF when using a 25% hospitalization rate in case of recurrence. Patients with a high initial response had extra cost of 191 FF and cost-utility was estimated to be 23,875 FF per QALY gained. For those patients, using a 25% hospitalization rate in case of recurrence, costs were lower at 1,174 FF and preventive strategy was dominating. CONCLUSION: Cost of maintenance therapy is partially balanced by the gain from recurrence prevention. It should be focused on patients with few residual symptoms or a high probability of hospitalization in case of recurrence.

Journal Article↗

Anxiety but not depression is associated with elevated blood pressure in a community group of French elderly.

OBJECTIVE: This study examined whether anxiety and depression were independently associated with elevated blood pressure in elderly persons. METHOD: The study group consisted of 1389 subjects aged 59 to 71 years recruited from the electoral rolls of the city of Nantes (France). Subjects completed the Center for Epidemiologic Studies-Depression scale (CES-D) and the Spielberger Inventory scales to assess depressive symptoms and anxiety symptoms, respectively. Data were collected on sociodemographic characteristics, smoking and drinking habits, medical history, and drug use. Two measures of systolic and diastolic blood pressure were taken after a 10-minute rest. Body mass index was computed from weight and height measurements. Subjects taking antihypertensive drugs (N = 281) were excluded from the present analysis. RESULTS: Depression and anxiety scores were significantly correlated (r = .61 in men; r = .65 in women; p<.001). In univariate analyses, anxiety scores were correlated with systolic and diastolic blood pressure in men, but not in women; blood pressure was not associated with depressive symptoms in either sex. Multivariate logistic regressions, controlling for possible confounders, showed that in both men and women, the risk of high blood pressure increased with increasing anxiety scores; odds ratios for high blood pressure were less than 1 in subjects with depressive symptomatology. CONCLUSIONS: This study suggested that anxiety but not depression was independently associated with an increased risk for high blood pressure.

Aged↗

[Clinico-economic assessment of milnacipran in the prevention of depressive episodes].

The objective of this study was to evaluate, for patients at risk of a new depressive episode, the net cost of maintenance therapy with milnacipran compared with a symptomatic treatment of further episodes. Using clinical decision analysis techniques, a Markov-state transition was constructed to estimate the 12 months direct costs of the two therapeutic strategies. Model construction and probabilities for performing the analysis were primarily based on a controlled phase III clinical trial demonstrating the prophylactic efficacy of milnacipran compared to placebo. Others parameters and unit costs were obtained from published sources. For each group (maintenance and episodic treatment groups), the model simulated the clinical evolution of patients on 6 successive 2-months cycles. Costs were affected for each health state period (remission, depression, abandonment of health care, suicide). The baseline analysis showed the mean costs per patient and year were 627 FF (105 US$) higher for maintenance treatment. Sensitivity analysis suggested that costs were equal under a 25% rate of hospitalization hypothesis for a depressive episode. Maintenance costs were 1,587 FF (265 US$) lower than episodic treatment costs for depressed subjects with a good initial response to milnacipran (HDRS-21 score at remission < 5); this economic benefit remained under a lower rate of hospitalization hypothesis (12%). Based on the study assumptions, maintenance treatment with milnacipran appears to be clinically and economically justified for patients at high risk of hospitalization when having a recurrence, and even more for patients with an excellent initial acute response.

Acute Disease↗

[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↗

[Hemispheric functional specialization and anxiety. Focus on an evaluation procedure].

Observations of brain-lesioned patients and experimental psychology studies have shown that the influence of the specific functioning of the two hemispheres of the brain on the regulation of emotional behaviour appears to be unequal and suggests a functional specialization of the right hemisphere for the expression and comprehension of the affective components of behaviour. However, the extension of this hypothesis to include all emotional experiences remains controversial. The observed superiority of the left hemisphere in the perception of positive emotions and the predominance of the right hemisphere in the treatment of negative emotions would appear to favour a joint and complementary participation of both cerebral hemispheres in emotional experiences. In the case of affective disorders, and particularly in anxiety symptoms, the hypothesis of a dysfunctioning of the right hemisphere is similarly questioned: while all metabolic studies corroborate this hypothesis, experimental psychological studies suggest the existence of a preferential involvement of one or the other hemisphere in relation to individual differences such as the "trait" anxiety score. Moreover, the few studies which have been undertaken with healthy volunteers raise the problem of their extrapolation to pathological situations. In view of the potential interest in the neuropsychological evaluations of subjects with different forms of pathological anxiety, we have developed an experimented with two tests aimed at evaluating the differential activity of the two hemispheres of the brain. These two tests, constructed on a "mirror-image" model from the specifications of a functional hemispheric specialization, are supposed to involve cognitive strategies pinpointing preferentially one hemisphere or the other.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Panic disorder and microcirculation. Controlled study of capillaries in anxiety disorders].

However varied the clinical descriptions of anxiety, a sizeable proportion is always allotted to the cardiovascular aspect. One is reminded of Krishaber's cerebral-cardiac neuropathy and Brissaud's conception of anxiety. The implication of the heart in anxiety disorders, especially paroxystic disorder, i.e. panic attacks (PA) is important. Cardiovascular symptoms (tachycardia, increased systolic blood pressure, chest pain) are among the most frequent manifestations of panic; furthermore, recent studies suggest that male panic disorder (PD) patients have an increased mortality risk from cardiovascular diseases. It is with this implication in mind that we undertook this study, the main aim of which was to confirm the existence of an abnormal microcirculation, characteristic of PD, taking the form of an excess number of twisted capillaries. Abnormal capillaries had been described previously in non-controlled studies of patients with psychiatric disorders diagnosed as neurasthenia, neurosis, neurovegetative disorders and more recently as neurocirculatory asthenia, a syndrome similar to PD. This led us to undertake a study of the total number of capillaries observed by photomicrography (capillaroscopy) in the supra-ungueal fold of the fingers of both hands (except thumbs), comparing the number of twisted capillaries of 16 subjects suffering from panic disorder with or without agoraphobia according to the DSM III-R criteria, with those of 16 healthy volunteers matched for age and sex and 14 subjects suffering from other anxiety disorders (10 of them fulfilling criteria for generalized anxiety disorders).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗