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Biomedical subjects

M Hamon

Publications and source records attributed to M Hamon.

At least 559 records · Page 31Linked to original sources
PubMedDate not supplied

Differential effects of N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) on various 5-HT receptor binding sites in the rat brain.

The effects of N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ), an alkylating agent producing irreversible blockade of various membrane bound receptors in brain, were investigated on four different types of serotonin receptors, 5-HT1A, 5-HT1B, 5-HT2A and 5-HT3, in various brain regions in the rat. In addition, the fate of central benzodiazepine- and "R"-zacopride-specific binding sites was also examined in rats treated with EEDQ. Membrane binding assays and/or quantitative autoradiography with appropriate radioligands indicated that EEDQ inactivated 5-HT1A, 5-HT1B and 5-HT2A sites, but was poorly active on 5-HT3, benzodiazepine and "R" sites. Among the receptors affected by EEDQ, hippocampal 5-HT1A sites were the most sensitive to the alkylating agent (ID50 approximately 1 mg/kg i.p.), followed by the cortical 5-HT2A (ID50 approximately 3 mg/kg i.p.) and the striatal 5-HT1B (ID50 approximately 6 mg/kg i.p.) sites. Pretreatment by selective ligands partially protected hippocampal 5-HT1A sites from irreversible inactivation by EEDQ (10 mg/kg i.p.) with the following order of efficacy: WAY 100635 > spiperone > BMY 7378 > ipsapirone. Similarly, pretreatment by spiperone (5 mg/kg i.p.) also reduced the ability of EEDQ to inactivated cortical 5-HT2A receptors. Analyses of the time-course recovery of respective binding sites after EEDQ administration showed that the turnover rate of 5-HT1A sites did not significantly differ in the dorsal raphe nucleus and in various forebrain areas (hippocampus, septum, cerebral cortex; half-life: approximately 4 days), but was lower than that of cortical 5-HT2A sites (half-life: 2.9 days).

Animals↗
PubMedDate not supplied

Aging associated changes in serotoninergic and dopaminergic pre- and postsynaptic neurochemical markers in the rat brain.

Measurements of endogenous levels of serotonin (5-HT), 5-hydroxyindole acetic acid (5-HIAA), dopamine (DA) and dihydroxyphenyl acetic acid (DOPAC), and biochemical and autoradiographic investigations on 5-HT and DA receptors were made in various brain regions in male rats at three different ages: 3 months, 10 months and 22 months. Age-dependent decreases in 5-HT levels associated with parallel increases in 5-HIAA/5-HT ratio were observed in the hypothalamus, striatum, hippocampus and cerebral cortex, suggesting an accelerated 5-HT turnover in aged rats. Similarly, DA levels were lower, and DOPAC/DA ratio was higher in the striatum of 22-month-old compared to 3-month-old or 10-month-old rats. Of the three different classes of 5-HT receptors which were examined, 5-HT1B sites exhibited the largest age-dependent decrease in density, followed by 5-HT2 sites, while 5-HT1A sites remained practically unchanged during aging. By comparison, the loss of striatal D2 receptors in 22-month-old rats compared to young adults was much greater than that of any 5-HT receptor subtype. Such differential age-dependent alterations of the various classes of 5-HT receptors and of dopaminergic versus serotoninergic synaptic markers might be responsible for at least some of the functional deficits in aged animals.

Aging↗
PubMedDate not supplied

Family-based association studies between 5-HT5A receptor gene and schizophrenia.

BACKGROUND: Pharmacological and neurodevelopmental data support the idea that the gene, which codes for the 5-HT(5A) receptor is an important candidate gene for schizophrenia susceptibility. However, previous genetic studies focusing on this gene yielded conflicting results, potentially because of: (i) stratification biases of case-control association studies, (ii) genetic and phenotypic heterogeneity of schizophrenia, and (iii) variability in the loci analyzed (the 5-HT(5A) gene having many polymorphic sites). METHODS: A transmission disequilibrium test was used in the present study aimed at investigating two polymorphisms in exon 1 of the 5-HT(5A) gene, the A12T silent substitution and the C43T transversion leading to a 15Pro --> Ser substitution, in 103 patients with DSM-IV diagnosis of schizophrenia, and their 206 parents. RESULTS: We found an excess of transmission of the 12T allele from the parents to their affected children (P = 0.02), with evidence for linkage disequilibrium between the 12T-43C haplotype and schizophrenia (P = 0.002). Furthermore, patients with the 12T allele had a significantly later age at onset (P = 0.003), and the Q-TDT approach confirmed that this allele was transmitted with an older age at onset (P = 0.01). CONCLUSIONS: These data provided convergent evidence for a significant role of the 5-HT(5A) gene in schizophrenia and more specifically in patients with later age at onset.

Adult↗
PubMedDate not supplied

Extracellular dopamine in the rat prefrontal cortex during reward-, punishment- and novelty-associated behaviour. Effects of diazepam.

Variations of extracellular dopamine (DA(ext)) levels in prefrontal cortex were assessed by in vivo microdialysis. In rats trained in an operant fixed interval (FI(30s)) schedule of food delivery, acute exposure to contingent foot shocks resulted in a suppression of responding that was reversed by diazepam (4 mg/kg, ip). No changes in cortical DA(ext) levels occurred during this period in both control and treated rats. By contrast, in control rats, cortical DA(ext) levels increased (+25-40%) during the nonpunished component of the operant session, and during noncontingent food delivery (+25%). Control rats placed into an unfamiliar brightly lit openfield exhibited a marked increase in cortical DA(ext) levels (+100%). This effect occurred neither in rats given diazepam at a dose (2 mg/kg) which stimulated motor activity, nor during a second exposure to the openfield. In conclusion, a benzodiazepine-sensitive activation of mesoprefrontal DA neurones is induced by exposure to novel stressful surroundings and by food availability and consumption. The fact that cortical DA(ext) levels remained unchanged in rats that exerted complete control upon negative stimuli indicates that an activation of the mesoprefrontal DA system is not required for punishment-induced behavioural blockade.

Animals↗
PubMedDate not supplied

Identification of presynaptic serotonin autoreceptors using a new ligand: 3H-PAT.

Binding studies with appropriate labelled ligands have revealed the existence of two types of serotonin (5-HT) receptor, 5-HT1 and 5-HT2, in the central nervous system of mammals. The 5-HT1 type is characterized by a higher affinity for agonists than for antagonists, whereas the 5-HT2 type binds preferentially to antagonists. However, neither of these receptor types apparently corresponds to the presynaptic autoreceptor controlling 5-HT release. In an attempt to identify the presynaptic autoreceptor directly, we synthesized the tritiated derivative of 8-hydroxy-2-(di-n-propylamino) tetralin (PAT), a new tetralin derivative with potent 5-HT agonist properties and carried out binding studies with rat brain membranes. As we report here, in the hippocampus, the properties of 3H-PAT binding sites correspond closely to those of 5-HT1 sites. In contrast, in the striatum, 3H-PAT binding sites exhibit a subcellular distribution and pharmacological characteristics usually associated with presynaptic autoreceptors. Furthermore, a marked loss of 3H-PAT binding sites occurs in the striatum (but not in the hippocampus) after the selective degeneration of serotoninergic fibres in 5,7-hydroxytryptamine (5,7-HT)-treated rats. Conversely, the sprouting of additional 5-HT terminals in the brain stem of adult rats treated at birth with 5,7-HT is associated with an increased density of 3H-PAT binding sites in this region. 3H-PAT thus seems to be a useful ligand for studying the biochemical and pharmacological characteristics of presynaptic autoreceptors in selected regions of rat brain.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMedDate not supplied

Micro method for liquid chromatographic determination of cyclosporin A in whole blood with use of a rapid extraction procedure.

In this precise, reversed-phase liquid chromatographic procedure, Cyclosporin A (Cy A) is extracted from 300 microL of whole blood with cyclosporin D as internal standard by liquid-liquid extraction. A 20-microL aliquot of the extract, injected onto a Nucleosil octyl analytical column heated at 72 degrees C, is eluted with a mixture of acetonitrile and 0.01 M phosphate buffer, pH 5.5 at a flow rate of 1 mL/min. Detection is set at 210 nm. The chromatography is complete within 10 min. The detection limit is 25 micrograms/L. Between-run CVs range from 2.3 to 6.2% and recovery is 92.1 +/- 6.3%. The major advantages of our extraction procedure are the rapid clean-up method and the small volume required. This procedure is especially suitable for cyclosporine determination in pediatric transplantations.

Chromatography, High Pressure Liquid↗
PubMedDate not supplied

New calibration method for gas chromatographic assay of carbon monoxide in blood.

The calibration method described is based on the in situ formation of carbon monoxide in a closed system by the reaction of hot concentrated sulfuric acid with formic acid. Carbon monoxide is released from hemoglobin by treatment with 85% phosphoric acid, diluted 1:2 (v/v). Carbon monoxide is analyzed by means of headspace gas chromatography on a Porapak Q 80-100 column, following catalytic reduction to methane, using a flame-ionization detector. The method was validated by comparing the results obtained for blood samples from patients suffering from carbon monoxide poisoning and previously analyzed by means of spectrophotometry.

Calibration↗
PubMedDate not supplied

Visits to the emergency room for asthma attacks and short-term variations in air pollution. A case-crossover study.

BACKGROUND: The 'case-crossover' design is a strategy fitted to studying transient effects of intermittent exposure on acute-onset disease occurring shortly after exposure. It has the important advantage of eliminating most confounding variables, allowing a stronger causality inference. OBJECTIVES: The objective of the study was to evaluate the relationships between emergency room (ER) visits for asthma attacks and gaseous air pollution changes. METHODS: The study included 549 individuals, 3-49 years old, visiting the ER during 1 year. Exposure to gaseous air pollutants (SO2, NO2, O3) on the same day and up to 4 days before was computed according to the patient's address. The statistical analysis included meteorological data as potential confounding variables. RESULTS: No association could be shown between ER visits and SO2 or NO2 levels. In contrast, there was a statistically significant association between ER visits and mean O3 levels, on the day of admission and also on D -2 and D -3. For an increase of 10 microg/m3, the risk of requiring an ER admission increased by 6-10%. CONCLUSIONS: Using this new strategy, we confirmed that ozone changes lead to a moderate increase in risk of requiring an ER admission in asthmatic subjects.

Adolescent↗
PubMedDate not supplied

Opposite changes in dopamine metabolites and met-enkephalin levels in the ventricular CSF of patients subjected to thalamic electrical stimulation.

High-frequency electrical stimulations of thalamic nuclei are currently used for the suppression of parkinsonian or essential tremor and for the relief of some types of intractable pain in man. However, the mechanisms by which such stimulations exert their therapeutic effects are essentially unknown. Attempts were made to provide some insight into these mechanisms by measuring the levels of the dopamine metabolites homovanillic acid (HVA) and 3,4-dihydroxyphenylacetic acid (DOPAC), the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) and met-enkephalin-like immunoreactivity in ventricular cerebrospinal fluid (CSF) of patients with Parkinson's disease (PD) or multiple sclerosis (MS) after a 30-minute therapeutic electrical stimulation of the ventralis intermedius nucleus of the thalamus. In nonstimulated control patients, the levels of these compounds did not significantly differ in two CSF samples taken 30 minutes apart. In stimulated patients, a decrease in dopamine metabolite levels associated with a relative increase in met-enkephalin-like immunoreactivity were observed in the CSF sample taken after the 30-minute stimulation as compared to the sample taken immediately before the stimulation. In contrast, the levels of 5-HIAA remained unaffected by the stimulation. These data confirmed the existence of negative interactions between dopaminergic and enkephalinergic systems in man similar to those previously demonstrated in rats. In addition, they suggest that alterations in dopaminergic or enkephalinergic neurotransmission might be involved in the therapeutic action of thalamic electrical stimulation in patients with parkinsonian symptoms and other patients.

Adult↗
PubMedDate not supplied

[Rotational vertebro-basilar insufficiency secondary to a fibrous band of the longus colli muscle: value of CT spiral angiography diagnosis].

A CASE REPORT: The authors report a case of rotational vertebro-basilar insufficiency causing "drop-attacks". To our knowledge, it is the first case of extraluminal vertebral artery compression caused by a fibrous band of the longus colli muscle, demonstrated by spiral computed tomographic angiography with volume rendering reformation.

Adult↗