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Biomedical subjects

D Bertrand

Publications and source records attributed to D Bertrand.

At least 55 records · Page 3Linked to original sources
PubMed2001

Blockade and activation of the human neuronal nicotinic acetylcholine receptors by atracurium and laudanosine.

BACKGROUND: Curaremimetic nondepolarizing muscle relaxants are widely used in clinical practice to prevent muscle contraction either during surgery or during intensive care. Although primarily acting at the neuromuscular junction, these compounds can cause adverse effects, including modification of cardiac rhythm, arterial blood pressure, and in the worst cases, triggering of seizures. In this study, we assessed the interaction of atracurium and its metabolite, laudanosine, with neuronal nicotinic receptors. METHODS: The human neuronal nicotinic receptors alpha4beta2, alpha3beta4, alpha3alpha5beta4, and alpha7 are heterologously expressed in Xenopus laevis oocytes, and the effect of atracurium and its degradation product, laudanosine, were studied on these receptors. RESULTS: Atracurium and laudanosine inhibited in the micromolar range the major brain alpha4beta2 receptor and the ganglionic alpha3beta4 or alpha3beta4alpha5 and the homomeric alpha7 receptors. For all four receptors, inhibition was rapid and readily reversible within less than 1 min. Atracurium blockade was competitive at alpha4beta2 and alpha7 receptors but displayed a noncompetitive blockade at the alpha3beta4 receptors. Inhibition at this receptor subtype was not modified by alpha5. Laudanosine was found to have a dual mode of action; first, it competes with acetylcholine and, second, it blocks the ionic pore by steric hindrance. At low concentrations, these two drugs are able to activate both the alpha4beta2 and the alpha3beta4 receptors. CONCLUSION: Adverse effects observed during atracurium administration may be attributed, at least partly, to an interaction with neuronal nicotinic receptors.

Animals↗
PubMed2001

Evaluation of a program to improve the prescription-writing quality in hospital.

This paper aims to evaluate the effectiveness of a program designed to improve the quality of drug prescription-writing at a university hospital in France. Improvement actions included feed-back from yearly audits and the dissemination of recommendations on how best to write the prescriptions. A random sample of 30 stays was selected from among the hospitalizations for the year 1996. From each patient, medical records were searched for the first prescription order of the stay and its quality was assessed according to standards. A total of 872 records were relevant and included 3,289 medications. The results were compared to those obtained for the two previous years. Actions to sensitize prescribers resulted in an insufficient improvement of most indicators of prescription-writing quality with results remaining well below ideal standards. The hospital staff concerned had a positive opinion of the program which led to an awareness of prescription problems. This assessment showed that the program had a moderate impact on prescribers' practice and efforts must be continued.

Drug Prescriptions↗
PubMed2001

The quest for universals in temporal processing in music.

Music perception and performance rely heavily on temporal processing: for instance, each event must be situated in time in relation to surrounding events, and events must be grouped together in order to overcome memory constraints. The temporal structure of music varies considerably from one culture to another, and so it has often been supposed that the specific implementation of perceptual and cognitive temporal processes will differ as a function of an individual's cultural exposure and experience. In this paper we examine the alternative position that some temporal processes may be universal, in the sense that they function in a similar manner irrespective of an individual's cultural exposure and experience. We first review rhythm perception and production studies carried out with adult musicians, adult nonmusicians, children, and infants in order to identify temporal processes that appear to function in a similar fashion irrespective of age, acculturation, and musical training. This review leads to the identification of five temporal processes that we submit as candidates for the status of "temporal universals." For each process, we select the simplest and most representative experimental paradigm that has been used to date. This leads to a research proposal for future intercultural studies that could test the universal nature of these processes.

Humans↗
PubMed2001

Incidence of male-killing Rickettsia spp. (alpha-proteobacteria) in the ten-spot ladybird beetle Adalia decempunctata L. (Coleoptera: Coccinellidae).

The diversity of endosymbiotic bacteria that kill male host offspring during embryogenesis and their frequencies in certain groups of host taxa suggest that the evolution of male killing and the subsequent spread of male-killing symbionts are primarily determined by host life history characteristics. We studied the 10-spot ladybird beetle, Adalia decempunctata L. (Coleoptera: Coccinellidae), in which male killing has not been recorded previously, to test this hypothesis, and we also assessed the evolution of the male killer identified by DNA sequence analysis. Our results show that A. decempunctata harbors male-killing Rickettsia (alpha-proteobacteria). Male-killing bacteria belonging to the genus Rickettsia have previously been reported only for the congeneric two-spot ladybird beetle, Adalia bipunctata L. Phylogenetic analysis of Rickettsia DNA sequences isolated from different populations of the two host species revealed a single origin of male killing in the genus Rickettsia. The data also indicated possible horizontal transfer of symbionts between host species. In addition, A. bipunctata is known to bear at least four different male-killing symbionts in its geographic range two of which coexist in the two locations from which A. decempunctata specimens were obtained for the present study. Since only a single male-killing taxon was found in A. decempunctata, we assume that the two closely related ladybird beetle species must differ in the number and/or geographic distribution of male killers. We discuss the importance of these findings to our understanding of the evolution and dynamics of symbiotic associations between male-killing bacteria and their insect hosts.

Animals↗
PubMed2001

[Early readmission as an indicator of hospital quality of care].

BACKGROUND: The purpose of this study was to assess early readmission as an indicator of quality of care, to estimate the frequency of avoidable emergency readmission in a French hospital, and then to describe the feasibility and contribution of routine use of this indicator. METHODS: A randomly selected sample of 469 readmissions within 30 days after a conventional hospitalization was chosen among the database of 40,242 hospitalizations during the first half of 1997. Two independent practitioners, whose true agreement was measured with a kappa test, studied the features of readmission recorded on the patient files, classing them as "unforeseeable" or "potentially avoidable". Database criteria that could automatically class the readmission in either group were analyzed. RESULTS: There were 119 unforeseeable readmissions (25.4%). The two physicians agreed on the unforeseeable nature of 97 of these readmissions and 50 of them were judged avoidable. None of the database criteria allowed identifying all unforeseeable and avoidable readmissions. Readmission via the emergency unit was a sure indicator of unforeseeable readmission in 66% of the cases and of avoidable readmissions in 60%. The frequency of unforeseen readmissions was estimated at 3.9% of all conventional stays during the first half of 1997. The frequency of avoidable readmissions was 1.5%. CONCLUSIONS: Unforeseen early readmission can be an indicator of quality of the care taking process. It is however impossible to use the current database to classify with certainty readmissions as "unforeseeable" or "avoidable". Emergency unit readmission could offer a possible approach to measuring the frequency of unforeseen readmission. This ratio can provide caretakers with information concerning the quality of care and thus help in making decisions concerning reorganization for improvement.

Academic Medical Centers↗
PubMed2000

CHRNB2 is the second acetylcholine receptor subunit associated with autosomal dominant nocturnal frontal lobe epilepsy.

Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) is an uncommon, idiopathic partial epilepsy characterized by clusters of motor seizures occurring in sleep. We describe a mutation of the beta2 subunit of the nicotinic acetylcholine receptor, effecting a V287M substitution within the M2 domain. The mutation, in an evolutionary conserved region of CHRNB2, is associated with ADNFLE in a Scottish family. Functional receptors with the V287M mutation are highly expressed in Xenopus oocytes and characterized by an approximately 10-fold increase in acetylcholine sensitivity. CHRNB2 is a new gene for idiopathic epilepsy, the second acetylcholine receptor subunit implicated in ADNFLE.

Acetylcholine↗
PubMed2000

[Evaluation of inpatient satisfaction. Comparison of different survey methods].

OBJECTIVES: To assess the impact of patient satisfaction survey method on response rate, data quality and satisfaction. PATIENTS AND METHODS: Four modes of data collection were assessed during a randomized trial that included 400 inpatients discharged from a teaching hospital. RESULTS: The response rate was 58% within the mail survey group (72% with follow-up letter) versus 73% and 81% within the home and telephone interview group (p < 0.01). 69% of the mailed questionnaires contained no missing values versus 94% and 96% for home and telephone interview modes (p < 0.01). The global satisfaction scale score was greater within the mail survey groups (8.1/10 without follow-up letter and 7.9 with follow-up letter) than within the telephone interview group (7.8) and the face to face interview group (7.3), (p < 0.05). CONCLUSION: Mail survey with follow-up letter constitutes an operational method despite lower data quality and overestimation of patients' satisfaction scores.

Adult↗
PubMed2000

A new look at the neuronal nicotinic acetylcholine receptor pharmacophore.

Interest in the field of nicotinic receptors has been recently stimulated both by the discovery of the potential therapeutic effects of new agonists, and by the discovery of an association between nicotinic receptor mutations and human neurological diseases. Expression of human receptors in an exogenous system allows their study in isolation. Receptors reconstituted by pairwise injection of either alpha4 or alpha3 with beta2 or beta4 subunits displayed important differences between the resulting receptor subtypes. These results were further compared with those obtained with alpha3:alpha4 fusion proteins. The modifications of either the ligand-binding site in the N-terminal domain or in the ionic pore domain were found to affect the pharmacological properties of the receptors. Finally, the analysis of non-natural derivatives of epibatidine demonstrates how an agonist can be modified to be selective at one receptor subtype or to become an antagonist. These data are well explained on the basis of a three-state allosteric model.

Acetylcholine↗
PubMed2000

The unusual nature of epibatidine responses at the alpha4beta2 nicotinic acetylcholine receptor.

The identification of an equatorial frog toxin, epibatidine, as a potent non-morphinic analgesic, selective for neuronal nicotinic acetylcholine receptors, provoked a marked renewal in our understanding of pain and its mechanisms. In this work we have examined the effects of epibatidine at the major brain rat alpha4beta2 nicotinic acetylcholine receptor expressed in a cell line. Fast drug applications obtained with a modified liquid filament system were used for the analyses of the currents evoked by acetylcholine, nicotine and epibatidine. Characterized by a slow onset and offset, epibatidine responses were of smaller amplitude to those evoked by acetylcholine or nicotine. About a thousand times more sensitive to epibatidine than acetylcholine, the alpha4beta2 receptor also displayed a more pronounced apparent desensitization to this compound. Finally, overnight exposure to 1 nM epibatidine failed to produce the functional upregulation observed with nicotine. These data indicate that, at the rat alpha4beta2 receptor, epibatidine acts as a partial agonist causing a pronounced inhibition of agonist evoked currents at concentrations that do not activate the receptors.

Algorithms↗
PubMed2000

Neuronal nicotinic acetylcholine receptors: from the gene to the disease.

The neuronal nicotinic acetylcholine receptors are excitatory ligand-gated channels. Widely expressed throughout the peripheral and central nervous system, their properties depend upon their subunit composition. Furthermore, genetic studies have revealed a high degree of variation at the genomic level and alternative splicing of the mRNAs coding for these integral membrane proteins. In particular, genes coding for alpha4 and alpha7 subunits harbour a high degree of polymorphisms. Although well characterised at their molecular and functional level, the role of these receptors in the central nervous system remains obscure. Despite accumulating evidence for the participation of nicotinic receptors in disorders of the central nervous system including nicotinic addiction, Parkinson's disease, Alzheimer's disease and Tourette's syndrome, the exact role of these receptors is still speculative. Because most of these phenotypes are complex and genetically heterogeneous, the investigation is difficult. However, in the past few years, significant progress has been made in understanding the contribution of nicotinic acetylcholine receptors to the origin of epilepsies and schizophrenia. By concentrating on the latest results gained for these diseases, we discuss in this review the possible relationships between neuronal nicotinic receptors and neurological and psychiatric disorders.

Alleles↗
PubMed2000

Magnocellular neurons of the rat supraoptic nucleus are endowed with functional nicotinic acetylcholine receptors.

Acetylcholine can stimulate the release of vasopressin. In organ-cultured hypothalamo-neurohypophyseal systems, acetylcholine enhanced vasopressin release by acting in or near the supraoptic nucleus Extracellular recordings suggested that acetylcholine can increase supraoptic neuron excitability. These effects could be mimicked, in part, by nicotine or blocked by nicotinic antagonists, suggesting that they might be mediated by nicotinic acetylcholine receptors. Autoradiography indicated that alpha-bungarotoxin binding sites are present in the supraoptic nucleus; however, neither acetylcholine nor nicotine binding sites could be detected. Thus, the existence, let alone the nature, of nicotinic receptors in the supraoptic nucleus has so far remained elusive. The present work attempts to determine: (i) whether functional nicotinic receptors are present in this nucleus; (ii) whether they are located on neurosecretory magnocellular cells or at presynaptic sites; (iii) what their pharmacological and biophysical properties are; (iv) whether they influence the activity of all or only part of supraoptic neurons. Whole-cell recordings were performed in hypothalamic slices or in acutely dissociated supraoptic neurons and the effect of nicotinic agonists was tested under voltage-clamp conditions. Autoradiography was done in coronal hypothalamic sections, using [3H]epibatidine and [125I]alpha-bungarotoxin as ligands. Our results indicate that supraoptic neurons possess functional nicotinic receptors containing the alpha7 subunit.

Acetylcholine↗
PubMed2000

[Neuropathologic consequences of status epilepticus].

Although the results of a number of histopathological studies have unequivocally shown that epileptic seizures are frequently associated with neurodegenerative mechanisms or other alterations in the brain structure, as it is not possible to carry out longitudinal studies the interpretation of these observations remains speculative. It is not clear whether these brain alterations are the cause or the result of epileptic seizures. It is now widely accepted that epileptic seizures correspond to the synchronization of neuronal activity and increase in their discharge frequency. It has been shown that this abnormal firing activity can lead to increase in intracellular calcium concentration in the nerve cells. A rise in intracellular calcium levels can trigger other processes within the cell, or be cytotoxic if these levels are sufficiently high. In this study, in the light of the most recent findings on cell death (apoptosis), the authors have examined the mechanisms whereby epileptic seizures can result in neuronal cell loss.

Humans↗
PubMed2000

Chemical modification of epibatidine causes a switch from agonist to antagonist and modifies its selectivity for neuronal nicotinic acetylcholine receptors.

BACKGROUND: Studies of ligand gated channels strongly rely on the availability of compounds that can activate or inhibit with high selectivity one set or a subset of defined receptors. The alkaloid epibatidine (EPB), originally isolated from the skin of an Ecuadorian poison frog, is a very specific agonist for the neuronal nicotinic acetylcholine receptors (nAChRs). We used EPB derivatives to investigate the pharmacophore of nAChR subtypes. RESULTS: Optically pure enantiomers of EPB analogues were synthesised. Analogues were obtained altered in the aromatic part: the chlorine was eliminated and the relative position of the pyridyl nitrogen changed. Voltage clamp electrophysiology was performed with these compounds on neuronal nAChRs reconstituted in Xenopus oocytes. The EPB derivatives show different activities towards the various nAChR subtypes. CONCLUSIONS: Small changes in the molecular structure of EPB produce marked changes in its capacity to activate the nAChRs. Subtype specificity can be obtained by changing the position of or by eliminating the pyridyl nitrogen.

Amino Acid Motifs↗
PubMed2000

Neuronal nicotinic acetylcholine receptors from Drosophila: two different types of alpha subunits coassemble within the same receptor complex.

Although neuronal nicotinic acetylcholine receptors from insects have been reconstituted in vitro more than a decade ago, our knowledge about the subunit composition of native receptors as well as their functional properties still remains limited. Immunohistochemical evidence has suggested that two alpha subunits, alpha-like subunit (ALS) and Drosophila alpha2 subunit (Dalpha2), are colocalized in the synaptic neuropil of the Drosophila CNS and therefore may be subunits of the same receptor complex. To gain further understanding of the composition of these nicotinic receptors, we have examined the possibility that a receptor may imbed more than one alpha subunit using immunoprecipitations and electrophysiological investigations. Immunoprecipitation experiments of fly head extracts revealed that ALS-specific antibodies coprecipitate Dalpha2, and vice versa, and thereby suggest that these two alpha subunits must be contained within the same receptor complex, a result that is supported by investigations of reconstituted receptors in Xenopus oocytes. Discrimination between binary (ALS/beta2 or Dalpha2/beta2) and ternary (ALS/Dalpha2/beta2) receptor complexes was made on the basis of their dose-response curve to acetylcholine as well as their sensitivity to alpha-bungarotoxin or dihydro-beta-erythroidine. These data demonstrate that the presence of the two alpha subunits within a single receptor complex confers new receptor properties that cannot be predicted from knowledge of the binary receptor's properties.

Acetylcholine↗
PubMed1999

A scorpion alpha-like toxin that is active on insects and mammals reveals an unexpected specificity and distribution of sodium channel subtypes in rat brain neurons.

Several scorpion toxins have been shown to exert their neurotoxic effects by a direct interaction with voltage-dependent sodium channels. Both classical scorpion alpha-toxins such as Lqh II from Leiurus quiquestratus hebraeus and alpha-like toxins as toxin III from the same scorpion (Lqh III) competitively interact for binding on receptor site 3 of insect sodium channels. Conversely, Lqh III, which is highly toxic in mammalian brain, reveals no specific binding to sodium channels of rat brain synaptosomes and displaces the binding of Lqh II only at high concentration. The contrast between the low-affinity interaction and the high toxicity of Lqh III indicates that Lqh III binding sites distinct from those present in synaptosomes must exist in the brain. In agreement, electrophysiological experiments performed on acute rat hippocampal slices revealed that Lqh III strongly affects the inactivation of voltage-gated sodium channels recorded either in current or voltage clamp, whereas Lqh II had weak, or no, effects. In contrast, Lqh III had no effect on cultured embryonic chick central neurons and on sodium channels from rat brain IIA and beta1 subunits reconstituted in Xenopus oocytes, whereas sea anemone toxin ATXII and Lqh II were very active. These data indicate that the alpha-like toxin Lqh III displays a surprising subtype specificity, reveals the presence of a new, distinct sodium channel insensitive to Lqh II, and highlights the differences in distribution of channel expression in the CNS. This toxin may constitute a valuable tool for the investigation of mammalian brain function.

Animals↗
PubMed1999

Localization of mRNA for CHRNA7 in human fetal brain.

The aim of this study was to determine the regional distribution in situ of the mRNA for the alpha 7 subunit of the neuronal nicotinic acetylcholine receptor in human fetal brain. We found high levels of alpha 7 gene expression in nuclei that receive sensory information, such as those of the neocortex and hippocampus, the thalamic nuclei, the reticular thalamic nucleus, the pontine nuclei and the superior olive complex. These data support a possible regulatory function for alpha 7-containing receptors in sensory processing, which may be involved in the pathological physiology of schizophrenia and autism. Early alpha 7 gene expression is also consistent with a morphogenetic role for alpha 7 receptors in central nervous system development.

Brain↗
PubMed1999

Neuronal nAChR stereoselectivity to non-natural epibatidine derivatives.

The frog toxin epibatidine is one of the most powerful ligands of the neuronal nicotinic receptors and derivatives show promising possibilities for labeling in positron emission tomography studies. In an attempt to reduce epibatidine toxicity, new methyl derivatives were synthesized, tested in positron emission tomography imaging and in electrophysiology. labeling as well as physiological experiments highlighted the differences in sensitivity of the neuronal nicotinic acetylcholine receptors between two methyl enantiomers and the reduction in sensitivity caused by introducing the methyl group. At present, epibatidine derivatives seem the most promising compounds for in vivo labeling of neuronal nicotinic acetylcholine receptors.

Animals↗