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Biomedical subjects

A Dresse

Publications and source records attributed to A Dresse.

At least 37 records · Page 2Linked to original sources
PubMed1998

[An acetylsalicylic acid-dypiridamole combination (Asasantine) in the prevention of the recurrence of cerebrovascular accidents (a cost-effectiveness analysis)].

On the basis of the results of the European stroke Prevention Study (ESPS 2) obtained on 6,602 patients, we used a Markov model to perform a cost-effectiveness analysis of a combination of a low-dose of acetylsalicylic acid (ASA) (25 mg b.i.d.) and sustained-release dipyridamole (DP) (200 mg b.i.d.) versus a low-dose of acetylsalicylic acid alone in the prevention of recurrent stroke in Belgium. The perspective was that of the Social Security. Total costs per patient over 5 years amounted to 1,317,718 FB for placebo, 1,312,015 FB for ASA and 1,326,526 FB for ASA-DP, with respectively 3.16, 3.25 and 3.33 stroke-free life years (SFLY). For 1,000 patients followed over 5 years, the number of SFLYs gained by ASA-DP is 170 when compared to placebo and 100 when compared to ASA. As compared to placebo, ASA is a dominant strategy and the combination AAS-DP has a cost-effectiveness ratio of 50,569 FB per SFLY gained. The cost-effectiveness ratio of ASA-DP vs. ASA was 176,963 FB per SFLY gained and was not substantially modified in sensitivity analyses. The favourable cost-effectiveness ratio for ASA-DP is mainly explained by the reduction of costs associated with the acute treatment of stroke.

Aspirin↗
PubMed1998

A quantitative pharmacological study of the cholinergic depolarization of hippocampal pyramidal cells in rat brain slices.

Intracellular recordings were performed in rat brain slices and the pharmacology of the depolarizing effect of cholinomimetic drugs on hippocampus CA1 pyramidal cells was quantitatively investigated. Acetylcholine (ACh) and muscarine induced a concentration-dependent depolarization of these cells. The EC50 values were respectively 159 +/- 54 microM and 0.7 +/- 0.15 microM. Physostigmine (1 microM) or tacrine (1 microM) induced a marked shift in the concentration-response curve for ACh. Both drugs were equipotent in this respect. The EC50 values for ACh became, respectively, 2.4 +/- 1.5 microM and 3 +/- 0.9 microM. The depolarizing effect of ACh was completely blocked by atropine, confirming the involvement of a receptor of the muscarinic type. In order to determine the subtype of muscarinic receptor involved, the EC50 values of muscarine were determined in the presence of atropine (100 nM), pirenzepine (1 microM) or AFDX116 (10 microM). The deduced pKB for the antagonists were, respectively, 8.9, 7.4 and 6.5. Comparison with binding data suggests that M1 receptors play a prominent role in the depolarizing effect of cholinomimetic drugs on CA1 pyramidal cells.

Acetylcholine↗
PubMed1997

Prominent dendritic localization in forebrain neurons of a novel mRNA and its product, dendrin.

A recently cloned rat brain cDNA derives from a novel gene, termed dendrin (DEN), expressed exclusively in forebrain structures, particularly in neocortex, olfactory bulb, hippocampus, caudate-putamen, and limbic system. In these structures, the cognate mRNA is present in neuronal cell bodies and their dendrites, whereas near exclusive dendritic localization is observed for the polypeptide product. In the hippocamus, DEN mRNA is highly expressed in the cell laminae and dendritic layers of the dentate gyrus and CA1 field, but expression is markedly reduced in the CA3 and CA4 areas. The predicted primary structure of the hydrophilic, highly basic 653-amino-acid polypeptide does not suggest a function. The restricted expression and dendritic location are compatible with a role for DEN in synaptic plasticity of central neocortical forebrain neurons.

Amino Acid Sequence↗
PubMed1997

Effect of potassium channel openers on the firing rate of hippocampal pyramidal cells and A10 dopaminergic neurons in vitro.

The effect of four KATP channel openers (KCOs) on the firing rate of CA1 pyramidal cells and A10 dopaminergic neurons was investigated using extracellular recording techniques in rat brain slices. Pinacidil, lemakalim, diazoxide and a new compound, BPDZ44, had an inhibitory effect on the electrical activity of CA1 pyramidal cells. They all had a similar potency. Only BPDZ44 and diazoxide inhibited the firing rate of A10 dopamine neurons. The sulfonylurea glipizide (1 microM) antagonized the effect of BPDZ44 and diazoxide on A10 neurons but failed to antagonize the effect of KCOs on CA1 pyramidal cells. These results show that differences exist among KCOs in their ability to decrease the electrical activity of various populations of central neurons.

Action Potentials↗
PubMed1996

Dibenzoazepine analogues: the electrophysiological properties of JL3, a potential atypical antidepressant.

JL3, 10-(4-methylpiperazin-1-yl)pyrido[4,3-b][1,4]benzothiazepine, has potent antidepressant-like activity in Porsolt's test in mice. Therefore, its influence on the electrical activity of central monoaminergic neurons was investigated in rats anaesthetized with chloral hydrate. JL3 induced a marked decrease of the firing rate of dorsal raphe serotonergic neurons (ID50 = 3.87 +/- 0.57 mg kg-1) and of locus coeruleus noradrenergic neurons (ID50 = 2.63 +/- 0.35 mg kg-1). The drug did not modify the electrical activity of A10 dopaminergic neurons. JL3 does not block amine uptake but it has affinity for 5-HT1A and 5-HT2 receptors. It is speculated that serotonergic mechanisms could play a role in the electrophysiological effects of JL3.

Animals↗
PubMed1995

Hydrogen peroxide hyperpolarizes rat CA1 pyramidal neurons by inducing an increase in potassium conductance.

It has been suggested that hydrogen peroxide is involved in cascades of pathological events affecting neural cells. The aim of this study was therefore to examine whether this molecule is able by itself to modify membrane properties of pyramidal neurons in the CA1 region of the rat hippocampus. Intracellular recordings in the slice preparation showed that 3.3 mM hydrogen peroxide hyperpolarized all neurons tested (n = 41) by 11 +/- 3 mV. This effect persisted in the presence of tetrodotoxin. It developed slowly, was reversible and reproducible. In the presence of tetrodotoxin, the extrapolated reversal potential of this effect was -95 +/- 5 mV in 2.5 mM external potassium. This value was not significantly different from the one obtained with the GABAB agonist baclofen (10 microM) (-98 +/- 5 mV). It shifted when the concentration of external potassium was increased to 10.5 mM (from -96 +/- 5 to -62 +/- 4 mV), in close agreement with the Nernst equation potassium ions. The hyperpolarization was significantly reduced (by 65 +/- 22%) by the potassium channel blocker barium (100 microM). We suggest that hydrogen peroxide is able to induce an increase in potassium conductance in rat CA1 pyramidal neurons. The exact mechanism by which it produces this effect (direct action on channels or indirect effect) remains to be determined.

Animals↗
PubMed1994

Towards a pharmacological approach of Alzheimer's disease based on the molecular biology of the amyloid precursor protein (APP).

After heart disease, cancer and stroke, Alzheimer's disease (AD) is the fourth major cause of death in the developed countries. Due to demographic changes, this situation will further worsen in the future. With the use of molecular biology techniques, important progress has recently been made in the understanding of the molecular changes leading to some forms of this disabling illness. The first step was the partial sequencing of the amyloid protein accumulating in the senile plaques and vascular deposits characteristic of AD. This allowed the cloning of a cDNA coding for a long amyloid precursor protein (APP). During the last few years, independent reports have described the presence of several reproducible point mutations in specific codons of APP in early onset familial Alzheimer patients. These mutations are responsible for an abnormal processing of APP, leading to the formation of pathological beta/A4 amyloid deposits. beta/A4 has been shown to possess neurotrophic properties in embryonic neurones and to be a potent neurotoxic agent in differentiated hippocampal neurones. More recently, modifications of intracellular calcium, activation of kinases, free radical generation and anomalies in potassium channels have been described as possible mechanisms of beta/A4 toxicity. Some forms of Apo-E lipoprotein may be an additional risk factor. Hence, it now seems possible to elaborate a coherent theory to explain the cascade of events leading to the development of AD. Genetically induced point mutations or environmental factors may produce a modification of the APP metabolism and processing. As a consequence, abnormal deposits of beta/A4 are formed. They may exert direct or indirect neurotoxic actions. A degeneration of cholinergic, catecholaminergic and other neurones follows, leading to the well known cognitive and behavioural changes of AD.

Alzheimer Disease↗
PubMed1993

A subtractive hybridization method to isolate tissue-specific transcripts: application to the selection of new brain-specific products.

A method based on subtractive hybridization of brain complementary DNAs with peripheral messenger RNAs has enabled us to construct an enriched brain-specific cDNA library. Single-stranded cDNAs (ssc DNAs) were synthesized from brain polyadenylated mRNAs and subsequently hybridized with peripheral mRNAs immobilized on nitrocellulose membrane. Unhybridized sscDNAs were converted into double-stranded cDNAs and cloned into plasmid pUC13. The screening of the resulting library showed that a high percentage of the cloned cDNAs corresponded to mRNAs specifically transcribed in the brain.

Animals↗
PubMed1992

Differential effects of picrotoxin and RO 15-1788 on high and low ethanol concentrations on rat locus coeruleus in vitro.

In an in vitro electrophysiological single-cell recording model, ethanol had an inhibitory effect on locus coeruleus (LC) neurons at both low (0.1 mmol/l) and high (500 mmol/l) concentrations. In order to test if the benzodiazepine-GABA (gamma-aminobutyric acid) receptor complex could be implicated in this effect, we tested the interaction of these ethanol concentrations with picrotoxin (100 mmol/l) and RO 15-1788 (10 nmol/l). RO 15-1788 reversed the inhibitory effect induced by ethanol 500 mmol/l, but not by ethanol 0.1 mmol/l; picrotoxin reversed the effects of both concentrations. This indicates that the mechanisms of action of ethanol on LC neurons are not the same for high and low concentrations. Furthermore, the effect of concentrations related to a behavioral effect (greater than 10 mmol/l) was reversed by a low-calcium medium that abolishes transmitter release. Therefore, the inhibition induced by ethanol 500 mmol/l seems to be due to the release of an endogenous benzodiazepine-like compound.

Animals↗
PubMed1991

[Contribution of electrophysiology to the study of tianeptine and other antidepressive agents].

Intravenous perfusion of tianeptine reduces the frequency of coeruleus locus neural discharge. It does not affect the rate of neural discharge in the dorsal raphe, increase the rate of neural discharge in the ventral tegument air and the rate of discharge in the pyramidal cells of the hippocampus (CA1). In comparison, intravenous perfusion of clomipramine decreases the rate of neural discharge in the coeruleus locus, the dorsal raphe, the ventral tegument air (temporarily) and the pyramidal cells of the hippocampus. Iontophoretic application of tianeptine does not affect the response of pyramidal cells in the hippocampus to application of serotonin or gamma amino-butyric acid (GABA), but lowers recovery time after iontophoretic administration of serotonin or GABA. Iontophoretic application of clomipramine increases pyramidal cell response to serotonin but not to GABA and lengthens the recovery time after serotonin and GABA. The results are in agreement with the fact that tianeptine, unlike clomipramine, increases serotonin capture. Tianeptine leads to an original electrophysiologic pattern distinct from classic antidepressants and clomipramine.

Animals↗
PubMed1991

Acute amphetamine-induced subsensitivity of A10 dopamine autoreceptors in vitro.

Extracellular recordings were obtained from spontaneously active, presumed dopamine (DA) neurons of the ventral tegmental area (VTA) of the rat in a slice preparation. Bath-applied (+)-amphetamine (AMPH) (1-30 microM) induced a concentration-dependent decrease in the firing rate of these neurons, which tended to saturate with the highest concentrations used (n = 11). This inhibitory effect was dependent on the activation of D2 receptors since it was reversed by the D2 antagonist sulpiride (n = 8). However, the most striking effect of AMPH was the induction of a prominent subsensitivity of DA autoreceptors: whereas in 18 out of 20 control neurons, the D2 agonist BHT 920 (100 nM) produced a rapid and complete inhibition of the firing, this was observed in none out of 11 neurons 10 min after the end of the application of AMPH (1-30 microM) (P less than 0.001). In these cells, the mean percent inhibition produced by BHT 920 was only 47 +/- 8%. This subsensitivity remained unchanged after 20 min and declined after one hour. This effect was specific, since the sensitivity of GABAB receptors to baclofen (500 nM-1 microM) was not modified by the application of AMPH (n = 12). These results suggest that AMPH-induced DA autoreceptor subsensitivity can be produced acutely and may be the first step in a cascade of events leading to behavioral sensitization to this compound.

Amphetamine↗
PubMed1991

Yohimbine can induce ethanol tolerance in an in vitro preparation of rat locus coeruleus.

Noradrenergic neurons have been implicated in the development of ethanol dependence and tolerance. Moreover, the development of an hyposensitivity of alpha 2 adrenoceptors has been postulated during long-term exposition to ethanol. In order to test the putative role of alpha 2 receptors in ethanol intoxication, we have studied the interaction between ethanol and yohimbine, an alpha 2 antagonist, on the spontaneous firing rate of rat locus coeruleus (LC) in an in vitro slice model. The spikes from single neurons were recorded by glass microelectrodes. Ethanol at 100 mM, a concentration that parallels the behavioral effects in the human and in the animals, inhibits the firing activity of some LC cells. This inhibition was quickly reversed after stopping the ethanol perfusion and was observed for each further administration. However, if yohimbine (20 microM) was simultaneously perfused, the ethanol-induced inhibition was rapidly antagonized. This effect is reversible after long time washout of yohimbine. This suggests that alpha 2 adrenoceptors could be implicated in the inhibitory effect of ethanol on LC noradrenergic neurons and perhaps in the development of tolerance. However, other hypotheses are discussed, because yohimbine can also antagonize other types of receptors.

Animals↗
PubMed1990

Evidence for the presence of N-methyl-D-aspartate receptors in the ventral tegmental area of the rat: an electrophysiological in vitro study.

Extracellular recordings were obtained from spontaneously active, presumed dopaminergic neurons of the ventral tegmental area (VTA) of the rat in a slice preparation. Bath-applied N-methyl-D-aspartate (NMDA) (1-20 microM) activated all neurons tested (n = 36). This effect was clearly concentration-dependent (n = 14), quickly reversible and reproducible. No bursting type of discharge was observed during NMDA infusion. The NMDA receptor blocker DL-2-amino-5-phosphonovaleric acid (50 microM) reversibly antagonized the increase in cell firing produced with 10 microM NMDA by 83.5 +/- 3% (mean +/- S.E.M.) (n = 8, P less than 0.05). Lowering the Mg2+ concentration of the perfusion fluid to one-third of its normal value significantly enhanced the excitatory effect of 5 microM NMDA (n = 7, P less than 0.05), but not of 500 nM carbachol (n = 6). Finally, NMDA did not modify the sensitivity of dopaminergic autoreceptors of VTA neurons (n = 8), when compared to controls (n = 10). These observations strongly support the presence of specific NMDA receptors in the VTA.

2-Amino-5-phosphonovalerate↗
PubMed1990

Influence of fenfluramine and norfenfluramine stereoisomers on the firing rate of central monoaminergic neurons in the rat.

The influence of acute administration of stereoisomers of fenfluramine and norfenfluramine on the firing rate of central monoaminergic neurons was investigated in rats anaesthetized with chloral hydrate. The firing rate of dorsal raphe (DR) and locus coeruleus (LC) neurons was inhibited. The parent drugs were more active on DR neurons than on LC neurons, and the converse was true for the demethylated metabolites. In both cases the d isomers were more active than the l isomers. No effect was observed on the electrical activity of A10 dopaminergic neurons. These differences in potency and selectivity could have therapeutic implications.

Animals↗
PubMed1990

Effect of BHT 920 on monoaminergic neurons of the rat brain: an electrophysiological in vivo and in vitro study.

BHT 920 was originally described as a dopamine autoreceptor agonist. In this study, the effect of this compound on the firing rate of noradrenergic locus coeruleus, serotonergic dorsal raphe and dopaminergic ventral tegmental area neurons was examined both in the anaesthetized rat and in rat brain slices. Extracellular recordings were performed in cells whose identity was determined by electrophysiological, pharmacological and histological criteria. In vivo, BHT 920 inhibited the firing of locus coeruleus neurons (ID50: 14.5 +/- 4.7 micrograms/kg, mean +/- SEM) and ventral tegmental area neurons (ID50: 7 +/- 3 micrograms/kg) at very low doses. As a comparison, the ID50 of clonidine on locus coeruleus cells was 5.5 +/- 0.6 microgram/kg and the ID50 of apomorphine on ventral tegmental area neurons was 13 +/- 3 micrograms/kg. BHT 920 also decreased the firing of dorsal raphe cells, but this effect was obtained at higher doses (ID50: 57 +/- 11 micrograms/kg). The in vitro study confirmed the results obtained in vivo. BHT 920 potently inhibited the firing of locus coeruleus cells (IC50: 71 +/- 28 nM) and was less potent than clonidine (IC50: 5.3 +/- 0.98 nM). The compound also inhibited the firing of ventral tegmental area neurons at very low concentrations (IC50: 21 +/- 3.3 nM), being more potent than apomorphine (IC50: 56 +/- 29 nM). BHT 920 only slightly decreased the firing rate of dorsal raphe neurons at 50 microM, showing that the drug has little direct effect on these cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1990

Comparison of the effect of morphine on locus coeruleus noradrenergic and ventral tegmental area dopaminergic neurons in vitro.

Extracellular single-cell recordings were performed on rat brain slices to compare the effects of morphine on noradrenergic neurons of the locus coeruleus (LC) and on dopaminergic neurons of the ventral tegmental area (VTA). Morphine inhibited the firing of LC neurons at very low concentrations. The mean IC50 was 13.4 +/- 1nM (mean +/- SEM) (n = 7). Moreover, the inhibitory effect of morphine was identical in slices obtained from rats anesthetized with chloral hydrate or from non-anesthetized rats. On the contrary, morphine did not have any influence on the firing of most VTA neurons (N = 20) up to 100 microM, and did not modify the sensitivity of their autoreceptors (N = 8). It is concluded that morphine potently inhibits the firing of LC neurons in vitro both in slices of anesthetized and not anesthetized animals and has no direct excitatory effect on VTA dopaminergic neurons of the rat.

Adrenergic Fibers↗