References of "Plenevaux, Alain"
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See detailThe Effect of Clonidine Infusion on Distribution of Regional Cerebral Blood Flow in Volunteers
Bonhomme, Vincent ULg; Maquet, Pierre ULg; Phillips, Christophe ULg et al

in Anesthesia and Analgesia (2008), 106(3), 899-909

BACKGROUND: Through their action on the locus coeruleus, alpha2-adrenoceptor agonists induce rapidly reversible sedation while partially preserving cognitive brain functions. Our goal in this ... [more ▼]

BACKGROUND: Through their action on the locus coeruleus, alpha2-adrenoceptor agonists induce rapidly reversible sedation while partially preserving cognitive brain functions. Our goal in this observational study was to map brain regions whose activity is modified by clonidine infusion so as to better understand its loci of action, especially in relation to sedation. METHODS: Six ASA I-II right-handed volunteers were recruited. Electroencephalogram (EEG) was monitored continuously. After a baseline H2(15)O activation scan, clonidine infusion was started at a rate ranging from 6 to 10 microg x kg(-1) x h(-1). A sequence of 11 similar scans was then performed at 8 min intervals. Plasma clonidine concentration was measured. Using statistical parametric mapping, we sought linear correlations between normalized regional cerebral blood flow (rCBF), an indicator of regional brain activity, and plasma clonidine concentration or spindle EEG activity. RESULTS: Clonidine induced clinical sedation and EEG patterns (spindles) comparable to early stage nonrapid eye movement sleep. A significant negative linear correlation between clonidine concentration and rCBF or spindle activity was observed in the thalamus, prefrontal, orbital and parietal association cortex, posterior cingulate cortex, and precuneus. CONCLUSIONS: The EEG patterns and decreases in rCBF of specific brain regions observed during clonidine-induced sedation are similar to those of early stage nonrapid eye movement sleep. Patterns of deactivated brain regions are also comparable to those observed during general anesthesia or vegetative state, reinforcing the hypothesis that alterations in the activity of a common network occur during these modified conscious states. [less ▲]

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See detailAttenuation and scatter correction accuracy of the microPET Focus 120 assessed with the NEMA NU-4 2008 phantom.
Bahri, Mohamed Ali ULg; Plenevaux, Alain ULg; Seret, Alain ULg

in European Journal of Nuclear Medicine and Molecular Imaging (2008), 35(S2), 193

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See detailCyclosporine, a P-glycoprotein modulator, increases [18F]MPPF uptake in rat brain and peripheral tissues: microPET and ex vivo studies.
Lacan, Goran; Plenevaux, Alain ULg; Rubins, Daniel J. et al

in European Journal of Nuclear Medicine and Molecular Imaging (2008), 35(12), 2256-66

PURPOSE: Pretreatment with cyclosporine, a P-glycoprotein (P-gp) modulator increases brain uptake of 4-(2'-methoxyphenyl)-1-[2'-(N-2"-pyridinyl)-p-[(18)F]fluorobenzamido]ethylpiperaz ine ([(18)F]MPPF) for ... [more ▼]

PURPOSE: Pretreatment with cyclosporine, a P-glycoprotein (P-gp) modulator increases brain uptake of 4-(2'-methoxyphenyl)-1-[2'-(N-2"-pyridinyl)-p-[(18)F]fluorobenzamido]ethylpiperaz ine ([(18)F]MPPF) for binding to hydroxytryptamine(1A) (5-HT(1A)) receptors. Those increases were quantified in rat brain with in vivo microPET and ex vivo tissue studies. MATERIALS AND METHODS: Each Sprague-Dawley rat (n = 4) received a baseline [(18)F]MPPF microPET scan followed by second scan 2-3 weeks later that included cyclosporine pretreatment (50 mg/kg, i.p.). Maximum a posteriori reconstructed images and volumetric ROIs were used to generate dynamic radioactivity concentration measurements for hippocampus, striatum, and cerebellum, with simplified reference tissue method (SRTM) analysis. Western blots were used to semiquantify P-gp regional distribution in brain. RESULTS: MicroPET studies showed that hippocampus uptake of [(18)F]MPPF was increased after cyclosporine; ex vivo studies showed similar increases in hippocampus and frontal cortex at 30 min, and for heart and kidney at 2.5 and 5 min, without concomitant increases in [(18)F]MPPF plasma concentration. P-gp content in cerebellum was twofold higher than in hippocampus or frontal cortex. CONCLUSIONS: These studies confirm and extend prior ex vivo results (J. Passchier, et al., Eur J Pharmacol, 2000) that showed [(18)F]MPPF as a substrate for P-gp. Our microPET results showed that P-gp modulation of [(18)F]MPPF binding to 5-HT(1A) receptors can be imaged in rat hippocampus. The heterogeneous brain distribution of P-gp appeared to invalidate the use of cerebellum as a nonspecific reference region for SRTM modeling. Regional quantitation of P-gp may be necessary for accurate PET assessment of 5-HT(1A) receptor density when based on tracer uptake sensitive to P-gp modulation. [less ▲]

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See detailCharacterization of 4-(2-hydroxyphenyl)-1-[2 '-[N-(2 ''-pyridinyl)-p-fluorobenzamido]ethyl]piperazine (p-DMPPF) as a new potent 5-HT1A antagonist
Defraiteur, Caroline ULg; Plenevaux, Alain ULg; Scuvée-Moreau, Jacqueline ULg et al

in British Journal of Pharmacology (2007), 152(6), 952-958

Background and purpose: The identification of potent and selective radioligands for the mapping of 5-HT receptors is interesting both for clinical and experimental research. The aim of this study was to ... [more ▼]

Background and purpose: The identification of potent and selective radioligands for the mapping of 5-HT receptors is interesting both for clinical and experimental research. The aim of this study was to compare the potency of a new putative 5-HT1A receptor antagonist, p-DMPPF, (4-(2-hydroxyphenyl)-1-[2'-[N-(2''-pyridinyl)-p-fluorobenzamido]-ethyl] piperazine) with that of the well-known 5-HT1A antagonists, WAY-100635(N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]-ethyl]-N-(2-pyridinyl) cyclohexanecarboxamide) and its fluorobenzoyl analogue, p-MPPF (4-(2-methoxyphenyl)-1-[2'-[N-(2''-pyridinyl)p-fluorobenzamido] ethyl] piperazine). Experimental approach: Single cell extracellular recordings of dorsal raphe (DR) neurones were performed in rat brain slices. The potency of each compound at antagonizing the effect of the 5-HT1A agonist, 8-OH-DPAT [8-hydroxy-2-(di-npropylamino)tetraline], was quantified using the Schild equation. The pharmacological profile of p-DMPPF was defined using competition binding assays. Key results: Consistently with a 5-HT1A receptor antagonist profile, incubation of slices with an equimolar (10 nM) concentration of each compound markedly reduced the inhibitory effect of 8-OH-DPAT on the firing rate of DR neurones, causing a significant rightward shift in its concentration-response curve. The rank order of potency of the antagonists was WAY-100635 > p-DMPPF >= p-MPPF. The sensitivity of DR neurones to the inhibitory effect of 8-OH-DPAT was found to be heterogeneous. The binding experiments demonstrated that p-DMPPF is highly selective for 5-HT1A receptors, with a K-i value of 7 nM on these receptors. Conclusions and implications: The potency of the new compound, p-DMPPF, as a 5-HT1A antagonist is similar to that of p-MPPF in our electrophysiological assay. Its selectivity towards 5-HT1A receptors makes it a good candidate for clinical development. [less ▲]

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See detailThe challenge of disentangling reportability and phenomenal consciousness in post-comatose states
Vanhaudenhuyse, Audrey ULg; Bruno, Marie-Aurélie ULg; Brédart, Serge ULg et al

in Behavioral And Brain Sciences (2007), 30(5-6), 529-530

Determining whether or not noncommunicative patients are phenomenally conscious is a major clinical and ethical challenge. Clinical assessment is usually limited to the observation of these patients ... [more ▼]

Determining whether or not noncommunicative patients are phenomenally conscious is a major clinical and ethical challenge. Clinical assessment is usually limited to the observation of these patients' motor responses. Recent neuroimaging technology and brain computer interfaces help clinicians to assess whether patients are conscious or not, and to avoid diagnostic errors. [less ▲]

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See detailRadiochemical synthesis and tissue distribution of p-[F-18]DMPPF, a new 5-HT1A ligand for PET, in rats
Defraiteur, Caroline; Lemaire, Christian ULg; Luxen, André ULg et al

in Nuclear Medicine & Biology (2006), 33(5), 667-675

Several studies have demonstrated the potential of p-[F-18]MPPF as a radiophanilaceutical to study the 5-HT1A receptor family in animals and humans. A structural modification leading to a higher ... [more ▼]

Several studies have demonstrated the potential of p-[F-18]MPPF as a radiophanilaceutical to study the 5-HT1A receptor family in animals and humans. A structural modification leading to a higher radioactive signal at an equipotent dose would greatly enhance this potential. With this goal, the desmethylated 4-(2'-methoxyphenyl)-1-[2'-[N-(2"-pyridinyl)-p-fluorobenzamidolethyl]-piperazine (p-MPPF), identified as p-DMPPF, was synthesized, labeled with fluorine-18 and evaluated through ex vivo tissue distribution in rats. The new compounds p-DMPPF, p-DMPPNO2, MEM-p-MPPF and MEM-p-MPPNO2 were isolated and fully identified (H-1 and C-13 NMR, LC-MS). The final compound, p-[F-18]DMPPF, was obtained ready for injection, with an overall radiochemical yield of 10% (EOB corrected) within 90 min and a specific activity of 62 GBq/mu mol. Tissue distributions showed that the carbon-fluorine bond was stable in vivo and that this compound could cross the blood-brain barrier. For kidney, lung, heart, spleen, bone, testicle, liver and muscle, the percentage of injected dose per gram of tissue obtained with p-[F-18]DMPPF was of the same order of magnitude as that of p-[F-18]MPPF. The amount of radioactivity reaching the brain was much higher (approximately fivefold at 60 min) for p-[F-18]DMPPF compared with p-[F-18]MPPF, which was taken as reference. The distribution and specificity were in total agreement with the known localization of 5-HT1A receptors in rats. The radioactivity increase was more important for specific tissues (hippocampus and frontal cortex) than for cerebellum or striatum, leading to better contrast (hippocampus/cerebellum=5.8 at 60 min). The levels of metabolites found in plasma showed that p-[F-18]DMPPF appears to be less metabolized than p-[F-18]MPPF. p-[F-18]DMPPF deserves further evaluation as a radiopharmaceutical candidate. (c) 2006 Elsevier Inc. All rights reserved. [less ▲]

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See detailDEVELOPPEMENT D'INHIBITEURS SELECTIFS DE LA TRYPTOPHANE HYDROXYLASE
Giacomelli, Fabrice ULg; Luxen, André ULg; Lemaire, Christian ULg et al

Conference (2006, February 03)

Comprendre la façon dont le cerveau travaille et en particulier le mode de communication de ses cellules est un rêve que beaucoup de chercheurs caressent. A l’heure actuelle, une des rares certitudes à ... [more ▼]

Comprendre la façon dont le cerveau travaille et en particulier le mode de communication de ses cellules est un rêve que beaucoup de chercheurs caressent. A l’heure actuelle, une des rares certitudes à son sujet est qu’un de ses modes de transmission d’informations utilise des « messagers » chimiques appelés neurotransmetteurs. Parmi ceux-ci, la sérotonine (5-HT) revêt une importance particulière. En effet, la 5-HT est impliquée dans de nombreuses fonctions (apprentissage, locomotion, sommeil,…) et pathologies (dépressions, démences, schizophrénies,…). Dès lors, l'étude in vivo chez l'homme des neurones sérotoninergiques ainsi que la quantification de la vitesse de biosynthèse de la 5-HT sont des domaines d'études fondamentaux pour lesquels la tomographie à émission de positons (TEP) constitue un outil de choix. Pour mener à bien ces différentes expérimentations, deux stratégies sont envisageables : - L’emploi d'un traceur capable de suivre la chaîne métabolique du tryptophane conduisant à la 5-HT tout en évitant les autres voies métaboliques. - L’utilisation d'un inhibiteur de la TrpOH (enzyme limitant du processus). Dans le cadre de cette présentation, nous nous intéresserons plus particulièrement à la deuxième stratégie. [less ▲]

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See detailSynthesis of protected meso-diaminopimelic acid.
Teller, N.; Lemaire, Christian ULg; Plenevaux, Alain ULg et al

Poster (2005, October 10)

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See detailSynthesis of anhydro-muranic acid derivatives as substrates for MurNAc amidase.
Mercier, F.; Lemaire, Christian ULg; Plenevaux, Alain ULg et al

Poster (2005, October 10)

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See detailRadiochemical Synthesis of OCH2F-[18F]MPPF a New Analogue of p-[18F]MPPF for the Study of 5-HT1A Receptors.
Defraiteur, C.; Lemaire, Christian ULg; Luxen, André ULg et al

in Journal of Labelled Compounds & Radiopharmaceuticals (2005), 48

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See detailEx Vivo Evaluation of p-[18F]D-MPPF for the Study of 5-HT1A Receptors.
Defraiteur, C.; Lemaire, Christian ULg; Luxen, André ULg et al

in Journal of Labelled Compounds & Radiopharmaceuticals (2005), 48

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See detailNew Methods For Halogenation of [18F]Fluorinated Benzyl Derivatives.
Kech, C.; Lemaire, Christian ULg; Brichard, L. et al

in Journal of Labelled Compounds & Radiopharmaceuticals (2005), 48

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See detailHighly enantioselective synthesis of no-carrier-added 6-[18F]Fluoro-L-dopa by chiral phase-transfer alkylation
Lemaire, Christian ULg; Gillet, Steve; Guillouet, Stéphane et al

in European Journal of Organic Chemistry (2004), (13), 2899-2904

[F-18]Fluoro-L-dopa, an important radiopharmaceutical for positron emission tomography (PET), has been synthesized using a phase-transfer alkylation reaction. A chiral quaternary ammonium salt derived ... [more ▼]

[F-18]Fluoro-L-dopa, an important radiopharmaceutical for positron emission tomography (PET), has been synthesized using a phase-transfer alkylation reaction. A chiral quaternary ammonium salt derived from a Cinchona alkaloid served as phase-transfer catalyst for the enantioselective alkylation of a glycine derivative. The active methylene group of this Schiff-base substrate was deprotonated with cesium hydroxide and rapidly alkylated by the 2-[F-18]fluoro-4,5-dimethoxybenzyl halide (X = Br, I). The reaction proceeded with high yield (> 90%) at 0 degreesC or room temperature in various solvents such as toluene or dichloromethane. Preparation of the [F-18]alkylating agent on a solid support was developed. After labelling, the labeled [F-18]fluoroveratraldehyde was trapped on a (t)C18 cartridge and then converted on the cartridge into the corresponding benzyl halide derivatives by addition of aqueous sodium borohydride and gaseous hydrobromic or -iodic acid. Hydrolysis and purification by preparative HPLC made 6-[F-18]fluoro-L-dopa ready for human injection in a 25-30% decay-corrected radiochemical yield in a synthesis time of 100 min. The product was found to be chemically, radiochemically and enantiomerically pure (ee > 95%). (C) Wiley-VCH Verlag GmbH [less ▲]

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