References of "Chiap, Patrice"
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See detailTriamcinolone acetonide after intra-articular injection in knee in sheep
Legrand, Nathalie ULiege; Tian, Jin; Douny, Caroline ULiege et al

Poster (2018, October 26)

Intra-articular injections of glucocorticoids aim to control pain and inflammation caused by osteoarthritis. There is a lack of evidence and pharmacokinetics (PK) studies to support the empirical ... [more ▼]

Intra-articular injections of glucocorticoids aim to control pain and inflammation caused by osteoarthritis. There is a lack of evidence and pharmacokinetics (PK) studies to support the empirical currently used dosage regimens. This study aimed 1) to determine the PK of triamcinolone hexacetonide (TH) and triamcinolone acetonide, its active metabolite (TA), in synovial fluid after intra-articular administration of a suspension of TH at 40mg and 10mg in sheep and 2) to compare the profiles of TA after injection of suspensions of TA or TH, both at 40mg. Twelve sheep were randomly allocated to three groups receiving respectively 40 mg TA (n=4), 40 mg TH (n=4) or 10 mg TH (n=4) in the left knee. Synovial fluids were sampled from day 1 up to day 21. The concentrations of TA and TH were measured by ultra-performance liquid chromatography mass spectrometry. TA concentrations measured after one day were higher in the group TA-40 mg (537762.3ng/ml) compared to those recorded in the group TH-40mg (22743.4ng/ml), On day 21, the corresponding values were 2.5 and 33.5 ng/ml due to a significant higher value of T1/2β of TA in group TH-40 mg (6.0 versus 1.9 days). The differences between the mean values of AUC and T1/2β of TA were not significantly different between the groups TH-10 and -40 mg but T1/2β of TH was significantly higher in the group TH-40mg. In conclusion, TH injection maintains TA concentrations for a longer period of time than TA administration. Due to a possible saturation of esterases, the PK profiles associated to the high and low doses of TH were rather close suggesting that a dose of 10mg could provide an optimal benefit-risk. [less ▲]

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See detailValidation d’une méthode UHPLC/MS-MS pour le dosage plasmatique du 15-F2t-isoprostane, biomarqueur du stress oxydant, en vue de l’établissement de valeurs de référence en routine clinique
Dubrowski, Thomas ULiege; PINCEMAIL, Joël ULiege; Vigor, Claire et al

Poster (2017, October)

Objectif : Cela fait des décennies que l’implication des isoprostanes dans le stress oxydant est mise en évidence dans la littérature. Malgré cela, il y a peu de concordances entre les différentes valeurs ... [more ▼]

Objectif : Cela fait des décennies que l’implication des isoprostanes dans le stress oxydant est mise en évidence dans la littérature. Malgré cela, il y a peu de concordances entre les différentes valeurs de référence publiées dans ces mêmes articles. Cela peut s’expliquer par le très grand nombre de composés apparentés à cette famille de molécules. L’Unité GLP-AEPT s’est concentrée sur le 15-F2t-isoprostane, biomarqueur « gold standard » de la peroxydation lipidique, afin de développer et valider une méthode de dosage fiable et utilisable en routine clinique. Cette méthode a ensuite été appliquée à l’analyse du plasma prélevé chez 61 volontaires sains en vue de déterminer les valeurs de référence pour ce biomarqueur du stress oxydant. Méthodes : Les échantillons plasmatiques sont purifiés par extraction liquide-solide avant d’être analysés par chromatographie liquide à ultra haute pression couplée à la spectrométrie de masse en tandem (UHPLC/MS-MS) au moyen du système UPLC Xevo TQ-S (Waters). Résultats : La méthode a été validée avec succès sur une gamme de concentrations allant de 25 à 2000 pg/ml en appliquant une stratégie basée sur l’erreur totale de mesure (incluant l’expression de la justesse et de la fidélité intermédiaire) et les profils d’exactitude. Les limites d’acceptation ont été fixées à ± 20 % pour les concentrations inférieures à 30 pg/ml et ± 15 % pour les concentrations égales ou supérieures à cette valeur. Cette approche garantit que seules 10 % des futures mesures d’échantillons inconnus seront en dehors de ces limites. Les concentrations obtenues pour les 61 volontaires sains sont distribuées selon une courbe gaussienne classique. L’intervalle de valeurs de référence pour le 15-F2t-isoprostane a été calculé et est compris entre 152 et 368 pg/ml [1]. Plusieurs corrélations ont ensuite pu être mises en évidence entre ce biomarqueur et d’autres paramètres biologiques connus pour affecter le niveau de stress oxydant de l’organisme (rapport Cu/Zn et glutathion total entre autres) [1]. Conclusion : Une méthode d’analyse fiable et compatible avec une application en routine clinique est à présent disponible afin de mesurer la concentration plasmatique en 15-F2t-isoprostane. Grâce à l’intervalle de valeurs de référence qui a été déterminé pour ce biomarqueur, le niveau de stress oxydant du patient peut être évalué. Références : 1. Pincemail J. et coll. Validated routine-ready UHPLC/MS-MS method for the reference range determination in human plasma of 15-F2t-isoprostane, biomarker of the oxidative stress. FRBM. 2017; 108 (1): page S42. [less ▲]

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See detailOPTIMIZATION OF A FULLY AUTOMATED ELECTROPHORETICALLY MEDIATED MICROANALYSIS SYSTEM FOR CYP1A1 ACTIVITY MONITORING
Farcas, Elena ULiege; Servais, Anne-Catherine ULiege; Lamalle, Caroline et al

Conference (2016, October 01)

Objective of the study Since CYP1A1, a member of cytochrome P450 superfamily, has been described to be over expressed in various types of cancer, our study was focused on the optimization of a fully ... [more ▼]

Objective of the study Since CYP1A1, a member of cytochrome P450 superfamily, has been described to be over expressed in various types of cancer, our study was focused on the optimization of a fully automated system for the monitoring of this particularly interesting enzyme. Moreover, the potentiality of this approach to screen CYP1A1 inhibitors was investigated. Materials and methods The experiments were carried out on a HP3DCE system using an on-column DAD. The EMMA procedure was performed by injecting a plug containing the co-factor(NADPH) and the substrate(7-ethoxycoumarin) between two plugs of CYP1A1 supersomes. The reaction was triggered by the application of a voltage switch. The voltage was then turned off to allow the metabolic reaction to occur. The separation of the components was then performed. Results Satisfying results were obtained using CYP1A1 at a concentration of 200 pmol/mL, while the incubation time was settled to 15 min. A DoE was performed to find the best mixing conditions. The amount of metabolite obtained was comparable to the one detected after conventional off-line metabolization. The ability of our system to monitor CYP1A1 inhibition was then proven with apigenin, a well-known CYP1A1 inhibitor. Conclusions The present study describes the development of a fully automatized in-capillary method for CYP1A1 activity monitoring and proves the potentialy of our system to be used for the screening of CYP1A1 inhibitors. The advantages of performing inline metabolization assays are mainly the miniaturization and the automatization of the process. Besides, the reagents consumption is drastically reduced due to the injection of few tens of nanoliters. [less ▲]

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See detailMise en place d’études cliniques portant sur des antioxydants
CHIAP, Patrice ULiege

Conference (2016, June 01)

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See detailFully automated electrophoretically mediated microanalysis for CYP1A1 activity monitoring optimized by multivariate approach
Farcas, Elena ULiege; Servais, Anne-Catherine ULiege; Lamalle, Caroline ULiege et al

in Electrophoresis (2016), 37(2), 248-255

In this study, a fully automatized in-capillary system was developed to monitor the activity of CYP1A1 in physiological conditions. Ethoxycoumarin, the selected substrate, undergoes an in-line bioreaction ... [more ▼]

In this study, a fully automatized in-capillary system was developed to monitor the activity of CYP1A1 in physiological conditions. Ethoxycoumarin, the selected substrate, undergoes an in-line bioreaction in the presence of CYP1A1 supersomes and NADPH as co-factor, giving rise to hydroxycoumarin, the product that was assayed. The optimization of the experimental conditions was supported by the application of a design of experiment, providing a better understanding of electrophoretic mixing parameters that influence the metabolic reactions. The results obtained in optimal conditions were compared not only to those achieved after off-line metabolization but also with liver microsomes. Finally, inhibition studies were conducted showing an important decrease of hydroxycoumarin formation using apigenin as CYP1A1 potent inhibitor. This study demonstrates the usefulness of our in-line system for the fully automated in vitro metabolism studies and the screening of new CYP1A1 inhibitors. [less ▲]

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See detailFULLY AUTOMATED ELECTROPHORETICALLY MEDIATED MICROANALYSIS SYSTEM FOR CYP1A1 ACTIVITY MONITORING
Farcas, Elena ULiege; Servais, Anne-Catherine ULiege; Lamalle, Caroline ULiege et al

Poster (2015, June 23)

Introduction Since the efficacy and toxicity of drugs are closely related to their pharmacokinetics, a good understanding of metabolic pathways is important at an early stage of development. The ... [more ▼]

Introduction Since the efficacy and toxicity of drugs are closely related to their pharmacokinetics, a good understanding of metabolic pathways is important at an early stage of development. The identification of the enzymes involved in drug metabolism is thus of critical importance for the design of further clinical studies. The availability of specifically expressed human CYPs, namely supersomes, allows the investigation of the contribution of a single metabolic enzyme to the biotransformation pathway of the compound under investigation. CYP1A1, a member of the cytochrome P450 superfamily, was studied in this project. Interestingly, it has been described to be over expressed in various types of cancer. Consequently, CYP1A1 has emerged as a particularly interesting target for cancer therapy. Methods All the experiments were carried out on a HP3DCE system equipped with an on-column DAD. The EMMA procedure was performed by injecting a plug containing CYP1A1 supersomes, followed by a plug that contained the co-factor and the substrate, then another plug of CYP1A1 supersomes. The reaction was triggered by the application of a voltage switch. The voltage was then turned off to allow the metabolic reaction to occur. The separation of the components was then performed at -25 kV. Results The present study describes the development of a fully automatized in-capillary method to follow metabolization of 7-hydroxycoumarin and screen CYP1A1 inhibitors. After preliminary studies, satisfying results were obtained using CYP1A1 at a concentration of 200 pmol/mL, while the incubation time was settled to 15 min. Equal reactant plugs were injected at -50 mbar for 6 sec. The short-end injection performed gave rise to a baseline separation of the molecules (substrate, product, CYP1A1 and NADPH) in less than 2 minutes. Adequate plugs overlap was obtained using electrophoretic mixing. The DoE performed highlighted that the voltage switch has a great impact on the metabolite formation. The amount of product obtained in the optimal conditions was found to be comparable to the one detected after conventional off-line metabolization. Besides the interest of developing an automatized CE approach for metabolisation studies, we also wanted to investigate the potentiality of this approach to screen CYP1A1 inhibitors. The ability of our system to monitor CYP1A1 inhibition was undertaken with apigenin, a well-known inhibitor. It is noteworthy that the compatibility of our system with MEKC ensures its applicability to a large variety of molecules. Novel aspect Monitoring CYP1A1 activity using a rapid and fully automated EMMA method that could be used for new anticancer agents screening. [less ▲]

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See detailFully automated electrophoretically mediated microanalysis system for CYP1A1 activity monitoring
Farcas, Elena ULiege; Servais, Anne-Catherine ULiege; Lamalle, Caroline ULiege et al

Conference (2015, May 28)

In order to evaluate the potentiality of capillary electrophoresis for CYP1A1 activity monitoring, an in-line method was developed with the well-known 7-ethoxycoumarin substrate. The electrophoretically ... [more ▼]

In order to evaluate the potentiality of capillary electrophoresis for CYP1A1 activity monitoring, an in-line method was developed with the well-known 7-ethoxycoumarin substrate. The electrophoretically mediated microanalysis approach was used with CYP1A1 supersomes to provide a rapid and fully automated method. The in-line homogenous enzyme assay was performed in physiological conditions (pH 7.4), whereas a MEKC buffer was used as background electrolyte. In order to reduce the analysis time, the short end injection was performed. Firstly a plug containing CYP1A1 supersomes was hydrodynamically injected into a fused silica capillary, followed by a plug of co-factor (NADPH) and substrate (7-ethoxycoumarin) and finally another plug of CYP1A1 (sandwich mode). The experimental conditions were finely investigated and tuned by design of experiment methodology. The metabolization rate measured in the optimized conditions was comparable with the one obtained after off-line metabolization. Finally, inhibition studies were conducted and a significant decrease of 7-hydroxycoumarin formation was observed using apigenin as CYP1A1 potent inhibitor. [less ▲]

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See detailAn HPLC-MS method for the analysis of 26 non-enzymatic metabolites of PUFAs in biological samples
Dupuy, Anne; Pinot, Edith; Vigor, Claire et al

Poster (2014, September)

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See detailNMR in the Pharmaceutical and Biomedical areas for identification and quantification of drugs and metabolomics applications
LAMBERT, Vincent ULiege; Dufour, Gilles ULiege; Chiap, Patrice ULiege et al

Conference (2014, June 23)

Nuclear Magnetic Resonance (NMR) is probably, with mass spectrometry, the most powerful analytical tool for the structural determination of organic compounds. For a long time and due to technical ... [more ▼]

Nuclear Magnetic Resonance (NMR) is probably, with mass spectrometry, the most powerful analytical tool for the structural determination of organic compounds. For a long time and due to technical limitations, the main applications of NMR were focused on chemistry (organic, inorganic and medicinal chemistry) or biochemistry (i.e. proteins and proteins ligands analysis). Indeed, despite of very interesting potential in terms of structural information, reproducibility, specificity, quantification, NMR suffered of a lack of sensitivity and sometime of resolution in the case of complex mixture analysis in comparison with other technics. However, since several years, important technical improvements such as huge increase in sensitivity, hyphenation of NMR with LC system, automation and development of 2D and presaturation sequences have opened new putative applications for NMR, specifically in the pharmaceutical and biomedical areas. Then, beside the mass and chromatographic technics classically used for drug analysis, NMR represents an interesting and complementary tool for many applications. In this presentation, we will describe some NMR applications related to the pharma area. Starting from the identification of xenobiotic metabolites by coupling LC-SPE-NMR data with LC-MS/MS results, quantification of cyclodextrines in complex media, identification of illicit compounds, we will finish with our recent metabolomics NMR developments. [less ▲]

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See detailStratégies analytiques pour la détection de contrefaçons de médicaments pour la dysfonction érectile
Sacre, Pierre-Yves ULiege; Deconinck, Eric; Marini Djang'Eing'A, Roland ULiege et al

in Spectra Analyse (2014), 43

Erectile dysfunction drugs are among the most counterfeit drug classes in industrialized countries. To fight against this plague, several analytical approaches are available for control laboratories. The ... [more ▼]

Erectile dysfunction drugs are among the most counterfeit drug classes in industrialized countries. To fight against this plague, several analytical approaches are available for control laboratories. The present article reviews the main used techniques and concludes presenting a general strategy for the detection and handling of drug counterfeits. [less ▲]

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See detailTriphenylphosphonium salts of 1,2,4-benzothiadiazine 1,1-dioxides related to diazoxide targeting mitochondrial ATP-sensitive potassium channels
Constant-Urban, C.; Charif, M.; Goffin, Eric ULiege et al

in Bioorganic and Medicinal Chemistry Letters (2013), 23

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See detailOptimization of the liquid chromatography enantioseparation of chiral acidic compounds using cellulose tris(3-chloro-4-methylphenylcarbamate) as chiral selector and polar organic mobile phases.
Dossou, K. S. S.; Farcas, Elena ULiege; Servais, Anne-Catherine ULiege et al

in Journal of Chromatography. A (2012), 1234

The LC enantioseparation of chiral acidic and zwitterionic drugs selected as model compounds was optimized using chlorine containing cellulose based chiral stationary phases and polar organic mobile ... [more ▼]

The LC enantioseparation of chiral acidic and zwitterionic drugs selected as model compounds was optimized using chlorine containing cellulose based chiral stationary phases and polar organic mobile phases. The main solvent of the mobile phase was acetonitrile, the temperature was settled at 25 degrees C and a stationary phase with cellulose tris(3-chloro-4-methylphenylcarbamate) as chiral selector (3-Cl-4-Me-PC) was selected. In the screening step, the nature and concentration of both acidic and basic additives were found to have a significant effect on retention, selectivity and resolution. Acetic acid (AcA) was selected as acidic additive for the optimization step since it could lead to the enantioseparation of more acidic compounds than trifluoroacetic acid (TFA) and formic acid (FA), while among the three basic additives tested, diethylamine (DEA) most often gave better results with respect to enantioresolution and selectivity than butylamine (BuA) and triethylamine (TEA). The optimization was performed using a central composite face-centered design with two factors, namely the concentration of acetic acid (0.1-0.3%) and the concentration of DEA (0.01-0.1%) in the mobile phase. On the basis of the results obtained in the screening and optimization steps, a strategy for the rapid development of methods for the enantioseparation of acidic or neutral compounds was proposed. [less ▲]

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See detailCurcumin-cyclodextrin complexes potentiate gemcitabine effects in an orthotopic mouse model of lung cancer.
Rocks, Natacha ULiege; Bekaert, Sandrine ULiege; Coia, I et al

in British Journal of Cancer (2012), 107(7), 1083-92

Background:Overall clinical outcome for advanced lung cancer remains very disappointing despite recent advances in treatment. Curcumin has been reported as potentially active against cancer.Methods:Owing ... [more ▼]

Background:Overall clinical outcome for advanced lung cancer remains very disappointing despite recent advances in treatment. Curcumin has been reported as potentially active against cancer.Methods:Owing to poor curcumin solubility, we have used cyclodextrins (CD) as an excipient allowing a considerable increase of aqueous solubility and bioavailability of curcumin. The effects of solubilised curcumin have been evaluated in cell cultures as well as in an in vivo orthotopic lung tumour mouse model.Results:Cell proliferation was reduced while apoptosis rates were increased when lung epithelial tumour cells were cultured in the presence of curcumin-CD complexes. For in vivo experiments, cells were grafted into lungs of C57Bl/6 mice treated by an oral administration of a non-soluble form of curcumin, CDs alone or curcumin-CD complexes, combined or not with gemcitabine. The size of orthotopically implanted lung tumours was reduced upon curcumin complex administration as compared with treatments with placebo or non-solubilised curcumin. Moreover, curcumin potentiated the gemcitabine-mediated antitumour effects.Conclusion:Our data demonstrate that curcumin, when given orally in a CD-solubilised form, reduces lung tumour size in vivo. In vitro experiments show impaired tumour cell proliferation and increased cell apoptosis. Moreover, our data underline a potential additive effect of curcumin with gemcitabine thus providing an efficient therapeutic option for antilung cancer therapy. [less ▲]

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See detailImpurity fingerprints for the identification of counterfeit medicines - a feasibility study
Sacré, Pierre-Yves ULiege; Deconinck, Eric; Daszykowski, Michal et al

Poster (2011, September)

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See detailOptimization of micro-HPLC peak focusing for the detection and quantification of low hepcidin concentrations.
Mansion, François ULiege; Chiap, Patrice ULiege; Houbart, Virginie ULiege et al

in Journal of Separation Science (2011), 34(15), 1820-1827

Micro-high-performance liquid chromatography is a miniaturized, economic and ecological chromatographic system allowing the use of reduced size chromatographic columns. Coupled with electrospray ... [more ▼]

Micro-high-performance liquid chromatography is a miniaturized, economic and ecological chromatographic system allowing the use of reduced size chromatographic columns. Coupled with electrospray ionization tandem mass spectrometry, this technique can be used to detect and quantify low concentrations of peptides. In this study, hepcidin was used as the model compound and analysed using octadecylsilica stationary phase by means of a gradient elution mode at a flow rate of 4 muL/min. Several parameters were studied to optimize peak focusing. Using the methodology of experimental design, the mobile-phase gradient conditions and the sample composition were optimized in order to maximize the sensitivity and minimize retention time. Stability of the target peptide in solution was also demonstrated. [less ▲]

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See detailImpurity fingerprints for the identification of counterfeit medicines - a feasibility study
Sacré, Pierre-Yves ULiege; deconinck, Eric; Daszykowski, Michal et al

Poster (2011, June 22)

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