42 results on '"Thomas Mercier"'
Search Results
2. The value of electricity storage arbitrage on day-ahead markets across Europe
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Thomas Mercier, Mathieu Olivier, Emmanuel De Jaeger, and UCL - SST/IMMC/MEED - Mechatronic, Electrical Energy, and Dynamics Systems
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Arbitrage ,Economics and Econometrics ,Energy storage ,General Energy ,Mixed-integer linear programming ,Grid fees ,Day-ahead market - Abstract
This paper investigates the historical value of electricity storage from the perspective of the storage owner in day-ahead markets (DAM) across Europe. A technology-neutral formulation is used, where the storage is modelled based on its round-trip efficiency and storage duration. A mixed-integer linear program (MILP) is built to compute the perfect-foresight value of a price-taker storage from arbitrage, using historical hourly DAM prices in all the bidding zones of the EU-28 countries, Norway, Switzerland, and Turkey. Depending on the bidding zones, the DAM price data starts between 2000 and 2017, and spans to 2021. The model is solved for varying round-trip efficiencies (50% to 100%) and storage durations (1 to 10 h) for every bidding zone and every year in the dataset. The results reveal significant variations in storage value from arbitrage, both geographically and temporally, with round-trip efficiency having a major impact on arbitrage value and storage duration having very low marginal value beyond 4 to 6 h. Additionally, the paper investigates the impact of variable grid fees on arbitrage value, using the case of Belgium, where fees depend on storage system size. The initial MILP is therefore augmented to account for the complex dependencies between storage size and the resulting grid fees. The augmented MILP shows that grid fees can decrease storage arbitrage value by 20% to 50%, and that they can also dramatically decrease storage participation in DAMs.
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- 2023
3. Right heart catheterization in advanced systolic heart failure. What are the most useful haemodynamic parameters for risk stratification?
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Pascal de Groote, Marie Delobelle, Eléonore Hebbar, Thomas Mercier, Marie Fertin, Céline Goéminne, Anju Duva Pentiah, André Vincentelli, Christophe Bauters, and Nicolas Lamblin
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Heart Failure ,Cardiac Catheterization ,Hypertension, Pulmonary ,Hemodynamics ,Humans ,General Medicine ,Cardiology and Cardiovascular Medicine ,Risk Assessment ,Heart Failure, Systolic ,Retrospective Studies - Abstract
Previous studies have shown that pulmonary hypertension is a predictor of mortality in patients with systolic heart failure (SHF). Persistent pulmonary hypertension after a reactivity test is associated with a worse outcome after transplantation. Recent studies have shown the utility of different haemodynamic parameters.To define best haemodynamic parameters for risk stratification in patients with advanced systolic heart failure.We included 425 consecutive patients who underwent a right heart catheterization with an inotropic challenge if indicated.During a median (interquartile range) follow-up of 1.67 (0.49-4.49) years, there were 151 major cardiac events (126 cardiovascular deaths and 25 postoperative deaths after ventricular assist device implantation or heart transplantation). The most powerful independent predictors of major cardiac events were baseline right atrial pressure (RAP) (hazard ratio [HR]: 1.09, 95% confidence interval [CI]: 1.06-1.12; P0.0001) and baseline pulmonary vascular resistance (PVR) (HR: 1.10; 95% CI: 1.03-1.17; P=0.002). After inotropic challenge, the only independent predictor was mean pulmonary arterial pressure (mPAP) (HR: 1.06; 95% CI: 1.03-1.09; P0.0001). The combination of PVR (≤or3 Wood units), RAP (or≥9mmHg) and mPAP after the inotropic challenge (≤or30mmHg) was the best predictor of major events.We suggest using a simple algorithm based on baseline PVR, baseline RAP and mPAP after the inotropic challenge for the risk stratification of stable patients with advanced systolic heart failure.
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- 2021
4. Author Reply to Peer Reviews of HDLs extract lipophilic drugs from cells
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Christian Widmann, Laurent Decosterd, Thomas Mercier, Carla Susana Mendes Ferreira, Gilles Dubuis, and Adi Zheng
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- 2021
5. Validation and clinical application of a multiplex high performance liquid chromatography - tandem mass spectrometry assay for the monitoring of plasma concentrations of 12 antibiotics in patients with severe bacterial infections
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Sabine Laila Lahrichi, Raphaël Burger, Jean-Luc Pagani, O. Marchetti, Nicole Guignard, Thomas Mercier, Nicolas Widmer, Chantal Csajka, Philippe Eggimann, Pascal André, Bertrand Rochat, Eva Choong, Benoît Pesse, Frédéric Lamoth, Sandra Cruchon, Laurent A. Decosterd, Thierry Buclin, and Beatrice Ternon
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Adult ,Male ,Clinical Biochemistry ,030226 pharmacology & pharmacy ,01 natural sciences ,Biochemistry ,Meropenem ,Tazobactam ,High-performance liquid chromatography ,Sensitivity and Specificity ,Analytical Chemistry ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Pharmacokinetics ,Tandem Mass Spectrometry ,medicine ,Humans ,Multiplex ,Chromatography, High Pressure Liquid ,Aged, 80 and over ,ddc:615 ,Chromatography ,medicine.diagnostic_test ,010401 analytical chemistry ,Selected reaction monitoring ,Reproducibility of Results ,Cell Biology ,General Medicine ,Bacterial Infections ,Amoxicillin ,Analysis ,Anti-bacterial agents ,Antibacterial ,Antibiotics ,Assay ,Beta-lactams ,Carbapenems ,Cefepime ,Ceftazidime ,Ceftriaxone ,Cephalosporins ,Cilastatin ,Concentration ,Daptomycin ,Ertapenem ,Flucloxacillin ,Imipenem ,Mass spectrometry ,Penicillins ,Piperacillin ,Plasma ,Quantification ,Rifampicin ,Therapeutic drug monitoring ,0104 chemical sciences ,Anti-Bacterial Agents ,chemistry ,Child, Preschool ,Female ,Drug Monitoring ,medicine.drug - Abstract
Objective Unpredictable pharmacokinetics of antibiotics in patients with life-threatening bacterial infections is associated with drug under- or overdosing. Therapeutic drug monitoring (TDM) may guide dosing adjustment aimed at maximizing antibacterial efficacy and minimizing toxicity. Rapid and accurate analytical methods are key for real-time TDM. Our objective was to develop a robust high-performance liquid chromatography-tandem mass spectrometry method (HPLC-MS/MS) for multiplex quantification of plasma concentrations of 12 antibiotics: imipenem/cilastatin, meropenem, ertapenem, cefepime, ceftazidime, ceftriaxone, piperacillin/tazobactam, amoxicillin, flucloxacillin, rifampicin, daptomycin. Methods A single extraction procedure consisting in methanol plasma protein precipitation and H2O dilution was used for all analytes. After chromatographic separation on an Acquity UPLC HSS-T3 2.1 × 50 mm, 1.8 µm (Waters®) column, quantification was performed by electro-spray ionisation-triple quadrupole mass spectrometry with selected reaction monitoring detection. Antibiotics were divided in two pools of calibration according to the frequency of analyses requests in the hospital routine antibiotic TDM program. Stable isotopically-labelled analogues were used as internal standards. A single analytical run lasted less than 9 min. Results The method was validated based on FDA recommendations, including assessment of extraction yield (96–113.8%), matrix effects, and analytical recovery (86.3–99.6%). The method was sensitive (lower limits of quantification 0.02–0.5 µg/mL), accurate (intra/inter-assay bias −11.3 to +12.7%) and precise (intra/inter-assay CVs 2.1–11.5%) over the clinically relevant plasma concentration ranges (upper limits of quantification 20–160 µg/mL). The application of the TDM assay was illustrated with clinical cases that highlight the impact on patients’ management of an analytical assay providing information with short turn-around time on antibiotic plasma concentration. Conclusion This simple, robust high-throughput multiplex HPLC-MS/MS assay for simultaneous quantification of plasma concentrations of 12 daily used antibiotics is optimally suited for clinically efficient real-time TDM.
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- 2020
6. Sultiame pharmacokinetic profile in plasma and erythrocytes after single oral doses: A pilot study in healthy volunteers
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Catherine Guittet, Thierry Buclin, Laurent A. Decosterd, Kim Dao, Thomas Mercier, Eva Choong, Sébastien Lebon, Monia Guidi, Carine Bardinet, Arnaud Castang, Paul Thoueille, and Luc-André Granier
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Adult ,Male ,Erythrocytes ,Metabolic Clearance Rate ,Cmax ,Thiazines ,Administration, Oral ,Pilot Projects ,volume of distribution ,clearance ,RM1-950 ,Pharmacology ,Urine ,030226 pharmacology & pharmacy ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Pharmacokinetics ,sultiame ,In vivo ,medicine ,Distribution (pharmacology) ,Humans ,General Pharmacology, Toxicology and Pharmaceutics ,pharmacokinetic ,Distribution Volume ,Whole blood ,Volume of distribution ,medicine.diagnostic_test ,Chemistry ,Original Articles ,Off-Label Use ,Neurology ,healthy volunteers ,Therapeutic drug monitoring ,030220 oncology & carcinogenesis ,Area Under Curve ,Original Article ,Therapeutics. Pharmacology - Abstract
A pilot study was conducted aiming at specifying sultiame's pharmacokinetic profile, completed by in vitro assays evaluating the intraerythrocytic transfer of sultiame and by a pharmacokinetic model assessing its distribution. Single oral doses of sultiame (Ospolot ® 50, 100, and 200 mg) were administered in open-label to four healthy volunteers. Serial plasma, whole blood, and urine samples were collected. A spiking experiment was also performed to characterize sultiame's exchanges between plasma and erythrocytes in vitro. Pharmacokinetic parameters were evaluated using standard noncompartmental calculations and nonlinear mixed-effect modeling. The plasma maximal concentrations (C max ) showed striking nonlinear disposition of sultiame, with a 10-fold increase while doses were doubled. Conversely, whole blood C max increased less than dose proportionally while staying much higher than in plasma. Quick uptake of sultiame into erythrocytes observed in vivo was confirmed in vitro, with minimal efflux. A two-compartment model with first-order absorption, incorporating a saturable ligand to receptor binding, described the data remarkably well, indicating apparent plasma clearance of 10.0 L/h (BSV: 29%) and distribution volume of 64.8 L; saturable uptake into an intracellular compartment of 3.3 L with a maximum binding capacity of 111 mg accounted for nonlinearities observed in plasma and whole blood concentrations. Pharmacokinetic characteristics of sultiame are reported, including estimates of clearance and volume of distribution that were so far unpublished. The noticeable nonlinearity in sultiame disposition should be taken into account for the design of future studies and the interpretation of therapeutic drug monitoring results.
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- 2020
7. Compassionate Use of Letermovir in a 2-Year-Old Immunocompromised Child With Resistant Cytomegalovirus Disease
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Julia Natterer, Kristina Murray, Katia Jaton-Ogay, Thomas Mercier, Pascal André, Mattia Rizzi, Maria Pérez Marín, Sandra A. Asner, Thierry Buclin, Onya Opota, Pascal Meylan, Marie-Hélène Perez, Laurent A. Decosterd, and Carole Gengler
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Compassionate Use Trials ,Ganciclovir ,medicine.medical_specialty ,Hepatitis, Viral, Human ,medicine.medical_treatment ,Pneumonia, Viral ,Congenital cytomegalovirus infection ,Cytomegalovirus ,Acetates ,Opportunistic Infections ,030230 surgery ,Antiviral Agents ,Polymerase Chain Reaction ,Immunocompromised Host ,03 medical and health sciences ,Letermovir ,Extracorporeal Membrane Oxygenation ,Fatal Outcome ,0302 clinical medicine ,Pharmacokinetics ,medicine ,Extracorporeal membrane oxygenation ,Humans ,Treatment Failure ,030212 general & internal medicine ,Cytomegalovirus disease ,Intensive care medicine ,Dose-Response Relationship, Drug ,medicine.diagnostic_test ,business.industry ,Compassionate Use ,General Medicine ,Viral Load ,medicine.disease ,Infectious Diseases ,Therapeutic drug monitoring ,Child, Preschool ,Cytomegalovirus Infections ,DNA, Viral ,Pediatrics, Perinatology and Child Health ,Quinazolines ,Female ,Drug Monitoring ,business ,medicine.drug - Abstract
Little information on the efficacy and pharmacokinetics of letermovir among immunocompromised children is currently available. We describe here the use of letermovir in a 2-year-old immunocompromised child with ganciclovir-resistant cytomegalovirus disease who required extracorporeal membrane oxygenation. Detailed information on therapeutic-drug-monitoring measures and dosage adjustments for letermovir is provided.
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- 2019
8. Interpréter la pop mainstream ? Critique musicale et légitimation
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Thomas Mercier-Bellevue
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musiques populaires ,General Engineering ,culture de masse ,General Earth and Planetary Sciences ,hiérarchies culturelles ,réception critique ,lcsh:P87-96 ,Art ,General Environmental Science ,lcsh:Communication. Mass media - Abstract
La critique musicale, parce qu’elle est un opérateur essentiel de légitimation, contribue au discrédit dont souffre la pop mainstream. En étudiant le paradigme de la traductibilité herméneutique, dont la critique est tributaire, nous souhaitons mettre au jour les racines théoriques du sceau d’illégitimité dont ce genre musical est frappé. Ainsi, nous poserons les bases d’une critique musicale prenant en considération les spécificités de la pop.
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- 2019
9. Population pharmacokinetics and pharmacodynamics of the artesunate–mefloquine fixed dose combination for the treatment of uncomplicated falciparum malaria in African children
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Jean-René Kiechel, Laurent A. Decosterd, Bernhards Ogutu, Chantal Csajka, Monia Guidi, Gwenaelle Carn, Manel Aouri, and Thomas Mercier
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Male ,0301 basic medicine ,medicine.medical_specialty ,lcsh:Arctic medicine. Tropical medicine ,lcsh:RC955-962 ,medicine.medical_treatment ,030231 tropical medicine ,030106 microbiology ,Population ,Artesunate ,Dihydroartemisinin ,lcsh:Infectious and parasitic diseases ,Antimalarials ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Pharmacokinetics ,Recurrence ,Internal medicine ,medicine ,Humans ,lcsh:RC109-216 ,Prospective Studies ,Population pharmacokinetics ,Malaria, Falciparum ,Artemisinin ,education ,education.field_of_study ,Dose-Response Relationship, Drug ,Mefloquine ,business.industry ,Antimalarials/pharmacokinetics ,Antimalarials/pharmacology ,Artesunate/pharmacokinetics ,Artesunate/pharmacology ,Child, Preschool ,Drug Combinations ,Female ,Infant ,Kenya ,Malaria, Falciparum/drug therapy ,Mefloquine/pharmacokinetics ,Mefloquine/pharmacology ,Research ,Area under the curve ,Infectious Diseases ,chemistry ,Pharmacodynamics ,Parasitology ,business ,medicine.drug - Abstract
Background The World Health Organization (WHO) recommends combinations of an artemisinin derivative plus an anti-malarial drug of longer half-life as treatment options for uncomplicated Plasmodium falciparum infections. In Africa, artesunate–mefloquine (ASMQ) is an infrequently used artemisinin-based combination therapy (ACT) because of perceived poor tolerance to mefloquine. However, the WHO has recommended reconsideration of the use of ASMQ in Africa. In this large clinical study, the pharmacokinetics (PK) of a fixed dose combination of ASMQ was investigated in an African paediatric population to support dosing recommendations used in Southeast Asia and South America. Methods Among the 472 paediatric patients aged 6–59 months from six African centres included in the large clinical trial, a subset of 50 Kenyan children underwent intensive sampling to develop AS, its metabolite dihydroartemisinin (DHA) and MQ PK models. The final MQ PK model was validated using sparse data collected in the remaining participants (NONMEM®). The doses were one or two tablets containing 25/55 mg AS/MQ administered once a day for 3 days according to patients’ age. A sensitive LC–MS/MS method was used to quantify AS, DHA and MQ concentrations in plasma. An attempt was made to investigate the relationship between the absence/presence of malaria recrudescence and MQ area under the curve (AUC) using logistic regression. Results AS/DHA concentration–time profiles were best described using a one-compartment model for both compounds with irreversible AS conversion into DHA. AS/DHA PK were characterized by a significant degree of variability. Body weight affected DHA PK parameters. MQ PK was characterized by a two-compartment model and a large degree of variability. Allometric scaling of MQ clearances and volumes of distribution was used to depict the relationship between MQ PK and body weight. No association was found between the model predicted AUC and appearance of recrudescence. Conclusions The population pharmacokinetic models developed for both AS/DHA and MQ showed a large variability in drug exposure in the investigated African paediatric population. The largest contributor to this variability was body weight, which is accommodated for by the ASMQ fixed dose combination (FDC) dosing recommendation. Besides body weight considerations, there is no indication that the dosage should be modified in children with malaria compared to adults. Trial registration Pan African Clinical Trials Registry PACTR201202000278282 registration date 2011/02/16
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- 2019
10. Cardiac Implantable Electronic Device–Related Infection Due to Granulicatella adiacens
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Thomas Mercier, Christoph auf der Maur, Beat Sonderegger, Bernd Klaeser, Kerstin Wustmann, Fabian Noti, Annina Elisabeth Büchi, Markus Schwerzmann, Corinne Ruppen, and Parham Sendi
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0301 basic medicine ,medicine.medical_specialty ,business.industry ,Granulicatella adiacens ,030106 microbiology ,Clinical course ,Nutritionally Variant Streptococci ,610 Medicine & health ,medicine.disease ,03 medical and health sciences ,0302 clinical medicine ,Infectious Diseases ,Oncology ,Curative treatment ,Device related infection ,570 Life sciences ,biology ,Medicine ,Endocarditis ,030212 general & internal medicine ,business ,Intensive care medicine ,Granulicatella ,biofilm infection ,cardiac device-related infection ,endocarditis ,nutritionally variant streptococci - Abstract
Cardiac implantable electronic device-related infection is clinically challenging. Curative treatment commonly includes system removal. A case caused by Granulicatella adiacens occurred in a 32-year-old woman. Clinical course, literature review, and biofilm investigations enabled successful antibiotic management without system removal.
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- 2019
11. Control of variable-speed pumps used as turbines for flexible grid-connected power generation
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Clément Hardy, Emmanuel De Jaeger, Pierre Van Tichelen, Mathieu Olivier, Thomas Mercier, and UCL - SST/IMMC/MEED - Mechatronic, Electrical Energy, and Dynamics Systems
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Variable-speed drives ,Stabillity ,Computer science ,020209 energy ,Energy Engineering and Power Technology ,02 engineering and technology ,Automotive engineering ,Power generation control ,0202 electrical engineering, electronic engineering, information engineering ,Pump-as-turbine ,Electrical and Electronic Engineering ,Hydropower ,Hydraulic turbines ,business.industry ,020208 electrical & electronic engineering ,Rotational speed ,Grid ,Hydroelectric power generation ,Renewable energy ,Power (physics) ,Electricity generation ,Transient (oscillation) ,business ,Stability ,Power control - Abstract
The increasing accommodation of intermittent renewable energies into power grids creates needs for additional flexibility in power generation. In the field of hydropower research, this has translated into significant attention paid to the larger control possibilities brought by power electronics converters. Through theoretical analysis and transient simulations, the present paper investigates the power control of a pump-as-turbine fed by a reservoir, and driving an induction machine, itself connected to the grid through a full-scale power converter. The modelling of each part of the system is thoroughly discussed and two control strategies are considered, namely the direct control of power through the electromagnetic torque, and the indirect control of power through the rotational speed. Theoretical analysis and transient simulations show that the first control strategy may lead to unstable operation, depending on the system and control parameters, while the second ensures the system stability.
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- 2019
12. Cardiac Implantable Electronic Device-Related Infection Due to
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Parham, Sendi, Kerstin, Wustmann, Annina E, Büchi, Fabian, Noti, Bernd, Klaeser, Beat, Sonderegger, Christoph, Auf der Maur, Thomas, Mercier, Markus, Schwerzmann, and Corinne, Ruppen
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nutritionally variant streptococci ,Brief Report ,cardiac device-related infection ,endocarditis ,Granulicatella adiacens ,biofilm infection - Abstract
Cardiac implantable electronic device–related infection is clinically challenging. Curative treatment commonly includes system removal. A case caused by Granulicatella adiacens occurred in a 32-year-old woman. Clinical course, literature review, and biofilm investigations enabled successful antibiotic management without system removal.
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- 2018
13. Corrigendum to 'LC–MS/MS method for the simultaneous analysis of seven antimalarials and two active metabolites in dried blood spots for applications in field trials: Analytical and clinical validation' [J. Pharm. Biomed. Anal. 154 (2018) 263–277]
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Thierry Buclin, Carine Bardinet, Blaise Genton, Thomas Mercier, Emilie Pothin, Sylvain Prod'hom, Laurent A. Decosterd, Joanna Gallay, and Dany Spaggiari
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Chromatography ,Spots ,Chemistry ,Clinical Biochemistry ,Drug Discovery ,Lc ms ms ,Pharmaceutical Science ,Dried blood ,Spectroscopy ,Active metabolite ,Analytical Chemistry - Published
- 2020
14. Interplay Between Phosphorylation and O-GlcNAcylation of Sarcomeric Proteins in Ischemic Heart Failure
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Thomas, Mercier, Marion, Bouvet, Emilie, Dubois-Deruy, Arthur, Dechaumes, Olivia, Beseme, Vincent, Richard, Paul, Mulder, and Florence, Pinet
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Endocrinology ,O-GlcNAcylation ,lcsh:RC648-665 ,phosphorylation ,rat models ,heart failure ,desmin ,systolic ,macromolecular substances ,interplay ,lcsh:Diseases of the endocrine glands. Clinical endocrinology ,Original Research - Abstract
Post-translational modifications (PTMs) of sarcomeric proteins could participate to left ventricular (LV) remodeling and contractile dysfunction leading in advanced heart failure (HF) with altered ejection fraction. Using an experimental rat model of HF (ligation of left coronary artery) and phosphoproteomic analysis, we identified an increase of desmin phosphorylation and a decrease of desmin O-N-acetylglucosaminylation (O-GlcNAcylation). We aim to characterize interplay between phosphorylation and O-GlcNAcylation for desmin in primary cultures of cardiomyocyte by specific O-GlcNAcase (OGA) inhibition with thiamet G and silencing O-GlcNAc transferase (OGT) and, in perfused heart perfused with thiamet G in sham- and HF-rats. In each model, we found an efficiency of O-GlcNAcylation modulation characterized by the levels of O-GlcNAcylated proteins and OGT expression (for silencing experiments in cells). In perfused heart, we found an improvement of cardiac function under OGA inhibition. But none of the treatments either in in vitro or ex vivo cardiac models, induced a modulation of desmin, phosphorylated and O-GlcNAcylated desmin expression, despite the presence of O-GlcNAc moities in cardiac desmin. Our data suggests no interplay between phosphorylation and O-GlcNAcylation of desmin in HF post-myocardial infarction. The future requires finding the targets in heart involved in cardiac improvement under thiamet G treatment.
- Published
- 2018
15. Tamoxifen prolongs survival and alleviates symptoms in mice with fatal X-linked myotubular myopathy
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E. Gayi, Hesham M. Ismail, Laurent A. Decosterd, Leonardo Scapozza, M. Sierra, Jocelyn Laporte, Belinda S. Cowling, Xènia Massana Muñoz, Olivier M. Dorchies, Thomas Mercier, L. Neff, Université de Lausanne = University of Lausanne (UNIL), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Lausanne University Hospital, and univOAK, Archive ouverte
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0301 basic medicine ,XLMTM ,Male ,Myotubularin ,General Physics and Astronomy ,Gene Expression ,Disease ,Dynamin II ,Mice ,Myofibrils ,Paralysis ,lcsh:Science ,skin and connective tissue diseases ,Excitation Contraction Coupling ,Class II Phosphatidylinositol 3-Kinases ,Mice, Knockout ,ddc:615 ,Multidisciplinary ,Protein Tyrosine Phosphatases, Non-Receptor ,Phenotype ,X-linked myotubular myopathy ,3. Good health ,Disease Progression ,Female ,medicine.symptom ,medicine.drug ,Myopathies, Structural, Congenital ,[SDV.OT]Life Sciences [q-bio]/Other [q-bio.OT] ,Science ,Longevity ,Motor Activity ,Protective Agents ,General Biochemistry, Genetics and Molecular Biology ,Article ,03 medical and health sciences ,Breast cancer ,medicine ,Animals ,Humans ,Muscle, Skeletal ,business.industry ,[SDV.OT] Life Sciences [q-bio]/Other [q-bio.OT] ,General Chemistry ,medicine.disease ,Electric Stimulation ,DNM2 ,Disease Models, Animal ,Tamoxifen ,030104 developmental biology ,Cancer research ,lcsh:Q ,Genes, Lethal ,business - Abstract
X-linked myotubular myopathy (XLMTM, also known as XLCNM) is a severe congenital muscular disorder due to mutations in the myotubularin gene, MTM1. It is characterized by generalized hypotonia, leading to neonatal death of most patients. No specific treatment exists. Here, we show that tamoxifen, a well-known drug used against breast cancer, rescues the phenotype of Mtm1-deficient mice. Tamoxifen increases lifespan several-fold while improving overall motor function and preventing disease progression including lower limb paralysis. Tamoxifen corrects functional, histological and molecular hallmarks of XLMTM, with improved force output, myonuclei positioning, myofibrillar structure, triad number, and excitation-contraction coupling. Tamoxifen normalizes the expression level of the XLMTM disease modifiers DNM2 and PI3KC2B, likely contributing to the phenotypic rescue. Our findings demonstrate that tamoxifen is a promising candidate for clinical evaluation in XLMTM patients., X-linked myotubular myopathy (XLMTM) is a severe muscle disease with no effective treatment. Here, the authors show that tamoxifen, a drug used to treat breast cancer, rescues the pathology in a mouse model of the disease, at least in part by normalizing expression of the disease modifier proteins DNM2 and BIN1
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- 2018
16. The Antimalarial Drug Artesunate Attenuates Cardiac Injury in A Rodent Model of Myocardial Infarction
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Thomas Mercier, Mara Rogazzo, Christoph Thiemermann, Amar Kapoor, Lukas Martin, Massimo Collino, Jianmin Chen, Areeg I. Khan, and Laurent A. Decosterd
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0301 basic medicine ,MAPK/ERK pathway ,Gerontology ,Male ,STAT3 Transcription Factor ,MAP Kinase Signaling System ,medicine.medical_treatment ,Myocardial Infarction ,Dihydroartemisinin ,Artesunate ,030204 cardiovascular system & hematology ,Pharmacology ,Critical Care and Intensive Care Medicine ,03 medical and health sciences ,chemistry.chemical_compound ,Antimalarials ,Phosphatidylinositol 3-Kinases ,0302 clinical medicine ,medicine ,Animals ,Myocardial infarction ,Rats, Wistar ,Glycogen synthase ,PI3K/AKT/mTOR pathway ,Active metabolite ,Glycogen Synthase Kinase 3 beta ,biology ,business.industry ,Myocardium ,medicine.disease ,Rats ,Disease Models, Animal ,030104 developmental biology ,Mechanism of action ,chemistry ,Emergency Medicine ,biology.protein ,medicine.symptom ,business ,Proto-Oncogene Proteins c-akt - Abstract
Ischemic heart disease remains the leading cause of morbidity and mortality in the Western world. Artesunate is the WHO-recommended drug of choice for complicated malaria (with organ failure). The administration of high doses of artesunate is safe in healthy volunteers (up to 8 mg/kg i.v.) and patients with severe malaria (2.4 mg/kg i.v.). We investigated the effects of artesunate (1 mg/kg) or its active metabolite dihydroartemisinin (DHA; 0.1 mg/kg) in a model of transient myocardial ischemia/reperfusion (I/R) and evaluated the mechanism of action of the observed cardioprotective effects of artesunate and DHA. We report here for the first time that the administration of artesunate at the onset of reperfusion attenuates the myocardial injury associated with I/R. The observed beneficial effects of artesunate are associated with activation of the PI3K/Akt/ERK 1/2 (RISK) pathway, activation of endothelial nitric oxide synthase, inhibition of glycogen synthase kinase-3β, inhibition of nuclear factor kappa B, and activation of the STAT3 (SAFE) pathway. In conclusion, as artesunate has an excellent safety profile, the above data should stimulate clinical trials in patients with acute coronary syndromes.
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- 2018
17. Is Penicillin Plus Gentamicin Synergistic Against Sessile Group B Streptococcal Isolates? An in Vivo Study With an Experimental Model of Foreign-Body Infection
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Corinne Ruppen, Thomas Mercier, Denis Grandgirard, Stephen L. Leib, Cristina El Haj, Oscar Murillo, Laurent Decosterd, and Parham Sendi
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0301 basic medicine ,Microbiology (medical) ,medicine.medical_specialty ,030106 microbiology ,Population ,lcsh:QR1-502 ,610 Medicine & health ,gentamicin ,medicine.disease_cause ,Gastroenterology ,Microbiology ,Group B ,lcsh:Microbiology ,Streptococcus agalactiae ,03 medical and health sciences ,0302 clinical medicine ,In vivo ,Internal medicine ,synergism ,medicine ,foreign bodies ,030212 general & internal medicine ,education ,Original Research ,education.field_of_study ,business.industry ,Streptococcus ,Estreptococs ,Penicillin ,biofilms ,penicillins ,Regimen ,Biofilms ,570 Life sciences ,biology ,Gentamicin ,business ,Penicil·lina ,medicine.drug - Abstract
The rate of invasive group B Streptococcus (GBS) infections is steadily increasing, particularly in older persons and in adults with diabetes and other comorbidities. This population includes persons with a foreign body (e.g., who have undergone arthroplasty). In a rat tissue cage model, we evaluated the efficacy of adjunctive gentamicin (GEN) administered systemically (5 mg/kg body weight) every 24 h, or locally (12.5 mg/L tissue cage concentration) every 24 or 72 h, in combination with penicillin (PEN) administered systemically (250,000 IU/kg body weight three times per day). The efficacy was evaluated on two different sessile forms of GBS: transition (i.e., in between planktonic and biofilm) and biofilm. After 3 days of treatment, the mean bacterial load reduction of transition-form GBS was greater in all PEN-GEN combination groups than in the PEN monotherapy group ( P ≤ 0.03). The 6-day regimen decreased the bacterial load significantly in comparison to the 3-day regimen, irrespective of growth form and adjunctive GEN ( P < 0.01). After 6 days of treatment, the mean reduction in transition-form GBS was greater with PEN plus GEN administered locally every 24 h than with PEN monotherapy ( P = 0.03). These results were not confirmed with biofilm GBS. The difference in mean bacterial load reduction between all PEN-GEN and PEN monotherapy groups was
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- 2018
18. Quantification of the next-generation oral anti-tumor drugs dabrafenib, trametinib, vemurafenib, cobimetinib, pazopanib, regorafenib and two metabolites in human plasma by liquid chromatography-tandem mass spectrometry
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Evelina Cardoso, Krisztian Homicsko, Manuel Diezi, Laurène Cagnon, Chantal Csajka, Kim Ellefsen-Lavoie, Anna Dorothea Wagner, Thierry Buclin, Laurent A. Decosterd, Thomas Mercier, Nicolas Widmer, and Olivier Michielin
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Indoles ,Pyridines ,Clinical Biochemistry ,Administration, Oral ,Imidazoles/administration & dosage/blood/chemistry/pharmacokinetics ,Tandem mass spectrometry ,01 natural sciences ,Biochemistry ,High-performance liquid chromatography ,Analytical Chemistry ,Indoles/administration & dosage/blood/chemistry/pharmacokinetics ,chemistry.chemical_compound ,0302 clinical medicine ,Piperidines ,Liquid chromatography–mass spectrometry ,Tandem Mass Spectrometry ,Limit of Detection ,Oximes ,Pyridones/administration & dosage/blood/chemistry/pharmacokinetics ,Child ,Chromatography, High Pressure Liquid ,Trametinib ,Sulfonamides ,ddc:615 ,medicine.diagnostic_test ,Pyrimidines/administration & dosage/blood/chemistry/pharmacokinetics ,Imidazoles ,General Medicine ,Sulfonamides/administration & dosage/blood/chemistry/pharmacokinetics ,030220 oncology & carcinogenesis ,Phenylurea Compounds/administration & dosage/blood/chemistry/pharmacokinetics ,medicine.drug ,Indazoles ,Pyridones ,Antineoplastic Agents/administration & dosage/blood/chemistry/pharmacokinetics ,Antineoplastic Agents ,Pyrimidinones ,Mass spectrometry ,Tandem Mass Spectrometry/methods ,03 medical and health sciences ,Azetidines/administration & dosage/blood/chemistry/pharmacokinetics ,Piperidines/administration & dosage/blood/chemistry/pharmacokinetics ,medicine ,Humans ,Pyridines/administration & dosage/blood/chemistry/pharmacokinetics ,Cobimetinib ,Oximes/administration & dosage/blood/chemistry/pharmacokinetics ,Chromatography ,Phenylurea Compounds ,010401 analytical chemistry ,Reproducibility of Results ,Dabrafenib ,Cell Biology ,0104 chemical sciences ,Pyrimidines ,chemistry ,Vemurafenib ,Therapeutic drug monitoring ,Linear Models ,Azetidines ,Pyrimidinones/administration & dosage/blood/chemistry/pharmacokinetics ,Chromatography, High Pressure Liquid/methods - Abstract
A sensitive and selective method of high performance liquid chromatography (HPLC) coupled to tandem mass spectrometry (MS/MS) has been developed for the simultaneous quantification of six anticancer protein kinase inhibitors (PKIs), dabrafenib, trametinib, vemurafenib, cobimetinib, pazopanib, regorafenib, and two active metabolites (regorafenib-M2 and regorafenib-M5) in human plasma. Plasma protein precipitation with methanol enables the sample extraction of 100 μL aliquot of plasma. Analytes are detected by electrospray triple-stage quadrupole mass spectrometry and quantified using the calibration curves with stable isotope-labeled internal standards. The method was validated based on FDA recommendations, including assessment of extraction yield (74-104%), matrix effects, analytical recovery (94-104%) with low variability (
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- 2018
19. LC-MS/MS method for the simultaneous analysis of seven antimalarials and two active metabolites in dried blood spots for applications in field trials: Analytical and clinical validation
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Dany Spaggiari, Joanna Gallay, Carine Bardinet, Blaise Genton, Emilie Pothin, Sylvain Prod'hom, Thierry Buclin, Laurent A. Decosterd, and Thomas Mercier
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Sulfadoxine ,medicine.medical_treatment ,Clinical Biochemistry ,Pharmaceutical Science ,Amodiaquine ,Lumefantrine ,030226 pharmacology & pharmacy ,01 natural sciences ,Analytical Chemistry ,03 medical and health sciences ,chemistry.chemical_compound ,Antimalarials ,Plasma ,0302 clinical medicine ,Pharmacokinetics ,Tandem Mass Spectrometry ,Drug Discovery ,Blood plasma ,medicine ,Humans ,Artemether ,Spectroscopy ,Quinine ,Fluorenes ,Chromatography ,Chemistry ,Mefloquine ,010401 analytical chemistry ,Temperature ,Reproducibility of Results ,Artemisinins ,3. Good health ,0104 chemical sciences ,Ethanolamines ,Dried Blood Spot Testing ,medicine.drug ,Chromatography, Liquid - Abstract
In epidemiological studies, antimalarials measurements in blood represent the best available marker of drugs exposure at population level, an important driver for the emergence of drug resistance. We have developed a liquid chromatography-tandem mass spectrometry method (LC-MS/MS) for the simultaneous quantification of 7 frequently used antimalarials (amodiaquine, chloroquine, quinine, sulfadoxine, pyrimethamine, mefloquine, lumefantrine) and 2 active metabolites (N-desethyl-amodiaquine, desbutyl-lumefantrine) in 10-μl dried blood spots (DBS). This sampling approach is suitable for field studies wherein blood samples processing, transportation and storage are problematic. Sample preparation included extraction from a 3 mm-disk punched out of the DBS with 100-μl of methanol + 1% formic acid containing deuterated internal standards for all drugs. Good performances were achieved in terms of trueness (-12.1 to +11.1%), precision (1.4-15.0%) and sensitivity, with lower limits of quantification comprised between 2 ng/ml (sulfadoxine) and 20 ng/ml (chloroquine, quinine, pyrimethamine, mefloquine, lumefantrine and desbutyl-lumefantrine). All analytes were stable in DBS kept for 24 h at room temperature and at 37 °C. The developed assay was applied within the frame of a pharmacokinetic study including 16 healthy volunteers who received a single dose of artemether-lumefantrine. Lumefantrine concentrations in plasma and in DBS were highly correlated (R = 0.97) at all time points, confirming the assumption that lumefantrine concentrations determined in DBS confidently reflect blood concentrations. The blood/plasma ratio of 0.56 obtained using the Bland-Altman approach (and corresponding to the slope of the linear regression) is in line with very low penetration of lumefantrine into red blood cells. This sensitive multiplex LC-MS/MS assay enabling the simultaneous analysis of antimalarials in DBS is suitable for epidemiological studies in field conditions.
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- 2017
20. Treatment of pleural malignancies by photo-induction combined to systemic chemotherapy: Proof of concept on rodent lung tumors and feasibility study on porcine chest cavities
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Solange Peters, Michaël Bensimon, Xingyu Wang, Elodie Debefve, Fabrizio Gronchi, Georges Wagnières, Igor Letovanec, Thomas Mercier, Hans-Beat Ris, Jean Yannis Perentes, and Laurent A. Decosterd
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Cisplatin ,Chemotherapy ,Pathology ,medicine.medical_specialty ,Lung ,business.industry ,medicine.medical_treatment ,Lipoplatin ,Photodynamic therapy ,Dermatology ,medicine.disease ,medicine.anatomical_structure ,medicine ,Adenocarcinoma ,Surgery ,Sarcoma ,Mesothelioma ,Nuclear medicine ,business ,medicine.drug - Abstract
Background: Low-dose, Visudyne (R)-mediated photodynamic therapy (photo-induction) was shown to selectively enhance tumor vessel transport causing increased uptake of systemically administered chemotherapy in various tumor types grown on rodent lungs. The present experiments explore the efficacy of photo-induced vessel modulation combined to intravenous (IV) liposomal cisplatin (Lipoplatin (R)) on rodent lung tumors and the feasibility/toxicity of this approach in porcine chest cavities. Material and Methods: Three groups of Fischer rats underwent orthotopic sarcoma (n = 14), mesothelioma (n = 14), or adenocarcinoma (n = 12) implantation on the left lung. Half of the animals of each group had photoinduction (0.0625 mg/kg Visudyne (R), 10 J/cm(2)) followed by IV administration of Lipoplatin (R) w (5 mg/kg) and the other half received Lipoplatin (R) without photo-induction. Then, two groups of minipigs underwent intrapleural thoracoscopic (VATS) photo-induction (0.0625 mg/kg Visudyne (R); 30 J/cm(2) hilum; 10 J/cm(2) apex/diaphragm) with in situ light dosimetry in combination with IV Lipoplatin (R) administration (5 mg/kg). Protocol I (n = 6) received Lipoplatin (R) immediately after light delivery and Protocol II (n = 9) 90 minutes before light delivery. Three additional animals received Lipoplatin (R) and VATS pleural biopsies but no photo-induction (controls). Lipoplatin (R) concentrations were analyzed in blood and tissues before and at regular intervals after photo-induction using inductively coupled plasma mass spectrometry. Results: Photo-induction selectively increased Lipoplatin (R) uptake in all orthotopic tumors. It significantly increased the ratio of tumor to lung Lipoplatin (R) concentration in sarcoma (P = 0.0008) and adenocarcinoma (P = 0.01) but not in mesothelioma, compared to IV drug application alone. In minipigs, intrapleural photo-induction combined to systemic Lipoplatin (R) was well tolerated with no toxicity at 7 days for both treatment protocols. The pleural Lipoplatin (R) concentrations were not significantly different at 10 and 30 J/cm(2) locations but they were significantly higher in protocol I compared to II (2.37 +/- 0.7 vs. 1.37 +/- 0.7 ng/mg, P < 0.001). Conclusion: Visudyne (R)-mediated photo-induction selectively enhances the uptake of IV administered Lipoplatin (R) in rodent lung tumors. Intrapleural VATS photo-induction with identical treatment conditions combined to IV Lipoplatin chemotherapy is feasible and well tolerated in a porcine model. Lasers Surg. Med. 47:807-816, 2015. (C) 2015 Wiley Periodicals, Inc.
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- 2015
21. Population Pharmacokinetics and Clinical Response for Artemether-Lumefantrine in Pregnant and Nonpregnant Women with Uncomplicated Plasmodium falciparum Malaria in Tanzania
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Dominic Mosha, Blaise Genton, Monia Guidi, Felista Mwingira, Thomas Mercier, Laurent A. Decosterd, Chantal Csajka, and Salim Abdulla
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Adult ,medicine.medical_specialty ,Artemether/lumefantrine ,Adolescent ,Pregnancy Trimester, Third ,Plasmodium falciparum ,Biological Availability ,Clinical Therapeutics ,Pharmacology ,Lumefantrine ,Severity of Illness Index ,Drug Administration Schedule ,Antimalarials ,chemistry.chemical_compound ,Pharmacokinetics ,Pregnancy ,medicine ,Humans ,Pharmacology (medical) ,Treatment Failure ,Malaria, Falciparum ,Biotransformation ,Fluorenes ,Models, Statistical ,Obstetrics ,business.industry ,Artemether, Lumefantrine Drug Combination ,Case-control study ,Odds ratio ,medicine.disease ,Artemisinins ,NONMEM ,Drug Combinations ,Infectious Diseases ,chemistry ,Ethanolamines ,Case-Control Studies ,Pregnancy Trimester, Second ,Female ,business ,Malaria ,medicine.drug - Abstract
Artemether-lumefantrine (AL) is the first-line treatment for uncomplicated malaria in the second and third trimesters of pregnancy. Its efficacy during pregnancy has recently been challenged due to altered pharmacokinetic (PK) properties in this vulnerable group. The aim of this study was to determine the PK profile of AL in pregnant and nonpregnant women and assess their therapeutic outcome. Thirty-three pregnant women and 22 nonpregnant women with malaria were treated with AL (80/480 mg) twice daily for 3 days. All patients provided five venous plasma samples for drug quantification at random times over 7 days. Inter- and intraindividual variability was assessed, and the effects of covariates were quantified using a nonlinear mixed-effects modeling approach (NONMEM). A one-compartment model with first-order absorption and elimination with linear metabolism from drug to metabolite fitted the data best for both arthemether (AM) and lumefantrine (LF) and their metabolites. Pregnancy status and diarrhea showed a significant influence on LF PK. The relative bioavailability of lumefantrine and its metabolism rate into desmethyl-lumefantrine were, respectively, 34% lower and 78% higher in pregnant women than in nonpregnant patients. The overall PCR-uncorrected treatment failure rates were 18% in pregnant women and 5% in nonpregnant women (odds ratio [OR] = 4.04; P value of 0.22). A high median day 7 lumefantrine concentration was significantly associated with adequate clinical and parasitological response ( P = 0.03). The observed reduction in the relative bioavailability of lumefantrine in pregnant women may explain the higher treatment failure in this group, mostly due to lower posttreatment prophylaxis. Hence, a modified treatment regimen of malaria in pregnancy should be considered.
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- 2014
22. A highly sensitive LC-tandem MS assay for the measurement in plasma and in urine of salbutamol administered by nebulization during mechanical ventilation in healthy volunteers
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Anne-Laure Sidler-Moix, Markoulina Berger-Gryllaki, Thomas Mercier, André Pannatier, Jacques Cotting, Ermindo R. Di Paolo, and Laurent A. Decosterd
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Pharmacology ,Analyte ,Chromatography ,Inhalation ,Chemistry ,Coefficient of variation ,Clinical Biochemistry ,Selected reaction monitoring ,General Medicine ,Urine ,Mass spectrometry ,Biochemistry ,High-performance liquid chromatography ,Analytical Chemistry ,Drug Discovery ,Salbutamol ,medicine ,Molecular Biology ,medicine.drug - Abstract
The new-generation nebulizers are commonly used for the administration of salbutamol in mechanically ventilated patients. The different modes of administration and new devices have not been compared. We developed a liquid chromatography-tandem mass spectrometry method for the determination of concentrations as low as 0.05 ng/mL of salbutamol, corresponding to the desired plasma concentration after inhalation. Salbutamol quantification was performed by reverse-phase HPLC. Analyte quantification was performed by electrospray ionization-triple quadrupole mass spectrometry using selected reaction monitoring detection ESI in the positive mode. The method was validated over concentrations ranging from 0.05 to 100 ng/mL in plasma and from 0.18 to 135 ng/mL in urine. The method is precise, with mean inter-day coefficient of variation (CV%) within 3.1-8.3% in plasma and 1.3-3.9% in urine, as well as accurate. The proposed method was found to reach the required sensitivity for the evaluation of different nebulizers as well as nebulization modes. The present assay was applied to examine whether salbutamol urine levels, normalized with the creatinine levels, correlated with the plasma concentrations. A suitable, convenient and noninvasive method of monitoring patients receiving salbutamol by mechanical ventilation could be implemented.
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- 2011
23. A single LC-tandem mass spectrometry method for the simultaneous determination of 14 antimalarial drugs and their metabolites in human plasma
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Blaise Genton, Piero Olliaro, Thomas Mercier, Boris Zanolari, Jérôme Biollaz, Jennifer Keiser, Eva Maria Hodel, and Laurent A. Decosterd
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medicine.medical_treatment ,Clinical Biochemistry ,Dihydroartemisinin ,Amodiaquine ,Lumefantrine ,030226 pharmacology & pharmacy ,01 natural sciences ,Biochemistry ,Analytical Chemistry ,03 medical and health sciences ,chemistry.chemical_compound ,Antimalarials ,0302 clinical medicine ,Liquid chromatography–mass spectrometry ,Tandem Mass Spectrometry ,Piperaquine ,medicine ,Humans ,Artemether ,Artemisinin ,Pyronaridine ,Chromatography ,Chemistry ,010401 analytical chemistry ,Cell Biology ,General Medicine ,3. Good health ,0104 chemical sciences ,Malaria ,medicine.drug - Abstract
Among the various determinants of treatment response, the achievement of sufficient blood levels is essential for curing malaria. For helping us at improving our current understanding of antimalarial drugs pharmacokinetics, efficacy and toxicity, we have developed a liquid chromatography–tandem mass spectrometry method (LC–MS/MS) requiring 200 μl of plasma for the simultaneous determination of 14 antimalarial drugs and their metabolites which are the components of the current first-line combination treatments for malaria (artemether, artesunate, dihydroartemisinin, amodiaquine, N-desethyl-amodiaquine, lumefantrine, desbutyl-lumefantrine, piperaquine, pyronaridine, mefloquine, chloroquine, quinine, pyrimethamine and sulfadoxine). Plasma is purified by a combination of protein precipitation, evaporation and reconstitution in methanol/ammonium formate 20 mM (pH 4.0) 1:1. Reverse-phase chromatographic separation of antimalarial drugs is obtained using a gradient elution of 20 mM ammonium formate and acetonitrile both containing 0.5% formic acid, followed by rinsing and re-equilibration to the initial solvent composition up to 21 min. Analyte quantification, using matrix-matched calibration samples, is performed by electro-spray ionization–triple quadrupole mass spectrometry by selected reaction monitoring detection in the positive mode. The method was validated according to FDA recommendations, including assessment of extraction yield, matrix effect variability, overall process efficiency, standard addition experiments as well as antimalarials short- and long-term stability in plasma. The reactivity of endoperoxide-containing antimalarials in the presence of hemolysis was tested both in vitro and on malaria patients samples. With this method, signal intensity of artemisinin decreased by about 20% in the presence of 0.2% hemolysed red-blood cells in plasma, whereas its derivatives were essentially not affected. The method is precise (inter-day CV%: 3.1–12.6%) and sensitive (lower limits of quantification 0.15–3.0 and 0.75–5 ng/ml for basic/neutral antimalarials and artemisinin derivatives, respectively). This is the first broad-range LC–MS/MS assay covering the currently in-use antimalarials. It is an improvement over previous methods in terms of convenience (a single extraction procedure for 14 major antimalarials and metabolites reducing significantly the analytical time), sensitivity, selectivity and throughput. While its main limitation is investment costs for the equipment, plasma samples can be collected in the field and kept at 4 °C for up to 48 h before storage at −80 °C. It is suited to detecting the presence of drug in subjects for screening purposes and quantifying drug exposure after treatment. It may contribute to filling the current knowledge gaps in the pharmacokinetics/pharmacodynamics relationships of antimalarials and better define the therapeutic dose ranges in different patient populations.
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- 2009
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24. Pharmacokinetic parameters of artesunate and dihydroartemisinin in rats infected with Fasciola hepatica
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Thomas Mercier, Jennifer Keiser, Laurent A. Decosterd, Nancy Perrottet, Boris Zanolari, and Marie-Stella Gruyer
- Subjects
Microbiology (medical) ,Fascioliasis ,medicine.medical_treatment ,Metabolite ,Dihydroartemisinin ,Artesunate ,Biology ,Pharmacology ,01 natural sciences ,Mass Spectrometry ,03 medical and health sciences ,chemistry.chemical_compound ,Plasma ,Pharmacokinetics ,Oral administration ,Animals ,Anthelmintics/administration & dosage/*pharmacokinetics ,Area Under Curve ,Artemisinins/administration & dosage/*pharmacokinetics ,Chromatography, Liquid ,Fasciola hepatica/drug effects ,Fascioliasis/*drug therapy/parasitology ,Female ,Plasma/*chemistry ,Rats ,Blood plasma ,medicine ,Fasciola hepatica ,Pharmacology (medical) ,Artemisinin ,Anthelmintics ,0303 health sciences ,030306 microbiology ,010401 analytical chemistry ,biology.organism_classification ,Artemisinins ,3. Good health ,0104 chemical sciences ,Infectious Diseases ,chemistry ,medicine.drug - Abstract
OBJECTIVES: The pharmacokinetic (PK) parameters of artesunate, recently discovered to possess promising trematocidal activity, and its main metabolite dihydroartemisinin (DHA) were determined in rats infected with hepatic and biliary stages of Fasciola hepatica and compared with uninfected rats after single intragastric and intravenous (iv) doses. METHODS: Rats infected with F. hepatica for 25 and 83 days and uninfected rats were cannulated in the right jugular vein and blood samples were withdrawn at selected timepoints following 10 mg/kg of iv and a single 100 mg/kg oral dose of artesunate. Plasma was analysed for artesunate and DHA by liquid chromatography coupled to tandem mass spectrometry. RESULTS: Rats harbouring juvenile and adult F. hepatica infections revealed considerable changes in PK parameters of artesunate and DHA. Following oral administration, maximum plasma concentrations (C(max)) of artesunate and DHA were 1.8-2.3-fold higher in infected rats [artesunate: 1334 +/- 1404 ng/mL (no infection) versus 2454 +/- 1494 ng/mL (acute infection) and 2768 +/- 538 ng/mL (chronic infection); DHA: 3802 +/- 2149 ng/mL (no infection) versus 6507 +/- 3283 ng/mL (acute infection) and 9093 +/- 884 ng/mL (chronic infection)]. The AUCs of artesunate and DHA were 2.1-4.4-fold greater in infected rats. An opposite trend was observed after iv injection. C(max) and AUC of artesunate and DHA following iv dosing were 5784 +/- 3718 and 140 938 +/- 128 783 ng.min/mL and 3849 +/- 3060 and 86 107 +/- 41 863 ng.min/mL, respectively, in uninfected rats versus 2623 +/- 1554 and 21 617 +/- 12 230 ng.min/mL and 2835 +/- 980 and 64 290 +/- 29 057 ng.min/mL, respectively, in rats harbouring a chronic infection. The elimination half-lives (t(1/2)) of artesunate and DHA were considerably altered in infected rats following oral and iv administration of artesunate. CONCLUSIONS: F. hepatica infections strongly influence the disposition kinetics of artesunate and its metabolite in rats. The clinical implications of this finding need to be carefully studied.
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- 2009
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25. High-throughput hydrophilic interaction chromatography coupled to tandem mass spectrometry for the optimized quantification of the anti-Gram-negatives antibiotic colistin A/B and its pro-drug colistimethate
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Frederic Tissot, Stéphane Wehrli, Thierry Buclin, Natascia Corti, C. Csajka, Oscar Marchetti, William Couet, Céline Gardiol, Laurent A. Decosterd, Monia Guidi, Thomas Mercier, Lausanne University Hospital, Lausanne university hospital, University hospital of Zurich [Zurich], Kantonsspital Winterthur (KSW), School of Pharmaceutical Sciences, University of Geneva [Switzerland], Pharmacologie des anti-infectieux (PHAR), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Poitiers - Faculté de Médecine et de Pharmacie, Université de Poitiers, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), University of Zurich, and Decosterd, Laurent A
- Subjects
1303 Biochemistry ,[SDV]Life Sciences [q-bio] ,610 Medicine & health ,Biochemistry ,High-performance liquid chromatography ,Analytical Chemistry ,Matrix (chemical analysis) ,Tandem Mass Spectrometry ,medicine ,Humans ,Prodrugs ,Solid phase extraction ,Chromatography, High Pressure Liquid ,ComputingMilieux_MISCELLANEOUS ,Polymyxin B ,Detection limit ,1602 Analytical Chemistry ,Chromatography ,medicine.diagnostic_test ,Colistin ,Chemistry ,Hydrophilic interaction chromatography ,Solid Phase Extraction ,Organic Chemistry ,General Medicine ,[SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences ,3. Good health ,10199 Clinic for Clinical Pharmacology and Toxicology ,Therapeutic drug monitoring ,Calibration ,Drug Monitoring ,Hydrophobic and Hydrophilic Interactions ,1605 Organic Chemistry ,medicine.drug ,Colistimethate - Abstract
Colistin is a last resort's antibacterial treatment in critically ill patients with multi-drug resistant Gram-negative infections. As appropriate colistin exposure is the key for maximizing efficacy while minimizing toxicity, individualized dosing optimization guided by therapeutic drug monitoring is a top clinical priority. Objective of the present work was to develop a rapid and robust HPLC-MS/MS assay for quantification of colistin plasma concentrations. This novel methodology validated according to international standards simultaneously quantifies the microbiologically active compounds colistin A and B, plus the pro-drug colistin methanesulfonate (colistimethate, CMS). 96-well micro-Elution SPE on Oasis Hydrophilic-Lipophilic-Balanced (HLB) followed by direct analysis by Hydrophilic Interaction Liquid Chromatography (HILIC) with Ethylene Bridged Hybrid--BEH--Amide phase column coupled to tandem mass spectrometry allows a high-throughput with no significant matrix effect. The technique is highly sensitive (limit of quantification 0.014 and 0.006 μg/mL for colistin A and B), precise (intra-/inter-assay CV 0.6-8.4%) and accurate (intra-/inter-assay deviation from nominal concentrations -4.4 to +6.3%) over the clinically relevant analytical range 0.05-20 μg/mL. Colistin A and B in plasma and whole blood samples are reliably quantified over 48 h at room temperature and at +4°C (6% deviation from nominal values) and after three freeze-thaw cycles. Colistimethate acidic hydrolysis (1M H2SO4) to colistin A and B in plasma was completed in vitro after 15 min of sonication while the pro-drug hydrolyzed spontaneously in plasma ex vivo after 4 h at room temperature: this information is of utmost importance for interpretation of analytical results. Quantification is precise and accurate when using serum, citrated or EDTA plasma as biological matrix, while use of heparin plasma is not appropriate. This new analytical technique providing optimized quantification in real-life conditions of the microbiologically active compounds colistin A and B offers a highly efficient tool for routine therapeutic drug monitoring aimed at individualizing drug dosing against life-threatening infections.
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- 2014
26. Operation ranges and dynamic capabilities of variable-speed pumped-storage hydropower
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Emmanuel Dejaeger, Mathieu Olivier, Thomas Mercier, and UCL - SST/IMMC/MEED - Mechatronic, Electrical Energy, and Dynamics Systems
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Flexibility (engineering) ,Pumped-storage hydroelectricity ,History ,business.industry ,Computer science ,020209 energy ,02 engineering and technology ,021001 nanoscience & nanotechnology ,Energy storage ,Computer Science Applications ,Education ,Renewable energy ,Reliability engineering ,Electric power system ,Electricity generation ,Power electronics ,0202 electrical engineering, electronic engineering, information engineering ,0210 nano-technology ,business ,Hydropower - Abstract
The development of renewable and intermittent power generation creates incentives for the development of both energy storage solutions and more flexible power generation assets. Pumped-storage hydropower (PSH) is the most established and mature energy storage technology, but recent developments in power electronics have created a renewed interest by providing PSH units with a variable-speed feature, thereby increasing their flexibility. This paper reviews technical considerations related to variable-speed PSH in link with the provision of primary frequency control, also referred to as frequency containment reserves (FCRs). Based on the detailed characteristics of a scale model pump-turbine, the variable-speed operation ranges in pump and turbine modes are precisely assessed and the implications for the provision of FCRs are highlighted. Modelling and control for power system studies are discussed, both for fixed- and variable-speed machines and simulation results are provided to illustrate the high dynamic capabilities of variable-speed PSH.
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- 2017
27. Multiplex Liquid Chromatography-Tandem Mass Spectrometry Assay for Simultaneous Therapeutic Drug Monitoring of Ribavirin, Boceprevir, and Telaprevir
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Chantal Csajka, Laurent A. Decosterd, Manel Aouri, Andri Rauch, Amalio Telenti, Thomas Mercier, Darius Moradpour, Thierry Buclin, and Matthias Cavassini
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Liver Cirrhosis ,Proline ,Metabolite ,Hepacivirus ,Pharmacology ,High-performance liquid chromatography ,Antiviral Agents ,Telaprevir ,Hepatitis ,chemistry.chemical_compound ,Pharmacokinetics ,Liquid chromatography–mass spectrometry ,Tandem Mass Spectrometry ,Boceprevir ,Ribavirin ,medicine ,Humans ,Pharmacology (medical) ,Chromatography ,medicine.diagnostic_test ,Infectious Diseases ,chemistry ,Therapeutic drug monitoring ,Drug Monitoring ,Oligopeptides ,medicine.drug ,Chromatography, Liquid - Abstract
New directly acting antivirals (DAAs) that inhibit hepatitis C virus (HCV) replication are increasingly used for the treatment of chronic hepatitis C. A marked pharmacokinetic variability and a high potential for drug-drug interactions between DAAs and numerous drug classes have been identified. In addition, ribavirin (RBV), commonly associated with hemolytic anemia, often requires dose adjustment, advocating for therapeutic drug monitoring (TDM) in patients under combined antiviral therapy. However, an assay for the simultaneous analysis of RBV and DAAs constitutes an analytical challenge because of the large differences in polarity among these drugs, ranging from hydrophilic (RBV) to highly lipophilic (telaprevir [TVR]). Moreover, TVR is characterized by erratic behavior on standard octadecyl-based reversed-phase column chromatography and must be separated from VRT-127394, its inactive C-21 epimer metabolite. We have developed a convenient assay employing simple plasma protein precipitation, followed by high-performance liquid chromatography coupled to tandem mass spectrometry (HPLC-MS/MS) for the simultaneous determination of levels of RBV, boceprevir, and TVR, as well as its metabolite VRT-127394, in plasma. This new, simple, rapid, and robust HPLC-MS/MS assay offers an efficient method of real-time TDM aimed at maximizing efficacy while minimizing the toxicity of antiviral therapy.
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- 2013
28. A highly sensitive LC-tandem MS assay for the measurement in plasma and in urine of salbutamol administered by nebulization during mechanical ventilation in healthy volunteers
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Anne-Laure, Sidler-Moix, Thomas, Mercier, Laurent A, Decosterd, Ermindo R, Di Paolo, Markoulina, Berger-Gryllaki, Jacques, Cotting, and André, Pannatier
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Adult ,Drug Stability ,Tandem Mass Spectrometry ,Nebulizers and Vaporizers ,Administration, Inhalation ,Humans ,Reproducibility of Results ,Albuterol ,Sensitivity and Specificity ,Chromatography, High Pressure Liquid - Abstract
The new-generation nebulizers are commonly used for the administration of salbutamol in mechanically ventilated patients. The different modes of administration and new devices have not been compared. We developed a liquid chromatography-tandem mass spectrometry method for the determination of concentrations as low as 0.05 ng/mL of salbutamol, corresponding to the desired plasma concentration after inhalation. Salbutamol quantification was performed by reverse-phase HPLC. Analyte quantification was performed by electrospray ionization-triple quadrupole mass spectrometry using selected reaction monitoring detection ESI in the positive mode. The method was validated over concentrations ranging from 0.05 to 100 ng/mL in plasma and from 0.18 to 135 ng/mL in urine. The method is precise, with mean inter-day coefficient of variation (CV%) within 3.1-8.3% in plasma and 1.3-3.9% in urine, as well as accurate. The proposed method was found to reach the required sensitivity for the evaluation of different nebulizers as well as nebulization modes. The present assay was applied to examine whether salbutamol urine levels, normalized with the creatinine levels, correlated with the plasma concentrations. A suitable, convenient and noninvasive method of monitoring patients receiving salbutamol by mechanical ventilation could be implemented.
- Published
- 2011
29. Multiplex Ultra-Performance Liquid Chromatography-Tandem Mass Spectrometry Method for Simultaneous Quantification in Human Plasma of Fluconazole, Itraconazole, Hydroxyitraconazole, Posaconazole, Voriconazole, Voriconazole-N-Oxide, Anidulafungin, and Caspofungin▿ †
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Thierry Calandra, Frederic Tissot, Oscar Marchetti, Thomas Mercier, Nicolas Widmer, Jacques Bille, Bertrand Rochat, Laurent A. Decosterd, Boris Zanolari, and Benoît Pesse
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Posaconazole ,Antifungal Agents ,Echinocandin ,Itraconazole ,Anidulafungin ,chemistry.chemical_compound ,Echinocandins ,Lipopeptides ,Liquid chromatography–mass spectrometry ,Caspofungin ,Tandem Mass Spectrometry ,medicine ,Humans ,Pharmacology (medical) ,Pharmacology ,Analytical Procedures ,Chromatography ,medicine.diagnostic_test ,Selected reaction monitoring ,Triazoles ,Infectious Diseases ,Pyrimidines ,chemistry ,Therapeutic drug monitoring ,Voriconazole ,Blood Chemical Analysis ,medicine.drug ,Chromatography, Liquid - Abstract
Therapeutic drug monitoring (TDM) may contribute to optimizing the efficacy and safety of antifungal therapy because of the large variability in drug pharmacokinetics. Rapid, sensitive, and selective laboratory methods are needed for efficient TDM. Quantification of several antifungals in a single analytical run may best fulfill these requirements. We therefore developed a multiplex ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method requiring 100 μl of plasma for simultaneous quantification within 7 min of fluconazole, itraconazole, hydroxyitraconazole, posaconazole, voriconazole, voriconazole- N -oxide, caspofungin, and anidulafungin. Protein precipitation with acetonitrile was used in a single extraction procedure for eight analytes. After reverse-phase chromatographic separation, antifungals were quantified by electrospray ionization-triple-quadrupole mass spectrometry by selected reaction monitoring detection using the positive mode. Deuterated isotopic compounds of azole antifungals were used as internal standards. The method was validated based on FDA recommendations, including assessment of extraction yields, matrix effect variability (
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- 2010
30. An ultra performance liquid chromatography-tandem MS assay for tamoxifen metabolites profiling in plasma: first evidence of 4'-hydroxylated metabolites in breast cancer patients
- Author
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E. Dahmane, Sandra Cruchon, Chantal Csajka, Khalil Zaman, Serge Leyvraz, Thomas Mercier, Boris Zanolari, Thierry Buclin, Nicole Guignard, and Laurent A. Decosterd
- Subjects
Antineoplastic Agents, Hormonal ,Formic acid ,Metabolite ,Clinical Biochemistry ,Breast Neoplasms ,Tandem mass spectrometry ,Hydroxylation ,Biochemistry ,High-performance liquid chromatography ,Sensitivity and Specificity ,Analytical Chemistry ,chemistry.chemical_compound ,Drug Stability ,Tandem Mass Spectrometry ,medicine ,Ammonium formate ,Protein precipitation ,Humans ,skin and connective tissue diseases ,Chromatography, High Pressure Liquid ,Chromatography ,Chemistry ,Selected reaction monitoring ,Reproducibility of Results ,Cell Biology ,General Medicine ,Tamoxifen ,Logistic Models ,Calibration ,Female ,medicine.drug - Abstract
There is increasing evidence that the clinical efficacy of tamoxifen, the first and most widely used targeted therapy for estrogen-sensitive breast cancer, depends on the formation of the active metabolites 4-hydroxy-tamoxifen and 4-hydroxy-N-desmethyl-tamoxifen (endoxifen). Large inter-individual variability in endoxifen plasma concentrations has been observed and related both to genetic and environmental (i.e. drug-induced) factors altering CYP450s metabolizing enzymes activity. In this context, we have developed an ultra performance liquid chromatography-tandem mass spectrometry method (UPLC-MS/MS) requiring 100 μL of plasma for the quantification of tamoxifen and three of its major metabolites in breast cancer patients. Plasma is purified by a combination of protein precipitation, evaporation at room temperature under nitrogen, and reconstitution in methanol/20 mM ammonium formate 1:1 (v/v), adjusted to pH 2.9 with formic acid. Reverse-phase chromatographic separation of tamoxifen, N-desmethyl-tamoxifen, 4-hydroxy-tamoxifen and 4-hydroxy-N-desmethyl-tamoxifen is performed within 13 min using elution with a gradient of 10 mM ammonium formate and acetonitrile, both containing 0.1% formic acid. Analytes quantification, using matrix-matched calibration samples spiked with their respective deuterated internal standards, is performed by electrospray ionization-triple quadrupole mass spectrometry using selected reaction monitoring detection in the positive mode. The method was validated according to FDA recommendations, including assessment of relative matrix effects variability, as well as tamoxifen and metabolites short-term stability in plasma and whole blood. The method is precise (inter-day CV%: 2.5-7.8%), accurate (-1.4 to +5.8%) and sensitive (lower limits of quantification comprised between 0.4 and 2.0 ng/mL). Application of this method to patients' samples has made possible the identification of two further metabolites, 4'-hydroxy-tamoxifen and 4'-hydroxy-N-desmethyl-tamoxifen, described for the first time in breast cancer patients. This UPLC-MS/MS assay is currently applied for monitoring plasma levels of tamoxifen and its metabolites in breast cancer patients within the frame of a clinical trial aiming to assess the impact of dose increase on tamoxifen and endoxifen exposure.
- Published
- 2010
31. Residual antimalarial concentrations before treatment in patients with malaria from Cambodia: indication of drug pressure
- Author
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Frédéric Ariey, Blaise Genton, Piero Olliaro, Socheat Duong, Laurent A. Decosterd, Eva Maria Hodel, Hans-Peter Beck, Boris Zanolari, and Thomas Mercier
- Subjects
Adult ,Male ,Serum ,Drug ,Adolescent ,Antimalarials/blood ,Cambodia ,Child ,Child, Preschool ,Chloroquine/blood ,Chromatography, Liquid ,Drug Resistance ,Female ,Humans ,Malaria, Falciparum/diagnosis ,Mefloquine/blood ,Middle Aged ,Quinine/blood ,Quinolines/blood ,Selection, Genetic ,Serum/chemistry ,Tandem Mass Spectrometry ,Young Adult ,medicine.medical_specialty ,media_common.quotation_subject ,Psychological intervention ,Drug resistance ,Pharmacology ,Antimalarials ,Chloroquine ,Internal medicine ,Piperaquine ,Immunology and Allergy ,Medicine ,Malaria, Falciparum ,media_common ,Quinine ,business.industry ,Mefloquine ,medicine.disease ,Infectious Diseases ,Quinolines ,business ,Malaria ,medicine.drug - Abstract
BACKGROUND: The Thai-Cambodian border has been known as the origin of antimalarial drug resistance for the past 30 years. There is a highly diverse market for antimalarials in this area, and improved knowledge of drug pressure would be useful to target interventions aimed at reducing inappropriate drug use. METHODS: Baseline samples from 125 patients with falciparum malaria recruited for 2 in vivo studies (in Preah Vihear and Pursat provinces) were analyzed for the presence of 14 antimalarials in a single run, by means of a liquid chromatography-tandem mass spectrometry assay. RESULTS: Half of the patients had residual drug concentrations above the lower limit of calibration for at least 1 antimalarial at admission. Among the drugs detected were the currently used first-line drugs mefloquine (25% and 35% of patients) and piperaquine (15% of patients); the first-line drug against vivax malaria, chloroquine (25% and 41% of patients); and the former first-line drug, quinine (5% and 34% patients). CONCLUSIONS: The findings demonstrate that there is high drug pressure and that many people still seek treatment in the private and informal sector, where appropriate treatment is not guaranteed. Promotion of comprehensive behavioral change, communication, community-based mobilization, and advocacy are vital to contain the emergence and spread of parasite resistance against new antimalarials.
- Published
- 2010
32. Residual Antimalarials in Malaria Patients from Tanzania – Implications on Drug Efficacy Assessment and Spread of Parasite Resistance
- Author
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Laurent A. Decosterd, Hans-Peter Beck, Blaise Genton, Piero Olliaro, Eva Maria Hodel, Aggrey Malila, Thierry Buclin, Boris Zanolari, Thomas Mercier, and Abdunoor M. Kabanywanyi
- Subjects
Male ,Public Health and Epidemiology/Screening ,Adolescent ,Adult ,Aged ,Animals ,Antimalarials/blood ,Antimalarials/pharmacology ,Antimalarials/therapeutic use ,Child ,Child, Preschool ,Drug Residues/analysis ,Drug Resistance/drug effects ,Female ,Geography ,Humans ,Infant ,Malaria/blood ,Malaria/drug therapy ,Middle Aged ,Parasites/drug effects ,Sulfadoxine/pharmacokinetics ,Sulfadoxine/pharmacology ,Sulfadoxine/therapeutic use ,Tanzania ,Treatment Outcome ,Young Adult ,medicine.medical_treatment ,Drug Resistance ,lcsh:Medicine ,Public Health and Epidemiology/Infectious Diseases ,Drug resistance ,Pharmacology ,chemistry.chemical_compound ,Chloroquine ,Artemether ,lcsh:Science ,education.field_of_study ,Multidisciplinary ,medicine.drug ,Research Article ,medicine.medical_specialty ,Sulfadoxine ,Population ,Lumefantrine ,Antimalarials ,Internal medicine ,medicine ,Parasites ,education ,business.industry ,lcsh:R ,Pharmacology/Drug Resistance ,medicine.disease ,Drug Residues ,Malaria ,Pyrimethamine ,chemistry ,lcsh:Q ,business - Abstract
BACKGROUND: Repeated antimalarial treatment for febrile episodes and self-treatment are common in malaria-endemic areas. The intake of antimalarials prior to participating in an in vivo study may alter treatment outcome and affect the interpretation of both efficacy and safety outcomes. We report the findings from baseline plasma sampling of malaria patients prior to inclusion into an in vivo study in Tanzania and discuss the implications of residual concentrations of antimalarials in this setting. METHODS AND FINDINGS: In an in vivo study conducted in a rural area of Tanzania in 2008, baseline plasma samples from patients reporting no antimalarial intake within the last 28 days were screened for the presence of 14 antimalarials (parent drugs or metabolites) using liquid chromatography-tandem mass spectrometry. Among the 148 patients enrolled, 110 (74.3%) had at least one antimalarial in their plasma: 80 (54.1%) had lumefantrine above the lower limit of calibration (LLC = 4 ng/mL), 7 (4.7%) desbutyl-lumefantrine (4 ng/mL), 77 (52.0%) sulfadoxine (0.5 ng/mL), 15 (10.1%) pyrimethamine (0.5 ng/mL), 16 (10.8%) quinine (2.5 ng/mL) and none chloroquine (2.5 ng/mL). CONCLUSIONS: The proportion of patients with detectable antimalarial drug levels prior to enrollment into the study is worrying. Indeed artemether-lumefantrine was supposed to be available only at government health facilities. Although sulfadoxine-pyrimethamine is only recommended for intermittent preventive treatment in pregnancy (IPTp), it was still widely used in public and private health facilities and sold in drug shops. Self-reporting of previous drug intake is unreliable and thus screening for the presence of antimalarial drug levels should be considered in future in vivo studies to allow for accurate assessment of treatment outcome. Furthermore, persisting sub-therapeutic drug levels of antimalarials in a population could promote the spread of drug resistance. The knowledge on drug pressure in a given population is important to monitor standard treatment policy implementation.
- Published
- 2009
33. De l’écriture au témoignage, les récits lazaréens de Jean Cayrol
- Author
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Thomas Mercier
- Abstract
Cet article est un compte-rendu du livre : Marie-Laure Basuyaux, Témoigner clandestinement. Les récits lazaréens de Jean Cayrol, Paris : Classiques Garnier, coll. « Études de littérature des XXe et XXIe siècles », 2009, p., EAN 9782812400261
- Published
- 2009
34. Le livre et l’éditeur
- Author
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Thomas Mercier
- Abstract
Cet article est un compte-rendu du livre : Eric Vigne, Le Livre et l’éditeur, Paris, Klinksieck, coll. "50 questions", 2008, 179p.
- Published
- 2008
35. Un poète et son éditeur
- Author
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Thomas Mercier
- Abstract
Cet article est un compte-rendu du livre : Théodore de Banville, Lettres à Auguste Poulet-Malassis, texte établi par Peter J. Edwards, avec la participation de Peter S. Hambly et une introduction de Eileen Souffrin-Le Breton, Paris, Champion, 2007.
- Published
- 2007
36. Jacques Doucet : histoire d’un mécène
- Author
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Thomas Mercier
- Abstract
Cet article est un compte-rendu du livre : François Chapon, C’était Jacques Doucet, Fayard, octobre 2006, 558 p.
- Published
- 2006
37. L’édition littéraire aujourd’hui
- Author
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Thomas Mercier
- Abstract
Cet article est un compte-rendu du livre : L'édition littéraire aujourd'hui, dirigé par Olivier Bessard-Banquy, Préface de Pascal Fouché, IUT Michel de Montaigne, Pôle des métiers du livre, Pessac, Presse Universitaires de Bordeaux, 12 avril 2006, 235 p.
- Published
- 2006
38. Figures de l’éditeur
- Author
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Thomas Mercier
- Abstract
Cet article est un compte-rendu du livre : Figures de l'éditeur. Représentations, savoirs, compétences, territoires, sous la direction de Bertrand Legendre & Christian Robin, Paris : Nouveau Monde Éditions, 2005.
- Published
- 2006
39. Naissance de l’éditeur
- Author
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Thomas Mercier
- Abstract
Cet article est un compte-rendu du livre : Pascal Durand, Anthony Glinoer, Naissance de l’éditeur. L’édition à l’âge romantique, préface d’Hubert Nyssen, Bruxelles : Les Impressions Nouvelles, 2005, 235 p.
- Published
- 2005
40. Performance, Reliability, and Manufacturability of AlGaN/GaN High Electron Mobility Transistors on Silicon Carbide Substrates
- Author
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D. S. Green, Brook Hosse, Jeffrey B. Shealy, Jeffrey D. Brown, Johnathan McKenna, Martin Young, Shawn R. Gibb, M. J. Poulton, Kevin Gratzer, Sangmin Lee, Yinbao Yang, Ramakrishna Vetury, and Thomas Mercier
- Subjects
Materials science ,business.industry ,Transistor ,Algan gan ,law.invention ,Design for manufacturability ,chemistry.chemical_compound ,Reliability (semiconductor) ,chemistry ,law ,Silicon carbide ,Electronic engineering ,Optoelectronics ,business ,High electron - Abstract
AlGaN/GaN High Electron Mobility Transistors (HEMTs) are receiving considerable attention as a technology that is well suited for high power, high efficiency, radio frequency(RF) and microwave applications. The demonstration of attractive performance of GaN based HEMT technology for applications such as wireless basestations, has been successfully achieved by several organizations, including RFMD. Development efforts are now directed toward understanding and resolving the issues associated with the manufacturability and reliability of this technology. We report on the status of this technology at RFMD with respect to the goals delivering a manufacturable and reliable GaN HEMT device technology. The material growth and process technology will be described. Results of device performance, wafer fab repeatability, and technology reliability are reported.
- Published
- 2006
41. Comparison against current standards of a DNA aptamer for the label-free quantification of tobramycin in human sera employed for therapeutic drug monitoring
- Author
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Anna M. Ferretti, Laurent A. Decosterd, Thomas Mercier, Nicolas Widmer, Carlotta Guiducci, Enrico Tenaglia, Dominique Werner, and Thierry Buclin
- Subjects
Aptamer ,Clinical Biochemistry ,Anti-Bacterial Agents/blood ,Pharmaceutical Science ,02 engineering and technology ,Computational biology ,DNA Aptamers ,01 natural sciences ,Analytical Chemistry ,Matrix (chemical analysis) ,Aptamers, Nucleotide/blood ,Drug Monitoring/methods/standards ,Drug Discovery ,medicine ,Tobramycin ,Humans ,In patient ,Spectroscopy ,ddc:615 ,medicine.diagnostic_test ,Chemistry ,010401 analytical chemistry ,Aptamers, Nucleotide ,Surface Plasmon Resonance ,021001 nanoscience & nanotechnology ,Anti-Bacterial Agents ,0104 chemical sciences ,Label-free quantification ,Therapeutic drug monitoring ,Drug Monitoring ,0210 nano-technology ,Tobramycin/blood ,medicine.drug - Abstract
The use of DNA aptamers in biosensors for the quantification of pharmaceuticals in the clinics would help to overcome the limitations of antibody-based detection for small molecules. The interest for such systems is proven by the ever-increasing number of aptamer-based solutions for analytics proposed in the literature as proof-of-concept demonstrators. Despite such diversity, these platforms often lack a comparative assessment of their performances against the current standard of practice in the clinics when using real samples. We employed an aptamer against tobramycin discovered in our laboratory to quantify through surface plasmon resonance the concentration of the antibiotic in clinical samples obtained from patients treated with tobramycin and undergoing therapeutic drug monitoring. We then compared the performances of our detection strategy against the current standard of practice. Our results show how, using adequate calibration and matrix complexity reduction, DNA aptamer-based direct assays can assess clinically relevant concentrations of small molecules in patient serum and with good correlation to current standards used in the clinics.
42. Le rôle du chirurgien-dentiste dans les troubles du comportement alimentaire chez l'adolescent et le jeune adulte
- Author
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Bock, Anne, Université de Lorraine (UL), Université de Lorraine, Dominique Desprez-Droz, and Thomas Mercier
- Subjects
Dissertation universitaire ,Adolescent ,[SDV]Life Sciences [q-bio] ,Jeune adulte ,Thèse d'exercice en chirurgie dentaire ,Troubles de l'alimentation ,Dentistes ,Chez l'adolescent ,Troubles du comportement alimentaire - Abstract
L'auteur de la thèse a souhaité limiter l'accès aux membres de l'Enseignement supérieur français.; Les troubles du comportement alimentaires constituent un trouble psychiatrique fréquent de nos jours, notamment chez les adolescents et jeunes adultes. Un diagnostic précoce, afin de prévenir les conséquences sur la santé générale et mentale, mais aussi dentaire est primordial. Le chirurgien-dentiste, ayant un accès régulier et privilégié à la cavité buccodentaire, se trouve en première ligne pour repérer l'installation de ce trouble psychiatrique par ses conséquences bucco-dentaires. Par ailleurs, il a un rôle à jouer dans la limitation des conséquences sur la sphère orale. Notre travail regroupe les signes et symptômes intra et extra oraux à reconnaître, la démarche à suivre pour aborder et orienter le patient souffrant d'un trouble de comportement alimentaire ainsi que les gestes qu'il est possible de mettre en place au niveau bucco-dentaire.
- Published
- 2018
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