Profilomic

Boulogne-Billancourt, France

Profilomic

Boulogne-Billancourt, France
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Baudoin R.,CNRS Biomechanical Engineering Laboratory | Legendre A.,CNRS Biomechanical Engineering Laboratory | Jacques S.,French Institute of Health and Medical Research | Jacques S.,French National Center for Scientific Research | And 4 more authors.
Journal of Pharmaceutical Sciences | Year: 2014

We investigated metabolic clearances of phenacetin, midazolam, propranolol, paracetamol, tolbutamide, caffeine, and dextromethorphan by primary rat hepatocytes cultivated in microfluidic biochips. The levels of mRNA of the HNF4α, PXR, AHR, CYP3A1, and CYP1A2 genes were enhanced in the biochip cultures when compared with postextraction levels. We measured a high and rapid adsorption on the biochip walls and inside the circuit for dextromethorphan and midazolam, a moderate adsorption for phenacetin and propranolol, and a low adsorption for caffeine, tolbutamide, and paracetamol. Drug biotransformations were demonstrated by the formations of specific metabolites such as paraxanthyne (caffeine), paracetamol (phenacetin), 1-OH midazolam (midazolam), paracetamol sulfate (paracetamol and phenacetin), and dextrorphan (dextromethorphan). We used a pharmacokinetic model to estimate the adsorption and in vitro intrinsic drug clearance values. We calculated in vitro intrinsic clearance values of 0.5, 3, 12.5, 83, 100, 160, and 900 μL/min per 106 cells for the tolbutamide, caffeine, paracetamol, dextromethorphan, phenacetin, midazolam, and propranolol, respectively. A second model describing the liver as a well-stirred compartment predicted in vivo hepatic clearances of 0.1, 13.8, 30, 44.1, 61, 72, 85, and 61 mL/min per kg of body mass for the tolbutamide, caffeine, paracetamol, midazolam, dextromethorphan, phenacetin, and propranolol, respectively. These values appeared consistent with previously reported data. © 2013Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 103:706-718, 2014.


Auge C.,French Institute of Health and Medical Research | Auge C.,French National Center for Scientific Research | Auge C.,Toulouse 1 University Capitole | Chene G.,Ambiotis | And 9 more authors.
European Journal of Pharmacology | Year: 2013

This work aimed at establishing the relevance of using the in vivo model of cyclophosphamide (CYP)-induced bladder inflammation in rats for in vivo pharmacological studies. Specifically, we measured visceral nociception, identified key inflammatory mediators and evaluated the effects of relevant pharmacological treatments. Cystitis was induced in female rats by a single CYP injection. Sensitivity of the lower abdomen to von Frey mechanical stimulation was determined as a nociceptive parameter. Bladders were assessed for weight, wall thickness and macroscopic damage. Inflammatory mediators were quantified in bladders and urines. The effects of aspirin, ibuprofen and morphine were investigated on all these parameters. A single CYP injection increased nociceptive scores and decreased nociceptive threshold in response to mechanical stimuli between 1 and 4 h post-administration. Increased bladder weight and wall thickness were associated with edema and hemorrhage. Bladder levels of IL-1β, IL-6, MCP-1 and VCAM, and urinary levels of PGE2 were increased. In contrast, a decrease in the urinary metabolites, indoxyl sulfate and pantothenic acid, was observed. Aspirin, ibuprofen and morphine decreased CYP-induced referred visceral pain. Aspirin and ibuprofen also reversed the increased wall thickness, macroscopic damage and levels of IL-1β, IL-6 and PGE2, and the decreased panthotenic acid levels. In contrast, morphine increased wall thickness, edema, hemorrhage, and bladder IL-6 and MCP-1 levels. This work presents a new and reliable method to evaluate visceral sensitivity in rats, and new relevant biomarkers identified in the bladder and urine to measure inflammation and pain parameters for in vivo pharmacological studies. © 2013 Elsevier B.V. All rights reserved.


Legendre A.,CNRS Biomechanical Engineering Laboratory | Baudoin R.,CNRS Biomechanical Engineering Laboratory | Alberto G.,CNRS Biomechanical Engineering Laboratory | Paullier P.,CNRS Biomechanical Engineering Laboratory | And 6 more authors.
Journal of Pharmaceutical Sciences | Year: 2013

The functionality of primary rat hepatocytes was assessed in an Integrated Dynamic Cell Cultures in Microsystem (IDCCM) device. We characterized the hepatocytes over 96h of culture and evaluated the impact of dynamic cell culture on their viability, inducibility, and metabolic activity. Reverse Transcription quantitative Polymerase Chain Reaction (RTqPCR) was performed on selected genes: liver transcription factors (HNF4α and CEBP), nuclear receptors sensitive to xenobiotics (AhR, PXR, CAR, and FXR), cytochromes P450 (CYPs) (1A2, 3A2, 3A23/3A1, 7A1, 2B1, 2C6, 2C, 2D1, 2D2, and 2E1), phase II metabolism enzymes (GSTA2, SULT1A1, and UGT1A6), ABC transporters (ABCB1b and ABCC2), and oxidative stress related enzymes (HMOX1 and NQO1). Microperfused-cultured hepatocytes remained viable and differentiated with in vivo-like phenotype and genotype. In contrast with postadhesion gene levels, the first 48h of perfusion enhanced the expression of xenosensors and their target CYPs. Furthermore, CYP3A1, CYP2B1, GSTA2, SULT1A1, UGT1A1, ABCB1b, and ABCC2 were upregulated in IDCCM and reached above postextraction levels all along the duration of culture. Metabolic activities were also confirmed with the detection of metabolism rate and induced mRNAs after exposure to several inducers: 3-methylcholanthrene, caffeine, phenacetin, paracetamol,, and midazolam. Finally, this metabolic characterization confirms that IDCCM is able to maintain rat hepatocytes functions to investigate drug metabolism. © 2013 Wiley Periodicals, Inc.


Spiteri M.,Eurofins | Dubin E.,Eurofins | Cotton J.,Profilomic | Poirel M.,Profilomic | And 4 more authors.
Analytical and Bioanalytical Chemistry | Year: 2016

A data fusion approach was applied to a commercial honey data set analysed by 1H-nuclear magnetic resonance (NMR) 400 MHz and liquid chromatography-high resolution mass spectrometry (LC-HRMS). The latter was performed using two types of mass spectrometers: an Orbitrap-MS and a time of flight (TOF)-MS. Fifty-six honey samples from four monofloral origins (acacia, orange blossom, lavender and eucalyptus) and multifloral sources from various geographical origins were analysed using the three instruments. The discriminating power of the results was examined by PCA first considering each technique separately, and then combining NMR and LC-HRMS together with or without variable selection. It was shown that the discriminating potential is increased through the data fusion, allowing for a better separation of eucalyptus, orange blossom and lavender. The NMR-Orbitrap-MS and NMR-TOF-MS mid-level fusion models with variable selection were preferred as a good discrimination was obtained with no misclassification observed for the latter. This study opens the path to new comprehensive food profiling approaches combining more than one technique in order to benefit from the advantages of several technologies. [Figure not available: see fulltext.] © 2016 Springer-Verlag Berlin Heidelberg


PubMed | Profilomic, Eurofins and French National Institute for Agricultural Research
Type: Journal Article | Journal: Analytical and bioanalytical chemistry | Year: 2016

A data fusion approach was applied to a commercial honey data set analysed by (1)H-nuclear magnetic resonance (NMR) 400MHz and liquid chromatography-high resolution mass spectrometry (LC-HRMS). The latter was performed using two types of mass spectrometers: an Orbitrap-MS and a time of flight (TOF)-MS. Fifty-six honey samples from four monofloral origins (acacia, orange blossom, lavender and eucalyptus) and multifloral sources from various geographical origins were analysed using the three instruments. The discriminating power of the results was examined by PCA first considering each technique separately, and then combining NMR and LC-HRMS together with or without variable selection. It was shown that the discriminating potential is increased through the data fusion, allowing for a better separation of eucalyptus, orange blossom and lavender. The NMR-Orbitrap-MS and NMR-TOF-MS mid-level fusion models with variable selection were preferred as a good discrimination was obtained with no misclassification observed for the latter. This study opens the path to new comprehensive food profiling approaches combining more than one technique in order to benefit from the advantages of several technologies. Graphical Abstract Data fusion between high resolution 1H-NMR and mass spectrometry.


Legendre A.,CNRS Biomechanical Engineering Laboratory | Jacques S.,French Institute of Health and Medical Research | Dumont F.,French Institute of Health and Medical Research | Cotton J.,Profilomic | And 3 more authors.
Toxicology in Vitro | Year: 2014

We investigated the effects of the liver damage induced by flutamide in primary rat hepatocytes using liver microfluidic biochips. Flutamide is a non-steroidal anti-androgenic drug. Two flutamide concentrations, 10. μM and 100. μM, were used to expose the hepatocytes for 24. h under perfusion. Thanks to the maintenance of hepatocyte differentiation phenotype and to the biotransformation performance in the microfluidic cultures, the metabolic ratio analysis of hydroxyflutamide, flutamide-gluthatione and hydroxyflutamide-gluthatione productions demonstrated saturation of the drug's biotransformation process and the maintenance of a high level of flutamide at 100. μM when compared to 10. μM. A microarray analysis comparing flutamide (10 or 100. μM) with controls revealed a common response for both concentrations illustrated by modulating the expression of the mRNA of genes associated with mitochondrial perturbation, of the proliferator-activated receptors (Ppar) signaling, lipid and fatty acid metabolism, antioxidant defense, and cell death pathways, consistently with in vitro and in vivo reports. Additionally to literature reports, our integration of the transcriptomic profiles demonstrated a specific dose dependent response. We found at 10. μM a typical pro-survival/apoptosis network activation (through IGF/PDGFD upstream route and via a downstream up regulation in CREB5, BCL2, IKBKG routes in the PI3K/signaling). We also found a down regulation of mRNA levels in sugar and amino acid metabolism pathways. At 100. μM a typical necrosis switch was observed associated with a down regulation of the tight junctions' pathway, a cellular aggregation and a reduction of the cell viability. Altogether our data demonstrated the potential and the sensitivity of our liver microfluidic cultures to evaluate xenobiotic toxicity by improving in vitro analysis and reproducing both in vitro and in vivo results. Finally, we proposed two integrated synthetic networks to describe the response of rat hepatocytes to both exposure concentrations of flutamide. © 2014 Elsevier Ltd.


PubMed | Biobanque de Picardie, Profilomic, CNRS Biomechanical Engineering Laboratory, University of Picardie Jules Verne and 2 more.
Type: Journal Article | Journal: Biopharmaceutics & drug disposition | Year: 2015

A new in vitro microfluidic platform (integrated insert dynamic microfluidic platform, IIDMP) allowing the co-culture of intestinal Caco-2 TC7 cells and of human primary hepatocytes was used to test the absorption and first-pass metabolism of two drugs: phenacetin and omeprazole. The metabolism of these drugs by CYP1A2, CYP2C19 and CYP3A4 was evaluated by the calculation of bioavailabilities and of intrinsic clearances using a pharmacokinetic (PK) model. To demonstrate the usefulness of the device and of the PK model, predictions were compared with in vitro and in vivo results from the literature. Based on the IIDMP experiments, hepatic in vivo clearances of phenacetin and omeprazole in the IIDMP were predicted to be 3.10 0.36 and 1.46 0.25 ml/min/kg body weight, respectively. This appeared lower than the in vivo observed data with values ranging between 11.9-19.6 and 5.8-7.5 ml/min/kg body weight, respectively. Then the calculated hepatic and intestinal clearances led to predicting an oral bioavailability of 0.85 and 0.77 for phenacetin and omeprazole versus 0.92 and 0.78 using separate data from the simple monoculture of Caco-2 TC7 cells and hepatocytes in Petri dishes. When compared with the in vivo data, the results of oral bioavailability were overestimated (0.37 and 0.71, respectively). The feasibility of co-culture in a device allowing the integration of intestinal absorption, intestinal metabolism and hepatic metabolism in a single model was demonstrated. Nevertheless, further experiments with other drugs are needed to extend knowledge of the device to predict oral bioavailability and intestinal first-pass metabolism.


Cotton J.,Profilomic | Leroux F.,Profilomic | Broudin S.,Profilomic | Poirel M.,Profilomic | And 3 more authors.
Water Research | Year: 2016

Screening of a large number of emerging pollutants is highly desirable for the control of water quality. In this respect, a novel, fully automated contaminant screening method based on an integrated sample preconcentration and liquid chromatography coupled to high resolution mass spectrometry (SPE-UHPLC-HRMS) has been developed. The optimal chromatographic column and experimental conditions allowing the retention and subsequent elution of the maximum number of analytes were defined. Liquid chromatography and Q-exactive (Orbitrap™) parameters were optimized to obtain the best separation of molecules of interest, and the lowest detection limits. Due to the large amount of data to compare, a script written in R language was developed to evaluate the quality of the data generated by the comparison of 14 experimental conditions. The developed method enables the simultaneous semi quantitative analysis of 539 compounds (pesticides and drug residues), in 36 min with only 5 mL of water. Method validation was achieved through studies of repeatability, selectivity, linearity and matrix effect. Application to 20 tap water samples collected in and around Paris showed the presence of 34 different compounds all with concentrations below 0.1 μg/L, the European Union limit for drinking water. Pesticides and transformation products frequently found in water resources such as atrazine and its metabolites, hexazinone, oxadixyl, propazine and simazine were detected. Drug residues such as valsartan and carbamazepine, usually not monitored, were also found. The next step will be to assess the ability of this method to highlight the presence of unexpected contaminants not present in our database. © 2016 Elsevier Ltd


Screening of a large number of emerging pollutants is highly desirable for the control of water quality. In this respect, a novel, fully automated contaminant screening method based on an integrated sample preconcentration and liquid chromatography coupled to high resolution mass spectrometry (SPE-UHPLC-HRMS) has been developed. The optimal chromatographic column and experimental conditions allowing the retention and subsequent elution of the maximum number of analytes were defined. Liquid chromatography and Q-exactive (Orbitrap) parameters were optimized to obtain the best separation of molecules of interest, and the lowest detection limits. Due to the large amount of data to compare, a script written in R language was developed to evaluate the quality of the data generated by the comparison of 14 experimental conditions. The developed method enables the simultaneous semi quantitative analysis of 539 compounds (pesticides and drug residues), in 36min with only 5mL of water. Method validation was achieved through studies of repeatability, selectivity, linearity and matrix effect. Application to 20 tap water samples collected in and around Paris showed the presence of 34 different compounds all with concentrations below 0.1g/L, the European Union limit for drinking water. Pesticides and transformation products frequently found in water resources such as atrazine and its metabolites, hexazinone, oxadixyl, propazine and simazine were detected. Drug residues such as valsartan and carbamazepine, usually not monitored, were also found. The next step will be to assess the ability of this method to highlight the presence of unexpected contaminants not present in our database.


Trademark
Profilomic | Date: 2011-12-13

Pharmaceutical and veterinary preparations for the prevention of metabolic or genetic diseases or of diseases having metabolic effects; sanitary preparations for medical use; dietetic foods adapted for medical use; food for babies; medicated bath preparations; chemical preparations for medical or pharmaceutical use, namely, for use in preventing metabolic-related or genetic diseases; medicinal herbs. Scientific evaluations, assessments and research in the fields of science and technology provided by engineers; design and development of computer hardware and software; product research and development for others; engineering services, particularly technical project planning and design engineering of lines for the processing of web products; development, design, installation, maintenance, updating or rental of software; computer programming; consultancy in the field of computer hardware; data conversion of computer programs and data other than physical conversion; conversion of data or documents from physical to electronic media.

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