A5082432867- Drug Transport and Resistance Mechanisms
- Pharmacological Effects and Toxicity Studies
- Pharmacogenetics and Drug Metabolism
- Barrier Structure and Function Studies
- Forensic Toxicology and Drug Analysis
- Cannabis and Cannabinoid Research
- Diet and metabolism studies
- Epilepsy research and treatment
- Neurotransmitter Receptor Influence on Behavior
- Botulinum Toxin and Related Neurological Disorders
- Poisoning and overdose treatments
- Nanoparticle-Based Drug Delivery
- Bariatric Surgery and Outcomes
- Radiopharmaceutical Chemistry and Applications
- CAR-T cell therapy research
- Neuroscience and Neuropharmacology Research
- Pharmaceutical studies and practices
- Chronic Lymphocytic Leukemia Research
- Trace Elements in Health
- Pain Mechanisms and Treatments
- Antibiotics Pharmacokinetics and Efficacy
- HIV/AIDS drug development and treatment
- Pharmacology and Obesity Treatment
- Bipolar Disorder and Treatment
- Pain Management and Opioid Use
Sorbonne Paris Cité
2012-2024
Inserm
2015-2024
Université Paris Cité
2015-2024
Hôpital Cochin
2015-2024
Assistance Publique – Hôpitaux de Paris
2015-2024
Optimisation Thérapeutique en Neuropsychopharmacologie
2019-2024
Centre de Recherche des Cordeliers
2024
Hôpital Lariboisière
2000-2022
Laboratoire d'Optique Appliquée
2022
Délégation Paris 5
2012-2021
We have investigated the transcriptomic and/or proteomic patterns of 71 solute carrier (SLC) and organic (OST) transporters, 34 ATP-binding cassette (ABC) 51 metabolizing enzymes in human brain microvessels. used quantitative RT-PCR LC–MS/MS to examine isolated microvessels cortex biopsies from 12 patients with epilepsia or glioma. SLC2A1/GLUT1, SLC1A3/EAAT1, SLC1A2/EAAT2 were main SLC proteins whereas ABCG2/BCRP, ABCB1/MDR1, ABCA2 ABCA8 ABC quantified microvessels; ABCG2/BCRP was 1.6-fold...
Abstract We have established the expression patterns of genes encoding ATP‐binding cassette (ABC) transporters and cytochromes P450 (CYPs) at adult human blood–brain barrier (BBB) using isolated brain microvessels cortex biopsies from patients with epilepsia or glioma. Microves synaptophysin (neurons) neuron‐glial antigen 2 (NG2) (pericytes). ABCG2 [breast cancer resistance protein ( BCRP )] ABCB1 MDR1 ) were main ABC transporter expressed in microvessels, 20 times more 25 than cortex. The...
Human cerebral microvascular endothelial cell line hCMEC/D3 is an established model of the human blood–brain barrier (BBB). The purpose present study was to determine, by means quantitative targeted absolute proteomics, protein expression levels in cells multiple transporters, receptors and junction proteins for comparison with our previously reported findings isolated brain microvessels. Among 91 target molecules, 12 2 receptors, 1 membrane marker were at quantifiable plasma fraction cells....
Cytochrome P450 (P450) enzymes and ATP-binding cassette (ABC) transporters modulate the transport metabolism of both endogenous exogenous substrates could play crucial roles in human brain. In this study, we report transcript expression profile seven ABC (ABCB1, ABCC1–C5, ABCG2), 24 P450s (CYP1, CYP2, CYP3 families CYP46A1), 14 related transcription factors [aryl hydrocarbon receptor, nuclear receptor (NR)1I2/pregnane X NR1I3/constitutive androstane NR1C/peroxisome proliferator-activated...
Abstract Astrocytes send out long processes that are terminated by endfeet at the vascular surface and regulate functions as well homeostasis interface. To date, astroglial mechanisms underlying these have been poorly addressed. Here we demonstrate a subset of messenger RNAs is distributed in astrocyte endfeet. We identified, among this transcriptome, pool bound to ribosomes, endfeetome, primarily encodes for secreted membrane proteins. detected nascent protein synthesis Finally, determined...
Drug interaction with P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) may influence its tissue disposition including blood-brain barrier transport result in potent drug-drug interactions. The limited data obtained using in-vitro models indicate that methadone, buprenorphine, cannabinoids interact human P-gp; but almost nothing is known about drugs of abuse BCRP. We used vitro P-gp BCRP inhibition flow cytometric assays hMDR1- hBCRP-transfected HEK293 cells to test 14...
It is difficult to predict the first-pass effect in human intestine due a lack of scaling factors for correlating vitro and vivo data. We have quantified cytochrome P450/3A4 (CYP3A4) two ABC transporters, P-glycoprotein (P-gp, ABCB1) breast cancer resistant protein BCRP (ABCG2), throughout small determine predicting clearance from intestinal microsomes develop physiologically based pharmacokinetic (PBPK) model. CYP3A4, P-gp proteins were by Western blotting and/or enzyme activities samples...
In the brain, most of vascular system consists a selective barrier, blood-brain barrier (BBB) that regulates exchange molecules and immune cells between brain blood. Moreover, huge neuronal metabolic demand requires moment-to-moment regulation blood flow. Notably, abnormalities these regulations are etiological hallmarks pathologies; including glioblastoma, stroke, edema, epilepsy, degenerative diseases (ex: Parkinson's disease, Alzheimer's disease), tumors, as well inflammatory conditions...
Protein expression levels of drug-metabolizing enzymes and transporters in human jejunal tissues excised from morbidly obese subjects during gastric bypass surgery were evaluated using quantitative targeted absolute proteomics. 15 cytochrome P450 (CYP) enzymes, 10 UDP-glucuronosyltransferase (UGT) NADPH-P450 reductase (P450R) microsomal fractions 28 49 plasma membrane 24 the same determined liquid chromatography-tandem mass spectrometry. Based on average values, UGT1A1, UGT2B15, UGT2B17,...
Abstract Brain mural cells form a heterogeneous family which significantly contributes to the maintenance of blood-brain barrier and regulation cerebral blood flow. Current procedures isolate them cannot specifically separate their distinct subtypes, in particular vascular smooth muscle (VSMCs) mid-capillary pericytes (mcPCs), differ among others by expression actin (SMA). We herein describe an innovative method allowing SMA + VSMCs − mcPCs be freshly isolated from rat cortex. Using...
The effect of cannabidiol (CBD), a high-affinity agonist the transient receptor potential vanilloid-2 (TRPV2) channel, has been poorly investigated in human brain microvessel endothelial cells (BMEC) forming blood–brain barrier (BBB). TRPV2 expression and its role on Ca2+ cellular dynamics, trans-endothelial electrical resistance (TEER), cell viability growth, migration, tubulogenesis were evaluated primary cultures BMEC (hPBMEC) or cerebral hCMEC/D3 line. Abundant was measured hPBMEC by...
Gemcitabine (2′,2′-difluorodeoxyribofuranosylcytosine; dFdC) is an anticancer nucleoside analog active against wide variety of solid tumors. However, this compound rapidly inactivated by enzymatic deamination and can also induce drug resistance. To overcome the above drawbacks, we recently designed a new squalenoyl nanomedicine dFdC [4-(<i>N</i>)-trisnorsqualenoyl-gemcitabine (SQdFdC)] covalently coupling gemcitabine with 1,1′,2-trisnorsqualenic acid; resultant displayed impressively greater...
Methadone is characterized by wide intersubject variability regarding the dose needed to obtain full therapeutic response. We assessed influence of sociodemographic, ethnic, clinical, metabolic and genotypic variables on methadone maintenance requirement in opioid-dependent responder patients.Eighty-one stable patients (60 men 21 women, 43.7 ± 8.1 years old, 63.1 50.9 mg day(-1) methadone), divided into quartiles with respect median daily dose, were enrolled underwent clinical examination,...
Deaths due to asphyxia as well following acute poisoning with severe respiratory depression have been attributed buprenorphine in opioid abusers. However, human and animal studies, exhibited ceiling effects, whereas its metabolite, norbuprenorphine, was assessed being a potent depressor rodents. Recently, contrast buprenorphine, shown vitro be substrate of P-glycoprotein, drug-transporter involved all steps pharmacokinetics including transport at the blood-brain barrier. Our objectives were...