A5089641018- Folate and B Vitamins Research
- HIV/AIDS drug development and treatment
- Biochemical and Molecular Research
- HIV Research and Treatment
- HIV/AIDS Research and Interventions
- Protein Degradation and Inhibitors
- Click Chemistry and Applications
- Pharmacological Effects and Toxicity Studies
- Drug Transport and Resistance Mechanisms
- Cancer Research and Treatments
- Cancer-related Molecular Pathways
- Reproductive System and Pregnancy
- Advanced biosensing and bioanalysis techniques
- HIV-related health complications and treatments
- Metabolomics and Mass Spectrometry Studies
- Analytical Chemistry and Chromatography
- Cancer Treatment and Pharmacology
- Pharmacogenetics and Drug Metabolism
- French Urban and Social Studies
- Tryptophan and brain disorders
- Mass Spectrometry Techniques and Applications
- Heavy Metal Exposure and Toxicity
- Cytomegalovirus and herpesvirus research
- Synthesis and Catalytic Reactions
- Chronic Myeloid Leukemia Treatments
CEA Paris-Saclay
2010-2024
Commissariat à l'Énergie Atomique et aux Énergies Alternatives
2015-2024
Technologies pour la Santé
2020-2024
Université Paris-Saclay
2016-2024
Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement
2018-2024
Institut National Polytechnique de Toulouse
2024
University of Modena and Reggio Emilia
2024
Inserm
2024
Institut de Biologie et Technologies
2010-2023
Unité de Technologies Chimiques et Biologiques pour la Santé
2021-2023
Abstract Depression is the leading cause of disability worldwide. Recent observations have revealed an association between mood disorders and alterations intestinal microbiota. Here, using unpredictable chronic mild stress (UCMS) as a mouse model depression, we show that UCMS mice display phenotypic alterations, which could be transferred from donors to naïve recipient by fecal microbiota transplantation. The cellular behavioral observed in were accompanied decrease endocannabinoid (eCB)...
ABSTRACT The aim was to evaluate emtricitabine (FTC) and tenofovir (TFV) neonatal ingestion through breast milk. Median TFV FTC milk doses represented 0.03% 2%, respectively, of the proposed oral infant doses. Neonatal simulated plasma concentrations were extremely low for but between half-maximal inhibitory concentration adult minimal expected FTC. rare children who will acquire HIV despite TDF-FTC therapy need be monitored viral resistance acquisition.
Multiple system atrophy (MSA) is a sporadic orphan neurodegenerative disorder. No treatment currently available to slow down the aggressive process, and patients die within few years after disease onset. The cytopathological hallmark of MSA accumulation alpha-synuclein (α-syn) aggregates in affected oligodendrocytes. Several studies point α-syn oligomerization aggregation as mediator neurotoxicity synucleinopathies including MSA. C-terminal truncation by inflammatory protease caspase-1 has...
Systemic inflammation (SI) is involved in the pathogenesis of acute decompensation (AD) and acute‐on‐chronic liver failure (ACLF) cirrhosis. In other diseases, SI activates tryptophan (Trp) degradation through kynurenine pathway (KP), giving rise to metabolites that contribute multiorgan/system damage immunosuppression. current study, we aimed characterize KP patients with cirrhosis, whom this poorly known. The serum levels Trp, key (kynurenine kynurenic quinolinic acids), cytokines (SI...
Drug delivery of combined cytotoxic and antivascular chemotherapies in multidrug nanoassemblies may represent an attractive way to improve the treatment experimental cancers. Here we made proof concept this approach on LS174-T human colon carcinoma xenograft nude mice model. Briefly, have nanoprecipitated anticancer compound gemcitabine conjugated with squalene (SQ-gem) together isocombretastatin A-4 (isoCA-4), a new isomer combretastatin (CA-4). It was found that these molecules...
Abstract The development of effective central nervous system (CNS) drugs has been hampered by the lack robust strategies to mimic blood-brain barrier (BBB) and cerebrovascular impairments in vitro . Recent technological advancements BBB modeling using induced pluripotent stem cells (iPSCs) allowed overcome some these obstacles, nonetheless pertinence for their use drug permeation study remains be established. This mandatory information requires a cross comparison vivo pharmacokinetic data...
We recently observed a significant CD4 cell count decline in patients receiving didanosine (ddI) 400 mg, tenofovir (TDF) and nevirapine (NVP), despite virological suppression.We identified from our computerized patient database subjects who initiated combinations containing ddI and/or TDF for reasons other than failure, including simplification or intolerance. Changes total, CD4+ CD8+ lymphocyte counts since the initiation of therapy were analysed retrospectively. Plasma concentration was...
ABSTRACT Recent work has demonstrated the existence of a systemic interaction between didanosine (ddI) and tenofovir disoproxyl fumarate (TDF) that leads to significant increase in plasma ddI levels when coadministered with TDF (40 50% increase). These two drugs are, respectively, nucleoside nucleotide analogues adenosine efficiently inhibit human immunodeficiency virus (HIV) reverse transcriptase transformed their triphosphate moieties intracellular (IC) medium (ddA-TP TFV-DP,...
Previous work has demonstrated the existence of systemic interaction between tenofovir (TFV) disoproxil fumarate (TDF) and didanosine as well TDF lopinavir-ritonavir (LPV/r). Here we investigated interactions with nucleoside reverse transcriptase inhibitors (NRTIs) lamivudine (3TC) abacavir (ABC), comparing both concentrations nucleoside/nucleotide in plasma intracellular their triphosphate metabolites (NRTI-TP) for human immunodeficiency virus-infected patients receiving these NRTIs after 4...
A number of men receiving prolonged suppressive highly active antiretroviral therapy (HAART) still shed human immunodeficiency virus (HIV) in semen. To investigate whether this seminal shedding may be due to poor drug penetration and/or viral production by long-lived cells within male genital tissues, we analyzed semen and reproductive tissues from macaques chronically infected with simian mac251 (SIVmac251) who were treated for 4 months HAART, which was intensified over the last 7 weeks an...
Administration of first-in-class anti-EGFR monoclonal antibody cetuximab is contingent upon extensive pharmacogenomic testing. However in addition to tumor genomics, drug exposure levels could play a critical, yet largely underestimated role, because several reports have demonstrated that pharmacokinetic parameters, particular clearance values, were associated with survival patients. Here, we developed an original bioanalytical method based the use LC-MS/MS technology and simplified sample...
Abstract Gonadal sexual fate in mammals is determined during embryonic development and must be actively maintained adulthood. In the mouse ovary, oestrogen receptors FOXL2 protect ovarian granulosa cells from transdifferentiation into Sertoli cells, their testicular counterpart. However, mechanism underlying protective effect unknown. Here, we show that TRIM28 required to prevent female-to-male sex reversal of ovary after birth. We found upon loss Trim28 , transdifferentiate through an...
Abstract There is still a need for direct determination (i.e. without dephosphorylation) of nucleoside reverse transcriptase inhibitor (NRTI) triphosphorylated nucleotides in the peripheral‐blood mononuclear cells (PBMCs) HIV‐positive patients. The objective this paper was first to improve our previously described liquid chromatography/tandem mass spectrometry (LC/MS/MS) assay stavudine triphosphate (d4T‐TP). Preparation PBMCs modified reduce degradation d4T‐TP during cell preparation and...
Brain penetration is characterized by its extent and rate influenced drug physicochemical properties, plasma exposure, brain protein binding BBB permeability. This raises questions related to physiology, interspecies differences in vitro/in vivo extrapolation. We herein discuss the use of vitro human animal model as a tool improve CNS compound selection. These cell-based models are low paracellular permeation, well-developed tight junctions functional efflux transporters. A study twenty...
Abstract Nonsteroidal anti-inflammatory drugs (NSAIDs) and analgesic drugs, such as acetaminophen (APAP), are frequently taken during pregnancy, even in combination. However, they can favour genital malformations newborn boys reproductive disorders adults. Conversely, the consequences on postnatal ovarian development female health after utero exposure unknown. Here, we found that mice, to therapeutic doses of APAP-ibuprofen combination sex determination led delayed meiosis entry progression...
Abstract The objective was to develop and validate a routine assay for active intracellular anabolites of stavudine (d4T), nucleoside reverse transcriptase inhibitor in human PBMC, applicable pharmacokinetic studies treatment monitoring. This achieved using liquid chromatography coupled tandem mass spectrometry (LC/MS/MS), which theoretically allies optimum sensitivity, specificity high sample throughput. After cellular lysis Tris/methanol buffer, the extract spiked with 2 [H 8 ]‐ATP...
LC/ESI-MS/MS is a promising alternative to immunoassays in improving the analysis of recombinant therapeutic proteins biological fluids for toxicity and pharmacokinetics purposes. To assess sensitivity validation issues associated with this technique, we use here as model EPI-hNE4, 56-amino acid protein, demonstrate that method based on tandem mass spectrometry combined liquid chromatography electrospray interface can reach similar ELISA but without its potential cross-reactivity. For...
Abstract Our previous negative ESI‐LC‐MS/MS method developed for nucleoside reverse transcriptase inhibitor (NRTI) triphosphate (‐TP) measurements in human peripheral blood mononuclear cells (PBMC) encountered some specificity problems several NRTI‐TP and simultaneous endogenous nucleotide triphosphates analysis. As LC‐MS/MS offers possibilities to circumvent such problems, we have investigated the contribution of positive electrospray ionization mode enhancing intracellular analyses...
ABSTRACT The intracellular metabolism of nucleoside reverse transcriptase inhibitors (NRTI) in mononuclear cells has been thoroughly studied, but that red blood (RBC) disregarded. However, the phosphorylation other analogous nucleosides (in particular, ribavirin) described previously. In this study, we investigated for first time NRTI human RBC. presence zidovudine (AZT) monophosphate, AZT triphosphate, lamivudine (3TC) and tenofovir (TFV) diphosphate, as well endogenous dATP, dGTP, dTTP,...
Combination microbicide vaginal rings may be more effective than single at reducing/preventing sexual transmission of HIV. Here, we report the pre-clinical development and macaque pharmacokinetics matrix-type silicone elastomer containing dapivirine darunavir.Macaque 25 mg dapivirine, 100 300 darunavir or dapivirine+300 were manufactured characterized by differential scanning calorimetry. In vitro release was assessed into isopropanol/water simulated fluid. Macaque fluid blood serum...
Apoptosis has been proposed as a key mechanism responsible for CD4+ T cell depletion and immune dysfunction during HIV infection. We demonstrated that Q-VD-OPH, caspase inhibitor, inhibits spontaneous activation-induced death of cells from SIV-infected rhesus macaques (RMs). When administered the acute phase infection, Q-VD-OPH was associated with (a) reduced levels death, (b) preservation CD4+/CD8+ ratio in lymphoid organs gut, (c) maintenance memory cells, (d) increased specific response...
Creatine transporter (CrT) deficiency is an X-linked intellectual disability caused by mutations of CrT. Aim: This work focus on the preclinical development a new therapeutic approach based microemulsion (ME) as drug delivery system for dodecyl creatine ester (DCE). Materials & methods: DCE-ME was prepared titration method. Novel object recognition (NOR) tests were performed before and after treatment Slc6a8-/y mice. Results: Intranasal administration with improved NOR performance in mice...