Nous souhaitons la bienvenue à Arnaud Pallotta, qui rejoint notre équipe en tant que Maître de Conférences en Chimie Analytique.
2018
Haiyan YU soutiendra sa thèse de doctorat intitulée "Etude de la biodisponibilité orale du S-nitrosoglutathion au moyen de modèles de la barrière intestinale par chromatographie en phase liquide couplée à la spectrométrie de masse après marquage par l’isotope 15 de l’azote" le mercredi 29 août à 14 h dans la salle du Conseil (Faculté de Pharmacie, rue Lionnois) à Nancy.
Le jury est composé de :
- Mme Emilie DESTANDAU (Rapporteur, MCU, ICOA UMR 7311, Institut de Chimie Organique et Analytique, Université d'Orléans, Orléans)
- Mme Elke RICHLING (Rapporteur, PR, Technical University of Kaiserslautern, Allemagne)
- Mr Pierre LEROY (Examinateur, PR, EA 3452 CITHEFOR, Université de Lorraine, Nancy, directeur de thèse)
- Mr Patrick CHAIMBAULT (Examinateur, PR, LCP-A2MC, EA 4632, Université de Lorraine, Metz, co-directeur de thèse)
Justine BONETTI, étudiante en 1ère année de doctorat en co-tutelle avec l’Université de Pise, a obtenu une bourse d’aide à la mobilité de l’université Franco-Italienne (programme VINCI), dans le cadre du projet « Potentiel thérapeutique des S-nitrosothiols dans la prévention de l’athérosclérose : modulation de la métaplasie des monocytes et cellules musculaires lisses en cellules spumeuses ».
L'article "Comparison between two derivatization methods of nitrite ion labeled with 15N applied to liquid chromatography-tandem mass spectrometry" vient de paraître dans le journal "Analytical Methods"
Auteurs : Haiyan Yu, Romain Schmitt, Anne Sapin-Minet, Patrick Chaimbault and Pierre Leroy
Référence de l'article : Analytical Methods, 2018, DOI: 10.1039/C8AY01206G
Abstract :
The fragmentations of the adducts resulting from the derivatization of nitrite ion by Griess method (formation of an azo compound) and 2,3-diaminonaphthalene (formation of 2,3-naphthotriazole (NAT)) were studied by tandem mass spectrometry (MS/MS). The transition used for quantification was selected according to the highest value of the signal-over-blank ratio (S/B) obtained from each adduct fragmentation. When derivatizing nitrite ion labeled with the stable 15N isotope, followed by liquid chromatography (LC)-MS/MS measurement, the lowest limit of quantification obtained was 5 nM with NAT. The method was applied to study the intestinal permeability of S-nitrosoglutathione, a drug candidate for the chronic treatment of cardiovascular disease.This coumpound was labeled with 15N and its permeability was studied in an ex vivo rat intestine model using an Ussing chamber.
Les conférences auront lieu dans l'Amphithéâtre BRUNTZ– 2ème hall
Le programme est le suivant :
- 09h15 Accueil du Pr Raphaël DUVAL, Doyen de la Faculté de Pharmacie
- 09h30 Prof. Zilin Chen and Prof. Haibing Zhou "Présentation of Wuhan University and of the Faculty of Pharmacy"
- 09h45 Prof. Zilin Chen (Vice Dean of School of Pharmaceutical Sciences, Wuhan University) "Solid Phase Microextraction and Capillary Electro-chromatographic Column Technology for Pharmaceutical Analysis"
- 10h15 Prof. Haibing Zhou (Vice Dean of School of Pharmaceutical Sciences, Wuhan University) "Novel Hybrid Conjugates with Dual Suppression of Estrogenic and Inflammatory Activities Display Significantly Improved Potency against Breast Cancer"
- 10h45 Haiyan YU (Ph D Student EA 3452 CITHEFOR) "Oral bioavailability studies of S-nitrosoglutathione using intestinal barrier models by liquid chromatography coupled with mass spectrometry after labeling with the isotope nitrogen 15"
Marie-Lynda BOURESSAM soutiendra sa thèse de doctorat intitulée "Importance de la S-nitrosation des récepteurs cérébrovasculaires de l’angiotensine II" le mercredi 4 juillet 2018 à 13h dans la salle des Thèses (Lionnois) à Nancy.
Le jury est composé de :
- Mme Isabelle MARGAILL (Rapporteur, PR, EA4475, Université Paris Descartes, Paris)
- Mr Daniel HENRION (Rapporteur, DR, UMR CNRS 6261 - INSERM 1083, Université d’Angers, Angers)
- Mme Isabelle LARTAUD (Examinateur, PR, EA3452 CITHEFOR, Université de Lorraine, Nancy, Directeur de thèse)
- Mr François DUPUIS (Examinateur, MCU, EA3452 CITHEFOR, Université de Lorraine, Nancy, Co-directeur de thèse)
- Mr Arnaud BIANCHI (Membre invité, IR1, UMR7365, Université de Lorraine, Vandoeuvre les Nancy)
L'article "Intestinal absorption of S-nitrosothiols: permeability and transport mechanisms" vient de paraître dans le journal "Biochemical Pharmacology"
Auteurs : Justine Bonetti, Yi Zhou, Marianne Parent, Igor Clarot, Haiyan Yu, Isabelle Fries-Raeth, Pierre Leroy, Isabelle Lartaud, Caroline Gaucher
Référence de l'article : Biochem Pharmacol. 2018 Jun 21. pii: S0006-2952(18)30231-4. doi: 10.1016/j.bcp.2018.06.018.
Abstract :
S-Nitrosothiols, a class of NO donors, demonstrate potential benefits for cardiovascular diseases. Drugs for such chronic diseases require long term administration preferentially through the oral route. However, the absorption of S-nitrosothiols by the intestine, which is the first limiting barrier for their vascular bioavailability, is rarely evaluated. Using an in vitro model of intestinal barrier, based on human cells, the present work aimed at elucidating the mechanisms of intestinal transport (passive or active, paracellular or transcellular pathway) and at predicting the absorption site of three S-nitrosothiols: S-nitrosoglutathione (GSNO), S-nitroso-N-acetyl-l-cysteine (NACNO) and S-nitroso-N-acetyl-d-penicillamine (SNAP). These S-nitrosothiols include different skeletons carrying the nitroso group, which confer different physico-chemical characteristics and biological activities (antioxidant and anti-inflammatory). According to the values of apparent permeability coefficient, the three S-nitrosothiols belong to the medium class of permeability. The evaluation of the bidirectional apparent permeability demonstrated a passive diffusion of the three S-nitrosothiols. GSNO and NACNO preferentially cross the intestinal barrier though the transcellular pathway, while SNAP followed both the trans- and paracellular pathways. Finally, the permeability of NACNO was favoured at pH 6.4, which is close to the pH of the jejunal part of the intestine. Through this study, we determined the absorption mechanisms of S-nitrosothiols and postulated that they can be administrated through the oral route.
L'EA 3452 a acquis récemment deux nouveaux équipements (voir photo), grâce au soutien financier du CPER (Contrat de Plan Etat-Région) :
- un appareil de dissolution à flux continu USP 4
- une électrode à monoxyde d'azote ainsi que son système d'acquisition
Ces deux appareils sont en service et viennent compléter l'équipement des plateaux techniques "formulation" et "physico-chimie".
L'article "No answer to the lack of specificity: mouse monoclonal antibody targeting the angiotensin II type 1 receptor AT1 fails to recognize its target" vient de paraître dans le journal "Naunyn-Schmiedeberg's Archives of Pharmacology"
Auteurs : Marie-Lynda Bouressam, Isabelle Lartaud, François Dupuis, Sandra Lecat
Référence de l'article : 2018 Jun 4. doi: 10.1007/s00210-018-1522-4. [Epub ahead of print]
Abstract :
Numerous antibodies targeting G protein-coupled receptors (GPCRs) have been described as non-specific among the polyclonal antibodies against angiotensin II type 1 receptor (AT1). We have tested the newly developed AT1 receptor mouse monoclonal antibody for its specificity. Human embryonic kidney (HEK293) cells, which do not endogenously express AT1 receptor, were transfected in order to overexpress a fluorescently labeled enhanced green fluorescent protein (EGFP)-tagged human AT1 receptor. Western blot and immunofluorescence assays were performed to test the specificity of the Santa Cruz monoclonal antibody sc-57036. These results were compared to the ones obtained with the polyclonal sc-1173 anti-AT1 receptor antibodies that have already been described as non-specific. While the positive controls using GFP antibodies detected the EGFP-tagged AT1 receptor, both polyclonal and monoclonal anti-AT1 receptor antibodies failed to specifically recognize the corresponding band by Western blot, as similar bands were revealed in either transfected or non-transfected cells. It also failed to detect AT1 receptor in immunofluorescence experiments. The lack of target recognition of the monoclonal AT1 receptor antibody in our experimental conditions suggests that this antibody could give misleading results such as misidentification of the protein. To our knowledge, no specific antibodies targeting AT1 receptors have been developed so far and the field is thus in need of new technical developments.

Conférence du Dr Amedea B Seabra du Center for Natural and Human Sciences Federal University of ABC (Brésil) le 15 juin à la Faculté de Pharmacie de Nancy
"Nitric oxide releasing biomaterials for biomedical and agricultural applications"
The free radical nitric oxide (NO) plays a key role in several biological processes in mammals, such as the control of vasodilation, the immunological responses, the inhibition of platelet adhesion, the cell communication, anti-cancer activities, and the wound healing. In addition, NO is recognized as important molecule in several physiologic process in plants, including break seed dormancy, stimulate plant germination and greening, control iron homeostasis in plants, and improve plant tolerance to salinity, metal toxicity, temperature and drought stress. As a free radical, NO donors are administrated in several applications. Among them, S-nitrosothiols (RSNOs) are an important class of NO donors, since they spontaneously decompose releasing NO, and this decomposition can be triggered by light irradiation (visible region). Several papers in the literature reveal that the combination of nanotechnology and RSNOs is a promising strategy to allow the therapeutic uses of NO. In this context, this presentation focuses on the synthesis strategies, characterization, in vitro and in vivo applications of NO-based metallic and polymeric nanoparticles, hydrogels and films for biomedical and agriculture applications.