Jaffre N

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Full name : Jaffre Nina

First name : Nina

Mail : Institut de Recherche Biomedicale des armees - Departement toxicologie et risques chimiques, Bretigny-sur-Orge

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Country : France

Email : nina.jaffre@irba.fr

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References (4)

Title : Baseline physiological data from anesthetized pigs in a VX intoxication model - Goulay_2024_Toxicol.Lett__
Author(s) : Goulay R , Femy F , Nervo A , Valentino S , Madi M , Joly AL , Servonnet A , Nachon F , Reymond C , Jaffre N
Ref : Toxicol Lett , : , 2024
Abstract : Over the past fifty years, swine models have been used for organophosphorus intoxication studies. Among these studies and others on the swine model in general, some physiological data, especially cholinesterase activity highly impacted by organophosphorus compounds like nerve agent VX, still need to be completed. To support and compare our model to others, we have published the experimental protocol, the physiological values of 31 juvenile anesthetized pigs, and the 6h-follow-up of six supplementary anesthetized control animals and 7 VX-intoxicated pigs. We reported hemodynamics and respiratory parameters, blood levels in several biochemical parameters, blood gas, and complete blood count and compared them to the literature. We also focused on tissue and blood cholinesterase activities and detailed them for acetylcholinesterase and butyrylcholinesterase. After establishing a broad physiological data set consistent with the literature, we reported several cardio-respiratory parameters that seem more affected by an organophosphate intoxication, like heart rate, arterial blood pressure, cardiac output, and respiratory rate. Within the blood, oxygen saturation (SpO(2)), lactatemia, base excess, and glycemia can also be measured and associated with the other parameters to evaluate the life-threatening status. This swine model is currently used to develop and evaluate medical countermeasures against organophosphate nerve agent intoxications.
ESTHER : Goulay_2024_Toxicol.Lett__
PubMedSearch : Goulay_2024_Toxicol.Lett__
PubMedID: 38768837

Title : Toxicokinetics of plasmatic VX in a swine model: comparison of a simple enzymatic titration method with a mass spectrometry method - Femy_2022_Arch.Toxicol__
Author(s) : Femy F , Meesemaecker G , Belverge N , Courageux C , Nervo A , Goulay R , Reymond C , Chantegreil F , Madi M , Nachon F , Taudon N , Jaffre N
Ref : Archives of Toxicology , : , 2022
Abstract : Recent events have shown that organophosphorus nerve agents (OPNAs) are a serious threat. Cholinesterase inhibition by OPNAs results in acetylcholine accumulation, a cholinergic crisis leading to death if untreated. Efficacy assessment of new medical countermeasures against OPNAs relies on translational animal models. We developed a swine model of percutaneous VX intoxication and a simple plate reader-based enzymatic method to quantify plasmatic VX over time. Juvenile pigs anesthetized with sevoflurane were poisoned with a single supralethal (n = 5; 1200 microg/kg) or sublethal (n = 6; 320 microg/kg) percutaneous dose of VX. These intoxicated animals were compared to 7 control animals. Repeated blood sampling was performed up to 6 h post-intoxication. Blood cholinesterase activities were measured using the Ellman assay. Nanomolar plasma concentrations of VX were measured by exogenous butyrylcholinesterase added to an aliquot of plasma. As expected, we observed a steady increase in plasma concentration of VX over time concomitant to a decrease in blood cholinesterase activities for all intoxicated pigs. Despite the simplicity of the enzymatic method, the results obtained are in good agreement with those of the liquid chromatography-mass spectrometry method. This method is also applicable to other OPNAs such as novichoks with minor adaptations.
ESTHER : Femy_2022_Arch.Toxicol__
PubMedSearch : Femy_2022_Arch.Toxicol__
PubMedID: 36326899

Title : Efficacy Assessment of an Uncharged Reactivator of NOP-Inhibited Acetylcholinesterase Based on Tetrahydroacridine Pyridine-Aldoxime Hybrid in Mouse Compared to Pralidoxime - Calas_2020_Biomolecules_10_
Author(s) : Calas AG , Hanak AS , Jaffre N , Nervo A , Dias J , Rousseau C , Courageux C , Brazzolotto X , Villa P , Obrecht A , Goossens JF , Landry C , Hachani J , Gosselet F , Dehouck MP , Yerri J , Kliachyna M , Baati R , Nachon F
Ref : Biomolecules , 10 : , 2020
Abstract : (1) Background: Human exposure to organophosphorus compounds employed as pesticides or as chemical warfare agents induces deleterious effects due to cholinesterase inhibition. One therapeutic approach is the reactivation of inhibited acetylcholinesterase by oximes. While currently available oximes are unable to reach the central nervous system to reactivate cholinesterases or to display a wide spectrum of action against the variety of organophosphorus compounds, we aim to identify new reactivators without such drawbacks. (2) Methods: This study gathers an exhaustive work to assess in vitro and in vivo efficacy, and toxicity of a hybrid tetrahydroacridine pyridinaldoxime reactivator, KM297, compared to pralidoxime. (3) Results: Blood-brain barrier crossing assay carried out on a human in vitro model established that KM297 has an endothelial permeability coefficient twice that of pralidoxime. It also presents higher cytotoxicity, particularly on bone marrow-derived cells. Its strong cholinesterase inhibition potency seems to be correlated to its low protective efficacy in mice exposed to paraoxon. Ventilatory monitoring of KM297-treated mice by double-chamber plethysmography shows toxic effects at the selected therapeutic dose. This breathing assessment could help define the No Observed Adverse Effect Level (NOAEL) dose of new oximes which would have a maximum therapeutic effect without any toxic side effects.
ESTHER : Calas_2020_Biomolecules_10_
PubMedSearch : Calas_2020_Biomolecules_10_
PubMedID: 32512884

Title : Superior efficacy of HI-6 dimethanesulfonate over pralidoxime methylsulfate against Russian VX poisoning in cynomolgus monkeys (Macaca fascicularis) - Reymond_2018_Toxicology_410_96
Author(s) : Reymond C , Jaffre N , Taudon N , Menneteau M , Chaussard H , Denis J , Castellarin C , Dhote F , Dorandeu F
Ref : Toxicology , 410 :96 , 2018
Abstract : Organophosphorus nerve agents still represent a serious risk to human health. In the French armed forces, the current emergency treatment against OP intoxications is a fully licensed wet-dry dual-chambered autoinjector (Ineurope (R)), that contains pralidoxime methylsulfate (2-PAM) to reactivate inhibited acetylcholinesterase (AChE), atropine sulfate (AS) and avizafone chlorhydrate (AVZ). While this treatment is effective against several of the known nerve agents, it shows little efficacy against the Russian VX (VR), one of the most toxic compounds. HI-6 dimethanesulfonate (HI-6 DMS) is an oxime able to reactivate in vitro and in vivo VR-inhibited AChE. To confirm the superiority of HI-6 DMS towards 2-PAM prior to licensing, we compared the two 3-drug-combinations (HI-6 vs 2-PAM, 33 and 18 mg/kg respectively, equimolar doses; AS/AVZ 0.25/0.175 mg/kg respectively) in VR-poisoned cynomolgus macaques, the model required by the French drug regulatory agency. In parallel we performed HI-6 pharmacokinetics analysis using a one compartment model. A better efficacy of the HI-6 DMS combination was clearly observed: up to 5 LD50 of VR (i.m.), a single administration of the HI-6 DMS combination, shortly after the onset of clinical signs, prevented death of the four intoxicated animals. Conversely 2-PAM only prevented death in one out of three subjects exposed to the same amount of VR. As expected with V agents, reinhibition of blood AChE was observed but without any apparent impact on the clinical recovery of the animals. A single administration of the HI-6 DMS combination was still but partially effective at 15 LD50 of VR, allowing a 50% survival rate.
ESTHER : Reymond_2018_Toxicology_410_96
PubMedSearch : Reymond_2018_Toxicology_410_96
PubMedID: 30218682