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International audience; Nowadays, infections caused by multidrug-resistant bacteria represent one of the biggest challenges in the medical field and there is an urgent need to develop efficient and well tolerated antibacterials targeting unique cellular processes.[1,2] Two-component signal transduction systems (TCS) are widely used for bacteria to translate an external signal into a cellular response. They are ubiquitous in bacteria, absent in mammals and are integrated into various pathogenic pathways.[3,4] In order to attenuate these signaling pathways, we aimed at targeting the TCS signal transducer histidine kinase by focusing on their highly conserved ATP-binding domain.[5] Preliminary modeling work carried out in our laboratory led to a series of thiophene derivatives. Twenty-four new molecules were synthesized and evaluated in vitro on bacterial histidine kinases PhoR, ResE and WalK. We identify eight compounds with significant inhibitory activity against these proteins. Nevertheless, only two compounds exhibited broad-spectrum antimicrobial activity.[6] That is the reason why in order to improve the biological activity of the synthesized molecules, a new series of amino thiophene has been developed. The nitro function of the preceding molecules was reduced by hydrogenation in situ using several conditions.

Poisoning by psychoactive substances is more and more frequent and over the last decade New Psychoactives Substances (NPS), whose toxicity is unknown have appeared. Poison control centers received regularly calls for patients exposed to severe poisoning, for which analytical evidence of the presence of these substances is often lacking, which limits its expert assessment. The main objective of the Fériatox study is to know, with analytical proof, the main psychoactive molecules that initially led to a management in an advanced medical post during SouthWest Ferias, and to describe their clinical pictures to improve their management. Blood samples by dried blood spot (DBS), urinary and hair samples were performed. 27 patients were included: 27 DBS, 24 hair samples and 14 urine samples. The main clinical symptoms were: mydriasis (52%), tachycardia (41%), coma (33%), agitation (30%). The most involved molecules were Cocaine (n = 9) and MDMA (n = 4). The clinical pictures were consistent with what was expected for these consumed substances. There were no deaths or admissions to resuscitation departement. No NPS were found on the DBS. Performing a similar study in music festivals could be relevant., Les intoxications par les substances psychoactives sont de plus en plus nombreuses et depuis une dizaine d’années des nouveaux produits de synthèse (NPS), dont la toxicité est inconnue ont fait leur apparition. Les centres antipoison sont régulièrement sollicités pour des intoxications graves, pour lesquelles les preuves analytiques de la présence de ces substances sont souvent manquantes, ce qui en limite l’expertise. L’objectif principal de l’étude Fériatox est de connaître avec preuve analytique à l’appui les principales molécules psychoactives ayant conduit initialement à une prise en charge dans un poste médical avancé au cours des férias, et de décrire ces tableaux cliniques pour en améliorer la prise en charge ultérieure. Des prélèvements sanguins par dried blood spot (DBS), urinaires et capillaires ont été effectués. 27 patients ont été inclus: 27 prélèvements DBS, 24 prélèvements de cheveux et 14 prélèvements urinaires. Les principaux signes cliniques rencontrés étaient : mydriase (52%), tachycardie (41%), coma (33%), agitation (30%). Les molécules les plus en cause sont la cocaïne (n=9) et la MDMA (n=4). Les tableaux cliniques sont cohérents avec ce qui était attendu pour les substances consommées. Il n’y a eu aucun décès ni d’admission en réanimation. Aucun NPS n’a été retrouvé sur les DBS. La réalisation d’une étude similaire dans les festivals de musique pourrait être pertinente.

International audience

International audience