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Le chemsex, phénomène récent et complexe, est de plus en plus reconnu comme un problème de santé publique. Cependant, les données françaises sur sa prévalence et ses caractéristiques spécifiques en France sont encore limitées. Cette enquête nationale vise à combler cette lacune en rassemblant des connaissances sur la prévalence du chemsex, les caractéristiques des personnes impliquées, les substances les plus couramment utilisées et leurs effets sur la santé, grâce à une collaboration impliquant plusieurs laboratoires de toxicologie à la demande de la Société française de toxicologie analytique (SFTA)

Le chemsex, phénomène récent et complexe, est de plus en plus reconnu comme un problème de santé publique. Cependant, les données françaises sur sa prévalence et ses caractéristiques spécifiques en France sont encore limitées. Cette enquête nationale vise à combler cette lacune en rassemblant des connaissances sur la prévalence du chemsex, les caractéristiques des personnes impliquées, les substances les plus couramment utilisées et leurs effets sur la santé, grâce à une collaboration impliquant plusieurs laboratoires de toxicologie à la demande de la Société française de toxicologie analytique (SFTA).

Les analyses toxicologiques accompagnent très souvent les autopsies et prennent une place conséquente dans les conclusions du décès. Pour autant, elles ne sont pas toujours à suivre aveuglement. Nous présentons ici le cas de Monsieur X., 33 ans, atteint de schizophrénie et de déficience intellectuelle majeure et décédé lors d’une hospitalisation dans une unité psychiatrique fermée. Le patient a été décrit par l’équipe infirmière comme conscient et ne présentant pas de vomissements, quelques heures avant son décès. S’étant plaint, le matin de son décès, de douleurs abdominales, le patient avait reçu du « DIFFU-K », une antalgie par paracétamol et phloroglucinol, ainsi que son traitement journalier habituel, dont des laxatifs à posologie maximale. Monsieur X n’a pas bénéficié d’imagerie ou d’un transfert au centre hospitalier le plus proche. Monsieur X. est retrouvé en arrêt cardiorespiratoire en début de soirée, et décèdera malgré les tentatives de réanimation. Un obstacle médicolégal est posé et une autopsie est réalisée.

Les intoxications accidentelles ou intentionnelles au carvédilol sont rarement rapportées. Ce cas de tentative de suicide avec une quantité importante de carvédilol à libération immédiate (75mg) et d’alcool permet une description d’une validation de méthode du dosage du carvédilol en LC-HRMS conforme aux standards américains « ANSI/ASB Standard » ainsi qu’une meilleure compréhension de l’intoxication au carvédilol.

We report the case of a 13-year-old girl, found dead by her father, with a glass containing 15g of white powder and a bottle containing 5g of white powder with a moistened appearance.

Cannabis is the most widely used drug in the world with a prevalence of 2.5%. France and Belgium are no exception […]. Moreover, pediatric cannabis intoxications are increasing due to the growing use of cannabis in the adult population. In this study, we seek to investigate whether there is a correlation between symptoms and biological data in order to facilitate the diagnosis of pediatric cannabis intoxication. Data were retrospectively collected from 11 French laboratories and 2 Belgian laboratories over 3-year period (2019–2021). This study involved 123 children aged 2 months to 4 years. There was a geographical gradient with an increase in intoxication cases from northern to southern regions. THC, 11-OH-THC and THC-COOH levels were respectively 24.4ng/mL (range=0.4–109ng/mL; median=17.3ng/mL), 26.3ng/mL (range=0.6–263ng/mL; median=18ng/mL) and 217ng/mL (range=0.6–921ng/mL; median=163ng/mL). The most frequently observed symptom was drowsiness in 60.2% of cases. Coma (13.8%, n = 17), convulsions (4.1%, n=5) and bradypnea (8.1%, n=10) were the most severe symptoms. The increase of THC content in cannabis products could explain the increase in poisoning severity. However, according to the data collected, it does not seem that the clinical symptoms observed are correlated with plasma or blood THC concentrations. Indeed, cases of coma with Glasgow Coma Scale at 3 have been observed with plasma THC concentrations between 7 and 29ng/mL.

Major histocompatibility complex (MHC) class II deficiency is a primary immunodeficiency. Lentiviral vectors are used for gene therapy in a mouse model of this disease. In addition, by a direct genetic correction approach, a diagnostic test to determine which of the four MHC II genes is defective in new MHC II-deficiency patients has been optimized.

Primary infection of macaques with pathogenic isolates of simian immunodeficiency virus (SIV) (as a model of HIV infection in humans) represents a unique opportunity to study early lentivirus/host interactions. We sought to determine whether there is a temporal relationship linking SIV replication and dissemination and the expression of the chemokine RANTES (regulated upon activation normal T cell expressed and secreted) and the SIV/HIV coreceptor CCR5 in different tissues during acute SIV infection of macaques. Four cynomolgus macaques were inoculated intravenously with a pathogenic primary isolate of SIVmac251. RT-PCR was used to monitor the expression of RANTES and CCR5 mRNA in fresh isolated mononuclear cells from blood, lymph node, and bronchoalveolar lavages. These expressions were compared to those of IFN-γ as an indicator of the development of the immune response and to another receptor for RANTES, CCR1, which is not described as a coreceptor for SIV/HIV-1 entry. An enhancement of CCR1/CCR5 mRNA expression was noticed during primary SIVmac251 infection of macaques, mainly in tissue. In the three different compartments investigated, IFN-γ and RANTES overexpression was noticed by the time of systemic viral replication containment. Our results put CCR5 and RANTES mRNA expression back in the context of inflammatory and immune responses to SIV primary infection.

We are developing a method of gene therapy of HIV infection based on the low constitutive expression of an interferon beta (IFN-beta) gene in HIV target cells. Herein we report the first step in the development of a relevant animal model, provided by the macaque (Macaca fascicularis) infected with a pathogenic SIVmac251 isolate. To avoid the possibility of in vivo rejection of macaque lymphocytes expressing Hu IFN-beta, we have PCRamplified and sequenced the Ma IFN-beta-coding sequence, and placed it under the control of a PstI-Nru I 0.6-kb fragment of the murine H-2Kb gene promoter in the MFG-KbMaIFN beta retroviral vector. Lymphocytic CEMX174 cells, transduced by coculture on packaging cells with this construct, harbored a mean of 0.07 to 1.2 copies of the IFN- beta transgene per cell, and were characterized by an IFN production ranging from 75 to 750 units per 5 X 10 5 cells per 3 days. The IFN-beta-transduced populations displayed an enhanced resistance against the pathogenic SIVmac251 isolate. Control experiments showed that the enhanced resistance could not be ascribed to the Ma IFN- beta released during the 3 days of coculture by the packaging cells, or to the mere transduction with a retroviral vector. Macaque lymphocytes transduced by the MFG-KbMaIFN beta retroviral vector by coculture on packaging cells, acquired a mean number of IFN- beta transgene copies per cell ranging from 0.03 to 0.1. Such transduction led to the release of IFN-beta into the culture medium, ranging from 10 to 20 units per 5 X 10 5 cells per 3 days. This increased the anti-SIV resistance of the lymphocytes, as demonstrated by a decreased p27 antigen release into the culture medium, without affecting lymphocyte proliferation.

To test the protection afforded by a weakly pathogenic HIV-2 isolate against the superinfection or development of SIV-induced disease, we intrarectally challenged six HIV-2-preinfected rhesus monkeys with a pathogenic isolate of SIVmac251. At the time of SIV challenge, none of these HIV-2-infected animals was positive for virus isolation, p27-Gag antigenemia, or HIV-2 provirus detection in PBMCs or peripheral lymph nodes. However, all monkeys exhibited anti-HIV-2 antibody titers ranging from 102to 103. Neutralizing antibodies against the challenge SIV strain were also detected in two animals. After rectal exposure to SIVmac251, five of the six HIV-2-preinfected macaques were superinfected. SIVmac251 DNA sequences were detected repeatedly in the PBMCs of the five superinfected animals and the two controls, whereas no HIV-2 provirus was detected for 14 months postchallenge. The one monkey that resisted superinfection was negative for all SIV infection criteria. This monkey exhibited the highest anti-SIV ELISA and cross-neutralizing antibody titers on the day of SIV challenge. Preinfection with a weakly pathogenic HIV-2 ROD isolate protected one of six macaques from infection with the closely related pathogenic SIVmac251 isolate, but no protection from the progression of disease was evidenced in the other five.

Sexual transmission is the major cause of the AIDS epidemic. For the development of new antiviral and vaccine strategies, we therefore need to understand the mechanisms by which lentiviruses cross the mucosal barrier and the subsequent pathogenic consequences. For this purpose, experimental approaches are greatly facilitated by the development of relevant animal models. In this study, macaques were inoculated intravenously, intrarectally, or intravaginally with a pathogenic cell-free isolate of SIVmac251. Patterns of virological and immunological events significantly differed between vaginally (transient viremia, late seroconversion) and intravenously or intrarectally inoculated monkeys (persistent viremia and early seroconversion). Two weeks after infection, analysis of theenvgene nucleotide sequences of proviruses recovered from PBMCs demonstrated that most of the differences were observed in the V1 loop. Three viral variants were specifically associated with vaginal transmission, whereas no such selection was evidenced after intravenous or intrarectal transmissions. These results are in favor of specific mechanisms associated with vaginal transmission, implicating viral envelope structure.

Comparison of immune responses to infection by a pathogenic or a nonpathogenic immunodeficiency virus in macaques may provide insights into pathogenetic events leading to simian AIDS. This work is aimed at exploring cytokine expression during infection by simian immunodeficiency virus (SIV). We used semiquantitative reverse transcription-PCR to monitor interleukin (IL)-2/interferon (IFN)-gamma (Th1-like), and IL-4/IL-10 (Th2-like) expression in unmanipulated peripheral blood mononuclear cells (PBMCs), during the acute phase of infection of eight cynomolgus macaques (Macaca fascicularis) with a pathogenic primary isolate of SIVmac251 (full-length nef), and of four other cynomolgus macaques by an attenuated molecular clone of SIVmac251 (nef-truncated). All the monkeys became infected, as clearly shown by the presence of infected PBMCs and by seroconversion. Nevertheless, PBMC-associated virus loads and p27 antigenemia in monkeys infected by the attenuated virus clone remained lower than those observed in animals infected with the pathogenic SIVmac251 isolate. A rise of IL-10 mRNA expression occurred in both groups of monkeys coincident with the peak of viral replication. In monkeys infected with the pathogenic SIVmac251, IL-2, IL-4, and IFN-gamma mRNAs were either weakly detectable or undetectable. On the contrary, animals infected by the attenuated virus exhibited an overexpression of these cytokine mRNAs during the first weeks after inoculation. The lack of expression of these cytokines in monkeys infected with the pathogenic primary isolate may reflect early immunodeficiency.

Abstract:We have used semiquantitative RT‐PCR to monitor the expression of mRNA encoding chemoattractant factors IP‐10, MIP‐1α, and IL‐16 in freshly isolated peripheral blood mononuclear cells (PBMCs), lymph node mononuclear cells (LNMCs), and mononuclear cells obtained after bronchoalveolar lavages (BALMCs) of two cynomolgus macaques inoculated intravenously with a pathogenic isolate of simian immunodeficiency virus, SIVmac251. Concomitant with the peak of systemic viral replication (two weeks after experimental inoculation) and proinflammatory cytokine IL‐6 mRNA expression, high levels of MIP‐1α and IP‐10 mRNA were produced in LNMCs and BALMCs. In BALMCs, in which we have reported a marked progressive overexpression of IFN‐γ mRNA coinciding with an increase in the CD8+ lymphocyte percentages, we noticed a progressive overexpression of IL‐16 mRNA. Our results suggest the role of chemokines IP‐10, MIP‐1α, and IL‐16 in the development of inflammatory and immune responses during the early stages of lentiviral infection.