[The advantages of the fire department nurse in managing a CBRN event]. / Les atouts de l'infirmier de sapeurs-pompiers dans la gestion d'un événement NRBC.

Nuclear, radiological, biological and chemical hazards are caused by agents of very different origins. They can be blatant or insidious, difficult to detect, accidental or intentional. In all cases, in addition to treating victims, the aim is to avoid contamination of hospital services. Faced with these risks, which are often seen as unlikely or too complex, the firefighter nurse represents an asset for his or her establishment, in terms of both crisis anticipation and management.

[The benefits of PSI when dealing with large numbers of victims]. / L'intérêt de disposer d'ISP lors de la prise en charge de nombreuses victimes.

The Many Victims plan describes aims to organize evacuations in a coherent manner, to preserve the human and material resources capacity of the fire and rescue service. The aim is to avoid postponing the disaster on the ground to the hospital and to guarantee the continuity of response to the current risk and an over-event. In this device, the firefighter nurse is an asset by his ability to take care of serious victims without the physical presence of a doctor, in a context of crisis.

The discovery of IDX21437: Design, synthesis and antiviral evaluation of 2'-α-chloro-2'-ß-C-methyl branched uridine pronucleotides as potent liver-targeted HCV polymerase inhibitors.

Herein we describe the discovery of IDX21437 35b, a novel RPd-aminoacid-based phosphoramidate prodrug of 2'-α-chloro-2'-ß-C-methyluridine monophosphate. Its corresponding triphosphate 6 is a potent inhibitor of the HCV NS5B RNA-dependent RNA polymerase (RdRp). Despite showing very weak activity in the in vitro Huh-7 cell based HCV replicon assay, 35b demonstrated high levels of active triphosphate 6 in mouse liver and human hepatocytes. A biochemical study revealed that the metabolism of 35b was mainly attributed to carboxyesterase 1 (CES1), an enzyme which is underexpressed in HCV Huh-7-derived replicon cells. Furthermore, due to its metabolic activation, 35b was efficiently processed in liver cells compared to other cell types, including human cardiomyocytes. The selected RP diastereoisomeric configuration of 35b was assigned by X-ray structural determination. 35b is currently in Phase II clinical trials for the treatment of HCV infection.

Design, synthesis and antiviral evaluation of 2'-C-methyl branched guanosine pronucleotides: the discovery of IDX184, a potent liver-targeted HCV polymerase inhibitor.

BACKGROUND: Ribonucleoside analogs possessing a ß-methyl substituent at the 2'-position of the d-ribose moiety have been previously discovered to be potent and selective inhibitors of hepatitis C virus (HCV) replication, their triphosphates acting as alternative substrate inhibitors of the HCV RdRp NS5B. Results/methodology: In this article, the authors detail the synthesis, anti-HCV evaluation in cell-based replicon assays and structure-activity relationships of several phosphoramidate diester derivatives of 2'-C-methylguanosine (2'-MeG). CONCLUSION: The most promising compound, namely the O-[S-(hydroxyl)pivaloyl-2-thioethyl]{abbreviated as O-[(HO)tBuSATE)]} N-benzylamine phosphoramidate diester derivative (IDX184), was selected for further in vivo studies, and was the first clinical pronucleotide evaluated for the treatment of chronic hepatitis C up to Phase II trials.

Synthesis of 1'-C-fluoromethyladenosine.

In search for new antiviral agents, we have been interested in 1'-C-fluoromethyl branched ribonucleosides. In this paper, we describe the synthesis of 1'-C-fluoromethyladenosine via electrophilic fluorination of exo-glycal.