High-performance liquid chromatography coupled with electrospray tandem mass spectrometry (LC/MS/MS) method for the simultaneous determination of diazepam, atropine and pralidoxime in human plasma

A high-performance liquid chromatography coupled with electrospray tandem mass spectrometry (LC/MS/MS) procedure for the simultaneous determination of diazepam from avizafone, atropine and pralidoxime in human plasma is described. Sample pretreatment consisted of protein precipitation from 100 μl of plasma using acetonitrile containing the internal standard (diazepam D5). Chromatographic separation was performed on a X-Terra® MS C8 column (100 mm × 2.1 mm, i.d. 3.5 μm), with a quick stepwise gradient using a formate buffer (pH 3, 2 mM) and acetonitrile at a flow rate of 0.2 ml/min. The triple quadrupole mass spectrometer was operated in positive ion mode and multiple reaction monitoring was used for drug quantification. The method was validated over the concentration ranges of 1–500 ng/ml for diazepam, 0.25–50 ng/ml for atropine and 5–1000 ng/ml for pralidoxime. The coefficients of variation were always <15% for both intra-day and inter-day precision for each analyte. Mean accuracies were also within ±15%. This method has been successfully applied to a pharmacokinetic study of the three compounds after intramuscular injection of an avizafone–atropine–pralidoxime combination, in healthy subjects

Organophosphorous neurotoxic antidotes : Pharmacokinetic analysis of avizafone hydrolysis and pralidoxime

Date du colloque&nbsp;: 04/2008</p

La toxicologie au coeur des problématiques de médecine légale : à propos de quelques observations

Date du colloque&nbsp;: 12/01/2009</p

Skin vascular resistance in the standing position increases significantly after 7 days of dry immersion

Actual and simulated microgravity induces hypovolemia and cardiovascular deconditioning, associated with vascular dysfunction. We hypothesized that vasoconstriction of skin microcirculatory bed should be altered following 7 days of simulated microgravity in order to maintain cardiovascular homeostasis during active standing. Eight healthy men were studied before and after 7 days of simulated microgravity modeled by dry immersion (DI). Changes of plasma volume and orthostatic tolerance were evaluated. Calf skin blood flow (laser-Doppler flowmetry), ECG and blood pressure signal during a 10-min stand test were recorded, and skin vascular resistance, central hemodynamics, baroreflex sensitivity and heart rate variability were estimated. After DI we observed increased calf skin vascular resistance in the standing position (12.0 +/- 1.0 AU-after- vs. 6.8 +/- 1.4 AU-before), while supine it was unchanged. Cardiovascular deconditioning was confirmed by greater tachycardia on standing and by hypovolemia (-16 +/- 3% at day 7 of DI). Total peripheral resistance and indices of cardiovascular autonomic control were not modified. In conclusion, unchanged autonomic control and total peripheral resistance suggest that increased skin vasoconstriction to standing involves rather local mechanisms-as venoarteriolar reflex-and might compensate insufficient vasoconstriction of other vascular beds

Suicide by Skull Stab Wounds: A Case of Drug-Induced Psychosis

Suicide by stabbing to the head and/or driving sharp objects into the skull is of extreme rarity. This article reports the case of a 27-year-old man, who committed suicide by multiple knife stabs and cuts to the head, the torso, one shoulder and the forearms. Autopsy showed a perforating wound of the skull and the 10-cm long broken blade of the knife being still embedded in the right temporal lobe of the brain. The deceased had no history of psychiatric illness but was currently treated by mefloquine, a quinine derivative associated with a high rate of psychiatric adverse effects. Toxicological examination confirmed a recent intake of mefloquine together with chloroquine, another antimalarial drug. To our knowledge, this is the first report of a completed suicide with very strong evidence of mefloquine implication. Discussion focuses upon mefloquine-induced psychiatric disorders and highlights the importance of performing toxicological investigations in cases of unusual suicides

Non-local rheology in dense granular flows -- Revisiting the concept of fluidity

Granular materials belong to the class of amorphous athermal systems, like foams, emulsion or suspension they can resist shear like a solid, but flow like a liquid under a sufficiently large applied shear stress. They exhibit a dynamical phase transition between static and flowing states, as for phase transitions of thermodynamic systems, this rigidity transition exhibits a diverging length scales quantifying the degree of cooperatively. Several experiments have shown that the rheology of granular materials and emulsion is non-local, namely that the stress at a given location does not depend only on the shear rate at this location but also on the degree of mobility in the surrounding region. Several constitutive relations have recently been proposed and tested successfully against numerical and experimental results. Here we use discrete elements simulation of 2D shear flows to shed light on the dynamical mechanism underlying non-locality in dense granular flows