Determination of RSD921 in human plasma by high-performance liquid chromatography-tandem mass spectrometry using tri-deuterated RSD921 as internal standard: application to a phase I clinical trial.

A fast, sensitive and specific method is presented for the quantification of RSD921 in human plasma by liquid chromatography coupled with tandem mass spectrometry using tri-deuterated RSD921 (3d-RSD921) as an internal standard. A single-step liquid/liquid extraction was performed with diethyl ether/hexane (80 : 20, v/v) using 0.5 ml of plasma. The plasma calibration curves were linear from 0.1 to 20 ng ml(-1) (r > 0.999). Between-run precision, based on the percent relative deviation for replicate (n = 40) quality controls, was < or =7.27% (0.5 ng ml(-1)), < or =7.39% (5.0 ng ml(-1)), and < or =5.06% (20.0 ng ml(-1)). Between-run accuracies, based on the relative error, were +/-2.59%, +/-1.23% and +/-1.64% respectively. The method was developed to evaluate the pharmacokinetic profile after 15 min of intravenous stepwise-ascending infusion dose of RSD921 in 18 healthy volunteers. A dissociation study of protonated RSD921 and 3d-RSD921 by collision-induced dissociation using in-source fragmentation and tandem mass spectrometry is also presented.     

Density-driven structural transformations in network forming glasses: a high-pressure neutron diffraction study of GeO(2) glass up to 17.5?GPa

The structure of GeO(2) glass was investigated at pressures up to 17.5(5)?GPa using in situ time-of-flight neutron diffraction with a Paris-Edinburgh press employing sintered diamond anvils. A new methodology and data correction procedure were developed, enabling a reliable measurement of structure factors that are largely free from diamond Bragg peaks. Calibration curves, which are important for neutron diffraction work on disordered materials, were constructed for pressure as a function of applied load for both single and double toroid anvil geometries. The diffraction data are compared to new molecular-dynamics simulations made using transferrable interaction potentials that include dipole-polarization effects. The results, when taken together with those from other experimental methods, are consistent with four densification mechanisms. The first, at pressures up to ??5?GPa, is associated with a reorganization of GeO(4) units. The second, extending over the range from ??5 to 10?GPa, corresponds to a regime where GeO(4) units are replaced predominantly by GeO(5) units. In the third, as the pressure increases beyond ～10?GPa, appreciable concentrations of GeO(6) units begin to form and there is a decrease in the rate of change of the intermediate-range order as measured by the pressure dependence of the position of the first sharp diffraction peak. In the fourth, at about 30?GPa, the transformation to a predominantly octahedral glass is achieved and further densification proceeds via compression of the Ge-O bonds. The observed changes in the measured diffraction patterns for GeO(2) occur at similar dimensionless number densities to those found for SiO(2), indicating similar densification mechanisms for both glasses. This implies a regime from about 15 to 24?GPa where SiO(4) units are replaced predominantly by SiO(5) units, and a regime beyond ～24?GPa where appreciable concentrations of SiO(6) units begin to form.     

Study of the 2-Benzimidazolylaminomethylphosphonic Acid Derivatives by Mass Spectroscopy

Abstract

The present paper reports the mass spectra of some compounds of 2-alkylenbenzimidazolylaminomethylphosphonates with the general formula:     

Contrasting effects of excess ferritin expression on the iron-mediated oxidative stress induced by tert-butyl hydroperoxide or ultraviolet-A in human fibroblasts and keratinocytes

Iron and/or ferritin accumulation are known to occur under pathological conditions in many inflammatory skin diseases or in human skin chronically exposed to UV light. Under such conditions, ferritin is believed to play an effective protective role in accommodating and 'deactivating' excess 'free' iron produced by the inflammatory process or the UV illumination. The present study compares the relationship between ferritin over-expression and effects of an oxidative stress induced chemically by tert-butyl hydroperoxide or photochemically by UV-A radiation. As shown by immunoassay, cultured MRC 5 and HS 68 fibroblasts treated for at least one day with transferrin or overnight with non-toxic concentrations of the ferric nitrilotriacetate complex express up to 10 times more ferritin than untreated cells, whereas a five-fold increase is obtained with NCTC 2544 keratinocytes. In all cases a parallel increase in soluble cellular iron is measured by inductive plasma emission spectroscopy. The superoxide dismutase and catalase activities and total glutathione levels are not modified by the iron treatment, whereas a transient increase in the Se-dependent glutathione peroxidase activity of keratinocytes is observed after a short incubation with the iron complex. In keratinocytes and fibroblasts, ferritin over-expression after iron treatment markedly inhibits lipid peroxidation but, paradoxically, not the mortality induced by tert-butyl hydroperoxide. In contrast, this excess ferritin does not protect cells from both the peroxidation and mortality induced by moderate doses (30 J/cm2) of UV-A radiation. As a consequence, protection against oxidative damage by excess ferritin synthesis clearly depends on the nature of the oxidative stress on cell targets and it seems to be of lesser importance in the case of photochemically induced oxidation.     

Concerted and stepwise proton-coupled electron transfers in aquo/hydroxo complex couples in water: oxidative electrochemistry of [Os(II)(bpy)(2)(py)(OH(2))](2+)

Successive oxidation of transition metal(II) aqua complexes (M(II)OH(2) to M(III)OH) is a domain in which proton-coupled electron transfer reactions are extremely common. The mechanism of these PCET reactions-concerted or stepwise-is an important issue in the understanding and design of natural or artificial systems catalyzing the formation of dioxygen by four-electron oxidation of water. Concerted proton-coupled electron transfer from an aqua metal(II) to a hydroxo metal(III) complex requires the close proximity of a proton-accepting group with a pK value between those of the aqua complexes. Otherwise, stepwise electron-proton or proton-electron pathways involving high-energy intermediates are followed. Concerted proton-electron pathways involving water as proton-acceptor or proton-donor group are inefficient. Cyclic voltammetry of the title complex in buffered aqueous solution and re-examination of previous results for the same complex attached to an electrode surface are used to establish these conclusions, which provide a starting point on the route to higher degrees of oxidation, such as those involved in the catalysis of water oxidation.     

High-pressure X-ray diffraction study of 1T-TaS2

We present a room temperature high-pressure X-ray diffraction study of the layered compound 1T-TaS₂ up to 20 GPa. This material is known to exhibit a variety of structural phase transitions that are ascribed to the stabilization of charge density wave states. It has been recently shown that at pressures larger than 3 GPa and up to 25 GPa, 1T-TaS₂ becomes superconductor below about 5 K. It was suggested that this superconductivity coexists with different CDW states, an hypothesis that can be tested by X-ray diffraction. Our first results at room temperature show that at around 1.9 GPa, the nearly-commensurate (NCCDW) phase transforms into a phase similar to the high temperature incommensurate phase (ICCDW). Above 9 GPa, we show the existence of another IC phase, still discernable up to 20 GPa despite the pressure-induced crystal damage above 13 GPa. These results are consistent with resistivity measurements, but call for a complete exploration of the P–T phase diagram of 1T-TaS₂.     

Influence of negative leader propagation on the triggering and guiding of high voltage discharges by laser filaments

The triggering and guiding of negative discharges using filaments induced by a femtosecond-terawatt laser pulse have been studied in sphere-plane gaps up to 4.5 meters. Fast-frame camera pictures allow the evaluation of the influence of the negative leader propagation on the triggering and guiding process. We show that the plasma channel can either trigger a space-leader discharge or act as a guiding path for the negative leader head. For the latter case the results suggest a linear dependence of the guided lengths up to 2.4 m, while the formation of a space-leader reduces this guided length by up to 50%. This effect is explained by the limited plasma lifetime of the filament that is measured to be about 1 μs.     

First improvements in the detection and quantification of label-free nucleic acids by laser-induced breakdown spectroscopy: Application to the deoxyribonucleic acid micro-array technology

The accurate quantification of nucleic acids is essential in many fields of modern biology and industry, and in some cases requires the use of fluorescence labeling. Yet, in addition to standardization problems and quantification reproducibility, labeling can modify the physicochemical properties of molecules or affect their stability. To address these limitations, we have developed a novel method to detect and quantify label-free nucleic acids. This method is based on stoichiometric proportioning of phosphorus in the nucleic acid skeleton, using laser-induced breakdown spectroscopy, and a specific statistical analysis, which indicates the error probability for each measurement. The results obtained appear to be quantitative, with a limit of detection of 10⁵ nucleotides/µm² (i.e. 2 × 10¹³ phosphorus atoms/cm²). Initial micro-array analysis has given very encouraging results, which point to new ways of quantifying hybridized nucleic acids. This is essential when comparing molecules of different sequences, which is presently very difficult with fluorescence labeling.