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Pharmacological Research (pharmacological + research)
Selected AbstractsCover Picture: Biotechnology Journal 3/2006BIOTECHNOLOGY JOURNAL, Issue 3 2006Article first published online: 17 MAR 200 Cover illustration: Yeast as a tool for Pharmacological Research. By Stéphane Bach, Jean-Yves Thuret and Marc Blondel. [source] Development of a bacterial challenge test for gnotobiotic sea bass (Dicentrarchus labrax) larvaeENVIRONMENTAL MICROBIOLOGY, Issue 2 2009K. Dierckens Summary The use of probiotic microorganisms in aquaculture is gaining a lot of interest. Gnotobiotic model systems are required in order to fully understand the effects and modes-of-action of these microorganisms, as the native microbial communities present in non-sterile animals can lead to false conclusions. In this study, a gnotobiotic sea bass larvae (Dicentrarchus labrax) test system was developed. In order to obtain bacteria-free animals, the eggs were disinfected with glutaraldehyde and subsequently incubated in a solution of rifampicin and ampicillin. Axenity was confirmed using culture-dependent and -independent techniques. The gnotobiotic larvae were fed axenic Artemia sp. from 7 days after hatching onwards. In the challenge test, one of the three opportunistic pathogens, Aeromonas hydrophila, Listonella anguillarum serovar O1 and O2a, was added to the model system via the water and encapsulated in Artemia sp. Only serovar O2a led to increased mortality in the sea bass larvae. The presented gnotobiotic model can be used for research on, among others, reciprocal metabolic effects between microorganisms and the host (e.g. as measured by gene expression), immunostimulants, pharmacological research and the histological development of the gastrointestinal tract and growth of larvae. [source] Development and validation of a liquid chromatographic/tandem mass spectrometric assay for the quantitation of nucleoside HIV reverse transcriptase inhibitors in biological matricesJOURNAL OF MASS SPECTROMETRY (INCORP BIOLOGICAL MASS SPECTROMETRY), Issue 1 2005Séverine Compain Abstract Besides liquid chromatographic (LC)/UV methods adapted to therapeutic drug monitoring, there is still a need for more powerful techniques that can be used for pharmacological research and clinical purposes. We developed an LC method coupled with tandem mass spectrometry (MS/MS) to separate, detect and quantify with high sensitivity the nucleoside analogues used in multitherapies (zidovudine, stavudine, zalcitabine, didanosine, lamivudine and abacavir) in plasma and in the intracellular medium. We worked on two essential issues: (i) the need to use two ionization modes in order to achieve the best sensitivity, which leads to the optimization of the chromatographic separation of drugs detected in the positive ionization mode and drugs detected in the negative ionization mode, and (ii) the need to optimize the extraction step in order to enhance sample recovery. The peripheral blood mononuclear cells were lysed in Tris buffer,MeOH. A clean-up procedure was performed by solid-phase extraction only for plasma samples. The LC separation was carried out on a Zorbax Stable Bond C18 column followed by MS/MS analysis after electrospray ionization in either the negative or positive mode. The positive ionization mode was applied at the beginning of the run to detect zalcitabine and lamivudine, then the ionization mode was changed to negative for the detection of didanosine, stavudine, internal standard and zidovudine. The calibration range for all the analytes was 0.5,200 ng ml,1. The recoveries were between 64 and 90%, with coefficients of variation (CVs) lower than 15%. The inaccuracy (bias) was ±15% with CVs always lower than 12%. The analytes were stable at room temperature and in the extraction solvent for at least 24 h, after storage at ,80 °C for 3 months, after three freeze,thaw cycles and in the injection solvent after 48 h at 4 °C. Together with the measurement of intracellular triphosphorylated metabolites thanks to the powerful plasma and intracellular assay method for intact drugs, it is possible to describe the behaviour of nucleoside analogues against HIV through plasma pharmacokinetics, cell membrane diffusion including drug transport involvement, and also the intracellular metabolism. Copyright © 2005 John Wiley & Sons, Ltd. [source] How to easily replace the independent atom model , the example of bergenin, a potential anti-HIV agent of traditional Asian medicineACTA CRYSTALLOGRAPHICA SECTION B, Issue 6 2009Birger Dittrich Bergenin, which has been isolated from a variety of tropical plants, has several pharmacological applications in traditional Asian medicine. Its electron-density distribution was obtained from a room-temperature low-resolution X-ray data set measured with point detection making use of multipole populations from the invariom library. Two refinement models were considered. In a first step, positional parameters and ADPs were refined with fixed library multipoles (model E1). This model was suitable to be input into a second refinement of multipoles (model E2), which converged smoothly although based on Cu,K, room-temperature data. Quantitative results of a topological analysis of the electron density from both models were compared with Hartree,Fock and density-functional calculations. With respect to the independent atom model (IAM) more information can be extracted from invariom modelling, including the electrostatic potential and hydrogen-bond energies, which are highly useful, especially for biologically active compounds. The reliability of the applied invariom formalism was assessed by a comparison of bond-topological properties of sucrose, for which high-resolution multipole and invariom densities were available. Since a conventional X-ray diffraction experiment using basic equipment was combined with the easy-to-use invariom formalism, the procedure described here for bergenin illustrates how it can be routinely applied in pharmacological research. [source] |