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31.
Storme T Mercier L Deroussent A Re M Martens T Royer J Bourget P Vassal G Paci A 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2005,820(2):251-259
A specific and sensitive quantitative assay has been developed using high performance liquid chromatography-electrospray ionization mass spectrometry (HPLC-ESI-MS) for the simultaneous quantitation of the antitumor drug ifosfamide (IFM) and its two metabolites, N2-deschloroethylifosfamide (N2-DCE-IFM) and N3-deschloroethylifosfamide (N3-DCE-IFM) in microsomal medium. The analytes and the internal standard (cyclophosphamide) were isolated by ethylacetate extraction from rat liver microsomes. They were analysed on a Nucleosil C18 HD column (125 mm x 4 mm, 5 microm) using a step gradient with the mobile phase (2 mM ammonium formate and methanol). The HPLC-ESI-MS method used selected ion monitoring of ions m/z 199.1 Th and m/z 261.1 Th and was validated in the concentrations ranges of 100-5000 ng/mL for IFM and 50-2500 ng/mL for its N-deschloroethylated metabolites (DCE-IFM) with good accuracy and precision (CV less than 15%). The low limits of quantitation (LLOQ) were found at 50 ng/mL for N-deschloroethylated metabolites and at 100 ng/mL for the parent drug (IFM). The method was applied for the determination of ifosfamide and its N-deschloroethylated metabolites in rat microsomal incubations. 相似文献
32.
Ronaldson PT Bendayan M Gingras D Piquette-Miller M Bendayan R 《Journal of neurochemistry》2004,89(3):788-800
We investigated the cellular/subcellular localization and functional expression of P-glycoprotein, an ATP-dependent membrane-associated efflux transporter, in astrocytes, a brain parenchyma compartment that is poorly characterized for the expression of membrane drug transporters. Analyses were carried out on primary cultures of astrocytes isolated from the cerebral cortex of neonatal Wistar rats and CTX TNA2, an immortalized rat astrocyte cell line. Both cell cultures display morphological features typical of type I astrocytes. RT-PCR analysis revealed mdr1a and mdr1b mRNA in primary cultures of astrocytes and in CTX TNA2 cells. Western blot analysis using the P-glycoprotein monoclonal C219 antibody detected a single band of appropriate size in both cell systems. Immunocytochemical analysis using the monoclonal antibodies C219 and MRK16 labeled P-glycoprotein along the plasma membrane, caveolae, coated vesicles and nuclear envelope. Immunoprecipitation studies using the caveolin-1 polyclonal H-97 antibody demonstrated that P-glycoprotein is physically associated with caveolin-1 in both cell culture systems. The accumulation of [(3)H]digoxin (an established P-glycoprotein substrate) by the astrocyte cultures was significantly enhanced in the presence of standard P-glycoprotein inhibitors and an ATP depleting agent. These results demonstrate the cellular/subcellular location and functional expression of P-glycoprotein in rat astrocytes and suggest that this glial compartment may play an important role in the regulation of drug transport in the CNS. 相似文献
33.
Le Goffic R Balloy V Lagranderie M Alexopoulou L Escriou N Flavell R Chignard M Si-Tahar M 《PLoS pathogens》2006,2(6):e53
Influenza A virus (IAV) is the etiological agent of a highly contagious acute respiratory disease that causes epidemics and considerable mortality annually. Recently, we demonstrated, using an in vitro approach, that the pattern recognition Toll-like receptor (TLR)3 plays a key role in the immune response of lung epithelial cells to IAV. In view of these data and the fact that the functional role of TLR3 in vivo is still debated, we designed an investigation to better understand the role of TLR3 in the mechanisms of IAV pathogenesis and host immune response using an experimental murine model. The time-course of several dynamic parameters, including animal survival, respiratory suffering, viral clearance, leukocyte recruitment into the airspaces and secretion of critical inflammatory mediators, was compared in infected wild-type and TLR3(-/-) mice. First, we found that the pulmonary expression of TLR3 is constitutive and markedly upregulated following influenza infection in control mice. Notably, when compared to wild-type mice, infected TLR3-/- animals displayed significantly reduced inflammatory mediators, including RANTES (regulated upon activation, normal T cell expressed and secreted), interleukin-6, and interleukin-12p40/p70 as well as a lower number of CD8+ T lymphocytes in the bronchoalveolar airspace. More important, despite a higher viral production in the lungs, mice deficient in TLR3 had an unexpected survival advantage. Hence, to our knowledge, our findings show for the first time that TLR3-IAV interaction critically contributes to the debilitating effects of a detrimental host inflammatory response. 相似文献
34.
Gasparini F Andres H Flor PJ Heinrich M Inderbitzin W Lingenhöhl K Müller H Munk VC Omilusik K Stierlin C Stoehr N Vranesic I Kuhn R 《Bioorganic & medicinal chemistry letters》2002,12(3):407-409
The synthesis of a new potent, subtype-selective radioligand [(3)H]-M-MPEP (2-methyl-6-((3-methoxyphenyl)ethynyl)-pyridine) and its in vitro pharmacological characteristics are described. Science Ltd. 相似文献
35.
Dsamou M Palicki O Septier C Chabanet C Lucchi G Ducoroy P Chagnon MC Morzel M 《Chemical senses》2012,37(1):87-95
The interindividual variation in the sensitivity to bitterness is attributed in part to genetic polymorphism at the taste receptor level, but other factors, such as saliva composition, might be involved. In order to investigate this, 2 groups of subjects (hyposensitive, hypersensitive) were selected from 29 healthy male volunteers based on their detection thresholds for caffeine, and their salivary proteome composition was compared. Abundance of 26 of the 255 spots detected on saliva electrophoretic patterns was significantly different between hypo- and hypersensitive subjects. Saliva of hypersensitive subjects contained higher levels of amylase fragments, immunoglobulins, and serum albumin and/or serum albumin fragments. It also contained lower levels of cystatin SN, an inhibitor of protease. The results suggest that proteolysis occurring within the oral cavity is an important perireceptor factor associated to the sensitivity to the bitter taste of caffeine. 相似文献
36.
37.
In��s Vigan-Womas Micheline Guillotte Alexandre Juillerat Audrey Hessel Bertrand Raynal Patrick England Jacques H. Cohen Olivier Bertrand Thierry Peyrard Graham A. Bentley Anita Lewit-Bentley Odile Mercereau-Puijalon 《PLoS pathogens》2012,8(7)
The ABO blood group influences susceptibility to severe Plasmodium falciparum malaria. Recent evidence indicates that the protective effect of group O operates by virtue of reduced rosetting of infected red blood cells (iRBCs) with uninfected RBCs. Rosetting is mediated by a subgroup of PfEMP1 adhesins, with RBC binding being assigned to the N-terminal DBL1α1 domain. Here, we identify the ABO blood group as the main receptor for VarO rosetting, with a marked preference for group A over group B, which in turn is preferred to group O RBCs. We show that recombinant NTS-DBL1α1 and NTS-DBL1α1-CIDR1γ reproduce the VarO-iRBC blood group preference and document direct binding to blood group trisaccharides by surface plasmon resonance. More detailed RBC subgroup analysis showed preferred binding to group A1, weaker binding to groups A2 and B, and least binding to groups Ax and O. The 2.8 Å resolution crystal structure of the PfEMP1-VarO Head region, NTS-DBL1α1-CIDR1γ, reveals extensive contacts between the DBL1α1 and CIDR1γ and shows that the NTS-DBL1α1 hinge region is essential for RBC binding. Computer docking of the blood group trisaccharides and subsequent site-directed mutagenesis localized the RBC-binding site to the face opposite to the heparin-binding site of NTS-DBLα1. RBC binding involves residues that are conserved between rosette-forming PfEMP1 adhesins, opening novel opportunities for intervention against severe malaria. By deciphering the structural basis of blood group preferences in rosetting, we provide a link between ABO blood grouppolymorphisms and rosette-forming adhesins, consistent with the selective role of falciparum malaria on human genetic makeup. 相似文献
38.
O Connor Áine Bradish Stephen Reed Thomas Moran James Regan Eugenie Visser Marjolein Gormally Mike Skeffington Micheline Sheehy 《Hydrobiologia》2004,524(1):133-144
Two methods were used to sample aquatic macroinvertebrates in three turloughs. Turloughs are systems that flood periodically from groundwater, in response to local rainfall patterns and contain rare aquatic species and assemblages. The first method used a standard pond net that was swept through the water column, while the second involved fixing a rectangular, open-bottomed box to the substrata and removing all organisms with a net. Similar overall sampling effort was applied to each method and individual box samples were found to take longer to gather than pond net samples. The box method, however, gave the maximum yield for a given sampling effort. Significantly more beetle species and individuals were recorded per unit area of bottom at all three turloughs using the box method. Multivariate analysis segregated samples, firstly according to site and secondly, with respect to method. The box method is a viable alternative to sampling with a pond net. It is more quantitative, objective, specific and reliable. This is particularly important in habitats distinguished by rare species and assemblages, and for which monitoring is driven by legislative needs. 相似文献
39.
Maria Fesatidou Panagiotis Zagaliotis Charalampos Camoutsis Anthi Petrou Phaedra Eleftheriou Christophe Tratrat Micheline Haroun Athina Geronikaki Ana Ciric Marina Sokovic 《Bioorganic & medicinal chemistry》2018,26(16):4664-4676
In continuation of our efforts to develop new compounds with antimicrobial properties we describe design, synthesis, molecular docking study and evaluation of antimicrobial activity of seventeen novel 2-{[5-(adamantan-1-yl)-1,3,4-thiadiazol-2-yl]-imino}-5-arylidene-1,3-thiazolidin-4-ones. All compounds showed antibacterial activity against eight Gram positive and Gram negative bacterial species. Twelve out of seventeen compounds were more potent than streptomycin and all compounds exhibited higher potency than ampicillin. Compounds were also tested against three resistant bacterial strains: MRSA, P. aeruginosa and E. coli. The best antibacterial potential against ATCC and resistant strains was observed for compound 8 (2-{[5-(adamantan-1-yl)-1,3,4-thiadiazol-2-yl]-imino}-5-(4-nitrobenzylidene)-1,3thiazolidin-4-one). The most sensitive bacterium appeared to be S. typhimirium, followed by B. cereus while L. monocitogenes and M. flavus were the most resistant. Compounds were also tested for their antifungal activity against eight fungal species. All compounds exhibited antifungal activity better than the reference drugs bifonazole and ketokonazole (3-115 times). It was found that compound 8 appeared again to be the most potent. Molecular docking studies on E. coli MurB, MurA as well as C. albicans CYP 51 and dihydrofolate reductase were used for the prediction of mechanism of antibacterial and antifungal activities confirming the experimental results. 相似文献
40.
We used a longitudinal capture-recapture study to estimate the age-specific probabilities of first return to the breeding colony and annual survival rates for male gray seals ( Halichoerus grypus ), based on resightings of seals branded as young on Sable Island. We estimated that the average age of first returns for seals born in 1969–1970 to be 9.1 (SE 0.4) yr; for seals born in 1973–1974 it is estimated to be 9.8 (SE 0.2) yr. The estimated annual survival rate of these males was estimated to be 0.976 (SE 0.003). 相似文献