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Vivo Screening (vivo + screening)
Selected AbstractsCorrelation between virulence of Candida albicans mutants in mice and Galleria mellonella larvaeFEMS IMMUNOLOGY & MEDICAL MICROBIOLOGY, Issue 2 2002Marc Brennan Abstract Candida albicans is a dimorphic human pathogen in which the yeast to hyphal switch may be an important factor in virulence in mammals. This pathogen has recently been shown to also kill insects such as the Greater Wax Moth Galleria mellonella when injected into the haemocoel of the insect larvae. We have investigated the effect of previously characterised C. albicans mutations that influence the yeast to hyphal transition on virulence in G. mellonella larvae. There is a good correlation between the virulence of these mutants in the insect host and the virulence measured through systemic infection of mice. Although the predominant cellular species detected in G. mellonella infections is the yeast form of C. albicans, mutations that influence the hyphal transition also reduce pathogenicity in the insect. The correlation with virulence measured in the mouse infection system suggests that Galleria may provide a convenient and inexpensive model for the in vivo screening of mutants of C. albicans. [source] The chick chorioallantoic membrane as a novel in vivo model for the testing of biomaterialsJOURNAL OF BIOMEDICAL MATERIALS RESEARCH, Issue 2 2002T.I. Valdes Abstract Current in vivo models for testing biomaterials are time and labor intensive as well as expensive. This article describes a new approach for testing biomaterials in vivo using the chorioallantoic membrane (CAM) of the developing chicken embryo, as an alternative to the traditional mammalian models. Fertilized chicken eggs were incubated for 4 days, at which time a small window was cut in the shell of the egg. After 1 week of incubation, the CAM received several test materials, including the endotoxin LPS, a cotton thread and a Silastic tubing. One day and 1 week later, the tissue response to the test materials was assessed using gross, histological, and scanning electron microscope evaluations. The inflammatory response of the chorioallantoic membrane to biomaterials was fully characterized and found to be similar to that of the mammalian response and was also seen to vary according to test materials. We also found that the structure and geometry of the test materials greatly influenced the incorporation of the samples in the CAM. The similarity of the tissue response of the CAM with the mammalian models, plus the low cost, simplicity, and possibility to continuously visualize the test site through the shell window make this animal model particularly attractive for the rapid in vivo screening of biomaterials. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res 62: 273,282, 2002 [source] In vivo study on the protection of indole-3-carbinol (I3C) against the mouse acute alcoholic liver injury by micro-Raman spectroscopyJOURNAL OF RAMAN SPECTROSCOPY, Issue 5 2009Aiguo Shen Abstract Micro-Raman spectroscopy (MRS) was utilized for the first time to evaluate the effect of indole-3-carbinol (I3C) on acute alcoholic liver injury in vivo. In situ Raman analysis of tissue sections provided distinct spectra that can be used to distinguish alcoholic liver injury as well as ethanol-induced liver fibrosis from the normal state. Sixteen mice with liver diseases including acute liver injury and chronic liver fibrosis, and eight mice with normal liver tissues, and eight remedial mice were studied employing the Raman spectroscopic technique in conjunction with biomedical assays. The biochemical changes in mouse liver tissue when liver injury/fibrosis occurs such as the loss of reduced glutathione (GSH), and the increase of collagen (,-helix protein) were observed by MRS. The intensity ratio of two Raman peaks (I1450/I666) and in combination with statistical analysis of the entire Raman spectrum was found capable of classifying liver tissues with different pathological features. Raman spectroscopy therefore is an important candidate for a nondestructive in vivo screening of the effect of drug treatment on liver disease, which potentially decreases the time-consuming clinical trials. Copyright © 2008 John Wiley & Sons, Ltd. [source] A First Comparative Study of Purpurinimide-based Fluorinated vs.PHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 5 2002Nonfluorinated Photosensitizers for Photodynamic Therapy ABSTRACT A first report on the synthesis and comparative in vitro,in vivo photosensitizing efficacy of various fluorinated and the corresponding nonfluorinated, purpurinimide-based photosensitizers is discussed. In preliminary in vivo screening, compared with the nonfluorinated analogs, purpurinimides bearing trifluoromethyl substituents showed enhanced photosensitizing efficacy. Among compounds (isomers) with similar lipophilicity, the position of the substituents was found to play a decisive role in biological efficacy. [source] High-throughput analysis in drug discovery: application of liquid chromatography/ion-trap mass spectrometry for simultaneous cassette analysis of ,-1a antagonists and their metabolites in mouse plasmaRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 8 2001Zongwei Cai The application of liquid chromatography/ion-trap mass spectrometry for simultaneous quantification of multiple drugs and detection of their metabolites for in vitro experiments was reported recently. In the current study, the use of these techniques was extended to in vivo pharmacokinetic (PK) studies of ,-1a antagonists. In combination with limited time-point PK, greatly increased throughput was demonstrated for the in vivo screening and investigation of in vivo,in vitro correlation. In addition to quantitative analyses, the technique allowed simultaneous detection of major in vivo metabolites without having to reanalyze the plasma samples. The drugs were individually dosed in mice intravenously via tail vein injection and the blood samples were collected 5,min and 2,h after dosing. After the plasma samples for the different drugs had been prepared separately, they were pooled for cassette analysis. The concentrations of five test compounds in the plasma samples at 2,h ranged from 36,1062,ng/mL, whereas their 5-min plasma levels were similar. From the same cassette analysis, major metabolites in the samples were also detected simultaneously through the interpretation of full-scan mass spectra. The metabolite identification confirmed the results from a previous report that the major sites of metabolism are hydroxylation of the phenyl ring not bearing the alkylsulfonamide substitutent, piperidine N-dealkylation, and N-demethylation of the alkylsulfonamide group. Copyright © 2001 John Wiley & Sons, Ltd. [source] Cassette-accelerated rapid rat screen: a systematic procedure for the dosing and liquid chromatography/atmospheric pressure ionization tandem mass spectrometric analysis of new chemical entities as part of new drug discoveryRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 5 2001Walter A. Korfmacher This report addresses the continuing need for increased throughput in the evaluation of new chemical entities (NCEs) in terms of their pharmacokinetic (PK) parameters by describing an alternative procedure for increasing the throughput of the in vivo screening of NCEs in the oral rat PK model. The new approach is called ,cassette-accelerated rapid rat screen' (CARRS). In this assay, NCEs are dosed individually (n,=,2 rats/compound) in batches of six compounds per set. The assay makes use of a semi-automated protein precipitation procedure for sample preparation in a 96-well plate format. The liquid chromatography/atmospheric pressure ionization tandem mass spectrometry (LC/API-MS/MS) assay is also streamlined by analyzing the samples as ,cassettes of six'. Using this new approach, a threefold increase in throughput was achieved over the previously reported ,rapid rat screen'. Copyright © 2001 John Wiley & Sons, Ltd. [source] Intracellular antibodies and cancer: New technologies offer therapeutic opportunitiesBIOESSAYS, Issue 7 2010David Pérez-Martínez Abstract Since the realisation that the antigen-binding regions of antibodies, the variable (V) regions, can be uncoupled from the rest of the molecule to create fragments that recognise and abrogate particular protein functions in cells, the use of antibody fragments inside cells has become an important tool in bioscience. Diverse libraries of antibody fragments plus in vivo screening can be used to isolate single chain variable fragments comprising VH and VL segments or single V-region domains. Some of these are interfering antibody fragments that compete with protein-protein interactions, providing lead molecules for drug interactions that until now have been considered difficult or undruggable. It may be possible to deliver or express antibody fragments in target cells as macrodrugs per se. In future incarnations of intracellular antibodies, however, the structural information of the interaction interface of target and antibody fragment should facilitate development of binding site mimics as small drug-like molecules. This is a new dawn for intracellular antibody fragments both as macrodrugs and as precursors of drugs to treat human diseases and should finally lead to the removal of the epithet of the ,undruggable' protein-protein interactions. [source] | |||||||||||||