Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0015672 (fatigue)
 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We previously reported a high concordance of in vitro micronucleus (MNvit) results obtained by flow cytometry to the known cytogenetic activity often commercially available compounds mentioned as validation compounds in an early draft of the OECD MNvit TG487 [Bryce et al., 2010; Organization for Economic Co-operation and Development(OECD), 2007]. The current study investigated this method in Chinese hamster V79 cells with pharmaceutical compounds of unknown genotoxic potential. Twenty-five compounds from several therapeutic areas such as oncology, neuroscience and immunological research were tested in the flow cytometry assay, and for comparison using the cytokinesis-block microscopy assay. Five of these 25 compounds were considered positive for micronucleus induction by the microscopy assessment. In all cases, the results from the flow cytometry assess ment matched the results of the microscopy assay. Thus, flow cytometry is a viable method for assessing the aneugenic/clastogenic potential of pharmaceutical drug candidates. The flow method offered several advantages over traditional microscopy. For instance, the ratio of micronuclei (MN) to 10,000 nuclei was evaluated in less than 2 min vs.15 min to manually assess 600 binucleate cells. Evaluation by flow cytometry can be automated,freeing resources and eliminating scorer fatigue.The assay may also provide for mechanistic understanding of MN formation based on size and the ratio of nuclei with sub-2N DNA content, allowing for discrimination between aneugenic and clastogenic compounds.
Environ Mol Mutagen 2011 Jun
PMID:In vitro micronucleus screening of pharmaceutical candidates by flow cytometry in Chinese hamster V79 cells. 2096 13

De Ste Croix, MBA, Hughes, JD, Lloyd, RS, Oliver, JL, and Read, PJ. Leg stiffness in female soccer players: intersession reliability and the fatiguing effects of soccer-specific exercise. J Strength Cond Res 31(11): 3052-3058, 2016-Low levels of leg stiffness and reduced leg stiffness when fatigue is present compromise physical performance and increase injury risk. The purpose of this study was to (a) determine the reliability of leg stiffness measures obtained from contact mat data and (b) explore age-related differences in leg stiffness after exposure to a soccer-specific fatigue protocol in young female soccer players. Thirty-seven uninjured female youth soccer players divided into 3 subgroups based on chronological age (under 13 [U13], under 15 [U15], and under 17 [U17] year-olds) volunteered to participate in the study. After baseline data collection, during which relative leg stiffness, contact time, and flight time were collected, participants completed an age-appropriate soccer-specific fatigue protocol (SAFT). Upon completion of the fatigue protocol, subjects were immediately retested. Intersession reliability was acceptable and could be considered capable of detecting worthwhile changes in performance. Results showed that leg stiffness decreased in the U13 year-olds, was maintained in the U15 age group, and increased in the U17 players. Contact times and flight times did not change in the U13 and U15 year-olds, but significantly decreased and increased, respectively, in the U17 age group. The data suggest that age-related changes in the neuromuscular control of leg stiffness are present in youth female soccer players. Practitioners should be aware of these discrepancies in neuromuscular responses to soccer-specific fatigue, and should tailor training programs to meet the needs of individuals, which may subsequently enhance performance and reduce injury risk.
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PMID:Leg Stiffness in Female Soccer Players: Intersession Reliability and the Fatiguing Effects of Soccer-Specific Exercise. 2906 79

The lymphocyte Cytokinesis-Block Micronucleus (CBMN) assay was originally developed for the measurement of micronuclei (MN) exclusively in binucleated (BN) cells, which represent the population of cells that can express MN because they completed nuclear division. Recently the assay has evolved into a comprehensive cytome method to include biomarkers that measure chromosomal instability and cytotoxicity by quantification of nuclear buds (NBUDs), nucleoplasmic bridges (NPBs) and apoptotic/necrotic cells. Furthermore, enumeration of mono- and polynucleated cells allows for computation of the nuclear division index (NDI) to assess mitotic activity. Typically performed by manual microscopy, the CBMN cytome assay is laborious and subject to scorer bias and fatigue, leading to inter- and intra-scorer variability. Automated microscopy and conventional flow cytometry methods have been developed to automate scoring of the traditional and cytome versions of the assay. However, these methods have several limitations including the requirement to create high-quality microscope slides, lack of staining consistency and sub-optimal nuclear/cytoplasmic visualization. In the case of flow cytometry, stripping of the cytoplasmic membrane makes it impossible to measure MN in BN cells, calculate the NDI or to quantify apoptotic or necrotic cells. Moreover, the absence of cellular visualization using conventional flow cytometry, makes it impossible to quantify NBUDs and NPBs. In this review, we propose that imaging flow cytometry (IFC), which combines high resolution microscopy with flow cytometry, may overcome these limitations. We demonstrate that by using IFC, images from cells in suspension can be captured, removing the need for microscope slides and allowing visualization of intact cytoplasmic membranes and DNA content. Thus, mono-, bi- and polynucleated cells with and without MN can be rapidly and automatically identified and quantified. Finally, we present high-resolution cell images containing NBUDs and NPBs, illustrating that IFC possesses the potential for completely automated scoring of all components of the CBMN cytome assay.
Mutat Res Genet Toxicol Environ Mutagen 2018 Dec
PMID:The potential for complete automated scoring of the cytokinesis block micronucleus cytome assay using imaging flow cytometry. 3038 63