| In vitro detoxification of cyclosarin in human blood pre-incubated ex vivo with recombinant serum paraoxonases. | |
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MedLine Citation:
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PMID: 21807078 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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An ex vivo protocol was developed to assay the antidotal capacity of rePON1 variants to protect endogenous acetylcholinesterase and butyrylcholinesterase in human whole blood against OP nerve agents. This protocol permitted us to address the relationship between blood rePON1 concentrations, their kinetic parameters, and the level of protection conferred by rePON1 on the cholinesterases in human blood, following a challenge with cyclosarin (GF). The experimental data thus obtained were in good agreement with the predicted percent residual activities of blood cholinesterases calculated on the basis of the rate constants for inhibition of human acetylcholinesterase and butyrylcholinesterase by GF, the concentration of the particular rePON1 variant, and its k(cat)/K(m) value for GF. This protocol thus provides a rapid and reliable ex vivo screening tool for identification of rePON1 bioscavenger candidates suitable for protection of humans against organophosphorus-based toxicants. The results also permitted the refinement of a mathematical model for estimating the efficacious dose of rePON1s variants required for prophylaxis in humans. |
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Authors:
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Yacov Ashani; Moshe Goldsmith; Haim Leader; Israel Silman; Joel L Sussman; Dan S Tawfik |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-7-23 |
Journal Detail:
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Title: Toxicology letters Volume: - ISSN: 1879-3169 ISO Abbreviation: - Publication Date: 2011 Jul |
Date Detail:
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Created Date: 2011-8-2 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7709027 Medline TA: Toxicol Lett Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2011. Published by Elsevier Ireland Ltd. |
Affiliation:
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Department of Structural Biology, The Weizmann Institute of Science, Kimmelman Bldg, Rm 661, Rehovot 76100, Israel; Department of Neurobiology, The Weizmann Institute of Science, Kimmelman Bldg, Rm 661, Rehovot 76100, Israel. |
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