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16583462

Source:http://linkedlifedata.com/resource/pubmed/id/16583462

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pubmed-article:16583462pubmed:abstractTextOximes are cholinesterase reactivators used in organophosphorus poisoning. Clinical experience with pralidoxime (PRX) and other oximes is disappointing and their routine use has been questioned. In addition it is known that not all oximes are equally effective against all existing organophosphorus compounds. There is a demand for broad-spectrum reactivators with a higher efficacy than PRX. Based on our previous in vitro work the protection conferred by the various new oximes against inhibition by paraoxon as quantified by the IC(50) shift (nM increase in the IC(50) of the inhibitor per microM oxime present) is: 0.3 (PRX), 0.4 (methoxime; MMC-4), 1 (K-33), 1.2 (BI-6), 1.5 (K-48) and 3.7 (K-27). The purpose of the study was to quantify in vivo the extent of oxime-conferred protection, using paraoxon (POX) as a cholinesterase inhibitor and to test whether in vitro efficacy translates to protection from mortality. There were seven groups of six rats in each cycle of the experiment. Group 1 (G1) received 1 micromol POX (approximately LD(75)), the other groups (G2-G7) received 1 micromol POX + of one the six reactivators. The animals were monitored for 48 h and the time of mortality was recorded. The procedure was repeated five times (cycles). All substances were applied i.p. The experiments were repeated using 2, 3, 5 and 10 micromol POX. Mortality data were compared and hazards ratios (relative risks) ranked using the Cox proportional hazards model using POX dose and group (reactivator) as time-independent covariables. The relative risk of death estimated by Cox analysis (95% CI) in oxime treated animals when compared with untreated animals, adjusted for POX dose (high/low) was K-27: 0.26 (0.19-0.35); K-48: 0.34 (0.25-0.45); methoxime: 0.38 (0.29-0.50); BI-6: 0.53 (0.41-0.69); PRX: 0.70 (0.54-0.91); K-33: 0.82 (0.63-1.07). It is concluded that K-27 and K-48 are the most promising new oximes. The compounds with the best results in vitro also confer the best protection in vivo. Further testing using methyl- and propyl-organophosphates are needed.lld:pubmed
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pubmed-article:16583462pubmed:authorpubmed-author:PetroianuG...lld:pubmed
pubmed-article:16583462pubmed:authorpubmed-author:NurulainS MSMlld:pubmed
pubmed-article:16583462pubmed:authorpubmed-author:Al-SultanM...lld:pubmed
pubmed-article:16583462pubmed:copyrightInfoCopyright 2006 John Wiley & Sons, Ltd.lld:pubmed
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pubmed-article:16583462pubmed:volume26lld:pubmed
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pubmed-article:16583462pubmed:pagination262-8lld:pubmed
pubmed-article:16583462pubmed:dateRevised2006-11-15lld:pubmed
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pubmed-article:16583462pubmed:articleTitleFive oximes (K-27, K-33, K-48, BI-6 and methoxime) in comparison with pralidoxime: survival in rats exposed to the organophosphate paraoxon.lld:pubmed
pubmed-article:16583462pubmed:affiliationUAE University, Al Ain-UAE. georg.petroianu@uaeu.ac.aelld:pubmed
pubmed-article:16583462pubmed:publicationTypeJournal Articlelld:pubmed
pubmed-article:16583462pubmed:publicationTypeComparative Studylld:pubmed
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