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大鼠模拟伤口污染后钋的联合螯合治疗

Combined chelation treatment for polonium after simulated wound contamination in rat.

作者信息

Volf V, Rencová J, Jones M M, Singh P K

机构信息

Forschungszentrum Karlsruhe, Technik und Umwelt, Institut für Toxikologie, Karlsruhe, Germany.

出版信息

Int J Radiat Biol. 1995 Oct;68(4):395-404. doi: 10.1080/09553009514551341.

Abstract

Contaminated puncture wounds were simulated in rat by intramuscular injection of 210Po. The aim of the study was to determine the effectiveness of chelation treatment as a function of time, dosage, and route of chelate administration. Ten newly synthesized substances containing vicinal sulphydryl and carbodithioate groups were used and their effect was compared with that of chelators clinically applicable in man--BAL (2,3-dimercaptopropane-1-ol), DMPS (2,3-dimercaptopropane-1-sulphonate), DMSA (meso-2,3-dimercaptosuccinic acid), and DDTC (sodium diethylamine-N-carbodithioate). The results indicate first that complete removal of 210Po from the injection site is achieved by only two local injections of DMPS, beginning as late as 2 h after injection of 210Po. Second, many of the substances used merely induce translocation of 210Po from the injection site into other tissues. Third, a combined local treatment at the injection site with DMPS plus repeated systemic, subcutaneous, treatments with HOEtTTC (N,N'-di-(2-hydroxyethyl)ethylenediamine-N,N-biscarbodithioate), a derivative of DDTC, results after 2 weeks in a reduction of the estimated total body retention of 210Po to about one-third of that in untreated controls. In the latter case the cumulative excretion of 210Po increased from 8 to 54%, mainly via the faeces.

摘要

通过向大鼠肌肉注射210钋来模拟受污染的穿刺伤口。本研究的目的是确定螯合治疗的有效性与时间、剂量以及螯合剂给药途径之间的关系。使用了十种新合成的含有邻位巯基和二硫代碳酸盐基团的物质,并将它们的效果与临床上可用于人体的螯合剂——二巯丙醇(BAL,2,3-二巯基丙醇-1-醇)、二巯丙磺钠(DMPS,2,3-二巯基丙醇-1-磺酸盐)、二巯基丁二酸(DMSA,内消旋-2,3-二巯基丁二酸)和二乙胺基二硫代甲酸钠(DDTC)的效果进行比较。结果首先表明,仅在注射210钋后2小时开始进行两次局部注射DMPS,就能完全从注射部位清除210钋。其次,所使用的许多物质仅仅促使210钋从注射部位转移到其他组织。第三,在注射部位用DMPS进行联合局部治疗,再加上用DDTC的衍生物N,N'-二(2-羟乙基)乙二胺-N,N-双二硫代碳酸盐(HOEtTTC)进行重复的全身皮下治疗,两周后估计全身210钋的滞留量减少到未治疗对照组的约三分之一。在后一种情况下,210钋的累积排泄量从8%增加到54%,主要通过粪便排泄。

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