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伊拉克疫情期间人体中毒时解毒剂去除甲基汞效果的测试。

Tests of efficacy of antidotes for removal of methylmercury in human poisoning during the Iraq outbreak.

作者信息

Clarkson T W, Magos L, Cox C, Greenwood M R, Amin-Zaki L, Majeed M A, Al-Damluji S F

出版信息

J Pharmacol Exp Ther. 1981 Jul;218(1):74-83.

PMID:7241391
Abstract

Three complexing agents and a thiolated resin were tested for their ability to reduce the T 1/2 of methylmercury in blood during an outbreak of human poisoning. The slope of the line relating the natural logarithm of the blood concentration to time during treatment was calculated by a parametric (linear regression) and a nonparametric (two-point) method. The mean slope for each treatment group was calculated and the T 1/2 was calculated from the mean slope. Both the linear regression and two-point methods yield similar mean values. The "two-point" T 1/2 will be quoted here. The mean T 1/2 in six patients receiving no specific treatment was 65 days and in 10 patients receiving placebo was 61 days, and these values did not differ from those reported in the literature. All four treatments significantly reduced the mean T 1/2 values below the mean for the combined placebo and no treatment groups. Sodium 2,3-dimercaptopropane-1-sulfonate was the most effective agent, reducing the mean T 1/2 in 10 patients to 10 days. The thiolated resin given to eight patients produced a mean T 1/2 of 20 days. The penicillamines also produced a significant reduction in T 1/2 values; the mean T 1/2 for D-penicillamine in 12 patients was 26 days and N-acetyl-DL-penicillamine in 17 patients yielded a mean T 1/2 of 24 days. This is the first report of the effects of sodium 2,3-dimercaptopropane-1-sulfonate and resin in human subjects exposed to methylmercury. No adverse effects were observed in any of the treatment groups. A clinical trial was not possible but it is concluded that agents that reduce blood levels and accelerate excretion are probably clinically useful if given before irreversible damage has occurred.

摘要

在一次人类中毒事件中,对三种络合剂和一种硫醇化树脂降低血液中甲基汞半衰期(T1/2)的能力进行了测试。通过参数法(线性回归)和非参数法(两点法)计算治疗期间血液浓度自然对数与时间关系曲线的斜率。计算每个治疗组的平均斜率,并根据平均斜率计算T1/2。线性回归法和两点法得出的平均值相似。此处引用“两点法”计算的T1/2。6名未接受特殊治疗的患者的平均T1/2为65天,10名接受安慰剂治疗的患者的平均T1/2为61天,这些值与文献报道的值无差异。所有四种治疗方法均显著降低了平均T1/2值,使其低于安慰剂组和未治疗组的平均值之和。2,3-二巯基丙磺酸钠是最有效的药物,可将10名患者的平均T1/2降至10天。给予8名患者的硫醇化树脂产生的平均T1/2为20天。青霉胺也显著降低了T1/2值;12名患者使用D-青霉胺的平均T1/2为26天,17名患者使用N-乙酰-DL-青霉胺的平均T1/2为24天。这是关于2,3-二巯基丙磺酸钠和树脂对接触甲基汞的人体影响的首次报告。在任何治疗组中均未观察到不良反应。由于无法进行临床试验,但得出的结论是,如果在不可逆损伤发生之前给予降低血液水平并加速排泄的药物,可能具有临床实用性。

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