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用抗秋水仙碱山羊特异性抗体逆转小鼠晚期秋水仙碱毒性。

Reversal of advanced colchicine toxicity in mice with goat colchicine-specific antibodies.

作者信息

Terrien N, Urtizberea M, Scherrmann J M

机构信息

Institut National de la Santé et de la Recherche Médicale (U. 26), Paris, France.

出版信息

Toxicol Appl Pharmacol. 1990 Jul;104(3):504-10. doi: 10.1016/0041-008x(90)90172-q.

Abstract

Colchicine-specific antibody (IgG(C] was tested in mice for reversal of colchicine toxicity. The mouse model was chosen because it reflects human pathophysiology in colchicine poisoning. IgG(C) was administered when at least 85% of colchicine was distributed in tissues. It resulted in a dramatic decrease in lethality from 85% (control group) to 10% (treated group). The decrease in toxic effects was confirmed by evaluating physiological parameters. The recovery of thermoregulation was very rapid in mice treated with IgG(C), while recovery in body weight was less marked. IgG(C) administration, therefore, decreases the intensity but may extend the duration of colchicine toxicity (reversible binding). The total neutralizing binding capacity of IgG(C) used was such that administered IgG(C) neutralizing binding sites were either 7 or 15% of the injected colchicine dose. In spite of this low neutralizing capacity the treatment was successful because of the ability of IgG(C) to buffer the amount of colchicine molecules on the critical slope of the dose-lethality curve.

摘要

秋水仙碱特异性抗体(IgG(C))在小鼠身上进行了逆转秋水仙碱毒性的测试。选择小鼠模型是因为它能反映人类秋水仙碱中毒的病理生理学情况。当至少85%的秋水仙碱分布在组织中时给予IgG(C)。这使得致死率从85%(对照组)大幅降至10%(治疗组)。通过评估生理参数证实了毒性作用的降低。用IgG(C)治疗的小鼠体温调节恢复非常迅速,而体重恢复则不太明显。因此,IgG(C)给药降低了秋水仙碱毒性的强度,但可能会延长其持续时间(可逆结合)。所用IgG(C)的总中和结合能力使得给药的IgG(C)中和结合位点为注射秋水仙碱剂量的7%或15%。尽管中和能力较低,但由于IgG(C)能够缓冲剂量-致死率曲线关键斜率上的秋水仙碱分子数量,治疗仍取得了成功。

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