AN INVITRO ASSAY SYSTEM FOR THE IDENTIFICATION OF POTENTIAL ANTI-MALARIAL DRUGS
AN INVITRO ASSAY SYSTEM FOR THE IDENTIFICATION OF POTENTIAL ANTI-MALARIAL DRUGS
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DOI：
10.2307/3281373
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发表时间：
1983-01-01
影响因子：
1.3
通讯作者：
JENSEN, JB
中科院分区：
文献类型：
--
作者：
GEARY, TG;DIVO, AA;JENSEN, JB
目前的抗疟疾药物筛选模型一般都是衡量感染伯氏豆属的药物治疗的啮齿动物的存活率。对现有的恶性疟原虫连续培养方法进行改进，可以快速、准确和经济地直接测定对人类病原体的药物效果。寄生虫培养可在添加人或兔血清或添加次黄嘌呤的牛血清的RPMI1640培养液中保持。4种药物氯喹、氯霉素、克林霉素和常青藤酮在这些血清中的抗寄生虫效果相同，在添加次黄嘌呤的牛血清中可以常规筛选药物来防治面型青霉病。通过监测~3H-次黄嘌呤在寄生虫核酸中的掺入情况，可以快速、准确地确定药物效应。用这项技术获得的结果与血液薄膜中寄生虫的目测计数结果高度相关。通过测定药物处理兔血清对培养中寄生虫的影响，可以进一步筛选出在培养中具有抗疟疾活性的化合物。讨论了该系统相对于目前用于抗疟筛查的模型的优势。
Current models for antimalarial drug screening generally measure the survival of drug-treated rodents infected with Phasmodium berghei. Modifications of existing continuous culture methods for P. falciparum allow the rapid, accurate and economical determination of drug effects directly against the human pathogen. Parasite cultures can be maintained in RPMI 1640 medium supplemented with human or rabbit serum or with hypoxanthine-supplemented bovine serum. The antiparasite effects of 4 drugs, chloroquine, chloramphenicol, clindamycin and halofuginone, are identical in these sera; drugs can be screened routinely against P. faciparum grown in bovine serum supplemented with hypoxanthine. Drug effects may be rapidly and accurately determined by monitoring the incorporation of 3H-hypoxanthine into parasite nucleic acids. Results obtained with this technique are highly correlated with those derived from visual counting of parasites in thin blood films. Compounds with antimalarial activity in culture may be further screened by measuring the effects of serum obtained from drug-treated rabbits on parasites in culture. The advantages of this system over models currently used for antimalarial screening were discussed.