Plasmodium vivax trophozoites insensitive to chloroquine.
Plasmodium vivax trophozoites insensitive to chloroquine.
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DOI：
10.1186/1475-2875-7-94
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发表时间：
2008-05-27
期刊：
影响因子：
3
通讯作者：
Russell B
中科院分区：
文献类型：
--
作者：
Sharrock WW;Suwanarusk R;Lek-Uthai U;Edstein MD;Kosaisavee V;Travers T;Jaidee A;Sriprawat K;Price RN;Nosten F;Russell B
间日疟原虫是疟疾的一个主要原因，目前仍主要用氯喹治疗。氯喹抑制血红素聚合成惰性的疟原虫色素。游离血红素单体被认为催化氧化损伤疟原虫属。滋养体，血红蛋白catenin最大的阶段。然而，对间日疟原虫临床分离株的初步体外观察表明，只有环期（早期滋养体）对氯喹敏感。在这项研究中，氯喹的阶段特异性作用在同步冻存的间日疟原虫菌株进行了研究。采用改良的WHO微量法和荧光SYBR绿色I法测定了11株间日疟原虫临床分离株和2株恶性疟原虫克隆（氯喹抗性K1和氯喹敏感FC 27）的成对环状体和滋养体对氯喹的体外敏感性。通过在处理开始后20小时洗掉氯喹来控制每个阶段暴露于氯喹处理的时间。在环期加入测定的间日疟原虫分离株对氯喹的中位IC 50显著低于在滋养体期加入的相同分离株（中位IC 50 12 nM vs 415 nM p < 0.01）。尽管仅36%（4/11）的SYBR绿色I间日疟原虫检测成功，但显微镜和SYBR绿色I检测均表明，只有间日疟原虫滋养体能够在氯喹浓度高于100 nM时发育成原虫。这项研究的数据证实了间日疟原虫滋养体对氯喹的敏感性降低，这一阶段被认为是这种药物的靶点。这些结果提出了关于氯喹的药效学作用的重要问题，并突出了间日疟原虫和恶性疟原虫之间氯喹活性的根本差异。
Plasmodium vivax is a major cause of malaria and is still primarily treated with chloroquine. Chloroquine inhibits the polymerization of haem to inert haemozoin. Free haem monomers are thought to catalyze oxidative damage to the Plasmodium spp. trophozoite, the stage when haemoglobin catabolism is maximal. However preliminary in vitro observations on P. vivax clinical isolates suggest that only ring stages (early trophozoites) are sensitive to chloroquine. In this study, the stage specific action of chloroquine was investigated in synchronous cryopreserved isolates of P. vivax. The in vitro chloroquine sensitivity of paired ring and trophozoite stages from 11 cryopreserved P. vivax clinical isolates from Thailand and two Plasmodium falciparum clones (chloroquine resistant K1 and chloroquine sensitive FC27) was measured using a modified WHO microtest method and fluorometric SYBR Green I Assay. The time each stage was exposed to chloroquine treatment was controlled by washing the chloroquine off at 20 hours after the beginning of treatment. Plasmodium vivax isolates added to the assay at ring stage had significantly lower median IC50s to chloroquine than the same isolates added at trophozoite stage (median IC50 12 nM vs 415 nM p < 0.01). Although only 36% (4/11) of the SYBR Green I assays for P. vivax were successful, both microscopy and SYBR Green I assays indicated that only P. vivax trophozoites were able to develop to schizonts at chloroquine concentrations above 100 nM. Data from this study confirms the diminished sensitivity of P. vivax trophozoites to chloroquine, the stage thought to be the target of this drug. These results raise important questions about the pharmacodynamic action of chloroquine, and highlight a fundamental difference in the activity of chloroquine between P. vivax and P. falciparum.
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影响因子：
3.7
作者：
Suwanarusk R;Russell B;Chavchich M;Chalfein F;Kenangalem E;Kosaisavee V;Prasetyorini B;Piera KA;Barends M;Brockman A;Lek-Uthai U;Anstey NM;Tjitra E;Nosten F;Cheng Q;Price RN
通讯作者：
Price RN
影响因子：
1.3
作者：
YA, Z;ASANTE, KSO;JUNG, A
通讯作者：
JUNG, A
影响因子：
64.8
作者：
SLATER, AFG;CERAMI, A
通讯作者：
CERAMI, A
DOI：
10.1073/pnas.54.2.521
发表时间：
1965-01-01
影响因子：
11.1
作者：
COHEN, SN;YIELDING, KL
通讯作者：
YIELDING, KL
影响因子：
16
作者：
Fidock, DA;Nomura, T;Wellems, TE
通讯作者：
Wellems, TE