Influence of oxygen on asexual blood cycle and susceptibility of Plasmodium falciparum to chloroquine: requirement of a standardized in vitro assay.

Influence of oxygen on asexual blood cycle and susceptibility of Plasmodium falciparum to chloroquine: requirement of a standardized in vitro assay.
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DOI:
10.1186/1475-2875-6-44
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发表时间:
2007-04-16
期刊:
影响因子:
3
通讯作者:
Pradines B
Pradines B
中科院分区:
医学3区
文献类型:
--
作者:
Briolant S;Parola P;Fusaï T;Madamet-Torrentino M;Baret E;Mosnier J;Delmont JP;Parzy D;Minodier P;Rogier C;Pradines B

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本研究的主要目的是评估气体混合物对体外恶性疟原虫生长的影响和氯喹的50%抑制浓度(IC 50)。该研究于2004年2月至2005年12月期间进行。用同位素微量法测定了136株恶性疟原虫对氯喹的IC_(50)。用血涂片和氚标记次黄嘌呤摄取法测定了氧对3D 7和W2无性系血液循环的影响。在5%O_2 ~ 21%O_2条件下,O_2浓度对3D_7和W_2无性系的体外杀虫效果不明显。在暴露于21%O2的成熟滋养体和寄生虫期间观察到寄生虫抑制效应,并增加了寄生虫生殖的长度。氯喹在10%O_2时的IC_(50)显著高于在21%O_2时的IC_(50),平均值分别为173.5 nM和121.5 nM(p < 0.0001)。特别令人感兴趣的是,在10%O2下对氯喹体外耐药(IC 50> 100 nM)的63个分离株中,17个在21%O2下对氯喹敏感(IC 50 < 100 nM)。根据这些结果,实验室应使用相同的气体混合物来实现同位素微量测试。需要进一步研究同位素和非同位素检测方法的比较,以建立标准化的体外检测方案来调查疟疾耐药性。
The main objective of this study was to assess the influence of gas mixtures on in vitro Plasmodium falciparum growth and 50% inhibitory concentration (IC50) for chloroquine. The study was performed between February 2004 and December 2005. 136 Plasmodium falciparum isolates were used to evaluate gas mixtures effect on IC50 for chloroquine by isotopic microtest. The oxygen effect on asexual blood cycle of 3D7 and W2 clones was determined by thin blood smears examination and tritiated hypoxanthine uptake. From 5% O2 to 21% O2 conditions, no parasiticide effect of O2 concentration was observed in vitro on the clones 3D7 and W2. A parasitostatic effect was observed during the exposure of mature trophozoïtes and schizonts at 21% O2 with an increase in the length of schizogony. The chloroquine IC50 at 10% O2 were significantly higher than those at 21% O2, means of 173.5 nM and 121.5 nM respectively (p < 0.0001). In particular of interest, among the 63 isolates that were in vitro resistant to chloroquine (IC50 > 100 nM) at 10% O2, 17 were sensitive to chloroquine (IC50 < 100 nM) at 21% O2. Based on these results, laboratories should use the same gas mixture to realize isotopic microtest. Further studies on comparison of isotopic and non-isotopic assays are needed to establish a standardized in vitro assay protocol to survey malaria drug resistance.
DOI: 10.1128/aac.49.8.3575-3577.2005
发表时间: 2005-08-01
影响因子: 4.9
作者:
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DOI: 10.4269/ajtmh.2000.62.82
发表时间: 2000-01-01
影响因子: 3.3
作者:
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DOI: 10.2307/3280864
发表时间: 1983-01-01
影响因子: 1.3
作者:
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通讯作者: HELSTOWSKI, LD
DOI: 10.1128/aac.27.1.21
发表时间: 1985-01-01
影响因子: 4.9
作者:
DIVO, AA;GEARY, TG;JENSEN, JB
通讯作者: JENSEN, JB