Sex- and stage-related sensitivity of Schistosoma mansoni to in vivo and in vitro praziquantel treatment

Sex- and stage-related sensitivity of Schistosoma mansoni to in vivo and in vitro praziquantel treatment
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DOI:
10.1016/j.ijpara.2003.12.003
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发表时间:
2004-03-29
影响因子:
4
通讯作者:
Cioli, D
Cioli, D
中科院分区:
医学2区
文献类型:
--
作者:
Pica-Mattoccia, L;Cioli, D

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吡喹酮对曼氏血吸虫波多黎各株的疗效进行了评估,在体内和体外的方法。在感染小鼠模型中,针对28日龄感染测定的药物有效剂量(50%)比针对7周龄寄生虫测定的药物有效剂量高约30倍。与双性感染相比,单性别女性感染在很大程度上也是难治性的,单性别男性感染也是中度难治性的。体外方法包括将寄生虫培养物暴露于各种药物浓度过夜,然后在无药物培养基中培养数天。体外结果证实了体内数据,并允许观察到吡喹酮暴露后的异常形态学现象。在所有情况下,即使暴露于亚致死浓度的吡喹酮或暴露于28天龄的大部分难治性寄生虫后,也观察到早期蠕虫收缩。然而,在这些情况下,蠕虫在药物去除后恢复运动和正常形状,并且能够存活。这些意见的推断吡喹酮的临床使用和其作用机制进行了讨论。(C)2004年澳大利亚寄生虫学会由爱思唯尔有限公司出版。保留所有权利。
The efficacy of praziquantel against a Puerto Rican strain of Schistosoma mansoni was assessed using both in vivo and in vitro approach. The drug effective dose (50%) in the infected mouse model was about 30 times higher when determined against 28-day-old infections than against 7-week-old parasites. Single-sex female infections were also largely refractory to treatment and single-sex male infections moderately refractory, in comparison with bisexual infections. The in vitro approach consisted of overnight exposure of parasite cultures to various drug concentrations, followed by several days of culture in drug-free medium. In vitro results confirmed in vivo data and allowed for the observation of schistosome morphological phenomena after praziquantel exposure. Early worm contraction was observed in all cases, even after exposure to sub-lethal concentrations of praziquantel or upon exposure of the largely refractory 28-day-old schistosomes. In these instances, however, worms resumed movements and normal shape upon drug removal and were able to survive. The inference of these observations on the clinical use of praziquantel and on its mechanism of action is discussed. (C) 2004 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.