摘要
The accumulation of the trypanocide isometamidium chloride (Samorin®, RMB Animal Health Ltd, UK) by a range of clones of Trypanosoma congolense with varying sensitivity to the drug, was measured by methods based on the fluorescence of isometamidium. Fluorescence microscopy and flow cytometry showed a reduction in drug accumulation by resistant clones. Fluorescence spectrophotometry demonstrated an inverse correlation between the intensity of cell-associated fluorescence and the level of resistance of the clones expressed in vivo. The addition of the metabolic inhibitor SHAM/glycerol to the incubation medium resulted in a reduction of this apparent difference in drug accumulation between the clones; those clones which were sensitive to isometamidium showed a reduction in fluorescence while a percentage increase in fluorescence was observed as clones became more resistant to the trypanocide. These observations may be of value for the in vitro detection of resistant T. congolense populations and may also be used to estimate the mean level of resistance in a given sample. The results also imply that decreased accumulation of isometamidium by drug-resistant clones of the parasite may be responsible for the reduction in sensitivity.
摘要译文
通过基于异构酰胺的荧光的方法测量一系列具有不同药物敏感性的锥虫（Trypanosoma congolense）克隆的锥虫酰胺异氰酰胺（Samorin®，RMB Animal Health Ltd，UK）。荧光显微镜和流式细胞术显示抗性克隆减少了药物积累。荧光分光光度法显示细胞相关荧光的强度与体内表达的克隆的抗性水平之间呈负相关。向培养基中加入代谢抑制剂SHAM /甘油导致克隆之间药物积累的这种明显差异减少;那些对异脒敏感的克隆显示荧光减少，而随着克隆对锥虫的抗性增强，观察到荧光增加百分比。这些观察结果对于抗性T. congolense种群的体外检测可能是有价值的，并且还可以用于估计给定样品中的平均抗性水平。结果还表明，寄生虫的抗药性克隆减少异构酰胺的积累可能是降低敏感性的原因。
I. A. Sutherland (a1); A. S. Peregrine (a2); J. D. Lonsdale-Eccles (a2);P. H. Holmes (a1). Reduced accumulation of isometamidium by drug-resistant Trypanosoma congolense[J]. Parasitology, 1991,103(2): 245-251