Stables J N, Lees G M, Rankin R
Department of Biochemical Microbiology, Wellcome Research Laboratories, Beckenham, Kent, England.
Trop Med Parasitol. 1988 Mar;39(1):25-8.
Transplanted infections of Brugia pahangi and Dipetalonema viteae in male BALB/c and CDI mice were investigated as models for evaluating potential antifilarial compounds. The physiology and genetics of the above mouse strains are better defined than any of the rodent species currently used for primary in vivo screening, facilitating a more reproducible means for predicting the filaricidal activity of compounds. The recoveries of B. pahangi macrofilariae, implanted intraperitoneally were greater than or equal to 50% up to six weeks after implant in both CDI and BALB/c mice. The recoveries of D. viteae macrofilariae, implanted subcutaneously, were greater than 50% up to four weeks post implant but had fallen to less than 30% by six weeks. The survival of B. pahangi and D. viteae macrofilariae simultaneously implanted into mice mimicked that seen with the mono-infections, but significantly better recoveries were obtained from dual implanted CDI mice compared to the BALB/c mice when the numbers of macrofilariae implanted were varied. Standard antifilarials were evaluated against D. viteae and B. pahangi dual implanted into either CDI mice or gerbils. The mouse dual implant detected significant worm reductions against D. viteae, B. pahangi or both with all antifilarials tested except CGP 6140. Similarly under the test conditions CGP 6140 was not detected in the gerbil assay, but there were marked differences in the results obtained with the mice and gerbil models. The reasons for these differences are discussed.
对雄性BALB/c和CDI小鼠移植感染彭亨布鲁线虫(Brugia pahangi)和魏氏双瓣线虫(Dipetalonema viteae)进行了研究,作为评估潜在抗丝虫化合物的模型。上述小鼠品系的生理学和遗传学比目前用于初步体内筛选的任何啮齿动物物种都有更明确的定义,这有助于采用更可重复的方法来预测化合物的杀丝虫活性。腹腔内植入的彭亨布鲁线虫成虫回收率在CDI和BALB/c小鼠植入后长达六周内均大于或等于50%。皮下植入的魏氏双瓣线虫成虫回收率在植入后四周内大于50%,但到六周时已降至30%以下。同时植入小鼠体内的彭亨布鲁线虫和魏氏双瓣线虫成虫的存活情况与单感染时相似,但当植入的成虫数量不同时,与BALB/c小鼠相比,从双植入CDI小鼠中获得的回收率明显更高。对植入CDI小鼠或沙鼠体内的魏氏双瓣线虫和彭亨布鲁线虫进行了标准抗丝虫药评估。除CGP 6140外,在所有测试的抗丝虫药作用下,小鼠双植入模型均检测到对魏氏双瓣线虫、彭亨布鲁线虫或两者的显著驱虫效果。同样,在测试条件下,在沙鼠试验中未检测到CGP 6140,但小鼠和沙鼠模型获得的结果存在显著差异。讨论了这些差异的原因。