Watts S D
Exp Parasitol. 1986 Oct;62(2):157-68. doi: 10.1016/0014-4894(86)90020-2.
Within 24 hr of treatment of the mouse host with BW484C, 2-[5-nitro-2-(pivaloylimino)-4-thiazoline-3-yl]diacetamide, pairs of Schistosoma mansoni exhibited "hepatic shift" and began to leave the mesenteric veins. The tegument of the males was altered, both morphologically and physiologically, while that of females was unaffected. This morphological damage to males correlated well with therapeutic efficacy against both sexes in a range of analogues of BW484C. However, parasites removed from mice after treatment but before the hepatic shift and then maintained in vitro were far from moribund as treated males could be maintained for 8 days in vitro, although this was 5 days less than males from untreated mice. Females survived as well as control worms. In contrast, male and female S. mansoni remaining in their host after therapy were invaded by host cells in the liver after 2 days. The morphological effects and reduction of the in vitro survival of males treated in the mouse and removed after 24 hr could be simulated by in vitro exposure for 24 hr to 10(-5) M BW484C. Females were not susceptible to this regime. It was concluded that worm pairs were swept to the liver as a result of drug dependent damage to the tegument of the male and that phagocytic invasion of male and female schistosomes by host cells within the liver was an important factor in the efficacy of BW484C. The biochemical events underlying the effects on the tegument of male worms remain unknown.
用BW484C（2-[5-硝基-2-(新戊酰亚氨基)-4-噻唑啉-3-基]二乙酰胺）处理小鼠宿主后24小时内，曼氏血吸虫虫对出现“肝转移”并开始离开肠系膜静脉。雄虫的体表在形态和生理上均发生改变，而雌虫体表未受影响。雄虫的这种形态损伤与一系列BW484C类似物对雌雄两性的治疗效果密切相关。然而，在治疗后但肝转移发生前从小鼠体内取出并在体外维持的寄生虫远未濒死，因为经处理的雄虫在体外可维持8天，尽管这比未处理小鼠的雄虫少5天。雌虫存活情况与对照虫相同。相比之下，治疗后留在宿主内的曼氏血吸虫雌雄虫在2天后被肝脏中的宿主细胞侵入。在小鼠体内处理24小时后取出的雄虫，其体外存活时间缩短以及形态学效应可通过在体外暴露于10(-5)M BW484C 24小时来模拟。雌虫对此处理不敏感。得出的结论是，由于药物对雄虫体表的依赖性损伤，虫对被扫向肝脏，并且肝脏内宿主细胞对雌雄血吸虫的吞噬性侵入是BW484C疗效的一个重要因素。对雄虫体表产生影响的生化事件仍不清楚。
