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甲氟喹对大鼠华支睾吸虫和犬卫氏并殖吸虫的疗效。

Effectiveness of mefloquine against Clonorchis sinensis in rats and Paragonimus westermani in dogs.

机构信息

National Institute of Parasitic Diseases, Chinese Center for Disease, Control and Prevention, Key Laboratory of Parasite and Vector Biology, MOH, WHO Collaborating Centre for Malaria, Schistosomiasis, and Filariasis, Shanghai, 200025, PR China.

出版信息

Parasitol Res. 2010 Nov;107(6):1391-7. doi: 10.1007/s00436-010-2007-7. Epub 2010 Aug 3.

Abstract

The aim of the study is to explore the effect of mefloquine against Clonorchis sinensis and Paragonimus westermani. For anti-C. sinensis study, a total of 71 rats were divided into four batches for oral infection of each rat with 50 C. sinensis metacercariae. Five to 7 weeks post-infection, groups of rats were treated orally with mefloquine at single doses or multiple daily doses while infected, but untreated rats served as control. All treated rats were euthanized 2 weeks post-treatment for assessment of efficacy. For anti-P. westermani study, two batches of eight and ten dogs were each infected intraperitoneally with 100 P. westermani metacercariae. Eighty-five to 96 days post-infection, groups of two or three dogs were treated orally with mefloquine and groups of two dogs were treated with praziquantel at a single dose or multiple doses. In each batch of test, three untreated but infected dogs served as control. All treated dogs were euthanized 26-30 days post-treatment for evaluation of efficacy. In rats infected with C. sinensis and treated orally with mefloquine at a single dose of 75 and 150 mg/kg, no effect against C. sinensis was observed. When the dose of mefloquine was increased to 250 mg/kg, one third (five out of 15) rats died 3-5 days post-treatment. Although the mean worm burden was lower than that of the control, the difference between the treated and control groups was not statistically significant (P>0.05) with worm burden reduction of 22.4%. Whereas, the group of infected rats received mefloquine at a daily dose of 100 mg/kg for 3 days, one out of five rats died after the last administration. The mean worm burden was significantly lower than that of the control with worm burden reduction of 67.6% (P<0.01). In the first test of mefloquine against P. westermani, three infected dogs received two oral doses of the drug, 50 mg/kg, given at a 4-h interval, the mean worm burden were similar to that of the control. While other two dogs were treated with praziquantel at the same dose schedule, the worm burden reduction of 78% was observed. In the second test, three and two dogs were treated with mefloquine 50 mg/kg daily for 5 days or 100 mg/kg daily for 2 days; the mean worm burdens of the two groups were lower than that of the control with worm burden reduction of 65.6% and 51.9%, respectively. However, only the difference of mean worm burdens between mefloquine 50 mg/kg given daily for 5 days and the control was statistically significant (P<0.05). Other two dogs treated with praziquantel at a single dose of 100 mg/kg were cured. The results indicate that under the appropriate dose schedule mefloquine exhibits less effect against C. sinensis in rats and P. westermani in dogs.

摘要

研究目的在于探索甲氟喹(mefloquine)对华支睾吸虫(Clonorchis sinensis)和并殖吸虫(Paragonimus westermani)的作用。在抗华支睾吸虫的研究中,共将 71 只大鼠分为 4 批,每批大鼠经口感染 50 个华支睾吸虫囊蚴。感染后 5-7 周,实验组大鼠经口给予甲氟喹治疗,剂量为单次或多次每日剂量,而未治疗的大鼠作为对照组。所有接受治疗的大鼠在治疗后 2 周内安乐死,以评估疗效。在抗并殖吸虫的研究中,将两批各 8 只和 10 只狗经腹腔感染 100 个并殖吸虫囊蚴。感染后 85-96 天,两组或三组狗经口给予甲氟喹治疗,两组狗给予吡喹酮(praziquantel)单次或多次剂量治疗。在每批试验中,3 只未治疗但感染的狗作为对照组。所有接受治疗的狗在治疗后 26-30 天内安乐死,以评估疗效。在感染华支睾吸虫的大鼠中,经口给予甲氟喹 75 和 150mg/kg 时,对华支睾吸虫无作用。当甲氟喹剂量增加至 250mg/kg 时,15 只大鼠中有 3 只(5 只中的 3 只)在治疗后 3-5 天死亡。虽然虫体负荷的平均值低于对照组,但治疗组与对照组之间的差异无统计学意义(P>0.05),虫体负荷减少 22.4%。然而,感染大鼠组每日接受 100mg/kg 甲氟喹治疗 3 天,最后一次给药后有 1 只大鼠死亡。虫体负荷的平均值明显低于对照组,减少 67.6%(P<0.01)。在第一个甲氟喹抗并殖吸虫的试验中,3 只感染的狗接受了两次口服给药,每次 50mg/kg,间隔 4 小时,虫体负荷与对照组相似。而其他 2 只狗接受了相同剂量方案的吡喹酮治疗,观察到 78%的虫体负荷减少。在第二个试验中,3 只和 2 只狗分别每日接受 50mg/kg 甲氟喹治疗 5 天或 100mg/kg 甲氟喹治疗 2 天;两组的虫体负荷均低于对照组,减少率分别为 65.6%和 51.9%。然而,只有每日接受 50mg/kg 甲氟喹治疗 5 天的组与对照组之间的平均虫体负荷差异具有统计学意义(P<0.05)。另外 2 只接受吡喹酮 100mg/kg 单次剂量治疗的狗被治愈。结果表明,在适当的剂量方案下,甲氟喹对大鼠的华支睾吸虫和狗的并殖吸虫的作用较弱。

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