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用阿糖腺苷5'-单磷酸、阿糖腺苷和膦甲酸对小鼠的三种人疱疹病毒实验性感染的死亡率和发病机制的改变

Alteration of mortality and pathogenesis of three experimental Herpesvirus hominis infections of mice with adenine arabinoside 5'-monophosphate, adenine arabinoside, and phosphonoacetic acid.

作者信息

Kern E R, Richards J T, Overall J C, Glasgow L A

出版信息

Antimicrob Agents Chemother. 1978 Jan;13(1):53-60. doi: 10.1128/AAC.13.1.53.

Abstract

The therapeutic effectiveness of adenine arabinoside 5'-monophosphate (ara-AMP), adenine arabinoside (ara-A), and phosphonoacetic acid (PAA) was compared in three experimental Herpesvirus hominis type 2 infections of mice. In animals inoculated with H. hominis by the intracerebral or intraperitoneal route, both ara-AMP and ara-A were highly effective in reducing mortality even when treatment was begun 48 to 96 h after viral inoculation. ara-AMP was the most effective in both models in that treatment could be initiated 24 to 48 h later in the course of infection than with ara-A and still confer significant protection. In mice inoculated intraperitoneally, protection due to ara-AMP therapy was associated with reduced replication of virus in visceral organs and complete inhibition of transmission of virus to the brain. PAA treatment of mice inoculated intraperitoneally was effective in reducing mortality only if initiated shortly after infection. Treatment with PAA did not reduce mortality of mice inoculated intracerebrally but did prolong the mean day of death. When mice were inoculated intranasally with H. hominis, none of the three drugs altered final mortality; however, treatment with ara-AMP did prolong the mean day of death. Treatment with ara-AMP effectively reduced viral replication in the lung and liver in this model infection, but failed to prevent transmission of virus through the trigeminal nerves from the nasopharynx to the brain.

摘要

在小鼠的三种实验性人疱疹病毒2型感染中,比较了阿糖腺苷5'-单磷酸(ara-AMP)、阿糖腺苷(ara-A)和膦甲酸钠(PAA)的治疗效果。在通过脑内或腹腔途径接种人疱疹病毒的动物中,即使在病毒接种后48至96小时开始治疗,ara-AMP和ara-A在降低死亡率方面都非常有效。ara-AMP在两种模型中都是最有效的,因为在感染过程中比ara-A晚24至48小时开始治疗仍能提供显著的保护。在腹腔接种的小鼠中,ara-AMP治疗带来的保护与内脏器官中病毒复制减少以及病毒向大脑传播的完全抑制有关。仅在感染后不久开始时,PAA治疗腹腔接种的小鼠才有效降低死亡率。PAA治疗脑内接种的小鼠不能降低死亡率,但能延长平均死亡天数。当小鼠经鼻接种人疱疹病毒时,三种药物均未改变最终死亡率;然而,ara-AMP治疗确实延长了平均死亡天数。在这种模型感染中,ara-AMP治疗有效降低了肺和肝中的病毒复制,但未能阻止病毒通过三叉神经从鼻咽向大脑传播。

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