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使用腺嘌呤核苷类似物 GS-441524 对临床诊断为神经型猫传染性腹膜炎的猫进行抗病毒治疗。

Antiviral treatment using the adenosine nucleoside analogue GS-441524 in cats with clinically diagnosed neurological feline infectious peritonitis.

机构信息

Department of Surgical and Radiological Sciences, School of Veterinary Medicine, Davis, California, USA.

Veterinary Medical Teaching Hospital, School of Veterinary Medicine, Davis, California, USA.

出版信息

J Vet Intern Med. 2020 Jul;34(4):1587-1593. doi: 10.1111/jvim.15780. Epub 2020 May 22.

Abstract

Feline infectious peritonitis (FIP) is caused by a mutant biotype of the feline enteric coronavirus. The resulting FIP virus (FIPV) commonly causes central nervous system (CNS) and ocular pathology in cases of noneffusive disease. Over 95% of cats with FIP will succumb to disease in days to months after diagnosis despite a variety of historically used treatments. Recently developed antiviral drugs have shown promise in treatment of nonneurological FIP, but data from neurological FIP cases are limited. Four cases of naturally occurring FIP with CNS involvement were treated with the antiviral nucleoside analogue GS-441524 (5-10 mg/kg) for at least 12 weeks. Cats were monitored serially with physical, neurologic, and ophthalmic examinations. One cat had serial magnetic resonance imaging (MRI), cerebrospinal fluid (CSF) analysis (including feline coronavirus [FCoV]) titers and FCoV reverse transcriptase [RT]-PCR) and serial ocular imaging using Fourier-domain optical coherence tomography (FD-OCT) and in vivo confocal microscopy (IVCM). All cats had a positive response to treatment. Three cats are alive off treatment (528, 516, and 354 days after treatment initiation) with normal physical and neurologic examinations. One cat was euthanized 216 days after treatment initiation following relapses after primary and secondary treatment. In 1 case, resolution of disease was defined based on normalization of MRI and CSF findings and resolution of cranial and caudal segment disease with ocular imaging. Treatment with GS-441524 shows clinical efficacy and may result in clearance and long-term resolution of neurological FIP. Dosages required for CNS disease may be higher than those used for nonneurological FIP.

摘要

猫传染性腹膜炎(Feline infectious peritonitis,FIP)是由猫肠道冠状病毒的突变生物型引起的。由此产生的 FIP 病毒(Feline infectious peritonitis virus,FIPV)通常在非渗出性疾病病例中引起中枢神经系统(Central nervous system,CNS)和眼部病理。尽管历史上使用了多种治疗方法,但超过 95%的 FIP 猫在诊断后数天至数月内会死于疾病。最近开发的抗病毒药物在治疗非神经型 FIP 方面显示出了希望,但神经型 FIP 病例的数据有限。4 例自然发生的 CNS 受累 FIP 用抗病毒核苷类似物 GS-441524(5-10mg/kg)治疗至少 12 周。通过体格检查、神经检查和眼科检查对猫进行连续监测。1 只猫进行了连续磁共振成像(Magnetic resonance imaging,MRI)、脑脊液(Cerebrospinal fluid,CSF)分析(包括猫冠状病毒 [Feline coronavirus,FCoV] 滴度和 FCoV 逆转录酶 [Reverse transcriptase,RT]-PCR)和使用傅里叶域光学相干断层扫描(Fourier-domain optical coherence tomography,FD-OCT)和体内共聚焦显微镜(In vivo confocal microscopy,IVCM)的连续眼部成像。所有猫对治疗均有阳性反应。3 只猫在治疗后存活(治疗开始后 528、516 和 354 天),体格检查和神经检查均正常。1 只猫在治疗开始后 216 天因原发性和继发性治疗后复发而被安乐死。在 1 例中,疾病的缓解定义为 MRI 和 CSF 结果正常,眼部成像显示颅后段疾病缓解。GS-441524 的治疗显示出临床疗效,并可能导致神经型 FIP 的清除和长期缓解。治疗 CNS 疾病所需的剂量可能高于治疗非神经型 FIP 的剂量。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3fda/7379040/266ab68ae197/JVIM-34-1587-g001.jpg

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