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喹诺酮类药物抗乙型肝炎病毒体外实验研究 总被引:4,自引:0,他引:4
本文以2.2.15细胞株为模型,以HBsAg、HBeAg、HBVDNA、细胞存活率为观察指标,综合评价了喹诺酮类药物吡哌酸(PipemidicAcid)、氟哌酸(Norfloxacin)、环丙氟哌酸(Ciproflosxacin)、氟嗪酸(Ofloxacin)体外抗HBV效果。结果表明:吡哌酸、氟哌酸、环丙氟哌酸、氟嗪酸对HBsAg、HBeAg50%抑制浓度(ID_(50))分别为11μg/ml、64μg/ml、93μg/ml、105μg/ml和199μg/ml、111μg/ml、24μg/ml、217μg/ml,细胞存活率为50%时的药物浓度(CD_(50))分别为219μg/ml、90μg/ml、181μg/ml、169μg/ml,在所选定的用药浓度范围内不同程度抑制培养上清液及细胞内HBVDNA及其复制中间体的产生。尤其对超螺旋结构DNA(scDNA)有不完全抑制作用。 相似文献
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对379例良、恶性肝组织进行的免疫组织化学研究显示,33%的慢性迁延性肝炎(6/18)、76%的慢性活动性肝炎(26/34)、92%的肝硬变(57/62)和97%的肝细胞性肝癌(HCC)(58/60)中有HBxAg表达,阳性率高于HBsAg或HBcAg。癌周肝中的HBxAg阳性率显著高于非癌周肝。与其它2种HBV抗原不同,HBxAg表达在细胞类型上有较明显的选择性,在肝小多角细胞(SPLC)、小细胞性不典型增生(SCD)及HCC中较强。与IGFⅡ、c-erbB-2、c-myc和EGF-R表达进行的对照研究表明HBxAg与IGFⅡ和c-erbB-2这2种HCC发生相关基因的表达关系密切。PCNA染色结果显示HBxAg阳性组织的细胞增殖活性显著高于HBxAg阴性组织。我们的结果还表明HBxAg表达与肝细胞不典型增生的发生和进展有关、提出HBVX基因可能通过其表达产物(HBxAg)首先激活IGFⅡ、c-erbB-2基因,继而引起显著的SPLC增生和SCD而参与HCC发生的. 相似文献
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大剂量国产胸腺肽联合干扰素治疗慢性乙肝疗效及其机理初探 总被引:3,自引:0,他引:3
本文研究大剂量胸腺肽联合干扰素对慢性乙肝患者的治疗作用,发现胸腺肽联合干扰素治疗三个月后,患者的ALT复常率、HBeAg转阴率、HBVDNA阴转率和HBVDNA有效下降率分别为760%、440%、560%和960%。T淋巴细胞亚群分析结果表明,联合治疗后,患者外周血CD4+淋巴细胞亚群上调,CD8+亚群下调,二者比值趋于正常,说明国产胸腺肽联合干扰素治疗慢性乙肝的治疗机理与免疫调节作用有关。 相似文献
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HBIG,无环鸟苷,干扰素联合对慢性乙型肝炎抗病毒效应观察 总被引:1,自引:0,他引:1
本文报道血清HBV复制标志阳性的慢乙肝54例,随机分为治疗组及对照组各27例进行HBIG、无环鸟苷、干扰素联合近、远期抗病毒效应观察。治疗组为无环鸟苷第一周按25~20mg/kg/d计后改17~15mg/kg/d×53天,共60天;人白细胞干扰素1×106U肌注每周3次×4周,后改1.0×106U肌注每周2次×6周,共10周;HBIG400U肌注隔日1次,共10周,对照组仅给予一般“保肝”药物。其中治疗组18例,对照组19例进行治后半年到2年追踪观察,结果近、远期HBcAg、DNAP、HBV-DNA阴转率治疗组均高于对照组,其中治疗组近、远期HBcAg,HBV-DNA阴转率均达40%以上,明显高于对照组(P<0.05~0.01),治疗组近、远期各有4例及2例HBsAg阴转,而对照组则无一例阴转,从近、远期综合抗病毒效应观察,治疗组全阴率分别为33.3%、44.4%,而对照组分别为3.79%及0%,P<0.01,治疗组无明显毒副反应。对比单用无环鸟苷,全阴率31.8%;无环鸟苷加干扰素两药联合全阴率37.5%,均有所提高,达到44.4%,值得进一步研究。 相似文献
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牛病毒性腹泻病毒基因组cDNA文库的构建 总被引:1,自引:0,他引:1
以牛病毒性腹泻病毒(BVDV)┥nL株的基因组RNA为模板,经逆向转录酶作用,合成第一链cDNA,再以RNadse/H与DNA聚合酶I联合作用合成dscDNA,并以dC同聚物尾化。pUC8DNA在Pst I酶解后,以dG同聚物尾化,两者退火构成重组质粒,转化到E.coli JM101受体菌中,另以γ-^32P-ATP标记BVDV RNA制备探针,通过菌落原位杂交筛选重组子。酶切分配表明重组质粒插入 相似文献
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病毒性肝炎HAV,HBV,HCV,HDV和HEV重叠感染的研究 总被引:1,自引:0,他引:1
采用ELISA法检测了108例乙型肝炎病毒(HBV)感染者血清中的五种肝炎病毒──甲型(HAV)、乙型(HBV)、丙型(HCV)、丁型(HDV)和成型(HEV)肝炎病毒的标志物,并采用PCR技术检测了患者血清HBVDNA、HCVRNA及HDVRNA。结果五种肝炎病毒重叠感染者35例(32.4%),单纯HBV感染者73例(67.6%)。HBV、HAVM重感染率为4.6%,HBV、HCV二重感染率为9.2%,HBV、HDVM重感染率为14.8%,HBV、HEV二重感染率为1.9%,HBV、HCV和HDV三重感 相似文献
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根据1996年公布的第6次国际病毒分类委员会材料,将原来的DNA病毒类的嗜肝病毒科,改称为DNA反转录病毒类嗜肝DNA病毒科,其下又分为:正嗜肝DNA病毒属「包括乙型肝为病毒(HBV)、土拨鼠肝炎病毒(WHV)、地松鼠肝炎病毒(GSHV)3个种」和禽类DNA嗜肝病毒属两个属,后者包括鸭乙型肝炎病毒(DHBV)和苍鹭乙型肝炎病毒(HHBV)2个种。1998年在美国圣地亚哥召开的HBV分子生物学会议上 相似文献
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丙型肝炎病毒核酸疫苗的免疫效果观察 总被引:3,自引:1,他引:2
将丙型肝炎病毒C+E1区基因克隆到不同的真核细胞表达载体pCDNA3.1(+)和pSVL中,通过肌肉注射和皮下注射免疫BALB/C及F1小鼠后,产生了抗HCV/C区抗体。其中核酸疫苗pcDNA3.1-HCV/C+E1的免疫高峰的出现早于pSVL-HCV/C+E1,F1小鼠的抗体应答强于BALB/小鼠。肌肉注射优于皮下注射。 相似文献
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To facilitate investigations of replication and host cell interactions in the hepadnavirus system, we have developed cell lines permitting the conditional replication of duck hepatitis B virus (DHBV). With the help of this system, we devised conditions for core particle isolation that preserve replicase activity, which was not found in previous preparations. Investigations of the stability of viral DNA intermediates indicated that both encapsidated DNA and covalently closed circular DNA (cccDNA) were turned over independently of cell division. Moreover, we showed that alpha interferon reduced the accumulation of RNA-containing viral particles. The availability of a synchronized replication system will permit the biochemical analysis of individual steps of the viral replication cycle, including the mechanism and regulation of cccDNA formation. 相似文献
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Antisense therapy of hepatitis B virus infection 总被引:2,自引:0,他引:2
Wolf-Bernhard Offensperger Silke Offensperger Hubert E. Blum 《Molecular biotechnology》1998,9(2):161-170
Chronic infection with the hepatitis B virus (HBV) is a major health problem worldwide. The only established therapy is interferon-a
with an efficacy of only 30–40% in highly selected patients. The discovery of animal viruses closely related to the HBV has
contributed to active research on antiviral therapy of chronic hepatitis B. The animal model tested and described in this
article are Peking ducks infected with the duck hepatitis B virus (DHBV). Molecular therapeutic strategies aimed at blocking
gene expression include antisense DNA. An antisense oligodeoxynucleotide directed against the 5′-region of the preS gene of
DHBV inhibited viral replication and gene expression in vitro in primary duck hepatocytes and in vivo in Peking ducks. These
results demonstrate the potential clinical use of antisense DNA as antiviral therapeutics. 相似文献
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J Bacher C Kassianides T J Moskal D M Mathews J H Hoofnagle 《Laboratory animal science》1989,39(1):67-68
The duck hepatitis B virus (DHBV), a member of the hepadna-virus group, has become a useful animal model for exploring important aspects in this family of viruses such as viral replication, course of infection, and the response to antiviral therapy. In chronically DHBV infected ducks, repeated analyses of liver tissue are important in defining the degree of viral replication and liver injury. We describe a technique for repeated liver biopsy using a Keyes skin punch biopsy. This technique provided sufficient quantities of liver tissue for serial analyses with minimal hemorrhage in 18 Pekin ducks. This procedure offers a safe and reliable method of obtaining serial liver biopsies. 相似文献
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Rapid resolution of duck hepatitis B virus infections occurs after massive hepatocellular involvement. 总被引:9,自引:0,他引:9
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A R Jilbert T T Wu J M England P M Hall N Z Carp A P O''''Connell W S Mason 《Journal of virology》1992,66(3):1377-1388
A study was carried out to determine some of the factors that might distinguish transient from chronic hepadnavirus infection. First, to better characterize chronic infection, Pekin ducks, congenitally infected with the duck hepatitis B virus (DHBV), were used to assess age-dependent variations in viremia, percentage of DHBV-infected hepatocytes, and average levels of DNA replication intermediates in the cytoplasm and of covalently closed circular DNA in the nuclei of infected hepatocytes. Levels of viremia and viral DNA were found to peak at about the time of hatching but persisted at relatively constant levels in chronically infected birds up to 2 years of age. The percentage of infected hepatocytes was also constant, with DHBV replication in virtually 100% of hepatocytes in all birds. Next, we found that adolescent ducks inoculated intravenously with a large dose of DHBV also developed massive infection of hepatocytes with an early but low-level viremia, followed by rapid development of a neutralizing antibody response. No obvious quantitative or qualitative differences between transiently and chronically infected liver tissue were detected in the intracellular markers of viral replication examined. However, in the adolescent duck experiment, DHBV infection was rapidly cleared from the liver even when up to 80% of hepatocytes were initially infected. In all of these ducks, clearance of infection was accompanied by only a mild hepatitis, with no evidence that massive cell death contributed to the clearance. This finding suggested that mechanisms in addition to immune-mediated destruction of hepatocytes might make major contributions to clearance of infections, including physiological turnover of hepatocytes in the presence of a neutralizing antibody response and/or spontaneous loss of the capacity of hepatocytes to support virus replication. 相似文献
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