热毒清滴眼液治疗单纯疱疹性角膜炎的实验研究

目的　评估中药热毒清滴眼液对兔实验性单纯疱疹性角膜炎 (herpessimplexkeratitis ,HSK)作用和超声雾化强化给药的疗效及急性毒性与眼的刺激反应。方法　 2 6只新西兰白兔 (5 2只眼 )角膜划痕接种I型单纯疱疹病毒 (herpessimplexvirus 1,HSV I)。HSK模型随机分为热毒清雾化组 :热毒清滴眼液通过超声雾化治疗 ;热毒清滴眼组 :热毒清滴眼液滴眼治疗 ;无环鸟苷组 :无环鸟苷滴眼液滴眼治疗 ;对照组 :生理盐水滴眼治疗。观察 18d时的疗效、对兔眼的刺激情况及对小鼠的不良反应。结果　三个治疗组有效率均显著高于对照组 (P <0 .0 5 ) ;热毒清雾化组有效率高于热毒清滴眼组和无环鸟苷组 ;热毒清滴眼液滴眼与无环鸟苷滴眼液滴眼疗效相同。对兔及小鼠都未发生全身和局部不良反应。结论　这个结果有力提示 ,中药热毒清滴眼液对HSK有明显疗效 ,超声雾化给药能强化药效。     

热毒清滴眼液治疗单纯疱疹性角膜炎的实验研究

目的　评估中药热毒清滴眼液对兔实验性单纯疱疹性角膜炎(herpessimplexkeratitis ,HSK)作用和超声雾化强化给药的疗效及急性毒性与眼的刺激反应。方法　2 6只新西兰白兔(5 2只眼)角膜划痕接种I型单纯疱疹病毒(herpessimplexvirus 1,HSV I)。HSK模型随机分为热毒清雾化组:热毒清滴眼液通过超声雾化治疗;热毒清滴眼组:热毒清滴眼液滴眼治疗;无环鸟苷组:无环鸟苷滴眼液滴眼治疗;对照组:生理盐水滴眼治疗。观察18d时的疗效、对兔眼的刺激情况及对小鼠的不良反应。结果　三个治疗组有效率均显著高于对照组(P<0.05) ;热毒清雾化组有效率高于热毒清滴眼组和无环鸟苷组;热毒清滴眼液滴眼与无环鸟苷滴眼液滴眼疗效相同。对兔及小鼠都未发生全身和局部不良反应。结论　这个结果有力提示,中药热毒清滴眼液对HSK有明显疗效,超声雾化给药能强化药效。     

无环鸟苷联合强的松龙及干扰素治疗单纯疱疹病毒性深层角膜炎

单纯液疹病毒性角膜炎目前已成为世界性最重要的致盲角膜病，而深层角膜炎又以其病情迁延、反复发作使临床医生感到棘手。我科1990年1月至1995年12月采用无环鸟苷联合强的松龙及干扰素治疗单纯疱疹病毒性深层角膜炎45例48只眼，现报告如下。临床资料一、一般资料深层角膜炎45例48只眼，男32只眼，女16只眼，年龄19～71岁。根据病变程度，将角膜炎分为浅实质型13只眼，深实质型35只眼，其中8只眼伴有虹膜炎。二、治疗方法用0．1％无环鸟苷滴眼每2小时一次，病重者可增加滴眼次数。强的松龙0．3ml球结膜下注射，一般注射1～2次（间隔一周），…     

无环鸟苷眼液治疗单纯疱疹性角膜炎的临床观察

无环鸟苷(ACV)是临床上治疗单纯疱疹病毒(HSV)性角膜炎(HSK)常用而有效的药物,本研究应用ACV滴眼液对100眼HSK进行治疗,观察每天滴药次数不同和持续治疗时间不同的治疗效果以及对角膜的损害作用,为临床合理应用药物提供依据,现报告如下。1资料与方法1·1一般资料:自2000年3月至     

苦参碱治疗单纯疱疹性角膜炎的药效学研究

目的观察苦参碱对病毒性角膜炎的治疗效果。方法采用单纯疱疹Ⅰ型病毒感染人羊膜细胞建立体外病毒感染模型;单纯疱疹Ⅰ型病毒感染兔角膜建立体内病毒感染模型。体外实验通过观察CPE及MTT法测定细胞存活率;体内实验采用不同浓度的苦参碱,荧光染色后,裂隙灯下观察对兔病毒性角膜炎模型的治疗作用。结果苦参碱具有明显抗单纯疱疹病毒作用。结论苦参碱对病毒性角膜炎有明显的治疗作用。     

夏枯草提取物对HSV-Ⅰ及单纯疱疹病毒性角膜炎的作用

目的考察夏枯草提取物对单纯性疱疹病毒性角膜炎的疗效。方法建立单纯性疱疹病毒Ⅰ型(herpes simplex virus-Ⅰ,HSV-Ⅰ)感染Vero细胞的体外模型,以细胞病变效应、治疗指数为观察指标,了解不同浓度夏枯草提取物体外抗病毒效果;采用单纯性疱疹病毒HSV-Ⅰ感染家兔角膜建立体内病毒感染模型,家兔分别用夏枯草提取物、阿昔洛韦、生理盐水治疗15 d,眼角膜每天经荧光素钠染色后,裂隙灯下观察药物对家兔病毒性角膜炎模型的治疗作用。结果体外试验表明夏枯草提取物对感染HSV-Ⅰ病毒的Vero细胞具有明显的抗病毒作用,最大无毒质量浓度TC0为516mg.L-1,治疗指数TI为28.03;体内试验结果显示,与模型组相比,夏枯草提取物和阿昔洛韦组均能有效地治疗单纯疱疹病毒性角膜炎,减轻角膜病变程度,缩短平均治愈时间,其疗效与阿昔洛韦组相似。结论夏枯草提取物对单纯疱疹病毒性角膜炎有显著的疗效,可实施新药研发。     

单纯疱疹病毒对常用抗病毒药物的耐药性

单纯疱疹病毒(HSV)与药物共同培养,传数代后,对单一抗病毒药物无环鸟苷(ACV)、环胞苷(CC)、丙氧鸟苷(DHPG)和膦羧基甲酸钠(PFA)均可产生耐药性。但耐药性产生的时间和程度各有不同。联合用药可延缓并减少病毒耐药株的发生,同时可降低用药浓度和剂量,从而减少毒性反应。不同耐药株的交叉药敏试验结果为临床合理用药提供了实验依据。     

透明质酸钠滴眼液对单纯疱疹病毒角膜炎上皮愈合的影响

目的 观察透明质酸钠眼液对上皮型单纯疱疹病毒角膜炎病程的影响.方法 26例上皮型单纯疱疹病毒角膜炎患者随机分为2组.在使用更昔洛韦眼膏基础上A组(14例)加滴0.1％爱丽眼液4次/d,B组(12例)加滴泰利必妥眼液4次/d.对比2组治疗后1周、2周时角膜上皮愈合情况以及矫正视力.结果 治疗后1周时,A组角膜上皮愈合情...     

白内障超声乳化术后早期单纯疱疹病毒感染的临床研究

目的 探讨白内障超声乳化术后早期单纯疱疹病毒(HSV)感染的治疗方法和评价治疗效果。方法 对28例(28只眼)白内障超声乳化术后早期HSV感染者应用无环鸟苷眼药水和a—干扰素眼药水以及低浓度地塞米松眼药水治疗，并与36例(36只眼)单纯疱疹病毒性角膜炎(HSK)采用同样方法治疗对比。结果 两组的疗效比较差异无显著性(P＞0．05)，两组的疗程比较有差异性(P＜0．05)或显著性差异(P＜0．01)。结论 白内障超声乳化术后早期HSV感染的治疗是有效的，其所需要疗程要比HSK的疗程长。     

鱼腥草治疗单纯疱疹病毒性角膜炎

目的评价鱼腥草治疗单纯疱疹病毒性角膜炎(HSK)的临床效果。方法治疗组60例67眼HSK患者用阿昔洛韦滴眼液联合鱼腥草滴眼液滴眼,静脉滴注阿昔洛韦注射液和鱼腥草注射液并观察临床效果,对照组38例43眼HSK患者单用阿昔洛韦滴眼液滴眼及静脉滴注阿昔洛韦注射液,比较两组的治愈率、有效率、疗程及复发率。结果治疗组治愈59眼,占88.06%,有效6眼,占8.96%,无效2眼(深层型),占2.99%,治疗天数平均19天,随访1年,54眼中复发5眼,复发率9.26%;对照组治愈25眼,占58.14%,有效12眼,占27.91%,无效6眼,占13.95%,治疗平均天数31天,随访1年,23眼复发7眼,复发率30.43%;两组比较,治疗组疗效和疗程均优于对照组(P<0.01),治愈患者随访1年,治疗组复发率比对照组明显低。结论应用鱼腥草治疗单纯疱疹病毒性角膜炎能提高疗效,缩短病程,降低复发率。     

酞丁安对实验性单疱角膜炎的作用

酞丁安(Tai-Ding-An,TDA)系我国自己设计合成的一个缩氨基硫脲类化合物。实验及临床研究证明具有抗沙眼衣原体与抗疱疹病毒作用。本文报道酞丁安对兔实验性单疱角膜炎的治疗作用。     

酞丁安对实验性单疱角膜炎的作用

The antiherpes virus effects of Tai-Ding-An (TDA) were studied in experimental herpetic keratitis in rabbits. Topical treatment With 1% or 2% TDA ointment 4 times daily was initiated 48h after virus inoculation in rabbits. Significant efficacy was obtained with herpetic epithelial keratitis. Responses to treatment with 2% TDA ointment were similar to those with 0.1% CC ointment. But 0.5% TDA ointment showed no significant effect. 1% TDA ointment was also not efficacious in the topical treatment of herpetic stromal keratitis in rabbits.     

(E)-5-(2-bromovinyl)-2'-desoxyuridine--a new nucleoside analog with selective inhibitory action against herpesviruses. Studies in cell culture and animal experiments

(E)-5-(2-Bromovinyl)-2'-deoxyuridine (1; BrVUdR) inhibits the replication of herpes simplex virus type 1 (HSV-1) and of varicella-zoster virus (VZV) in vitro at concentrations of 0.01 to 0.23 mumol/l, whereas herpes simplex virus type 2 (HSV-2) is influenced only at 5.5 to 27 mumol/l. In comparison to some classical and newly developed antiherpetics, i. e. 5-iodo-2'-desoxyuridine (2; idoxuridine, IDU), 9-beta-D-arabinofuranosyladenine (4; vidarabine Ara-A), 9-(2-hydroxyethoxymethyl) guanine (5; acyclovir, ACV) and 2'-fluoro-5-iodo-1-beta-D-aracytosine (6;FIAC) the following order of decreasing activity was found:1 greater than 6 greater than 5 greater than 2 greater than 4 (against HSV-1) and 6 greater than 2 greater than 5 greater than 1 greater than 4 (against HSV-2). The high selectivity of the antiviral effect of BrVUdR towards HSV-1 and TZV is based on the fact, that proliferation of different mammalian cell lines is inhibited by 50% only at concentrations as high as 90 to 170 mumol/l, resulting in a therapeutical index of 1000 to 10,000. Successful treatment of an HSV-1 encephalitis in mice as well as an HSV-1 keratitis of rabbits confirmed the efficiency of 1 in experimental animal infections. No toxic side effects in both local and systemic applications were observed. Promising data from cell culture and animal experiments recommend 1 as a potential candidate for the local and systemic treatment of HSV-1 and VZV infections in man.     

Ganciclovir ophthalmic gel 0.15%: in acute herpetic keratitis (dendritic ulcers)

Dendritic epithelial keratitis is most commonly caused by infections of herpes simplex virus (HSV) type 1 (HSV-1), and less frequently by HSV type 2 (HSV-2). Ganciclovir, a guanosine nucleoside analogue, is a well established broad-spectrum antiviral agent that inhibits replication of viral DNA and is active against both HSV-1 and -2 and several other viruses. Ganciclovir ophthalmic gel 0.15% is a five-times-daily topical preparation that is indicated for the treatment of acute herpetic keratitis (dendritic ulcers). A randomized, open-label, phase III trial in immunocompetent patients with acute herpetic keratitis showed that ganciclovir ophthalmic gel 0.15% applied five times daily provided effective clinical resolution of dendritic ulcers following 7 days of treatment (primary endpoint). Moreover, a retrospective analysis of noninferiority showed that ganciclovir ophthalmic gel 0.15% was no less effective than aciclovir (acyclovir) ointment 3%. A pooled analysis of three randomized, single-masked, phase II multinational trials also showed high rates of dendritic ulcer healing at day 7 for eyes treated with ganciclovir ophthalmic gel 0.15% and aciclovir ointment 3%. Furthermore, in the individual phase II trials, most patients showed evidence of healed dendritic and geographic ulcers at day 14 in either treatment arm. Median healing times with either treatment ranged from 6 to 10 days. Ganciclovir ophthalmic gel 0.15% was generally well tolerated and was associated with a significantly lower incidence of visual disturbances than aciclovir ointment 3% in the phase III trial.     

Efficacy of bromovinyldeoxyuridine in the treatment of herpes simplex virus and varicella-zoster virus eye infections

As has been established in rabbits, (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU) is superior to 5-iodo-2'-deoxyuridine (IDU) in the topical treatment of epithelial HSV-1 (herpes simplex virus type 1) keratitis, and superior to 5-trifluoromethyl-2'-deoxyuridine (TFT) in the topical treatment of deep stromal HSV-1 keratitis and HSV-1 uveitis. BVDU 0.1% eye drops have also proven efficacious in the treatment of patients with dendritic corneal ulcers, geographic corneal ulcers and stromal keratitis, and combined treatment of BVDU 0.1% eye drops with oral BVDU at 375 mg/day for 5 days led to a prompt healing of keratouveitis and skin lesions in patients with ophthalmic herpes zoster.     

Antiherpetic activity and mechanism of action of 9-(4-hydroxybutyl)guanine

9-(4-Hydroxybutyl)guanine was synthesized and tested for antiherpes activity. In cell cultures, different strains of herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) were inhibited by 50% at 2–14 μM of 9-(4-hydroxybutyl)guanine, while a HSV-1 mutant lacking thymidine kinase (HSV-1 TK^-) was resistant. Linear competitive inhibition of purified HSV-1-induced thymidine kinase (TK) with thymidine as a variable substrate was observed for 9-(4-hydroxybutyl)guanine with an apparent K_i value of 2.06 μM while the corresponding K_i value for the cellular TK was > 250 μM. By using high performance liquid chromatography, the formation of 9-(4-hydroxybutyl)guanine monophosphate by HSV-1 TK was measured and the rate of product formation was found to be about 10% of that found by using thymidine as a substrate. A selective inhibition of HSV-1 DNA synthesis by 9-(4-hydroxybutyl)guanine was observed in infected Vero cells. 9-(4-Hydroxybutyl)guanine had a low cellular toxicity. A weak therapeutic effect on herpes keratitis in rabbits was observed whereas cutaneous HSV-1 infection in guinea pigs and systemic HSV-2 infection in mice were not affected by this compound.     

Evaluation of (E)-5-(2-bromovinyl)- and 5-vinyl-1-beta-D-arabinofuranosyluracil (BrVaraU, VaraU) in the treatment of experimental herpes simplex virus type 1 keratitis in rabbits: comparison with (E)-5-(2-bromovinyl)-2'-deoxyuridine (BrVUdR)

The 5-substituted 1-beta-D-arabinofuranosyl (araU) analogues, (E)-5-(2-bromovinyl)-araU (BrVaraU) and 5-vinyl-araU (VaraU), which can be considered as structural analogues of (E)-5-(2-bromovinyl)-2'-deoxyuridine (BrVUdR), are potent and selective inhibitors of herpes simplex virus type 1 (HSV-1) replication in vitro. BrVaraU and VaraU have been compared with BrVUdR for their therapeutic effect on acute HSV-1 keratitis in rabbits. Both araU derivatives applied as 0.1% eyedrops suppressed the development of keratitis as monitored by the reduced number of herpes efflorescences. The healing effect of BrVaraU and VaraU was less pronounced than that of 0.1% BrVUdR eyedrops, the difference between BrVUdR and VaraU being statistically significant at the 10th day of treatment. As a further indication of the healing effect the number of cornea with opacities seen after cessation of drug treatment were 3.3, 7.4, 27.6 and 46.9% for the BrVUdR-BrVaraU-, VaraU- and placebo-treated eyes, respectively.     

Synthesis and antiherpes simplex virus activity of 9-[(1,3-dihydroxy-2-propylthio)methyl]guanine

The synthesis of the thio analogue (thio-DHPG, 2) of 9-[(1,3-dihydroxy-2-propoxy)methyl]guanine (DHPG, 1) is described. The synthesis of 2 proceeded via the condensation of acetoxymethyl sulfide 9 with diacetylguanine 10 to give the protected nucleoside analogue 11. Although catalytic hydrogenolysis failed, the benzyl ether functionalities of 11 were successfully cleaved by an acetolysis reaction to furnish 14. Ammonolysis of 14 gave 2, which was also transformed to sulfoxide 15 and sulfone 16. Preliminary in vitro screening indicated that 2 exhibited comparable activity to DHPG against herpes simplex virus type 1 (HSV-1) but was less active against the type 2 virus (HSV-2) and human cytomegalovirus (HCMV). In a mouse encephalitis model (HSV-2), subcutaneous treatment with 2 led to a 53% reduction in mortality at a dose of 100 mg/kg per day.     

Potentiating effect of ribavirin on the anti-herpes activity of acyclovir.

The combined antiviral effects of acyclovir (ACV) and ribavirin (Rbv) on herpes simplex virus type 1 (HSV-1) and pseudorabies virus (PRV) in cell cultures and on experimental HSV-1 keratitis in rabbits were studied. The antiviral activity in vitro was based on cytopathogenicity inhibition and yield reduction. The combination of the two drugs exhibited synergy as evaluated graphically (isobolograms). Rbv also potentiated the antiviral effect of ACV in vivo, in the experimental HSV-1 keratitis model in rabbits. This was evident from both the severity of corneal lesions and virus shedding in the tear film. The potentiating effect of Rbv on the anti-HSV-1 activity of ACV in vitro was reversed by guanosine.     

Antiviral activity of serum from the American alligator (Alligator mississippiensis)

Serum from wild alligators was collected and tested for antibiotic activity against three enveloped viruses using cell-based assays. Alligator serum demonstrated antiviral activities against human immunodeficiency virus type 1 (HIV-1; IC50=0.9%), West Nile virus (WNV; IC50=4.3%), and Herpes simplex virus type 1 (HSV-1; IC50=3.4%). The inhibitory concentration (IC50) is defined as the concentration of serum that inhibits 50% of viral activity. The antiviral effects of the alligator serum were difficult to evaluate at high concentrations due to the inherent toxicity to the mammalian cells used to assay viral activities. The TC50 (serum concentration that reduces cell viability to 50%) values for the serum in the HIV-1, WNV, and HSV-1 assays were 32.8, 36.3 and 39.1%, respectively. Heat-treated serum (56 degrees C, 30 min) displayed IC50 values of >50, 9.8 and 14.9% for HIV-1, WNV and HSV-1 viruses, respectively. In addition, the TC50 values using heat-treated serum were substantially elevated for all three assays, relative to untreated serum (47.3 to >50%). Alligator serum complement activity has been shown to be heat labile under these conditions. HIV-1 antiviral action was heat-sensitive, and thus possibly due to the action of serum complement, while the anti-WNV and anti-HSV-1 activities were not heat labile and thus probably not complement mediated.