单纯疱疹病毒2型药物敏感性测定及其阿昔洛韦耐药株的建立

目的应用空斑抑制试验测定单纯疱疹病毒2型(HSV-2)药物敏感性,并建立体外耐药病毒株。方法将HSV-2接种于乳兔肾细胞中,加入不同浓度的阿昔洛韦(ACV),培养72h后固定、染色、清点空斑数并计算药物的半数抑制浓度(IC50),通过IC50来判断HSV-2的药物敏感性。将HSV-2在含ACV环境中连续培养9代,分别在第3,6和9代测定其IC50。结果ACV对HSV-2标准株Sav毒株的IC50为1.1μg/mL。HSV-2在含ACV的环境中连续培养3代后即产生了耐药性,第3,6和9代的IC50分别为8.4μg/mL,56.9μg/mL和121.3μg/mL。结论空斑抑制试验是测定病毒药物敏感性的有效、实用的方法,建立的体外耐药病毒株可用于HSV-2的耐药性研究。     

小檗碱衍生物HB-13体外抗单纯疱疹病毒的研究

目的 探讨小檗碱衍生物HB-13及其前体小檗碱体外抗HSV-1和HSV-2的活性.方法 利用Vero细胞体外培养模型,以阿昔洛韦(ACV)为对照药,通过观察细胞病变效应,检测HB-13和小檗碱的细胞毒性、HSV-1和HSV-2液的病毒滴度及药物抑制病毒致细胞病变效应.结果 HB-13、小檗碱和阿昔洛韦的半数中毒质量浓度(TC50)分别为31.99,380和>800 μg/mL;对HSV-1的半数抑制质量浓度(IC₅₀)分别为1.328,>100和0.443 μg/mL,治疗指数分别为24.09,<3.80和>1805.87;对HSV-2的IC₅₀分别为1.344,>100和0.679μg/mL;治疗指数分别为23.80,<3.80和>1178.20.结论 HB-13具有明显的抗HSV作用,而小檗碱无实用抗HSV活性.     

新一代抗疱疹病毒药——伐昔洛韦

伐昔洛韦(valaciclovir),即盐酸万乃洛韦,是阿昔洛韦(ACV)——无环鸟苷的前体药,并且具有与母体相似的抗疱疹病毒感染的作用^[1].现将与伐昔洛韦治疗作用有关的主要药效学、药代动力学、动物毒性试验及临床验证资料等介绍如下。一、伐昔洛韦的体外抗病毒作用由于伐昔洛韦具有抗单纯疱疹病毒1、2型(HSV-1、2)的作用,故可用Vero细胞培养的方法观察本品对细胞的毒性及其抗单纯疱疹病毒的活性,并与阿昔洛韦进行比较。     

不同剂量和疗程伐昔洛韦治疗复发性生殖器疱疹的随机双盲研究

目的 比较不同剂量和疗程伐昔洛韦治疗复发性生殖器疱疹的疗效和安全性。方法 选择复发性生殖器疱疹为研究对象,采用多中心、随机、双盲、对照临床研究。试验组伐昔洛韦每天2次,每次500 mg,口服5天,对照组伐旨洛韦每天2次,每次300 mg,口服7天。分别于用药前及用药后第1天、第2天取疱液或创面分泌物行疱疹病毒细胞培养,并于用药后第1、2、7天随访观察疗效和不良反应。结果 入组142例,全分析集(FAS)分析142例,符合方案集(PPS)分析133例。治疗后第1、2、7天,试验组和对照组的症状体征积分下降值及有效率比较差异均无统计学意义(P>0.05)。FAS集分析单纯疱疹病毒(HSV)的培养阳性率,治疗后第1天试验组由87.50%下降到28.85%,对照组由92.86%下降到54.55%,两组间差异有统计学意义(P=0.007)。PPS集分析HSV的培养阳性率,治疗后第1天试验组由90.00%下降到28.00%,对照组由92.59%下降到55.56%,两组比较差异有统计学意义(P=0.005)。试验组和对照组不良反应发生率分别为0%和4.23%。结论 加大伐昔洛韦用量治疗复发性生殖器疱疹能显著提高治疗后第1天HSV的清除率,缩短HSV在皮损局部的存在时间。     

环孢素A、雷公藤内酯醇及红霉素与5-脂氧合酶产物的关系

目的 探索环孢素A、雷公藤内酯醇及红霉素对5-脂氧合酶的影响及建立相应的药效学方法。方法 采用反相高效液相色谱法检测5-脂氧合酶产物——白三烯B4和5-羟花生四烯酸量的变化来反映该酶活性的改变。结果 环孢素A可抑制白三烯B4和5-羟花生四烯酸的生成,呈剂量依赖性,IC₅₀值分别为38.0和0.96μg/mL。雷公藤内酯醇(T₀)可抑制白三烯B4和5-羟花生四烯酸的生成,呈剂量依赖性,IC₅₀值分别为2.3×10^-6和1.14×10^-6μg/mL。红霉素无剂量依赖性。结论 雷公藤的抗炎作用与抑制5-脂氧合酶活性有关,环孢素A的抑制浓度超出了其药理浓度,无实际意义,红霉素氧合酶活性无影响。     

新生隐球菌对立福康唑和氟康唑的体外敏感性实验

目的 了解临床和环境中分离所得的新生隐球菌对立福康唑和氟康唑的体外敏感性。方法 采用美国国家实验室标准委员会(NCCLS)M27-A方案推荐的酵母菌微量稀释法,检测77株来自临床和环境中分离所得新生隐球菌对立福康唑和氟康唑的MIC值。结果 氟康唑、立福康唑的MIC范围分别为2.0～128μg/mL、0.008～0.5μg/mL,前者MIC₅₀、MIC₉₀几何均数值分别为4μg/mL、8μg/mL,后者几何均数值分别为0.125μg/mL、0.25μg/mL。其中,对氟康唑敏感菌株占81.8%(63/77),中度敏感或剂量依赖性敏感菌株占16.9%(13/77),耐药菌株占1.3%(1/77)。中度敏感和耐药的14株菌中,临床分离株占85.7%,尽管在临床菌株与环境分离株间差异无显著性(P>0.05),但仍应引起临床医师重视。结论 虽然部分新生隐球菌对氟康唑出现中度敏感或耐药,但立福康唑对其均具有较好的体外抗菌活性,有望成为治疗隐球菌病药物的又一选择。     

病毒性皮肤病

20101774伐昔洛韦治疗带状疱疹临床疗效观察/龚宪军(山东枣庄矿业中心医院皮科)∥中国性科学.-2010,19(6).-37~40140例患者,随机分为两组各70例。试验组予伐昔洛韦0.3g2次/d,对照组阿昔洛韦0.2g5次/d口服,疗程均为10天。结果:止痛、止疱、结痂时间试验组明显快于对照组,痊愈、显效、有效率前者亦明显优于后者。认为伐昔洛韦治疗带状疱疹疗效好,不良反应少,服用方便,安全有效。表2参2(张锦章)20101775窄谱中波紫外线联合伐昔洛韦口服治疗老年性带状疱疹临床观察/李梅(上海奉贤镇塘外卫生院)∥中国中西医结合皮肤性病学杂志.-2010,9(2).-120将患者随机分     

盐酸伐昔洛韦治疗带状疱疹临床疗效观察

目的:评价盐酸伐昔洛韦治疗带状疱疹的临床疗效。方法:将入选患者随机分为两组,治疗组患者给予盐酸伐昔洛韦0.3g,每日2次口服;对照组患者给予阿昔洛韦0.2g,每日5次口服。疗程均为10d,并于用药后观察记录临床症状和体征改善情况。结果:盐酸伐昔洛韦的平均止痛、止疱、结痂时间均比阿昔洛韦短,治疗组有效率为91.4%,对照组有效率为54.3%,两组有效率比较,差异有显著性意义(P0.01)。结论:盐酸伐昔洛韦治疗带状疱疹疗效好,不良反应少,是一个安全有效的药物。     

伐昔洛昔联合甘露聚糖肽治疗复发性生殖器疱疹疗效观察

目的观察伐昔洛韦胶囊联合甘露聚糖肽针剂治疗复发性生殖器疱疹的疗效。方法治疗组45例口服伐昔洛韦胶囊0.3g/次,2次/d;甘露聚糖肽针5mg加利多卡因0.5mL局部皮下注射,3日1次,共10次。对照组40例予口服伐昔洛韦胶囊0.3g/次,2次/d。疗程均为1个月。治疗结束,随访1年。结果治疗组复发率22.2%,低于对照组复发率55.0%,无明显的不良反应。结论伐昔洛韦胶囊联合甘露聚糖肽针治疗生殖器疱疹疗效满意。     

病毒性皮肤病

20110403元通合剂联合伐昔洛韦治疗带状疱疹疗效观察/冯永芳(武汉市中西医结合医院)∥湖北中医杂志.-2010,32(3).-55治疗组口服元痛合剂(院内制剂,包括龙胆草、柴胡、黄芩、栀子、泽泻、车前子、木通、板蓝根、延胡索、当归、生地等)50mL,盐酸伐昔洛韦分散片0.3g,均2次/d。对照组只服伐昔洛韦0.3g,2次/d。两组均治疗10天后观察疗效。结     

Frequency of acyclovir-resistant herpes simplex viruses isolated from the general immunocompetent population and patients with acquired immunodeficiency syndrome

BACKGROUND: Herpes simplex virus (HSV) infections are usually chronically recurrent in the normal population and represent a significant cause of morbidity in immunocompromised patients. Acyclovir (ACV) is widely used for the treatment and prophylaxis of HSV infections. The emergence of ACV-resistant strains has been frequently reported as a result of long-term ACV therapy. AIM: Despite the widespread use of ACV, there are no data available in our area on the frequency of ACV-resistant HSVs. The purpose of this study was to evaluate the susceptibility of HSV isolated from normal subjects and patients with acquired immunodeficiency syndrome (AIDS) to ACV. METHODS: HSVs were isolated from the orofacial region of normal individuals and patients with AIDS. The susceptibility of isolated HSV strains to various concentrations of ACV was determined by plaque reduction assay. The sensitivity of the viral strains was expressed as IC(50) (the concentration of drug reducing the viral plaque by 50%). RESULTS: One hundred and thirty-three isolates from 102 normal subjects and 31 patients with AIDS were tested. One HSV-1 isolate from normal individuals had intermediate susceptibility. Two ACV-resistant isolates (one HSV-1 and one HSV-2), with IC(50) > or = 2 to < or = 3 microg/mL, and one highly resistant HSV-2 isolate, with IC(50) > or = 5 microg/mL, were detected in patients with AIDS. CONCLUSIONS: Our data show that the prevalence of ACV-resistant strains is very low in the general immunocompetent population; however, in patients with AIDS, the prevalence of ACV-resistant strains is remarkable (P = 0.001). Alternative antiherpetic agents should be employed to control and reduce the emergence of ACV-resistant strains in patients with AIDS.     

Herpes simplex virus: isolation,cytopathological characterization and antiviral sensitivity

BACKGROUND

Herpes simplex virus (HSV) infection is an endemic disease and it is estimated that 6095% of the adult population are infected with symptoms that are usually self-limiting, though they can be serious, extensive and prolonged in immunocompromised individuals, highlighted by the emergence of drug-resistant strains. The study of the wild-type HSV strains based on the cytopathogenic features and its antiviral sensitivity are important in the establishment of an antivirogram for controlling the infection.

OBJECTIVE

This study sought to isolate and examine the cytopathological characteristics of circulating strains of the Herpes simplex virus, from clinical specimens and their sensitivity to commercially available antiherpesvirus drugs, acyclovir, phosphonophormic acid and trifluridine.

METHODS

Herpes simplex virus isolation, cytopathological features and antiviral sensitivity assays were performed in cell culture by tissue culture infectious dose or plaque forming unit assay.

RESULTS

From twenty-two clinical specimens, we isolated and adapted nine strains. Overall, the cytopathic effect was detected 24 h post-infection (p.i.) and the presence of syncytia was remarkable 48 h p.i., observed after cell staining. Out of eight isolates, four developed plaques of varying sizes. All the isolates were sensitive to acyclovir, phosphonophormic and trifluridine, with the percentage of virus inhibition (%VI) ranging from 49.7-100%.

CONCLUSIONS

The methodology for HSV isolation and characterization is a straightforward approach, but the drug sensitivity test, regarded as being of great practical importance, needs to be better understood.     

阿昔洛韦与万乃洛韦治疗生殖器疱疹的疗效比较

目的：观察阿昔洛韦与万乃洛韦治疗生殖器疱疹的临床疗效。方法：35例生殖器疱疹随意分为2组。A组用阿昔洛韦，B组用万乃洛韦治疗。分别观察其起效时间，皮损清除时间等临床指标。结果：在各项临床指标的改善程度方面，万乃洛韦明显优于阿昔洛韦。结论：与阿昔洛韦相比，万乃洛韦在治疗生殖器疱疹时显示出更好的临床疗效。     

八角茴香挥发油抗念珠菌活性的体外研究

目的 探讨八角茴香挥发油体外抗念珠菌活性及与氟康唑在联合抑菌实验中的相互作用。方法 参照NCCLSM27-A方案中的微量液基稀释法检测八角茴香挥发油对130株临床分离念珠菌的最小抑菌浓度(MIC)与最小杀菌浓度(MFC),并以氟康唑作为质控药物;同时采用棋盘微量稀释法对18株念珠菌进行了八角茴香挥发油与氟康唑的体外联合抑菌实验。结果 八角茴香挥发油对临床分离念珠菌的MIC及MFC分别为白念珠菌1517.16μg/mL与2248.55μg/mL、光滑念珠菌1169.24μg/mL与2338.49μg/mL、近平滑念珠菌1320.03μg/mL与1741.79μg/mL、热带念珠菌1203.50μg/mL与2407.01μg/mL、克柔念珠菌1516.32μg/mL与2144.40μg/mL及季也蒙念珠菌1072.64μg/mL与2144.40μg/mL。八角茴香挥发油与氟康唑联用对氟康唑敏感株及耐药株均表现出较好的协同相加作用,而且未发现有拮抗作用,两组间分数抑菌浓度指数(FICI)差异无显著性(P=0.67)。结论 八角茴香挥发油对临床常见致病性念珠菌有程度相似的抗菌作用;八角茴香挥发油与氟康唑联用对念珠菌主要表现为协同相加作用。     

阿昔洛韦与万乃洛韦治疗带状疱疹的疗效比较

目的:观察阿昔洛韦与万乃洛韦治疗带状疱疹的临床疗效。方法:30例带状疱疹随机分为2组。A组用阿昔洛韦,B组用万乃洛韦治疗。分别观察其起效时间,皮损清除时间,带状疱疹相关性疼痛(ZAP)缓解率及带状疱疹后遗神经痛(PHN)发生率等临床指标;结果:在两组中万乃洛韦显示出比阿昔洛韦更好的临床疗效。在各项临床指标的改善程度方面,万乃洛韦明显优于阿昔洛韦;结论:与阿昔洛韦相比,万乃洛韦在带状疱疹方面显示出更好的临床疗效。使用万乃洛韦治疗带状疱疹在改善带状疱疹的相关性痛及后遗神经疼痛方面显著优于阿昔洛韦,尤其是对老年带状疱疹患者。     

Quantitation of herpes simplex DNA in blood during aciclovir therapy with competitive PCR ELISA

BACKGROUND: Monitoring viral load in blood has already been introduced into clinical routine for human immunodeficiency virus and hepatitis C virus. OBJECTIVE: This study was conducted to monitor the decline of herpes simplex (HSV) viral load in the blood of a patient with gingivostomatitis herpetica prior and during acyclovir therapy. Methods: Analysis was done by quantitative PCR ELISA using an internal quantitation standard. RESULTS: Copy numbers were 66/microl blood prior to therapy, 60 during oral medication with valaciclovir, 97 and 72 copies/microl blood during the first 2 days of intravenous acyclovir therapy, followed by a sharp decline to 8 and 9 copies on days 3 and 4. During the following days, HSV was no longer detectable. Conclusion: As this quantitative approach can be easily adjusted to any other PCR, it provides a reliable, easy-to-apply method for monitoring therapy, also during new antiviral clinical trials.     

Disseminated primary HSV-2 infection of the face

We report the case of a 44-year-old, heterosexual, man, who presented for lesions of the face that appeared 3 days earlier; the eruption was associated with a burning sensation. He had sexual intercourse 12 days prior to presentation with a new partner. On clinical examination, there were confluent vesicules and a few pustules localized on the cheeks, forehead, nose, mouth, and ears. A swab for immunofluorescence (IF) came back as positive for HSV-2. The patient was treated with oral acyclovir. The lesions were healed when he was seen for follow-up 1 week later. The virus responsible for herpes is a double-stranded DNA virus named Herpes simplex virus (HSV). The virus generally enters damaged epithelium or mucosal surfaces, secondary to abrasions or trauma. Most primary orolabial infections occur during childhood as herpetic gingivostomatitis. However, there are forms that could be more atypical. The spread of the virus was probably promoted by shaving the beard. In immunocompromised patients or those with skin barrier disorders, HSV infection tends to disseminate and is accompanied by visceral involvement. Hence, the need to detect a state of immunodepression (including AIDS) in any patient with diffuse herpes infection. Three oral antiviral agents are commonly used: acyclovir, famciclovir, and valaciclovir.     

雷公藤内酯醇对HaCaT细胞表皮生长因子受体磷酸化及其下游信号激酶MEK的影响

目的 探讨雷公藤内酯醇对表皮生长因子(EGF)信号刺激HaCaT细胞后EGF受体磷酸化以及下游MEK途径的影响.方法 在HaCaT细胞培养体系中,用外源性重组人EGF为刺激信号,用免疫印迹法检测总EGF受体及其磷酸化受体,以及总MEK及其磷酸化激酶的表达.结果 雷公藤内酯醇对rhEGF引起的细胞总EGF受体表达无明显影响,但抑制磷酸化EGF受体表达,抑制作用呈剂量依赖性,IC₅₀值为2.38×10^-10mol/L.对细胞总MEK1/2表达也不影响,但明显下调磷酸化MEK,抑制作用的IC₅₀值约为6.03×10^-11mol/L.结论 雷公藤内酯醇对EGF信号引起的EGF受体磷酸化及下游MEK激酶磷酸化均有抑制作用.