恩替卡韦治疗慢性乙型肝炎的疗效分析

目的探讨恩替卡韦治疗慢性乙型肝炎的临床效果和不良反应情况。方法慢性乙型肝炎初治患者50例予恩替卡韦口服,观察治疗第12周、24周、48周ALT复常率、HBV-DNA阴转率、HBe Ag阴转率等指标。结果 HBe Ag阳性患者ALT复常率在治疗第12周、24周、48周分别为50%、56.7%、96.7%;HBe Ag阴性患者ALT复常率在治疗第12周、24周、48周分别为35%、45%、90%,HBe Ag阳性和阴性患者之间比较差异无统计学意义(P>0.05)。HBe Ag阳性患者HBV-DNA阴转率在治疗第12周、24周、48周分别为70%、80%、96.7%;HBe Ag阴性患者HBV-DNA阴转率在治疗第12周、24周、48周分别为60%、70%、85%,HBe Ag阳性和阴性患者之间比较差异无统计学意义(P>0.05)。HBe Ag阳性患者HBe Ag阴转率在治疗第12周、24周、48周分别为26.6%、33.3%、53.3%,其中12周与48周比较有统计学意义(P<0.05)。患者在应用替卡韦治疗期间均无明显不良反应发生。结论恩替卡韦治疗慢性乙型肝炎疗效良好,安全性高。     

恩替卡韦与替比夫定治疗慢性乙型肝炎的临床效果对比分析

目的 对比恩替卡韦与替比夫定治疗慢性乙型肝炎(CHB)的临床效果.方法 选取2013年3月至2015年3月本院感染科收治的120例CHB患者,根据随机数字表法将患者随机分为恩替卡韦组(ETV组,60例)与替比夫定组(LDT组,60例).治疗周期为72周.比较两组丙氨酸转氨酶(GTP)转复率、HBeAg阴转率、HBV-DNA阴转率及HBeAg血清学转换率等应答情况,并分析治疗24周后患者HBV-DNA转阴情况对其治疗72周后疗效的影响.结果 治疗后12周、24周、48周、72周,两组GTP转复率、HBeAg阴转率、HBeAg血清学转换率比较,差异均无统计学意义(P＞0.05);治疗24周时,ETV组HBV-DNA水平明显低于LDT组(P＜0.05),但在治疗12周、48周、72周时两组HBV-DNA水平比较,差异均无统计学意义(P＞0.05).无论是ETV组还是LDT组,HBV-DNA＜31g拷贝/ml组在72周时的GTP转复率、HBeAg阴转率均明显高于HBV-DNA≥31 g拷贝/ml组.结论 CHB患者治疗24周后HBV-DNA水平能有效预测患者的长期疗效,在治疗CHB方面,恩替卡韦与替比夫定的疗效、耐药率、不良反应等效果相当,但恩替卡韦的早期抗HBV-DNA效果明显优于替比夫定.     

恩替卡韦与阿德福韦酯对核苷初治HBeAg阳性慢性乙型肝炎48周疗效比较

目的比较恩替卡韦(ETV)与阿德福韦酯(ADV)对核苷初治HBeAg阳性慢性乙型肝炎(chronic hepatitis B,CHB)患者48周时的疗效。方法 117例CHB患者随机分为ETV组和ADV组,分别给予0.5 mg/d ETV和10 mg/d ADV治疗,疗效的主要观测指标有:血清HBV-DNA、HbeAg转阴及ALT复常。结果 48周时,ETV与ADV组血清HBV-DNA转阴率分别为66.1%和18.2%,差异有统计学意义(P<0.05);两组ALT复常率分别为82.3%和56.4%,差异也有统计学意义(P<0.05);两组HBeAg转阴率(24.2%和16.4%)、抗-HBe转换率(8.06%和5.45%)及不良反应发生率(3.23%和3.64%),差异无统计学意义(P>0.05)。结论 ETV在促使CHB患者HBV-DNA转阴及ALT恢复正常方面显著优于ADV,在血清HBeAg转阴率、抗-HBe转换率及不良反应发生率方面二者相近。     

聚乙二醇干扰素α-2a联合阿德福韦治疗HBeAg阳性慢性乙型肝炎的疗效观察

目的:观察聚乙二醇干扰素α-2a(Peg-INFα-2a)联合阿德福韦(ADV)治疗乙肝E抗原(HBe Ag)阳性慢性乙型肝炎(CHB)的临床疗效。方法:采用开放随机对照临床试验,将70例HBe Ag阳性CHB患者按随机数字表法分为观察组与对照组,各35例。观察组患者使用Peg-INFα-2a与ADV联合治疗,对照组患者单用Peg-INFα-2a治疗,分别在治疗24周和48周进行疗效评估与安全性评价。结果:治疗24周后,观察组与对照组患者的丙氨酸转氨酶(ALT)复常率分别为51.43%、25.71%,乙肝病毒基因(HBV-DNA)阴转率分别为68.57%、37.14%,组间比较差异均有统计学意义(P<0.05);乙肝表面抗原(HBs Ag)阴转率与HBe Ag血清转换率比较差异无统计学意义(P>0.05)。治疗48周后,观察组与对照组患者的ALT复常率分别为77.14%、54.29%,HBe Ag血清转换率分别为54.29%、31.43%,HBV-DNA阴转率分别为82.86%、42.86%,组间比较差异均有统计学意义(P<0.05);HBs Ag阴转率及不良反应发生情况比较差异无统计学意义(P>0.05)。结论:Peg-INFα-2a联合ADV治疗HBe Ag阳性CHB疗效较好,优于Peg-INFα-2a单药治疗,且不良反应较小。     

恩替卡韦联合胸腺肽α1治疗慢性乙型肝炎的疗效观察

目的 探索恩替卡韦联合胸腺肽α1治疗慢性乙型肝炎(CHB)的疗效.方法 将58例HBeAg阳性慢性乙型肝炎患者采用随机数字表法分为观察组29例和对照组29例.观察组采用恩替卡韦联合胸腺肽α1治疗,对照组采用恩替卡韦治疗,治疗48周进行疗效评价.比较两组患者ALT复常率、AST复常率、HBsAg阴转率、HBeAg阴转率、HBeAg/HBeAb血清学转换率、HBV DNA阴转率和不良反应的差异.结果 治疗48周末,观察组ALT复常率(93.10%)、AST复常率(96.55%)、HBsAg阴转率(10.34%)、HBeAg阴转率(51.72%)、HBeAg/HBeAb血清学转换率(31.03%)、HBV DNA阴转率(82.76%)均高于对照组,其中HBeAg阴转率、HBV DNA阴转率、ALT复常率、HBeAg/HBeAb血清学转换率差异有统计学意义(P<0.05);但是AST复常率、HBsAg阴转率差异无统计学意义(P>0.05).结论 恩替卡韦联合胸腺肽α1治疗慢性乙型肝炎较单用恩替卡韦有较显著疗效,并且能提高慢乙肝患者HBeAg、HBV DNA阴转率,且未增加不良反应,安全性较高.     

恩替卡韦和阿德福韦酯治疗HBeAg阳性慢性乙型肝炎疗效和安全性的Meta分析

目的评价恩替卡韦(ETV)和阿德福韦酯(ADV)对核苷初治的乙型肝炎e抗原(HBe Ag)阳性慢性乙型肝炎(CHB)患者的疗效和安全性。方法计算机检索Pub Med、Ovid(SP)、中国期刊全文数据库(CNKI)、中文科技期刊数据库(VIP)、中国生物医学文献数据库(CBM)(建库至2013年12月)公开发表的有关ETV和ADV对核苷初治的HBe Ag阳性CHB患者疗效的随机对照试验(RCTs),并追查已获文献的参考文献。由两名研究者独立筛选文献,提取数据,按照改良后的Jadad评分标准进行质量评价。采用Rev Man 5.2软件进行Meta分析。结果最终纳入12个RCTs,共922例患者。采用固定效应模型,Meta分析结果显示,治疗48周时,ETV组在血清乙型肝炎病毒(HBV)DNA转阴率(RR=1.62,95%CI 1.41~1.87,P<0.000 01),血清丙氨酸转氨酶(ALT)复常率(RR=1.14,95%CI 1.06~1.21,P=0.000 2),HBe Ag转阴率(RR=1.35,95%CI 1.08~1.69,P=0.01)和HBe Ag血清学转换率(RR=1.67,95%CI 1.02~2.76,P=0.04)方面均显著高于ADV组。ETV组和ADV组在不良反应发生率方面无显著差异(P>0.05)。结论核苷初治的HBe Ag阳性CHB患者治疗48周时,ETV在降低血清HBV DNA、促使ALT复常、清除HBe Ag和促进HBe Ag血清学转换方面的疗效均优于ADV。ETV和ADV在安全性方面相似。     

耐替比夫定慢性乙型肝炎患者的挽救性治疗

目的 探讨慢性乙型肝炎(CHB)患者运用替比夫定(LdT)初治失败耐药后的后续挽救治疗方案的临床疗效.方法 将LdT初治耐药的CHB患者64例随机分为A组22例,B组22例,C组20例,分别给予拉米夫定(LAM)联合阿德福韦酯(ADV)、LdT联合ADV、恩替卡韦(ETV)联合ADV,进行后续抗病毒治疗.观察3组患者慢性乙型肝炎病毒(HBV) -DNA变化、HBV转阴及血清丙氨酸氨基转移酶(ALT)复常情况.结果 A、B、C组治疗12,24,48周后HBV-DNA及ALT水平均较治疗前下降(P＜0.05),HBV-DNA转阴率及ALT复常率亦差异有统计学意义.治疗24周后C组的HBV-DNA水平较A、B两组下降更明显(P＜0.05).结论 对LdT初治耐药的CHB患者给予LAM＋ADV、LdT＋ADV、ETV＋ADV三种救援方案挽救治疗均可取得良好效果,而ETV＋ADV可使HBV-DNA和ALT下降更快,并可获得更佳的HBV-DNA转阴率和ALT复常率.     

替诺福韦酯与恩替卡韦治疗HBeAg阳性慢性乙型肝炎对比研究

目的探究替诺福韦酯与恩替卡韦治疗HBe Ag阳性慢性乙型肝炎(CHB)的效果。方法从本院2012年3月至2013年6月收治的HBe Ag阳性CHB患者80例,按照随机数表法随机抽取组成替诺福韦酯组和恩替卡韦组,每组40例。替诺福韦酯组给予300 mg·d-1替诺福韦酯治疗,恩替卡韦组采用0.5 mg·d-1恩替卡韦治疗。对2组患者治疗前的年龄、性别、HBV DNA定量和ALT水平进行检测比较;对2组患者治疗24周和48周后的ALT复转、HBe Ag阴转和HBV DNA阴转水平进行检测比较;对2组患者治疗48周后的HBV DNA高度应答率进行统计比较。结果治疗24周和48周后,替诺福韦酯组HBe Ag阴转水平均高于恩替卡韦组(P<0.05),HBV DNA阴转和ALT复常水平相似,差异无统计学意义(P>0.05);2组患者的HBV DNA高度应答率差异无统计学意义(P>0.05)。结论替诺福韦酯与恩替卡韦在治疗HBe Ag阳性CHB患者时,替诺福韦酯在患者HBe Ag阴转方面作用显著,安全性较高。     

替诺福韦酯治疗多重耐药慢性乙型肝炎的回顾性分析

目的:观察替诺福韦酯(TDF)治疗多重耐药慢性乙型肝炎(CHB)的短期疗效及不良反应。方法:回顾性分析32例多重耐药CHB患者病历资料,所有患者治疗前均进行乙型肝炎病毒(HBV)耐药基因检测,存在多位点耐药,并给予TDF口服治疗。观察TDF治疗前、后丙氨酸氨基转移酶(ALT)复常率、HBV-DNA阴转率、乳酸、肾功能等指标。结果:治疗第3个月时,ALT复常率达100%,治疗半年时HBV-DNA阴转率达96.88%,治疗中患者未出现乳酸水平升高及肾功能异常。结论:TDF治疗多重耐药CHB疗效迅速,未出现明显不良反应。     

联合阿德福韦酯或换用恩替卡韦治疗拉米夫定耐药慢性乙型肝炎患者的临床观察

目的观察拉米夫定(LAM)耐药的慢性乙型肝炎(CHB)患者,加用阿德福韦酯(ADV)联合治疗与换用恩替卡韦(ETV)挽救治疗的疗效。方法将拉米夫定治疗失败的CHB患者52例分为两组,31例接受ADV(10mg/d)联合LAM(100mg/d)治疗(ADV联合组),21例给予ETV(1mg/d)治疗(ETV组),治疗至72周,观察24、48、72周时丙氨酸转氨酶(ALT)复常率、HBV DNA载量、血清学标志及病毒学突破情况。结果①ADV联合组和ETV组治疗24周时的生化学应答率分别为61.3%和57.1%,治疗48周时分别为74.2%和66.7%,治疗72周时分别为80.6%和76.2%。两组患者的生化学应答率无统计学差异(P>0.05)。②治疗72周时两组HBV DNA阴转率分别是71.0%和42.9%,差异具有统计学意义(P<0.05).在治疗24周、48周时,ADV联合组和ETV组的血清HBV DNA较基线下降的平均水平相似(分别为-2.0、-2.1,-2.4、-2.3log10copies/mL),治疗72周时,ADV联合组的HBV DNA下降更加明显(-4.4、-2.4log10copies/mL,P<0.05)。治疗72周时两组分别有2例和3例患者发生病毒学突破。③治疗72周时两组有5例HBeAg阴转,其中2例HBeAg血清转换,3例HBeAb阴性。两组的血清学转换率均较低。结论在拉米夫定耐药CHB患者中,ADV联合组和ETV组治疗72周,两组生化学应答及24、48周的抗病毒效果相似,但随着治疗时间延长至72周,ADV联合组病毒学应答率显著高于ETV组,且ADV联合组治疗的患者病毒学突破发生率更低。     

Quantitative in vivo and in vitro sex differences in artemisinin metabolism in rat

1. The pharmacokinetics of the antimalarial compound artemisinin were compared in the male and female Sprague-Dawley rat after single dose i.v. (20 mg.kg) or i.p. (50 mg.kg) administration of an emulsion formulation. 2. Plasma clearance of artemisinin was 12.0 (95% confidence interval: 10.4, 13.0) l.h. kg in the male rat and 10.6 (95% CI: 7.5, 15.0) l.h. kg in the female rat suggesting high hepatic extraction in combination with erythrocyte uptake or clearance. Artemisinin half-life was 0.5 h after both routes of administration in both sexes. Values for plasma clearance and half-lives did not statistically differ between the sexes. 3. After i.p. administration artemisinin AUCs were 2-fold higher in the female compared with male rat (p 0.001). Artemisinin disappearance was 3.9-fold greater in microsomes from male compared with female livers and it was inhibited in male microsomes by goat or rabbit serum containing antibodies against CYP2C11 and CYP3A2 but not CYP2B1 or CYP2E1. 4. The unbound fraction of artemisinin in plasma was lower (p 0.001) in plasma obtained from the male (8.8 2.0%) compared with the female rat (11.7 2.2%). 5. The possibility of a marked sex difference, dependent on the route of administration, has to be taken into account in the design and interpretation of toxicological studies of artemisinin in this species.     

Quantitative in vivo and in vitro sex differences in artemisinin metabolism in rat

1. The pharmacokinetics of the antimalarial compound artemisinin were compared in the male and female Sprague-Dawley rat after single dose i.v. (20 mg x kg(-1)) or i.p. (50 mg x kg(-1)) administration of an emulsion formulation. 2. Plasma clearance of artemisinin was 12.0 (95% confidence interval: 10.4, 13.0) 1 x h(-1) x kg(-1) in the male rat and 10.6 (95% CI: 7.5, 15.0) 1 x h(-1) x kg(-1) in the female rat suggesting high hepatic extraction in combination with erythrocyte uptake or clearance. Artemisinin half-life was approximately 0.5 h after both routes of administration in both sexes. Values for plasma clearance and half-lives did not statistically differ between the sexes. 3. After i.p. administration artemisinin AUCs were 2-fold higher in the female compared with male rat (p < 0.001). Artemisinin disappearance was 3.9-fold greater in microsomes from male compared with female livers and it was inhibited in male microsomes by goat or rabbit serum containing antibodies against CYP2C11 and CYP3A2 but not CYP2B1 or CYP2E1. 4. The unbound fraction of artemisinin in plasma was lower (p < 0.001) in plasma obtained from the male (8.8 +/- 2.0%) compared with the female rat (11.7 +/- 2.2%). 5. The possibility of a marked sex difference, dependent on the route of administration, has to be taken into account in the design and interpretation of toxicological studies of artemisinin in this species.     

Interindividual variability in metabolic activation in humans in vivo

In assessing interindividual variability in metabolic activation, the toxic metabolite is often too unstable for conventional analysis. Possible alternatives include a stable product of the reactive metabolite e.g. cysteinyl derivatives of N-acetyl-4-benzoquinoneimine, the toxic metabolite of paracetamol, adducts with DNA or protein, and indirect measurement of the activity of the enzyme(s) producing the active metabolite. An example of the last approach is the use of furafylline, a highly specific inhibitor of human CYP1A2, to determine the extent of the metabolic activation of the cooked food mutagens PhIP and MeIQx. The extent of inhibition, determined from levels of unchanged amine in urine, is an indirect measure of the activity of the activation pathway. Further refinement of this approach, allied to improved measures of the biological process of interest should prove of value in evaluating interindividual variability and its role in the risk assessment process.     

Theophylline kinetics in peripheral tissues in vivo in humans

Several biochemical and cellular effects have been described for methylxanthines under in vitro conditions. However, it is unknown, whether threshold concentrations required to exert these effects are attained in target tissues in vivo. We therefore employed the microdialysis technique for measuring theophylline concentrations in peripheral tissues under in vivo conditions.Following in vitro and in vivo calibration, microdialysis probes were inserted into the medial vastus muscle and into the periumbilical subcutaneous adipose layer of healthy volunteers. Following single oral dose administration of 300 mg or i.v. infusion of 240 mg theophylline, in vivo time courses of theophylline concentrations were monitored in tissues and plasma. Major pharmacokinetic parameters (c_max, t_max, AUC) were calculated for plasma and tissue time courses. The mean AUC_tissue /AUC_plasma-ratio was 0.56 (p.o.) and 0.55 (i.v.) for muscle and 0.55 (p.o.) and 0.72 (i.v.) for subcutaneous adipose tissue.We conclude that microdialysis provides important information on the distribution and the tissue pharmacokinetics of theophylline.Abbreviations FPIA Fluorescence polarisation immuno assay - AUC Area under the curve - t_max Time to peak concentration - c_max Peak concentration     

休克时血中氧自由基的变化

本实验测定10名休克患者血浆和红细胞的丙二醛(MDA)、血浆总抗的氧化活性(AOA)的含量。结果表明:休克病人红细胞膜和血浆 MDA 含量(4.298±0.722;5.348±0.834)与对照组(3.235±0.682;4.356±1.081)比较明显增高(P<0.05);血浆 AOA(39.65±7.858)与对照组(48.21±10.81)比较明显降低(P<0.01)。提示:休克时,患者机体内自由基反应增强是引起组织细胞损伤的原因之一。     

Changes in angiopoietin expression in glomeruli involved in glomerulosclerosis in rats with daunorubicin-induced nephrosis

AIM: To study the potential pathological role of endogenous angiopoietins in daunorubicin-induced progressive glomerulosclerosis in rats. METHODS: Seventy male Wistar rats were allocated randomly into a daunorubicin group (DRB; n=40) or a control group (n=30). The rats in the DRB group were injected with DRB (15 mg/kg), in their tails. Subsequently, at intervals of 1, 2, 4, 6, 8, and 12 weeks, 5 male Wistar rats in each group were chosen randomly for 24 h urinary protein quantitative measurements (24 h UPQM), and determination of plasma tumor necrosis factor alpha (TNF-alpha), angiopoietin-1 (Ang1), and angiopoietin-2 (Ang2) levels. Kidney sections were examined by electron microscopy, Periodic Acid Schiff (PAS) staining, immunohistochemical staining and in situ hybridization histochemistry. RESULTS: As glomerulosclerosis progressed in the DRB group, expression of Ang1 mRNA and protein in glomeruli decreased and expression of TNF-alpha protein, Ang2 mRNA and protein in glomeruli increased. Expression of Ang1 mRNA and protein in glomeruli were negatively correlated with 24 h UPQM, Fn protein expression, and mean area of extracellular matrix (MAECM). In comparison, expression of Ang2 mRNA and protein in glomeruli were positively correlated with 24 h UPQM, Fn protein expression and MAECM; furthermore, there was a positive correlation between plasma Ang2 and 24 h UPQM. Plasma TNF-alpha and expression of TNF-alpha in glomeruli were positively correlated with expression of Ang2 mRNA and protein in glomeruli. There was a negative correlation between Ang1 protein expression and Ang2 protein expression in glomeruli. CONCLUSION: During DRB-induced glomerulosclerosis, podocyte injury led to a shift in the balance of Ang1 and Ang2 in glomeruli. Increased TNF-alpha in plasma and glomeruli may upregulate Ang2 expression in glomeruli. Elevated Ang2 in both plasma and glomeruli may mediate protein permeability through the glomerular filtration barrier. Moreover, local expression of Ang2 may facilitate the progress of glomerulosclerosis by upregulating a component expression of extracellular matrix.     

Trichinellosis in immigrants in Switzerland

We describe a case of trichinellosis diagnosed at the Division of Infectious Diseases, Hospital of Lugano, in January 2009. This case was associated with a cluster of cases and was traced to the consumption of contaminated meat after a wild boar hunt in Bosnia.