HBsAg多肽刺激树突状细胞联合大黄蛰虫丸治疗肝纤维化的疗效

目的 探讨HBsAg多肽刺激树突状细胞(DCs)联合大黄蛰虫丸治疗肝纤维化的临床疗效.方法 慢性乙型肝炎(CHB)或肝炎代偿期肝硬化患者45例,随机分为两组:治疗组25例,用DCs细胞联合大黄蛰虫丸治疗;对照组20例,仅用大黄蛰虫丸治疗.疗程均为3个月.检测并比较治疗前、治疗3个月和两组患者的肝功能(AST、ALT和谷氨酰转肽酶、肝纤维化指标(透明质酸和Ⅳ型胶原)及治疗有效率的B超评估.结果 治疗组的中医症状、证候和肝功能、肝纤维化指标的改善均明显优于对照组(P＜0.05或P＜0.01);治疗组B超诊断的有效率也明显优于对照组(P＜0.05).结论 HBsAg多肽刺激的DCs联合大黄蛰虫丸治疗肝纤维化具有一定疗效.     

拉米夫定联合前列地尔对慢性肝炎患者CD3~+ CD25~+ Foxp3~+调节T细胞水平的影响

目的观察拉米夫定联合前列地尔治疗慢性乙型肝炎(CHB)的疗效及对CD3+ CD25+ Foxp3+调节T细胞水平的影响。方法 2010-2013年我院收治的148例慢性乙型肝炎患者随机分为实验组和对照组,每组74例,两组均接受综合保肝治疗和前列地尔注射,在此基础上实验组口服拉米夫定,对照组口服阿德福韦酯,观察两组患者HBV-DNA阴转率、ALT及CD3+ CD25+ Foxp3+调节T细胞水平变化。结果治疗后两组患者ALT水平均呈下降趋势,实验组在6、12、24、72周时显著低于对照组,差异有统计学意义(P<0.05)。治疗后两组患者HBV-DNA阴转率均逐渐升高,在24周后实验组显著高于对照组(P<0.05)。在中度、重度CHB治疗后,实验组Treg水平显著低于对照组(P<0.05)。结论拉米夫定联合前列地尔能有效抗病毒,保护肝细胞,对慢性乙型肝炎有较好的治疗效果,能显著降低CD3+ CD25+ Foxp3+调节T细胞水平。     

α干扰素对慢性乙型肝炎患者树突状细胞表型的影响

目的观察α干扰素治疗对慢性乙型肝炎患者树突状细胞(Dendriticcells,DCs)表型的影响,进一步探讨α干扰素治疗慢性乙型肝炎的具体机制。方法分离32例慢性乙型肝炎患者及10名健康人外周血中的单个核细胞(Peripheralbloodmononuclearcells,PBMCs)进行体外诱导培养,使之发育成DCs,流式细胞仪测定其表面共刺激分子的表达。对32例慢性乙型肝炎患者进行α干扰素治疗3个月后,再次检测DCs表面分子的表达水平,并将治疗前后的数据进行分析、比较。结果与正常对照组相比较,慢性乙型肝炎患者组PBMCs来源的DCs表面共刺激分子CD83、CD86的表达水平明显降低(P<0.05)。在α干扰素治疗3个月后,慢性乙肝患者组其DCs表面CD83、CD86的表达水平与治疗前相比均明显升高(P<0.05),与正常对照组相比无明显差异(P>0.05)。结论α干扰素可以上调DCs表面共刺激分子的表达水平,促进DCs的成熟,这可能是α干扰素治疗慢性乙肝的重要机制之一。     

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.     

自体LAK细胞回输治疗慢性乙型肝炎的研究

众所周知,我国是乙型肝炎发病率较高的国家之一,临床上对慢性乙型肝炎血清标志物HBsAg、HBeAg、抗—HBc阳性(大三阳)病例在治疗上一直深感棘手。我院自1992年7月引进自体LAK细胞回输技术治疗慢性乙型肝炎,对矫治HBeAg阴转效果显著,现将治疗结果报告如下。     

干扰素α-2b联合三氧治疗慢性乙型肝炎效果

目的探讨干扰素(Interferon,IFN)α-2b联合三氧治疗慢性乙型病毒性肝炎(ChronichepatitisB,CHB)患者的临床疗效。方法将60例慢性乙型肝炎患者随机分为两组:对照组30例,接受干扰素α-2b治疗,500万U,肌肉注射,3次/周;治疗组患者30例,在使用干扰素α-2b治疗的同时,加用三氧自体血回输疗法,前12周3次/周,后10周2次/周。两组患者干扰素使用疗程均为24周。分别在治疗开始前、治疗12、24周以及治疗停药后24周观察CHB患者血清谷丙转氨酶(ALT)、HBeAg定量以及HBV-DNA水平的变化。结果干扰素α-2b联合三氧治疗组血清HBeAg阴转率、HBVDNA阴转率、完全应答率明显高于干扰素α-2b治疗组(P<0.05),ALT复常率两组无明显差异(P>0.05)。结论干扰素α-2b联合三氧治疗慢性乙型肝炎的疗效优于单用干扰素α-2b。     

自体LAK细胞回输治疗慢性乙型肝炎30例远期疗效观察

我院自1992年采用自体LAK细胞回输技术治疗慢性乙型肝炎,对治疗HBeAg阴转获明显效果,近期疗效已做报道,兹将随访1年后的远期疗效报告如下。 临床资料 一、病例选择 将我院慢性乙型肝炎病例随机分为治疗组和观察组各30例,治疗组中慢性活动性乙     

逍遥丸辅助阿德福韦酯对慢性乙型肝炎患者的临床疗效评价

目的分析并评价逍遥丸辅助阿德福韦酯对慢性乙型肝炎患者的临床疗效。方法随机将108例慢性乙型肝炎患者分成观察组与对照组各54例,对照组口服阿德福韦酯,观察组口服阿德福韦酯并加服逍遥丸;两组患者均连续治疗12个月为一个疗程。结果两组在治疗第1、3、6个月后的ALT复常率、HBV-DNA阴转率、HBeAg阴转率、HBeAg血清转换率方面比较差异均无统计学意义(P>0.05)。在治疗第12个月后,观察组的HBV-DNA阴转率以及HBeAg阴转率方面显著高于对照组,差异有统计学意义(P<0.05)。观察组的ALT复常率与HBeAg血清转换率均高于对照组,但两组比较差异无统计学意义(P>0.05)。在治疗第3、6、12个月后,观察组在CD4+、CD8+、CD4+/CD8+方面与对照组相比,差异均有统计学意义(P<0.05)。结论逍遥丸辅助阿德福韦酯治疗慢性乙型肝炎可明显提高HBeAg及HBV-DNA的阴转率,临床疗效明显。     

恩替卡韦联合苦参素治疗HBeAg阳性慢性乙型肝炎的疗效观察

目的 观察恩替卡韦联合苦参素抗病毒治疗对HBeAg阳性慢性乙型肝炎患者病毒复制指标及T淋巴细胞亚群的影响.方法 将60例慢性乙型肝炎患者随机分为联合组和对照组.联合组30例,给予恩替卡韦联合苦参素治疗;对照组30例,单用恩替卡韦治疗.两组疗程均为48周.结果 疗程结束后,联合组HBVDNA、HBeAg阴转率以及HBeAg/抗HBe转换率显著高于对照组,差异有统计学意义(P均＜0.05);治疗组CD4+以及CD4+/CD8+也较对照组明显升高,差异有统计学意义(P均＜0.05).结论 恩替卡韦联合苦参素抗病毒治疗对HBeAg阳性慢性乙型肝炎患者有较好疗效.     

合并非酒精性脂肪性肝病慢性乙型肝炎患者抗病毒治疗的疗效分析

【搞要】目的探讨合并非酒精性脂肪性肝病的慢性乙型肝炎患者抗病毒的疗效分析。方法通过对30例合并非酒精性脂肪性肝病的慢性乙型肝炎患者抗病毒的疗效及30例单纯性慢性乙型肝炎患者抗病毒治疗的疗效分析。结果纯性CHB抗病毒治疗效果明显高于合并HAFLD的CHB患者,差异有统计学意义(P<0.05);治疗前后两组患者的ALT、AST、GGT均较治疗前明显改善,且与单纯性CHB患者的对照组相比,观察组的改善程度较为明显(P<0.05);经治疗8周、12周、24周时,两组患者的HBVDNA阴转率均不断升高,且在24周时,观察组患者的HBVDNA阴转率明显高于对照组(P<0.05);经治疗8周、12周、24周时,两组的HBVDNA较基线下降水平进行比较,差异有统计学意义(P<0.05)。结论合并NAFLD的CHB患者抗病毒治疗疗效明显低于单纯性CHB患者的抗病毒治疗疗效。     

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.