厄贝沙坦氢氯噻嗪治疗轻中度原发性高血压疗效观察

目的:观察厄贝沙坦氢氯噻嗪(厄贝沙坦150 mg/氢氯噻嗪12.5 mg复方制剂)治疗单用厄贝沙坦150 mg控制不良的轻中度高血压患者的疗效和安全性.方法:经厄贝沙坦150 mg 1次/日治疗4周,血压仍未正常(收缩压≥145 mmhg,舒张压≥95mmhg)的99例高血压患者随机分为两组,治疗组给于厄贝沙坦氢氯噻嗪1片,1次/日,对照组继续服用厄贝沙坦150 mg,1次/日,疗程8周.在治疗4周和结束时评估药物的安全性和有效性.结果:在轻中度高血压患者中厄贝沙坦氢氯噻嗪1片,天比单用厄贝沙坦150 mg/天血压下降达标率高.治疗结束时平均坐位收缩压降低4 mmHg,平均坐位舒张压下降2.5mmhg,血压控制<140/90mmHg的患者在厄贝沙坦氢氯噻嗪1片/天组和单用厄贝沙坦150 mg/天组分别为53.9%和40.9%.结论:轻中度原发性高血压患者采用厄贝沙坦氢氯噻嗪1片/天降压有效率及达标率优于厄贝沙坦150 mg/天组.厄贝沙坦氢氯噻嗪适用于厄贝沙坦单药控制不良的轻中度原发性高血压患者.     

厄贝沙坦氢氯噻嗪胶囊在健康人体的生物等效性

目的研究厄贝沙坦氢氯噻嗪胶囊(抗高血压药)在健康人体的生物等效性。方法 22名健康志愿者,随机双交叉单剂量口服厄贝沙坦氢氯噻嗪胶囊(试验制剂)和厄贝沙坦氢氯噻嗪片(参比制剂),剂量为厄贝沙坦300 mg、氢氯噻嗪25 mg。分别于服药后36 h内,多点抽取静脉血,用高效液相色谱法分别测定血浆中厄贝沙坦和氢氯噻嗪的浓度。用DAS程序计算相对生物利用度,并评价2种制剂生物等效性。结果单剂量口服厄贝沙坦氢氯噻嗪胶囊和片剂后的药代动力学参数,厄贝沙坦:Cmax分别为(2.61±0.62)和(2.57±0.46)mg·L-1;AUC0-36分别为(15.14±3.43)和(15.39±3.91)mg·h·L-1;AUC0-∞分别为(16.37±3.42)和(16.80±4.28)mg·h·L-1;相对生物利用度为(100.75±19.42)%。氢氯噻嗪:Cmax分别为(162.51±27.55)和(168.18±25.71)μg·L-1;AUC0-36分别为(1115.41±147.34)和(1144.15±171.62)μg·h·L-1;AUC0-∞分别为(1212.68±160.77)和(1252.75±211.2...     

液相色谱-串联质谱法同时测定人血浆中厄贝沙坦和氢氯噻嗪的浓度及药动学

目的建立液相色谱-串联质谱法同时测定血浆中厄贝沙坦和氢氯噻嗪的浓度,并用于人体药动学研究。方法 20名健康受试者单剂量口服试验制剂1片(厄贝沙坦150 mg,氢氯噻嗪12.5 mg)后,在0～36 h内不同时间点分别采集血样,分取血浆,以氯沙坦为内标,经甲醇沉淀蛋白浓缩后流动相溶解,采用CuroSil-PFP色谱柱(Phenomenex 250 mm×4.6 mm,5μm),用含4%冰醋酸的水和含4%冰醋酸的甲醇-乙腈(1∶1,V/V)的流动相梯度洗脱分离,电喷雾离子化串联质谱选择性反应监测(SRM),分别采用正和负离子切换测定厄贝沙坦和氢氯噻嗪在血浆中的浓度。结果厄贝沙坦和氢氯噻嗪血浆样品分别在10～4 000μg.L-1和1～400μg.L-1的浓度范围内质谱响应线性良好。定量下限(LLOQ)分别为10.0μg.L-1和1.0μg.L-1,准确度和精密度良好。受试者单剂量口服厄贝沙坦氢氯噻嗪片1片后,测得氢氯噻嗪的ρmax、tmax、AUC0-36和t1/2分别为(86.96±34.99)μg.L-1、(1.75±0.69)h、(434±143)μg.h.L-1和(7.91±1.31)h;厄贝沙坦的相应参数分别为(1 670±409)μg.L-1、(1.55±0.70)h、(7 396±274)μg.h.L-1和(9.45±5.20)h。结论本方法专属性强、灵敏度高、准确性高,满足厄贝沙坦和氢氯噻嗪药动学研究的要求。     

厄贝沙坦-氢氯噻嗪片对原发性高血压患者血尿酸的影响

目的观察厄贝沙坦-氢氯噻嗪片对原发性高血压患者血尿酸的影响。方法原发性高血压患者29例服用厄贝沙坦-氢氯噻嗪片1片,qd,共8 wk。观察治疗前后血压及血尿酸的变化,并与15例服用氯沙坦50mg.d-1、15例服用厄贝沙坦50mg+氢氯噻嗪≥12.5 mg.d-1超过8 wk的同期住院的原发性高血患者的血压、血尿酸进行比较。结果①厄贝沙坦-氢氯噻嗪片治疗后血压降低明显,与治疗前比P<0.01,与氯沙坦组及氯沙坦加氢氯噻嗪组降压效果相当;②厄贝沙坦-氢氯噻嗪片治疗后尿酸降低,但与治疗前比较无差异(P>0.05);而与单用氯沙坦及氯沙坦加氢氯噻嗪组比较尿酸降低有显著差异(P<0.01)。氯沙坦组与氯沙坦加氢氯噻嗪组比较,尿酸有降低趋势但无统计学意义。结论厄贝沙坦-氢氯噻嗪片降低原发性高血压患者血尿酸浓度比氯沙坦加氢氯噻嗪效果明显。     

LC-MS/MS测定人血浆中厄贝沙坦和氢氯噻嗪的含量及其应用

目的 建立可同时测定人血浆中厄贝沙坦(irbesartan,IBST)和氢氯噻嗪(hydrochlorothiazide,HCZ)浓度的LC-MS/MS测定方法,并用于厄贝沙坦氢氯噻嗪(IBST/HCZ)片人体生物等效性研究.方法 血浆样品经过蛋白沉淀法处理后上样,采用IBST-d4和甲氯噻嗪(chlorothiazi...     

厄贝沙坦-氢氯噻嗪治疗原发性高血压合并高尿酸血症的疗效观察

目的 观察厄贝沙坦-氢氯噻嗪治疗原发性高血压合并高尿酸血症的临床疗效.方法 选择120例原发性高血压1～2级患者,血尿酸440～530μmol/L,随机分成两组:厄贝沙坦氢氯噻嗪组(厄贝沙坦150mg/d,氢氯噻嗪12.5mg/d)62例,氯沙坦组(50mg/d)58例,平均8周,进行治疗前后血压、血尿酸的对比研究.结果 厄贝沙坦-氢氯噻嗪治疗原发性高血压的临床效果同氯沙坦一样有效,两组总有效率分别为95.2%和93.1%(P>0.05);治疗后两组高尿酸水平有明显的下降(P<0.05).结论 厄贝沙坦-氢氯噻嗪除有良好的降压作用外,尚能安全有效地降低原发性高血压患者合并的高尿酸血症.     

厄贝沙坦-氢氯噻嗪治疗原发性高血压合并高尿酸血症的疗效观察

目的 观察厄贝沙坦-氢氯噻嗪治疗原发性高血压合并高尿酸血症的临床疗效.方法 选择120例原发性高血压1～2级患者,血尿酸440～530μmol/L,随机分成两组:厄贝沙坦氢氯噻嗪组(厄贝沙坦150mg/d,氢氯噻嗪12.5mg/d)62例,氯沙坦组(50mg/d)58例,平均8周,进行治疗前后血压、血尿酸的对比研究.结果 厄贝沙坦-氢氯噻嗪治疗原发性高血压的临床效果同氯沙坦一样有效,两组总有效率分别为95.2%和93.1%(P>0.05);治疗后两组高尿酸水平有明显的下降(P<0.05).结论 厄贝沙坦-氢氯噻嗪除有良好的降压作用外,尚能安全有效地降低原发性高血压患者合并的高尿酸血症.     

厄贝沙坦-氢氯噻嗪治疗原发性高血压合并高尿酸血症的疗效观察

目的 观察厄贝沙坦-氢氯噻嗪治疗原发性高血压合并高尿酸血症的临床疗效.方法 选择120例原发性高血压1～2级患者,血尿酸440～530μmol/L,随机分成两组:厄贝沙坦氢氯噻嗪组(厄贝沙坦150mg/d,氢氯噻嗪12.5mg/d)62例,氯沙坦组(50mg/d)58例,平均8周,进行治疗前后血压、血尿酸的对比研究.结果 厄贝沙坦-氢氯噻嗪治疗原发性高血压的临床效果同氯沙坦一样有效,两组总有效率分别为95.2%和93.1%(P>0.05);治疗后两组高尿酸水平有明显的下降(P<0.05).结论 厄贝沙坦-氢氯噻嗪除有良好的降压作用外,尚能安全有效地降低原发性高血压患者合并的高尿酸血症.     

厄贝沙坦-氢氯噻嗪治疗原发性高血压合并高尿酸血症的疗效观察

目的 观察厄贝沙坦-氢氯噻嗪治疗原发性高血压合并高尿酸血症的临床疗效.方法 选择120例原发性高血压1～2级患者,血尿酸440～530μmol/L,随机分成两组:厄贝沙坦氢氯噻嗪组(厄贝沙坦150mg/d,氢氯噻嗪12.5mg/d)62例,氯沙坦组(50mg/d)58例,平均8周,进行治疗前后血压、血尿酸的对比研究.结果 厄贝沙坦-氢氯噻嗪治疗原发性高血压的临床效果同氯沙坦一样有效,两组总有效率分别为95.2%和93.1%(P>0.05);治疗后两组高尿酸水平有明显的下降(P<0.05).结论 厄贝沙坦-氢氯噻嗪除有良好的降压作用外,尚能安全有效地降低原发性高血压患者合并的高尿酸血症.     

厄贝沙坦氢氯噻嗪片治疗原发性高血压的疗效观察

目的比较厄贝沙坦氢氯噻嗪片与厄贝沙坦治疗轻、中度原发性高血压的临床疗效。方法将lOO傩者随机分为2组：观察组50例,厄贝沙坦氢氯噻嗪片（含厄贝沙坦150mg,氢氯噻嗪12．5mg）,1片／d;对照组50例,厄贝沙坦150mg／d。用药4周后进行疗效分析。结果观察组总有效率为98％,对照组总有效率为80％,2组比较差异有统计学意义（P〈0．05）。结论厄贝沙坦氢氯噻嗪片治疗轻、中度原发性高血压疗效优于单独使用厄贝沙坦。     

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.