不同剂量辛伐他汀治疗老年冠心病78例观察

目的观察不同剂量辛伐他汀治疗老年冠心病的效果。方法将78例老年冠心病患者随机分为观察组和对照组,治疗组39例患者每晚服用40mg辛伐他汀,对照组39例患者每晚服用20mg辛伐他汀,观察两组治疗前后血脂、肝功能、肾功能等指标变化情况。结果每天服用40mg辛伐他汀可以显著降低总胆固醇（TC）、三酰甘油（TG）和低密度脂蛋白（LDL）水平,升高高密度脂蛋白（HDL）水平。结论对于老年冠心病患者,每天服用辛伐他汀40mg是较安全的调脂剂量,可达到理想调脂水平。     

辛伐他汀治疗冠心病合并混合性血脂紊乱的疗效及不良反应观察

目的：观察不同剂量辛伐他汀治疗冠心病合并混合性血脂紊乱的疗效及不良反应。方法：选取我院2011年5月～2012年5月96例冠心病合并混合性血脂紊乱患者为研究对象,按照不同剂量辛伐他汀将患者抽签随机分为A组（10mg）、B组（20mg）、C组（40mg）,每组32例,观察三组治疗前后总胆固醇（TC）、甘油三酯（TG）、高密度脂蛋白胆固醇（HDL-C）、低密度脂蛋白胆固醇（LDL-C）水平等血脂水平及不良反应。结果：治疗后A组TC（5.66±0.63）mmol/L、LDL-C（3.56±0.36）mmol/L水平与B组（4.52±0.58） mmol/L、（2.79±0.37）mmol/L,C组（4.05±0.65）mmol/L、（1.91±0.33）mmol/L比较呈递减趋势,三组两两比较差异有统计学意义（P＜0.05）;B组总不良反应发生率低于C组,差异明显（P＜0.05）。结论：临床首选20mg辛伐他汀治疗冠心病合并混合性血脂紊乱,效果较好,调脂作用明显且不良反应发生率较低,若疗效不佳可调整剂量至40mg以有效控制病情。     

不同剂量辛伐他汀的降血脂作用

目的：比较不同剂量辛伐他汀降血脂效果。方法：43例病人随机分为A、B两组，A组辛伐他汀开始剂量为5mg/d，治疗12周效果不好者剂量增加到10mg/d;B组开始剂量为10mg/d,效果不好，剂量增加20mg/d。疗程均为12周。结果：与治疗前比，A组5mg/d使TC、LDL分别下降10．4％和15．4％；只有27．3％的病人TC降低到正常值，无1例降到理想水平；9．1％的病人LDL降低到正常，4．5％病人降到理想值。剂量增加到10mg/d,TC、LDL分别下降24．6％和26．3％；50％病人TC降到正常，36．4％和22．7％病人TC和LDL降低到理想水平。B组20mg/d,可使80．9％和66．7％的病人TC及LDL降到正常，76．2％和80．9％的病人TC，LDL降到理想水平。结论：辛伐他汀5mg/d不能很好降低血脂，10mg/d可以使30％－50％病人血脂降到正常，只有20mg/d才能使大多数病人血脂降低到理想水平。     

辛伐他汀对急性冠脉综合征患者降脂分析

目的：探讨中国人群不同剂量的辛伐他汀(舒降之)治疗急性冠脉综合征(ACS)患者血脂异常24周的疗效及安全性。方法：回顾性分析697例ACS病人资料，共分为3组，A组182例未服用辛伐他汀，B组247例口服辛伐他汀10mg，每晚1次，C组268例口服辛伐他汀20mg，每晚1次。均没有服用其它降脂药物，随访24周，观察血脂(TC、LDL—C、HDL—C、TG)的变化及不良反应。结果：降脂作用方面与A组比较B、C两组有显著性差异(P＜0．01)，C组优于B组(P＜0．01)。不良反应3组间元差异(P＞0．05)。结论：辛伐他汀明显降低ACS患者中TC、LDL—C，并能明显升高HDL—C，且有剂量依赖性，不良反应少，安全性高。     

不同剂量辛伐他汀治疗冠心病合并高脂血症的效果及安全性对比

目的观察和分析不同剂量辛伐他汀治疗冠心病合并高脂血症患者的临床效果和安全性。方法选取2012年6月~2013年6月本院收治的冠心病合并高脂血症患者120例,随机分为A组64例,B组56例。在常规治疗基础上,A组给予辛伐他汀40 mg/d,B组给予辛伐他汀20 mg/d,疗程为12周。比较两组治疗前和治疗后8、12周的血脂水平、血脂达标率及不良反应发生率。结果两组治疗后8周TC比较差异有统计学意义（P〈0.05）。两组治疗后12周TC、TG、LDL-C和HDL-C比较差异有统计学意义（P〈0.05）。A组TC达标率为75.00%,明显高于B组的50.00%,差异有统计学意义（P〈0.05）。A组LDL-C达标率为76.56%,明显高于B组的64.28%,差异有统计学意义（P〈0.05）。A组不良反应发生率为10.94%,B组不良反应发生率为8.93%,两组比较差异无统计学意义（P〉0.05）。结论在常规药物治疗基础上,采用辛伐他汀40 mg/d治疗冠心病合并高脂血症患者的效果优于20 mg/d,且安全性较高,值得临床推广应用。     

辛伐他汀治疗老年高脂血症合并高血压的最佳剂量研究

目的 探讨不同剂量辛伐他汀治疗老年高脂血症合并高血压的临床疗效及安全性.方法 将96例老年高脂血症合并高血压患者采用信封法随机分为2组,每组48例,观察组采用40 mg/d辛伐他汀每晚顿服,对照组采用20 mg/d辛伐他汀每晚顿服,两组在治疗期间均给予健康指导,并行低脂饮食,且不再使用其他降血脂或调血脂药物.观察两组治疗前后血压及血脂情况及有无心脏事件及其他不良反应发生.结果 两组患者治疗前血脂水平比较差异无统计学意义,治疗后观察组TC、TG、LDL-C水平均明显低于对照组,HDL-C明显高于对照组,两组比较差异有统计学意义（P〈0.05）.观察组降血脂疗效总有效率为95.83%,对照组为83.33%,观察组优于对照组,两组比较差异有统计学意义（P〈0.05）;观察组降血压疗效总有效率为93.75%,对照组为89.58%,两组比较差异无统计学意义（P〉0.05）.两组治疗期间均无心脏事件发生,也无血尿常规及肝肾功能异常,观察组6例（12.50%）发生不良反应,对照组4例（8.33%）发生不良反应,两组不良反应发生率比较差异无统计学意义（P〉0.05）.结论 大剂量（40 mg/d）辛伐他汀治疗老年高脂血症合并高血压与小剂量（20 mg/d）相比,调脂疗效更佳,不增加不良反应的发生率,安全可靠.     

泰脂安与半量辛伐他汀联用对糖尿病高脂血症的疗效观察

目的评价泰脂安与半量辛伐他汀联合应用治疗糖尿病并发高血脂患者的疗效和安全性.方法120例2型糖尿病并高血脂患者随机分为3组泰脂安加辛伐他汀10 mg组(A组)40例,口服泰脂安胶囊0.9 g,tid,同时睡前服用辛伐他汀10mg;辛伐他汀20 mg组(B组)40例,睡前服用辛伐他汀20 mg;泰脂安加辛伐他汀20 mg组(C组)40例,口服泰脂安胶囊0.9g,tid,同时睡前服用辛伐他汀20 mg.3组均治疗12周,观察治疗前后血脂的变化和不良反应.结果A组TC、TG、LDL-C依次下降28.8%,18.2%,26.3%,B组依次下降29.4%,19.4%,24.6%,C组依次下降31.8%,20.6%,28.2%,3组HDL-C升高分别为23.5%,29.4%,29.8%,治疗前后差异均有显著性(均P＜0.05),但组间差异无显著性(均P＞0.05),糖化血红蛋白治疗前后无明显变化.A组未见明显不良反应,而B组和C组分别有7.5%和5%的患者出现转氨酶升高.结论对糖尿病并发高血脂患者的血脂异常,泰脂安与辛伐他汀10 mg·d-1联用同辛伐他汀20 mg·d.单用或与泰脂安联用具有相似的调脂作用,但前者可减轻辛伐他汀20 mg·d-1所引起的不良反应,安全性好.     

辛伐他汀治疗合并高血压血脂异常的2型糖尿病患者的疗效观察

目的观察有无合并高血压的血脂异常的2型糖尿病患者服用辛伐他汀的降脂疗效,以期指导辛伐他汀的个体化用药。方法伴血脂异常的2型糖尿病患者80例使用辛伐他汀进行降脂治疗,分为A、B组各40例。分别对患者服药后4周、8周、36周的胆固醇（TC）、三酰甘油（TG）、高密度脂蛋白胆固醇（HDL-C）、低密度脂蛋白胆固醇（LDL-C）进行测定。结果服用辛伐他汀4周后A组的TG、LDL值水平较B组组更低,8周后A组TC、TG、LDL值较B组更低,而36周后A组TC、LDL值较B组更低,差异有统计学意义。2组HDL水平差异无统计学意义（P〉0.05）。结论高血压伴血脂异常的2型糖尿病患者服用辛伐他汀的降脂疗效显著。     

辛伐他汀联合非诺贝特治疗高脂血症50例疗效评价

目的 探讨辛伐他汀联合非诺贝特治疗高脂血症的疗效及安全性,为临床高脂血症的治疗提供用药参考。方法 选取2011年1月至2014年1月收治的100例高脂血症患者,随机分为两组。A组(50例)睡前服用辛伐他汀10 mg,B组(50例)在此基础上于早、午各口服非诺贝特100 mg。连续治疗8周后比较两组患者调脂效果和不良反应。结果 两组患者治疗8周后,血脂水平均有改善,但B组的总胆固醇(TC)、三酰甘油(TG)水平均明显低于A组,血清高密度脂蛋白胆固醇(HDL-C)水平均明显高于A组(P<0.05);B组的降TC有效率及升HDL-C有效率均高于A组,但不良反应发生率与A组比较,差异无统计学意义(P>0.05)。结论 辛伐他汀联合非诺贝特治疗高脂血症疗效可靠,安全性良好。     

辛伐他汀调脂剂量及安全性探讨

目的　观察辛伐他汀调脂合适剂量及其安全性。方法　168例高脂血症病人分为A、B、C、D四组。A组(无冠心病或糖尿病，口服5—10mg／d)54例；B组(冠心病或糖尿病，口服5—10mg／d)30例；C组(无冠心病或糖尿病，口服20mg／d)54例；D组(冠心病或糖尿病，口服20mg／d)30例，比较服药前、服药后4周、12周血脂等变化。结果A、B、C、D组降胆固醇均有显效，C、D组降甘油三脂亦有显效，辛伐他汀对合并或不合并冠心病或糖尿病的病人同样有效。四组的血糖、尿素氖、肌酐、ALT、AST、CK变化差异元显著意义。结论　辛伐他汀调脂疗效肯定，小剂量(5—10mg／d)降胆固醉，较大剂量(20mg／d)同时降甘油三脂，且安全可靠。     

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.     

Deoxynivalenol in cereals in Russia

A survey of the occurrence of deoxynivalenol (DON) and zearalenone (ZEN) in wheat, rye, barley and maize harvested in 1989-2001 in several regions of Russia has been conducted. A total of 5652 samples of cereals were analysed for DON and ZEN by using TLC and normal-phase HPLC with UV-detector. DON was detected in 69% of 2166 samples from Krasnodar region which is considered to be the major Fusarium endemic region of Russia. The contamination levels ranged from 0.1 till 8.6 ppm, MTEL was exceeded in 37% of these samples. The positive correlation between DON concentration and a percentage of Fusaria-damaged wheat kernels has been shown. DON occurrence and contamination levels were much lower that for wheat. Based on the results of monitoring and the data of average actual consumption of wheat products in Russia, the estimated daily intake of DON per 1 kg of body weight (EDI)was calculated. EDI varied from 0.07 ug in 1990-1991 till 1.40 ug in 1992. Although average EDI were lower than adopted tolerable daily intake (TDI, 3 ug/kg body weight) EDIs for the North-Caucasian region in some cases exceeded TDI.