脑心通胶囊联合胞磷胆碱钠治疗急性脑梗死恢复期的临床研究

目的 探讨脑心通胶囊联合胞磷胆碱钠胶囊治疗急性脑梗死恢复期的临床疗效。方法 选取2019年4月—2020年4月在天津市第五中心医院治疗的脑梗死恢复期患者126例，随机分为对照组和治疗组，每组各63例。对照组患者口服胞磷胆碱钠胶囊，2粒/次，3次/d。治疗组在对照组的基础上口服脑心通胶囊治疗，3粒/次，3次/d。两组患者均治疗4周。观察两组患者临床疗效，同时比较治疗前后两组患者神经功能缺损评分和Barthel指数，全血高切黏度、全血低切黏度、血浆黏度和红细胞压积，及血小板蛋白激酶C（PKC）、五正聚蛋白3（PTX3）、血管紧张素Ⅱ（Ang ΙΙ）和α颗粒膜蛋白（GMP-140）水平。结果 治疗后，对照组和治疗组临床有效率分别为77.78%和92.06%，两组比较差异有统计学意义（P<0.05）。治疗后，两组Barthel指数、全血高切黏度、全血低切黏度、血浆黏度和红细胞压积均明显高于治疗前（P<0.05），且治疗组显著高于对照组（P<0.05）。治疗后，两组患者神经功能缺损评分、PKC、PTX3、Ang ΙΙ和GMP-140水平明显降低（P<0.05），且治疗组比对照组降低更为显著（P<0.05）。结论 脑心通胶囊联合胞磷胆碱钠胶囊可改善神经功能缺损和血液流变学指标，降低PKC、PTX3、Ang ΙΙ和GMP-140水平，提高患者的日常生活活动能力。     

扎冲十三味丸联合丁苯酞治疗急性脑梗死的临床研究

目的 探讨扎冲十三味丸联合丁苯酞治疗急性脑梗死的临床疗效。方法 选取2019年9月-2021年9月漯河市中医院治疗的80例急性脑梗死患者,按照随机数字法将所有患者分为对照组和治疗组,每组各40例。对照组患者口服丁苯酞软胶囊, 0.2 g/次, 3次/d。治疗组在对照组的基础上口服扎冲十三味丸, 5~9粒/次, 1次/d。两组患者用药14 d观察治疗效果。对比两组的疗效及症状好转时间;比较两组治疗前后全血高切黏度、血浆黏度、血小板黏附率、纤维蛋白原、神经功能缺损评分(NIHSS)、日常生活能力评分(Barthel)、白细胞介素6(IL-6)、同型半胱氨酸(Hcy)、白细胞介素8(IL-8)、C-反应蛋白(CRP)的变化情况。结果 治疗后,治疗组患者总有效率是97.50%,显著高于对照组的77.50%(P<0.05)。治疗组患者失语、肢体麻木、头晕、口角歪斜等症状好转时间均明显短于对照组(P<0.05)。治疗后,两组血浆黏度、血小板黏附率、纤维蛋白原、全血高切黏度均显著降低(P<0.05);治疗后,治疗组血液流变学指标改善优于对照组(P<0.05)。治疗后,两组NIHSS评分均显著降低, Barthel评分显著增高(P<0.05);治疗后,治疗组NIHSS评分和Barthel评分改善优于对照组(P<0.05)。治疗后,两组IL-6、IL-8、Hcy、CRP水平均较治疗前显著降低(P<0.05);治疗后,治疗组血清因子水平低于对照组(P<0.05)。结论 扎冲十三味丸联合丁苯酞治疗急性脑梗死具有较好的临床疗效,可显著改善急性脑梗死患者的症状和日常生活能力,并能有效改善机体血液流变学指标,降低机体炎症反应,值得临床借鉴。     

蛭龙血通胶囊联合长春西汀注射液治疗脑梗死恢复期的临床研究

目的 观察蛭龙血通胶囊联合长春西汀注射液治疗脑梗死恢复期的临床效果。方法 选取2018年7月—2021年4月石河子大学第一附属医院收治的121例脑梗死恢复期患者,随机数字表法将患者分为对照组（60例）和治疗组（61例）。对照组患者静脉滴注长春西汀注射液,溶于250 mL生理盐水中,初始剂量20 mg/次,视患者耐受情况逐渐加至30 mg/次,1次/d。治疗组在对照组治疗的基础上口服蛭龙血通胶囊,4粒/次,3次/d。两组均连续治疗2周。比较两组的临床疗效、量表评分、血清神经损伤指标。结果 治疗后,治疗组的总有效率高于对照组（P＜0.05）。治疗后,两组美国国立卫生研究院卒中量表（NIHSS）评分下降,日常生活能力量表（ADL）评分升高（P＜0.05）,且治疗组NIHSS评分显著低于对照组,ADL评分高于对照组（P＜0.05）。治疗后,两组血清S100β蛋白、神经元特异性烯醇化酶（NSE）、心型脂肪酸结合蛋白（H-FABP）水平均显著下降（P＜0.05）,且治疗组血清神经损伤指标水平均显著低于对照组（P＜0.05）。结论 蛭龙血通胶囊联合长春西汀注射液治疗脑梗死恢复期疗效较好,可促进患者日常生活能力恢复、减轻神经功能损伤。     

复方地龙胶囊联合胞二磷胆碱钠治疗急性脑梗死恢复期的临床研究

目的 探讨复方地龙胶囊联合胞二磷胆碱钠片治疗急性脑梗死恢复期的临床疗效。方法 选择2021年4月—2022年4月在天津市北辰医院诊治的82例急性脑梗死恢复期患者,根据用药的差别分为对照组（41例）和治疗组（41例）。对照组口服胞二磷胆碱钠片,0.2 g/次,3次/d;在此基础上,治疗组口服复方地龙胶囊,0.56 g/次,3次/d。两组患者均治疗4周。观察两组患者临床疗效,比较治疗前后两组患者NIHSS评分、FMMS评分、HPLPⅡ评分、AROM评分、SS-QOL评分和BBS评分,血清基质细胞衍生因子-1（SDF-1）、神经营养因子-3（NT-3）、同型半胱氨酸（Hcy）、氧化应激骨桥蛋白（OPN）和脑源性神经营养因子（BDNF）水平,脑血流灌注指标收缩期最大流速（PSV）、平均流速（TMV）和阻力指数（RI）,血清纤维蛋白原、D-二聚体和血浆比黏度水平。结果 治疗后,治疗组临床有效率为97.56%,显著高于对照组（80.49%,P＜0.05）。治疗后,两组NIHSS评分明显降低,而FMMS评分、HPLPⅡ评分、AROM评分、SS-QOL评分和BBS评分明显升高（P＜0.05）,且治疗组评分改善最为明显（P＜0.05）。治疗后,两组血清SDF-1、Hcy和OPN水平明显降低,而BDNF、NT-3水平明显升高（P＜0.05）,并以治疗组改善最为明显（P＜0.05）。治疗后,两组脑血流灌注指标PSV和TMV明显升高,而RI明显降低（P＜0.05）,并以治疗组改善最为明显（P＜0.05）。治疗后,两组血清纤维蛋白原、D-二聚体及血浆比黏度水平均明显降低（P＜0.05）,并以治疗组下降的最为明显（P＜0.05）。结论 复方地龙胶囊联合胞二磷胆碱钠片治疗急性脑梗死恢复期可有效促进神经功能恢复,提高患者运动、平衡功能及健康行为改善。     

高压氧疗联合注射用丹参多酚酸治疗脑梗死的疗效分析及对患者血液流变学的影响

目的 探讨高压氧疗联合注射用丹参多酚酸治疗脑梗死的疗效及对患者血液流变学的影响。方法 选取2016年1月-2018年2月周口市中心医院收治的脑梗死患者80例,随机分为两组,两组患者均给予降血脂、降血压、改善微循环、降低颅内压、抗凝、抗血小板聚集及脑神经保护药等常规治疗。对照组应用注射用丹参多酚酸,将100 mg注射用丹参多酚酸与250 mL 0.9%的NaCl注射液混合后为患者静脉滴注,1次/d;观察组应用高压氧疗（氧疗压力为0.25~0.30 MPa,时间为3min;氧浓度为80%~90%,温度为18~25℃）联合注射用丹参多酚酸;1个疗程为14 d,连续治疗4个疗程。比较两组患者血细胞比容、全血低切黏度、全血高切黏度、血浆黏度、治疗疗效、巴塞尔（Barthel）指数、神经功能（CSS）分值、神经功能缺损（NIHSS）分值以及血清肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）、神经生长因子（NGF）浓度。结果 治疗后两组患者血细胞比容、全血低切黏度、全血高切黏度、血浆黏度均显著降低,同组治疗前后比较差异有统计学意义（P<0.05）;且观察组各指标均显著低于对照组（P<0.05）。观察组治疗疗效显著优于对照组（P<0.05）。治疗后两组患者Barthel指数明显升高,同组治疗前后比较差异有统计学意义（P<0.05）;且观察组显著高于对照组（P<0.05）。治疗后两组患者CSS分值、NIHSS分值明显降低,同组治疗前后比较差异有统计学意义（P<0.05）;且观察组显著低于对照组（P<0.05）。治疗后两组患者血清TNF-α、IL-6浓度均明显降低,同组治疗前后比较差异有统计学意义（P<0.05）;且观察组显著低于对照组（P<0.05）。治疗后两组患者血清NGF浓度均明显升高,同组治疗前后比较差异有统计学意义（P<0.05）;且观察组显著高于对照组（P<0.05）。结论 高压氧疗联合注射用丹参多酚酸治疗脑梗死疗效确切。     

注射用丹参多酚酸治疗急性脑梗死患者的疗效及对hs-CRP和血液流变学的影响

目的 评价注射用丹参多酚酸治疗脑梗死急性期患者的疗效及对超敏C反应蛋白（hs-CRP）和血液流变的影响。方法 将80例脑梗死急性期患者依据随机数字表法分为观察组与对照组,每组40例。对照组采用常规西药治疗,观察组在对照组治疗基础上加用注射用丹参多酚酸0.13 g用0.9%氯化钠注射液稀释,静脉滴注1次/d。两组疗程均为14 d。比较两组治疗后疗效变化,治疗前后NIHSS评分、细胞炎症因子和血流变学水平的变化,并记录药物不良反应。结果 治疗后,观察组总有效率95.0%,高于对照组的77.5%,两组比较差异有统计学意义（P<0.05）;两组NIHSS评分均较治疗前下降,同组治疗前后比较差异有统计学意义（P<0.05）;且观察组下降幅度高于对照组,差异有统计学意义（P<0.05）。治疗前,两组患者hs-CRP水平,血浆黏度、血沉、全血黏度高切、全血黏度低切水平相似,差异无统计学意义;治疗后,两组患者血清hs-CRP水平、血浆黏度、血沉、全血黏度高切、全血黏度低切水平均降低,同组治疗前后比较差异有统计学意义（P<0.05）;但观察组患者的降低幅度明显于对照组,差异比较有统计学意义（P<0.05）。治疗过程中,两组患者无明显的药物不良反应。结论 注射用丹参多酚酸治疗脑梗死急性期患者疗效明确,可以降低hs-CRP水平和改善血液流变学,且比较安全。     

心悦胶囊联合美托洛尔治疗冠心病心绞痛的临床研究

目的 观察心悦胶囊联合琥珀酸美托洛尔缓释片治疗冠心病心绞痛的临床疗效。方法 选取2018年4月—2021年2月郑州大学第一附属医院收治的136例冠心病心绞痛患者作为观察对象,根据随机数字表法分为对照组（68例）和治疗组（68例）。对照组口服琥珀酸美托洛尔缓释片,1片/次,1次/d。治疗组患者在对照组治疗的基础上口服心悦胶囊,2粒/次,3次/d。两组治疗疗程均为4周。观察两组临床疗效、心电图疗效,比较两组心绞痛症状、心功能指标、心肌损伤指标、血液流变学指标。结果 治疗后,治疗组的临床疗效总有效率为94.12%,高于对照组的80.88%,治疗组的心电图疗效总有效率为92.65%,高于对照组的76.47%,组间对比差异有统计学意义（P<0.05）。治疗后,两组心绞痛发作频率降低、持续时间缩短（P<0.05）,与对照组相比,治疗后治疗组心绞痛发作频率降低、持续时间缩短更显著（P<0.05）。治疗后,两组左心室射血分数（LVEF）、心排血量（CO）较治疗前升高（P<0.05）,与对照组相比,治疗后治疗组的LVEF、CO升高更显著（P<0.05）。治疗后,两组全血低切黏度、全血高切黏度、血浆黏度、纤维蛋白原较治疗前降低（P<0.05）。与对照组相比,治疗后治疗组全血低切黏度、全血高切黏度、血浆黏度、纤维蛋白原降低更显著（P<0.05）。治疗后,两组肌酸激酶同工酶（CK-MB）、心肌肌钙蛋白I（cTnI）、脑钠肽（BNP）水平较治疗前降低（P<0.05）,与对照组相比,治疗后治疗组CK-MB、cTnI、BNP水平降低更显著（P<0.05）。结论 心悦胶囊联合琥珀酸美托洛尔缓释片治疗冠心病心绞痛具有较好的临床疗效,能够改善血液流变学、心功能,减轻心肌损伤,安全性好。     

颈痛颗粒联合替扎尼定治疗神经根型颈椎病的疗效观察

目的 探讨颈痛颗粒联合盐酸替扎尼定片治疗神经根型颈椎病的临床疗效。方法 选取2021年1月-2022年12月漯河市郾城区中医院收治的82例神经根型颈椎病患者作为研究对象,按照随机数字表法将所有患者分为对照组和治疗组,每组各41例。对照组口服盐酸替扎尼定片,3次/d,2片/次。治疗组患者在对照组基础上餐后半小时开水冲服颈痛颗粒,1袋/次,3次/d。两组患者连续治疗6周。观察两组的临床疗效,比较两组患者的手臂疼痛程度、颈椎功能障碍程度、颈部活动度和全血比黏度、血浆比黏度、纤维蛋白原水平。结果 治疗后,治疗组的总有效率为95.12%,明显高于对照组的总有效率78.05%,组间差异显著(P<0.05)。治疗后,两组的VAS、NDI评分均明显降低(P<0.05),治疗组的VAS、NDI评分低于对照组(P<0.05)。治疗后,两组患者的颈部左右旋转、左右侧屈的活动度显著升高(P<0.05),且治疗组颈部左右旋转、左右侧屈的活动度较对照组升高更明显(P<0.05)。治疗后,两组的全血比黏度、血浆比黏度、纤维蛋白原低于治疗前(P<0.05),且治疗后治疗组的全血比黏度、血浆比黏度、纤维蛋白原低于对照组(P<0.05)。结论 颈痛颗粒联合盐酸替扎尼定片治疗神经根型颈椎病的临床疗效显著,能降低患者手臂疼痛程度和颈椎功能障碍程度,提高颈部活动度,改善血液流变学水平,且不良反应发生率低。     

脑安滴丸联合长春胺治疗急性脑梗死恢复期的疗效观察

目的 探讨脑安滴丸联合长春胺缓释胶囊治疗血栓性脑梗死恢复期的临床疗效。方法 选取2021年3月—2022年3月在运城市中心医院诊治的80例血栓性脑梗死恢复期患者,根据用药的差别分为对照组（40例）和治疗组（40例）。对照组口服长春胺缓释胶囊,30 mg/次,2次/d;在对照组基础上,治疗组口服脑安滴丸,20粒/次,2次/d。两组患者均治疗4周。观察两组患者临床疗效,比较治疗前后两组患者NIHSS、FMA、AROM、SS-QOL和MBI评分,血清高密度脂蛋白（HDL-C）、低密度脂蛋白胆固醇（LDL-C）、三酰甘油（TG）、总胆固醇（TC）水平,颈总动脉和大脑中动脉的收缩期峰值流速（PSV）、舒张期末流速（EDV）和血管阻力指数（RI）水平,及血清纤维蛋白原、D-二聚体和血浆比黏度水平。结果 治疗后,对照组临床有效率为80.00%,明显低于治疗组（97.50%,P＜0.05）。治疗后,两组NIHSS评分明显下降,而FMA评分、AROM评分、SS-QOL评分和MBI评分明显升高（P＜0.05）,且以治疗组评分改善的最为明显（P＜0.05）。治疗后,两组血清HDL-C水平明显升高,而LDL-C、TG、TC水平明显降低（P＜0.05）,并且治疗组血脂水平明显好于对照组（P＜0.05）。治疗后,两组颈总动脉、大脑中动脉PSV、EDV明显升高,而PI明显降低（P＜0.05）,且治疗组血流动力学指标明显好于对照组（P＜0.05）。治疗后,两组血清纤维蛋白原、D-二聚体及血浆比黏度水平明显降低（P＜0.05）,并以治疗组降低最为明显（P＜0.05）。结论 脑安滴丸联合长春胺缓释胶囊治疗血栓性脑梗死恢复期可有效促进患者神经功能恢复,保护脑神经功能,提高患者运动功能,促使患者生活质量提高。     

脑心通胶囊联合阿司匹林治疗急性心肌梗死的临床研究

目的 探讨脑心通胶囊联合阿司匹林治疗急性心肌梗死的临床研究。方法 选取2019年9月—2021年1月阜阳市肿瘤医院心血管内科收治的86例急性心肌梗死患者作为研究对象,按照治疗方法将86例患者分为对照组和观察组,各有43例。对照组口服阿司匹林肠溶片,100 mg/次,1次/d。观察组在对照组的基础上口服脑心通胶囊,0.8 g/次,3次/d。两组均连续治疗4周。观察两组患者的临床疗效,同时比较两组治疗前后的纤维蛋白原、血浆黏度、全血高切黏度、D-二聚体和红细胞压积（HCT）水平,检测两组左室射血分数（LVEF）、心搏出量（CO）水平。运用WHO生活质量量表（WHOQOL）对患者的生活质量进行评估。记录两组患者不良反应的发生情况。结果 治疗后,观察组患者的总有效率为95.35%,显著高于对照组的81.40%,组间比较差异有统计学意义（P<0.05）。治疗后,两组的LVEF、CO均显著升高（P<0.05）;治疗后,观察组的LVEF、CO显著高于对照组,差异有统计学意义（P<0.05）。治疗后,两组纤维蛋白原、血浆黏度、全血高切黏度、D-二聚体显著降低,HCT水平显著升高（P<0.05）;治疗后,观察组的纤维蛋白原、血浆黏度、全血高切黏度、D-二聚体和HCT水平显著优于对照组,差异有统计学意义（P<0.05）。治疗后,两组的WHOQOL评分均显著降低（P<0.05）,以观察组降低更明显（P<0.05）。两组的药物不良反应的发生率无明显差异。结论 脑心通胶囊联合阿司匹林可提高急性心肌梗死的疗效,改善患者血液流变学和心功能,增强生活质量,具有良好的疗效。     

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     

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.     

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。     

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.     

Polymorphisms in genes involved in neurotransmission in relation to smoking

Smoking behavior is influenced by both genetic and environmental factors. The genetic contribution to smoking behavior is at least as great as its contribution to alcoholism. Much progress has been achieved in genomic research related to cigarette-smoking within recent years. Linkage studies indicate that there are several loci linked to smoking, and candidate genes that are related to neurotransmission have been examined. Possible associated genes include cytochrome P450 subfamily polypeptide 6 (CYP2A6), dopamine D₁, D₂, and D₄ receptors, dopamine transporter, and serotonin transporter genes. There are other important candidate genes but studies evaluating the link with smoking have not been reported. These include genes encoding the dopamine D₃ and D₅ receptors, serotonin receptors, tyrosine hydroxylase, trytophan 2,3-dioxygenase, opioid receptors, and cannabinoid receptors. Since smoking-related factors are extremely complex, studies of diverse populations and of many aspects of smoking behavior including initiation, maintenance, cessation, relapse, and influence of environmental factors are needed to identify smoking-associated genes. We now review genetic polymorphisms reported to be involved in neurotransmission in relation to smoking.     

Genotoxic effects of chlorophenoxy herbicide diclofop-methyl in mice in vivo and in human lymphocytes in vitro

Diclofop-methyl (DM) is a chlorophenoxy derivative used in large quantities for the control of annual grasses in grain and vegetable crops. In this study, the genotoxic effects of DM were investigated by measuring chromosomal aberrations (CAs) in mouse bone-marrow cells and CA and the comet assay in human peripheral lymphocytes. Mice were treated with 15.63, 31.25, 62.5, and 125?mg/kg body weight of DM intraperitoneally for 24 hours, and 15.63-, 31.25-, 62.5-, 125-, and 250-µg/mL concentrations were applied to human lymphocytes for both 24 and 48 hours. In in vivo treatments, DM significantly, but not dose dependently, increased the total chromosome aberrations, compared to both negative and solvent controls. Cell proliferation was significantly, but not dose dependently, affected by all doses. In in vitro treatments, DM (except 15.63 µg/mL) significantly and dose dependently increased the frequency of chromosome aberrations. Also, 250 µg/mL of 48-hour treatment was found to be toxic. Cell proliferation was significantly and dose dependently affected by DM applications, when compared to negative control. In in vitro treatments, DM significantly decreased the mitotic index only at the highest concentration for 24 hours, and 62.5- and 125-µg/mL concentrations for 48 hours. In the comet assay, a significant and dose-dependent increase in comet-tail intensity was observed at 62.5-, 125-, and 250-µg/mL concentrations. The mean comet-tail length was significantly increased in all concentrations. Our results demonstrate that DM is genotoxic in mammalian cells in vivo and in vitro.     

2010调脂治疗领域进展

2010年在调脂治疗领域针对他汀治疗心血管病的防治又进行了许多探索。本文通过综述他汀类药物的国际大规模临床试验结果,重新评价了他汀类药物在冠心病一级预防和冠心病二级预防中的地位,阐明了强化他汀治疗的意义;对他汀的心肾保护作用和安全性新证据进行了说明。     

Pradigastat disposition in humans: in vivo and in vitro investigations

1.?Pradigastat is a potent and specific diacylglycerol acyltransferase-1 (DGAT1) inhibitor effective in lowering postprandial triglycerides (TG) in healthy human subjects and fasting TG in familial chylomicronemia syndrome (FCS) patients.

2.?Here we present the results of human oral absorption, metabolism and excretion (AME), intravenous pharmacokinetic (PK), and in vitro studies which together provide an overall understanding of the disposition of pradigastat in humans.

3.?In human in vitro systems, pradigastat is metabolized slowly to a stable acyl glucuronide (M18.4), catalyzed mainly by UDP-glucuronosyltransferases (UGT) 1A1, UGT1A3 and UGT2B7. M18.4 was observed at very low levels in human plasma.

4.?In the human AME study, pradigastat was recovered in the feces as parent drug, confounding the assessment of pradigastat absorption and the important routes of elimination. However, considering pradigastat exposure after oral and intravenous dosing, this data suggests that pradigastat was completely bioavailable in the radiolabeled AME study and therefore completely absorbed.

5.?Pradigastat is eliminated very slowly into the feces, presumably via the bile. Renal excretion is negligible. Oxidative metabolism is minimal. The extent to which pradigastat is eliminated via metabolism to M18.4 could not be established from these studies due to the inherent instability of glucuronides in the gastrointestinal tract.