大鼠多次口服双环醇和拉米夫定后对血浆药代动力学的相互影响

目的研究大鼠多次口服双环醇和拉米夫定后对两药血浆药代动力学的影响。方法SD大鼠分别口服双环醇（200mg/kg）和拉米夫定（15mg/kg）,每日1次,连续7天。末次给药后16h一次口服拉米夫定（15mg/kg）或双环醇（200mg/kg）。应用LC-MS和HPLC法测定血浆中双环醇和拉米夫定浓度,计算药代动力学参数。 结果正常组和双环醇（200mg/kg）给药组大鼠一次口服拉米夫定（15mg/kg）后血浆浓度均于给药后40min达峰,达峰浓度分别为2.68mg/L和2.99mg/L;AUC（0-t）分别为10.535mg/（L·h）和10.176mg/（L·h）。正常组和拉米夫定给药组大鼠一次口服双环醇（200mg/kg）后血药浓度分别于给药后4h和3h达峰,达峰浓度分别为10.215mg/L和8.984mg/L;AUC（0-t）分别为54.998μg/（L·h）和42.342mg/（L·h）。结论大鼠多次口服双环醇或拉米夫定后对两药血浆药代动力学参数无显著相互影响。     

左旋和右旋奥硝唑在大鼠体内的药代动力学

目的:研究大鼠口服和静注左旋、右旋奥硝唑,比较两者药代动力学行为差异。方法:大鼠分别口服和静注左旋、右旋奥硝唑后,用HPLC法测定血浆中药物的浓度。色谱柱为Lichrospher C18柱,流动相为甲醇-0.4%HOAc(30∶70),流速0.8 mL/min,柱温40℃,紫外检测波长316 nm。结果:口服给药后,左旋、右旋奥硝唑的t1/2分别为2.49和3.42 h,AUC分别为168.21和207.19μg.h/mL,CL/F分别为0.11和0.09 L/h。静脉注射给药后,左旋、右旋奥硝唑的t1/2分别为2.19和3.23h,AUC分别为138.40和203.09μg.h/mL,CL分别为0.08和0.05 L/h。结论:左旋、右旋奥硝唑在大鼠体内的药代动力学行为存在一定的差异。     

隐丹参酮单剂量和多剂量给药在大鼠体内药代动力学研究

目的 评价单剂量和多剂量灌胃隐丹参酮(Cryptotanshinone,CTS)的药动学特征.方法 将20只SD雄性大鼠随机分为单剂量组(隐丹参酮10 mg/kg,1d)、多剂量组(隐丹参酮10 mg/kg,每天1次,连续10 d)给予灌胃后,用LC-MS/MS法测定血浆中隐丹参酮的浓度.血药浓度数据用DAS 2.0药代动力学软件处理,按两室模型拟合并求算药代动力学参数.结果 隐丹参酮单剂量给药后,Cmax为(12.16±14.11)ng/mL,Tmax为(2.88±2.56)h,T1/2为(3.70±3.50)h,MRT为(6.69±0.54)h,AUC0-24为(58.40±25.73)ng·h/mL;多剂量给药后,Cav为(1.95±0.61)ng/mL,Tmax为(3.20±2.08)h,T1/2为(7.12±5.06)h,AUCss为(46.74±14.51)ng·h/mL,DF为2.42±0.28.单剂量和多剂量的AUC0-24、Tmax、T1/2差异无统计学意义.结论 隐丹参酮长期给药后无蓄积风险.     

LC-MS/MS法测定大鼠血浆中芹黄春浓度及其在药代动力学研究中的应用

目的：研究大鼠分别灌胃和静脉给药芹黄春（芹菜素-7-O-β-D吡喃葡萄糖苷）溶液后,血浆中的芹黄春药物浓度及其药代动力学性质。方法6只雌性Sprague Dawley大鼠随机分为两组,每组3只,分别经灌胃(10 mg/kg)和静脉注射(2 mg/kg)给予芹黄春溶液后,按设计的时间点从大鼠眼内眦静脉丛采集血液样品,置于肝素化的离心管中,低温离心得血浆。采用甲醇沉淀法处理血浆生物样品,利用LC-MS/MS方法对血浆生物样品进行分析。药代动力学参数由Kinetica 2000软件进行计算。结果芹黄春浓度在1~2000 ng/mL范围内线性关系良好(r=0.9974),定量下限为1 ng/mL,低(8 ng/mL)、中(100 ng/mL)、高(1200 ng/mL)3个浓度的提取回收率均大于90%,日内日间精密度和稳定性的RSD均小于12.8%,日内日间准确度在91.5%~107%,方法学考察均符合要求。大鼠经静脉注射和灌胃芹黄春后,Cmax分别为(2363±96) ng/mL和(13.3±5.8) ng/mL,AUC0~∞分别为(796±201) h· ng/mL和(28.9±9.2) h· ng/mL,大鼠经静脉注射和后t1/2为(1.20±0.17) h,芹黄春的口服生物利用度约为0.6%。结论所建立的LC-MS/MS分析方法方便、快速,灵敏度高,准确度好,可用于大鼠血浆芹黄春浓度测定及其药代动力学的研究。     

HPLC-MS/MS法测定大鼠血浆中紫杉醇含量及其脂质体药代动力学研究

目的:建立一种测定大鼠血浆中紫杉醇浓度的高效液相色谱串联质谱（HPLC-MS/MS）分析方法,并研究其脂质体的药代动力学。方法:对6只SD大鼠静脉注射1 mg/kg的紫杉醇脂质体注射液,分别于给药后0、0.5、1、2、4、8、12、24、48 h自眼眶取血0.2 mL,C18反相色谱柱作为固定相,水（1 mmoL/L甲酸铵-0.05%甲酸）-甲醇作为流动相,ESI+扫描模式,MRM监测模式,药代动力学参数采用DAS 2.0软件进行计算。结果:紫杉醇在1～5 000 ng/mL范围内线性较好（R2 =0.999 7）,定量下限（LLOQ）为1 ng/mL,日内和日间精密度均低于10%,紫杉醇脂质体给药后血药浓度-时间曲线满足二室模型,主要药代动力学参数t1/2、Cmax、AUC0→t分别为（4.79±0.85）h、（49 785.12±1 618.45）μg/L、（38 753.08±6 144.66）μg/L·h。结论:本方法专属性和灵敏度高,结果可靠,能满足测定大鼠血浆中紫杉醇的定量需求。     

牛磺酸在大鼠体内的药代动力学

目的:建立牛磺酸(TAU)在血浆和组织中HPLC的测定方法,进行TAU在大鼠体内的药代动力学研究.方法:Wistar大鼠在清醒状态下以60 mg/kg尾静脉注射TAU,分别于给药前和给药后1、3、5、10、15、20、30、45 min,l、1.5、2h,从內眦静脉取血0.5mL,分离血浆后,以乙腈沉淀蛋白,2,4-二硝基氟苯(DNFB)进行柱前衍生化处理后,采用RP-HPLC法,以A:乙酸钠溶液(pH7.0),B:乙腈-水(40∶60,v/v)为二元流动相,经Venusil C18(250 mm×4.6 mm,5μm)色谱柱分离,紫外检测器于波长360 nm处测定血浆中TAU含量,根据测定结果绘制TAU血药浓度-时间曲线并计算其药代动力学参数.结果:TAU以40 mg/kg、80 mg/kg、160 mg/kg尾静脉注射给药后,血中能迅速检测到TAU,其在大鼠体内药时过程符合非线性动力学,在房室模型的拟合上,符合一房室模型,其药代动力学参数T1/2分别为20.61、37.36和77.55 min,C0分别为317.28、477.63和818.02μg/mL,AUC(0-t)分别为10 132.0、18 305.5和59 508.6μg/(mL· min);3个剂量之间T1/2相比有统计学差异(P＜0.01),随剂量增加而延长,AUC(0-1)明显随剂量增加而增大,并且与剂量不成比例;统计矩参数MRT(0-t)分别为28.579、42.549和49.701 min.结论:建立了HPLC法测定大鼠血浆中TAU的方法,能满足研究药物在大鼠体内的药代动力学过程,其动力学行为符合一房室非线性动力学模型.     

富马酸替诺福韦二吡呋酯胶囊在中国人体内的药代动力学

研究富马酸替诺福韦二吡呋酯胶囊在中国人体内的药代动力学特征。12名健康受试者依次进行低剂量(300mg)单、多次给药;高(600 mg)剂量单次给药和低剂量饮食影响单次给药的药代动力学试验,计算药代动力学参数。受试者单次口服300 mg和600 mg受试制剂后,替诺福韦的cmax分别为(305.4±96.4)和(590.0±149.6)ng/mL,AUC0-72 h分别为(2 396±489)和(4 465±1 042)ng.h/mL,t1/2分别为(19.9±2.4)和(21.9±3.0)h。结果显示替诺福韦在300～600 mg剂量范围内呈现线性药代动力学特征,体内过程不受性别差异的影响。与空腹给药相比,高脂餐后给药的tmax延后1.6 h,AUC0-72 h提高约32%。多次给药达稳态后,替诺福韦的稳态血药浓度波动度为2.7±0.6,累积常数Rcmax为1.3±0.3,RAUC为1.7±0.4,在人体内的暴露量增加约70%。     

注射用紫杉醇聚合物胶束小鼠体内药代动力学

目的:建立一种测定小鼠血液中紫杉醇含量的HPLC方法,研究注射用紫杉醇聚合物胶束(PTX-PM)的药代动力学。方法:血样经乙醚提取后进行HPLC分析,色谱柱为Lichrospher C18(4.6mm×25mm,4.6μm),流动相为甲醇-水-乙腈(28∶36∶36),检测波长为227nm,地西泮为内标。小鼠尾静脉给药,特素(市售紫杉醇注射液)给药剂量为20mg/kg,PTX-PM给药剂量为50mg/kg(以药液中紫杉醇含量计)。采用3P87程序计算紫杉醇的药代动力学参数。考察PTX-PM给药剂量分别为30,40,50mg/kg时,剂量与药代动力学参数之间的相关性。结果:两种制剂体内过程均符合二室模型,特素和PTX-PM的cmax分别为(60.37±17.16)μg/mL和(84.17±12.29)μg/mL,AUC分别为56.02μg/mL.h和56.64μg/mL.h,t1/2(β)分别为1.31h和1.06h。在3种给药剂量下,PTX-PM的AUC0-8h与剂量之间有线性相关性。结论:PTX-PM给药后,紫杉醇迅速地分布于组织,血液中药物浓度低,降低了血液毒性。     

甲磺司特活性代谢物M-1的人体药代动力学

目的:研究甲磺司特活性代谢物4-(3-乙氧基-2-羟基丙氧基)-丙烯酰苯胺(M-1)在健康志愿者体内的药代动力学特征。方法:10名健康志愿者男女各半,单次及多次口服甲磺司特颗粒剂后,采用HPLC-MS法测定人血浆中甲磺司特活性代谢物M-1的浓度,计算药代动力学参数。结果:单次口服甲磺司特颗粒剂100 mg后,甲磺司特活性代谢物M-1的血药达峰浓度为(9.84±2.41)ng/mL;达峰时间为(3.0±1.3)h;AUC为(80.58±10.49)ng.h/mL;消除半衰期为(6.5±1.4)h。多次口服甲磺司特颗粒剂后,甲磺司特活性代谢物M-1的血药达峰浓度为(14.08±1.79)ng/mL;达峰时间为(2.5±1.2)h;AUC为(82.20±12.17)ng.h/mL;消除半衰期为(8.3±1.6)h。结论:多次给药后甲磺司特活性代谢物M-1的人体药代动力学参数与单次给药的药代动力学参数基本一致,AUC与tmax均与性别无关。     

吲哚美辛口服自微乳化给药系统的大鼠体内药动学研究

目的 研究吲哚美辛口服自微乳化给药系统(IDM-SMEDDS)在大鼠体内的药动学特征.方法 大鼠灌胃给予IDM-SMEDDS(给药剂量按IDM计为8.0 mg/kg),采用HPLC法测定IDM在大鼠血浆中的药物浓度,以IDM原料药制备混悬液作为参比,绘制两者血药浓度-时间曲线,DAS Ver2.0药动学软件计算药动学参数.结果 IDM-SMEDDS的药动学过程符合二室模型,权重因子为1/C2,IDM混悬液的药动学过程符合一室模型,权重因子为1/C2;大鼠口服IDM-SMEDDS的Cmax为42.56 μg/mL、Tmax为1h、AUC0-48h为814.25(μg·h)/mL,口服IDM混悬液的Cmax为9.72 μg/mL、Tmax为6h、AUC0-48 h为134.57(μg·h)/mL.结论 自微乳化给药系统可以提高吲哚美辛的口服生物利用度.     

Value of D-Dimers in patients with acute aortic dissection

Objective: To evaluatel the value of D-dimers in patients with acute aortic dissection (AAD). Methods: This study consisted of 16 patients with AAD and 27 non-AAD patients. Serum D-dimets were measured by Sta-Liatest D-DI immunoturbidimetric assay. Results: D-dimer level was higher (P ＜ 0.001) in patients with AAD(7.91 ± 5.52 μg/ml) than that in non- AAD group(1.57±1.24 μg/ml). D-dimer was positive (＞0.4 μg/ml) in all patients with AAD and in 10 control group patients (37%). Among patients with acute AAD, D-dimers tended to be higher in Stanford A than in Stanford B (8.67 ± 4.31 μg/ml vs. 3.24±1.27 μg/ml, P ＜0.01). D-dimer values tended to be higher in more extended disease(3.84 ± 1.65 μg/ml, 8.57 ± 3.58 μg/ml and 11.87 ± 5.69 μg/ml in thoracic aorta, thoracic and abdominal aorta, thoracic and abdominal aorta and iliacal arteries, respectively, P ＜ 0.05 for both 8.57 ± 3.58 and 11.87 ± 5.69 vs. 3.84 ± 1.65 ). Including the control group into the analysis, we found a sensitivity of 100%, a negative predictive value of 100%, and a specificity of 66% and a positive predictive value of 64% for D-dimer in diagnosis of AAD in our patients with suspected AAD. Conclusion: D-dimer was elevated in patients with AAD. A negative D-dimer test result could be useful in excluding AAD.     

Research of combined liver-kidney transplantation model in rats

Objective： To set up a simple and reliable rat model of combined liver-kidney transplantation. Methods： SD rats served as both donors and recipients. 4℃ sodium lactate Ringer＇s was infused from portal veins to donated livers,and from abdominal aorta to donated kidneys, respectively. Anastomosis of the portal vein and the inferior vena cava （IVC） inferior to the right kidney between the graft and the recipient was performed by a double cuff method, then the superior hepatic vena cava with suture. A patch of donated renal artery was anastomosed to the recipient abdominal aorta. The urethra and bile duct were reconstructed with a simple inside bracket. Results： Among 65 cases of combined liver-kidney transplantation, the success rate in the late 40 cases was 77.5%. The function of the grafted liver and kidney remained normal. Conclusion： This rat model of combined liver-kidney transplantation can be established in common laboratory conditions with high success rate and meet the needs of renal transplantation experiment.     

BLOOD PRESSURE CHANGE WITH AGE IN SALT-SENSITIVE TEENAGERS

Objective To observe blood pressure change with age in salt-sensitive teenagers whose salt sensitivity were determined by repeated testing.Methods Salt sensitivity was determined through intravenous infusion of normal saline combined with volume-depletion by oral diuretic furosemide in 55 teenagers. After five years, salt sensitivity was re-examined and subject blood pressure was followed up. Blood pressure changes in salt-sensitive teenagers were compared to that of non-salt sensitive teenagers over five years.Results After 5 years, the repetition rate of salt sensitivity determined by intravenous saline loading is 92.7%. In teenagers with salt sensitivity on the baseline, both the systolic blood pressure increments and increment rates were much higher than non-salt sensitive teenagers (12.7±12.1 mmHg vs. 2.8±5.2 mmHg, P＜ 0.01; 12.2%± 12.0% vs. 2.5% ±4.4%, P＜ 0.001,respectively). There was a similar trend for diastolic blood pressure (8.4 ± 6.4 mmHg vs. 3.7 ± 6.4 mmHg, P = 0.052; 13.2% ±10.6 % vs. 6.8%± 10.1%, P = 0.053, respectively).Conclusions Salt sensitivity determined by intravenous saline loading showed good reproducibility. Blood pressure increments with age were much higher in salt-sensitive teenagers than non-salt sensitive teenagers, especially in terms of systolic blood pressure.     

安心颗粒对急诊经皮冠状动脉介入术后生活质量影响的研究

目的：评价使用安心颗粒对急诊经皮冠状动脉介入术（PPCI）术后生活质量的影响.方法：将160例接受PPCI的急性ST段抬高型心肌梗死患者随机分为安心颗粒组（术前顿服安心颗粒8.8g,术后安心颗粒4.4 g/次,每日2次）和对照组（仅接受基础药物治疗）.所有患者均服用阿司匹林、氯吡格雷和阿托伐他汀.分别在入院时、出院前1d、出院后180 d时,应用心肌梗死多维度量表（MIDAS）、中文版SF-36评价量表对患者生活质量评分.并观察术后30 d以内的出血并发症、血小板减少症发生情况.结果：入院时和出院前1d,两组患者的心肌梗死MIDAS、SF-36量表评分比较无差异（P＞0.05）;出院后180 d时,与对照组比较,安心颗粒组MIDAS、SF-36评分明显减低（P＜0.05）;组内与入院时比较,两组出院前1d、出院后180 d时,MIDAS、SF-36评分均降低（P＜0.05）.两组患者在随访期间均无大量出血、少量出血、重度和极重度血小板减少症发生,安心颗粒组有4例、对照组有7例发生不明显出血（P＞0.05）.两组发生轻度血小板减少症的患者数比较无差异（P＞0.05）.结论：PPCI使用安心颗粒,能改善急性ST段抬高型心肌梗死患者的生活质量,且不增加出血风险.     

The comparative studies of the influences of Urapidil and Nicardipine on sino-atrial node function, atrio-ventricular node function and hemodynamics

Objective:To investigate the influences of urapidil and nicardipine on rabbit sinus function,atrio-ventricular node function and hemodynamics.Methods:Thirty-two Angora's rabbits were selected and randomly divided into four groups.U1 group:urapidil 0.25 mg/kg;U2 group:urapidil 0.5 mg/kg;N1 group:nicardipine 10 μg/kg;N2 group:nicardipine 20 μg/kg.All these medicine were administrated within 30 seconds.Measurements were taken before and after the administration of urapidil or nicardipine for the following data:mean blood pressure(MAP),heart rate(HR),sino-atrial conduction time(SACT),maximal sinoatrial recovery time(SNRTmax)corrected sinus node recovery time(CSNRT),index of sinus node recovery time(SNRTI),Wenckebach A-V conduction frequency (WB),and P-R interval.Results:Significant MAP and HR changes were identified in all of the four groups before and after administration of both urapidil and nicardipine.No significant changes could be found in the rest of the parameters.Intergroup analysis showed that SACT and CSNRT of N1 and N2 groups were shorter than those of the U2 group(P＜0.01);the MAP decreased(P＜0.01)and the HR increased drastically(P＜0.01).Conclusions:Neither urapidil(0.25 mg/kg,0.5 mg/kg)nor nicardipine(10μg/kg,20μg/kg)has any significant influence on rabbit sinus function or rabbit atrio-ventricular node function.Nicardipine could be a better choice than urapidil for parafunctional sinus node patients.     

Expression of OPGmRNA and ODFmRNA in the patients of hip fracture due to osteoporosis

Objective：To investigate the gene expression of osteoprotegerin（OPG） and osteoclast differentiation factor（ODF） in the bone tissue of patients with hip fracture due to osteoporosis. Methods：OPGmRNA and ODFmRNA in the bone tissue in 50 cases of osteoporosis sufferers（over 50 years old） with hip fracture（Observer Group） and 30 cases of hip facture sufferers with no osteoporosis（Control group） were analyzed with the Semi-Quantitative RT-PCR method. Results：The mRNA expressed of ODF, OPG were both high in the patients with hip fracture. In the control group, the expression of OPG mRNA was observed, while the expression of ODF mRNA was very slight. Conclusion：Aged patients contained all signals including OPG, ODF that are essential for inducing osteoclastogenesis and promoting bone resorption.     

The clinicopathological and immuohistochemical analysis of solid-pseudopapillary tumor of the pancreas： report of 9 cases

Objective：To investigate the clinical features, pathological characteristics and immunophenotype of solid-pseudopapillary tumor of the pancreas（SPTP）. Methods：Nine surgically treated cases of SPTP were retrospectively reviewed. Hematoxylin and Eosin（HE） staining and immunohistochemical staining were used to analyze all cases, and the general clinical data was collected. Results：Six patients were asymptomatic except for a palpable mass. Two patients complained of vague-epigastric pain. One patient appeared jaundice. The tumor was encapsulated and solid tissues alternately with cystic tissues. Histologically, the histological structure of solid portion was pseudopapillary with a fibrovascular core. Tumor cells were uniform and medium-sized which were arranged in sheets ets or nests or pseudopapillary patterns. Immunohistochemical studies demonstrated that SPTP proved positive in vimentin（9/9 cases）, AAT（9/9 cases）, NSE（9/9 cases）, ACT（7/9 cases）, CK20（2/9 cases）, CgA（1/9 cases）, S-100（3/gcases）, PR（4/gcases）, Syn（3/9 cases） and CD56（5/9cases）, negative in CEA and ER. Conclusion：SPTP is a tumor predominantly occurring in young women frequently without special symptoms. This tumor has various characteristical histological patterns with different immunophenotype.     

Scientific principles and rigorous processes should be followed in developing clinical guidelines for therapeutic interventions of integrative medicine

A clinical guideline for the therapeutic interventions of integrative medicine may be defined as a written document which states a series of recommendations on therapeutic interventions of integrative medicine for a special disease or condition. The guideline may provide assistance to medical professionals in making clinical decisions aimed at improving the clinical outcome of patients and reducing the costs of medical care（~＇4~. Recommendations issued by a guideline should be based on the best available evidence in both Western and Chinese medicine. For fulfilling this purpose, the development of clinical guidelines for therapeutic interventions in the field of integrative medicine should follow scientific principles and undergo a rigorous processes.     

Dynamic Changes in Serum Estradiol and Progesterone levels in Patients of Premenstrual Syndrome with Adverse Flow of Liver-qi

Objective:To probe into the influence of changes of ovarian hormones on the pathogenesis of the specific sub-type premenstrual syndrome(PMS)and reveal partial microcosmic mechanisms of adverse flow of liver-qi.Methods:Estradiol(E2)and progesterone(P)levels in serum were determined at different phases of menstrual cycle by radioimmunoassay.Results:In the group of PMS with adverse flow of liver-qi.the secretive peak value Of E2 and P at the follicular phase significantly decreased,and the secretive peak value at the luteal phase did not come into being.Conclusions:Low E2 and P secretive peak at the follicular phase and absence of secretive peak at the luteal phase is one of the microcosmic mechanisms of PMS with adverse flow of liver-qi.One of the pathophysiologic mechanisms of specific sub-type PMS is probably the continuous low level of E2and P.     

Real-time Three-dimensional Echocardiography in Assessment of Left Ventricular and Right Ventricular Volumes

Real-time three-dimensional echocardiography (RT3DE)is a new ultrasound technique that enables dynamic threedimensional visualization and quantification of the heart in real time. Investigation of feasibility and methodology of RT3DE in determining left ventricular (LV) and right ventricular (RV) volumes, RT3DE was performed in 35 normal adults using Philips SONOS 7500 system with a 2-4 MHz matrix array transducer. The 60°×60° "pyramid" volume database was obtained and analyzed on a TomTec echo workstation. Both LV and RV volumes were calculated with four 3DE methods (i.e. apical 2, 4, 8, and 16-plane) through manually tracing ventricular endocardial borders in end diastole and end systole. Stroke volumes were then calculated. LV volume was also measured by 2DE Simpson's rule using GE VIVID 7 ultrasound machine.