~(14)C-久效磷灌胃后的小鼠体内毒物动力学研究

~(14)C-久效磷在小鼠体内的动力学研究发现,灌胃后血中毒物浓度-时间曲线符合一级吸收两室开放模型。主要动力学参数:T_(1/2)K_α 0.04h,T_(1/2α) 0.39 h,T_(1/2β) 4.78h,Vd1.06L/kg,Cl 0.15L/kg·h,AUC 20.06 mg/L·h。经矩量分析计算,其动力学参数与室模型基本接近。人体的~(14)C-久效磷广泛分布于各脏器和组织,以肝、肾含量最高,脑、脂肪含量最少,未显示亲脂性。~(14)C-久效磷主要经肾脏排出,经胃肠道吸收快,分布快,排出也快,与其快速产生毒效应的一过性相一致。     

厚朴中苯乙醇苷类化合物厚朴苷A的大鼠体内药动学研究

目的:建立血浆样品中厚朴苷A的测定方法,研究厚朴苷A在大鼠体内的药动学特征。方法:大鼠经口服和尾静脉注射给药,以黄芩苷为内标,采用高效液相色谱法测定不同时间点大鼠血浆中的厚朴苷A浓度。使用岛津LC-20A高效液相色谱仪,色谱柱为Agilent Zobax SB-C18(250 mm×20 mm,5μm),甲醇/水溶液梯度洗脱(0~15 min,甲醇15%~85%),流速为1 mL·min~(-1)。采用DAS 2.0软件对所得的需要浓度进行拟合,计算相应的药动学参数。结果:大鼠经口服给药200 mg·kg~(-1)、尾静脉注射给药5 mg·kg~(-1),目标物质量浓度在0.3~100μg·mL~(-1),内线性关系良好(r=0.999 6),标准曲线定量下限为0.3μg·mL~(-1);批内精密度RSD7.1%,批间精密度RSD12.4%;准确度RE3.3%~5.9%;回收率83.5%~99.0%。大鼠经口服给药的药动学参数AUC(0-t)为(15.6±7.4)mg·h/L,CL为(14.5±6.1)L·h/kg,Vd为(13.5±2.8)L/kg,t1/2为(1.16±0.8)h。大鼠尾静脉注射给药的药动学参数AUC(0-t)为(17.8±9.9)mg·h/L,CL为(0.34±0.14)L·h/kg,Vd为(0.08±0.04)L/kg,t1/2为(0.15±0.03)h。结论:该实验建立了一种简便、准确、快速地测定厚朴苷A浓度的方法,首次报道了厚朴苷A在大鼠体内的药物代谢动力学特征。     

~(35)S—敌枯双在妊娠大鼠和小鼠体内的毒物代谢动力学研究

对致畸剂量的~(35)S-敌枯双一次经口给予妊娠大鼠和小鼠后的动力学进行了比较。两种动物血毒物浓度-时间曲线均符合两室模型:C=Ne~(-Καt)+Le~(-αt)+Me~(-βt)。主要动力学参数;T_(1/2)β:4.75 h(小鼠)和32.05 h(大鼠);T_(1/2):4.73h(小鼠)和6.45 h(大鼠);Vd:88.84ml/kg(小鼠)和801.36 ml/kg(大鼠);Cl:12.85 ml/h(小鼠)和43.96 ml/h(大鼠)。组织分布均以肾和肝最高,脑和脂肪最低,敌枯双可通过胎盘屏障进入胚胎。各组织的排出半衰期大鼠长于小鼠2～6倍,尤以子宫为最。等量烟酰胺不影响敌枯双在这种妊娠动物体内的代谢动力学。     

辛酰伯喹在家兔体内的药代动力学研究

本文阐述了辛酰伯喹在家兔体内的药代动力学。应用最优化理论中的单纯形法自编计算机程序处理家兔静注辛酰伯喹丙二醇后的血药浓度-时间数据,拟合曲线以开放性三室模型描述较为适宜,其药代动力学参数为:T_(1/2)(λ_3、λ_2和λ_1相)3.410±1.394,0.5420±0.4373和0.1232±0.1045h;V_c 1.261±1.138 1/kg;Vd(ss)6.383±5.072 1/kg;Vd(λ_3)15.59±9.937 1/kg;AUC 9.108±3.793μg·h·ml~(-1);Cl_s 3.158±1.220 1·kg~(-1)·h~(-1);k_(10) 4.315±2.775h~(-1);k_(12)2.003±1.312h~(-1),k_(21) 2.373±0.7639h~(-1),k_(13) 1.127±0.9859h~(-1),k_(31) 0.3107±0.1158h~(-1)。     

头孢羟氨苄胶囊人体生物利用度及生物等效性研究

目的:研究头孢羟氨苄胶囊在健康志愿者体内的生物利用度及生物等效性。方法:20例健康志愿者随机交叉口服2种头孢羟氨苄胶囊各1000mg,以对氨基苯甲酸为内标,采用反相HPLC法测定血中药物浓度。结果:健康志愿者口服2种头孢羟氨苄胶囊1000mg后Cmax分别为(23.37±3.64)μg/ml和(23.62±3.15)μg/ml;Tmax分别为(1.6±0.3h)和(1.7±0.3)h;AUC0-8分别为(84.61±10.93)μg·h/L和(88.24±10.99)μg·h/L;T1/2分别为(1.74±0.28)h和(1.68±0.21)h。各参数经统计学双单侧t检验,均差异有显著性(P<0.05)。结论:2种头孢羟氨苄胶囊在健康志愿者体内的药动学参数相似,具有生物等效性。     

用室模型与非室模型研究铬剂在家兔体内的药代动力学

作者给家兔静注和口服三价有机铬剂 1 mg/kg,于给药前及给药后不同时间取血,用原子吸收光谱法测得血中铬浓度,以室模型和非室模型分析法计算各药代动力学参数。结果表明:静注铬剂后其血药浓度的变化符合二室模型,T_(1/2)α=1.28h,T_(1/2)β=52.2h,V_d=1.26 (L/kg),Cl=0.022(L/h·kg)。用非室模型法计算所得参数值与上述各数据相近。口服铬剂后其血药液度变化不符合室模型理论,故用非室模型法计算各参数。口服铬剂吸收不良,生物利用度F=4.39％。     

葛根芩连汤配伍黄芩苷在犬体内药动学研究

目的测定葛根芩连汤剂和黄芩单煎剂灌胃后犬血中黄芩苷的含量,分析配伍对其体内过程的影响。方法采用高效液相色谱法,测定不同时间点犬血浆黄芩苷的含量,WinNonlin软件计算药动学参数。结果葛根芩连汤全方及黄芩单煎剂中黄芩苷在犬体内过程均符合一室模型,主要药动学参数分别为:AUC(单)=(18.44±0.53)h·μg/ml,AUC(全)=(17.25±0.13)h·μg/ml,Tmax(单)=(8.92±0.02)h,Tmax(全)=(8.95±0.36)h,Cmax(单)=(1.01±0.03)μg/ml,Cmax(全)=(1.02±0.01)μg/ml。CL(单)=(130.47±2.5)L/h,CL(全)=(93.97±0.96)L/h。结论葛根芩连汤配伍后黄芩苷入血的Cmax、t1/2(K01)及t1/2(K10)没有明显变化,而AUC降低、清除速率减慢。     

用高效液相色谱法研究阿糖胞苷在家兔中的药代动力学

我们建立用高效液相色谱法(HPLC)测定血浆中阿糖胞苷(Ara-C)浓度的方法。Ara-C血浆浓度在1～10μg/ml范围内为直线相关,r=0.9994。方法回收率为96.67％。最低检测限为5ng;血浆中最低检测浓度为200ng/ml。5只家兔,每只静脉注射Ara-C 5mg-剂量,用本文的HPLC方法测定其血浆浓度,所得药代动力学参数平均值为:K=0.7611 h~(-1),t_(1/2)=0.9324h,Vd=2.935L/kg,Cl=2.246L/(h·kg)。其结果符合单室模型,对本法的优点作了讨论。     

帕罗西汀片在健康人体的药代动力学

目的 研究帕罗西汀片在健康人体内的药代动力学.方法 20名健康志愿者单剂量121服40 mg帕罗西汀片后,用高效液相色谱法测定血浆中帕罗西汀浓度,并用3P97软件统计处理.结果 帕罗西汀片药-时曲线经拟合呈二室模型,其Cmax、Tmax 、AUC0.120、AUC0.inf分别为(64.74±18.43)ng/ml、(5.64±1.84)h、(20.03±5.33)h、(976.47±309.49)ng·h/ml和(1086.75±376.54)ng·h/ml.结论 帕罗西汀片在人体内的药代动力学呈二房室开放模型.     

一种新的基于微透析技术研究靶器官药代动力学方法

目的:采用微透析技术结合液相色谱-质谱联用法(LC-MS/MS)研究金刚烷胺在大鼠纹状体细胞外液中的药代动力学(药动学)过程,探讨靶器官药动学研究方法。方法:SD大鼠(雄性,8~10周龄)行乌拉坦麻醉(1.0 g/kg)后,手术植入微透析探针于大鼠纹状体,以人工脑脊液恒速(2μL/min)灌注探针。灌注1 h后,腹腔注射盐酸金刚烷胺(1.0 mg/kg),注射后立即收集透析液样本,样本收集间隔时间为12 min,连续6 h。用LC-MS/MS法检测透析样本中金刚烷胺浓度,药物浓度-时间曲线及计算药动学参数用DAS软件拟合。结果:金刚烷胺在大鼠纹状体细胞外液中浓度-时间变化呈一室开放模型,其主要药动学参数T_(max)、C_(max)、t_(1/2)和AUC_(0-∞)为(1.78±0.59)h、(38.56±9.10)μg/L、(2.07±0.35)h和(591.84±278.39)μg/(L·h)。结论:本实验建立了一种基于微透析采样结合LC-MS/MS法研究金刚烷胺在大鼠纹状体细胞外液中药代动力学过程的实验方法,该方法操作简单、灵敏度高,为研究药物在靶器官中的药动学过程提供了方法学基础。     

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.     

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.     

SCREENING FOR A 21-CHROMOSOME ABNORMALITY IN PREIMPLANTED EMBRYOS OF ELDERLY WOMEN

Increasing maternal age is the only etiological factor unequivocally linked to Down's syndrome in humans. The occurrence rate of newborns with Down's syndrome is about 1/220 in women over 35 years old. However, the occurrence rate in embryos fertilized in vitro, of the elder woman is unclear. Using FISH we screened the number of chromosome 21 in preimplanted embryos of 5 elderly women (average age, 38.4 years) to study the feasibility and necessity of screening trisomy 21 in embryos in patients over 35 years old at the in vitro fertilization (IVF) center.     

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.     

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.