酮康唑微囊在兔体内的药动学研究

目的:研究酮康唑微囊在兔体内的药动学特征.方法:以复凝聚法制备酮康唑微囊,采用紫外分光光度法直接测定微囊中酮康唑含量.采用HPLC法测定兔血浆中酮康唑浓度,其条件为:以乙腈直接沉淀血浆蛋白,色谱柱为配有Waters保护柱的sunfire C18(150 mm×4.6 mm,5 μm)色谱柱;流动相为甲醇:磷酸盐缓冲液(80:20),流速1.0 ml·min-1;检测波长235 nm;进样20μl;柱温(35±1)℃;外标法峰面积定量.结果:血浆中酮康唑浓度分别在20～400 ng·ml-1和400～4 000ng·ml-1范围内,浓度与峰面积之间有良好的线性关系,线性相关系数r2分别为0.998 4和0.999 7;口服酮康唑微囊后,24 h内血浆中酮康唑浓度平稳,酮康唑微囊的药动学特征符合一室模型,主要药动学参数分别为:t1/2(4.62±0.05)h;tmax(2.0±1.03)h;cmax(2 154.52±43.07)ng·ml-1;Ke(0.15±0)h-1;AUC0～∞(16 075.38±98.50)ng·h·ml-1.结论:酮康唑微囊化后,较之普通片及其原料药血药浓度更高,作用时间更长,生物利用度有显著提高.     

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。     

磷脂复合物改善丹参素口服生物利用度的研究

目的考察丹参素磷脂复合物在大鼠体内的药动学特性,并与丹参素原料药进行比较。方法灌胃给予大鼠丹参素和丹参素磷脂复合物(含丹参素等量),LC-MS/MS法测定大鼠血浆中丹参素的浓度,通过DAS2.1.1软件计算药动学参数。结果丹参素组Cmax为(1.28±0.13)×103ng/mL,Tmax为(51±8.22)min,AUC0-t为(2.05±0.24)×105 ng/(mL·min);丹参素磷脂复合物组Cmax为(1.88±0.07)×103 ng/mL,Tmax为(90±18.37)min,AUC0-t为(3.07±0.50)×105ng/(mL·min)。结论磷脂复合物能够增加丹参素的口服生物利用度。     

玉米多糖铁在毕格犬体内的药代动力学研究

目的:采用原子吸收分光光度法对玉米多糖铁在毕格犬体内的药代动力学特征进行研究。方法:毕格犬灌胃(11.0 mg/kg、5.7 mg/kg、2.9 mg/kg)给予玉米多糖铁后,不同时间点测定犬体内铁离子的浓度,所得数据用DAS软件求算药动学参数并分析。结果:当玉米多糖铁中铁离子浓度在0.2⁵μg/ml范围内时其线性关系良好,标准曲线的相关系数r=0.999 65μg/ml范围内时其线性关系良好,标准曲线的相关系数r=0.999 6⁰.999 9,平均回收率达到91%以上、RSD值低于15%。药动学参数表明其在毕格犬体内的药动学模型符合二室模型,其中三个剂量组的t1/2分别为(1.69±0.25)×103、(1.4±0.51)×103和(1.88±1.41)×103min;AUC0-∞分别为(5.87±1.39)×103、(4.53±1.11)×103和(3.91±2.12)×103mg/(L·min)。结论:本研究数据为进一步研究玉米多糖铁的临床应用提供了极具价值的实验参数。     

尼扎替丁片在健康人体的药代动力学及生物等效性研究

目的研究尼扎替丁片在健康人体的药代动力学和生物等效性.方法采用随机开放双交叉自身对照试验,22名健康自愿者单剂量口服尼扎替丁(片或胶囊) 150 mg,用高效液相色谱法测定尼扎替丁在血浆中的浓度.结果尼扎替丁片达峰时间为(1.261±0.366)h,峰浓度为(1 105.626±187.378)ng/ml,曲线下面积为(3 832.598±431.311) ng·h·ml-1,尼扎替丁胶囊达峰时间为(1.091±0.382)h,峰浓度为(1 371.916±280.980)ng/ml,曲线下面积为(3 978.227±611.387)ng·h·ml-1.统计检验结果表明各药动学参数间均无显著性差异(P>0.05).尼扎替丁片的相对生物利用度为97.4%.结论健康人单剂量口服150 mg尼扎替丁片与尼扎替丁胶囊生物等效.     

阿托伐他汀大鼠体内药动学及肠肝循环研究

目的建立测定大鼠血浆、胆汁中阿托伐他汀的浓度的LC-MS方法,研究其在大鼠体内的药动学和肠肝循环情况.方法测定大鼠静脉注射和灌胃给予阿托伐他汀后血浆中的药物浓度,对灌胃给药的吸收程度进行研究;测定大鼠给药后12 h胆汁中的药物浓度,计算其累积排泄率;运用大鼠肠肝循环模型研究阿托伐他汀在大鼠体内从胆汁重吸收的药动学过程,经3P87程序计算药动学参数.结果大鼠静脉注射和灌胃给予阿托伐他汀后体内药动学过程均符合二房室一级吸收模型,灌胃给药的绝对生物利用度为10.2%,两种途径给药后12 h的胆汁累积排泄率分别是(7.3±1.4)%和(3.3±0.02)%.大鼠肠肝循环模型表明,胆汁供体组大鼠的AUC和胆汁受体组大鼠的AUC分别是(26 383.0±9 870.5)ng/mL·min和(2 636.8±1 815.0)ng/mL·min.结论阿托伐他汀在大鼠体内口服吸收程度较低,静脉注射给药后存在肠肝循环现象.     

茶苯海明口崩片的人体药代动力学及相对生物利用度研究

目的:比较茶苯海明口崩片和普通市售片的人体内药代动力学及相对生物利用度.方法:8名健康志愿者均分为2组,分别为口含单剂量茶苯海明口崩片(25 mg/片)和口服茶苯海明普通市售片(25 mg/片)后,分别服药前和服药后用高效液相色谱法测定血药浓度.色谱条件:色谱柱:Nova Pak C18(4μm,3.9 mm×150 mm),保护柱:Nova-Pak C18(4μm,3.9 mm×30 mm),流动相为甲醇:三乙胺缓冲液(磷酸4 ml,三乙胺7 ml,加50%甲醇稀释至1 000 ml,用磷酸调节pH 3.2),流速1.0 ml/min,检测波长225 nm,进样量20μl,室温.进行口崩片与普通市售片的药代动力学和生物利用度研究.结果:茶苯海明在人空白血浆中的标准曲线方程:C=0.004 4 A 4.745,R2=0.996,在5～500 ng/ml的浓度范围内线性良好.最低检测限2 ng/ml.平均回收率为(90.55±4.69)%,RSD=0.041%.低、中、高3种浓度的日内RSD分别为9.27%,4.93%,2.95%(n=5).目间RSD分别为9.97%,3.81%,3.06%(n=5).取血样3 ml处理后进样,两剂型血药浓度有显著差异,口崩片为:茶苯海明血药浓度-时间曲线下面积(AUC)=(602.04±113.82)ng·h·ml,峰浓度(Cmax)=(95.86±21.28)ng·ml,达峰时间(TPeak)=(1.8±0.32)h,市售片的药动学参数为:AUC=(342.73±84.96)ng·h·ml1,Cmax=(46.34±10.32)ng·ml-1,TPeak=(2.65±0.24)h,口崩片与普通片的生物利用度的差异有统计学意义(P＜0.01),相对生物利用度为175.66%.结论:所研制的口崩片能显著提高茶苯海明的生物利用度.     

反相高效液相层析法测定血浆中氯雷他定浓度及药动学研究

目的:建立测定血浆中氯雷他定浓度的反相高效液相层析方法,并对其在人体内的药动学进行研究.方法:血浆中氯雷他定用正己烷-甲基叔丁基醚(1:1)作液-液萃取挥干后,加流动相进样分析.反相高效液相层析方法采用Hypersil-BDS层析柱,流动相为乙腈-水(65:35,磷酸调pH 3.8),流速1.0 ml/min;紫外检测波长为248 nm.结果:氯雷他定在0.506 0～50.60 ng/ml血浆浓度范围内线性良好(r=0.999 5),平均相对回收率＞95.0%,日间和日内RSD＜15.0%.主要药代动力学参数:t1/2为(1.57±0.18)h;MRT为(2.46±0.19)h;Cl/F为(583.7±215.0)L/h cmax为(37.40±8.92)ng/ml;tmax为(1.0±0.20)h;AUC0～8 h为(73.24±21.30)ng·h/ml AUC0～∞为(75.57±21.70)ng·h/ml.结论:该方法操作方便,结果准确,可用于血浆中氯雷他定药代动力学研究.     

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。     

人血浆中屈昔多巴的测定及药代动力学研究

目的 建立测定人血浆中屈昔多巴的方法,并应用于药代动力学研究.方法 12例健康受试者单剂量口服屈昔多巴胶囊200 mg后,血样经高氯酸沉淀蛋白,通过HPLC-荧光检测法测定屈昔多巴的浓度,并运用3P87分析软件计算其药代动力学参数.结果 屈昔多巴测定的线性范围为0.025～2μg/ml,其主要的药动学参数T1/2(108.50±30.78)min,曲线下峰面积(AUC)(185.74±26.41)μg·ml-1·min-1,消除率(CL)(1.08±0.08)ml/min,Tmax(99.90±10.05)min,Cmax(0.74±0.08)μg/ml,服药10 h后屈昔多巴几乎从血液中完全消除.结论 本方法灵敏度高,重现性好,操作简便,可用于血浆样品中屈昔多巴的定性定量检测;屈昔多巴在体内的药代动力学过程符合二室模型.     

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.     

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.