健康志愿者盐酸奥昔布宁缓释制剂与普通制剂药代动力学及生物等效性研究

目的:对健康男性志愿者进行单剂量和多剂量口服奥昔布宁缓释片/胶囊药代动力学的研究,考察缓释制剂达稳态的趋势和程度。方法:18名健康志愿者分别口服试验制剂奥昔布宁缓释片(T1)、缓释胶囊(T2)和参比制剂(R)10mg,取血浆经去蛋白处理,采用液相-质谱法(LC-MS)测定单剂量和多剂量给药奥昔布宁血浓度,计算各制剂奥昔布宁主要药代动力学参数。结果:单剂量给药奥昔布宁缓释胶囊、缓释片半衰期延长,血药浓度峰值降低,相对于普通片生物利用度F(%)分别为(107.17±10.89)%和(104.52±10.48)%。多剂量给药,奥昔布宁缓释胶囊波动系数明显小于普通片。结论:试验制剂与参比制剂为生物等效制剂。试验制剂具有释放缓慢(达峰时延迟)、波动度小的特点。     

醋柳黄酮缓释片的药动学初步研究

目的:研究醋柳黄酮缓释片在家犬体内的药动学过程,测定其药动学参数,计算缓释片相对于普通片的生物利用度。方法:将实验动物分为两组,分别用醋柳黄酮缓释片和普通片进行口服给药,用高效液相色谱法测定血浆药物浓度,应用3P97软件求算药动学参数。结果:醋柳黄酮缓释片及普通片的tm ax分别为4.87 h和2.87 h,Cm ax分别为每小时0.46μg.L-1和每小时0.56μg.L-1,缓释片的相对生物利用度为111.7%。结论:醋柳黄酮缓释片与普通片均符合一室模型,缓释片与普通片具有生物等效性,且醋柳黄酮缓释片有明显的缓释效果。     

阿昔洛韦缓释片的体外和体内实验研究

研制阿昔洛韦缓释片,并对其体外释放特点和初步的体内过程进行了研究。分别采用紫外分光光度法和高效液相色谱荧光检测法对阿昔洛韦进行体外释放度和体内血药浓度测定。采用４例志愿者单剂量口服缓释片和市售片,测定血药浓度并计算药动学参数。该缓释片在体外和体内均具有缓释作用,与参比制剂比较,服用缓释片组血药浓度较为平稳和持久,ＡＵＣ增大,峰浓度降低,达峰时间延长。     

硝苯地平缓释微丸家犬体内药动学和生物利用度

目的 :研究硝苯地平缓释微丸在家犬体内的药动学及生物利用度。方法 :家犬自身交叉对照分别口服单剂量硝苯地平缓释微丸 (A)和进口硝苯地平控释片 (B)各 30mg ,采用反相高效液相色谱法测定血药浓度 ,应用 3P87药动学程序对血药浓度数据进行拟合。结果 :硝苯地平缓释微丸和进口硝苯地平控释片的药动学参数 :Tmax分别为 3.4 7和 5 .4 1h ;Cmax分别为2 5 .7和 2 0 .2ng·mL-1 ;AUC0～∞ 分别为 2 1 6和 1 6 8mg·h·mL-1 。以B为参比制剂 ,单剂量给药时A的相对生物利用度为1 2 9%。结论 :两种制剂单剂量给药 30mg为生物不等效     

盐酸拉贝洛尔缓释片在犬体内的药代动力学研究

目的研究盐酸拉贝洛尔缓释片在犬体内单剂量和多剂量口服给药后的药代动力学过程.方法采用反相高效液相色谱法测定犬血浆中拉贝洛尔的浓度.流动相为乙腈-0.01 mol/L磷酸二氢钠(28∶72),色谱柱为Shimadzu VP-ODS,5μ, 150 mm×4.6 mm I.D.,检测波长218 nm,流速1.2 ml/min.动物试验分别采用12只健康成年犬,进行单剂量和多剂量给药,并于相应的时间点取血测定血浆中的药物浓度.结果所建立的HPLC-UV方法的最低检测浓度为0.10 μg/ml.12只犬按性别和体重区组随机口服两种拉贝洛尔制剂后(均为100 mg),测得普通片和缓释片拉贝洛尔的药动学参数分别为k=0.1187±0.0755 h-1和0.0984±0.0255 h-1,tmax1.15±0.49 h和3.83±1.17 h,cmax3.19±0.42和1.97±0.84 μg/ml.另采用12只犬按性别和体重区组随机实验设计多剂量口服两种拉贝洛尔制剂,5 d后血药浓度达到稳态水平,受试制剂和参比制剂的css分别为1.84±0.54和1.99±0.29 μg/ml(经剂量校正).结论缓释片与普通片相比,达峰时间有所延长,达峰浓度有所降低,多剂量给药后缓释片每天2次和普通片每天3次给药的波动度无差异,说明缓释片具有一定的缓释效果,多剂量给药后拉贝洛尔在犬体内的药代动力学特性未发生改变.     

家兔多剂量口服溴吡斯的明缓释片的药动学和生物利用度评价

目的 以溴吡斯的明普通片为对照,通过多剂量口服给药后,评价溴吡斯的明缓释片的药动学和生物利用。方法 6只新西兰兔随机分成2组,采用自身交叉对照实验,多剂量口服溴吡斯的明缓释制片或普通片后,采用高效液相色谱法测定血浆中溴吡斯的明浓度,计算药动学参数和相对生物利用度。 结果 溴吡斯的明普通片与缓释片给药后,药动学参数如下：tmax分别为（2.00 ± 0）h和（4.00 ± 0）h; Cmax 分别为（25.477 ± 0.177）mg•L-1和（19.236 ± 0.446）mg•L-1;AUC0-∞分别为（321.424 ± 4.955）mg•h•L-1和（370.083 ± 12.229）mg•h•L-1;与普通片相比,缓释片的相对生物利用度为119.15%。结论 溴吡斯的明缓释片具有缓释动力学特征,与普通片生物等效。     

氧化苦参碱生物黏附缓释片在Beagle犬体内的药动学

目的:考察氧化苦参碱生物黏附缓释片在Beagle犬体内的药动学过程.方法:建立LC-MS法同时测定Beagle犬血浆中的氧化苦参碱及其代谢产物苦参碱.采用BAPP 2.3程序估算犬服用市售普通胶囊(参比制剂)和氧化苦参碱生物黏附缓释片(受试制剂)后的药动学参数.结果:氧化苦参碱血药浓度.时间曲线符合双室模型特征.受试制剂的生物利用度为110.9,且cmsx降低、tmax延长,具有缓释效果.服用受试制剂后测得苦参碱的量为服用参比制剂后测得量的90.5%.结论:氧化苦参碱生物黏附缓释片与市售普通胶囊相比,生物利用度等效,具有明显的缓释效果.     

溴吡斯的明缓释片的药代动力学和相对生物利用度研究

目的 研究溴吡斯的明缓释片与其普通片在兔体内的药代动力学与相对生物利用度.方法 6只新西兰兔随机分成2组,采用自身交叉对照实验,单剂量口服溴吡斯的明缓释片或普通片后,采用高效液相色谱法测定血浆中溴吡斯的明浓度,计算药动学参数和相对生物利用度.结果 溴吡斯的明普通片与缓释片给药后,药动学参数如下:tmax分别为2 h和 ...     

硝苯啶缓释微球在兔体内的药物动力学及生物利用度

目的：研究自制的硝苯啶缓释微球在兔体内的药物动力学及生物利用度。方法：以瑞士产硝苯啶缓释片为参比对照品，以组间对照方式，给予新西兰兔单剂量口服１０ｍｇ缓释微球和对照品。用毛细管气相色谱法测定血浆中药物浓度。结果：硝苯啶缓释微球相对于缓释片的生物利用度为９９．７％，两种制剂的达峰时间、达峰浓度和体内驻留时间等参数均无显著性差异（Ｐ＞０．０５）。微球的体内吸收百分率与体外溶出百分率呈显著相关性（Ｐ＜０．０１）。结论：自制的硝苯啶缓释微球具有较好的生物利用度和缓释作用，与进口缓释片剂具有生物等价性。     

硫酸沙丁胺醇缓释片的制备及其在健康人体内的药动学研究

制备了硫酸沙丁胺醇骨架型缓释片（８ｍｇ／片），以释放度为指标筛选出了适宜处方，并对该处方缓释片与市售普通片对照进行了健康人体单剂量及多剂量随机交叉给药药动学研究。用高效液相荧光色谱法测定了血浆中的药物浓度。缓释片的药动学参数Ｔｍａｘ，Ｃｍａｘ，ＡＵＣ０→∞及ＰＴＦ（波动分数）分别为（４．６±０．８）ｈ，（７．９±１．４）ｎｇ／ｍｌ，（１２１．１±１２．３）ｈ·ｎｇ／ｍｌ及０．９３±０．２６，而普通片的相应药动学参数则分别为（１．４±０．４）ｈ，（１５．１±２．４）ｎｇ／ｍｌ，（１０３．３±８．７）ｈ·ｎｇ／ｍｌ及１．３１±０．２７。经双单侧检验两制剂ＡＵＣ０→∞无显著性差异，而ＰＴＦ则有显著性差异。缓释片相对于普通片的生物利用度为１０６．０％。缓释片具有给药次数少（一日二次）、给药后血药浓度波动较小的特点。     

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.     

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.