氧化苦参碱磷脂复合物肠溶缓释胶囊在小鼠体内的药代动力学及相对生物利用度研究

目的:研究氧化苦参碱磷脂复合物肠溶缓释胶囊在小鼠体内的药代动力学及相对生物利用度。方法 :84只健康昆明种小鼠,随机分为两组,在规定时间内采血,用高效液相色谱法(HPLC)测定小鼠经灌胃氧化苦参碱及氧化苦参碱磷脂复合物肠溶缓释胶囊内容物后的血药浓度。以PKSolver 2.0药动学软件进行曲线拟合,按口服吸收单房室模型计算药动学参数。结果:小鼠灌胃给药氧化苦参碱及氧化苦参碱磷脂复合物肠溶缓释胶囊内容物后的浓度-时间曲线均符合口服吸收单房室模型,氧化苦参碱及氧化苦参碱磷脂复合物肠溶缓释胶囊的达峰时(Tmax)分别为(1.14±0.17)h和(1.91±0.22)h,峰浓度(Cmax)分别为(2.59±0.07)μg/m L和(3.48±0.87)μg/m L,血药浓度-时间曲线下面积(AUC)分别为(8.11±1.24)μg/m L·h和(17.46±2.16)μg/m L·h。结论:氧化苦参碱磷脂复合物肠溶缓释胶囊的相对生物利用度为215.29%,能显著提高氧化苦参碱的生物利用度。     

健康受试者口服复方替米沙坦片后替米沙坦的药动学研究

目的 建立口服复方替米沙坦片后替米沙坦血药浓度的液相色谱-质谱(LC-MS/MS)测定法,进行人体药动学研究.方法 20名健康受试者随机分成两组,分别口服低剂量(1片)和高剂量(2片)受试制剂复方替米沙坦片,应用LC-MS/MS法测定样品中替米沙坦的血药浓度.结果 健康受试者单次口服低剂量复方替米沙坦片后,主要药代动力学参数cmax为(111±75)μg/L,tmax为(1.74±1.1)h,AU0-t为(1 186±877)μ·h·L-1,AUC0-∞为(1 268±935)μg·h·L-1,t1/2为(17.6±3.3)h,CLz/F为(52.7 ±35.7)L/h,Vz/F为(1 268±840)L,MRT为(16.8±3.7)h.单次口服高剂量复方替米沙坦片后,主要药代动力学参数cmax为(651±449)μg/L,tmax为(1.3±0.7)h,AUGM0-t为(4 201±3 052)μg·h·L-1,AUC0-∞为(4 477±3 313)μ·h·L-1,t1/2为(17.7±4.5)h,CLz/F为(41.64±51.9)L/h,Vz/F为(959±1 231)L、MRT为(15.0±2.7)h.结论 本方法结果准确、灵敏度高,替米沙坦进人人体分布后,其主要药动学参数与文献报道的单方替米沙坦数据一致.     

阿昔洛韦片在健康人体内的药代动力学及相对生物利用度

目的 测定阿昔洛韦片在健康人体内的药代动力学参数及相对生物利用度.方法 18名健康男性志愿者单剂量随机交叉口服500 mg阿昔洛韦片后,用高效液相色谱法测定血浆药物浓度.结果 口服海南金晓制药有限公司或天津药业集团新郑股份有限公司生产的阿昔洛韦片后的药代动力学参数分别为:T12(4.53±0.59)h和(4.65±0.55)h,Cmax分别为(451.08±77.19)μg·L-1(454.88±72.62)μg·L-1,Tmax分别为(1.67±0.24)h和(1.72±0.31)h,AUG01(2 312.1±372.2)μg·h·L-1和(2 249.8±258.9)μg·h·L-1.AuCo→∞.分别为(2 516.6±393.0)μg·h·L"和(2 446.1±272.5)μg·h.·L-1.两种阿昔洛韦片主要药动学参数间均无统计学意义(P＞0.05),受试阿昔洛韦片的相对生物利用度F为103.01%.结论 两种制剂具有生物等效性.可确保临床用药的安全有效.     

环磷酰胺对丁硫氨酸亚砜胺在大鼠体内的药代动力学影响

目的研究环磷酰胺(CTX)对丁硫氨酸亚砜胺(BSO)在SD大鼠体内的药代动力学的影响. 方法 SD大鼠腹腔注射CTX 20mg/kg(用药组)或生理盐水(对照组)4d后,静脉注射BSO 200mg/kg.以邻-苯二甲醛(OPA)柱前衍生反相HPLC为检测手段,测定血浆中BSO的浓度.以3P87软件对实验数据进行拟合,判断房室模型并计算药代动力学参数. 结果 SD大鼠静脉注射BSO 200mg/kg,体内的动力学过程为二室模型,T1/2α为27.4±5.3min, T1/2β为159.3±107.3min,CLs为11.8±2.3ml*min-1*kg-1,AUC为299.36±50.13μg*ml-1*h;SD大鼠在用CTX后,BSO在其体内动力学特征也是二室模型,T1/2α为25.2±2.2min,T1/2β为114.3±25.9min,CLs为13.8±3.8ml*min-1*kg-1,AUC为256.55±66.28μg*ml-1*h.用药组和对照组的药代动力学参数无显著性差异.结论 CTX不影响BSO在大鼠体内的药代动力学过程.     

葛根素及其磷脂复合物在Beagle犬体内的药动学比较

目的研究葛根素及其磷脂复合物中葛根素在B eag le犬体内药动学。方法采用HPLC法测定犬血中葛根素,以同组犬(3只,雄性)交叉口服葛根素及其磷脂复合物,药-时曲线数据经3P 97药动学计算程序处理。结果分别以葛根素及其磷脂复合物给B eag le犬口服(剂量为葛根素52.5 m g/kg),葛根素的药-时过程符合开放型双室一级动力学模型,葛根素口服的AUC、Cm ax、tm ax分别为(10.91±4.83)m g.h/L、(3.00±1.13)m g/L、(1.62±0.30)h,而葛根素磷脂复合物的AUC、Cm ax、tm ax分别为(13.67±2.72)m g.h/L、(1.91±0.51)m g/L、(2.38±1.27)h,统计结果表明AUC之间差异有显著性。结论形成磷脂复合物可提高葛根素在B eag le犬体内的吸收。     

HPLC法测定芎?汤活血有效部位中阿魏酸在大鼠体内药代动力学特征

目的:研究大鼠灌服芎?汤活血有效部位后,有效成分阿魏酸在大鼠体内的药物代谢动力学规律。方法:大鼠灌服活血有效部位后,采集不同时间点的大鼠血样,采用HPLC法测定血样中阿魏酸的血药浓度并计算其药代动力学参数,建立药物代谢曲线。结果:阿魏酸在0.6132~81.76μg·m L-1范围内线性关系良好,方法回收率均大于86%,日内日间精密度RSD均小于3%,其主要药动学参数分别为t1/2(37.8400±8.4090)min、Cmax(59.4200±17.9400)μg·m L-1、AUC0-t(4815.7100±57.3400)μg·m L-1·min-1。结论:本试验建立了芎?汤活血有效部位中有效成分阿魏酸在大鼠血浆中的HPLC测定方法,可用于大鼠血浆中阿魏酸血药浓度的测定及药动学研究。     

吴茱萸碱新型纳米乳在大鼠体内的药代动力学及生物等效性

目的 建立HPLC法测定吴茱萸碱新型纳米乳(evodiamine novel nano emulsion,ENNE)中吴茱萸碱(evodiamine,EVO)在大鼠体内的血药浓度,研究ENNE在大鼠体内的药代动力学行为,比较ENNE与EVO的生物等效性.方法 12只SD大鼠平均分为两组,分别灌胃给予ENNE(相当于EVO 100 mg/kg)与EVO(100mg/kg),采用HPLC法测定5 min、10 min、15 min、30 min、45min、1h、2h、5h、8h、12 h、24 h、48 h、72 h大鼠体内EVO的血药浓度.HPLC法色谱条件:流动相为甲醇-0.1％甲酸水溶液(66∶34,体积比),流速为1.0mL/rmin,进样体积为100 μL,检测波长为225nm.绘制血药浓度-时间曲线,用DAS 2.1.1软件计算主要药代动力学参数与生物等效性.结果 建立的HPLC法线性关系良好,准确度与精密度符合分析方法学要求.ENNE与EVO的AJC0-∞分别为(8 248.88±69.92)μg·h·L-1、(884.82±83.52) μg·h·L-1,半衰期分别为(1.70±0.60)h、(1.05±0.45)h.ENNE的相对生物利用度约为EVO的9倍,半衰期约为EVO的1.62倍,ENNE与EVO不具有生物等效性.结论 ENNE较EVO更能促进药物的吸收,提高生物利用度;ENNE与EVO不具生物等效性.     

格列吡嗪片的药代动力学及相对生物利用度

目的 测定格列吡嗪片在健康人体的药代动力学参数及相对生物利用度.方法 18名健康男性志愿者单剂量随机交叉口服10 mg格列吡嗪片后,用高效液相色谱法测定血浆药物浓度.结果 口服海南金晓制药有限公司或天津药业集团新郑股份有限公司生产的格列吡嗪片后的药代动力学参数分别为:T1/2(3.239±0.69)h和(3.461±0.59)h,Cmax(675.3±151.7)mg·L-1和(647.1±166.7)mg·L-1,Tmax(2.389±0.50)h和(2.333±0.49)h,AUC0-t(3565.4±733.4)μg·h·L-1和(3304.8±588.4)μg·h·L-1.两种格列吡嗪片主要药代动力学参数间无统计学意义(P＞0.05),受试格列吡嗪片的相对生物利用度F为93.204%.结论 两种制剂具有生物等效性,可确保临床用药的安全有效.     

对乙酰氨基酚在大鼠体内药动学研究

目的应用反相高效液相色谱法（RP-HPLC）测定大鼠血浆中对乙酰氨基酚浓度,研究单剂量口服不同剂量对乙酰氨基酚片在大鼠体内的药代动力学。方法3组SD大鼠分别按体重单剂量口服对乙酰氨基酚片300 mg/kg、600 mg/kg、1 200 mg/kg后,采用RP-HPLC测定血浆中药物的浓度,绘制血药浓度-时间曲线,计算其药代动力学参数。结果3个剂量组的对乙酰氨基酚药-时曲线均符合口服吸收的一级动力学二室模型,主要药代动力学参数：Tmax分别为（0.78±0.17）h、（1.07±0.12）h、（1.19±0.12）h;Cmax分别为（158.99±26.08）μg/ml、（226.26±20.38）μg/ml、（402.95±86.46）μg/ml;T1/2kα分别为（0.24±0.09）h、（0.39±0.11）h、（0.43±0.14）h;T1/2ke分别为（3.78±0.33）h、（3.66±0.32）h、（4.33±0.47）h;AUC0→24分别为（718.71±143.03）μg·h^-1·ml^-1（1 578.53±246.76）μg·h^-1·ml^-1（3 734.67±665.58）μg·h^-1·ml^-1AUC0→∞分别为（757.16±155.29）μg·h^-1·ml^-1（1 594.61±247.11）μg·h^-1·ml^-1（3 847.99±692.03）μg·h^-1·ml^-1结论所建立RP-HPLC法能够准确地测定对乙酰氨基酚血药浓度,能满足药代动力学的研究需求;低剂量组和中剂量组的药代动力学过程基本相似,但高剂量组则与上述两组则有所不同,这可能与其剂量过高有关。     

RP-HPLC法测定人血浆奥氮平浓度及其在健康志愿者的药代动力学研究

目的建立测定人血浆中奥氮平浓度的高效液相色谱法并进行药代动力学研究。方法10名男性健康志愿者单剂量口服奥氮平片20mg,血浆样品经液-液提取,用高效液相色谱法检测奥氮平的浓度,并用3P97程序进行数据处理。结果此方法适用于人血浆中奥氮平浓度的检测。单剂量口服奥氮平后,其血浆药-时曲线符合二室模型;主要药代动力学参数Cmax、Tmax、t1/2、AUC0-144、AUC0-inf分别为(113.7±33.1)μg·L-1、(5.07±0.65)h、(35.44±4.21)h、(2235±257)μg·h·L-1和(2516±301)μg·h·L-1。结论该方法灵敏、准确,能快速检测人血浆中奥氮平浓度。     

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.     

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.