重组葡激酶在大鼠静脉注射给药后的药代动力学

目的　研究重组葡激酶 (r Sak)在大鼠静脉注射后的药代动力学。方法　大鼠静注r Sak 10 0、30 0与90 0 μg·kg-1,采用生物免疫发色底物法和牛奶板溶圈法测定活性 ,以单抗测定含量。结果　r Sak静注后 ,在大鼠体内过程符合二室模型。测定活性表明 ,3种剂量r Sak的T1/2α分别为 (1.79± 0 .76 )、(1.99± 0 .6 0 )及(2 .2 2± 1.0 1)min ;T1/2 β分别为 (2 0 .2 4± 11.15 )、(2 5 .32± 9.2 6 )及 (2 6 .45± 11.6 4)min ;AUC0 T 分别为(182 .88± 6 4.0 7)、(376 .2 6± 71.14)及 (1311.4± 36 9.4)HI·min·mL-1;测定含量表明 ,3种剂量r Sak的T1/2α分别为 (1.5 8± 0 .86 )、(1.2 2± 0 .5 7)及 (1.49± 0 .47)min ;T1/2 β分别为 (16 .5 8± 6 .75 )、(12 .94± 3.13)及 (15 .5 4± 3.88)min ;AUC0 T分别为 (2 .0 5± 0 .75 )、(5 .6 5± 2 .5 3)及 (13.18± 5 .43) μg·min·mL-1。结论　r Sak在大鼠体内过程符合二室模型 ,经方差检验 ,各剂量间药代动力学参数均无显著性差异 (P >0 .0 5 )。     

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 2 0mg/kg(用药组 )或生理盐水 (对照组 ) 4d后 ,静脉注射BSO 2 0 0mg/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 2 0 0mg/kg ,体内的动力学过程为二室模型 ,T1/2α为 2 7.4±5 .3min ,T1/2 β为 15 9.3± 10 7.3min ,CLs 为 11.8± 2 .3ml·min-1·kg-1,AUC为 2 99.36± 5 0 .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 2 5 .2± 2 .2min ,T1/2 β为 114 .3± 2 5 .9min ,CLs 为 13.8± 3.8ml·min-1·kg-1,AUC为 2 5 6 .5 5± 6 6 .2 8μg·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。     

青木香和冠心苏合胶囊中马兜铃酸A的药动学研究

目的研究青木香及复方制剂冠心苏合胶囊中马兜铃酸A在小鼠体内的药动学特点及小鼠在ig给予含相同量马兜铃酸A的青木香和冠心苏合胶囊后,马兜铃酸A的吸收、分布规律的差异。方法采用RP-HPLC法测定血浆中马兜铃酸A的量。色谱条件色谱柱为DiamonsilTMC18柱(250mm×4.6mm,5μm),流动相为甲醇-水-冰醋酸(72∶27∶1),体积流量为1.0mL/min,检测波长为315nm,柱温为20℃。结果药动学实验结果显示小鼠分别ig给予青木香和冠心苏合胶囊(相当于2.5mg/kg马兜铃酸A)后,其体内的药动学房室模型均符合一室模型,青木香中马兜铃酸A主要药动学参数t1/2ka、t1/2ke,tmax、AUC、Cmax分别为5.103min、43.63min、17.89min、80.45(μg·min)/mL、0.9168μg/mL;冠心苏合胶囊中相应的参数分别为5.294min、43.50min、18.32min、33.08(μg·min)/mL、0.3818μg/mL。结论小鼠给予含马兜铃酸A相同剂量的青木香和冠心苏合胶囊后,冠心苏合胶囊中马兜铃酸A的Cmax明显低于青木香中的Cmax,说明复方配伍作用可减少马兜铃酸A的吸收。     

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.     

水苏碱在大鼠体内的药动学

目的:研究水苏碱在大鼠体内的药动学。方法:采用柱前衍生化HPLC法,色谱条件为Kromasil C18色谱柱(4.6 mm×250 mm,5μm);流动相:甲醇-水(70∶30);流速:0.8 ml/min;检测波长:259 nm。从大鼠尾静脉注射盐酸水苏碱溶液,测定不同时间的血药浓度。用3P87药动学程序对血药浓度-时间数据进行拟合。结果:主要药动学参数为T1/2α(12.00min),T1/2β(101.07 min),Vc(0.298 L/kg),AUC(3833.456 min.μg/ml),CLs(0.0026 L.kg-1/min)。结论:水苏碱在大鼠体内呈二室开放模型。     

依替膦酸罗格列酮与马来酸罗格列酮的生物等效性研究

目的 研究依替膦酸罗格列酮在家犬体内药代动力学特征,并以马来酸罗格列酮为比较进行生物等效性研究.方法 采用随机、交叉自身对照试验,4只犬单次口服给予依替膦酸罗格列酮或马来酸罗格列酮0.43 mg/kg,用高效液相色谱法测定血浆中罗格列酮浓度.结果 罗格列酮单次口服后在体内呈1级吸收1室模型(权重为1)规律.依替膦酸罗格列酮的药动学参数为T1/2kα(32.829±16.46)min,T1/2ke(115.247 8±16.996 3)min,AUC(155.339 0±19.593 7)μg·ml-1·min,Cmax(0.820±0.119)μg/ml.马来酸罗格列酮为Ti/2kα(44.17±16.345 2)min,T1/2ke(107.596 5±21.161 2)min,AUC(158.830 7±16.070 5)μg·ml-1·min,Cmax(0.806±0.074)μg/ml.与马来酸罗格列酮比较,在同剂量(等摩尔浓度)下依替膦酸罗格列酮的相对生物利用度不低于马来酸罗格列酮.lnAUC0-540,lnAUC0-α和lnCmax均具有生物等效性.结论 依替膦酸罗格列酮的生物利用度与马来酸罗格列酮相似.     

A771726在大鼠体内的药代动力学

目的研究A771726在大鼠体内的药代动力学过程。方法单剂量口服给药3个剂量的A771726,根据大鼠体内血药浓度经时过程,计算相应的药代动力学参数。结果A771726(3、6、12mg/kg)的血药经时过程均符合一级吸收的一房室模型,其主要药动学参数T1/2Ka(h)3.91±3.43、5.63±2.07、6.73±1.67;T1/2Ke(h)17.45±10.79、9.68±4.65、7.63±1.39;AUC(0~tn)(mg/L.h-1)163.83±17.88、447.88±148.60、843.72±175.41;Cmax(mg/L)7.05±1.17、24.00±1.87、39.93±3.90;Tmax(h)8.00±0.00、6.67±2.06、8.00±0.00;MRT(0~tn)(h)19.87±4.25、19.54±1.11、19.29±2.47。结论单剂量口服A7717263个剂量组的药物代谢均成线性关系,其血药浓度-时间曲线符合一级吸收的一房室模型。     

红花黄色素A在大鼠体内的药动学研究

目的　研究红花黄色素 A在大鼠体内的药动学。方法　建立 RP-HPLC法定量测定大鼠血浆中红花黄色素 A含量。色谱条件 :色谱柱为 Hypersil ODS2柱 (2 0 0 mm× 4.6mm,5 μm) ;流动相为甲醇 -0 .2 %乙酸水溶液(2 4∶ 76) ;流速为 0 .8m L/min;核黄素为内标 ;检测波长为 410 nm。健康大鼠禁食 2 4h后 ,尾 iv红花黄色素 A生理盐水溶液 ,测定不同时间的血药浓度。用 3 P87药动学程序对血药浓度 -时间数据进行拟合。结果　大鼠 iv红花黄色素 A后 ,其主要药动学参数为 :Vc(0 .3 0± 0 .0 4) L/kg,CL (1.12± 0 .3 3 ) m L/mim,Ke(0 .91± 0 .19) h-1 ,t1 / 2(0 .76± 0 .10 ) h,曲线下面积 AUC(2 4.97± 4.83 ) (μg· h) /m L。结论　红花黄色素 A在大鼠体内呈一室开放模型 ,进入体内迅速分布 ,代谢消除也较快     

5-单硝酸异山梨酯缓释胶囊的人体相对生物利用度、释放度及药代动力学

目的　研究我国珠海和德国两家药厂研制的两种长效异乐定 5 0胶囊的人体相对生物利用度、释放度及药代动力学。方法　采用气相色谱法测定 2 1名健康志愿者血浆中 5 单硝酸异山梨酯 (5 ISMN)的浓度 ,采用液相色谱法测定释放度 ,计算两者的药代动力学参数、相对生物利用度。结果　口服 5 ISMN缓释试验胶囊后的药动学参数分别为 :tmax为 (5 .6 2± 0 .5 0 )h ,ρmax为 (4 5 0 .0 4± 95 .0 2 )ng/mL ,MRT为 (10 .85± 0 .79)h ,T1/ 2 为(6 .48± 0 .89)h ,AUC0～ 3 6h为 (6 90 5 .6 8± 130 0 .0 0 )ng/(mL·h) ,AUC0～∞ 为 (712 1.2 8± 135 4.78)ng/(mL·h) ;口服 5 ISMN缓释参比胶囊后的药动学参数分别为 :tmax为 (5 .5 7± 0 .75 )h ,ρmax为 (4 5 7.13± 98.0 0 )ng/mL ,MRT为 (10 .95± 0 .79)h ,T1/ 2 为 (6 .5 7± 0 .96 )h ,AUC0～ 3 6h为 (712 2 .0 2± 1439.90 )ng/(mL·h) ,AUC0～∞ 为(736 6 .6 8± 15 2 3.30 )ng/(mL·h)。结论　试验胶囊的AUC与参比胶囊相比 ,无显著性差异 ,试验胶囊与参比胶囊生物等效。试验胶囊平均相对生物利用度为 (98± 11) % (n =2 1,以AUC0～T计算 )。将试验胶囊和参比胶囊的药动学参数进行方差分析 ,无显著性差异     

UPLC-MS/MS法测定大鼠血浆甘草酸及其代谢物的浓度及药物动力学研究

目的 建立测定大鼠血浆中甘草酸及其代谢产物甘草次酸含量的超高效液相色谱-串联四极杆质谱(UPLC-MS/MS)方法，进行大鼠体内药物动力学研究。方法 采用ACQUITY UPLC BEH C₁₈(2.1 mm×150 mm, 1.7μm),以5 mmol/L乙酸铵(A)-乙腈(B)为流动相，梯度洗脱，流速0.3 mL/min,电喷雾离子源，负离子模式下，多反应监测(MRM)方式，以格列喹酮为内标；大鼠口服给药，取血后血样经甲醇沉淀蛋白，检测大鼠血药浓度。结果 甘草酸与甘草次酸血浆浓度在0.009 9～2.899 0μg/mL与0.040 0～26.890 0μg/mL范围内线性关系良好，方法学各项指标均符合要求。药动学参数甘草酸T_max为(1.83±0.41) h, C_max为(0.42±0.04)μg/mL,AUC_0-∞为(2.13±0.43) h·μg^-1·mL^-1,t_1/2为(16.74±8.45) h。代谢产物甘草次酸T     

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.