重组人内皮抑素的125Ⅰ标记及其体内代谢

目的探讨重组人内皮抑素(rhEndo)的125Ⅰ标记及其标记物(125Ⅰ-rhEndo)的生物学活性和体内药代动力学.方法采用小剂量Iodogen多次重复标记法标记rhEndo,细胞增殖抑制试验和亲和力试验检测125Ⅰ-rhEndo活性,并研究其在大鼠体内的药代动力学.结果0.5μg Iodogen 3次重复标记rhEndo的标记率可达84%,放射化学纯度(94.7±2.44)%.125Ⅰ-rhEndo抑制bFGF诱导内皮细胞增殖的作用与未标记rhEndo相当,且能与其竞争结合内皮细胞表面受体.大鼠单次股静脉注射125Ⅰ-rhEndo 2 μg后,血药浓度-时间曲线符合两室模型,T1/2α为(0.45±0.12)h,T1/2β为(19.53±3.41)h,AUC为(484.57±137.99)ng·h·mL-1.结论小剂量Iodogen多次重复125Ⅰ标记不影响rhEndo蛋白的生物学活性.125Ⅰ-rhEndo大鼠体内单次静脉注射的药代动力学符合两室模型,半衰期约19 h.125Ⅰ-rhEndo标记为肿瘤的靶向显像和治疗奠定了基础.     

重组人内皮抑素的~(125)I标记及其体内代谢

目的探讨重组人内皮抑素(rhEndo)的~(125)I标记及其标记物(~(125)I-rhEndo)的生物学活性和体内药代动力学。方法采用小剂量Iodogen多次重复标记法标记rhEndo,细胞增殖抑制试验和亲和力试验检测~(125)I-rhEndo活性,并研究其在大鼠体内的药代动力学。结果0.5μg Iodogen3次重复标记rhEndo的标记率可达84%,放射化学纯度(94.7±2.44)%。~(125)I-rhEndo抑制bFGF诱导内皮细胞增殖的作用与未标记rhEndo相当,且能与其竞争结合内皮细胞表面受体。大鼠单次股静脉注射~(125)I-rhEndo2μg后,血药浓度-时间曲线符合两室模型,T1/2α为(0.45±0.12)h,T1/2β为(19.53±3.41)h,AUC为(484.57±137.99)ng·h·mL-1。结论小剂量Iodogen多次重复~(125)I标记不影响rhEndo蛋白的生物学活性。~(125)I-rhEndo大鼠体内单次静脉注射的药代动力学符合两室模型,半衰期约19h。~(125)I-rhEndo标记为肿瘤的靶向显像和治疗奠定了基础。     

重组人内皮抑素的^125I标记及其体内代谢

目的探讨重组人内皮抑素(rhEndo)的125Ⅰ标记及其标记物(125Ⅰ-rhEndo)的生物学活性和体内药代动力学.方法采用小剂量Iodogen多次重复标记法标记rhEndo,细胞增殖抑制试验和亲和力试验检测125Ⅰ-rhEndo活性,并研究其在大鼠体内的药代动力学.结果0.5μg Iodogen 3次重复标记rhEndo的标记率可达84%,放射化学纯度(94.7±2.44)%.125Ⅰ-rhEndo抑制bFGF诱导内皮细胞增殖的作用与未标记rhEndo相当,且能与其竞争结合内皮细胞表面受体.大鼠单次股静脉注射125Ⅰ-rhEndo 2 μg后,血药浓度-时间曲线符合两室模型,T1/2α为(0.45±0.12)h,T1/2β为(19.53±3.41)h,AUC为(484.57±137.99)ng·h·mL-1.结论小剂量Iodogen多次重复125Ⅰ标记不影响rhEndo蛋白的生物学活性.125Ⅰ-rhEndo大鼠体内单次静脉注射的药代动力学符合两室模型,半衰期约19 h.125Ⅰ-rhEndo标记为肿瘤的靶向显像和治疗奠定了基础.     

~(99)Tc~m-MAG_3-K237的制备及其在健康动物体内的药代动力学和分布研究

目的探讨99Tcm标记血管内皮生长因子受体2(vascular endothelial growth factor receptor-2,VEGFR-2,KDR)小分子拮抗肽K237的方法,研究标记物在健康动物体内的药代动力学特性及体内分布特点。方法化学方法合成制备MAG3-K237,并用99Tcm标记;鉴定标记物的理化性质;测定标记物经新西兰大白兔静脉注射后不同时相血液放射性浓度,得出最佳房室模型与药代动力学参数;分别测定经尾静脉注射7.4MBq标记物后的昆明小鼠各器官质量和放射性计数,经参考源校正后计算各脏器每克组织百分注射剂量率(%ID/g);经耳缘静脉注射37MBq标记物,在SPECT下观察其在兔体内的动态分布。结果99Tcm-MAG3-K237的放化纯度为(97.98±0.76)%,比活度为(3.54±0.03)TBq/mmol;室温(25℃)下保存8h后放化纯度为(96.15±0.37)%;半胱氨酸置换率为0.2%～0.37%;不与血清蛋白结合;兔体内动力学过程符合权重为1/c2的三室模型,快分布相半衰期(t1/2α)、慢分布相半衰期(t1/2β)及消除相半衰期(t1/2γ)分别为(4.00±3....     

125I标记的[Tyr3]-Octreotide在小鼠体内的分布及其药代动力学研究

目的 探讨^125ICh-T法标记生长抑素类似物奥曲肽的方法，观察其在小鼠体内的生物学分布。方法用Ch-T法进行[Tyr3]-octreotide的^125I标记，标记完成后加入NH4HAc以防止标记物的再氧化。SephadexG-10分离纯化，纸层析测定放化纯，并行小鼠体内分布和药代实验。结果 ^125I[Tyr^3]-octreotide比活度为5.92TBq／mmol。标记率为76％，放化纯为95％。注射后1．0h血液中放射性下降了90％，肠道、肝脏和肾脏中均有浓集，标记物24h内排出体外。结论 ^125I的Ch-T法标记[TyT^3]-octreotide放化纯高，方法简便，标记物的稳定性尚可。^125I-[TyT^3]-octreotide在小鼠体内血液清除快，药代动力学符合二室开放模型，T1/2a为5．28min，T1/2β为141.3min，经肠-肝途径和泌尿系统排除。     

聚乙二醇修饰干扰素α2b的体内药代动力学研究

目的：运用同位素示踪法－^125I标记和SDS－PAGE研究聚乙二醇修饰干扰素2b的药代动力学。方法：以大鼠为研究对象,分别按1,3,5μg／kg的的剂量股静脉注射给药,颈动脉采血。利用SDS－PAGE测定血液中原形药物放射量与总放射量的百分比,以校正全血血药浓度。用小鼠测定^125I－干扰素α2b和^125I－单修饰干扰素α2b的组织分布和尿粪排泄,用大鼠测定其胆汁排泄。结果：^125I－干扰α2b和^125I－单修饰干扰素α2b静脉注射给药符合一级消除动力学的二房室模型,按低,中,高三个剂量组,^125I－干扰α2b的消除半衰期（t1/2β）分别为1．020,0．914,0．665h,^125I－单修饰干扰素α2b的消除半衰期（t1/2β）分别为2．72,3．17,2．69h,^125I－单修饰干扰素α2b在肾中的分布明显减少,在肝中的分布明显增加。结论：聚乙二醇修饰能够显著延长干扰素α2b的体内半衰期。     

乙胺碘呋酮及其主要代谢产物的临床药代动力学和药效学研究 专业:药学(临床药理)

按用药时间不同,将14例过速性心律失常病人分为两组。采用静脉注射给药方式,观察给药后乙胺碘呋酮及其主要代谢产物去乙基乙胺碘呋酮在病人体内药代动力学及药效学变化。采用静脉注射二房室模型对药物在体内动力学过程进行拟合。乙胺碘呋酮在单剂量静脉注射病人体内α分布相的半衰     

放射性核素示踪法对多肽VEGF125-136在家兔体内的药代动力学研究

目的 探讨VEGF125-136在家兔体内的药代动力学.方法 采用放射性核素99Tcm对VEGF125-136进行间接标记.测定6 只家兔静脉注射37 MBq 99Tcm-VEGF125-136后不同时间血浆中药物的放射性浓度,用DAS软件编制放射性浓度-时间曲线,并计算药代动力学参数.结果 99Tcm-VEGF125-136的放射化学纯度大于97%,99Tcm-VEGF125-136在家兔体内的代谢符合三室模型,快分布相半衰期(t1/2α)为(5.327±2.351) min,慢分布相半衰期(t1/2β)为(26.446±6.502) min,消除相半衰期(t1/2γ)为(304.41±216.811) min,转运速率常数K10、K12、K21 、K31 及K13分别为(0.047±0.034)、(40.65±68.54)、(0.111±0.058)、(0.111±0.058) min-1及(0.002±0.004) min-1,清除率(CL)为(4.00±1.00) ml/min.结论 VEGF125-136在家兔体内的药代动力学符合三室模型,且血液清除快而周边血管丰富的组织停留时间相对较长.     

重组人纤溶酶原Kringle 5的体内药代动力学及应用价值

目的 研究纤溶酶原Kringle 5体内药代动力学及其显像和治疗价值.方法 应用基因工程技术重组人纤溶酶原Kringle5(rhK5),Iodogen法和直接法分别制备123I-rhK5、131I-rhK5和99mTc-rhK5.MTT比色法检测rhK5、125I-rhK5和99mTc-rhK5的活性.应用3p87程序分析125I-rhK5的药代动力学.制作肺癌移植瘤裸鼠模型,按3.7 MBq经尾静脉注射99mTc-rhK5,于不同时间点观察显像情况.按7.4 MBq经尾静脉注射131I-rhK,观察肿瘤生长及其微血管密度(MVD)和血管内皮生长因子(VEGF)表达,同时设立单纯rhK5蛋白治疗组和阴性对照组进行比较分析.结果 125I-rhK5、131I-rhK5和99mTc-rhK5的标记率分别为86%、84%、90%,放化纯度均＞90%;活性检测发现,标记与未标记rhK5之间无显著差异;125I-rhK5经尾静脉单剂量给药后,选择二室模型拟合药-时曲线,分布相半衰期(T1/2(a))为(0.31±0.03)h,清除相半衰期(T1/2(β))为(14.48±0.73)h,药-时曲线下面积(AUC)为(436.58±34.60)ng·mL-1·h-1.注射99mTc-rhK5后1 h可见放射性浓聚,4 h显像更趋清晰,肿瘤部位呈"热区".与rhK5蛋白治疗组和阴性对照组比较,131I-rhK5治疗组肿瘤生长明显受到抑制(抑瘤率为34.14%),且MVD和VEGF表达显著减少.结论 核素标记rhK5进行肿瘤显像和治疗是可行的.rhK5体内应用每天注射1次即可,为体内用药提供了实验依据.     

五加皮Age蛋白的药动学研究

目的研究五加皮Age蛋白的药动学特征。方法采用氯胺T法用125I标记Age蛋白,形成125I-Age复合物。S180荷瘤小鼠iv给药后,采用同位素示踪法结合SDS-PAGE电泳测定血浆中Age蛋白质量浓度。用3P87药动学软件分析血浆中Age蛋白的药动学参数。结果小鼠iv125I-Age后,Age蛋白在体内的代谢符合二房室分布模型。按剂量50、100、200μg/kgiv后,测得Age蛋白分布相半衰期(t1/2α)分别为0.34、0.45、0.26h,消除相半衰期(t1/2β)为14.13、16.49、17.42h,全身清除率(CLs)为0.0454、0.0491、0.0533mL/(h·kg)。结论Age蛋白在荷瘤小鼠体内药动学行为符合线性二室模型,在体内的分布和消除均较慢。     

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.