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.     

黄连、吴茱萸药对中盐酸小檗碱在急性胃溃疡模型大鼠体内的药代动力学研究

目的比较黄连-吴茱萸药对提取液中盐酸小檗碱在急性胃溃疡模型大鼠与正常大鼠体内的药代动力学差异,探讨病理状态对盐酸小檗碱体内过程的影响。方法分别灌胃给予正常大鼠和急性胃溃疡模型大鼠黄连-吴茱萸(6:1)药对提取液,采用高效液相色谱方法测定大鼠体内盐酸小檗碱的血浆浓度,色谱柱:Diamonsil C18(150mm×4.6mm,5μm);流动相:乙腈-甲醇-0.05mol/L磷酸二氢钾溶液(23∶12∶65),流速:1.0ml/min;检测波长:345nm;柱温:30℃。结果盐酸小檗碱在正常组的药代动力学参数:Cmax=0.064±0.01μg/ml;Tmax=(0.42±0.13)h;t1/2=(5.96±1.16)h;AUC0-t=(0.42±0.08)μg/(ml.h);AUC0-∞=(0.45±0.09)μg/(ml.h)。盐酸小檗碱在模型组的药代动力学参数:Cmax=(0.069±0.01)μg/ml;Tmax=(0.54±0.11)h;t1/2=(5.11±1.78)h;AUC0-t=(0.60±0.17)μg/(ml.h);AUC0-∞=(0.63±0.18)μg/(ml.h)。结论黄连-吴茱萸药对在乙醇致急性胃溃疡模型大鼠中吸收减慢,但是吸收量多,体内滞留时间稍延长。     

双氯芬酸钠肠溶片的血药浓度测定及人体药代动力学研究

目的:研究双氯芬酸在正常志愿者的血药浓度及体内的药代动力学,为临床用药提供依据.方法:16名健康男性志愿者,单剂量口服双氯芬酸钠肠溶片100mg,在不同时间点取静脉血,血药浓度采用高效液相色谱法(HPLC)测定.由血药浓度数据获得各自的主要药动力学参数.结果:志愿者单次服用100 mg双氯芬酸钠肠溶片后的药代动力学参数AUC0→∞、AUC0→8、Cmax、Tmax分别为(5.98±1.47)mg.h/L、(6.15±1.52)mg.h/L、(2.96±0.84)mg.h/L、(2.25±0.32)h.结论:双氯芬酸钠肠溶片在我国正常志愿者的药代动力学参数与国外的相似.     

苦参素片人体生物等效性研究

目的:进行苦参素片与苦参素胶囊的人体生物等效性研究,为新药报批及其临床应用提供依据。方法:将健康志愿者20名分为两组,分别于试验当日晨空腹1次口服苦参素片或苦参素胶囊600mg,于药前和药后取经时肘静脉血4ml,采用高效液相色谱法测定氧化苦参碱血浓度。计算试验制剂和参比制剂的药代动力学参数,评价两种制剂的生物等效性。结果:苦参素试验制剂和参比制剂主要药代动力学参数(以氧化苦参碱计)t1/2分别为(1.28±0.25)、(1.26±0.14)h,Tmax分别为(2.45±0.77)、(2.48±0.79)h,Cmax分别为(0.81±0.19)、(0.84±0.20)μg·ml鄄1,AUC0～6分别为(2.17±0.48)、(2.20±0.51)μg·ml·h鄄1,AUC0～∞分别为(2.41±0.56)、(2.43±0.60)μg·ml·h鄄1。试验制剂苦参素片相对生物利用度F(以氧化苦参碱计)为(99.56±12.32)%。结论:苦参素试验制剂和参比制剂单剂口服双交叉试验主要药代动力学参数无显著性差异,个体间、周期间和剂型间符合生物等效的假设,为生物等效制剂。     

苦参素胶囊在慢性乙肝患者体内的药代动力学研究

目的研究苦参素胶囊在慢性乙肝患者体内的药代动力学,比较其在慢性乙肝患者及健康受试者的药代动力学差异,以指导临床用药。方法10例慢性乙肝患者和10例健康受试者分别单次口服苦参素胶囊600mg,采用液相色谱-质谱法(liquid chromatography-mass spectrography,LC-MS),测定血浆中不同时间点的药物浓度,用DAS程序计算药代动力学参数。结果口服苦参素胶囊后其在慢性乙肝患者及健康受试者的体内过程均符合药代动力学二室模型,慢性乙肝患者和健康受试者的主要药代动力学参数分别为T1/2(Ka)(0.91±0.50),(0.99±0.42)h;T1/2(α)(1.40±1.17),(1.35±0.74)h;T1/2(β)(2.41±2.14),(2.15±1.51)h;tmax(2.30±0.89),(2.50±1.03)h;Cmax(396.78±67.86),(392.11±121.24)μg/L;V/F(8.94±13.42),(10.01±17.46)L/kg;AUC(0~12 h)(1 617.27±169.67),(1 723.08±531.65)μg/L.h-1;Cl/F(2.02±1.34),(2.30±1.69)L/h.kg-1。经统计学处理,2组药代动力学参数均无显著性差异(P>0.05)。结论苦参素胶囊在慢性乙肝患者和健康人体内的药代动力学过程无显著性差异。     

大鼠血浆中藏红花素的HPLC法测定及其药代动力学研究

目的建立大鼠血浆中藏红花素的RP-HPLC测定法,研究藏红花素的药代动力学特征。方法血样经乙腈预处理后,进行HPLC分析,色谱柱为Lichrospher C18(5 m,250 mm×4.6 mm),流动相为乙腈-甲醇-0.5%乙酸溶液(15:20:50,v/v)。10只健康大鼠肌肉注射藏红花素水溶液,计算主要药动学参数。结果在1.08~10.80μg/ml范围内藏红花素浓度与峰面积线性关系良好(r=0.9996),定量限为1.08μg/ml,日内精密度为1.86%~12.98%、日间精密度均小于为2.08%~9.75%,回收率为85.4%~91.7%。龙胆苦苷在家兔的主要药代动力学参数tmax、Cmax、t1/2和AUC分别为87.0 min、3.74μg/ml、140.4 min和768μg.min/ml。结论所建分析方法灵敏、准确、简便,适合于藏红花素的药代动力学研究。     

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.     

对乙酰氨基酚缓释干混悬剂在家犬体内的药代动力学及相对生物利用度

目的:研究单剂量口服对乙酰氨基酚缓释干混悬剂在家犬体内的药代动力学和相对生物利用度.方法:采用反相高效液相色谱法,测定6条成年健康家犬(体质量10.5～11.5 kg,雌雄各半)单剂量(650 mg/只)口服对乙酰氨基酚缓释干混悬剂(受试制剂)和对乙酰氨基酚控释片(泰诺林)(参比制剂)后不同时间点(给药前及给药后0.25、0.5、1.0、1.5、2.0、3.0、4.0、5.0、6.0、8.0、10.0、15.0和24.0 h)血浆中对乙酰氨基酚的浓度,绘制血药浓度-时间曲线,计算药代动力学参数及相对生物利用度.结果:本所建立的方法不受血浆中内源性物质的干扰,线性范围0.10～20.00 μg/ml(r=0.999 9),日内、日间精密度RSD＜7.0%,3种浓度(0.50、5.00、20.00μg/ml)的方法回收率分别为(104.21±6.57)%、(97.23±4.21)%、(99.57±1.19)%.对乙酰氨基酚缓释干混悬剂与参比制剂血浆中对乙酰氨基酚的tmax分别为(2.1±0.5)和(3.0±0.6)h;cmax分别为(9.09±3.58)和(8.77±3.40)μg/ml;用梯形法计算AUC0～24 h分别为(34.31±13.54)和(33.28±12.16)μg·h·ml-1,AUC0～∞分别为(34.96±13.46)和(33.88±12.18)μg·h·ml-1;受试制剂相对于参比制剂的平均生物利用度F0～∞为(102.58±10.15)%.结论:对乙酰氨基酚缓释干混悬剂与乙酰氨基酚控释片(泰诺林)在家犬体内的药代动力学过程相似,两种制剂具有生物等效性.     

抗高血压新药美林洛尔在大鼠体内的药代动力学和生物利用度

目的建立测定美林洛尔血药浓度的方法,探讨美林洛尔在大鼠体内的药代动力学及生物利用度。方法灌胃和静脉给予大鼠美林洛尔5 mg/kg,采用颈动脉取血并用高效液相-荧光法测定血浆中美林洛尔浓度,应用3P87药动学程序对血药浓度数据进行拟合,计算药代动力学参数,评价其绝对生物利用度。结果美林洛尔在0.02~3.00μg/ml浓度范围内与样品峰面积/内标峰面积呈良好线性关系,其相关系数r=0.9999。提取平均回收率大于80%,日内、日间RSD<10%。大鼠静脉注射美林洛尔后体内药动学符合开放双室模型,其分布相和消除相的半衰期分别为(4.22±5.58)min和(58.53±17.60)min。曲线下面积、中央室分布容积和血浆清除率分别为(133.40±9.27)(μg.min)/ml、(0.27±0.15)L/kg和(7.50±0.53)ml/(g.min)。灌胃给药符合开放单室模型,其达峰时间、最大血药浓度和药时曲线下面积分别为(14.29±3.28)min、(0.64±0.11)μg/ml和(54.35±9.34)(μg.min)/ml。结论建立的高效液相-荧光法专属性强、灵敏度高,可用于美林洛尔的体内定量分析。美林洛尔在大鼠体内的绝对生物利用度为40.74%。     

单剂口服利巴韦林片在健康人体的药代动力学研究探讨

目的:探讨单剂口服利巴韦林在健康人体的药代动力学研究情况。方法:遴选30名身体健康的男性志愿者,使用标准二阶段交叉设计研究法进行自身对照实验,分别单剂量口服两种利巴韦林片进行药代动力学研究,使用液相色谱-串联质谱检测法对志愿者服药后72小时内的血浆样本进行利巴韦林浓度检测。结果:A样品利巴韦林片的Tmax为(3.56±2.98)小时,Cmax为(209.21±67.21)μg/L,AUC(0-72h)为(5123.21±1562.21)μg.h/L;B样品利巴韦林片的Tmax为(3.31±2.67)小时,Cmax为(213.9±59.98)μg/L,AUC(0～72h)为(5098.87±1489.32)μg.h/L。两种利巴韦林片的主要药物动力学参数,没有显著性差异,P>0.05,没有统计学意义。结论:对两种利巴韦林片进行药代动力学研究发现,两种利巴韦林片具有生物等效性。     

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.