罗红霉素胶囊人体相对生物利用度研究

目的估算试验罗红霉素胶囊(T)的药代动力学参数及相对生物利用度,并以相同规格的罗红霉素胶囊作为参比制剂(R),判断两种胶囊是否具有生物等效性。方法22名健康志愿者单剂量口服罗红霉素胶囊(150mg)后48h内多点采集血样,微生物法测定人血清中罗红霉素的浓度。双周期两制剂交叉试验设计。血药浓度-时间数据经DAS软件处理后得药代动力学数据,并进行等效性检验。结果两种罗红霉素胶囊的血药浓度经时变化和药代动力学参数相近,AUC0～tT为(50.448±11.964)mg·h/L,AUC0～tR为(48.990±9.113)mg·h/L;AUC0～∞T为(50.538±12.806)mg·h/L,AUC0～∞R为(50.099±8.917)mg·h/L;CmaxT为(11.098±0.869)mg/L,CmaxR为(11.133±1.269)mg/L;TmaxT为(1.500±0.154)h,TmaxR(1.280±0.271)h;T1/2βT为(3.637±1.362)h,T1/2βR”为(3.522±0.575)h。以参比药作对照,计算罗红霉素的相对生物利用度,F为103.56%±19.67%,F′为100.91%±19.03%,均符合生物等效性要求。结论两种罗红霉素胶囊的口服生物利用度具有生物等效性。     

盐酸格拉司琼胶囊健康人体药代动力学研究

目的:建立测定人血浆中格拉司琼浓度的LC/MS/MS法,并应用于健康人体药代动力学研究.方法:12例健康受试者单剂量口服2 mg盐酸格拉司琼胶囊,LC/MS/MS法测定血浆中格拉司琼浓度,采用非房室模型统计矩法计算药代动力学参数.结果:单剂量口服2 mg盐酸格拉司琼胶囊后,主要的药代动力学参数Cmax、tmax 、t1/2、MRT、Cl/F、AUC0 24和AUC0-∞分别为(6.93±1.90)ng/ml,(1.35±0.29)h,(5.59±1.87)h,(8.05±1.84)h,(54.23±16.08)L/h,(36.61±8.87)ng·h·ml-1和(39.32±9.36)ng·h·ml-1.结论:本分析方法的准确度、灵敏度、专属性及定量线性范围等均符合生物样品的分析要求,适用于盐酸格拉司琼胶囊的人体药代动力学研究.     

巴马香猪多次灌胃洛伐他汀的药动学研究

目的 探讨巴马香猪多次灌胃洛伐他汀后体内药代动力学特征. 方法 5头雄性巴马香猪,连续7 d清晨空腹灌胃洛伐他汀2.4 ms/(kg·d),采用RP-HPLC法测定其血药浓度后,并计算药动学参数. 结果 巴马香猪连续灌胃洛伐他汀2.4 mg/(kg·d),给药第4,5,6天的谷浓度低于检测下限.第1天和第7天的药代动力学参数Tmax分别为(3.02±0.24),(2.87±0.26)h;Cmax分别为(11.04±0.67),(12.95±0.87)ng/ml;T1/2α分别为(2.79±0.15),(2.13±0.21)h;T1/2β分别为(2.93±0.27),(3.45±0.75)h;AUC分别为(94.57±14.23),(109.53±13.29)ng·h/ml;CL/F分别为(0.025±0.007),(0.022±0.005)ml/min均无统计学差异(P>0.05). 结论 巴马香猪多次灌胃洛伐他汀,药代动力学特点不改变,连续给药无蓄积,与洛伐他汀在人体的药代动力学特点相近,提示巴马香猪可作为洛伐他汀药代研究的良好模型,同时为药物代谢动力学的研究提供新的实验动物品种.     

米诺环素片生物等效性研究

目的:研究米诺环素片的药代动力学和相对生物利用度.方法:采用HPLC法测定20名健康男性志愿受试者随机自身交叉单剂量口服米诺环素片和米诺环素胶囊200 mg后的血药浓度,得出相应的药时曲线,计算各药代参数和相对生物利用度.结果:半衰期T1/2分别为(19.53±2.67)和(19.52±2.32)h,达峰时间Tmax分别为(1.72±0.41)和(1.72±0.70)h,峰值血浆浓度Cmax分别为(3.404±1.050)和(3.284±0.472)mg/L,药时曲线下面积AUC(0～60 h)分别为(62.50±11.77)和(56.93±7.33)(mg·h)/L.两种制剂的药动学参数差异无统计学意义(P>0.05),受试制剂的相对生物利用度(F)为111.5%.结论:两种制剂具有生物等效性.     

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。     

奥美拉唑肠溶胶囊的生物等效性研究

目的:研究奥美拉唑肠溶胶囊在健康人体的药代动力学,并评价其与同剂量制剂间的生物等效性。方法:采用双交叉试验设计,18名健康志愿者口服奥美拉唑肠溶胶囊试验和参比制剂40 mg,服药后0~12 h内间隔取血,用HPLC法测定血药浓度。计算主要药代动力学参数,并以参比制剂计算奥美拉唑肠溶胶囊的相对生物利用度,判断其生物等效性。结果:奥美拉唑肠溶胶囊试验和参比制剂的体内药代动力学参数Cmax(0.632±0.383)mg/L和(0.626±0.415)mg/L、5Tmax(2.39±0.40)h和(2.33±0.42)h、T1/2(1.92±0.64)h和(2.01±0.73)h、Vd/F(81.21±46.68)L和(94.07±89.46)L、CL/F(32.99±20.92)L/h和(31.68±20.41)L/h、AUC0→12(2.03±1.99)mg/(h.L)-1和(1.89±1.62)mg/(h.L)-1;受试奥美拉唑肠溶胶囊的相对生物利用度F=(104.7±17.7)%。结论:2种制剂具有生物等效性。     

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。     

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.     

慢性肝病患者单剂量静脉滴注异甘草酸镁药代动力学研究

目的 研究10例慢性肝病患者单剂量静脉滴注异甘草酸镁后的药代动力学,为临床合理用药提供依据.方法 所有受试者单剂量静脉滴注异甘草酸镁注射液100 mg (5%葡萄糖力注射液稀释到250 mL),采用高效液相色谱-紫外检测法测定各时间点血浆药物浓度.数据用3p97软件拟合处理,计算药代动力学参数.用SPSS软件比较慢性肝病患者与文献中健康志愿者体内的药代动力学参数.结果 异甘草酸镁在慢性肝损伤患者体内的血浆药代动力学特征表现为一级消除的二房室模型,单次静脉滴注异甘草酸镁100 mg 后的主要药代动力学参数:Cmax为(26.67±4.55)mg/L、t1/2α为(1.51±0.37)h、t1/2β为(27.60±7.82)h、Vd为(3.58±0.54)L、CLs为(0.19±0.04)L/h、AUC0-t为(460.8±77.9)mg·L-1·h-1,经t检验,与健康志愿者体内的药代动力学参数比较,差异无统计学意义(P>0.05).结论 异甘草酸镁在轻度慢性肝病患者体内消除半衰期约为27 h,有利于临床每天一次的给药方案.     

慢性肝病患者单剂量静脉滴注异甘草酸镁药代动力学研究

目的 研究10例慢性肝病患者单剂量静脉滴注异甘草酸镁后的药代动力学,为临床合理用药提供依据.方法 所有受试者单剂量静脉滴注异甘草酸镁注射液100 mg (5%葡萄糖力注射液稀释到250 mL),采用高效液相色谱-紫外检测法测定各时间点血浆药物浓度.数据用3p97软件拟合处理,计算药代动力学参数.用SPSS软件比较慢性肝病患者与文献中健康志愿者体内的药代动力学参数.结果 异甘草酸镁在慢性肝损伤患者体内的血浆药代动力学特征表现为一级消除的二房室模型,单次静脉滴注异甘草酸镁100 mg 后的主要药代动力学参数:Cmax为(26.67±4.55)mg/L、t1/2α为(1.51±0.37)h、t1/2β为(27.60±7.82)h、Vd为(3.58±0.54)L、CLs为(0.19±0.04)L/h、AUC0-t为(460.8±77.9)mg·L-1·h-1,经t检验,与健康志愿者体内的药代动力学参数比较,差异无统计学意义(P>0.05).结论 异甘草酸镁在轻度慢性肝病患者体内消除半衰期约为27 h,有利于临床每天一次的给药方案.     

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.