盐酸曲马多缓释片的制备及药动学研究

研制了盐酸曲马多缓释片，其体外溶出符合一级动力学过程，释药常数Ｋｒ＝０．１９８ｈ＾－１。盐酸曲马多体内吸收符合一室模型，药动学参数为Ｋａ＝０．５７０２ｈ＾－１，Ｋ＝０．０８５６ｈ＾－１，Ｃｍａｘ＝２１９．５７ｎｇ／ｍｌ、Ｔｍａｘ＝４．６２ｈ，ＡＵＣ０→∞＝３７２１．０９ｎｇ／ｍｌ．ｈ。经双单侧ｔ检测，结果表明普通胶囊与缓释片的Ｃｍａｘ、Ｔｍａｘ具有显著性差异，而ＡＵＣ０→∞无差异，表明两制剂生物等     

单硝酸异山梨酯缓释片的释放度及相对生物利用度

对试制的单硝酸异山梨酯缓释片与德国麦克乐制药公司（ Ｍｅｒｃｋｌｅ Ｇｍｂ Ｈ） 缓释胶囊剂进行体外释放度、体内血浓测定比较;体外含量测定采用 Ｈ Ｐ Ｌ Ｃ 法,体内采用 Ｇ Ｃ 法。体内数据按口服单室模型,经计算机处理求得药动学参数：缓释胶囊： Ｋａ ＝ ０ ．２５０ ｈ － １ , Ｋｅ ＝ ０ ．１３７９ ｈ － １ , Ｔｍ ａｘ ＝ ５ ．３６ ｈ , Ｃｍ ａ ｘ ＝ ３５１ ．９８ ｎｇｍｌ, Ａ Ｕ Ｃ０ →∞ ＝５３８２ ．７９ ｈ·ｎｇｍｌ , Ｆ Ｉ＝ １ ．８６ 。缓释片： Ｋａ ＝ ０ ．２４７９ ｈ － １ , Ｋｅ ＝ ０ ．１４０３ ｈ － １ , Ｔｍ ａｘ ＝ ５ ．３５ ｈ , Ｃｍａ ｘ ＝ ３７７ ．０９ ｎｇｍｌ , Ａ Ｕ Ｃ０ →∞ ＝ ５７２８ ．５１ ｈ·ｎｇｍｌ , Ｆ Ｉ＝ １ ．９７ 。研制的单硝酸异山梨酯缓释片对德国麦克乐制药公司缓释胶囊相对生物利用度为（１０６ ．２８ ±３ ．４３） ％ 。     

硫酸沙丁胺醇缓释片的制备及其在健康人体内的药动学研究

制备了硫酸沙丁胺醇骨架型缓释片（８ｍｇ／片），以释放度为指标筛选出了适宜处方，并对该处方缓释片与市售普通片对照进行了健康人体单剂量及多剂量随机交叉给药药动学研究。用高效液相荧光色谱法测定了血浆中的药物浓度。缓释片的药动学参数Ｔｍａｘ，Ｃｍａｘ，ＡＵＣ０→∞及ＰＴＦ（波动分数）分别为（４．６±０．８）ｈ，（７．９±１．４）ｎｇ／ｍｌ，（１２１．１±１２．３）ｈ·ｎｇ／ｍｌ及０．９３±０．２６，而普通片的相应药动学参数则分别为（１．４±０．４）ｈ，（１５．１±２．４）ｎｇ／ｍｌ，（１０３．３±８．７）ｈ·ｎｇ／ｍｌ及１．３１±０．２７。经双单侧检验两制剂ＡＵＣ０→∞无显著性差异，而ＰＴＦ则有显著性差异。缓释片相对于普通片的生物利用度为１０６．０％。缓释片具有给药次数少（一日二次）、给药后血药浓度波动较小的特点。     

环孢素胶丸的药代动力学和相对生物利用度

采用高效液相色谱法进行环孢素胶丸的药代动力学和生物利用度研究，１０名健康志愿者随机交叉单剂量ｐｏ温州第二制药厂和瑞士Ｓａｎｄｏｚ公司的环孢胶丸（２００ｍｇ），其血药浓度－时间曲线均符合一级吸收的双室模型，温州产环孢素胶丸的主要药动学参数ｔ１／２Ｋｄ＝１．０９±０．４６ｈ，ｔ１／２α＝０．３４±０．１５ｈ，ｔ１／２β＝５．１３±１．４１ｈ，ｔｍａｘ＝１．１９±０．１９ｈ，Ｃｍａｘ＝８７８．２±１６７．２ｎｇ／ｍｌ，ＡＵＣ＝４１２７．７±８５４．１ｎｇ·ｈ·ｍｌ－１，其相对生物利用度为（１０４．２±１１．９）％     

人血浆中盐酸氟桂嗪HPLC测定及其药代动力学

建立了盐酸氟桂嗪的ＨＰＬＣ测定法。血浆样品碱化后用正已烷提取，以ＭｉｃｒｏＰａｃＭＣＨ－５为固定相，６５％甲醇，３５％水（含０．０２ｍｏｌ／Ｌ四丁基溴化铵，ｐＨ３．０）为流动相，紫外检测波长２５４ｎｍ。最低检出浓度为５．０ｎｇ／ｍｌ，线性范围１０．０～２００．０ｎｇ／ｍｌ（ｒ＝０．９９９８，ｎ＝６），平均回收率为（９７．５５±２．６８）％（ＲＳＤ２．１３％。用本法测定了８名健康男性志愿者分别服用杨森产盐酸氟桂嗪胶囊和新昌产盐酸氟桂嗪片剂的血药浓度。结果表明，其血药浓度－时间曲线均符合一房室模型。新昌产盐酸氟桂嗪片的主要药代动力学参数Ｔ１／２Ｋａ＝（０．７７±０．１１）ｈ，Ｔ１／２Ｋｅ＝（５．０７±０．５２）ｈ，Ｔｍａｘ＝（２．７９±０．２４）ｈ，Ｃｍａｘ＝（９５．００±４．５２）ｎｇ／ｍｌ，ＡＵＣ＝（９９７．６±６２．５）ｎｇ·ｈ／ｍｌ，相对生物利用度为９６．４％。     

用化学发光法研究家兔穿心莲内酯的药物动力学参数

穿心莲内酯是穿心莲的主要有效成分之一，为了解穿心莲内酯药动学与药效学的关系，本文采用高灵敏的有机偶合化学发光法对穿心莲内酯的血药浓度进行监测，求出系列药动学参数。实验表明，穿心莲内酯在动物体内达峰快，消除半衰期长，生物利用度高。它的几个主要药动学参数为：Ｋａ＝１．３４３ｈ－１±０．０８，Ｋ１２＝０．３３６ｈ－１±０．０１，Ｋ２１＝０．６３３ｈ－１ｈ±０．０６，Ｔ１／２（α）＝０．６９２ｈ±０．０７，ｔ１／２（β）＝１２．１２ｈ±１．９，ＡＵＣ＝５０１．０９μｇ．ｈ／ｍＬ±９．８。     

枸橼酸他莫昔芬片剂的药代动力学和相对生物利用度研究

采用高效液相色谱法进行枸橼酸他莫昔芬片的药代动力学和生物利用度研究。８名健康受试者分别随机ｐｏ屯溪产和上海产枸橼酸他莫昔芬片３０ｍｇ，其血药浓度－时间曲线均符合－房室模型。屯溪产枸橼酸他莫昔芬片的主要药代动力学参数Ｔ１／２ｋα＝０．７８±０．２３ｈ，Ｔ１／２ｋｅ＝１２．０９±２．４５ｈ，Ｔ（ｍａｘ）＝３．７３±０．８１ｈ，Ｃ（ｍａｘ）＝１１８．８±２９．０ｎｇ／ｍｌ，ＡＵＣ＝２３８４±４４５ｎｇ·ｈ·ｍｌ－１。其相对生物利用度为１０４．２％。     

葛根素滴眼液眼内药代动力学的研究

本文利用高效液相色谱法测定了房水浓度中葛根素浓度，建立了灵敏、精确、简便、重现性好的分析方法。适用于眼内的药代动力学的研究。实验数据按ＣＡＰＰ房室模型程度计算，结果表明葛根素滴眼液在家兔眼内的药物动力学过程符合二房室模型，其拟合动力学方程为：Ｃ（ｔ）＝２１３ｅ－１００ｔ＋０２３ｅ－００８３ｔ－２３６ｅ－５０６ｔ，其主要药动学参数分别为：Ａ＝２１３μｇ·ｍｌ－１；Ｂ＝０３３μｇ·ｍｌ－１；α＝１００ｈ－１；β＝０８３ｈ－１；ｔ１／２α＝０６９ｈ；ｔ１／２β＝８３２ｈ；Ｋα＝５０６ｈ－１；Ｋ２１＝０１９ｈ－１；Ｋ１０＝０４３ｈ－１；Ｋ１２＝０４６ｈ－１；Ｃｍａｘ＝０９６３μｇ·ｍｌ－１；Ｔｍａｘ＝２００ｈ；ＡＵＣ＝５１６μｇ·ｈ·ｍｌ－１。     

诺氟沙星体内浓度测定及其药动学研究

作者用反相高效液相色谱（ＲＰ—ＨＰＬＣ）测定方法，进行体内诺氟沙星的药代动力学研究。波动相：乙腈—甲醇—磷酸盐缓冲液（ｐＨ３．００）３３∶３３∶３４，奎宁为内标，荧光２９０／４５０ｎｍ检测，线性范围０．２４４～２．９２８μｇ／ｍｌ。平均提取回收率：９７．１７±２．６８％。用本法测定１０名健康受试者口服诺氟沙星的体内药代动力学，药一时曲线符合一室模型，药代动力学参数分别为：ＡＵＣ＝４２９５．０２ｎｇ·Ｌ￣（－１）ｈ；Ｃ＿（ｍａｘ）＝７７６．９７ｎｇ／ｍｌ；Ｔ＿（ｍａｘ）＝１．３８ｈ；Ｔ１／２β＝３．１０ｈ。     

HPLC法测定SHR血清中硝苯地平浓度及其药代动力学研究

目的建立血清中硝苯地平浓度的ＨＰＬＣ测定法，研究其在自发性高血压大鼠（ＳＨＲ）体内的药动学。方法ＳＨＲ灌胃给与硝苯地平１０ｍｇ／ｋｇ，用ＨＰＬＣ法测定硝苯地平血清浓度。用乙酸乙酯提取出血清中的硝苯地平，在５０℃水浴中用氮气吹干，残渣用流动相溶解后进样。选用ｓｈｉｍＰａｃｋＣＬＣ－ＯＤＳ柱，甲醇－水（６∶４）作流动相，检测波长２３５ｎｍ。结果：硝苯地平最低检出浓度为０．０２μｇ／ｍｌ，标准曲线线性范围为０．０２～５．０μｇ／ｍｌ（ｒ＝０．９９９７），血样平均回收率为９８．０９％。硝苯地平在大鼠体内的药动学符合一定开放模型，其参数为Ｔ１／２ｋａ＝０．８２８±０．５５ｈ，Ｔ１／２ｋｅ＝３．１７±２．３２ｈ，Ｔｍａｘ＝２．１２±１．４７ｈ，Ｃｍａｘ＝２．７８±１．５０μｇ／ｍｌ和ＡＵＣ＝２４．５±２９．２ｈ·μｇ／ｍｌ。结论本法能满足血清中硝苯地平浓度测定及药动学研究的需要。     

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.