1,6-二磷酸果糖的体内过程研究

目的:研究1,6-二磷酸果糖的体内过程。方法:取SD大鼠,静脉注射三种剂量的[32P]FDP,考察其在大鼠体内吸收、分布、代谢、排泄过程。结果:三种剂量给药后的药物动力学显示血浆半衰期约为10min,表观分布容积与体重相当。心、肝、肾、脾和肺的放射性浓度高,肌肉和脂肪中的浓度低。给药后第1天约通过尿排泄10%。结论:[32P]FDP静脉注射后迅速随血流分布,心中浓聚,此研究为其治疗心血管、慢性阻塞性肺病(COPD)等疾病提供临床理论依据。     

苦豆碱的气相色谱测定及其药代动力学

建立了气相色谱仪测定组织中苦豆碱含量的方法,并研究其在动物体内的时间过程。兔ⅳ苦豆碱的血浓-时间曲线符合二房室模型。分布半衰期t_(1/2)为5.5 min,消除半衰期为2 h,组织分布广,心、肝、肺、脂肪中含量均较血浆中高;剂量25 mg/kg时的分布容积V_((?))高达2.21L/kg;大鼠36 h内尿排泄药量为13.4%±5.0%,胆道几乎不排泄。牛血清白蛋白结合率为76.8%±5.1%。小鼠灌胃后以一级过程吸收,半量吸收时间为80.8 min。     

单剂量美罗培南静脉制剂在健康受试者体内的药代动力学研究

目的:对单剂量美罗培南静脉制剂在健康受试者体内的药代动力学过程进行分析与研究。方法:选取健康受试者15名,对受试者随机分组交叉注射美罗培南静脉制剂,静滴给药100、300、500mg。在受试者静脉给药后每隔0.5小时取患者血样,每隔2、4、6、12小时取患者尿液。利用高效液相色谱仪对患者血液中以及尿液中的药物浓度进行测定。用药代学公式对实验测定的血药浓度和尿药浓度进行药物代谢分析。对于美罗培南静脉制剂在体内的药代动力学过程进行研究。结果:15例健康受试者在接受药物注射后的血药浓度分别为(7.14±1.76)mg/L、(19.45±3.02)mg/L、(40.37±3.17)mg/L。半衰期分别为(1.71±0.46)h、(1.53±0.32)mg/L、(1.29±0.05)mg/L。AUC分别是(15.68±5.48)mg·h/L、(35.65±4.78)mg·h/L、(67.84±9.58)mg·h/L。记录每个时间段的尿药排泄率分别为31.8%、30.4%、33.6%。结论:美罗培南注射后再人体内由肾脏排泄,不随着给药量的增多而增加血药浓度,不存在体内累积的现象,会随着时间逐渐被肾脏代谢。     

99mTc-MAG3-ASON药代动力学研究

目的：研究99mTc标记的MAG3-ASON螯合物的药代动力学特征.方法：制备99mTc-MAG3-ASON螯合物;随后用放射性计数法测定其半衰期,用3P97软件求出其分布半衰期、消除半衰期、中央室分布容积、总表观分布容积、总清除率;最后用三氯醋酸法测定其血浆蛋白结合率.结果：99mTc-MAG3-ASON的分布半衰期是2.11min;消除半衰期是95.19min;中央室分布容积是114.9ml;总表观分布容积是2430.8ml;总清除率是17.7ml/min.与人血浆孵育1.5h后,血浆蛋白结合率为11.82%.结论：99mTc-MAG3-ASON螯合物在体内的转运过程符合二室模型,其良好的药代动力学特征,可望用于肿瘤的显像诊断和治疗.     

VM-26小鼠腹腔内应用药物动力学研究

目的 :测定VM - 2 6(鬼臼噻吩甙 )腹腔内应用后的血浆药代动力学参数 ,肝脏、肾脏、肠壁的药物浓度分布 ,为治疗卵巢癌腹腔化疗提供理论依据。方法 :1 50只小鼠随机分为两组 (30mg/kg和 50mg/kg)腹腔给药 ,血药浓度及肝、肾、肠壁内药物浓度 ,测定用高效液相法 (HPLC) ,数据用 3P87软件处理。结果 :30mg/kg、50mg/kg血浆药物浓度 (Cmax)分别为 9.53mg/L和 1 9.1 8mg/L ,峰浓度时间 (Tpeak)分别为 2 .2 7h和 3 .2 1h ,药———时曲线下面积(AUC)分别为 79.32mg/ (h·L)和 2 0 7.95mg/ (h·L) ,三者经统计学处理有显著性差异 (P <0 .0 0 1 ) ,证明腹腔内给药剂量不同 ,上述三项参数呈剂量依赖性关系。两剂量组的表观分布容积 (V)分别为 2 .61L和 1 .48L ,经统计学处理P <0 .0 5 ,即给药剂量不同 ,表观分布容积也不相同。血浆清除半衰期 (t1 / 2 )两剂量组分别为 8.66h和 6 .76h ,血浆清除率分别为 0 .73mg/ (kg·h)与 0 .31mg/ (kg·h) ,前者经统计学处理P >0 .1 0。表明剂量不同 ,其半衰期无差异。组织中药物浓度分布从高到低的是 :肠壁、肝脏、肾脏 ,但达高浓度值的时间不恒定 ,一般在 0 .5～ 2h之间 ,8h下降至最低点 ,1 2h又略有上升。讨论 :VM - 2 6腹腔内注射 ,对于治疗卵巢癌是安全、可靠、毒性小的     

安托可金(0325k_(1-1)在大鼠体内的药代动力学

以原子吸收法测定了大鼠血浆、组织与胆汁、尿、粪便中安托可金的浓度。大鼠静注安托可金后符合二房室模型处置特征 ,分布半衰期平均为 0 .2 5± 0 .0 2h ,消除半衰期平均为 1 1 .4± 0 .57h ,中央室分布容积为 0 .1 6± 0 .0 5L/kg。静注安托可金后该药可很快向机体的各组织分布 ,大多数组织在 6min即达到较高浓度 ;其中以肾脏浓度最高 ,肝、肺、子宫、皮肤、瘤体等组织也有较高的浓度。静注给药后 ,2 4h的累积尿排泄率平均为 (77.6± 1 0 .3 ) % ,1 2 0h的累积排泄率平均为 (90 .7± 3 .80 ) % ,说明肾脏是该药的主要排泄途径 ;安托可金在粪中的排泄较少 ,1 2 0h的累积排泄率平均为 (2 .87± 0 .4 6) % ,2 4h的胆汁累积排泄率平均为(1 .0 1± 0 .2 9) % ,说明粪和胆汁不是该药的主要排泄途径。安托可金与大鼠的血浆蛋白结合率平均为 (4 0 .7± 3 .4 9) %。     

丙磺舒等药物对大鼠双环铂肾排泄的影响及其机理研究

目的比较丙磺舒、甲氨蝶呤、地高辛、维拉帕米等不同药物转运蛋白底物对大鼠双环铂肾排泄的影响。方法采用原子吸收法测定大鼠尿液中铂浓度,计算4h尿药累积排泄率。结果合用不同转运蛋白底物后,双环铂在尿中的排泄量均有所降低,双环铂组4h累积排泄百分率为(70.7±9.8)%,而合用丙磺舒、维拉帕米、地高辛或甲氨蝶呤后,其累积排泄百分率分别降为(28.8±4.1)%、(34.2±10.1)%、(43.6±2.8)%和(47.4±8.5)%,肾组织铂浓度则由(278.8±112.0)μg/g分别降低或升高为(179.6±122.2)μg/g、(309.5±88.8)μg/g、(374.4±90.1)μg/g和(266.0±107.5)μg/g。结论合用丙磺舒等药物可抑制双环铂的肾排泄速度,双环铂及其代谢物的肾排泄过程中可能有P-gp、OAT或OATP等药物转运蛋白参与。     

药物半衰期与临床用药

<正>药物治疗在临床医学中占有重要地位,当患者诊断明确后.必须正确地选择药物,正确地给药,才能获得应有的治疗效果.近年来,药学领域内发展了一些新的理论,为制定合理的给药方案提供了依据.使临床用药的水平有了很大的提高.但是在一些医院,特别是基层医院,临床用药往往忽视药物的半衰期,例如庆大霉素药物半衰期为2.0h ,临床上仍按1日2次,1次8万单位,肌注,这样药物在体内消除很快,体内药物浓度达不到最小抑制浓度(MIC)时间过长,因而治疗效果不理想;复方磺胺甲基异恶唑的药物半衰期为12h,但有的临床医生仍按常规给药,1日3次次1g,这样就造成药物在体内蓄积,易引起肾脏损害,青霉素在体内代谢及排泄极快.消除半衰期为0.65～0.70h,用药后3～4h约90%已排泄.     

临床医学

,80088老年用药特点/张仿灵//中国乡村医药一1997,4(8)一29~30 老年人用药除需要根据病理情况及药理作用外,还要考虑其①生理特点:注意给药方法和药特选择;②药效学方面特点:对器官敏感性及自身稳定机制;③药动学方面特点:吸收功能减少,急症宜采用静脉给药。血浆蛋白结合比青壮年减少20%,对某些药物老人宜减量慎用.对多数药物分布容积增大,如安定、保泰松、甲塘宁、利多卡因等,也有减少的,如地高辛、酒精、氨茶碱等.肝代谢,老年人肝微粒体酶活性下降,受此酶灭活的药物半衰期显著延长,血药浓度升高.肾排泄下降,自肾排泄消除的药物剂量必须相…     

洛伐他汀在巴马香猪体内的分布和排泄

目的研究洛伐他汀在巴马香猪体内的分布和排泄特点。方法以抗动脉粥样硬化药物洛伐他汀为模型药,选择健康6月龄雄性巴马香猪为实验对象,经灌胃途径给药(45 mg/kg或2.4 mg/kg),采用RP-HPLC方法测定各组织及体液中的药物浓度,并对其分布和排泄过程进行研究。血浆蛋白结合率通过透析法测定。结果给药后,洛伐他汀快速分布到贲门、胃、小肠、肝、大肠、胰、前列腺、肺、肾、心、肌肉、睾丸、肾上腺、膀胱、脑和脾。以胃、肠、肝组织中药物浓度较高。单次给药4h后,贲门、胃、小肠、肝、心、肾上腺、膀胱药物浓度同给药后1h相比略有下降,其余组织均高于1 h。血浆蛋白结合率为95%以上,同正常人血浆非常一致。96 h尿中累积排泄量为给药量的7.4%,原形药经胆汁及粪排泄量达到80%以上。结论洛伐他汀在巴马香猪体内同人的分布排泄和血浆蛋白结合率相似,均在组织中广泛分布,血浆结合率达到95%以上,主要经胆汁和粪排泄。     

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.