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142.
143.
SS Bollapragada F MacKenzie JD Norrie O Eddama S Petrou M Reid JE Norman 《BJOG : an international journal of obstetrics and gynaecology》2009,116(9):1185-1195
Objective To determine whether isosorbide mononitrate (IMN), self-administered vaginally by women at home, improves the process of induction of labour.
Design Randomised double blind placebo-controlled trial.
Setting Large UK maternity hospital.
Population or Sample Nulliparous women with a singleton pregnancy, cephalic presentation ≥37 weeks gestation, requiring cervical ripening prior to induction of labour.
Methods IMN ( n = 177) or placebo ( n = 173) self-administered vaginally at home at 48, 32 and 16 hours prior to the scheduled time of admission for induction.
Main outcome measures Admission to delivery interval and women's experience of induction of labour.
Results IMN did not shorten the admission to delivery interval as compared with placebo [mean difference of −1.6 hours (95% CI −5.1,1.9, P = 0.37)], despite being more effective than placebo in inducing a change in Bishop score [mean difference of 0.65 (95% CI 0.14,1.17, P = 0.013)]. While both groups found the overall experience of home treatment to be positive, (mean score of 3.8/10 ± 2.3/10 for the IMN group, where 1 = extremely good and 10 = not at all good) women in the placebo group found it marginally more positive than those in the IMN group (just over half a unit on a 10-point scale, P = 0.043). There were no differences between the groups in the pain or anxiety experienced or willingness to take the treatment in a subsequent pregnancy.
Conclusions IMN self-administered vaginally at home does not shorten admission to delivery interval despite a significant effect on cervical ripeness assessed using the Bishop score. However, women report positive views on cervical ripening at home, and the setting deserves further investigation. 相似文献
Design Randomised double blind placebo-controlled trial.
Setting Large UK maternity hospital.
Population or Sample Nulliparous women with a singleton pregnancy, cephalic presentation ≥37 weeks gestation, requiring cervical ripening prior to induction of labour.
Methods IMN ( n = 177) or placebo ( n = 173) self-administered vaginally at home at 48, 32 and 16 hours prior to the scheduled time of admission for induction.
Main outcome measures Admission to delivery interval and women's experience of induction of labour.
Results IMN did not shorten the admission to delivery interval as compared with placebo [mean difference of −1.6 hours (95% CI −5.1,1.9, P = 0.37)], despite being more effective than placebo in inducing a change in Bishop score [mean difference of 0.65 (95% CI 0.14,1.17, P = 0.013)]. While both groups found the overall experience of home treatment to be positive, (mean score of 3.8/10 ± 2.3/10 for the IMN group, where 1 = extremely good and 10 = not at all good) women in the placebo group found it marginally more positive than those in the IMN group (just over half a unit on a 10-point scale, P = 0.043). There were no differences between the groups in the pain or anxiety experienced or willingness to take the treatment in a subsequent pregnancy.
Conclusions IMN self-administered vaginally at home does not shorten admission to delivery interval despite a significant effect on cervical ripeness assessed using the Bishop score. However, women report positive views on cervical ripening at home, and the setting deserves further investigation. 相似文献
144.
Ericksen SS Cummings DF Weinstein H Schetz JA 《The Journal of pharmacology and experimental therapeutics》2009,328(1):40-54
We have uncovered a significant allosteric response of the D(2) dopamine receptor to physiologically relevant concentrations of sodium (140 mM), characterized by a sodium-enhanced binding affinity for a D(4)-selective class of agonists and antagonists. This enhancement is significantly more pronounced in a D(2)-V2.61(91)F mutant and cannot be mimicked by an equivalent concentration of the sodium replacement cation N-methyl-D-glucamine. This phenomenon was explored computationally at the molecular level by analyzing the effect of sodium binding on the dynamic properties of D(2) receptor model constructs. Normal mode analysis identified one mode (M(19)), which is involved in the open/closed motions of the binding cleft as being particularly sensitive to the sodium effect. To examine the consequences for D(2) receptor ligand recognition, one of the ligands, L-745,870 [3-{[4-(4-chlorophenyl) piperazin-1-yl]-methyl}-1H-pyrrolo[2,3-b]pyridine or CPPMA, chlorophenylpiperazinyl methylazaindole], was docked into conformers along the M(19) trajectory. Structurally and pharmacologically well established ligand-receptor interactions, including the ionic interaction with D3.32(114) and interactions between the ligand aryl moieties and V2.61(91)F, were achieved only in "open" phase conformers. The docking of (-)-raclopride [3,5-dichloro-N-(1-ethylpyrrolidin-2-ylmethyl)-2-hydroxy-6-methoxybenzamide] suggests that the same binding cleft changes in response to sodium-binding perturbation account as well for the enhancements in binding affinity for substituted benzamides in the wild-type D(2) receptor. Our findings demonstrate how key interactions can be modulated by occupancy at an allosteric site and are consistent with a mechanism in which sodium binding enhances the affinity of selected ligands through dynamic changes that increase accessibility of substituted benzamides and 1,4-DAP ligands to the orthosteric site and accessibility of 1,4-DAPs to V2.61(91)F. 相似文献
145.
146.
147.
J. MØSS B. SCHARLING M. EZBAN† T. MØLLER SØRENSEN‡ 《Journal of thrombosis and haemostasis》2009,7(2):299-305
Summary. Background: NN1731 is a recombinant activated factor VII (rFVIIa) analog with enhanced activity. Objectives: This clinical trial aimed to assess the safety and pharmacokinetics of single doses of NN1731 in healthy male subjects. Methods : This was a randomized, placebo-controlled dose - escalation trial with four dose tiers (NN1731 5 – 30 μg kg−1 ). Eight subjects were randomized to either NN1731 ( n = 6) or placebo ( n = 2) in each tier. Results: No thromboembolic or serious adverse events were reported and no antibody formation towards NN1731 was detected. NN1731 was demonstrated to be pharmacologically active based on coagulation-related parameters (prothrombin fragment 1+2, activated partial thromboplastin time and prothrombin time). There were five mild/moderate adverse events in three subjects. The FVIIa activity of NN1731 after ascending single-dose administration of NN1731 fits well with a two-compartment model, indicating a bi-exponential decline with a rapid initial distribution of approximately 73% FVIIa activity (half-life = 20 min), followed by a less rapid terminal elimination phase eliminating the remaining 27% (half-life = 3 h). Dose proportionality in healthy male subjects at the dose levels investigated (5 – 30 μg kg−1 ) was supported by the FVIIa activity data. Conclusions: Based on the results of this trial, NN1731 appears safe and well tolerated in healthy subjects at doses up to 30 μg kg−1 . No immunogenic or thromboembolic events were reported. The pharmacokinetic profile of NN1731 as measured by FVIIa activity appears to follow two-compartment pharmacokinetics characterized by an initial rapid distribution phase followed by a less rapid elimination phase. 相似文献
148.
目的:已有理论提出急性心肌梗死后骨髓和外周血中的CD34 干细胞具有自身动员的潜能,观察这一潜能的变化特征及其对心肌梗死组织再生能力的影响。方法:实验于2004-09/2005-02在阜外心血管病医院完成。①实验动物:雄性SD大鼠40只,随机数字表法分为心肌梗死组、假手术组,20只/组。②实验方法:心肌梗死组大鼠采用冠状动脉结扎法建立心肌梗死模型。心电图ST段抬高或有室性心律出现,前壁心肌呈苍白色为造模成功。假手术组仅作开胸手术,前降支不予结扎。③实验评估:于心肌梗死后3,7,14,28d,流式细胞仪检测骨髓和外周血中CD34 干细胞的含量。用免疫组化方法检测梗死心肌组织中的Ki67细胞和毛细血管数量。结果:①外周血及骨髓CD34 干细胞含量的变化:心肌梗死组外周血中的CD34 干细胞数量于造模后3d开始上升,7d后明显高于假手术组(P<0.01),至14,28d时逐渐回落至假手术组水平(P>0.05)。心肌梗死组骨髓中的CD34 干细胞数量于造模后各时间点始终无明显变化(P>0.05)。②组织学评定:心肌梗死组梗死区Ki67细胞和毛细血管数量于造模后3d开始增多,7d时明显多于非梗死区(P<0.05);至14,28d梗死区Ki67细胞数量明显少于造模后7d(P<0.05),毛细血管数量的减少不明显(P>0.05)。免疫组化染色显示少数Ki67细胞分化为血管内皮细胞,未见向心肌细胞分化。③相关性分析:梗死区Ki67细胞、毛细血管数量于造模后7d与外周血中CD34 干细胞数量呈显著正相关(r=0.913,P=0.021;r=0.887,P=0.035)。结论:机体CD34 干细胞的自体动员、增殖反应的潜能随急性心肌梗死时间的延长而逐渐减弱,自体动员的干细胞功能尚不足以达到修复梗死心肌组织的效果。 相似文献
149.
150.
本文用DSC和激光拉曼光谱研究抗癌药物足叶乙甙(4-去甲基表鬼臼毒素-β-D-乙叉吡喃葡萄糖甙,简称VP 16-213)与二棕榈酰磷脂酰胆碱(DPPC)脂质体的作用。VP 16-213分子掺入DPPC脂质体双层中,不但使相转变温度向高温移动,而且吸热峰的半高宽度随VP 16-213浓度增加而变宽。其Raman光谱在频率2850 cm~(-1)处的C-H键对称伸缩振动亦随着药物浓度增加而减弱。这些结果表明VP 16-213分子是定域在脂双层中DPPC分子链的C_1~C_9亚甲基区域,使脂质体的有序性提高而流动性降低。 相似文献