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1.
目的为探求卵巢切除大鼠在行振动运动后对全血粘度等血液流变学指标的影响。方法实验动物采用正常雌性Wistar大鼠,体重250±10g。所有大鼠分假手术组(SO)和卵巢切除组(OVX)和卵巢切除雌激素替代组(ERT),每组又随机分成非振动组和振动组(-V),每组10只大鼠。ERT组大鼠卵巢切除4w后,行戊酸雌二醇替代4w,800mg/kg/d。振动运动组行全身的振动运动,频率为280次/min,最大振幅6mm,每天一次,每次60min。下腔静脉取血,行红细胞压积、高低切变率下的全血粘度和红细胞变形指数等血液流变学指标的检测。结果卵巢切除后的大鼠尾椎骨的骨密度值明显小于SO组和ERT组,采用振动运动的大鼠的骨密度值在均值上大于非运动组,但差异不明显。各振动运动组的低切变率(10s-1)下的全血粘度值明显小于其相应的非振动组,P<0.05;而高切变率(100s-1和150s-1)下的全血粘度值、红细胞变形指数相应组间的差异不明显。结论雌激素替代治疗结合一定频率和幅度的振动运动,可使低切变率下的全血粘度值明显降低。  相似文献   

2.
目的通过血液流变学的实验研究,探讨诃子醇提物对大鼠微观血液流变学指标的影响。方法选取SD雄性大鼠随机分为对照组、血瘀模型组、诃子醇提物组,阳性对照组(复方丹参片)。采用皮下注射肾上腺素加冰水冷浴法造大鼠血瘀模型,通过测定全血粘度、血浆粘度,红细胞压积,红细胞在不同切变率下的变形、取向指数,红细胞膜的渗透脆性等血液流变学指标来观察诃子醇提物对大鼠微观血液流变学的影响。结果正常对照组,诃子醇提物组,阳性对照组各血液流变学指标间的差异不明显。但与血瘀模型组比较,诃子醇提物能明显降低全血粘度、血浆粘度、红细胞压积,增强红细胞变形、取向能力,提高红细胞的抗低渗能力。结论诃子醇提物可以有效改善急性应激性血瘀大鼠的微观血液流变学特性。  相似文献   

3.
目的 观察夏至草醇提物对高分子右旋糖苷(Dextran 500)致急性微循环障碍(AMD)大鼠血液流变性的影响.方法 Wistar雄性大鼠随机分为夏至草组、模型组和对照组.前二组静注10%Dextran 500(10mL/kg)复制急性微循环障碍模型(对照组以等量生理盐水代替).6min后,夏至草组自颈静脉缓慢推注夏至草醇提物(1g/mL.6g/kg),其它两组以等量生理盐水代替.40min后,观察全血粘度、血浆粘度、红细胞变形性等血液流变学指标.结果 ①模型组在高、中、低切变率下的全血粘度、血浆粘度、全血相对粘度及红细胞压积均显著高于对照组;夏至草组不同切变率下的全血粘度、血浆粘度、全血相对粘度及全血还原粘度、红细胞压积等指标均显著低于模型组,除全血相对粘度及全血还原粘度显著低于对照组外,其它指标与对照组均无统计学差异.②模型组及夏至草组的血沉长度、红细胞电泳时间均长于对照组;模型组及夏至草组的红细胞电泳长度与迁移率均低于对照组;模型组在不同切变率下的变形性与对照组无统计学差异,而夏至草组在不同切变率下的红细胞变形性均显著高于对照组及模型组.结论 夏至草醇提物能明显降低Dextran 500致AMD大鼠的全血粘度和血浆粘度,提高红细胞变形能力.  相似文献   

4.
常用血液流变学指标及其影响因素   总被引:15,自引:1,他引:15  
血液流变学是一门研究血液及其组份流动和变形规律的科学,近年来国内血液流变学的基础理论与临床应用研究进展很快,本文就常用血液流变学指标及其影响作一概述。1血液粘度流变学检测中两个重要指标为全血粘度和血浆粘度。1.1影响全血粘度的因素(1)血细胞数量、体积及结构是影响全血粘度的主要决定因素。全血粘度主要与血液有形成份特别是红细胞数量、红细胞压积密切相关。全血粘度随着红细胞压积的增高而增高,如真性红细胞增多症、慢性阻塞性肺病(COPD)、脱水等均有全血粘度增高。当细胞压积达80%时,血液几乎完全失去其…  相似文献   

5.
紫外线照射充氧回输对肺心病患者血液流变学特性的影响   总被引:1,自引:0,他引:1  
紫外线照射充氧回输是肺心病常规治疗的基础上加用的辅助治疗,观察治疗前后的血液流变学改变及治疗结果,结果发现肺心病患者经该疗地辅助治疗后红细胞压积,纤维蛋白含量,血浆比粘度及在切变率为1s^-1时的全血粘度较治疗前有明显改变,红细胞聚集指数及在切变率为200s^-1和100s^-1时的全血粘度与治疗前比较差异十分明显,而对照治疗组患者除血浆比粘度及红细胞聚集指数在治疗前后在明显发迹外,红细胞压积,纤  相似文献   

6.
目的观察2.硫脲嘧啶对高脂血症大鼠模型血液流变学特性的影响。方法采用0.5%的胆盐和4%的胆固醇加入基础饲料建立高脂血症模型,观察2.硫脲嘧啶对模型大鼠血浆甘油三酯(TG)、总胆固醇(Tc)、低密度脂蛋白胆固醇(LDL.C)、高密度脂蛋白胆固醇(HDL.C)、血糖(Glu)、全血表观粘度( ηb)、全血还原粘度( ηre)、血浆粘度( ηp)、红细胞压积(Hct)、红细胞电泳率、红细胞的变形、取向指数、红细胞聚集等流变学特性的影响。结果与对照组相比,高脂组TC、TG、LDL.C、GIu、红细胞聚集指数、全血表观粘度、全血还原粘度明显增高,HDL.C、红细胞的变形及取向指数、、红细胞电泳率降低;与高脂组相比,甲减组大鼠TC、TG、LDL.C、Glu、红细胞聚集指数、全血还原粘度增高,HDL.C、红细胞的变形及取向指数、红细胞电泳率降低、全血表观粘度降低。结论2.硫脲嘧啶能够升高血糖血脂,恶化血液流变学指标。  相似文献   

7.
冠心病患者血液流变性研究   总被引:11,自引:4,他引:11  
目的用血液流变学探讨冠心病发病机制。方法分析了68例冠心病患者血液流变学伞血高切粘度,全血低切粘度,血浆粘度,红细胞压积,全血高切还原粘度,全血低切还原粘度,红细胞变形指数,红细胞聚集指数及体外血栓形成指标变化;与68例健康人比较。结果冠心病患者血液流变学全血高切粘度,全血低切粘度,血浆粘度,红细胞压积,全血高切还原粘度,全血低切还原粘度,红细胞变形指数,红细胞聚集指数均高于正常人。体外血栓形成指标:血栓长度、血栓湿重、血栓干重也明显大于健康人。结论血液粘度增高是冠心病的诱因,也是其结果;调整冠心病患者血液流变学指标,有益于冠心病患者治疗;健康人定期检测血液流变学指标,有利于预防冠心病的发生。  相似文献   

8.
100例老年肺栓塞患者血液流变学指标检测分析   总被引:1,自引:0,他引:1  
目的探讨老年肺栓塞患者血液流变性的改变。方法对100例老年肺栓塞患者全血粘度(高切、低切)和血浆粘度、红细胞压积,红细胞最大聚集指数、红细胞最大变形指数等有关血液流变学指标进行测定。结果老年肺栓塞患者全血粘度(高切、低切)、血浆粘度、红细胞压积、红细胞最大聚集指数和变形指数明显增高。结论老年人容易患血流滞缓,血液呈高度的浓、粘、聚状态,造成血液流变异常,是肺栓塞的重要因素。  相似文献   

9.
目的观察盐酸特拉唑嗪对代谢综合征大鼠模型血液流变学性质的影响。方法采用高脂饲料饮食和丙硫氧嘧啶建立代谢综合征模型,观察盐酸特拉唑嗪对模型大鼠血浆甘油三酯(TG)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、极低密度脂蛋白胆固醇(VLDL-C)、高密度脂蛋白胆固醇(HDL-C)、血糖(Glu)、全血表观粘度(ηb)、全血还原粘度(ηre)、血浆粘度(ηP)、红细胞压积(Hct)、红细胞电泳率、红细胞的变形、取向、红细胞的聚集等生化指标和流变学特性的影响及动脉的病理改变。结果与对照组相比,高脂甲减组TC、TG、LDL-C、Glu、肝重、红细胞聚集指数、全血还原粘度明显增高,体重、HDL-C、红细胞的变形及取向指数、红细胞电泳率、全血表观粘度明显降低,动脉平滑肌下泡沫细胞明显增多;与高脂甲减组相比,药物干预组TC、TG、LDL-C、GIU、红细胞的聚集指数、全血还原粘度明显降低,而体重、HDL-C、红细胞变形及取向指数、红细胞电泳率明显升高,动脉平滑肌下泡沫细胞数量明显减少。结论盐酸特拉唑嗪能显著降低代谢综合征大鼠血糖血脂、动脉平滑肌下泡沫细胞的数量及改善其血液流变学特性。  相似文献   

10.
目的探讨2型糖尿病患者血液流变学指标的变化与其并发血管性疾病的关系.方法用LBYN6A型血流仪测定糖尿病病人和正常人的血液流变学指标(全血粘度、血浆粘度、红细胞压积、全血还原粘度、红细胞聚集指数、红细胞变形指数、纤维蛋白原),进行统计学处理.结果患病组与正常组存在显著差异(P<0.05);其中,血浆粘度和红细胞压积、纤维蛋白原这三项指标差异显著(P<0.01).结论通过观察糖尿病患者的血液流变学指标的变化有利于控制糖尿病血管性病变的发生发展.  相似文献   

11.
Our objective was to compare ophthalmic artery flow velocity waveforms in unilateral oophorectomized patients not on hormone replacement therapy with findings in bilateral oophorectomized patients on hormone replacement therapy. Ten patients who underwent hysterectomy and unilateral oophorectomy and 10 women treated by hysterectomy and bilateral oophorectomy were studied using color and pulsed Doppler ultrasonography 1 day before and on days 7 and 28 after surgery. Serum estradiol levels were measured serially. Bilateral oophorectomy patients were given hormone replacement therapy (conjugated estrogen, 0.625 mg/day, and medroxyprogesterone acetate, 2.5 mg/day) orally starting on day 8 after surgery. The pulsatility index values of the ophthalmic artery in unilateral oophorectomy patients were 1.93 +/- 0.41, 2.10 +/- 0.26, and 1.68 +/- 0.27 for 1 day before and on days 7 and 28 after surgery, respectively. The pulsatility index values of the ophthalmic artery in bilateral oophorectomy patients were 1.99 +/- 0.39, 2.17 +/- 0.47, and 1.75 +/- 0.32 for 1 day before and on days 7 and 28 after surgery, respectively. No significant differences were found between pulsatility index values in the unilateral and bilateral oophorectomy patients in each time period. The pulsatility index values on day 28 decreased significantly compared with the findings on day 7 in both groups (P < 0.05). The serum estradiol levels were significantly reduced from 1 day before to day 7 day after surgery and were significantly elevated by day 28 after surgery (P < 0.05) in both groups of patients. No significant differences were found between the serum estradiol levels in the unilateral and bilateral oophorectomy patients in each time period. Vascular tone in the ophthalmic artery seems to change according to serum estradiol levels, a finding that may help explain some of the beneficial effects of hormone replacement therapy for bilateral oophorectomized patients.  相似文献   

12.
BACKGROUND: Cardiovascular disease (CVD) is less prevalent in premenopausal women and women receiving estrogen replacement therapy (ERT) than in postmenopausal women or men. It proposed that the cardiovascular effects of estrogen are mediated, at least in part, through the ability of estrogen to increase nitric oxide (NO) synthesis. This study investigated the effect of estrogen on serum NO concentrations in normotensive and deoxycorticostrone acetate (DOCA) Salt hypertensive ovariectomized rats. METHODS: Forty-eight female rats were ovariectomized and randomly divided into six groups. Hypertension was induced by DOCA Salt method. DOCA was injected 30 mg/kg of body weight subcutaneously, twice a week with NaCl 1% instead of tap water for drinking throughout the treatment period. Estradiol valerate (Es) was injected i.m. once a week. The groups were as follows: (2) DOCA (4 weeks) and DOCA+Es (6 weeks), (22) DOCA (10 weeks), (222) normal saline (N/S) (4 weeks)+Es (6 weeks), (2V) N/S (10 weeks), (V) DOCA (4 weeks), and (V2) N/S (4 weeks). Serum NO concentrations were measured in groups 1, 3 and 4 before and after treatment. Other groups were used as control. RESULTS: Results showed that in normotensive animals, serum NO concentrations were increased after estrogen treatment significantly (90.20 +/- 18.67 vs. 19.11 +/- 1.78 micromol/l) (p < 0.05). Also, estrogen increased serum NO concentrations in DOCA Salt hypertensive rats (73.54 +/- 22.55 vs. 36.94 +/- 10.73 micromol/l) (p = 0.06). CONCLUSION: Estrogen can increase serum NO concentrations in normotensive and DOCA Salt hypertensive animals and it may be important in cardiovascular effects of estrogen.  相似文献   

13.
背景:抗氧化作用可能是雌激素对晶状体保护作用的机制之一,但此机制的具体途径目前仍不明确,同时临床上常用的几种雌激素替代治疗方法对晶状体氧化损伤的影响至今少见报道。目的:观察雌二醇及其联合孕酮对萘诱导去卵巢雌性大鼠晶状体氧化损伤模型中晶状体混浊情况、晶状体氧化防御系统、脂质过氧化产物及可溶性蛋白水平的影响。方法:将SD大鼠随机分为假手术组、模型组、雌二醇组、雌二醇+孕酮组,后3组均行双侧卵巢切除。术后2周,4组均用萘混悬液灌胃,定期行裂隙灯显微镜检查观察各组大鼠晶状体变化;灌胃6周后检测晶状体氧化防御系统、脂质过氧化产物及可溶性蛋白水平,测定血清雌二醇和孕酮水平。结果与结论:与模型组相比,雌二醇组、雌二醇+孕酮组及假手术组晶状体混浊程度轻,出现时间晚,而晶状体超氧化物歧化酶、谷胱甘肽、维生素C,可溶性蛋白含量,血清雌二醇与孕酮水平增高(P<0.05或P<0.01),丙二醛水平降低(P<0.05)。结果证实,雌二醇及其联合孕酮两种替代治疗方法对萘诱导去卵巢雌性大鼠晶状体的氧化损伤均有抑制作用,其机制与晶状体氧化防御系统的活性、抑制脂质过氧化产物的形成并维持可溶性蛋白的水平有关,抑制晶状体的氧化损伤是雌激素替代治疗发挥晶状体保护作用的机制之一。  相似文献   

14.
背景:抗氧化作用可能是雌激素对晶状体保护作用的机制之一,但此机制的具体途径目前仍不明确,同时临床上常用的几种雌激素替代治疗方法对晶状体氧化损伤的影响至今少见报道。目的:观察雌二醇及其联合孕酮对萘诱导去卵巢雌性大鼠晶状体氧化损伤模型中晶状体混浊情况、晶状体氧化防御系统、脂质过氧化产物及可溶性蛋白水平的影响。方法:将SD大鼠随机分为假手术组、模型组、雌二醇组、雌二醇+孕酮组,后3组均行双侧卵巢切除。术后2周,4组均用萘混悬液灌胃,定期行裂隙灯显微镜检查观察各组大鼠晶状体变化;灌胃6周后检测晶状体氧化防御系统、脂质过氧化产物及可溶性蛋白水平,测定血清雌二醇和孕酮水平。结果与结论:与模型组相比,雌二醇组、雌二醇+孕酮组及假手术组晶状体混浊程度轻,出现时间晚,而晶状体超氧化物歧化酶、谷胱甘肽、维生素C,可溶性蛋白含量,血清雌二醇与孕酮水平增高(P〈0.05或P〈0.01),丙二醛水平降低(P〈0.05)。结果证实,雌二醇及其联合孕酮两种替代治疗方法对萘诱导去卵巢雌性大鼠晶状体的氧化损伤均有抑制作用,其机制与晶状体氧化防御系统的活性、抑制脂质过氧化产物的形成并维持可溶性蛋白的水平有关,抑制晶状体的氧化损伤是雌激素替代治疗发挥晶状体保护作用的机制之一。  相似文献   

15.
BACKGROUND: Cardiovascular disease (CVD) is the leading cause of death in developed countries. Previous studies have shown that hormone replacement therapy reduces the risk of CVD in postmenopausal women, however, the mechanism remains unclear. This study was designed to evaluate the effect of estrogen on serum vascular endothelial growth factor (VEGF) concentration in normotensive and hypertensive ovariectomized rats. METHODS: Forty-eight female rats were ovariectomized and randomly divided into 6 groups. Hypertension was induced by DOCA-Salt method. DOCA was injected 30 mg/kg of body weight subcutaneously, twice a week with NaCl 1% instead of tap water for drinking throughout the experiment. Estradiol valerate (Es) was injected 2 mg/week i.m. The groups were as follows: (i) DOCA (4 weeks) and DOCA+Es (6 weeks); (ii) DOCA (10 weeks); (iii) Normal saline (N/S) (4 weeks) and Es (6 weeks); (iv) N/S 10 weeks; (v) DOCA (4 weeks), and (vi) N/S (4 weeks). Serum VEGF concentration was measured in groups 1 to 4. RESULTS: Results showed that in normotensive animals that received estrogen treatment, serum VEGF concentration was significantly higher than those not receiving estrogen (269+/-41 vs. 106+/-36 pg/ml) (P<0.05). In hypertensive group, serum VEGF level was also increased after estrogen therapy compare to those not receiving estrogen (326+/-55 vs. 121+/-28 pg/ml (P<0.05). CONCLUSION: It is possible that the increase in serum VEGF concentration after estrogen therapy may contribute to the cardiovascular effects of estrogen in normotensive and hypertensive conditions.  相似文献   

16.
背景近年来,中药麻黄用于肥胖症的治疗并有一定的效果,但麻黄对围绝经期妇女的肥胖是否有效有待研究.目的观察口服麻黄水煎剂对去卵巢肥胖大鼠体质量、血脂、血糖及激素水平的影响.设计完全随机分组设计,对照实验.单位兰州大学基础医学院生理学和心理学研究所.材料实验于2006-02/06在甘肃省新药临床前研究重点实验室和兰州大学基础医学院生理学和心理学研究所实验室完成.选用健康雌性SD大鼠44只,随机分为4组,每组11只,分别为假手术组,去卵巢组,雌激素替代治疗组和麻黄组.方法①大鼠用氯胺酮(110 mg/kg)麻醉,除假手术组外全部行双侧去卵巢术.假手术组进行同样的手术过程,但不切除卵巢.②假手术组和去卵巢组大鼠术后每天皮下注射芝麻油(0.2 mL/只),持续到实验结束.③雌激素替代治疗组大鼠术后每天皮下注射雌激素(1 mg/kg),持续到实验结束.④麻黄组大鼠术后自然口服1%浓度的麻黄水煎剂,到第6天浓度逐渐增至8%,持续到实验结束.⑤每天测定大鼠的摄食量,每隔10天测定大鼠的体质量.⑥实验结束时,所有实验动物禁食12 h后,颈动脉取血测定血清指标.同时测定体质量和体长计算李氏指数[(g)×103/体长(cm)].主要观察指标①不同时间点各组大鼠体质量及李氏指数.②不同时间点各组大鼠摄食量结果.③大鼠血脂和血糖水平.④不同组别大鼠血清雌激素、孕激素和胰岛素水平. 结果大鼠44只全部进入结果分析.①不同时间点各组大鼠体质量及李氏指数结果去卵巢组大鼠实验开始第20,30,40,50天体质量分别为(256.4±14.3),(271.3±16.1),(276.4±12.7),(285.7±24.2)g,均大于假手术组大鼠相应时间点[(226.5±11.5),(241.8±12.6),(243.1±13.5),(251.1±22.4)g,P<0.05~0.01],李氏指数大于假手术组(317.2±13.5,280.4±11.2,P<0.01).雌激素替代治疗组实验开始第40,50天体质量分别为(243.7±14.8),(246.2±11.9)g,低于去卵巢组相应时间点(P<0.05~0.01),李氏指数为289.9±13.5,小于去卵巢组(P<0.01).麻黄组大鼠实验开始第40,50天体质量分别为(245.4±14.1),(252.4±14.9)g,李氏指数为294.4±11.0,小于去卵巢组(P<0.05).②不同时间点各组大鼠摄食量结果麻黄组大鼠实验开始第30,40,50天摄食量分别为(17.8±2.4),(22.3±3.9),(26.1±3.5)g/d,与去卵巢组比减少[(25.9±4.7),(28.5±5.3),(32.8±5.5)g/d,P<0.05].③大鼠血脂和血糖水平去卵巢组大鼠血清三酰甘油、胆固醇、低密度脂蛋白胆固醇含量分别为(1.73±0.32),(1.45±0.50),(0.78±0.19)mmol/L,高于假手术组[(0.94±0.29),(1.05±0.30),(0.08±0.11)mmol/L,P<0.01].雌激素替代治疗后三酰甘油、胆固醇、低密度脂蛋白胆固醇含量及血糖浓度分别为(1.10±0.34),(1.14±0.30),(0.17±0.05),(5.88±1.21)mmol/L,低于去卵巢组(P<0.05~0.01),高密度脂蛋白胆固醇含量高于去卵巢组[(1.11±0.31),(0.88±0.21)mmol/L,P<0.05].麻黄组三酰甘油、胆固醇、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇含量分别为(0.97±0.16),(1.11±0.20),(0.59±0.07),(0.45±0.061)mmol/L,低与去卵巢组(P<0.05~0.01).④不同组别大鼠血清雌激素、孕激素和胰岛素水平去卵巢组大鼠雌激素、孕激素水平分别为(17.09±9.00)ng/L,(28.51±7.99)μg/L,低于假手术组[(58.69±12.11)ng/L,(62.73±10.93)μg/L,P<0.01],胰岛素含量高于假手术组[(31.74±6.69),(23.75±6.66)mU/L,P<0.01].雌激素替代治疗组及和麻黄组雌激素水平为(36.03±8.83),(30.18±8.61)ng/L,高于去卵巢组(P<0.05~0.01),胰岛素水平分别为(21.34±4.57),(24.86±6.20)mU/L,低于去卵巢组(P<0.05~0.01),麻黄组孕激素水平为(17.68±6.19)μg/L,低于去卵巢组(P<0.01).结论麻黄能明显降低去卵巢肥胖大鼠的体质量,降低血脂和胰岛素水平,增加血中雌激素水平.  相似文献   

17.
Thisresearchconstructedratmodelofestrogenreplacementtherapyandestrogencombinedwithprogesteronereplacementther-apy;analyzedandstudiedthechangeofratcardiovascularprotectivefunctionofestrogenreplacementtherapyafteraddingofprogesteronewithindexsuchasER,hemorrheologyandcytokines.1Materialandmethod1.1Material(1)Agentsandinstruments:radioactivityofNENwas222×106Bq/mmol(producedbyNewEnglandNuclear);benzoestrofol,Progesterone(producedbyninthpharmaceuticalfac-tory);17β…  相似文献   

18.
ObjectiveThe purpose of this study was to analyze the morphometric effects of mechanical vibration with a duration of 4 or 8 weeks on the femur of oophorectomized Wistar rats.MethodsSixty-four female rats were submitted to oophorectomy or a sham operation, and each of those 2 groups were randomized into 4 groups: untreated and euthanized at week 12, untreated and euthanized at week 16, treated for 4 weeks and euthanized at week 12, and treated for 8 weeks and euthanized at week 16. The vibration treatment was performed for 10 min/d, with a frequency of 60 Hz, 3 d/wk. The rats were then euthanized and the right femur dissected. Subsequently, histomorphometric analysis was performed on the proximal epiphysis and diaphysis of the spongy and cortical bone, respectively.ResultsAs expected, the oophorectomy groups presented reduction of spongy and cortical bone tissue. Further, the vibration therapy of 4 and 8 weeks’ duration in the oophorectomized groups led to increased bone mass, observed as an increased percentage of spongy tissue, and increased thickness and percentage of cortical tissue. However, the variables of femoral neck diameter, mean area of the shaft, and number of osteocytes were not altered by oophorectomy and vibration.ConclusionThe mechanical vibration was effective in increasing the bone mass of the femur of oophorectomized Wistar rats, observed by increasing the percentage of spongy bone and increasing the percentage and thickness of cortical bone.  相似文献   

19.
Suitable ester prodrugs of 17beta-estradiol are identified, thus permitting effective sustained and controlled estrogen replacement therapy (ERT) from an elastomeric, silicone intravaginal ring (IVR). IVR devices of reservoir design were prepared by blending silicone elastomer base with n-propylorthosilicate (cross-linker) and 10% w/w of 17beta-estradiol or an ester prodrug, the mix being activated with 0.5% w/w stannous octoate and cured at 80 degrees C for 2 min. A rate-controlling membrane was similarly prepared, without the active agent. IVR devices were of cross-sectional diameter 9 mm, outer diameter 54 mm, with core cross-sectional diameter of 2 mm and core length varied as required. Sink conditions were evident for the 17beta-estradiol esters in 1.0% aqueous benzalkonium chloride solution. The low release rates into 0.9% w/v saline of the lipophilic valerate and benzoate esters were due to their intrinsically low aqueous solubilities. In vivo, these esters failed to raise plasma estradiol above baseline levels in postmenopausal human volunteers, despite good in vitro release characteristics under sink conditions. The best release rates under sink conditions, in combination with substantial aqueous solubilities as indicated by the release rates into saline, were observed for the acetate and propionate esters. A combination of drug release characteristics, short plasma half-life and a toxicologically acceptable hydrolysis product indicated that 17beta-estradiol-3-acetate was the prodrug of choice for IVR delivery of ERT. In vivo, an IVR device releasing 100 microg/day of estradiol as its 3-acetate ester maintained over 84 days a circulating plasma concentration in the region of 300 pmoll(-1), within the clinically desirable range for ERT.  相似文献   

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