氟他胺对大鼠及小鼠前列腺肥大的抑制作用(英文)

观察氟他胺（Ｆｌｕ）抗前列腺肥大的作用方法：以两种动物模型：阉割大鼠每只每日ｓｃ睾酮０．５ｍｇ引起前列腺肥大和小鼠前列腺中植入同系 １６ ｄ龄胎鼠的尿生殖窦组织, ｉｇ Ｆｌｕ　１０, ２５,和５０ ｍｇ·ｋｇ－１ ３０ ｄ或 ｓｃ雌二醇（Ｅｓｔ）,两模型分别持续３０ ｄ和 １４ｄ．结果：１） Ｆｌｕ能显著抑制大鼠各叶前列腺体积和重量,使其降至对照组的１０％至５０％,并呈良好的剂量效应关系．腺体上皮萎缩,腺腔直径缩小,其效应比Ｅｓｔ强．２）Ｆｌｕ治疗组前列腺体积和重量均减小,但只有体积项呈剂量效应关系此模型中,Ｅｓｔ的作用较Ｆｌｕ强．结论： Ｆｌｕ具有抑制前列腺肥大的作用。     

氟他胺治疗良性前列腺增生研究进展

良性前列腺增生(benign prostatic hy- perplasia,BPH)是老年男性最常见的良性肿瘤,50a以上的男性约有30%～50%有不同程度的前列腺增生,它是造成老年男性排尿困难最常见的原因.经尿道前列腺切除术是近50年来治疗BPH的有效方案,在美国每年有近3万病人行前列腺切除术,其费用高达2亿美元,但术后仍有20%的病人对疗效不满意,手术并发症约占18%,因此能够取代手术方案用于治疗BPH的药物具有很大的发展前途.基础研究表明,前列腺是雄激素依赖性器官,雄激素必须达到一定水平才能维持前列腺的增生状态.非甾体类抗雄激素药氟他胺(flutamide)是由美国先令公司在70年代初期开发的,现本校红旗制药厂也有生产.该药本身无激素活性,临床上最初用于治疗前列腺癌.随着对     

氟他胺与2-羟基氟他胺对大鼠前列腺增生的抑制作用(英文)

目的 :研究氟他胺与 2 羟基氟他胺对诱导的前列腺增生大鼠前列腺萎缩和细胞凋亡的作用。方法 :SD大鼠去势 ,皮下注射丙酸睾丸素诱导前列腺增生。前列腺增生大鼠随机分成以下 5组 :对照组、氟他胺组 5 0与 1 0 0mg·kg-1,2 羟基氟他胺组2 5与 5 0mg·kg-1,用药时间为 1 0d。比较前列腺各侧叶湿重 ,以HE染色及TUNEL染色法观察细胞凋亡并计算凋亡发生率。结果 :氟他胺及 2 羟基氟他胺可明显降低前列腺增生大鼠前列腺各侧叶湿重 ,差异有显著意义 ,并可观察到明显的凋亡细胞。结论 :氟他胺与 2 羟基氟他胺可诱导前列腺增生大鼠的前列腺萎缩和细胞凋亡     

氟他胺与2-羟基氟他胺诱导正常大鼠前列腺细胞凋亡

目的　研究氟他胺及其活性代谢产物 2 羟基氟他胺诱导正常大鼠前列腺细胞凋亡的作用。方法　大鼠设正常组、去势组及给药组 ,比较前列腺各侧叶湿重 ,以HE染色及TUNEL染色法观察细胞凋亡并计算凋亡发生率。结果　氟他胺 10 0mg·kg-1及 2 羟基氟他胺 5 0mg·kg-1给药 7d可明显降低前列腺各侧叶湿重 ,并可观察到明显的凋亡细胞。结论　氟他胺与 2 羟基氟他胺可诱导正常大鼠前列腺细胞凋亡。     

氟人胺与2—羟基氟他胺诱导正常大鼠前列腺细胞凋亡

目的 研究氟他胺及其活笥代谢产物２－羟基氟他胺诱恨正常大鼠前列腺细胞凋亡作用。方法 大鼠设正常组,去势组及给药组,比较前列腺各侧叶湿重,以ＨＥ染色ＴＵＮＥＬ染色法观察细胞凋亡并计算凋亡发生率。结果 氟他胺１００ｍｇ．ｋｇ＾－１及２－羟基氟他胺５０ｍｇ．ｋｇ＾－１人药７ｄ可明显降低前列腺各侧叶湿重,并可观察到明显的凋亡细胞。结论 氟他胺与２－羟基氟他胺可诱导正常大鼠前列腺细胞凋亡。     

氟他胺及其代谢产物2—羟基氟他胺在正常及肝损伤大鼠的药物动力学

AIM: To develop a new HPLC assay to study the pharmacokinetics of flutamide (Flu) and its active metabolite 2-hydroxyflutamide (HF) in rats. METHODS: Normal or hepatic injury rats were given i.g. Flu 50 mg.kg-1. Reverse phase HPLC was developed with a mu-Bondapak C 18 column. Internal standard was methyltestosterone. The mobile phase was a mixture of methanol:acetonitrile:water:diethyl ether = 40:20:35:1 (vol). Absorbance was measured at lambda 234 nm. RESULTS: The pharmacokinetic parameters of Flu were as follows: in normal rats, K = 0.62 +/- 0.16 h-1, Cl = 6.0 +/- 1.0 L.kg-1.h-1, AUC = 8.6 +/- 1.3 mg.L-1.h, Cmax = 2.4 +/- 0.7 mg.L-1; in hepatic injury rats, K = 0.16 +/- 0.03 h-1, Cl = 0.63 +/- 0.29 L.kg-1.h-1, AUC = 100 +/- 44 mg.L-1.h, Cmax = 6.7 +/- 2.8 mg.L-1. The pharmacokinetic parameters of HF were as follows: in normal rats, K(m) = 0.07 +/- 0.01 h-1, AUC = 219 +/- 22 mg.L-1.h, Cmax = 8.6 +/- 0.6 mg.L-1; in hepatic injury rats, K(m) = 0.05 +/- 0.01 h-1, AUC = 170 +/- 42 mg.L-1.h, Cmax = 3.8 +/- 0.8 mg.L-1. There were significant differences between the parameters of normal and hepatic injury rats (P < 0.01) except AUC of HF (P > 0.05). CONCLUSION: This HPLC assay was sensitive and precise, and the elimination of Flu and HF was inhibited significantly due to hepatic injury.     

氟他胺生产工艺改进

目的研究氟他胺硝化工序在不同的温度条件下,产品质量及收率的影响。方法采取冷冻盐水的方法来减低氟他胺硝化反应的温度。结果氟他胺硝化物收率由55%提高到70%。结论采取冷冻盐水的方法来减低氟他胺硝化反应的温度可提高氟他胺的收率。     

围手术期应用度他雄胺对经尿道前列腺等离子切除术出血量的影响

目的 对比围术期是否应用度他雄胺对TURP出血量,评价度他雄胺疗效与安全性.方法 以2014年1月到2015年12月,医院收治的择期BPH患者作为研究对象,观察组、对照组各入选50例,前者围术期应用度他雄胺,两组均采用经尿道前列腺等离子切除术治疗.结果 观察组退出2例,对照组退出5例;术前,观察组前列腺最大血流速度低于用药前、对照组,观察组术中出血量、术后出血量低于对照组,差异具有统计学意义(P＜0.05),两组用药前、术前前列腺体积、手术时间差异无统计学意义(P＞0.05);两组均未见不良反应,术后随访均未见再出血.结论 围手术期应用度他雄胺可降低经尿道前列腺等离子切除术出血量,可能与其可改变前列腺血流动力学状态有关.     

氟他胺邻位硝基异构体的研究

氟他胺邻位硝基异构体的研究杨征宇，夏奕，郑筠青，夏鹏（上海医科大学药学院有机化学教研室上海２０００３２；中国科学院上海有机化学研究所上海２０００３２）氟他胺（ｆｌｕｔａｍｉｄｅ，Ｉ）是美国先灵药厂生产的一种非甾体抗雄激素药物，临床上用于治疗前列腺癌。...     

康士得与氟他胺应用于晚期前列腺癌患者的不良反应分析

目的：探讨康士得和氟他胺治疗晚期前列腺癌的不良反应。方法：将37例患者分为两组,一组18例,联合手术或LHRHa,康士得口服,每日一次50mg,服用至病情进展或不良反应不可耐受;一组19例,联合手术或LHRHa,氟他胺口服,每日三次,每次一片250mg,服用至病情进展或不良反应不可耐受。两组三个月为一个观察周期,连续观察四个周期后评价其不良反应。结果：康士得组可见不良反应为潮热,皮疹;氟他胺组可见不良反应为潮红、腹泻、血尿、肝功能改变。结论：康士得联合手术或LHRHa治疗晚期前列腺癌不良反应可以耐受。     

Effect of sodium houttuyfonate on myocardial hypertrophy in mice and rats

Objectives The aim of the study was to determine the effect of sodium houttuyfonate on myocardial hypertrophy and its mechanism of action in mice and rats. Methods A mouse model of myocardial hypertrophy was established by subcutaneous injection with isoproterenol. Mice were randomly divided into five groups: normal control; isoproterenol control; isoproterenol plus metoprolol; isoproterenol plus low‐ and high‐dose sodium houttuyfonate. A rat model of myocardial hypertrophy was established by intraperitoneal injection with l ‐thyroxine. Rats were randomly divided into five groups: normal control; l ‐thyroxine control; l ‐thyroxine plus captopril; l ‐thyroxine plus low‐ and high‐dose sodium houttuyfonate. At the end of the experiments, the left ventricular weight index and heart weight index were determined in mice and rats, the size of cardiomyocytes was measured in rats and the concentrations of cAMP in plasma and angiotensin II in ventricular tissue of mice were detected by radioimmunoassay. The endothelin‐1 concentration was measured by radioimmunoassay and the hydroxyproline content was measured by a digestive method in ventricular tissue of rats. Key findings After 7–9 days of treatment, sodium houttuyfonate significantly reduced the left ventricular weight index and heart weight index in mice and rats with myocardial hypertrophy, decreased the size of cardiomyocytes in rats, and reduced the content of cAMP and angiotensin II in mice with myocardial hypertrophy. It also decreased the endothelin‐1 concentration and the hydroxyproline content in ventricular tissue in rats. Conclusions Sodium houttuyfonate can inhibit myocardial hypertrophy in mouse and rat models by restricting the activity of the sympathetic nervous system and decreasing the levels of angiotensin II and endothelin‐1 in ventricular tissue.     

Alcohol and chlordiazepoxide increase suppressed aggression in mice

The purpose of the present experiments was to investigate conditions under which alcohol and chlordiazepoxide (CDP) enhance aggression. Alcohol (300, 600, and 1200 mg/kg orally) and CDP (5, 10, and 20 mg/kg) failed to alter attack behavior in male mice confronting intruder mice in their home cages. When confrontations between attack-experienced mice and group-housed mice occurred in a neutral cage, attack and threat behavior was suppressed to about 50% of that in the resident's home cage. A low dose of alcohol (300 mg/kg) more than doubled the frequency of attacks and threats in the neutral cage. Higher doses of both drugs decreased attacks in the neutral cage. Combined administration of low doses of alcohol (150 and 300 mg/kg) and CDP (2.5 and 5.0 mg/kg) increased attack and threat frequency in the neutral cage to a larger extent than when either drug was given itself. The aggression-enhancing effects of alcohol and CDP in the neutral cage situation are consistent with the view that both drugs can lead to behavioral disinhibition. Alternatively, the results could reflect simply the ratedependency of alcohol effects on attack behavior, that is, low rates are increased whereas high rates remain unaffected. The present results also provide evidence for an additive interaction of both drugs in their depressant effects and, also, in their aggressionheightening effects.     

Flutamide, an androgen receptor antagonist, improves heatstroke outcomes in mice

Flutamide has been used as an adjunct for decreasing the mortality from subsequent sepsis. Heatstroke resembles septic shock in many aspects. We hypothesized that heat-induced multiple organ dysfunction syndromes and lethality could be reduced by flutamide therapy. In heatstroke groups, mice were exposed to whole body heating (41.2°C, for 1h) in a controlled-environment chamber. The heat-stressed mice were returned to normal room temperature (24°C) after whole body heating. Mice still alive on day 4 of WBH treatment were considered survivors. Physiological and biochemical parameters were monitored for 2.5h post-WBH. Heatstroke mice were subcutaneously treated with flutamide (12.5-50mg/kg body weight in 0.05 ml) or vehicle solution (0.05 ml/kg body weight) once daily for 3 consecutive days post-WBH. We evaluated the effect of flutamide in heatstroke mice and showed that flutamide significantly (i) attenuated hypothermia, (ii) reduced the number of apoptotic cells in the hypothalamus, the spleen, the liver, and the kidney, (iii) attenuated the plasma index of toxic oxidizing radicals (e.g., nitric oxide metabolites and hydroxyl radicals), (iv) diminished the plasma index of the organ injury index (e.g., lactate dehydrogenase), (v) attenuated plasma systemic inflammation response molecules (e.g., tumor necrosis factor-α and interleukin-6), (vi) reduced the index of infiltration of polymorphonuclear neutrophils in the lung (e.g., myeloperoxidase activity), and (vii) allowed three times the fractional survival compared with vehicle. Thus, flutamide appears to be a novel agent for the treatment of mice with heatstroke or patients in the early stage of heatstroke.     

槲皮素降低大鼠心率和心肌钙振荡频率和抑制小鼠心肌肥厚

目的 研究槲皮素对心肌兴奋收缩耦联及构型重建的影响。方法 经动脉插管记录大鼠血流动力学,缩窄小鼠腹主动脉致心肌肥厚;检测Ｆｕｒａ２－ＡＭ负载的培养大鼠心肌细胞内游离钙（Ｃａ＾２＋）ｉ及钙振荡。结果：槲皮素剂量相关地降低大量窦性心率,而动脉血压,左室压及其微分改变轻微;１０－２５０μｍｏｌ．Ｌ＾－１时浓度依赖性降低培养心肌血发钙振荡频率,１００μｍｏｌ．Ｌ＾－１时预防异丙肾上腺素及哇巴因加速钙振荡频     

Cardiac responses after norepinephrine-induced ventricular hypertrophy in rats.

The increase in norepinephrine (NE) blood levels in human heart failure correlates with prognosis. In this study, we determined whether continuous NE infusion alters the positive inotropic and chronotropic responses of isolated rat cardiac muscles. Osmotic minipumps were implanted subcutaneously (s.c.) in 43 adult male rats to deliver NE (160 micrograms/kg/h for 14 days); 42 rats were sham-operated. Isolated left and right atria and left and right ventricular (LV, RV) papillary muscles were prepared to measure positive inotropic or chronotropic responses to NE, phenylephrine, forskolin, dibutyryl cyclicAMP (dbcyclicAMP), and calcium chloride. NE infusion caused (a) a 22% increase in LV wet weight without altering atrial or RV wet weights; (b) an 18% decrease in maximal inotropic response to calcium chloride in LV papillary muscles only; (c) a significantly decreased peak response to NE [72 +/- 5 vs. 93 +/- 5% (sham rats) of calcium chloride] but not to forskolin or dbcyclicAMP in RV papillary muscles; (d) an increased incidence of ectopy at low concentrations of NE, forskolin, and dbcyclicAMP in LV papillary muscles; (e) no alteration in papillary muscle responses to phenylephrine but significantly increased left atrial inotropic responses [51 +/- 5 vs. 33 +/- 2% (sham rats) of calcium chloride] and right atrial chronotropic responses [30 +/- 2 vs. 18 +/- 4 (sham rats) beats/min]; and (f) a selective decrease in beta 1-adrenoceptor density in both ventricles. Thus, NE infusion causes selective LV hypertrophy; responses of compounds that increase intracellular cyclicAMP are affected to a greater extent in papillary muscles from the hypertrophied ventricle than in tissues from the other chambers of the heart.     

Flutamide: Hirsutism in Women

This Hospital Pharmacy feature is extracted from Off-Label Drug Facts, a publication available from Wolters Kluwer Health. Off-Label Drug Facts is a practitioner-oriented resource for information about specific drug uses that are unapproved by the US Food and Drug Administration. This new guide to the literature enables the health care professional or clinician to quickly identify published studies on off-label uses and determine if a specific use is rational in a patient care scenario. References direct the reader to the full literature for more comprehensive information before patient care decisions are made. Direct questions or comments regarding Off-Label Drug Uses to ude.uk@larenegj.