Effects of Topically Applied Spironolactone on Androgen Stimulated Sebaceous Glands in the Hamster Pinna

The effects of spironolactone (5% SYC-201G, a preparation developed for clinical use in acne vulgaris by Searle Yakuhin K.K.), which is known to have antiandrogenic effects by competitively inhibiting dihydrotestosterone at androgen receptor sites, was topically applied to the androgen stimulated sebaceous glands of adult female golden hamsters. Androgen stimulation, induced by intramuscular injection of testosterone propionate (TP) every other day over a two week period, resulted in a 2.5 to 2.7 time increase in the size of the sebaceous glands of the hamster pinna. Once-daily treatment with 5% SYC-201G or matching placebo was applied to androgen-stimulated hamsters on one pinna only during the same period as TP injection. Comparison between the treated and untreated sides revealed a significant suppression in the sebaceous gland size (p<0.05) by 5% SYC-201G; no such effect was observed with placebo. The difference in the suppression rate of the sebaceous gland size between 5% SYC-201G (23%) and matching placebo (–4.7%) was significant (p<0.01).     

常规应用螺内酯联合依那普利治疗老年扩张型心肌病心力衰竭

目的评价螺内酯联合依那普利治疗老年人扩张型心肌病（DCM）心力衰竭的有效性和安全性。方法以148例老年DCM心力衰竭患者作研究对象,按随机化原则分为观察组（74例）和对照组（74例）。对照组为依那普利,加上基础用药（地高辛、双氢克尿噻）;观察组为对照组用药加上螺内酯。治疗6周后复查两组的动态心电图、超声心动图。结果治疗后两组的左室射血分数（LVEF）均有增加,左室收缩末期容积（LVESV）和左室舒张末期容积（LVEDV）均有减少,24 h室性早搏（VA）数也均有减少;观察组与对照组比较,LVEF显著增加。两组均未发现高血钾及肝肾功能损害。结论在老年DCM心力衰竭常规用药的基础上,常规加用螺内酯联合依那普利的治疗有效、安全,可显著改善左室重构和防治猝死。     

Improved bioavailability and clinical response in patients with chronic liver disease following the administration of a spironolactone: β-cyclodextrin complex

Aims To compare the absorption and clinical effect of spironolactone from an inclusion complex with β-cyclodextrin (SP-COMP) to Aldactone tablets (ALD) in chronic liver disease.
Methods Patients, admitted with chronic liver disease, completed a randomized crossover steady state study. They received their spironolactone dose as either daily SP-COMP or ALD for 7 days. Serial blood samples were drawn over a 24  h period from day 7 of each therapy. Accurate fluid balance was recorded on days 5–7 and 12–14. Thirteen (six females) whose mean (s.d.) age and weight was 58.4(9.3) years and 74.3(19.0)  kg completed the study.
Results The mean (95% confidence limits) relative bioavailability for SP-COMP (compared with ALD) from steady state serum concentrations of canrenone, 6β-hydroxyl 7α-thiomethyl spironolactone and 7α-thiomethyl spironolactone was 310.0 (265.4, 336.7), 233.4(212.9, 250.8) and 254.8(230.8, 279.0)%, respectively. Improvements in clinical status and fluid balance occurred over the last 3 days of SP-COMP with a mean (s.d.) net loss, in fluid balance, of 1370(860)ml compared with a gain of 228(936)ml during ALD.
Conclusions Better absorption of spironolactone from the spironolactone: β-cyclodextrin complex formulation should lead to a reduction in dosage and perhaps a more consistent effect in patients with chronic liver disease.     

低剂量螺内酯治疗充血性心力衰竭临床疗效观察

目的观察低剂量螺内酯治疗充血性心力衰竭(CHF)的临床疗效.方法100例CHF患者随机分成螺内酯组52例,对照组48例,螺内酯组在常规治疗的基础上加用螺内酯20～40 mg/d,连续应用8周以上.结果螺内酯组与对照组比较左室射血分数、每搏输出量和临床疗效差异有显著性(P＜0.05).结论螺内酯治疗充血性心力衰竭有较好的临床疗效,可改善心功能和临床症状,降低病死率.     

Is spironolactone safe for dialysis patients?

BACKGROUND: Spironolactone is useful in heart failure, but is not given to dialysis patients for fear of hyperkalaemia. This study evaluated the safety of spironolactone administration in haemodialysis patients. METHODS: Fifteen haemodialysis outpatients with mean serum potassium <5.6 mEq/l over the preceding 4 months were treated with spironolactone 25 mg daily for 28 days. Serum potassium was measured before every haemodialysis during the study. Aldosterone and renin were measured at the beginning and end of the study. Patients were monitored for side effects. Data were examined with a paired t-test, with patients serving as their own controls and P < 0.05 considered significant. A sample size of 14 was required to achieve a power of 0.8 and a P = 0.05 to detect a potassium difference of 0.5 +/- 0.6 mEq/l. All patients were analysed as intention-to-treat. RESULTS: The mean potassium level was 4.6 +/- 0.6 mEq/l at baseline and 4.9 +/- 0.9 mEq/l at study completion (P = 0.14). Thirteen patients completed the trial with no potassium levels >6.0 mEq/l. Four patients had potassium levels between 5.5 and 6.0 mEq/l. One patient was withdrawn at day 20 after developing hyperkalaemia (7.6 mEq/l). Another patient was withdrawn at day 25 after missing a dialysis treatment. There were no differences in either baseline or 28 day aldosterone or renin levels (16.8 +/- 28.8 vs 11.7 +/- 6.1 ng/dl and 3.5 +/- 3.9 vs 3.5 +/- 3.5 ng/ml/h, respectively). Infrequent side effects included dry mouth, nosebleed, pruritis, gynecomastia and diarrhoea. No significant leukopenia or anaemia was noted. CONCLUSIONS: Spironolactone may be considered as a treatment option for selected chronic haemodialysis patients with heart disease.     

螺内酯，氯沙坦及二者合用对急性心肌梗死大鼠早期新生血管的影响

目的:探讨螺内酯80mg/(d·kg)和氯沙坦10mg/(d·kg)对急性心肌梗死(AMI)大鼠早期根四周围侧枝循环的影响。方法:随机将雄性Wister健康大鼠60只分为假手术组(n=12)与心肌梗死(MI)组(n=48)。将建立MI模型术后72小时存活大鼠随机分为AMI组(n=12),AMI 氯沙坦组(n=12),AMI 螺内酯组(n=12)AMI 螺内酯 氯沙坦组(n= 12)。利用免疫组化的方法,方法,测定AMI早期大鼠MI周围非梗死区心肌基质金属蛋白酶-2,-9(mmp-2,-9)及其抑制物-1(Timp-1)蛋白的表达,并对各组梗死周围非梗死区毛细血管密度进行比较。结果:MI组及MI用药组在MI后1周和2周时,梗死周围区毛细血管密度均高于假手术组;MI用药组在MI后1周和2周时,梗死周围区毛细血管密度均高于MI组。与MI组相比,螺内酯,氯沙坦及二者合用时mmps/timp-1比值先高而后趋于平衡。结论:螺内酯80mg/(d·kg)、氯沙坦80mg/(d·kg)及二者合用时,通过mmp-2,-9及其Timp-1起作用,促进梗死周围非梗死区侧枝循环的形成。     

缬沙坦和螺内酯对高血压大鼠心肌胰岛素样生长因子-1的作用

目的观察自发性高血压大鼠(SHR)和WKY大鼠心肌胰岛素样生长因子1(IGF1)的浓度和表达及缬沙坦与螺内酯对SHRIGF1的影响,探讨IGF1与心肌肥厚的病理机制。方法将18只6周龄SHR随机分成3组,每组6只。其中2组分别灌胃缬沙坦30mg·kg-1·d-1和螺内酯20mg·kg-1·d-1,SHR阳性对照组给正常饮水,并与雄性同周龄WKY大鼠比较。实验期为13周,放射免疫法检测心肌IGF1的浓度,免疫组化法检测4组大鼠心肌IGF1的表达。结果SHR对照组IGF1表达和浓度均明显高于WKY组(P<0.01),缬沙坦组和螺内酯组的IGF1较SHR对照组下降(P<0.01),而且缬沙坦组比螺内酯组下降的更明显(P<0.05),两组血压、LVMBW均显著低于SHR组(P<0.01)。结论IGF1在肥厚心肌中表达明显增加,而缬沙坦和螺内酯在降压的同时可以抑制IGF1的表达,提示IGF1在心肌肥厚发展中起一定作用。     

Effects of Spironolactone Treatment in Elderly Women With Heart Failure and Preserved Left Ventricular Ejection Fraction

BackgroundAlthough spironolactone has been shown to decrease morbidity and mortality in patients with heart failure and reduced left ventricular ejection fraction, its role in patients with heart failure and preserved left ventricular ejection fraction (HFpEF) is not well defined. In this study we investigated the mechanisms involved when elderly women with HFpEF are treated with spironolactone.Methods and ResultsForty-eight women with HFpEF were enrolled in a randomized placebo-controlled trial and were assigned to 25 mg spironolactone daily (n = 24) or placebo (n = 24) for 6 months. Six-minute walk distance, clinical composite score, Doppler echocardiography, and biomarkers were determined at baseline and after 3 and 6 months of therapy. Six months of spironolactone treatment stabilized clinical symptoms, as demonstrated by significant worsening of the clinical composite score in the placebo group (P = .02). In addition, spironolactone treatment improved diastolic function by significantly increasing early diastolic tissue Doppler velocity of the lateral mitral annulus (lateral e′; P = .003) and significantly reducing the mitral peak E velocity to lateral e′ ratio (lateral E/e′; P = .0001). Finally, spironolactone favorably affected remodeling through a reduction in myocardial fibrosis measured by a reduction in type III procollagen levels (P = .035). Six-minute walk distance did not significantly improve with spironolactone treatment compared with placebo.ConclusionsSpironolactone stabilizes functional capacity and symptoms and improves diastolic function, possibly through its ability to suppress type III procollagen synthesis.     

疏血通注射液联合脑络舒通汤治疗急性脑梗死的疗效分析

目的：探讨疏血通注射液联合脑络舒通汤治疗急性脑梗死的临床疗效。方法选取急性脑梗死患者95例,随机分为研究组（n=48）和对照组（n=47）。对照组予以疏血通注射液治疗,研究组予以疏血通注射液联合脑络舒通汤治疗,分析2组治疗效果。结果治疗后研究组各症状症候积分和全血粘度(4.02±0.15)、血浆粘度(1.46±0.14)、红细胞聚集指数水平(2.36±0.47)均优于对照组,差异有统计学意义（P<0.05）。结论疏血通注射液联合脑络舒通汤治疗可显著缓解急性脑梗死的临床症状,优化患者血循环,值得临床推广应用。