Effect of allopurinol on damage caused by free radicals to cryptorchid testes

Cryptorchidism causes apoptosis of germ cells. It has been suggested that the redox regulatory system is involved in this process. The free radicals produced are thought to be generated during the production of uric acid, a reaction catalyzed by xanthine oxidase. This enzyme is inhibited by allopurinol; however, the role of allopurinol in neonate rats with inguinal cryptorchidism has not been assessed yet. Sixty male Wistar rats were used and five groups were formed: a control, a sham, a sham group with allopurinol administration and two groups with surgical unilateral cryptorchidism, which either did not receive, or received, allopurinol. The rats were assessed at 40 days post-partum. Reactive oxygen species concentration and epithelial area were measured and the histopathological, apoptotic and cellular proliferation indexes were determined. We found a decrease in reactive oxygen species, histopathological and apoptotic indexes and an increase in proliferation index and epithelial area in rats with cryptorchidism treated with allopurinol in comparison with rats with untreated cryptorchidism. We suggest that the over-production of reactive oxygen species plays an important role in the damage of the cryptorchid testes. Allopurinol administration decreases reactive oxygen species concentrations as well as the damage to the germ epithelium.     

Inhibitory effect of allopurinol on adjuvant arthritis in rats

The effect of Allopurinol (ALLO), on adjuvant arthritis was studied in rats and compared with the effect of indomethacin (IND). Drugs were given by intraperitoneal injection for each day beginning from the day of adjuvant injection (day 0) and continued until the 16th day. Paw swelling was measured on days 4, 17 and 29, and secondary lesions were assessed on days 17 and 29. Polymorphonuclear leukocyte (PMNs) count was also evaluated on day 17.ALLO, at relatively high doses (25–50 mg/kg), reduced paw swelling of the adjuvant-injected extremity on day 4; lower doses (6.25–12.5 mg/kg), however, elicited the same inhibitory effect on day 17. IND (0.25 mg/kg) also prevented paw swelling on days 4 and 17. Both ALLO and IND reduced the secondary lesions on days 17 and 29 and prevented the increase in polymorphonuclear leukocytes during the development of adjuvant arthritis. Possible mechanisms of the antiinflammatory effect of ALLO in adjuvant arthritis are discussed.     

别嘌呤醇对大鼠应激性肺损伤的影响

用大白鼠复制冷束缚应激性肺损伤动物模型,以别嘌呤醇灌胃作预处理,与生理盐水灌胃作对照,观察别嘌呤醇对应激性肺损伤的保护作用。结果表明,预处理组动物的肺水肿严重程度及肺透明膜形成等均比对照组轻(P<0.05)。别嘌呤醇的保护作用提示氧衍生自由基参与了应激性肺损伤的发病。     

别嘌呤醇对急性心肌梗死患者心功能、内皮功能、炎症指标的影响

目的:观察应用别嘌呤醇控制高尿酸血症对急性心肌梗死患者心功能、内皮功能及炎症指标的影响。方法:98例急性心肌梗死伴高尿酸血症患者随机分为治疗组与对照组。治疗组采用饮食控制加别嘌呤醇治疗,对照组仅采用饮食控制,疗程均为6wk,观察2组治疗前、后心功能、内皮功能及炎症指标的变化。结果:治疗组血尿酸降低明显(t=2.317,P=0.046);治疗组左室射血分数、血流依赖性舒张功能较对照组改善明显(t=—2.106,P=0.073;t=—3.47,P=0.007);治疗组C反应蛋白较对照组降低明显(t=4.78,P=0.002)。结论:别嘌呤醇可降低血清尿酸,改善血管内皮功能、心功能及炎症反应。     

高效液相色谱法测定别嘌醇片的含量

目的:建立高效液相色谱法测定别嘌醇片含量的方法。方法:采用Shim-pack C18(150 mm×4．6 mm,5μm)分析柱,流动相为甲醇-水-冰醋酸(75:25:0．2),检测波长为251 nm;流速为1 ml·min-1。结果:别嘌醇浓度在8～72μg·ml-1范围内与峰面积呈良好的线性关系,r=0．999 9。平均回收率为99．3％,RSD为1．5％(n=9)。结论:本方法简便、快速、准确,可作为别嘌醇片的含量测定方法。     

An unusual patient with kidney stones composed of 1-methyluric acid

An unusual case with kidney stones composed mainly of 1-methyluric acid is described. The patient, a Caucasian male of Celtic descent, reportedly drank at least eight cups of coffee per day and had a long history of rheumatoid arthritis, gouty attacks and renal colics—the latter attributed to nephrocalcinosis and analgesic nephropathy. He was treated with allopurinol. At 54 years, a bilateral nephrolithotomy was performed. Stone samples were analysed by thermogravimetry and infrared spectroscopy and reported to be 12–25% calcium oxalate, the remainder being organic uric acid-like material. Analysis of the extracts by HPLC confirmed that the organic material contained 67% of 1-methyluric acid and 33% of uric acid. Possible mechanisms leading to the precipitation of 1-methyluric acid from urine are discussed. We conclude that the high caffeine intake resulted in extremely elevated urinary concentrations of 1-methyluric acid favouring the formation of 1-methyluric acid stones.     

The effect of benzbromarone on allopurinol/oxypurinol kinetics in patients with gout

Summary The objectives of this study were to establish if, and to what extent, benzbromarone affects allopurinol/oxypurinol kinetics, and to compare the uric acid lowering capabilities of Allomaron^® (allopurinol 100 mg plus benzbromarone 20 mg) with the effects of allopurinol alone in patients with confirmed gout.We studied 14 adult men in an open randomized cross-over study. After a 14 day run-in period with Zyloprim^® (2×100 mg allopurinol tablets in the morning), the patients were randomly allocated to morning doses of either Allomaron^® (2 tablets) or Zyloprim^® (2 tablets). Seven days later cross-over was effected and the alternative treatment was taken for a further 7 days.On days 7 and 14 the patients came into hospital and venous blood samples were taken over 24 h for allopurinol and oxypurinol assays by HPLC. Serum uric acid was determined on days -14, 1, 7, and 14.Benzbromarone lowered plasma oxypurinol concentrations (Allomaron^®/Zyloprim^® mean ratio of AUC₀₂₄ was 59%; 95% confidence interval 54–64%), but did not affect plasma allopurinol concentrations.Despite this pharmacokinetic interaction of benzbromarone with allopurinol, resulting in lower plasma concentrations of oxypurinol, Allomaron^® was superior to allopurinol alone in lowering serum uric acid, probably because of the added uricosuric effect of benzbromarone.     

A method for determination of the inhibition of xanthine oxidase activity in plasma during allopurinol treatment

Summary A micromethod suitable for measuring the combined blood levels of allopurinol and alloxanthine has been developed. The two compounds display marked inhibition of xanthine oxidase activity (K_i=6.3×10^–10 and 5.4×10^–10 M), so the amounts found in 20 µl serum from allopurinol-treated patients can cause marked inhibition of xanthine oxidase activity in vitro under appropriate conditions. If the concentrations of compounds acting in an allopurinol-like manner are expressed in terms of allopurinol, activity equivalent values are obtained which reflect the effective drug concentration during therapy. The procedure is simple and suitable for serial examinations. It also satisfies the demands of the clinician, in that it can reveal any disturbance in the absorption of allopurinol and in excretion of the drug and its active metabolite, alloxanthine.     

非布司他与别嘌醇治疗慢性肾脏病合并高尿酸血症的疗效比较

目的探讨非布司他与别嘌醇在治疗慢性肾脏患者合并高尿酸血症的临床疗效分析比较。方法回顾性分析2013年1月至2015年2月中国人民解放军第174医院收治的78例慢性肾脏病合并高尿酸血症患者,并根据治疗方法将其分为对照组和治疗组。2组患者均采用优质低蛋白饮食、降压[钙通道阻滞剂和(或)β受体阻滞剂]、纠正贫血(促红细胞生长素)、补充α酮酸(开同)及纠正水、电解质酸碱平衡(碳酸氢钠)等综合治疗;观察组加用非布司他20 mg/d,对照组加用别嘌醇100 mg/d;2组均治疗观察24周。分析治疗前后2组患者血肌酐、血尿酸及临床疗效,并进行统计学分析。结果 2组治疗前后实验室相关指标比较结果表明2组治疗后血尿酸与治疗前比较,均有显著改善(均P0.05),且治疗组患者治疗后尿酸与对照组行组间比较有统计学差异(P0.05)。治疗组治疗后血肌酐与治疗前比较明显降低,有统计学差异(P0.05);而对照组治疗前后血肌酐无明显变化(P0.05)。治疗组临床总有效率高于对照组(P0.05)。2组均未发现明显的不良反应。结论非布司他相对于别嘌醇降低血尿酸水平的作用更强,且可改善肾功能,药物不良反应较小,因此在治疗慢性肾脏合并高尿酸血症患者上具有良好的应用前景。