Renal urate transport during variations in urate synthesis in the rat

Summary In order to determine the effect of intrarenal synthesis of urate upon the urinary urate excretion in the rat, we effected large changes in urate synthesis by increasing it with hypoxanthine and decreasing it with allopurinol. Hypoxanthine infusion increased plasma urate rapidly and also increased the urinary urate excretion and its renal clearance. However, when the plasma urate was maintained constant, hypoxanthine had no effect upon renal urate transport. Conversely, allopurinol infusion rapidly diminished the plasma urate, urinary urate excretion and its renal clearance. Again, the maintenance of a constant plasma urate concentration prevented any change in urate transport during allopurinol. The urinary degradative purine metabolite pattern was altered pre-dictably by hypoxanthine and allopurinol. Assuming that any putative intrarenal component of urate synthesis would be affected predictably and consistently by hypoxanthine and allopurinol, these results suggest that changes in intrarenal urate synthesis are not an important determinant of urate excretion in the rat.Reported in abstract form in Clinical Research23, 508 A (1975)     

非布司他用于预防小细胞肺癌化疗后急性肿瘤溶解综合征效果观察

目的探讨非布司他用于预防小细胞肺癌(SCLC)化疗期间出现急性肿溶解综合征(ATLS)的效果.方法收集2016—2020年盘锦市中心医院收治的SCLC化疗患者50例,随机分为对照组和观察组各25例.两组患者分别于化疗前1 d开始口服药物预防ATLS出现,对照组采用别嘌醇,对照组采用非布司他.比较两组患者用药前后不同时间点血尿酸(SUA)、肌酐(Scr)和尿素氮(BUN)变化情况,及化疗前期间ATLS发生情况.结果两组患者D0时间点SUA、Scr、BUN差异无统计学意义(P>0.05);经治疗后,D₁时间点SUA、Scr、BUN呈增加趋势,D₂和D₃时间点SUA、Scr、BUN呈下降趋势,两组患者D₁、D₂、D₃时间点SUA、Scr、BUN差异有统计学意义(P<0.05).化疗期间对照组ATLS发生率为24.00%;观察组ATLS发生率为4.00%,差异有统计学意义(P<0.045).结论非布司他能够进一步控制SCLC患者化疗期间血尿酸水平,并且有效保护患者肾脏功能,减少ATLS的发生.     

别嘌呤醇对离体大鼠缺血再灌注心肌的保护作用

为探讨别嘌呤醇(allo)对心肌的保护作用与机理,采用离体大鼠心脏灌注模型,研究allo对缺血再灌注心肌的保护作用。结果表明心肌缺血再灌注后磷酸肌酸肌酶(CPK)释放增多,超氧化物歧化酶(SOD)活性降低,黄嘌呤氧化酶(XO)活性和丙二醛(MDA)量增加,心肌超微结构破坏明显。allo通过抑制氧自由基的生成对缺血再灌注心肌起保护作用。     

Xanthine oxidase inhibition by allopurinol affects the reliability of urinary caffeine metabolic ratios as markers for N-acetyltransferase 2 and CYP1A2 activities

Objectives: To evaluate the in vivo effect of xanthine oxidase (XO) inhibition by allopurinol on the determination of polymorphic N-acetyltransferase 2 (NAT2) and cytochrome P450 1A2 (CYP1A2) with urinary caffeine metabolic ratios. Methods: In an open, prospective study involving 21 healthy subjects (eight fast, 13 slow NAT2 acetylators) allopurinol (300 mg perday) was administered orally on trial days 1–8, followed by a wash-out period of 8 days. Urinary caffeine tests (200 mg caffeine p.o.) were performed repetitively. Urine was collected for 8 h and venous blood samples for the determination of allopurinol, oxypurinol and uric acid were drawn. The urinary caffeine metabolites 1-methyluric acid (1MU), 1-methylxanthine (1MX), 1,7-dimethyluric acid (17MU), 1,7-dimethylxanthine (17MX), 5-acetylamino-6-formylamino-3-methyluracil (AFMU), plasma allopurinol and oxypurinol were analysed using high-performance liquid chromatography (HPLC). Results: During XO inhibition by allopurinol, the formation of 1MU from 1MX and therefore the XO ratio 1MU/1MX decreased to 15.9 (1.2)% [mean with (SEM)] of baseline values (P < 0.005). The NAT2 ratio AFMU/1MX decreased likewise to 56.7 (6.3)% (P < 0.005). AFMU/(AFMU + 1MX + 1MU), an alternative NAT2 ratio, remained constant, but the CYP1A2 ratio (AFMU + 1MX + 1MU)/17MU, used to express CYP1A2 activity, transiently increased to 167 (13)% (P < 0.005). The NAT2 phenotype did not influence CYP1A2 and XO ratios or plasma oxypurinol pharmacokinetics. Conclusions: Several caffeine metabolic ratios are commonly used to express the activities of NAT2, CYP1A2 and XO both in healthy volunteers and in polymedicated patients, although their reliability has not been evaluated thoroughly during concurrent drug administration. The findings of this study suggest that NAT2 phenotyping should be performed using the ratio AFMU/(AFMU + 1MX + 1MU) if an XO inhibitor may be present. It also shows that the determination of CYP1A2 activity with caffeine as a metabolic probe is considerably altered under these conditions. Thus, concomitant drug administration may impair the robustness of multiple pathways of the complex caffeine test. This points to the need for alternative probes, designed to assess only the activity of a single enzyme because, in contrast to healthy volunteers, in patients known or unknown drug interactions may often be present. Received: 10 August 1998 / Accepted in revised form: 5 October 1998     

Lipopolysaccharide-induced platinum accumulation in the cerebral cortex after cisplatin administration in mice: Involvement of free radicals

The relationship between the accumulation of platinum in the cerebral cortex following cisplatin administration and injury to the blood-brain barrier after lipopolysaccharide (LPS) treatment was investigated. The appearance of intravenously injected fluorescein in the brain was significantly increased 10–24 h after LPS treatment, the effect being dose-dependent. Platinum was detectable in the cerebral cortex of cisplatin-treated mice 24 h after LPS treatment, but not without LPS treatment. In mice pretreated with -tocopherol, LPS administration did not significantly augment fluorescein penetration into the brain, whereas pretreatment with either allopurinol or ascorbic acid did not modify the LPS-induced increase in fluorescein penetration. In contrast, platinum in the cerebral cortex after cisplatin administration was still detectable in the allopurinol-, ascorbic acid-, and -tocopherol-pretreated groups, and the levels of platinum in these groups were not significantly different from those in the group treated with LPS only. Administration of superoxide dismutase (SOD), but not of catalase, tended to inhibit the penetration of fluorescein. Both SOD and catalase significantly lowered platinum content in the cerebral cortex following cisplatin administration in mice treated with LPS. Thus, free radicals may injure the blood-brain barrier in mice challenged with LPS, and allow cisplatin to penetrate into the cerebral cortex, resulting in platinum accumulation.     

别嘌呤醇对睾丸扭转的治疗作用

目的 研究睾丸扭转以后组织的受损情况，观察别嘌呤醇药物对睾丸扭转的治疗意义。方法 以大鼠为研究对象，测定一侧睾丸扭转后两侧睾丸组织的脂质过氧化物含量。按扭转时间分组，分析睾丸扭转、复位、药物应用以后局部的损伤变化情况。结果 单侧睾丸扭转以后，两侧组织的脂质过氧化物含量都明显上升。脂质过氧化物的含量与扭转时间有关。别嘌呤醇应用后，能降低扭转2h以内的两侧睾丸脂质过氧化物产量，以及扭转6h以内的对侧睾丸脂质过氧化物含量。结论 别嘌呤醇对改善睾丸扭转损伤有治疗意义，临床上应提倡早期用药。     

The possible antianginal effect of allopurinol in vasopressin-induced ischemic model in rats

The anti-anginal effects of allopurinol were assessed in experimental model rats of angina and their effects were evaluated with amlodipine. In the vasopressin-induced angina model, oral administration of allopurinol in dose of 10 mg/kg revealed remarkably analogous effects in comparison with amlodipine such as dose-dependent suppression of vasopressin-triggered time, duration and severity of ST depression. In addition, allopurinol produced dose dependent suppression of plasma Malondialdehyde (MDA) level, systolic blood pressure, cardiac contractility and cardiac oxygen consumption; while in contrast, amlodipine minimally suppressed the elevation of plasma MDA level. Endothelial NO synthase (eNOS) expression, serum nitrate were strikingly increased, however lipid profile was significantly reduced. Seemingly, allopurinol was found to be more potent than amlodipine – a calcium channel antagonist. To conclude, it was explicitly observed and verified that on the ischemic electrocardiography (ECG) changes in angina pectoris model in rats, allopurinol exerts a significant protective effects, reminiscent of enhancement of vascular oxidative stress, function of endothelial cells, improved coronary blood flow in addition to the potential enhancement in myocardial stress. Moreover, our findings were in conformity with several human studies.     

奥曲肽治疗别嘌呤醇所致严重腹泻1例

患者因服用别嘌呤醇所致引发多种严重的药物不良反应,皮疹等不良反应经H1受体拮抗剂、激素等处理后好转,但严重腹泻经常规用药治疗无法得以改善,予以使用奥曲肽注射液以药理作用治疗后即好转,提示奥曲肽可能适用于药物不良反应引起的难治性严重腹泻。     

降尿酸治疗对脑梗死患者血管内皮功能的影响

目的:研究高尿酸血症的急性脑梗死患者降尿酸治疗对血管内皮功能及血压的影响。方法:搜集同一中心共138例患者入选该研究。高尿酸血症并急性脑梗死者入选92例,随机（随机数字法）分为实验组46例,对照组46例,同时入选同期血尿酸正常的急性脑梗死患者46例,实验组口服别嘌醇3个月治疗高尿酸血症。对这些人群进行抽血化验,记录治疗前后血尿酸、血脂及hs-CRP,同时检测患者血压、体质量指数（BMI）,并采用超声无创血流介导的血管舒张功能（FMD）进行血管内皮功能评估,治疗前后各组之间比较并进行统计学分析。结果:别嘌醇治疗3个月后实验组血尿酸[(479.7±49.0) μmol/L vs. (381.2±76.7)μmol/L]、hs-CRP[(8.1±6.7) mg/L vs. (5.1±4.6) mg/L]、收缩压[(124.7±26.3) mmHg vs. (97.4±13.5) mmHg]明显降低( P<0.05),FMD[(7.6±3.5%) vs. (11.2±3.9%)]明显升高( P<0.05),FMD升高的程度与血尿酸降低的程度呈正相关( r=0.463, P<0.01),多元回归分析显示血尿酸是FMD的独立影响因子（ β=-0.229, P=0.035)。 结论:高尿酸血症的急性脑梗死患者中降尿酸治疗可明显改善患者的血管内皮功能,改善炎症状态,降低患者血压,进一步印证了高尿酸血症导致血管内皮功能紊乱,促进动脉粥样硬化的发生与发展。     

高尿酸血症大鼠模型的实验研究

以含腺嘌呤的饲料在SD大鼠建立高尿酸血症动物模型 ,以别嘌呤醇治疗能降低高尿酸血症大鼠血尿酸值