高尿酸血症对未透析慢性肾脏病残余肾功能的影响及非布司他的保护效果分析

目的 分析高尿酸血症(HUA)对未透析慢性肾脏病(CKD)病人残余肾功能的影响及非布司他的保护效果.方法 回顾性纳入2017年8月至2018年8月于滁州市第一人民医院肾病科住院的未透析CKD病人188例,其中合并HUA者86例,无HUA者102例.对合并HUA者的86例根据治疗方法不同分为非布司他组(46例)和别嘌醇组(40例).病人均接受常规治疗,别嘌醇组给予别嘌醇片口服,非布司他组给予非布司他片口服,4周为1个疗程,持续治疗6个疗程.检测合并HUA组和无HUA组入组时的空腹血尿酸、肾功能指标[血清肌酐、血尿素氮、估算肾小球滤过率(eGFR),检测非布司他组和别嘌醇组治疗前后的血尿酸水平及肾功能指标、血浆白蛋白、总胆固醇、三酰甘油水平的变化.结果 合并HUA组病人的血尿酸(510.42±124.28)μmol/L、血尿素氮(23.64±6.27)mmol/L、血清肌酐(358.88±92.14)μmol/L水平均显著高于无HUA组的血尿酸(388.95±98.26)μmol/L、血尿素氮(18.20±5.70)mmol/L、血清肌酐(270.33±75.26)μmol/L,eGFR(38.24±10.74)mL·min?1·(1.73 m2)?1水平显著低于无HUA组(46.20±12.68)mL·min?1·(1.73 m2)?1(P<0.05);Pearson相关性分析显示,合并HUA的病人血尿酸水平与eGFR负相关(r=-0.526,P<0.05),与血尿素氮、血清肌酐水平正相关(r=0.422、0.398,P<0.05);非布司他组的治疗有效率91.30％显著高于别嘌醇组70.00％(P<0.05),治疗后非布司他组的血尿酸(320.44±60.38)μmol/L、血尿素氮(14.23±2.78)mmol/L、血清肌酐(230.52±44.21)μmol/L水平均显著低于别嘌醇组的血尿酸(388.24±64.55)μmol/L、血尿素氮(16.53±3.33)mmol/L、血清肌酐(278.55±60.23)μmol/L,eGFR(56.92±12.38)mL·min?1·(1.73 m2)?1水平显著高于别嘌醇组eGFR(49.70±12.70)mL·min?1·(1.73m2)?1(P<0.05);非布司他组和别嘌醇组治疗前后的白蛋白、总胆固醇、三酰甘油水平比较,均差异无统计学意义(P>0.05).结论 HUA可对未透析CKD病人残余肾功能造成严重影响;非布司他对病人肾功能具有保护作用,采用非布司他积极治疗可有效降低血尿酸水平,或可延缓CKD进展.     

欧盟批准新型痛风治疗药Adenuric上市

2008年5月5日，Ipsen公司宣布欧盟批准Adenuric（Febuxostat，非布索坦）治疗痛风患者的高尿酸血症。Febuxostat是一种非嘌呤类黄嘌呤氧化酶选择性抑制剂。临床研究显示，与别嘌呤醇相比，Febuxostat可使更高比例的患者血尿酸水平降低到6mg&#183;dL^-1以下。在用药船周时，与别嘌呤醇组相比，Febuxostat组也有更高比例的患者血尿酸水平降低到6mg&#183;dL^-1以下。     

降尿酸中药方对慢性肾脏病3~5期合并高尿酸血症患者的作用

目的:观察改良四妙散方联合非布司他降低尿酸对慢性肾脏病(chronic kidney disease,CKD)3~5期合并高尿酸血症患者的作用,评估中药方联合非布司他降尿酸的安全性及有效性。方法:选择2018年4月至2019年4月在上海市静安区闸北中心医院治疗、年龄18~75岁、CKD 3~5期合并高尿酸血症的患者120例,随机分为两组,每组60例。观察组用降尿酸中药方联合半剂量非布司他(20 mg,qd),对照组单用非布司他(40 mg,qd)降尿酸治疗。分别检测治疗0、3、6个月患者的血清肌酐、血尿素氮、血尿酸、尿蛋白等指标,记录治疗前后的中医症候积分,以估算肾小球滤过率(estimated glomerular filtration rate,eGFR)的降幅>10%、进行透析、发生心脑血管事件为观察终点事件。结果:与治疗前相比,观察组患者治疗6个月的eGFR升高[(28.01±13.37)ml/(min·1.73 m²)vs(23.36±10.80)ml/(min·1.73 m²)]、血尿素氮下降[(12.52±4.58)mmol/L vs(14.62±4.99)mmol/L],血尿酸下降[(325.32±43.45)μmol/L vs(543.53±54.75)μmol/L],24 h尿蛋白下降[(1624.32±1153.00)mg/d vs(2156.01±1322.43)mg/d],差异均有统计学意义(P<0.05)。观察组患者的中医症候积分明显降低,与对照组比较,差异有统计学意义(P<0.05)。观察组有1例患者到达终点事件;对照组有3例患者到达终点事件,其中1例进行血液透析治疗。观察组和对照组的降尿酸治疗有效率分别为98.3%和91.7%,差异无统计学意义(P=0.173)。结论:降尿酸中药方联合半剂量非布司他降尿酸治疗,能够明显降低尿酸,提高eGFR,明显改善CKD 3~5期合并高尿酸血症患者的临床症状,表明治疗安全、有效。     

不同剂量非布司他对痛风伴高尿酸血症患者血尿酸水平及血清ET-1、NO和MPO的影响

目的 探讨不同剂量非布司他对痛风伴高尿酸血症患者血尿酸水平及血清内皮素-1(ET-1)、一氧化氮(NO)和髓过氧化物酶(MPO)的影响.方法 对2013年10月-2014年12月诊治的痛风伴高尿酸血症60例的临床资料进行回顾性分析.根据入院时间分为A、B、C组,每组20例.A组应用非布司他片40 mg,B组给予非布司片他80 mg,C组给予别嘌呤醇片300 mg.治疗疗程均为24周.检测并记录3组治疗前1d、治疗12和24周后血尿酸水平、血清ET-1、NO、MPO水平变化及不良反应发生情况.结果 与治疗前1d相比,3组治疗后12、24周后血尿酸、ET-1、MPO水平降低,NO水平升高,B组治疗24周后血清ET-1水平低于治疗12周后(P＜0.05).3组均未出现严重不良反应.结论 不同剂量非布司他片及别嘌呤醇片均能有效降低痛风伴高尿酸血症患者血清ET-1与血尿酸水平,40 mg非布司他片改善患者炎症状态稳定性好,且安全性较高.     

Lesinuard钠盐合成路线图解

<正>痛风及高尿酸血症是由于体内尿酸合成过多或尿酸排泄过少而导致体内血尿酸水平过高,尿酸盐结晶在关节、肾脏中沉积,进而诱导引发一系列炎症反应的代谢性疾病。该病严重威胁人类健康,是仅次于糖尿病的第二大代谢疾病。通过药物降低血尿酸水平是预防和治疗痛风以及高尿酸血症的有效方法,临床常用的药物包括黄嘌呤氧化酶(xanthine oxidase,XO)抑制剂别嘌呤醇(allopurinol)、非布索坦(febuxostat)和托匹司他(topir-     

别嘌呤醇与厄贝沙坦联用对慢性肾脏疾病合并高尿酸血症患者的炎症因子及心脏功能的影响

目的:观察别嘌呤醇与厄贝沙坦联用对慢性肾脏疾病(CKD)患者的血尿酸、超敏C反应蛋白(hs-CRP)、血管性血友病因子(vWF)、心脏结构与功能的影响。方法:将CKD合并高尿酸血症患者48例分成A、B组,各24例。A组接受厄贝沙坦治疗,B组接受厄贝沙坦加别嘌呤醇治疗。入组第2天及别嘌呤醇治疗满12个月后清晨空腹抽血检测血尿酸、hs-CRP和vWF水平,行心脏超声检查。结果:治疗后,A、B组血尿酸、hs-CRP、vWF水平均较治疗前有显著下降(P<0.05),但B组下降更明显(P<0.05);治疗后,A、B组左心房内径、左心室舒张末期内径、左心室舒张末期容量、左心室收缩末期容量较治疗前显著下降(P<0.05),短轴缩短率、射血分数较治疗前显著升高(P<0.05),但B组变化更明显(P<0.05)。结论:别嘌呤醇可改善CKD合并高尿酸血症患者的微炎症状态,保护血管内皮功能和心脏功能,与厄贝沙坦联用效果更显著。     

合并高血压的高尿酸血症药物治疗进展

高尿酸血症是高血压发病的独立危险因素,二者之间关系密切。近年研究发现,别嘌呤醇、非布司他、苯溴马隆在降低血尿酸的同时能降低血压,而某些降压药物如氯沙坦也会降低血尿酸水平。因此,对于合并高血压的高尿酸血症患者,可以优先选择协同降压的降尿酸药物,合理联用降血尿酸的降压药物,避免应用升高血尿酸的其他相关药物。本文查阅国内外文献,对近年来合并高血压的高尿酸血症药物治疗进展作一综述。     

中药制剂联合非布司他治疗高尿酸血症的随机对照试验的Meta分析

目的 本研究旨在评估中药制剂联合非布司他治疗高尿酸血症（Hyperuricemia,HUA）的临床疗效,以及其对血尿酸水平的影响,以期为临床提供可靠的证据支持。方法 通过计算机检索中国知识基础设施项目数据库（CNKI）、中国生物医学文献数据库（CBM）、万方数据、VIP、Pubmed、Cochrane图书馆和Embase数据库中关于中药制剂联合非布司他治疗高尿酸血症的随机对照试验（Randomized Controlled Trail,RCT）。检索年限：各数据库建立至2023年1月1日,由2名研究者独立搜集中药联合非布司他治疗高尿酸血症的相关文献资料。使用Cochrane评价手册对偏倚风险进行评估,使用RevMan5.3软件及Excel表格统计软件,系统评价中医药制剂联合非布司他干预高尿酸血症的临床疗效以及对血尿酸值的影响。结果 经过筛查最终纳入11篇符合条件的文献,涵盖845例患者。研究结果显示：相对于单纯非布司他组,中药制剂联合非布司他组治疗高尿酸血症患者的临床总疗效[OR=2.39,95%CI(1.58,3.62),P <0.001]更好、血尿酸水平[MD=-42.67,...     

半夏泻心汤加味联合非布司他治疗高尿酸血症的临床疗效及其安全性

目的探讨半夏泻心汤加味联合非布司他治疗高尿酸血症的临床疗效及其安全性。方法选取高安市人民医院2018年10月—2019年10月收治的高尿酸血症患者60例,采用抽签法分成普通组和联合组,各30例。普通组给予非布司他治疗,联合组给予半夏泻心汤加味联合非布司他治疗。比较2组治疗前后血尿酸(SUA)水平、空腹血糖(GLU)水平、尿素氮(BUN)水平、体质指数(BMI)。比较2组临床疗效、不良反应发生率。结果治疗前2组SUA、GLU、BUN、BMI比较,差异无统计学意义(P>0.05);治疗后联合组SUA、GLU、BUN、BMI低于普通组(P<0.05)。联合组总有效率高于普通组(P<0.05)。治疗期间2组均未出现严重不良反应。结论半夏泻心汤加味联合非布司他治疗高尿酸血症的临床疗效确切,可保障各体质水平恢复,且安全性较高。     

苯溴马隆与非布司他在治疗2型糖尿病伴高尿酸血症的获益及安全性

目的评价苯溴马隆与非布司他在治疗2型糖尿病伴高尿酸血症的获益及安全性。方法将85例已确诊的2型糖尿病伴尿酸升高的患者随机分为苯溴马隆组(A组,44例)和非布司他组(B组,41例)。两组均给予饮食控制、口服降糖药和(或)胰岛素治疗,A组给予苯溴马隆50 mg/d口服,B组给予非布司他40 mg/d口服,疗程为3个月。结果与苯溴马隆比较,非布司他能够更快、更有效地降低血尿酸水平(P<0.05),但最终达标率比较差异无统计学意义(P>0.05)。两组均出现不同程度的不良反应,B组痛风发作率较高,而A组发生其他不良反应较多。治疗后两组患者Hb A1c均改善(P<0.05),两组比较差异无统计学意义(P>0.05)。治疗前、后两组空腹C肽水平比较差异无统计学意义(P>0.05)。治疗3个月后,A组患者120分C肽水平得到改善(P<0.05),但非布司他组未见明显改善(P>0.05)。结论在2型糖尿病合并高尿酸血症的患者中,应用非布司他及苯溴马隆治疗均能有效降低血尿酸水平,改善患者血糖。苯溴马隆能改善餐后C肽水平。     

Efficacy of gut lavage,hemodialysis, and hemoperfusion in the therapy of paraquat or diquat intoxication

Clinical and in vitro investigations were carried out to test the efficacy of gut lavage, hemodialysis, and hemoperfusion in the treatment of poisoning with paraquat or diquat. In a patient suffering from diquat intoxication 130 times more diquat was removed by gut lavage 30 h after ingestion than was removed by complete aspiration of the gastric contents.Determination of in vitro clearances for paraquat and diquat by hemodialysis showed that, at serum concentrations of 1–2 ppm, such as are frequently encountered in poisoning in man, toxicologically relevant quantities of herbicide cannot be removed from the body. At a concentration of 20 ppm, on the other hand, hemodialysis proved to be effective, the clearance being 70 ml/min at a blood flow rate of 100 ml/min. The efficacy of hemoperfusion with coated activated charcoal was on the whole better. Especially at concentrations around 1–2 ppm, the clearance values for hemoperfusion were some 5–7 times higher than those for hemodialysis.In a patient suffering from paraquat poisoning, both hemodialysis as well as hemoperfusion were carried out. The in vitro results could be confirmed: At serum concentrations of paraquat less than 1 ppm no clearance could be obtained by hemodialysis while by hemoperfusion with activated charcoal quite high clearance values were measured and the serum level dropped down to zero.

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Zusammenfassung Klinische Untersuchungen und Laboratoriumsversuche wurden durchgeführt, um die Wirksamkeit von Darmspülung, Hämodialyse und Hämoperfusion bei Paraquat- und Deiquat-Vergiftungen zu prüfen.Bei einem Patienten wurde 30 Std nach Deiquat-Aufnahme durch Darmspülung 130mal mehr Deiquat entfernt als durch vollständige Aspiration des Mageninhaltes. In vitro-Versuche ergaben, daß bei Blutserumkonzentrationen von 1–2 ppm, die bei Vergiftungen oft gemessen werden, durch Hämodialyse keine toxikologisch relevanten Paraquat- oder Deiquat-Mengen entfernt werden können. Dagegen erwies sich die Hämodialyse bei 20 ppm und einer Blutumlaufgeschwindigkeit von 100 ml/min mit einer Clearance von 70 ml/min als wirksam. Die Hämoperfusion mit beschicheter Aktivkohle war in diesen Versuchen aber eindeutig überlegen, denn insbesondere bei Konzentrationen um 1–2 ppm waren die Clearance-Werte 5–7mal höher als bei der Hämodialyse.Die in vitro-Ergebnisse wurden bei einem Patienten mit einer Paraquat-Vergiftung bestätigt: Bei Konzentrationen unter 1 ppm war die Hämodialyse wirkungslos, während durch Hämoperfusion relativ hohe Clearance-Werte erreicht wurden, so daß der Serumspiegel rasch unter die Nachweisgrenze abfiel.

     

In vitro studies on sterically stabilized liposomes (SL) as enzyme carriers in organophosphorus (OP) antagonism

This study describes a new approach for organophosphorous (OP) antidotal treatment by encapsulating an OP hydrolyzing enzyme, OPA anhydrolase (OPAA), within sterically stabilized liposomes. The recombinant OPAA enzyme was derived from Alteromonas strain JD6. It has broad substrate specificity to a wide range of OP compounds: DFP and the nerve agents, soman and sarin. Liposomes encapsulating OPAA (SL)* were made by mechanical dispersion method. Hydrolysis of DFP by (SL)* was measured by following an increase of fluoride ion concentration using a fluoride ion selective electrode. OPAA entrapped in the carrier liposomes rapidly hydrolyze DFP, with the rate of DFP hydrolysis directly proportional to the amount of (SL)* added to the solution. Liposomal carriers containing no enzyme did not hydrolyze DFP. The reaction was linear and the rate of hydrolysis was first order in the substrate. This enzyme carrier system serves as a biodegradable protective environment for the recombinant OP-metabolizing enzyme, OPAA, resulting in prolongation of enzymatic concentration in the body. These studies suggest that the protection of OP intoxication can be strikingly enhanced by adding OPAA encapsulated within (SL)* to pralidoxime and atropine.     

Aquatic Insects and Trace Metals: Bioavailability,Bioaccumulation, and Toxicity

Abstract

The uptake of metals from food and water sources by insects is thought to be additive. For a given metal, the proportions taken up from water and food will depend both on the bioavailable concentration of the metal associated with each source and the mechanism and rate by which the metal enters the insect. Attempts to correlate insect trace metal concentrations with the trophic level of insects should be made with a knowledge of the feeding relationships of the individual taxa concerned. Pathways for the uptake of essential metals, such as copper and zinc, exist at the cellular level, and other nonessential metals, such as cadmium, also appear to enter via these routes. Within cells, trace metals can be bound to proteins or stored in granules. The internal distribution of metals among body tissues is very heterogeneous, and distribution patterns tend to be both metal and taxon specific. Trace metals associated with insects can be both bound on the surface of their chitinous exoskeleton and incorporated into body tissues. The quantities of trace meals accumulated by an individual reflect the net balance between the rate of metal influx from both dissolved and particulate sources and the rate of metal efflux from the organism. The toxicity of metals has been demonstrated at all levels of biological organization: cell, tissue, individual, population, and community. Much of the literature pertaining to the toxic effects of metals on aquatic insects is based on laboratory observations and, as such, it is difficult to extrapolate the data to insects in nature. The few experimental studies in nature suggest that trace metal contaminants can affect both the distribution and the abundance of aquatic insects. Insects have a largely unexploited potential as biomonitors of metal contamination in nature. A better understanding of the physico-chemical and biological mechanisms mediating trace metal bioavailability and exchange will facilitate the development of general predictive models relating trace metal concentrations in insects to those in their environment. Such models will facilitate the use of insects as contaminant biomonitors.     

Alzheimer’s disease – current trends in basic and clinical research. Highlights from the 16th ECNP

Advances in the molecular biological knowledge of neuronal nicotinic acetylcholine receptors (nAChRs) have led to a growing interest by the pharmaceutical industry in the development of novel compounds that selectively modulate nAChR function. The ability of (-)-nicotine, an activator of nAChRs, to enhance attentional aspects of cognition in animals and humans, to exert neuroprotective and anxiolytic-like effects, and presumably to mediate the negative correlation between smoking and Alzheimer's (and Parkinson's) Disease, has focused interest on the potential therapeutic utility of modulators of nAChR function for treatment of some of the deficits associated with these progressive, neurodegenerative conditions. Numerous compounds are known which activate nAChRs and which might serve as lead compounds toward the development of such agents. The pharmacologic diversity of neuronal nAChR subtypes suggests the possibility of developing selective compounds which would have more favourable side-effect profiles than existing agents. This broader class of agents, collectively called cholinergic channel modulators (ChCMs), is anticipated to encompass compounds which would have more favourable side-effect profiles than existing agents, which generally exhibit low selectivity. This selectivity may be achieved by preferentially activating some subtypes of nAChRs (i.e., Cholinergic Channel Activators, ChCAs) or inhibiting the function of other subtypes (Cholinergic Channel Inhibitors, ChCIs). An overview of the biology of nAChRs and the rationale for the use of ChCMs for the treatment of dementia related to neurodegenerative diseases are presented, followed by a discussion of lead compounds and compounds under consideration for clinical evaluation.     

Steroidal sapogenin contents in some domestic plants

In order to find out the values of the steroid resources for the future use. the compositions and contents of steroidal sapogenins from 13 domestic plants have been investigated. As a result,Dioscorea nipponica, D. quinqueloba andSmilax china were found to have large amount of diosgenin. And pennogenin inTrillium kamtschaticum andParis verticillata, yuccagenin inAllium fistulosum, hecogenin inAgave americana and neochlorogenin inSolanum nigum were appeared to be major steroidal sapogenins.