Non-steroidal anti-inflammatory drugs have anti-amyloidogenic effects for Alzheimer's beta-amyloid fibrils in vitro

The pathogenesis of Alzheimer's disease (AD) is characterized by cerebral deposits of amyloid beta-peptides (A beta) and neurofibrillary tangles which are surrounded by inflammatory cells. Long-term use of non-steroidal anti-inflammatory drugs (NSAIDs) reduces the risk of developing AD and delays the onset of the disease. In the present study, we used fluorescence spectroscopy with thioflavin T and electron microscopy to examine the effects of NSAIDs such as ibuprofen, aspirin, meclofenamic acid sodium salt, diclofenac sodium salt, ketoprofen, flurbiprofen, naproxen, sulindac sulfide and indomethacin on the formation, extension, and destabilization of beta-amyloid fibrils (fA beta) at pH 7.5 at 37 degrees C in vitro. All examined NSAIDs dose-dependently inhibited formation of fA beta from fresh A beta(1-40) and A beta(1-42), as well as their extension. Moreover, these NSAIDs dose-dependently destabilized preformed fA betas. The overall activity of the molecules examined was in the following order: ibuprofen approximately sulindac sulfide >or= meclofenamic acid sodium salt>aspirin approximately ketoprofen >or= flurbiprofen approximately diclofenac sodium salt>naproxen approximately indomethacin. Although the mechanisms by which these NSAIDs inhibit fA beta formation from A beta, and destabilize preformed fA beta in vitro are still unclear, NSAIDs may be promising for the prevention and treatment of AD.     

非甾体类消炎药致消化道出血的临床分析

目的探讨非甾体类消炎药（NSAIDs）致消化道出血的临床特点。方法回顾性分析广东省东莞市东坑人民医院收治的经病理证实存在消化道出血及在出血前10d内有服用NSAIDs史的患者100例的临床资料,将其分为老年组62例和中青年组38例,按照使用NSAIDs的不同和患者的年龄进行研究。结果老年组NSAIDs相关性上消化道出血发生率明显高于中青年组（P〈0·01）,老年组服用的NSAIDs药物以阿司匹林为主显著高于中青年组（P〈0·01）;中青年组以布洛芬为主显著高于老年组（P〈0·01）;老年组消化道出血以溃疡性病变为主,中青年组以黏膜糜烂为主。两组患者的Hp感染差异无统计学意义（P〉0·05）。结论老年人患NSAIDs相关性上消化道出血具有其自身特点,不同于中青年患者,应该进行个体化的预防和治疗。     

白内障超声乳化术后应用激素和非甾体抗炎药的临床观察

目的探讨糖皮质激素药物联合非甾体抗炎药对超声乳化白内障吸除术后炎症的临床疗效。方法选择临床确诊为单纯性白内障的128例患者,测量眼压,均进行超声乳化白内障吸除并联合人工晶体植入手术,分为3组,术后均使用滴眼液控制炎症反应。其中,典必殊组单用典必殊滴眼液4周;普南扑灵组单用普南扑灵滴眼液4周;联合组先将典必殊和普南扑灵分别轮换、联用1周,后3周只单用普南扑灵滴眼液。术后第3天、第7天,第14天及第30天,分别观察三组患者的症状、体征,测量房水闪辉及细胞反应及眼压。结果术后第3天、第7天及第14天时,联合组症状和体征的综合评分显著低于典必殊组及普南扑灵组,差异有统计学意义(P<0.05)。手术后,除第30天外,其余几个时间点联合组房水闪辉值均显著低于两单用药组(P<0.05)。在各时间点,三组房水细胞比较差异无统计学意义(P>0.05)。眼压与术前比,除典必殊组术后第30天眼压较术前增加(P<0.05),其余时间点内三组患者术后眼压与术前比较,差异均无统计学意义(P>0.05)。结论超声乳化白内障吸除并联合人工晶体植入术后,典必殊和普南扑灵联用1周,再单用普南扑灵的抗炎效果优于单用典必殊或普南扑灵,并能避免长期使用典必殊等激素而引起的眼压升高。     

非甾体抗炎药致中青年患者上消化道出血临床分析（附81例）

目的探讨非甾体抗炎药（NSAIDs）致中青年患者上消化道出血的临床特点。方法回顾分析81例非甾体抗炎药中青年患者的临床资料。结果本组81患者2周内均有服用NSAIDs病史,都经大便潜血及纤维胃镜确诊。伴有腹部疼痛症状18例占22．2％（18／81）;有嗜咖啡或酸辣饮食习惯53例（占65．4％）;有吸烟史48例（占59．3％）。结论中青年人群服用NSAIDs引起的上消化道出血起病隐匿、临床症状轻和体征不明显的特点,应引起临床医师和药师的警惕。     

非甾体抗炎药和幽门螺杆菌感染与消化性溃疡发病的关系

目的 探讨服用非甾体抗炎药(NSAIDs)、幽门螺杆菌(Hp)感染与消化性溃疡之间的关系.方法 2008年1月至2010年1月在新疆医科大学第一临床医学院消化内科住院的消化性溃疡患者152例,均行内镜确诊(除外复合溃疡),并行病理学检查排除胃癌.依据溃疡病因将患者分为3组:单纯HP感染组、单纯服用NSAIDs组、Hp感染合并服用NSAIDs组.结果 入选患者152例,男106例,女46例,年龄13～88(51±18)岁.其中单纯Hp感染组93例、单纯服用NSAIDs组41例、Hp感染合并服用NSAIDs组18例,单纯Hp感染组患者年龄明显低于其他2组(P=0.000).服用NSAIDs所治疗的疾病包括:心脑血管疾病,如脑梗死、冠心病、偏头痛等,共33例,占55.9％;骨关节疾病,如类风湿性关节炎、骨性关节病,共13例,占22.0％;其他,如发热、牙痛、痛经等共13例,占22.0％.单纯服用NSMDs组对溃疡并发出血危险性比其他2组高( OR =5.623,95％ CI2.446～12.924,P=0.000),单纯Hp感染或合并服用NSAIDs并未增加溃疡并发出血的危险性(OR=0.223,95％ CI0.110～0.451:OR=1.327,95％ CI0.493～3.569).Hp感染合并服用NSAIDs组溃疡发生的时间(1.7±2.6)个月比单纯服用NSAIDs组的时间(4.5±5.3)个月早(P=0.010).结论 单纯Hp感染或合并服用NSAIDs并未增加溃疡并发出血的危险性,Hp感染合并服用NSAIDs组溃疡发生的时间比单纯服用NSAIDs组的时间早,表明在消化性溃疡的发生上它们之间存在协同性.     

非甾体抗炎药治疗我国中老年骨关节炎疗效和安全性的网状Meta分析

目的 系统评价不同非甾体抗炎药(NSAIDs)治疗中国中老年骨关节炎(OA)患者的疗效和安全性.方法 检索PubMed、Cochrane Library、CNKI、WanFang Data和VIP数据库,搜集关于NSAIDs治疗中国中老年OA患者的随机对照试验,检索时限均从建库至2020年11月17日.由两位研究人员独...     

Comparative study between direct analysis in whole blood,oral fluid,and declaration of consumption for the prevalence of nonsteroidal anti-inflammatory drugs and acetaminophen in ultratrail runners

Ultratrail running is a sport with growing number of adherents. To complete ultratrail despite physical issues such as joint and muscle pain, many runners use nonsteroidal anti-inflammatory drugs (NSAIDs) and acetaminophen. Studies asking participants about their consumption of drugs during ultratrail revealed a prevalence of NSAIDs and acetaminophen up to 70% and 25%, respectively. The aims of the present study were to determine the prevalence of NSAIDs and acetaminophen for 81 runners during the 2021 Ultratrail du Mont Blanc® (UTMB®) using direct analysis of dried blood spots (DBS) and oral fluid (OF) and to compare results with the declaration of consumption by runners; this is to identify the most relevant method to study the prevalence of drugs. Our results show a prevalence of NSAIDs of 46.6% using DBS, 18.5% using OF, and 13.8% based on a questionnaire. Prevalence of acetaminophen were 30.1%, 30.9%, and 22.5% using DBS, OF, and questionnaire, respectively. From this study, we conclude that the analysis of drugs directly in DBS is the most relevant tool to determine the prevalence in ultratrail events.     

Analytical strategy for the confirmatory analysis of the non-steroidal anti-inflammatory drugs firocoxib, propyphenazone, ramifenazone and piroxicam in bovine plasma by liquid chromatography tandem mass spectrometry

A sensitive and selective method for the simultaneous determination of non-steroidal anti-inflammatory drugs in bovine plasma was developed. Confirmatory analysis was carried out by liquid chromatography coupled with an electrospray ionisation tandem mass spectrometer (LC-ESI-MS/MS). Target compounds were acidified in plasma and extracted with acetonitrile. Sodium chloride was added to assist separation of the plasma and acetonitrile mixture. The acetonitrile extract is then subjected to liquid-liquid purification by the addition of hexane. Accuracy of the methods in plasma was between 93 and 102%. The precision of the method for the basic NSAIDs in plasma expressed as % RSD, for the within-laboratory reproducibility was less than 10%. Decision limit (CCα values) and detection capability (CCβ) values were established. The methods were validated according to Commission Decision 2002/657/EC.     

The effects of aspirin and other non-steroid anti-inflammatory/analgesic drugs on gastro-intestinal mucus glycoprotein biosynthesis in vivo: relationship to ulcerogenic actions.

Aspirin and certain other ulcerogenic non-steroid antiinflammatory (NSAI) drugs inhibit the incorporation in vivo of [³⁵S]sulphate into the mucus glycoproteins isolated from the gastric mucosa of rats. Some NSAI drugs, which are shown to be relatively non-ulcerogenic in a sensitive gastric ulcer assay and the analgesic drugs paracetamol and dextropropoxyphene (which are non-ulcerogenic) did not inhibit the biosynthesis of sulphated mucus glycoproteins in vivo. A relationship is therefore shown between the ulcerogenicity of NSAI drugs and the inhibitory effects on gastric mucus biosynthesis. Some potent intestinal ulcerogens (e.g. indomethacin) also inhibit the incorporation of [³⁵S]sulphate into the glycoproteins from the upper intestinal mucosa. Aspirin in contrast stimulates the incorporation of [³⁵S]sulphate into intestinal mucus glycoproteins. The inhibition of the biosynthesis of sulphated gastric mucus glycoproteins by aspirin is shown to (1) depend on the presence of high concentrations of salicylates in the mucosal tissue, (2) be as a consequence of combined inhibitory capacity of aspirin, salicylate and possibly traces of metabolites in the mucosa and (3) be due to an inhibition of the sulphotransferase activity in vitro. Aspirin also inhibits the incorporation into gastric glycoproteins of [¹⁴C]acetate, but not [¹⁴C]threonine, but the effect on [¹⁴C]acetate incorporation may be due to the redistribution of the isotope in vivo.