塞来昔布对大鼠心脏移植急性排斥反应的抑制作用

目的观察塞来昔布对大鼠心脏移植急性排斥反应的抑制作用。方法以SD大鼠为供者,Wistar大鼠为受者,进行40次腹部异位心脏移植。采用HE染色和原位末端标记(TUN EL)技术检测移植心切片,进行排斥反应的病理分级并计算移植心肌细胞的凋亡指数(AI)。结果移植心的细胞凋亡主要发生于心肌细胞;移植后第3、5d,塞来昔布治疗组心肌细胞凋亡指数分别为:1.03±0.42和3.28±2.42;对照组分别为2.35±1.51和11.35±3.46;两组比较,差异有统计学意义(P<0.001)。结论细胞凋亡是心脏移植急性排斥中组织损伤的重要机制;塞来昔布能明显抑制心肌细胞凋亡。     

Celecoxib对胆囊癌细胞GBC-SD增殖的抑制作用

目的研究Celecoxib对人胆囊癌细胞GBC-SD生长和凋亡的影响及其作用机制.方法采用免疫细胞化学SABC法检测GBC-SD环氧合酶-2(Cox-2)蛋白表达,采用四唑氮蓝(MTT)比色法检测细胞增殖,流式细胞仪测定细胞周期和凋亡,酶联免疫吸附试验(LISA)检测前列腺素E2(PGE2)含量.结果 Celecoxib可下调GBC-SD细胞Cox-2蛋白表达.Celecoxib抑制GBC-SD细胞增殖作用呈时间依赖性,作用2天后就有轻度抑制,第3、第4和第5天抑制作用已相当明显(P<0.05,与对照组相比),并且这种增殖抑制作用能被200 g/ml GE2拮抗.Celecoxib诱导GBC-SD细胞G1-S期阻滞,40 μmol/L(P<0.05)和20 μmol/L(P<0.05)Celecoxib组G0-G1 期细胞含量比对照组( μmol/L)明显增高,而S期和G2/M期细胞含量比对照组明显降低(P<0.05).40 μmol/L(P<0.05)和20 μmol/L(P<0.05)Celecoxib处理48 后GBC-SD细胞凋亡率明显上升.结论 Celecoxib通过Cox-2和PGE2途径抑制GBC-SD细胞生长和诱导凋亡.     

塞来昔布对胃癌细胞生长抑制及诱导凋亡的实验研究

目的：研究塞来昔布对胃癌细胞株SGC-7901生长抑制及诱导凋亡的作用。方法：12．5～100μM的塞来昔布处理胃癌细胞株SGC-7901 24小时后，用MTT法测定塞来昔布对胃癌细胞的生长抑制率，流式细胞仪检测细胞周期、细胞凋亡率及MDRl表达水平。结果：12．5～100μM的塞来昔布对胃癌细胞均有抑制作用，首先表现为S期阻滞，继而出现细胞凋亡，且呈剂量依赖性。胃癌细胞MDRl表达水平在12．5μM药物浓度作用时MDRl表达上调，25～100μM药物浓度作用时MDRl表达水平明显下调，且随药物浓度的增高，MDRl表达水平逐渐下降。结论：塞来昔布通过诱导细胞凋亡对胃癌细胞具有明显抑制作用，同时塞来昔布具有下调胃癌细胞MDRl表达，逆转多药耐药性的作用，但在药物浓度较低时，则为上调MDRl表达。     

塞来昔布诱导SGC-7901人胃癌细胞凋亡及其影响端粒酶活性的实验研究

目的探讨选择性环氧化酶-2（COX-2）抑制剂塞来昔布对SGC-7901人胃癌细胞生长、端粒酶活性，细胞凋亡及相关基因的影响，研究其抗肿瘤的作用机制。方法终浓度为100、200及300μmol／L的塞来昔布作用于SGC-7901人胃癌细胞后，采用MTT比色法测定细胞的生长抑制率，采用半定量-TRAP银染法检测端粒酶活性，流式细胞仪检测细胞周期、细胞凋亡率及bcl-2表达水平变化。结果不同浓度的塞来昔布对SGC-7901人胃癌细胞均有抑制作用，抑制率与对照组相比，差异均有显著性（P〈0．05）；流式细胞学检测到凋亡峰，细胞阻滞于G0／G1期。同时它也显著抑制胃癌细胞的端粒酶活性，其抑制作用呈时间-剂量依赖性，且端粒酶活性的降低与bcl-2表达水平下降有关。结论塞来昔布能抑制胃癌细胞的增殖，诱导细胞凋亡，降低端粒酶活性，其作用机制与bcl-2表达水平下降有关，此可能是COX-2抑制剂抗肿瘤的机制之一。     

中效原理在胃癌联合化疗中的应用及药物抗癌机制的初步探索

目的 运用中效原理分析姜黄素联合顺铂或塞来昔布对胃癌SGC-7901细胞的化疗效应,并初步探索上述三种药物对胃癌的抗癌机制.方法 将实验组分为姜黄素组、顺铂组、塞来昔布组、姜黄素联合顺铂组、姜黄素联合塞来昔布组,用相应药物作用于胃癌SGC-7901细胞,阴性对照组为不含药物组.然后采用MTT法测定药物对SGC-7901细胞的增殖抑制率,并运用中效原理分析药物联用的效果;同时采用流式细胞术检测细胞凋亡率;实时荧光定量RT-PCR法检测COX-2 mRNA的表达;分光光度法检测Caspase-3的活性.结果 姜黄素、顺铂和塞来昔布组均能抑制SGC-7901细胞的增殖,且呈浓度依赖性;姜黄素与顺铂或塞来昔布联用时可增强这种抑制,表现为协同作用.上述三种药物均能诱导胃癌SGC-7901发生凋亡,两药联用组的细胞凋亡率较单药作用组均显著升高（均P＜0.01）.单药作用组细胞中COX-2 mRNA的表达较阴性对照组均显著下降（均P＜0.01）.单药作用组细胞中Caspase-3的活性较阴性对照组均显著升高（均P＜0.01）.结论 在一定药物浓度范围内,姜黄素、顺铂和塞来昔布均能抑制胃癌SGC-7901细胞的增殖、诱导其凋亡.姜黄素与顺铂或塞来昔布联用时均呈现协同作用,这可能与三药均能抑制COX-2 mRNA的表达、提高Caspase-3的活性有关.     

塞来昔布联合正清风痛宁片对类风湿关节炎的疗效分析

目的:探讨塞来昔布联合正清风痛宁片对类风湿关节炎患者外周淋巴细胞的影响及疗效。方法:类风湿关节炎患者122例,随机分为两组:对照组57例,单用塞来昔布治疗;观察组65例,塞来昔布联合正清风痛宁片治疗,疗程4周。比较两组患者治疗前后IL-1、IL-6、TNF-α水平及类风湿因子(RF);肿胀疼痛关节数、VAS疼痛评分及疗效。结果:(1)总有效率观察组高于对照组(66.15%vs.52.63%,P<0.05);(2)治疗后观察组RF、IL-6、TNF-α水平均低于对照组[(19.27±3.81)vs.(36.64±4.11)]U/m L、[(10.34±1.64)vs.(14.37±3.21)]ng/L、[(8.54±2.47)vs.(12.58±1.69)]μg/L,均P<0.05;(3)治疗后观察组与对照组比较,肿胀疼痛关节数差异有统计学意义(P<0.05),但VAS疼痛评分比较差异无统计学意义(P>0.05)。结论:塞来昔布联合正清风痛宁片治疗类风湿关节炎,能够显著改善患者症状,缓解疼痛,减轻炎症反应,其疗效优于单用塞来昔布治疗。     

Pharmakologie der COX-2-Hemmer

Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used to treat pain and inflammation in osteoarthritis and rheumatoid arthritis. However, their long-term use is often limited by gastrointestinal mucosal injury and complications like bleeding, ulceration and perforation. Hence, the hope evolved that selective COX-2 inhibitors, a newly developed class of anti-inflammatory drugs, may be equally effective but better tolerated than nonselective NSAIDs. However, this enthusiasm was partly dampened by the fact that the exclusive use of selective COX-2 inhibitors is probably not justified. Particularly in patients treated with low-dose of aspirin for cardiovascular prophylaxis, the COX-2 inhibitors seem to have no obvious advantages over conventional NSAIDs. Furthermore, use of COX-2 inhibitors has recently been associated with enhanced cardiovascular risk. There is some evidence that COX-2 inhibitors may act via COX independent pathways and might be used for indications other than arthritic pain and inflammation.     

塞来昔布治疗类风湿关节炎（RA）的临床效果及对临床症状类风湿因子的影响

目的 探讨塞来昔布治疗类风湿关节炎（RA）效果及对临床症状类风湿因子（RF）的影响。方法 选取2017年1月至2018年9月本院收治的96例类风湿关节炎患者,根据随机数字表法分为观察组与对照组,各48例。对照组采用布洛芬联合甲氨蝶呤治疗,观察组采用塞来昔布联合甲氨蝶呤治疗,比较两组临床疗效、临床症状及类风湿因子改善情况。结果 观察组治疗总有效率（95.83%）高于对照组（83.33%）,差异有统计学意义（P<0.05）。治疗后,观察组关节疼痛评分、肿胀评分及血沉水平明显低于对照组,晨僵时间明显短于对照组,差异均有统计学意义（P<0.05）。治疗后,观察组RF、肿瘤坏死因子-α（TNF-α）均低于对照组,差异有统计学意义（P<0.05）。结论 塞来昔布治疗类风湿关节炎效果显著,可改善临床症状、类风湿因子,临床应用价值高。     

Pro-apoptotic effect of nonsteroidal anti-inflammatory drugs on synovial fibroblasts

Abstract

Rheumatoid arthritis (RA) is a systemic inflammatory disease that mainly affects the articular synovial tissues. Although the etiology of RA has not yet been elucidated, physical and biochemical inhibition of synovial hyperplasia, which is the origin of articular destruction, may be an effective treatment for RA. Nonsteroidal anti-inflammatory drugs (NSAIDs) have long been used for the treatment of RA. The mechanism of action of NSAIDs generally involves the inhibition of cyclooxygenase (COX) at sites of inflammation. Thus, NSAIDs were not generally considered to have a so-called anti-rheumatic effect, including inhibition of progressive joint destruction and induction of remission. However, certain conventional NSAIDs and celecoxib, a selective COX-2 inhibitor, have been reported to inhibit synovial hyperplasia by inducing the apoptosis of human synovial fibroblasts. Therefore, it has been suggested that such NSAIDs may not only have an anti-inflammatory effect but also an anti-rheumatic effect. In this review, we summarize findings about the pro-apoptotic effect, in other words, anti-proliferative effect of NSAIDs on synovial fibroblasts from patients with RA.     

Integration in Interorganizational Hospice Care Systems

Hospice programs currently have a need to improve the integration of their services across organizational and professional boundaries. Coordination of decision making and client flow patterns are defined in this paper as integrative mechanism which must be employed by all hospice programs which are interorganizational in nature: that is, the program is delivered by a cluster of agencies providing care to the same population of patients. Also discussed are four system characteristics which determine the choice of these integrative mechanisms: scope of service, intensity of service, centrality of the system, and division of labor. The results of an empirical study of two different hospice service delivery systems indicate that as scope and intensity increase, the amount of integration must increase also. If it does not, the findings suggest that a “poor fit” results. It is shown that service integration fit can be measured by a discrepancy score: a high discrepancy is predictive of dissatisfaction with service effectiveness among hospice workers.