奥施康定联合塞来昔布治疗妇科恶性肿瘤中重度疼痛的疗效观察

目的:观察奥施康定联合塞来昔布治疗妇科恶性肿瘤中重度疼痛的临床疗效。方法:选取我院收治的79例妇科中重度癌痛患者作为研究对象，随机分为两组，对照组患者（n=33）在一般治疗的基础上加用奥施康定进行镇痛，观察组患者（n=46）在此基础上加用塞来昔布进行镇痛。统计分析两组患者镇痛效果、5-羟色胺（5-HT）、去甲肾上腺素（NE）水平及不良反应。结果:经过治疗后，观察组患者NRS评分低于对照组患者，观察组患者治疗有效缓解率高于对照组患者，观察组患者5-HT、NE水平均低于对照组患者，差异具有统计学意义（P<0.05）；观察组患者便秘发生率低于对照组患者，差异具有统计学意义（P<0.05）。结论:奥施康定联合塞来昔布治疗妇科恶性肿瘤中重度疼痛具有确切的效果，可降低单纯应用奥施康定的不良反应，值得临床推广。     

Potentially inappropriate concomitant medicine use with the selective COX-2 inhibitor celecoxib: Analysis and comparison of spontaneous adverse event reports from Australia,Canada and the USA.

Background: To perform an international comparison and analysis of celecoxib spontaneous adverse event reports (AERs) from Canada, Australia and the United States, focusing on gastrointestinal, renal and cardiovascular events. This study also examined concomitant medicines use which may have potentiated the risk of the reported adverse events.

Research, design and methods: Three databases were searched for spontaneous AERs associated with celecoxib, submitted within the past 10 years: Australian Therapeutic Goods Administration Database of Adverse Event Notifications; Canada Vigilance Adverse Reaction Online Database; and the United States Food and Drug Administration Adverse Event Reporting System Database. Analysis of the AERs focussed on the identification of gastrointestinal, cardiovascular and renal adverse events and concomitant medications suspected of potentiating adverse event risks.

Results: A total of 24,232 celecoxib AERs were identified. Gastrointestinal disorders were the most frequently reported adverse events at the system organ class (SOC) level in the AERs. A large number of AERs documented the use of potentially inappropriate concomitant medicines which may have increased the risk of the reported adverse events.

Conclusions: The large number of reports that involved a concomitant medicine that was in contravention with prescribing guidelines indicates an increased need for efforts to support the safe prescribing of celecoxib.     

Celecoxib is a substrate of CYP2D6: Impact on celecoxib metabolism in individuals with CYP2C9*3 variants

Celecoxib was characterized as a substrate of human cytochrome P450 (CYP) 2D6 in vitro. In recombinant CYP2D6, celecoxib hydroxylation showed atypical substrate inhibition kinetics with apparent K_m, K_i, and V_max of 67.2 μM, 12.6 μM, and 1.33 μM/min, respectively. In human liver microsomes (HLMs), a concentration-dependent inhibition of celecoxib hydroxylation by quinidine was observed after CYP2C9 and CYP3A4 were inhibited. In individual HLMs with variable CYP2D6 activities, a significant correlation was observed between celecoxib hydroxylation and CYP2D6-selective dextromethorphan O-demethylation when CYP2C9 and CYP3A4 activities were suppressed (r = 0.97, P < 0.0001). Molecular modeling showed two predominant docking modes of celecoxib with CYP2D6, resulting in either a substrate or an inhibitor. A second allosteric binding antechamber, which stabilized the inhibition mode, was revealed. Modeling results were consistent with the observed substrate inhibition kinetics. Using HLMs from individual donors, the relative contribution of CYP2D6 to celecoxib metabolism was found to be highly variable and dependent on CYP2C9 genotypes, ranging from no contribution in extensive metabolizers with CYP2C9*1*1 genotype to approximately 30% in slow metabolizers with allelic variants CYP2C9*1*3 and CYP2C9*3*3. These results demonstrate that celecoxib may become a potential victim of CYP2D6-associated drug-drug interactions, particularly in individuals with reduced CYP2C9 activity.     

塞来昔布辅助治疗对老年肺癌患者炎性介质及肺功能的影响

目的 探讨塞来昔布辅助治疗对老年肺癌患者炎性介质及肺功能的影响。方法 选取2014年1月—2016年6月在新乡市中心医院进行诊治的130例老年非小细胞肺癌患者,按治疗方法分为观察组、对照组,各65例,对照组使用培美曲塞联合顺铂进行化疗,观察组在对照组治疗的基础上给予塞来昔布辅助治疗,两组治疗观察3个月。比较两组的疗效及毒副反应情况,比较两组治疗前后的炎症因子、肺功能并随访到2017年12月,记录患者生存期。结果 治疗后观察组与对照组的总有效率分别为72.31%和53.80%,观察组显著高于对照组,差异有统计学意义（P<0.05）。治疗期间观察组的皮肤反应、骨髓抑制、消化道反应等毒副反应与对照组相比无显著差异,所有毒副反应对症处理后好转。观察组与对照组治疗后的血清IL-2与IL-6水平较治疗前显著降低,同组治疗前后比较差异有统计学意义（P<0.05）;观察组更明显,组间差异有统计学意义（P<0.05）。治疗后两组的FEV1值较治疗前显著升高,同组治疗前后比较差异有统计学意义（P<0.05）;观察组明显高于对照组,差异有统计学意义（P<0.05）。观察组与对照组的中位生存期分别为（13.44±2.12）个月和（11.94±3.19）个月,KM法分析显示观察组高于对照组,差异有统计学意义（P<0.05）。结论 塞来昔布辅助治疗老年肺癌患者能有效抑制炎性介质的释放,改善患者的肺功能,安全性好,从而有利于提高治疗效果与延长患者的生存期。     

IL-17A stimulates the expression of inflammatory cytokines via celecoxib-blocked prostaglandin in MC3T3-E1 cells

Objective

The prostaglandins (PGs) released from osteoblasts can alter the process of bone remodelling. Recently, we showed that compressive force induced the expression of pro-inflammatory cytokine interleukin (IL)-17s and their receptors in osteoblastic MC3T3-E1 cells and that IL-17A was expressed most highly. Consequently, in the current study we examined the effect of IL-17A and/or celecoxib on PGE₂ production and the expression of cyclooxygenases (COXs) and inflammatory cytokines in MC3T3-E1 cells. We also examined the effects of PGE₂ and cyclohexamide on the expression of inflammatory cytokines.

Methods

Cells were cultured with or without IL-17A (0.1, 1.0, or 10 ng/ml) in the presence or absence of 10 μM celecoxib, a specific inhibitor of COX-2, for up to 72 h. Cells were pretreated with or without 10 μg/ml cycloheximide, protein synthesis inhibitor, for 30 min, and then cultured with 10 ng/ml IL-17A for 24 h. Cells were also cultured with or without 1.5 ng/ml PGE₂ for 24 h. PGE₂ production was determined by ELISA. The expression of COX-1, COX-2, IL-1α, IL-6, IL-8, IL-11, and TNF-α mRNAs and proteins was determined by real-time PCR and ELISA, respectively.

Results

The expression of COX-2, IL-1α, IL-6, IL-8, IL-11, and TNF-α, as well as PGE₂ production increased in the presence of IL-17A, whereas COX-1 expression did not change. Celecoxib blocked the stimulatory effect of IL-17A on the expression of COX-2, IL-1α, IL-6, IL-8, and IL-11 as well as PGE₂ production, whereas it did not block TNF-α expression. Cycloheximide pretreatment suppressed the expression of IL-17-induced inflammatory cytokines. The expression of IL-1α, IL-6, IL-8, and IL-11 increased by the addition of PGE₂, whereas TNF-α expression was not affected.

Conclusion

These results suggest that IL-17A stimulates the expression of bone resorption-related inflammatory cytokines through an autocrine mechanism involving celecoxib-blocked PGs, mainly PGE₂, in osteoblasts.     

痹祺胶囊联合刃针治疗膝骨性关节炎的疗效观察

目的 探究痹祺胶囊联合刃针治疗早期膝骨性关节炎（knee osteoarthritis,KOA）的疗效。方法 采用随机数字表法将70例KOA患者随机分成2组,各35例。2组患者均用刃针治疗,1次/周,共2次;对照组患者联合口服塞来昔布胶囊200 mg/次,1次/d;试验组患者联合口服痹祺胶囊1.2 g/次,3次/d;治疗14 d。比较治疗前后及3个月随访的视觉模拟评分（visual analogue scale,VAS）及西安大略和麦克马斯特大学（Western Ontario and McMaster University,WOMAC）骨关节炎指数量表评分来判定疗效。结果 纳入研究的70例KOA患者中有8例脱落,共有62例纳入分析。2组治疗后VAS及WOMAC评分较治疗前均显著降低（P<0.01）,但对照组比试验组的VAS分值降低更明显（P<0.05）,WOMAC评分在治疗2周后和3个月随访均为试验组降低更明显（P<0.05）。治疗2周后,2组有效率较接近（试验组96.9%,对照组90%）,3个月随访试验组有效率（93.8%）优于对照组（63.3%）（P<0.01）。结论 采用痹祺胶囊联合刃针与塞来昔布联合刃针治疗KOA均疗效显著,但痹祺胶囊联合刃针改善关节功能更明显,且疗效更稳定持久。     

长安郭氏“循经取穴”冲击波治疗膝关节骨性关节炎临床研究

目的:探讨长安郭氏“循经取穴”冲击波治疗膝关节骨性关节炎的临床疗效。方法:选取96例膝关节骨性关节炎患者,依照随机数字表法分为对照组和观察组,每组48例。对照组采用塞来昔布治疗,观察组采用循经取穴冲击波联合塞来昔布治疗,两组治疗时间均为3个月。结果:治疗后两组中医症状评分均降低,且观察组低于对照组; 治疗后两组膝关节功能评分均增高,且观察组高于对照组(均P<0.05)。治疗后观察组总有效率高于对照组(P<0.05)。治疗后两组关节液白细胞介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)、基质金属蛋白酶-3(MMP-3)水平均降低,且观察组低于对照组(均P<0.05)。治疗期间两组不良反应发生率比较,差异无统计学意义(P>0.05)。结论:长安郭氏“循经取穴”冲击波联合塞来昔布治疗膝关节骨性关节炎能够改善患者临床症状及膝关节功能,抑制炎症反应,疗效较好。