盐酸氨基葡萄糖联合塞来昔布对膝关节骨性关节炎的临床疗效观察

目的:观察盐酸氨基葡萄糖联合塞来昔布治疗膝关节骨性关节炎的效果及对不同程度关节炎Lequesne评分的影响,为关节炎的临床治疗提供参考。方法:选取2012年6月至2014年3月我院收治的膝关节骨性关节炎患者60例,根据治疗方法不同,将所选患者分为观察组和对照组,每组30例。对照组患者给予盐酸氨基葡萄糖单药治疗,观察组患者给予盐酸氨基葡萄糖和塞来昔布联合治疗。观察两种治疗方案的不良反应发生率,比较两组患者治疗前后的Lequesne评分。结果:对照组患者不良反应的发生率为26.67%,观察组为23.33%,差异无统计学意义(P0.05)。两组患者治疗后的Lequesne评分均低于治疗前,且观察组患者Lequesne评分显著低于对照组,差异具有统计学意义(P0.05)。观察组不同程度膝关节骨性关节炎患者的Lequesne评分均显著低于对照组,差异具有统计学意义(P0.05)。结论:盐酸氨基葡萄糖联合塞来昔布治疗膝关节骨性关节炎具有良好的临床效果,应进一步推广应用。     

Celecoxib decreases growth and angiogenesis and promotes apoptosis in a tumor cell line resistant to chemotherapy

Background

During the last few years it has been shown in several laboratories that Celecoxib (Cx), a non-steroidal anti-inflammatory agent (NSAID) normally used for pain and arthritis, mediates antitumor and antiangiogenic effects. However, the effects of this drug on a tumor cell line resistant to chemotherapeutical drugs used in cancer have not been described.Herein we evaluate the angiogenic and antitumor effects of Cx in the development of a drug-resistant mammary adenocarcinoma tumor (TA3-MTXR).

Results

Cx reduces angiogenesis in the chick embryonic chorioallantoic membrane assay (CAM), inhibits the growth and microvascular density of the murine TA3-MTXR tumor, reduces microvascular density of tumor metastases, promotes apoptosis and reduces vascular endothelial growth factor (VEGF) production and cell proliferation in the tumor.

Conclusion

The antiangiogenic and antitumor Cx effects correlate with its activity on other tumor cell lines, suggesting that Prostaglandins (PGs) and VEGF production are involved. These results open the possibility of using Celecoxib combined with other experimental therapies, ideally aiming to get synergic effects.     

Novel pyrazoline derivatives as bi-inhibitor of COX-2 and B-Raf in treating cervical carcinoma

Twenty four pyrazoline derivatives modified from Celecoxib were designed and synthesized as bi-inhibitor of COX-2 and B-Raf. They were evaluated for their COX-1/COX-2/B-Raf inhibitory and anti-proliferation activities. Compound A3 displayed the most potent activity against COX-2 and HeLa cell line (IC₅₀ = 0.008 μM; GI₅₀ = 19.86 μM) and showed superb COX-1/COX-2 selectivity (>500), being more potent and selective than positive control Celecoxib or 5-fluorouracil. Compounds A5 and B5 were introduced best B-Raf inhibitory activities (IC₅₀ = 0.15 μM and 0.12 μM, respectively). Compound A4 retained superb bioactivity against COX-2 and HeLa cell line (IC₅₀ = 0.015 μM; GI₅₀ = 23.82 μM) and displayed moderate B-Raf inhibitory activity (IC₅₀ = 3.84 μM). Docking simulation was conducted to give binding patterns. QSAR models were built using bioactivity data and optimized conformations to provide a future modification of COX-2/B-Raf inhibitors.     

双氯芬酸钠与塞来昔布治疗类风湿关节炎的疗效及对心血管的影响研究

目的：探讨双氯芬酸钠和塞来昔布治疗类风湿关节炎的临床疗效及用药安全性。方法：将我院2011 年1 月-2012 年1 月门诊收治的98 例类风湿性关节炎患者随机分为对照组和观察组,每组49 例。对照组给予双氯芬酸钠治疗,观察组给予塞来昔布治疗,观察两组临床治疗效果及心血管不良事件的发生情况。结果：观察组总有效率为91.84%显著高于对照组的75.51%,两组比较差异具有统计学意义（P〈0.05）;观察组ESR及CRP 分别为（110.65± 7.28）mm/h 和（10.42± 0.98）mg/L显著低于治疗前和对照组,比较差异具有统计学意义（P〈0.05）;观察组心血管不良事件发生率为8.16%显著低于对照组的20.41%,两组比较差异具有统计学意义（P〈0.05）。结论：塞来昔布治疗类风湿关节炎具有较好的临床疗效,可有效改善患者疼痛、僵硬或功能受限等症状,且心血管不良事件发生率低,值得临床进一步推广和应用。     

COX-2和P-STAT_3、P-STAT_5在肝癌细胞株SMMC-7721中的表达及意义

目的观察COX-2和P-STAT3、P-STAT5在人肝癌细胞株SMMC-7721中的表达及其相互关系,探讨环氧合酶2表达与JAK/STAT信号转导通路之间的关系。方法培养人肝癌SMMC-7721细胞,应用免疫组化法检测COX-2抑制剂塞来昔布处理人肝癌细胞株SMMC-7721前后COX-2、P-STAT3、P-STAT5表达的变化。结果COX-2、P-STAT3、P-STAT5在人肝癌细胞株SMMC-7721均呈高表达,并且COX-2与P-STAT3、P-STAT5的表达呈显著正相关;应用COX-2抑制剂塞来昔布后COX-2、P-STAT3、P-STAT5的表达均显著降低,用药前后相比差异有显著性(P<0.01);但用药后COX-2与P-STAT3、P-STAT5的表达无显著相关性。结论COX-2和JAK/STAT通路有密切联系,抑制COX-2的过度表达可能影响JAK/STAT细胞信号转导通路的活性。     

手术前后注射帕瑞昔布钠对脑膜瘤切除术后的镇痛效果评价

目的:比较手术前后注射帕瑞昔布钠对脑膜瘤切除术后的镇痛效果。方法:收集我院收治的120例行脑膜瘤切除术患者,随机分为术前组、术后组以及对照组,每组40例。术前组在麻醉前15 min静注帕瑞昔布钠40 mg所有患者行麻醉诱导(咪达唑仑+异丙酚+罗库溴铵+舒芬太尼)静脉注射,维持麻醉采用异丙酚+瑞芬太尼静脉泵注,行脑膜瘤切除术术毕根据患者具体情况停用异丙酚、瑞芬太尼术后组患者在手术结束前15 min静注帕瑞昔布钠40 mg,对照组患者在手术结束前15 min静注生理盐水2mL。观察并比较三组患者各时间点的疼痛视觉模拟评分(VAS)、简易智能状态量表(MMSE)评分、血清皮质醇(cortisol)水平以及患者不良反应发生率。结果:与对照组相比术前组、术后组患者术后1 h的VAS评分水平较低差异具有统计学意义(P0.05);与术后组相比术前组患者的术后1 h的VAS评分水平较低差异具有统计学意义(P0.05);术后三组患者的MMSE评分与术前相比均下降(P0.05),与对照组相比术前组患者的术后1 h、术后24h MMSE评分较高差异具有统计学意义(P0.05);与对照组相比术前组、术后组患者术后1 h以及术后24 h的皮质醇水平较低差异具有统计学意义(P0.05);与术后组相比术前组患者的皮质醇水平较低差异具有统计学意义(P0.05);三组患者的副作用发生率相比无明显差异(P0.05)。结论:术前注射帕瑞昔布钠的镇痛效果较术后注射更好术后认知功能恢复较快。     

风湿祛痛胶囊联合塞来昔布胶囊治疗强直性脊柱炎的疗效及对血液流变学和血清炎性因子的影响

摘要 目的：探讨强直性脊柱炎（AS）患者经风湿祛痛胶囊联合塞来昔布胶囊治疗后的疗效及对血液流变学和血清炎性因子的影响。方法：选取2014年8月-2021年12月在联勤保障部队第九八三医院治疗的80例AS患者。按照随机数字表法分为对照组（常规治疗及塞来昔布胶囊治疗，40例）和研究组（常规治疗及风湿祛痛胶囊联合塞来昔布胶囊治疗，40例），两组患者均治疗8周。对比两组血液流变学指标、血清炎性因子指标、视觉模拟评分法（VAS）评分、C反应蛋白（CRP）、巴氏强直性脊柱炎疾病活动指数（BASDAI）评分、红细胞沉降率（ESR），同时记录两组治疗期间不良反应发生情况。结果：研究组治疗8周后BASDAI、VAS评分低于对照组（P<0.05）。研究组治疗8周后CRP、ESR低于对照组（P<0.05）。研究组治疗8周后全血高切黏度、血浆黏度、全血低切黏度、红细胞压积低于对照组（P<0.05）。研究组治疗8周后白介素-23（IL-23）、肿瘤坏死因子-α（TNF-α）、白介素-1β（IL-1β）均低于对照组（P<0.05）。两组不良反应发生率对比无差异（P>0.05）。结论：风湿祛痛胶囊联合塞来昔布胶囊治疗AS，可有效缓解患者的临床症状，抑制疾病进展，可能与调节血液流变学、降低炎性因子水平有关。     

Formulation development of self-nanoemulsifying drug delivery system of celecoxib for the management of oral cavity inflammation

The oral administration of celecoxib (CLX) is a real problem because of its low aqueous solubility that results in high variability in absorption and its severe adverse effect such as cardiotoxic effects and gastrointestinal toxicity. Self-nanoemulsifying drug delivery systems (SNEDDS) can enhance the poor dissolution and erratic absorption of poorly water-soluble drugs such as CLX. This study was conducted to investigate the potential of SNEDDS to enhance the efficacy of CLX on inflamed mucous tissue and reduce systemic adverse effects by increasing its poor dissolution properties. A pseudo-ternary phase diagram was derived from the results of CLX solubility experiments in various excipients. These studies revealed the use of Labrafil M 2515 CS as oil, tween 80 as a surfactant, and polyethylene glycol 400 as a co-surfactant for the optimization of SNEDDS formulations. Eight formulations were formulated and characterized by their particle size, polydispersity index, viscosity, globular shape, drug solubility, self-emulsification efficiency, in vitro drug release, and permeation. The anti-inflammatory effect of CLX-SNEDDS was evaluated by carrageenan-induced cheek oedema in rats. The cheeks were treated with CLX-SNEDDS before oedema induction and then noticed for narrow periods (2?h) followed by histopathological studies to determine the efficacy of treatment. The selected formulations (F3 and F5) showed spherical morphologies under transmission electron microscopy, mean droplet sizes of 116.9?±?1.78 and 124?±?1.87?nm, respectively, complete in vitro drug release, and high cumulative amounts of drug permeation in 8?h. They also showed significant remarkable cheek oedema inhibition in comparison with the control groups (p?<?0.05). CLX-SNEDDS was found to achieve effective local therapeutic concentration and intended to reduce cheek oedema, congestive capillary, inflammatory cells, and side effects due to lower dose size.