Long-term oral plus topical mesalazine in frequently relapsing ulcerative colitis

BACKGROUND: In cross-sectional studies, it was demonstrated that the therapeutic effect of mesalazine is closely related to its mucosal concentration. AIM: This study was carried out to verify in a longitudinal study if it was possible to improve the clinical course of ulcerative colitis at high risk of recurrence by increasing mucosal mesalazine concentration. METHODS: Eighteen consecutive ulcerative colitis patients on continuous oral 5-ASA treatment (2.4-3.2 g/day) in clinical remission who had had at least four moderate to severe relapses in the preceding 2 years (referred period) were assigned to assume oral (3.2-4.8 g/day) and topical (4 g/day) mesalazine in order to increase mucosal drug concentration and were followed up for 2 years (study period). The localisation of disease was 12 pancolitis, six left colitis. The number and severity of recurrences, number of visits and endoscopies, courses of steroids and days of hospitalisation were compared with those of the previous 2 years. Rank signed test for paired data was used for statistical analysis. RESULTS: The total number of recurrences was significantly lower during the study period in comparison with that of referred period (8 versus 80, respectively, p < 0.0001). No courses of steroids or hospitalisation were necessary during study period in comparison with those of referred period (0 versus 33, p < 0.0001; 0 versus 93, p = 0.03, respectively). A total number of 249 visits were done during the referred period and 116 during the study period (p < 0.0001) with a total of 87 endoscopies during referred period and 44 during study period (p < 0.0001). CONCLUSIONS: The continuous use of topical mesalazine associated with a high oral dosage significantly improves the clinical course of ulcerative colitis patients at high risk of relapse.     

Measurement of Human Cytochrome P450 Enzyme Induction Based on Mesalazine and Mosapride Citrate Treatments Using a Luminescent Assay

Drug metabolism mostly occurs in the liver. Cytochrome P450 (CYP) is a drug-metabolizing enzyme that is responsible for many important drug metabolism reactions. Recently, the US FDA and EU EMA have suggested that CYP enzyme induction can be measured by both enzymatic activity and mRNA expression. However, these experiments are time-consuming and their inter-assay variability can lead to misinterpretations of the results. To resolve these problems and establish a more powerful method to measure CYP induction, we determined CYP induction by using luminescent assay. Luminescent CYP assays link CYP enzyme activity to firefly luciferase luminescence technology. In this study, we measured the induction of CYP isozymes (1A2, 2B6, 2C9, and 3A4) in cryopreserved human hepatocytes (HMC424, 478, and 493) using a luminometer. We then examined the potential induction abilities (unknown so far) of mesalazine, a drug for colitis, and mosapride citrate, which is used as an antispasmodic drug. The results showed that mesalazine promotes CYP2B6 and 3A4 activities, while mosapride citrate promotes CYP1A2, 2B6, and 3A4 activities. Luminescent CYP assays offer rapid and safe advantages over LC-MS/MS and qRT-PCR methods. Furthermore, luminescent CYP assays decrease the interference between the optical properties of the test compound and the CYP substrates. Therefore, luminescent CYP assays are less labor intensive, rapid, and can be used as robust tools for high-throughput CYP screening during early drug discovery.     

益阳汤结合益生菌及美沙拉嗪治疗溃疡性肠炎的临床分析

目的观察益阳汤结合益生菌、美沙拉嗪治疗溃疡性肠炎的临床疗效。方法对我院2015年8月~2016年10月期间所收治的136例溃疡性肠炎患者的临床资料进行回顾性分析,按照患者治疗方式的不同将其分为研究组与对照组,每组68例,对照组患者应用美沙拉嗪与益生菌联合治疗,研究组在此基础上加用益阳汤治疗,对比分析两组患者的临床疗效、用药时间、症状消失时间和不良反应发生情况,并对两组患者的炎症因子水平进行比较。结果研究组患者的临床总有效率(94.12%)明显高于对照组(82.35%),不良反应发生率(4.41%)低于对照组(20.59%),研究组治疗后的各项炎症因子水平也均优于对照组,且研究组用药时间[(9.52±2.18)d]与症状消失时间[(5.01±1.12)d]均短于对照组[(14.89±2.03)d、(9.23±1.56)d],差异有统计学意义(P0.05)。结论益阳汤结合益生菌、美沙拉嗪治疗溃疡性肠炎的临床效果远高于单纯应用西药治疗的效果,中西医结合治疗手段能够有效改善患者的临床症状,缩短患者的用药时间,且具有不良反应少的优势,值得临床应用。     

美沙拉嗪对溃疡性结肠炎患者肠道黏膜屏障功能和免疫功能的系统评价

目的探讨美沙拉嗪应用于溃疡性结肠炎对患者肠道黏膜屏障功能与免疫功能的影响。方法选取2016年3月~2017年2月在我院接受治疗的溃疡性结肠炎患者93例,按照用药不同,分成美沙拉嗪组(n=47)和柳氮磺吡啶组(n=46),于用药前和用药1疗程、2疗程后,比较两组免疫功能、肠道黏膜屏障功能变化及肠黏膜恢复情况。结果用药前,两组Ig A、Ig G、Ig M、Fas/Fas L及CD4+、CD8+和CD4+/CD8+差异均不显著(P0.05),用药1疗程、2疗程后,两组各项指标均显著变化,且用药1疗程后的各项指标与2疗程后均有显著差异(P0.05),美沙拉嗪组用药1疗程、2疗程后Ig A、Ig G、Ig M、CD4+、CD4+/CD8+显著高于柳氮磺吡啶组,Fas/Fas L、CD8+显著低于柳氮磺吡啶组(P0.05);用药前,两组肠道黏膜屏障功能指标差异均不显著(P0.05),用药1疗程、2疗程后,两组各项肠道黏膜屏障功能表达水平均显著降低,且用药1疗程与用药2疗程各项指标间有显著差异(P0.05),实验组用药1疗程、2疗程后DAO、LAC、PCT、LPS、D-LA均显著低于柳氮磺吡啶组(P0.05);用药前,两组肠黏膜临床症状总积分无显著差异(P0.05),用药1疗程、2疗程后,两组临床症状总积分均显著下降,美沙拉嗪组显著低于柳氮磺吡啶组(P0.05)。结论对于溃疡性结肠炎患者,可采取美沙拉嗪进行治疗,能够有效促进肠黏膜恢复,其作用机制可能和改善肠道黏膜屏障功能与调节免疫功能有关。     

美沙拉嗪干预溃疡性结肠炎相关癌变小鼠的实验研究

目的:观察美沙拉嗪防治溃疡性结肠炎相关癌变小鼠的实验研究。方法:60只清洁级Balb/c小鼠随机分5组,每组12只,正常组、模型组、低、中、高剂量治疗组;除外正常组,其余各组采用DMH/DSS复合法制备溃结癌变模型,模型组予等剂量生理盐水、治疗组分别予不同剂量美沙拉嗪干预9周。第9周末将全部小鼠脱椎处死,截取全部结肠(回盲部-肛门),肉眼及光镜下观察小鼠结肠组织形态学变化。结果:模型组小鼠结肠肉眼可见浆膜层散在、多处息肉状隆起变化,镜下见腺体萎缩、高级别上皮内瘤变,部分癌变;低剂量组肉眼见结肠黏膜充血水肿,部分可见溃疡样改变,镜下见黏膜充血肿胀,部分腺体萎缩;中、高剂量组肉眼见结肠黏膜充血、水肿,糜烂,镜下见黏膜上皮脱落,充血肿胀,未见溃疡及癌变,与模型组比较,有统计学意义(P0.05)。各剂量组之间比较,无统计学意义(P0.05)。结论:美沙拉嗪具有防治溃结相关癌变的生物学效应。     

猴头菌提取物颗粒联合美沙拉秦治疗溃疡性结肠炎的临床研究

目的探讨猴头菌提取物颗粒联合美沙拉秦肠溶片治疗溃疡性结肠炎的临床疗效。方法选取2016年4月—2018年4月咸阳市第一人民医院收治的120例溃疡性结肠炎患者作为研究对象,将所有患者根据随机数字表法分为对照组和治疗组,每组各60例。对照组患者口服美沙拉秦肠溶片,1片/次,3次/d;治疗组患者在对照组治疗的基础上口服猴头菌提取物颗粒,3g/次,3次/d。两组患者均持续治疗4周。观察两组的临床疗效,比较两组的血清炎性因子水平、疾病活动指数(DAI)评分、临床症状改善时间。结果治疗后,对照组和治疗组的总有效率分别为81.67%、95.00%,两组比较差异有统计学意义(P0.05)。治疗后,两组患者白细胞介素-8(IL-8)、肿瘤坏死因子-α(TNF-α)和白细胞介素-6(IL-6)水平均显著降低,同组治疗前后比较差异有统计学意义(P0.05);并且治疗组血清炎性因子水平明显低于对照组,两组比较差异有统计学意义(P0.05)。治疗后,两组患者DAI评分显著降低,同组治疗前后比较差异有统计学意义(P0.05);并且治疗组DAI评分明显低于对照组,两组比较差异有统计学意义(P0.05)。治疗后,治疗组患者治愈时间、黏液脓血便消失时间均短于对照组,两组比较差异有统计学意义(P0.05)。结论猴头菌提取物颗粒联合美沙拉秦肠溶片治疗溃疡性结肠炎具有较好的治疗效果,可改善患者临床症状,降低血清炎性因子水平,具有一定临床推广应用价值。     

比较美沙拉嗪与柳氮磺吡啶治疗溃疡性结肠炎的疗效与安全性的meta分析

目的比较美沙拉嗪与柳氮磺吡啶2种药物治疗溃疡性结肠炎（UC）的疗效与安全性。方法计算机检索PubMed、Cochrane Library、EMbase、CNKI、CBM和万方数据库,查找所有比较2种药物治疗UC的随机对照试验（RCT）,检索时限均为建库至2014年2月12日。按照纳入与排除标准选择文献、评价质量并提取资料后,采用RevMan 5.2软件进行meta分析,并采用Jadad评价量表进行质量评价。结果共纳入13个RCT,其研究质量均为中等。合计1 104例UC患者。Meta分析结果显示,美沙拉嗪对比柳氮磺吡啶治疗UC总有效率差异有统计学意义[RR=1.21,95%CI（1.12,1.32）,P〈0.01],美沙拉嗪组总有效率高于柳氮磺吡啶组;共有3个RCT报道了复发率,结果显示,美沙拉嗪对比柳氮磺吡啶治疗UC,在复发率方面,差异有统计学意义[RR=0.60,95%CI（0.37,0.96）,P=0.03],美沙拉嗪组复发率低于柳氮磺吡啶组。共有9个RCT报道了不良反应,采用随机效应模型,meta分析结果显示：两组差异有统计学意义[RR=0.45,95%CI（0.33,0.59）,P〈0.01],美沙拉嗪组不良反应发生率低于柳氮磺吡啶组。结论现有证据显示,美沙拉嗪治疗UC的疗效和安全性均优于柳氮磺吡啶。     

美沙拉秦灌肠液联合布拉氏酵母菌散治疗溃疡性结肠炎的疗效观察

目的：探讨美沙拉秦灌肠液联合布拉氏酵母菌散治疗溃疡性结肠炎的临床效果。方法选择本院2013年7月—2014年4月收治的轻、中度活动性溃疡性结肠炎患者80例,随机分为治疗组和对照组,各40例。治疗组给予美沙拉秦灌肠液联合布拉氏酵母菌散治疗,对照组仅给予美沙拉秦灌肠液治疗。观察两组患者的临床效果及不良反应。结果治疗后,治疗组总有效率为97.5%（39/40）,高于对照组的77.5%（31/40）,差异有统计学意义（P〈0.05）。两组患者的不良反应未通过特殊处理均自行缓解。结论美沙拉秦灌肠液联合布拉氏酵母菌散治疗溃疡性结肠炎疗效确切。     

枫蓼肠胃康冲剂联合美沙拉秦缓释片对反复发作型溃疡性结肠炎的临床疗效及安全性研究

目的观察枫蓼肠胃康冲剂联合美沙拉秦缓释片治疗反复发作型溃疡性结肠炎患者的疗效及安全性。方法将52例反复发作型溃疡性结肠炎患者随机分为2组,每组26例。对照组患者给予美沙拉秦缓释片1 g/次口服,4次/d,共治疗4周。观察组患者在对照组的基础上,加服枫蓼肠胃康冲剂3.0 g(1包)/次,3次/d。两组患者均配合口服补液盐或补液、补钾等辅助治疗。治疗前后均进行结肠镜检查,比较两组患者临床疗效及治疗后结肠镜检结果。治疗前后均进行血压检查,密切观察两组患者治疗期间不良反应发生情况。随访半年,观察比较两组患者结肠炎复发情况。结果观察组、对照组总有效率分别为92.31%、69.23%,观察组疗效明显优于对照组(P<0.05)。观察组结肠镜检查0级12例,1级8例;对照组0级7例,1级5例,两组比较差异有统计学意义(P<0.05)。两组患者治疗前血压比较差异无统计学意义,观察组治疗后SBP、DBP均明显高于对照组(P<0.05)。两组患者均未出现肝肾功能异常及血常规异常。观察组、对照组分别有3例、2例发生不良反应,两组不良反应比较差异无统计学意义。随访半年期间,对照组、观察组分别有1例(3.85%)、6例(23.08%)复发,观察组复发率明显低于对照组(P<0.05)。结论枫蓼肠胃康冲剂联合美沙拉秦缓释片治疗反复发作型溃疡性结肠炎,疗效确切,不良反应少,可明显降低疾病复发率。     

美沙拉嗪联合灌肠治疗溃疡性结肠炎的临床研究

目的分析研究美沙拉嗪口服联合灌肠治疗溃疡性结肠炎的临床疗效。方法将2010年3月至2011年3月期间在我院治疗的68例患者随机分成治疗组和对照组各34例,治疗组口服美沙拉嗪缓释颗粒同时给予美沙拉嗪灌肠剂;对照组给予口服柳氮磺胺吡啶,比较两组的临床疗效及治疗前后肠镜检查肠黏膜变化情况。结果治疗组的总有效率为94.12%,对照组的总有效率为85.29%。两组临床疗效比较差异有统计学意义(uc=-6.854,P<0.05),且治疗组不良反应发生率低于对照组(P<0.05),与治疗前比较,两组肠黏膜的充血水肿、溃疡、糜烂、出血点及瘢痕治疗后均显著减轻(P<0.05),但治疗前、后两组间比较差别均无统计学意义(P>0.05)。结论美沙拉嗪联合灌肠治疗溃疡性结肠炎疗效确切,不良反应发生率低,安全可靠,值得临床推广应用。