Sodium salicylate and 5-aminosalicylic acid synergistically inhibit the growth of human colon cancer cells and mouse intestinal polyp-derived cells

As colon cancer is one of the most common cancers in the world, practical prevention strategies for colon cancer are needed. Recently, treatment with aspirin and/or 5-aminosalicylic acid-related agents was reported to reduce the number of intestinal polyps in patients with familial adenomatous polyposis. To evaluate the mechanism of aspirin and 5-aminosalicylic acid for suppressing the colon polyp growth, single and combined effects of 5-aminosalicylic acid and sodium salicylate (metabolite of aspirin) were tested in the two human colon cancer cells with different cyclooxygenase-2 expression levels and intestinal polyp-derived cells from familial adenomatous polyposis model mouse. The combination induced cell-cycle arrest at the G1 phase along with inhibition of cell growth and colony-forming ability in these cells. The combination reduced cyclin D1 via proteasomal degradation and activated retinoblastoma protein. The combination inhibited the colony-forming ability of mouse colonic mucosa cells by about 50% and the colony-forming ability of mouse intestinal polyp-derived cells by about 90%. The expression level of cyclin D1 in colon mucosa cells was lower than that in intestinal polyp-derived cells. These results suggest that this combination may be more effective in inhibiting cell growth of intestinal polyps through cyclin D1 down-regulation.     

美沙拉嗪联合双歧杆菌三联活菌治疗溃疡性结肠炎的效果

目的探讨美沙拉嗪联合双歧杆菌三联活菌治疗溃疡性结肠炎的效果。方法回顾性分析2018年1月至2020年1月本院收治的100例溃疡性结肠炎患者的临床资料,根据治疗方法将患者分为单独治疗组(n=50,美沙拉嗪单独治疗)与联合治疗组(n=50,美沙拉嗪联合双歧杆菌三联活菌治疗)。比较两组患者的临床疗效、血清炎性因子水平、免疫功能。结果联合治疗组的治疗总有效率高于单独治疗组(P<0.05)。治疗后,两组的血清IL-6、IL-8、hs-CRP及TNF-α水平均降低,且联合治疗组低于单独治疗组(P<0.05)。治疗后,两组的血清IgA、IgG、IgM水平、CD8+均降低,CD3+、CD4+及CD4+/CD8+均升高,且联合治疗组优于单独治疗组(P<0.05)。结论相较于美沙拉嗪单独治疗,美沙拉嗪联合双歧杆菌三联活菌治疗溃疡性结肠炎的效果更显著。     

Acute interstitial nephritis due to mesalazine

A case of mesalazine-induced acute interstitial nephritis (AIN) in a 41-year-old patient with ulcerative colitis (UC) is reported here. Clinical symptoms such as fever and arthralgia, and laboratory findings such as eosinophilia and renal failure suggested AIN, which was confirmed by biopsy. With withdrawal of mesalazine and intravenous methylprednisolone the patient's renal function was recovered. It is observed that early discontinuation of mesalazine is associated with amelioration of interstitial nephritis in most patients, so the recommendation is that patients receiving mesalazine should undergo routine monitoring of renal function. Delayed diagnosis may lead to permanent renal function impairment.     

Obstructing Crohn's disease of the duodenum: Is surgery always mandatory?

Crohn's disease may involve any part of the alimentary tract. But, Crohn's disease of the duodenum is a very rare condition. Systemic steroid therapy had been shown to be effective in patients with Crohn's disease, and the most common indication for surgical intervention is duodenal obstruction. We report a case with Crohn's disease of the duodenum presenting with duodenal obstruction. Medical treatment option was successful as a first line of therapy because of young age and new diagnosis. The patient was administered mesalazine as a treatment, and the obstruction was resolved. The patient is still in remission for the last 2 years.     

反相高效相色谱法测定马沙拉嗪的含量

目的 建立反相高效液相色谱法测定马沙拉嗪的含量。方法 采用Hypersil C18（4．6mm×250mm，5μm）色谱柱，流动相为甲醇-水溶液（60：40），检测波长为210nm，进样体积20μL。结果马沙拉嗪在5～300μg·mL^-1，线性关系良好（r＝o．9999）。结论 该法的专属性强，用于马沙拉嗪含量测定，准确可靠。     

Oral and topical 5-aminosalicylic acid (mesalazine) in inducing and maintaining remission in mild-moderate relapse of ulcerative colitis: one-year randomised multicentre trial

BACKGROUND: The association of oral 5-aminosalicylic acid (mesalazine) and enema is effective in treatment of mild-moderate forms of ulcerative colitis. However no study has been aimed at determining optimal duration of this association in active ulcerative colitis. AIM: To determine whether longer duration of therapy: 1. increases the rate of patients achieving remission, and 2. reduces relapse rate during the maintenance period in patients in remission. PATIENTS AND METHODS: A total of 149 patients, (89 male, 60 female), were randomly assigned to a regimen with 5-aminosalicylic acid tablets 2.4 g/day associated with 5-aminosalycilic enema 2 g/day for a 4-week (n = 73) or 8-week regimen (n = 76). After this acute therapy, patients were submitted to clinical, endoscopic and histological examinations and those in remission were assigned to a follow-up (maintenance) period with oral mesalazine alone at a dosage of 1.2 g/day. A clinical visit, including laboratory tests, at 6 months and an endoscopic-histological control at 12 months were carried out to exclude symptoms and endoscopic-histological signs of activity. Relapse of disease, i.e., presence of clinical symptoms or abnormal laboratory tests, was confirmed by endoscopy and histology. RESULTS: At end of acute phase, clinical, endoscopic and histological remission was comparable in the two groups: 42/76 (55%), in the 4-week, and 47/73 patients (64%), in the 8-week regimen. No difference was found stratifying patients according to extension of disease. Of these 89 patients in remission, 75 (34 from 4-week regimen; 41 from 8-week regimen) completed 12 months' follow-up. At end of follow-up, a similar percentage of patients in the 4-week regimen (50%) and 8-week regimen (51%) were still in remission. No significant difference between cumulative relapse rates of the two groups was found. Stratifying patients according to extension of disease, in the 8-week regimen group, those with left-sided colitis showed a higher remission rate than that of patients with diffuse colitis (66% versus 35%, p < 0.05). All regimens were well tolerated by most patients during the entire study period. CONCLUSIONS: An additional 4 weeks of topical treatment does not increase the remission rate in patients with mild-moderate active ulcerative colitis but seems to reduce the probability of relapse in patients with left-sided colitis.     

孕烷X受体/NF-κB信号通路在美沙拉嗪改善大鼠溃疡性结肠炎中的作用

目的研究孕烷X受体/NF-κB(PXR/NF-κB)信号通路在美沙拉嗪(Mes)干预溃疡性结肠炎(UC)大鼠中的作用。方法SPF级雄性SD大鼠一次性结肠灌注2,4,6-三硝基苯磺酸(TNBS)每只0.8 mL,连续4 d。每天观察各组大鼠体质量,粪便性状,计算病变活动指数(DAI),DAI为正常组的2倍以上,则为造模成功。模型大鼠按照分组每天分别ig给予Mes 300 mg·kg^-1(模型+Mes组)、利福平(Rif)50 mg·kg^-1+Mes组(模型+Mes+Rif组)和酮康唑(Ket)35 mg·kg^-1+Mes组(模型+Mes+Ket组),均先给Rif和Ket、给药4 d后给予Mes,连续7 d。HE染色观察结肠病理改变;ELISA法测定血浆肿瘤坏死因子α(TNF-α)、γ干扰素(IFN-γ)、白细胞介素4(IL-4)和IL-13含量;比色法检测结肠髓过氧化物酶(MPO)活性;实时PCR和Western印迹法检测结肠PXR,NF-κB,NF-κB p65和κB抑制因子α(IκB-α)蛋白和mRNA水平。结果模型组大鼠体质量明显下降,并伴有稀便和血便的症状。与UC模型组相比,模型+Mes组大鼠体质量明显升高(P<0.05),HE染色见结肠组织病变程度减轻;血浆TNF-α与IFN-γ含量、结肠组织中MPO活性、NF-κB mRNA及p-P65蛋白水平显著降低(P<0.05),而血浆IL-4和IL-13含量及结肠组织Pxr,NF-κB p65和IκB-αmRNA水平均显著升高(P<0.05)。与模型+Mes组相比,模型+Mes+Rif组结肠组织Pxr和NF-κB通路相关靶基因表达水平差异无统计学意义,而模型+Mes+Ket组结肠中Pxr和IκB-αmRNA水平显著下降(P<0.05)。结论Mes对UC的治疗效果很可能与激活PXR/NF-κB信号通路有关。