益赛普与柳氮磺胺吡啶治疗强直性脊柱炎的Mete分析

目的评价益赛普与柳氮磺胺吡啶治疗强直性脊柱炎的疗效和副作用。方法计算机检索Cochrane Library（2013年第3期）,MEDLINE（1966~2013.10）,EMbase（1974~2013.10）,中国生物医学文献数据库（1978~2013.10）,中国期刊全文数据库（1994~2013.10）,中文科技期刊全文数据库（1989~2013.10）,万方数据库（1980~2013.10）中所有益赛普与柳氮磺胺吡啶治疗强直性脊柱炎的随机对照试验和半随机对照试验。由两名评价员独立提取资料,并对其方法学质量进行评价。对符合纳入标准的研究用RevMan5.2软件进行Meta分析。结果共纳入7个研究940例患者,Meta分析结果示：益赛普较柳氮磺胺吡啶治疗强直性脊柱炎患者能有效提高达到ASA20的病例数[OR=2.71,95%CI（2.22,3.32）],改善治疗终点时Bath强直性脊柱炎测量指数（BASMI）[MD=-0.43,95%CI（-0.46,-0.40）],提高脊柱活动度（Schober试验）[MD=0.54,95%CI（0.04,1.03）],降低红细胞沉降率[MD=-6.23,95%CI（-7.83,-4.63）],降低C-反应蛋白[MD=-5.12,95%CI（-6.79,-3.45）]。在骶髂关节MRI炎症评分两药间差异无统计学意义[MD=-0.26,95%CI（-0.76,0.24）]。两种药物用药期间发生呼吸道感染事件差异无统计学意义[OR=1.33,95%CI（0.26,6.85）],发生胃肠道反应事件差异有统计学意义[OR=0.33,95%CI（0.12,0.89）]。结论益赛普较柳氮磺胺吡啶在改善患者功能,降低红细胞沉降率,炎症反应蛋白更有效,而且发生胃肠道反应的事件更少。     

Anti-inflammatory effects of Vicenin-2 on dextran sulfate sodium-induced colitis in mice

The objective of the present work was to evaluate the anti-inflammatory effects of Vicenin-2 on dextran sulfate sodium (DSS)-induced colitis model. Colitis was induced in C57BL/6J mice by administration of 2% DSS in drinking water for 7 days. In addition to DSS, Vicenin-2 (50 mg kg⁻¹/day⁻¹) was administrated orally to the test group. The ulceration extent and severity were assessed macroscopically, histopathologically, and by disease activity index. The Vicenin-2 treated group showed significant differences in physiological parameters including bodyweight, colon weight, and colon length, compared to DSS-induced colitis group. In addition, Vicenin-2 treatment effectively reduced stool consistency and bleeding scores. Myeloperoxidase (MPO) activity, expressions of pro-inflammatory cytokines, and specific key inflammatory markers (iNOS and COX-2) significantly increased in DSS-induced colitis colon tissues. However, administration of Vicenin-2 effectively reduced the MPO activity, attenuated the expression of pro-inflammatory cytokines and key inflammatory markers, in DSS-induced colitis mice. These results were comparable with sulfasalazine, an anti-inflammatory drug used routinely for ulcerative colitis (UC). These findings suggest that Vicenin-2 effectively suppresses DSS-induced colitis by attenuating expressions of key inflammatory mediators and found to be an attractive therapeutic drug for treating UC.     

Total glucosides of paeony for the treatment of rheumatoid arthritis: A methodological and reporting quality evaluation of systematic reviews and meta-analyses

ObjectiveTo assess the methodological, reporting and evidence quality of systematic reviews and meta-analyses of total glucosides of paeony (TGP) for rheumatoid arthritis (RA).MethodsWe comprehensively searched the literature in numerous databases from inception to July 29th, 2020. Two appraisers collected data and assessed the methodological and reporting quality of the included reviews by revised A MeaSurement Tool to Assess systematic Reviews (AMSTAR-2) tool and the Preferred Reporting Items for Systematic reviews and Meta-analyses (PRISMA), respectively. The level of evidence quality was evaluated by employing the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) scale.ResultsEleven relevant articles were collected. The results from AMSTAR-2 showed that the methodological quality of all included reviews was critically low; no authors met the standard of those critical domains (0%), particularly in item 2, item 4 and item 7. The PRISMA scores ranged from 16.5 to 25, and one meta-analysis almost conformed to the PRISMA structure. According to GRADE, the 11 studies included 59 outcomes: 27 had very low quality, 22 had low quality, 10 had moderate quality, and none had high quality evidence. The most prominent downgrading factors were risk of bias, followed by publication bias, inconsistency, imprecision, and indirectness.ConclusionsAlthough included studies summarized that TGP was effective and safe in the treatment of RA, the methodological and reporting quality and the quality of evidence was poor overall; decision-makers should be prudent when using TGP in treating RA patients. High-quality and multicenter studies investigating TGP for RA are urgently needed.     

ORIGINAL ARTICLE: Effect of Sulfasalazine on Basal and Bacteria‐Stimulated Interleukin‐8 Production by Endocervical Epithelial Cells

Problem Sulfasalazine (SASP) inhibits lipopolysaccharide‐induced nuclear‐factor kappa B activation and interleukin‐8 (IL‐8) production by cultured explants of placenta, amnion and choriodecidua. Bacteria‐induced IL‐8 production in the cervix is a potential mechanism for premature cervical ripening that may lead to preterm birth. Our objective was to determine if SASP inhibits IL‐8 production by endocervical cells stimulated with bacterial pathogens associated with preterm birth. Method of study Human endocervical cells were incubated with 0–1.6 mm SASP and then stimulated with Ureaplasma parvum, Escherichia coli, or Gardnerella vaginalis. Conditioned medium was then harvested and production of IL‐8 was quantified by ELISA. Viability of the cells was ascertained at the end of the experiment with the MTT‐assay. Results At the highest concentration tested (1.6 mm ), SASP significantly inhibited IL‐8 production by cultures stimulated with E. coli (P < 0.001), U. parvum (P < 0.001), and G. vaginalis (P < 0.001). Viability of the cells, however, was significantly reduced by SASP at 0.8 and 1.6 mm in both the presence and absence of bacteria for all experiments. Conclusion Although high concentrations of SASP inhibit IL‐8 production by cultures of endocervical cells stimulated with pathogens associated with preterm birth, this effect may be because of toxicity of the antibiotic on the cells.     

分光光度法测定柳氮磺胺吡啶及其代谢物磺胺吡啶浓度的研究

目的 建立不经分离同时测定血浆中SASP和SP的浓度，并对SASP和SP的体内过程进行研究。方法 紫外分光光度法。结果 SASP的线性范围为1-46mg／L，平均回收率99．1％，相对标准偏差7．3％(n＝5)。SP的线性范围为4—42mg／L，平均回收率80．5％，相对标准偏差6．6％(n＝5)。柳氮磺胺吡啶栓剂进入体内，代谢物SP的血药浓度大于SASP的血药浓度，SP在体内有较高的生物利用度。结论 紫外分光光度法简单、快速、灵敏，可用于柳氮碘胺吡啶(SASP)及其代谢物碘胺吡啶(SP)的体内浓度研究。     

Acetylator phenotype and serum levels of sulfapyridine in patients with inflammatory bowel disease

Summary Twenty-eight outpatients receiving sulfasalazine for inflammatory bowel disease were monitored. Assessment of acetylator phenotype according to the percentage of acetylated sulfapyridine in serum provided a clear distinction between rapid and slow acetylators. In comparison, the percentage of acetylated sulfapyridine in saliva or urine was a less precise index of phenotype. Determination of saliva concentrations of sulfapyridine and N⁴-acetylsulfapyridine did not provide a reliable estimate of serum levels. Slow acetylators had significantly higher serum concentrations of sulfapyridine (21.9±14.0 [SD] µg/ml) than rapid acetylators (8.8±4.3 µg/ml) and had a higher incidence of toxicity (not statistically significant,p>0.05). Serum concentrations of sulfapyridine were significantly higher in patients with symptoms of toxicity (23.2±15.9 µg/ml) than those without (13.9±9.5 µg/ml) (p<0.05). However, serum concentrations of total sulfapyridine (sulfapyridine plus N⁴-acetylsulfapyridine) were not significantly different in patients with (32.9±21.2 µg/ml) or without (22.8±12.0 µg/ml) toxicity (p>0.05). For all patients serum concentrations of sulfapyridine (total sulfapyridine) ranged from 3.5 to 73.1 (5.7 to 95.1) µg/ml in patients with controlled disease and 6.3 to 38.0 (14.0 to 54.7) µg/ml in patients with active disease. A significant correlation between clinical status of disease and serum drug concentrations was only apparent for rapid acetylators (p<0.05). The daily sulfasalazine dosage (mg/kg of body weight, log value) and serum drug concentrations (log values) were highly correlated (p<0.05). For clinical evaluation of inflammatory bowel disease patients determination of serum sulfapyridine concentrations appears to be more important for monitoring toxicity than therapeutic efficacy of sulfasalazine. Assessment of acetylator status appears to be useful for predicting serum sulfapyridine levels in patients receiving sulfasalazine therapy.     

柳氮磺胺吡啶联合甲氨喋呤治疗强直性脊柱炎的临床疗效分析

目的：比较柳氮磺胺吡啶联合甲氨喋呤与单用甲氨喋呤治疗强直性脊柱炎的临床疗效与副反应。方法：回顾性总结了１０９例甲氨喋呤对组与１６例柳氮磺胺吡啶联合甲氨喋呤治疗组１年后,绎腰背痛、晨僵时间、外周关节痛、胸廓扩张度、Ｓｃｈｏｂｅｒ试验、血沉、Ｃ反应蛋白、Ｘ线骶髂关节改变的影响。结果：治疗组总有效率优于对照组,尤其对改善晨僵时间、外周关节痛、枕墙距、ＣＲＰ优于对照组。两组副反应均较轻,无差异。结论：柳氮     

A Case of Sulfasalazine-Induced Hypersensitivity Syndrome Confirmed by Enzyme-Linked Immunospot Assay

A 24-year-old male with a history of spondyloarthropathy presented with high fever, cervical lymphadenopathy and generalized maculopapular rash. He was treated with prednisolone for chronic uveitis before being switched to sulfasalazine 3 weeks prior to admission. Laboratory findings revealed marked leukocytosis with frequent atypical lymphocytes. Sulfasalazine was discontinued and the etiology of mononucleosis syndrome explored. During admission, he developed acalculous cholecystitis and hypotension. All symptoms quickly improved following administration of systemic corticosteroids. The investigation for infectious mononucleosis yielded negative results and a diagnosis of sulfasalazine-induced hypersensitivity syndrome was confirmed using enzyme-linked immunospot assays.     

Effects of sulfasalazine and tofacitinib on the protein profile of articular chondrocytes

Abstract

Objective. Sulfasalazine (SSZ) and tofacitinib are effective for treating rheumatoid arthritis, however, their effects on chondrocytes have not been fully understood. We here tried to elucidate their effects on chondrocyte proteins.

Methods. We treated chondrocytes from five osteoarthritis patients with IL-1β, IL-1β+ SSZ, IL-1β+ tofacitinib, SSZ alone, and tofacitinib alone. Then, we compared protein profiles of the chondrocytes using two-dimensional differential gel electrophoresis. Further, we identified altered proteins by mass spectrometry.

Results. Out of 892 detected protein spots, the IL-1β stimulation changed intensity of 43 spots more than 1.3-fold or less than 1/1.3-fold significantly. SSZ suppressed the IL-1β-induced intensity alteration in 16 (37%) out of the 43 protein spots. Tofacitinib suppressed the IL-1β-induced alteration in 4 (9.3%) out of the 43 spots. The production of AMP deaminase 2 and procollagen-lysine, 2-oxoglutarate 5-dioxygenase 2 were increased by IL-1β and the increase was suppressed by SSZ and by tofacitinib. SSZ alone altered intensity of 273 (31%) out of the 852 spots significantly, whereas tofacitinib alone altered intensity of only 24 (2.7%) out of them.

Conclusion. SSZ and, to lesser extent, tofacitinib suppress the effects of IL-1β on the protein profiles of chondrocytes. Our data would promote understanding of effects of the drugs on chondrocytes.