益肾壮督汤联合西药治疗强直性脊柱炎随机平行对照研究

[目的]观察益肾壮督汤联合西药治疗强直性脊柱炎疗效。[方法]使用随机平行对照方法,将60例门诊及住院患者按随机数字表法随机分为两组,对照组30例柳氮磺胺吡啶片,1g/次,2次/d,治疗组30例益肾壮督汤（杜仲、骨碎补、狗脊、续断、熟地各15g,独活12g,乌梢蛇10g,制川乌8g,桂枝10g,白芍12g,知母15g,炙麻黄、防风各10g,炙甘草6g）,1剂/d,水煎200mL,早晚口服,西药治疗同对照组,连续治疗2个月为1疗程。观测临床症状、脊柱功能、Bath疾病活动指数（BASDAI）、Bath功能指数（BASFI）、晨僵时间、血沉（ESR）、C-反应蛋白（CRP）不良反应。连续治疗3疗程,判定疗效。[结果]治疗组临床缓解7例,显效14例,有效7例,无效2例,总有效率93.30%。对照组临床缓解6例,显效5例,有效14例,无效5例,总有效率83.30%。治疗组疗效优于对照组（P〈0.05）。脊柱功能及症状、实验室指标两组均有改善（P〈0.01）,Schober实验、指地距、BASDAI、BASFI、晨僵时间、ESR、CRP治疗组改善均优于对照组（P〈0.05）,胸廓扩张度、枕墙距两组间无明显差异（P〉0.05）。[结论]益肾壮督汤联合西药治疗强直性脊柱炎疗效满意。     

葡萄籽提取物与柳氮磺吡啶联合用药对实验性溃疡性结肠炎的作用

目的 研究葡萄籽提取物（GSPE）与柳氮磺吡啶（SASP）联合用药治疗葡聚糖硫酸钠（DSS）诱导的小鼠溃疡性结肠炎的效果及作用机制。方法 将SPF级C57小鼠随机分为对照组、模型组、GSPE （250 mg/kg）组、SASP （250 mg/kg）组、联合用药（SASP 250 mg/kg+SASP 250 mg/kg）组,对照组给予正常饮用水,其他组均自由饮用3% DSS水溶液,连续饮用7 d,诱发小鼠溃疡性结肠炎模型;造模第1天同步开始ig给药,每天记录小鼠体质量、便血、便型等症状变化;7 d后断头取血,收集结肠和脾脏,记录结肠长度、脾脏质量变化情况。HE染色评估小鼠结肠黏膜组织病理变化,ELISA法检测血清和结肠组织中炎症因子肿瘤坏死因子（TNF-α）、白细胞介素（IL）-1β、IL-6和NO的表达变化以及丙二醛（MDA）、超氧化物歧化酶（SOD）细胞因子的含量变化,免疫组化分析结肠组织上皮细胞中NF-κB-p65、Nrf2、HO-1和Keap-1含量的变化。应用金氏Q值法分析联合用药的作用效果。结果 与模型组比较,各给药组的小鼠体质量下降幅度显著降低（P<0.01）,小鼠腹泻、便血症状改善明显,其中联合用药组小鼠体质量较单独给药组下降更缓,小鼠腹泻、便血程度改善更明显（P<0.05）。各给药组小鼠血清及结肠组织中IL-1β、IL-6、TNF-α、NO、MDA含量较模型组显著降低,SOD含量则显著升高（P<0.01）;病理组织切片分析发现,各给药组小鼠结肠黏膜病理损伤较模型组显著减轻,其中联合用药组小鼠结肠黏膜病理损伤较单独给药组降低更为显著（P<0.05）。免疫组化分析结果也显示,各给药组小鼠的NF-κB-p65、Keap-1蛋白表达与模型组比较显著下调（P<0.01）,Nrf2、HO-1蛋白表达显著上调（P<0.01）。联合给药组与单独给药组比较,NF-κB-p65、Keap-1蛋白表达显著降低（P<0.05）,Nrf2、HO-1蛋白表达显著升高（P<0.05）。金氏Q值法评价两药合用后对IL-1β、IL-6、TNF-α、NO、MDA、NF-κB-p65、Keap-1的作用效果均大于1.15,说明GSPE与SASP具有协同作用。结论 GSPE与SASP联合用药治疗实验性溃疡性结肠炎效果优于单独给药,联合用药增强GSPE和SASP的抗氧化和抗炎作用,GSPE与SASP配伍治疗溃疡性结肠炎可进一步发挥协同增效的作用。     

Fourier Transform-Raman Spectroscopy for the Qualitative and Quantitative Characterization of Sulfasalazine-Containing Polymeric Microspheres

FT-Raman spectroscopy (FTRS) has been used to characterize microspheres produced from the pharmaceutical polymer Eudragit RS containing a range of concentrations of the drug sulfasalazine. While pure sulfasalazine produced an intense and complex Raman spectrum, the spectrum of drug-free Eudragit RS microspheres was considerably weaker in intensity and contained only a few prominent Raman scattering peaks. In spectra of the drug–polymer micro-spheres, peaks arising from the individual components could be identified. This enabled a quantitative analysis to be undertaken by calculating the ratio between the area of a sulfasalazine peak and the area of a Eudragit RS peak for each microsphere spectrum. A correlation was shown between the peak area ratio and the microsphere sulfasalazine content. FTRS was then applied to a series of microsphere samples which had been dissoluted into pH 7 buffer for 1, 3, 6, 9, 12, or 24 hr. For each spectrum, the drug-polymer peak area ratio was determined and this in turn enabled calculation of the residual drug content of the microsphere sample. FTRS-calculated data showed good agreement with microsphere drug content values determined spectrophotometrically.     

溃结汤对大鼠溃疡性结肠炎治疗及肠黏膜NF-κB的影响

目的探讨溃疡性结肠炎（UC）大鼠肠黏膜NF-κB的活化以及本科自拟中药溃结汤（KJT）对其影响和对UC的治疗作用。方法取50只健康成年Wistar大鼠,应用复合法（2,4-二硝基氯苯＋乙酸）制备细胞免疫反应性UC大鼠模型。取已造模成功Wistar大鼠40只,随机均分为模型组、KJT低剂量组、KJT高剂量组、柳氮磺胺吡啶（SASP）组,并设正常对照组Wistar大鼠10只。观察指标包括结肠重量,大体形态黏膜损伤程度评分,HE染色病理观察,扫描电镜肠黏膜损伤观察,NF-κB p65免疫组化染色（应用图像分析系统处理）。结果模型组结肠重量,大体形态黏膜损伤程度评分较对照组显著增加,NF-κB p65的表达水平显著升高,KJT低剂量组、KJT高剂量组、SASP组上述指标较模型组显著下降。结论 NF-κB表达的增加可能与UC的发生、发展有关;KJT和SASP的抗炎作用可能是通过抑制NF-κB的表达实现。     

Suppression of experimental autoimmune encephalomyelitis by sulfasalazine

It has recently been suggested that the sulfidopeptide leukotriene C4 (LTC4), a 5-lipoxygenase product of the arachidonic acid metabolism and one of the most potent mediators of vascular permeability, might be involved in the pathogenesis of experimental autoimmune encephalomyelitis (EAE) and multiple sclerosis (MS). Subsequently, 20 guinea pigs with EAE were treated with sulfasalazine, a substance with a proved leukotriene inhibiting effect, which has previously been described as exerting beneficial effects in patients with inflammatory bowel disease and rheumatoid arthritis. The sulfasalazine-treated guinea pigs showed a significantly better clinical outcome, as well as a significantly lower histological inflammation score compared with 19 controls.     

Drug hypersensitivity syndrome induced by sulfasalazine: A case report

Introduction:Drug hypersensitivity syndrome (DHS) induced by sulfasalazine is a serious systemic delayed adverse drug reaction, which is associated with significant morbidity and mortality.Patient concerns:A 52-year-old man was hospitalized for developing a rash after 3 weeks of sulfasalazine treatment for ulcerative colitis (UC).Diagnosis:The patient was diagnosed with DHS based on his drug history, clinical manifestations, and laboratory test results.Interventions:The patient was administered intravenous glucocorticoids. The patient’s condition improved after treatment with human immunoglobulin and antihistamines.Outcomes:Combination therapy of glucocorticoid and gamma globulin, the whole-body pruritus disappeared, and no new rash appeared. The whole-body rash subsided or turned dark red.Conclusion:This article describes the diagnosis and treatment process of a case of sulfasalazine-induced DHS and reviews the relevant literature to improve clinician understanding and avoid misdiagnosis and missed diagnosis.     

复方血竭制剂与5-氨基水杨酸在溃疡性结肠炎临床维持缓解治疗中的疗效比较

目的比较复方血竭灌肠液及口服5-氨基水杨酸（SASP）在溃疡性结肠炎（UC）临床维持缓解治疗中的疗效。方法以血竭、白芨为原料制备复方血竭灌肠液,对51例UC患者（血竭组）进行灌肠治疗6个月;SASP组给予SASP1.5g1次/d口服维持6个月,比较两组患者的复发率及治疗中的副作用。结果血竭组和SASP组疗效间差别无显著性意义（P〉0.05）;血竭组消化道反应、血液系统毒性、肝肾功能损害明显小于对照组（P〈0.01）。结论复方血竭灌肠可用于高危患者及SASP治疗无效者的维持治疗方案。     

ORIGINAL ARTICLE: Can Sulfasalazine Prevent Infection‐Mediated Pre‐Term Birth in a Murine Model?

Citation Nath CA, Ananth CV, Smulian JC, Peltier MR. Can sulfasalazine prevent infection‐mediated pre‐term birth in a murine model? Am J Reprod Immunol 2010; 63: 144–149 Problem Sulfasalazine (SASP) blocks activation of nuclear factor‐kappa B (NF‐κB) in gestational tissues in vitro– one of the earliest signals in the inflammatory response. We hypothesized that the administration of SASP would reduce the rate of infection‐mediated pre‐term birth in a murine model. Method of study CD‐1 mice (n = 40) were assigned on gestational day (gd) 14.5 to 1 of 3 treatments: (1) Sham infection and vehicle; (2) 10⁴ CFU Escherichia coli and vehicle; or (3) 10⁴ CFU E. coli and SASP (150 mg/Kg daily). Mice were observed twice daily and deliveries prior to gd 18.5 were considered pre‐term. Results Significantly more mice delivered prior to gd 18.5 when infected with 10⁴ CFU E. coli than sham‐infected mice (P < 0.001) and this effect was significantly reduced in mice also treated with SASP (P = 0.002). SASP also tended to increase litter size (P = 0.060) and significantly increased weight of pups born to dams with intrauterine infections (P = 0.001). Conclusion SASP reduced rates of pre‐term delivery and improved pregnancy outcomes for mice infected with 10⁴ CFU E. coli. This suggests that SASP has the potential to play a role in strategies to prevent pre‐term birth in women.     

Emerging drugs for complications of end-stage liver disease

Background: The prevalence of end-stage liver disease is rising rapidly and constitutes a major healthcare burden currently. Many cases are diagnosed at a later stage when liver transplantation is the only effective treatment option. There is thus an urgent need for novel treatments to reverse the earlier stages of cirrhosis as well as to treat the many associated life-threatening complications. Objectives: To review the current drugs available for treating the complications of advanced liver disease. To address novel treatment strategies that are in development, with particular reference to the rapidly developing area of antifibrotic therapy. To assess how the obstacles that have so far impeded the development of effective new drugs for end-stage liver disease may be overcome in the future. Methods: The literature was reviewed to define current therapies and therapies in clinical trials. We used the current models of the molecular basis of liver fibrogenesis to determine potential new therapeutic targets for antifibrotic therapy. Conclusions: Insights into the pathogenesis of liver injury and fibrosis have opened up new avenues for therapy and there are now candidates and targets with real potential for the development of a new generation of antifibrotic therapies.