灌肠方治疗溃疡性结肠炎的临床疗效及对血清D-二聚体和血小板参数的影响

目的:观察灌肠方对溃疡性结肠炎(UC)患者的临床疗效及对血清D-D、PLT和MPV的影响。方法:收集40例UC患者,随机分为灌肠方治疗组(20例)和柳氮磺胺吡啶对照组(20例)。治疗3周后,观察临床症状以及治疗前后血清D-D、PLT和MPV水平的变化。结果:治疗组临床症状改善优于对照组。治疗组患者血清D-D和PLT水平降低、MPV水平升高较对照组显著(P0.05)。结论:灌肠方治疗UC疗效显著;降低血清D-D和PLT水平以及升高MPV水平可能是其治疗UC的机制之一。     

柳氮磺吡啶结肠溶胶囊微生物限度检查方法的研究

目的建立柳氮磺吡啶结肠溶胶囊的微生物限度检查方法。方法通过测定该品种对5个规定试验菌种的回收率来确定其抑菌活性。结果该品种对金黄色葡萄球菌和枯草杆菌有强抑菌活性。结论细菌计数采用离心沉淀集菌法＋培养基稀释法＋中和法联用的综合方法。控制菌检查用常规法即可检出。     

Sulfasalazine could modulate the CD44v9‐xCT system and enhance cisplatin‐induced cytotoxic effects in metastatic bladder cancer

The prognostic role of CD44v9, a variant isoform of CD44 and a new cell surface marker of cancer stem cells, remains unclear in bladder cancer (BC) patients. Furthermore, limited information is available on the functional role of sulfasalazine (SSZ), which could modulate the CD44v9‐xCT system in order to enhance cisplatin (CDDP)‐induced cytotoxicity and inhibit the metastatic potential of BC. CD44v9 protein expression was examined immunohistochemically in 63 muscle invasive BC (MIBC) patients who underwent radical cystectomy. CD44v9 expression was independently associated with disease recurrence and cancer‐specific death in MIBC. Cytotoxic effects, glutathione levels, and reactive oxygen species production by SSZ and CD44v9 and phospho‐p38^MAPK protein expression by SSZ with or without CDDP were assessed in MBT‐2V cells with highly metastatic potential. Sulfasalazine exerted cytotoxic effects against MBT‐2V cells by inhibiting glutathione levels and inducing the production of reactive oxygen species. Sulfasalazine in combination with CDDP appeared to exert strong cytotoxic effects against MBT‐2V cells by inhibiting CD44v9 expression and upregulating phospho‐p38^MAPK expression. The inhibitory effects of SSZ with or without CDDP were also investigated using an MBT‐2V lung metastatic model. In the murine lung metastatic BC model, SSZ significantly prolonged animal survival. Furthermore, the combination of SSZ with CDDP exerted stronger inhibitory effects on the establishment of lung tumor nodules than SSZ or CDDP alone. CD44v9 expression could be a clinical biomarker for predicting poor outcomes in MIBC patients. Sulfasalazine in combination with CDDP has potential as a novel therapy against metastatic BC.     

美沙拉嗪治疗老年溃疡性结肠炎的临床效果观察

目的探讨美沙拉嗪治疗老年溃疡性结肠炎(UC)的临床效果。方法选择该院收治的68例老年UC患者随机分为观察组和对照组各34例,其中使用美沙拉嗪治疗的为观察组,使用柳氮磺吡啶治疗的为对照组。比较两组患者治疗前后临床症状、结肠镜检查结果、大便次数及肝肾功能的变化。结果观察组患者的总有效率为94.1%,对照组为79.4%,观察组治疗效果优于对照,差异有统计学意义(P0.05);观察组不良反应发生率为8.8%,对照组为29.4%,差异有统计学意义(P0.05)。结论美沙拉嗪治疗老年UC具有明显的治疗效果,并且药物的不良反应低,安全性较高。     

Potential use of the anti-inflammatory drug,sulfasalazine, for targeted therapy of pancreatic cancer

Pancreatic cancer is an aggressive, drug-resistant disease; its first-line chemotherapeutic, gemcitabine, is only marginally effective. Intracellular depletion of glutathione, a major free-radical scavenger, has been associated with growth arrest and reduced drug resistance (chemosensitization) of cancer cells. In search of a new therapeutic approach for pancreatic cancer, we sought to determine whether specific inhibition of the plasma membrane x_c⁻ cystine transporter could lead to reduced uptake of cysteine, a key precursor of glutathione, and subsequent glutathione depletion. Sulfasalazine (approximately 0.2 mmol/L), an anti-inflammatory drug with potent x_c⁻-inhibitory properties, markedly reduced l-[¹⁴C]-cystine uptake, glutathione levels, and growth and viability of human MIA PaCa-2 and PANC-1 pancreatic cancer cells in vitro. These effects were shown to result primarily from inhibition of cystine uptake mediated by the x_c⁻ cystine transporter and not from inhibition of nuclear factor κB activation, another property of sulfasalazine. The efficacy of gemcitabine could be markedly enhanced by combination therapy with sulfasalazine both in vitro and in immunodeficient mice carrying xenografts of the same cell lines. No major side effects were observed in vivo.The results of the present study suggest that the x_c⁻ transporter plays a major role in pancreatic cancer by sustaining or enhancing glutathione biosynthesis, and as such, represents a potential therapeutic target. Sulfasalazine, a relatively nontoxic drug approved by the U.S. Food and Drug Administration, may, in combination with gemcitabine, lead to more effective therapy of refractory pancreatic cancer.     

Mucosal healing in inflammatory bowel disease: results from a Norwegian population-based cohort

BACKGROUND AND AIMS: Mucosal healing (MH) in inflammatory bowel disease may be an important sign of efficacy of treatment and a prognostic marker of long-term disease. The aim of the study was to examine both the possible predictors of mucosal healing and the impact of healing on subsequent course of disease. METHODS: In 740 incident patients diagnosed with ulcerative colitis (UC) or Crohn's disease (CD) between 1990 and 1994 (before biologic therapy was available), demographics and symptoms were recorded. Clinical and endoscopic evaluations were done at baseline before treatment and repeated after 1 and 5 years in 495 patients. RESULTS: In UC patients, education longer than 12 years and extensive disease at diagnosis were significant predictors of MH after 1 year (adjusted P = .004 and P = .02, respectively). MH was significantly associated with a low risk of future colectomy (P = .02). In patients with CD, fever at diagnosis and medical treatment without steroids were significant predictors for MH (adjusted P = .03 and P = .01, respectively). MH was significantly associated with less inflammation after 5 years (P = .02), decreased future steroid treatment (P = .02). CONCLUSIONS: Several factors predicted subsequent MH. Education as predictor may implicate the importance of coping, compliance, or lifestyle. MH after 1 year of treatment is predictive of reduced subsequent disease activity and decreased need for active treatment. The present results give further strength to the use of mucosal healing as a clinical indicator and treatment goal in inflammatory bowel disease.     

HPLC法测定柳氮磺吡啶肠溶片的含量

目的：建立用HPLC测定柳氮磺吡啶肠溶片含量的方法。方法：色谱柱为YMC-Pack Pro C18 RS（250 mm×4.6 mm,5μm）,流动相0.1mol?L-1醋酸铵（冰醋酸调节pH值至4.8）-甲醇（60︰40）,检测波长362nm。结果：柳氮磺吡啶浓度在2.9～735.8 μg?ml-1范围内线性关系良好（r=0.9999）,平均回收率为99.1%（n=9）。结论：本方法准确,专属性强,可用于柳氮磺吡啶肠溶片的含量测定。     

Opposite in vivo effects of agents that stimulate or inhibit the glutamate/cysteine exchanger system on the inhibition of hippocampal LTP by Aß

Aggregated amyloid ß‐protein (Aß) is pathognomonic of Alzheimer's disease and certain assemblies of Aß are synaptotoxic. Excess glutamate or diminished glutathione reserve are both implicated in mediating or modulating Aß‐induced disruption of synaptic plasticity. The system antiporter promotes Na⁺‐independent exchange of cystine with glutamate thereby providing a major source of extracellular glutamate and intracellular glutathione concentrations. Here we probed the ability of two drugs with opposite effects on system , the inhibitor sulfasalazine and facilitator N‐acetylcysteine, to modulate the ability of Aß1‐42 to inhibit long‐term potentiation (LTP) in the CA1 area of the anaesthetized rat. Whereas acute systemic treatment with sulfasalazine lowered the threshold for Aß to interfere with synaptic plasticity, N‐acetylcysteine prevented the inhibition of LTP by Aß alone or in combination with sulfasalazine. Moreover acute N‐acetylcysteine also prevented the inhibition of LTP by TNFα, a putative mediator of Aß actions, and repeated systemic N‐acetylcysteine treatment for 7 days reversed the delayed deleterious effect of Aß on LTP. Since both of these drugs are widely used clinically, further evaluation of their potential beneficial and deleterious actions in early Alzheimer's disease seems warranted. © 2016 Wiley Periodicals, Inc.     

Fulminant Liver Failure After Vancomycin in a Sulfasalazine-Induced DRESS Syndrome: Fatal Recurrence After Liver Transplantation

DRESS syndrome (drug rash with eosinophilia and systemic symptoms) is a rare drug hypersensitivity reaction with a significant mortality. We describe a 60-year-old man with polyarthritis treated with sulfasalazine who developed DRESS and fulminant liver failure after additional vancomycin treatment. Liver histology revealed infiltration of granzymeB+ CD3+ lymphocytes in close proximity to apoptotic hepatocytes. After a superurgent liver transplantation and initial recovery, the patient developed recurrent generalized exanthema and eosinophilia, but only moderate hepatitis. Histology showed infiltration of FasL+ lymphocytes and eosinophils in the transplanted liver. Treatment with high-dose methylprednisolone was unsuccessful. Postmortem examination revealed extensive necrosis of the liver transplant. This case report illustrates that patients with DRESS may develop fulminant liver failure and that DRESS recurrence can recur in the transplanted liver. Histological and immunological investigations suggest an important role of granzymeB and FasL mediated cell death in DRESS associated hepatitis.