来氟米特对胶原性关节炎大鼠CD4+CD25+调节性T细胞的影响

目的:探讨来氟米特对胶原性关节炎中免疫抑制性CD4+CD25+调节性T细胞的作用.方法:II型胶原诱导Wistar大鼠,建立胶原性关节炎模型;检测关节炎大鼠多发性关节炎评分,每周2次;流式细胞仪检测脾淋巴细胞中CD4+CD25+调节性T细胞的比例;RT-PCR检测脾淋巴细胞中Foxp3 mRNA的表达.结果:与模型组比...     

来氟米特水溶液化学稳定性的研究

目的：研究广泛pH范围内来氟米特的化学稳定性。方法：建立来氟米特的HPLC测定方法,测定不同温度下不同pH值时来氟米特分解的速度常数,得到不同pH值时的分解活化能及不同温度下的最稳定pH值。结果：常温（20-40℃）下来氟米特最稳定的pH范围是2.85-4.56,活化能数值恰在此范围内出现极大值。最稳定的pH范围随温度升高而向低pH值方向移动,当温度大于60℃时,最稳定pH值为1.80以下。结论：适当调整溶液的pH值可以显著改善来氟米特的化学稳定性,为其制剂学研究提供了部分依据。     

来氟米特凝胶剂的制备与质量控制

目的制备来氟米特凝胶剂，并建立其质量控制方法。方法以壳聚糖为凝胶材料制备来氟米特凝胶剂，采用高效液相色谱法测定来氟米特含量。结果来氟米特质量浓度在10～100μg／mL范围内与峰面积线性关系良好，平均回收率为100．3％，RSD为0．67％（n=6）。结论制备工艺合理、简单，含量测定方法可行，制剂质量稳定。     

Challenges and treatment options for rheumatoid arthritis during pregnancy

Introduction: Rheumatoid arthritis (RA) can spontaneously improve during pregnancy. However, a considerable proportion of patients can experience a flare and high disease activity has been associated with an increased risk of adverse pregnancy outcome. Thus, the treatment of RA in pregnant women should be selected taking into account both the potential harmful effects of the treatment and the risk associated with discontinuation.

Areas covered: Recent publications regarding safety of the most important disease modifying anti-rheumatic drugs (DMARDs) during pregnancy has been reviewed. A systematic literature search of MEDLINE was conducted using pregnancy, teratogenicity, adverse effects, embryo/foetal-toxicity as key search terms for each DMARD.

Expert opinion: A great body of evidence suggest that hydroxychloroquine, sulfasalazine, and non-fluorinated steroids can be continued throughout pregnancy, while methotrexate and leflunomide should be discontinued 3 months before pregnancy. Continuation of TNFi during the first part of pregnancy should be considered when benefits outweigh the potential risk of teratogenicity. Data regarding other biologics are scant and, at present, they should be stopped before pregnancy.     

Pharmacotherapy of post-transplant viral infections

Background: Management of a number of significant viral pathogens in transplant recipients remains challenging. Objectives: To define an optimal antiviral approach to the management of cytomegalovirus (CMV), human herpes virus-6 (HHV-6), Epstein–Barr (EBV)-associated post-transplant lymphoproliferative disorder (PTLD), and polyoma virus-associated nephropathy in transplant recipients. Methods: Clinical trials and existing data regarding use of antiviral agents for these viruses were reviewed to develop evidence-based recommendations for their management. Conclusions: Weighing the current evidence regarding the use of valganciclovir as pre-emptive therapy or prophylaxis, the former approach offers a greater benefit for the overall prevention of CMV disease. Limited data show that prophylaxis with antiviral agents is associated with a reduction in the risk of EBV-associated PTLD. Treatment options for HHV-6 and polyoma virus-associated nephropathy are still limited.     

来氟米特在肾脏病中的应用

来氟米特是一种新型选择性抑制T细胞和B细胞增殖的免疫调节剂 ,它在治疗类风湿关节炎方面有可靠疗效。目前尝试将它用于肾移植、狼疮肾炎、肾小球肾炎、间质性肾炎中 ,并取得良好效果。本文将它在肾脏领域中的应用及其不良反应做一综述。     

Inhibitory effect of leflunomide on hepatic fibrosis induced by CCl4 in rats

AIM: To study the effect of leflunomide on CC14-induced hepatic fibrosis in rats. METHODS: Hepatic fibrosis was induced by subcutaneous injection with 50 % CCl4 in Sprague-Dawley rats. The amount of CC14 administered was 1 mg/kg. The alanine aminotransferase (ALT), aspartate aminotransferase (AST), nitric oxide (NO) levels in plasma and hydroxyproline (Hyp) contents in liver tissue were assayed by spectrophotometry. The hyaluronic acid (HA) and procollagen III (PC III) were assessed by radioimmunoassay. The transforming growth factor-β1(TGF-β1) in serum was determined by ELISA. The nuclear factor-kappa B (NF-κB) in liver tissue was examined by immunohistochemistry. Liver samples collected after 12 weeks ofCC14 treatment were stained with hematoxy-lin and eosin. RESULTS: Leflunomide (1, 3, and 9 mg/kg) significantly decreased indices of liver and spleen, the serum transaminase (AST, ALT) activities, HA and PC III levels, and Hyp contents in liver tissue in rats of hepatic fibrosis. Histopathological examination showed leflunomide had inhibitory effect on fibrogenesis and formation of pseudolobulus. Furthermore, leflunomide significantly inhibited NF-κB expression in liver tissue, and reduced elevated serum TGF-κB and NO levels in rats of hepatic fibrosis. CONCLUSION: Leflunomide showed inhibitory action on hepatic fibrosis induced by CC14 in rats.     

来氟米特对佐剂性关节炎大鼠的治疗作用及部分机制研究

目的　研究来氟米特 (Lef)对佐剂关节炎 (AA)大鼠的治疗作用。方法　观察佐剂性关节炎 (AA)大鼠给药后继发性足肿胀、免疫功能及前列腺素释放水平的变化 ,并检测Lef的活性产物A77172 6体外对正常小鼠T细胞亚群的影响。结果　Lef(2 ,6与 18mg·kg-1)灌胃给药 (ig)可明显抑制AA大鼠继发性的关节肿胀 ,改善AA大鼠多发性关节炎病变症状。对AA大鼠低下的ConA诱导的增殖反应和IL 2无明显影响 ,但对AA大鼠过高的IL 1产生有明显的抑制作用。体外培养发现Lef的活性产物A77172 6(0 1,0 5 ,2 5 ,12 5 ,2 5 ,10 0 μmol·L-1)可抑制正常小鼠ConA诱导的Th 细胞 ,对ConA诱导的Ts 细胞无明显影响。而只有高浓度A77172 6(10 0 μmol·L-1)对AA大鼠PMΦ产生的过高PGE2 有明显的抑制作用。结论　Lef具免疫抑制作用 ,通过抑制细胞免疫功能 ,实现对AA大鼠的治疗作用     

来氟米特对免疫性肝损伤的影响

目的　研究来氟米特对小鼠免疫性肝损伤的影响。方法　利用BCG+LPS诱导免疫性肝损伤;分光光度法检测血中ALT ,AST和NO水平及肝匀浆MDA和GSHpx含量;ELISA法测定血中TNF-α含量;细胞增殖法测定IL-1,IL-2及ConA诱导的脾淋巴细胞增殖反应。结果　在BCG+LPS诱导的免疫性肝损伤中,来氟米特(4,12 ,36mg·kg^-1 )ig给药明显降低免疫性肝损伤小鼠增高的血浆ALT和AST活性及肝匀浆MDA含量,使降低的肝匀浆GSHpx水平增高。进一步研究发现来氟米特明显抑制免疫性肝损伤小鼠TNF-α的产生,降低增高的血清NO水平,抑制PM_Ф产生过高的IL-1,对低下的IL-2产生和ConA诱导的脾淋巴细胞增殖反应有进一步抑制作用。结论　来氟米特对免疫性肝损伤具有保护作用     

复方夏天无片治疗活动期类风湿性关节炎120例临床观察

目的:观察复方夏天无片治疗活动期类风湿关节炎的临床疗效.方法:180例活动期类风湿关节炎患者随机分为对照组(60例)予来氟米特、柳氮磺吡啶、塞来昔布;治疗组(120例)在对照组基础上加用复方夏天无片,每次2片,3次/d,疗程均为3个月.观察2组患者治疗前后临床症状、红细胞沉降率、C-反应蛋白、类风湿因子、免疫球蛋白的变化.结果:治疗组总效率94.2％;夏天无组总有效率80.0％;对照组总有效率81.7％.3组差异具统计学意义(P＜0.01或P＜0.05),治疗组疗效优于夏天无组,夏天无组优于对照组.结论:常规治疗复方夏天无片治疗活动期类风湿关节炎疗效显著.