Wild chamomile (Matricaria recutita L.) mouthwashes in methotrexate-induced oral mucositis

Oral mucositis is a known complication of methotrexate (MTX) therapy, but a single efficacious intervention or agent for prophylaxis or management of this side effect has not yet been identified. We report a case of MTX-induced oral mucositis in a patient with rheumatoid arthritis, who was successfully treated with Wild chamomile mouthwashes.     

Determination of methotrexate in serum by high-performance liquid chromatography

A sensitive high-performance liquid chromatographic method with ultraviolet detection was developed to quantitate methotrexate in serum-based calibrators, controls and patient samples. Sample clean-up was achieved with C₁₈ Sep-Pak Classic cartridges. The chromatographic separation was accomplished on a 5-μm Ultrasphere ODS Beckman column. 8-Chlorotheophylline was used as an internal standard. The method was validated by recovery, linearity, accuracy and precision studies. Two standard curves were constructed to cover the high and the low ends of the calibrator range (0.05–1.0 μmol/l). Response was found linear over the whole range of the calibrator set with a correlation coefficient of 0.999 and 1.00 for the low-level and the high-level curves, respectively. Accuracy varied from 12% at the lowest level to 1.2% at the highest level. The precision study showed a C.V. of 14.4% at the lowest level and 3.3% at the highest level.     

Progressive formation of DNA lesions during treatment with anti-metabolites without incorporation of the drugs into DNA

Anti-metabolites, such as methotrexate, 5-fluoropyrimidines or hydroxyurea, induced progressive formation of DNA lesions. 5-Fluoropyrimidines induce DNA lesions either by incorporation of the drug into DNA or by a mechanism not involving incorporation. The second mechanism, not involving incorporation, is also seen with methotrexate and hydroxyurea. The three anti-metabolites have in common their ability to reduce intracellular levels of nucleotides, resulting in reduced efficiency of repair of DNA lesions. The lesions probably appear spontaneously, independently of the drug treatment.     

剖宫产瘢痕妊娠治疗方案的探讨

目的:探讨剖宫产瘢痕妊娠(CSP)的合理治疗方案。方法:回顾性分析2007年1月至2013年12月我院收治的26例CSP患者的临床资料,对其病史、临床表现、处理及结局进行总结分析,重点探讨其治疗方案与预后的关系。结果:采用的治疗方式包括口服米非司酮配伍米索前列醇后超声监测下清宫术6例、超声监测下局部甲氨蝶呤注射3例、全身甲氨蝶呤注射后清宫术2例、子宫动脉(化疗)栓塞后清宫术16例、经腹病灶切除术1例、经腹全子宫切除术1例。前三种方法尽管具有一定的成功率,但均有较高的术后大出血风险。子宫动脉(化疗)栓塞在CSP的初始及抢救治疗中均具有很高的成功率。结论:CSP治疗方案的选择需根据患者的病情、妊娠部位、生育要求等多方面进行综合考虑。在现有的治疗方案中,子宫动脉(化疗)栓塞后清宫术具有较大的优势。     

戈利木单抗联合雷公藤多甙对甲氨蝶呤治疗反应不佳活动性类风湿关节炎的效果及安全性分析

目的:分析戈利木单抗联合雷公藤多苷对甲氨蝶呤(MTX)治疗反应不佳活动性类风湿关节炎(RA)的临床效果及安全性。方法:选择MTX治疗反应不佳(MTX治疗超3个月,但应答不足)的活动性RA患者66例,按照随机数字表法分为对照组与试验组各33例,对照组单用雷公藤多苷治疗,试验组加用戈利木单抗治疗,测定两组治疗前后血沉(ESR)、C反应蛋白(CRP)、类风湿因子(RF)水平的变化,记录晨僵时间、关节肿胀数目、关节压痛数目,评定治疗效果,采用视觉模拟评分法(VAS)评定患者关节疼痛程度、患者对疾病总体症状的耐受情况,监测两组不良事件的发生情况。结果:(1)治疗后,两组ESR、CRP、RF均降低,与同组治疗前对比差异有统计学意义(P0.05),试验组ESR、CRP降低幅度高于对照组(P0.05);(2)治疗后,两组晨僵时间减少、关节肿胀及压痛数目均减少,与治疗前对比差异有统计学意义(P0.05),试验组各指标改善幅度均高于对照组(P0.05);(3)治疗后,两组VAS评分均降低,与治疗前对比差异有统计学意义(P0.05),试验组降低幅度高于对照组(P0.05);(4)试验组ACR50、ACR70所占比例均高于对照组(P0.05);(5)试验组、对照组不良反应发生率对比差异无统计学意义(P0.05)。结论:戈利木单抗联合雷公藤多苷治疗MTX反应不佳活动性RA疗效肯定,可下调患者ESR、CRP水平,缩短晨僵时间,显著改善患者症状,减轻关节疼痛程度,且安全性高。     

Methotrexate and aminopterin lack in vivo antimalarial activity against murine malaria species

The antifolate anticancer drug methotrexate (MTX) has potent activity against Plasmodium falciparum in vitro. Experience of its use in the treatment of rheumatoid arthritis indicates that it could be safe and efficacious for treating malaria. We sought to establish a murine malaria model to study the mechanism of action and resistance of MTX and its analogue aminopterin (AMP). We used Plasmodium berghei, Plasmodium yoelii yoelii, Plasmodium chabaudi and Plasmodium vinckei. None of these species were susceptible to either drug. We have also tested the efficacy of pyrimethamine in combination with folic acid in P. berghei, and data indicate that folic acid does not influence pyrimethamine efficacy, which suggests that P. berghei may not transport folate. Since MTX and AMP utilise folate receptor/transport to gain access to cells, their lack of efficacy against the four tested murine malaria species may be the result of inefficiency of drug transport.     

Synthesis of 6-deoxy-6-chloro and 6-deoxy-6-bromo derivatives of scleroglucan as intermediates for conjugation with methotrexate and other carboxylate containing compounds

Polysaccharides are widely used as carriers in the field of drug delivery. We present a methodology to obtain water soluble drug-conjugates based on scleroglucan. Selective C-6 halogenation gives access to C-6 esters; conjugates between methotrexate and scleroglucan are described, potentially useful for antitumour therapy or in rheumatoid arthritis treatment.     

依那西普联合甲氨蝶呤治疗类风湿关节炎疗效分析

目的:探讨依那西普联合甲氨蝶呤治疗类风湿关节炎的疗效。方法:选取2011年至2013年风湿免疫科的60例类风湿关节炎患者,分为对照组和治疗组,其中对照组15例,治疗组45例,两组患者都应用甲氨蝶呤治疗,治疗组患者联合使用依那西普治疗,总疗程12周。比较两组患者治疗前后的临床及实验室指标。采用美国风湿病学会的核心标准作为疗效评定标准。结果:治疗组患者肿瘤坏死因子(tumor necrosis factor,TNF)和白细胞介素(interleukin,IL-1)下降明显,与对照组患者相比差异均有统计学意义(P0.05);治疗后两组患者超敏C反应蛋白(hs-CRP)均较治疗前明显降低,差异均有统计学意义(P0.05);治疗组患者关节疼痛、关节肿胀和晨僵情况较对照组均有显著的改善(P0.05);治疗组患者的休息痛、患者评分以及HAQ评分均显著优于对照组(P0.05);治疗组患者ACR20和ACR70缓解的比例均高于对照组,且治疗组患者达ACR50缓解的比例显著高于对照组(P0.05)。结论:依那西普联合甲氨蝶呤治疗类风湿关节炎的疗效优于单纯的甲氨蝶呤治疗。     

A synthetic analog of prostaglandin E(1) prevents the production of reactive oxygen species in the intestinal mucosa of methotrexate-treated rats

Administration of methotrexate to rats results in severe enterocolitis and death. Previous our studies showed that a synthetic analog of prostaglandin E(1), OP-1206 [17S, 20-dimethyl-trans-Delta(2)-prostaglandin E(1)] ameliorated the anticancer agent-induced enterocolitis of rats. In the current study, we have focused on the biochemical effect of OP-1206 on the methotrexate-induced intestinal inflammation implicating reactive oxygen species (ROS). Methotrexate (15 mg/kg body weight) was orally administered to rats once daily for 5 days. OP-1206 (0.5 microg/kg body weight) was orally administered to rats twice a day for 5 days. On the 6th day, the chemiluminescence from the jejunum was measured to evaluate the generation of ROS. Spontaneous chemiluminescence from the jejunum of the methotrexate-treated rats increased significantly, compared with the control. Luminol-enhanced chemiluminescence from inflamed mucosal scrapings from the jejunum of the methotrexate-treated rats indicated more remarkable enhancement than the control rats. The treatment of OP-1206 with methotrexate showed significantly lower chemiluminescence of both the jejunum and mucosal scrapings than those of the methotrexate-treated rats. The alkaline phosphatase (ALP) activity, as a marker of small intestinal differentiation, in the intestinal mucosa of the methotrexate-treated rats decreased remarkably, but that of the methotrexate and OP-1206-treated rats was significantly higher than that of the methotrexate-treated rats. Thus, OP-1206 may possibly help the anticancer chemotherapy by protecting the small intestine from the methotrexate-induced damage.