Inhibition of methylprednisolone elimination in the presence of clarithromycin therapy

BACKGROUND: Macrolide antibiotics have long been used as steroid-sparing agents in patients with severe steroid-dependent asthma. Their efficacy and their propensity to potentiate glucocorticoid adverse effects have been attributed in part to their ability to delay glucocorticoid clearance. OBJECTIVE: We sought to determine whether clarithromycin, a newer macrolide antibiotic, can alter the pharmacokinetic profile of oral glucocorticoids and thereby increase the risk of steroid-induced adverse effects. METHODS: An open-label study in a paired design (before and after treatment) was conducted in a hospital-based outpatient clinic. Participants were 6 adult patients (mean age, 30 years) with mild-to-moderate asthma. Prednisone (40 mg/1.73 m2) and methylprednisolone (40 mg/1.73 m2) were given as single randomized doses on consecutive study days before and on days 8 and 9 of a clarithromycin (500 mg twice daily) course. Twelve-hour pharmacokinetic profiles with measurement of plasma methylprednisolone and prednisolone levels were taken before and after clarithromycin therapy. RESULTS: Clarithromycin therapy resulted in a 65% reduction of methylprednisolone clearance and significantly higher mean plasma methylprednisolone concentrations compared with preclarithromycin concentrations but had no significant effect on prednisolone clearance or mean prednisolone plasma concentrations. CONCLUSIONS: Clinicians must be aware of potential drug interactions that could place patients at increased risk for steroid-induced adverse effects. Such an effect has been demonstrated between clarithromycin and methylprednisolone, two drugs that may be administered concomitantly in asthma. To avoid potential steroid-enhancing effects, prednisone should be substituted for methylprednisolone during prolonged courses of clarithromycin therapy.     

人OX40-Fc分子的构建、真核表达及活性研究

目的构建人OX40-Fc基因的真核表达质粒，并表达有生物学活性的纯化人OX40-Fc融合蛋白。方法从活化的人T细胞cDNA文库中以PCR方法扩增OX40膜外区cDNA编码基因，并导入真核表达载体pcDNA3中。测序证实后，进行酶切并与人IgG1Fc基因一起装入真核表达载体pcDNA3中，采用脂质体法稳定转染COS-7细胞，用夹心ELISA检测其表达情况，经蛋白A亲和纯化，用SDS-PAGE与Western blotting进行鉴定。检测其对活化后Jurkat细胞增殖的抑制活性。结果测序证实构建的OX40膜外区与OX40-Fc cDNA阅读框完整，连接部位序列正确；ELISA证实OX40-Fc蛋白的表达；SDS-PAGE与Western blotting证实其为OX40-Fc蛋白。增殖实验证明其对活化后的Jurkat细胞有抑制增殖作用。结论成功构建了人OX40-Fc真核表达载体，并使有生物学活性的OX40-Fc融合蛋白在COS-7细胞上获得了稳定表达。为进一步研究该蛋白在自身免疫性疾病治疗中的作用及调节免疫自稳机制中的地位奠定了基础。     

甲基化特异性PCR联合结合重亚硫酸盐限制性内切酶法在胃癌抑癌基因甲基化检测中的应用

目的探讨甲基化特异性PCR(MSP)方法检测胃癌组织中抑癌基因甲基化的准确性,联合应用MSP方法与结合重亚硫酸盐限制性内切酶法(COBRA)检测抑癌基因甲基化状态的意义。方法采用MSP检测胃癌组织抑癌基因Runx3启动子区甲基化的状态,随后再采用COBRA检测胃癌组织标本的甲基化状态。分析两种方法检测结果的关系。结果经MSP方法检测54例肿瘤组织中共有30例标本发生Runx3基因启动子区异常甲基化,甲基化阳性率为55.6%。经COBRA方法检测54例肿瘤组织中有27例出现酶切条带即存在甲基化,甲基化阳性率为50.0%。经COBRA方法检测,在MSP方法检测的30例阳性标本中有3例未出现酶切条带即为假阳性。在MSP方法检测Runx3基因甲基化阴性的24例标本中,经COBRA方法检测,Runx3基因甲基化阴性的标本亦为24例。两种检测方法检测结果的阳性率差异无统计学意义(P>0.05)。结论甲基化特异性PCR方法在检测胃癌抑癌基因甲基化状态的研究中具有较高的灵敏度,COBRA方法可以检测出MSP方法中的假阳性标本,联合应用两种方法检测胃癌组织中抑癌基因的甲基化状态会使实验结果更可靠、准确。     

双水平正压通气对老年肺心病失代偿期患者血浆脑钠素、内皮素-1和血管紧张素Ⅱ水平的影响

目的探讨老年慢性肺心病失代偿期时血浆脑钠素(BNP)、内皮素-1(ET-1)和血管紧张素II(AngⅡ)水平的变化及双水平正压通气(BiPAP)治疗对其影响。方法老年慢性肺心病失代偿期患者60例,随机分为BiPAP治疗组(30例)和常规治疗组(30例)。常规治疗组为降肺动脉压、强心、利尿剂、血管扩张剂等药物并加用鼻导管给氧治疗。BiPAP治疗组,在常规内科治疗同时加用BiPAP治疗,分别观察治疗72h后两组患者临床症状、体征、心率(HR)、呼吸频率(RR)、血压、血气分析、一秒钟用力呼气容积(FEV1)、肺动脉压(PAP)以及血浆BNP、ET-1和AngⅡ的变化。结果与常规治疗组比较,BiPAP组治疗72h后,患者临床症状与体征改善明显,其SaO2、PaO2和FEV1显著升高(P<0.05),PAP、HR、RR显著下降(P<0.05)。BiPAP治疗后血浆BNP、ET-1和AngⅡ水平随缺氧的纠正而显著降低(P<0.01),与PaO2呈显著负相关(P<0.01),与PAP呈显著正相关(P<0.01)。结论BiPAP在改善老年慢性肺心病失代偿期患者氧和功能和降低PAP的同时,也降低患者血浆BNP、ET-1和AngⅡ水平。     

温莪术内生真菌的分离及其抗菌活性的初步研究

&nbsp;目的研究温莪术内生真菌的种群组成及其代谢产物抗菌活性。方法采用内生菌常规分离法对健康温莪术植株体内的内生真菌进行了分离鉴定。以大肠杆菌、金黄色葡萄球菌、链球菌、沙门氏菌、巴氏杆菌为测试菌种,对温莪术根、茎、叶中分离的56株内生真菌进行抗菌活性筛选。结果经初步鉴定,这些内生真菌为5目、6科、24属;抑菌实验表明,56株内生真菌中有39株对5种测试菌均有不同程度的抑制作用。结论温莪术植物含有丰富多样的内生真菌,且多数内生真菌都表现为较高的抑菌活性。     

基于转化医学理念临床医学研究生的科研能力培养

【摘要】 我国现行临床医学研究生培养体系中存在临床实践与基础研究严重脱节现象,将“转化医学”理念导入我国的临床医学研究生教育,将有利于产生新的培养模式。转化医学是基础研究与临床实践之间双向转化的培养体系,在此探索通过优化教学体系、临床技能培养、基础科研训练、凝炼临床课题、参与并申报课题与人文素质培养的方式培养临床医学研究生的“转化”能力,最终造福患者。     

Comparison of side effects of oxytetracycline and talc pleurodesis: an experimental study

Background&nbsp;&nbsp;

Chemical pleurodesis is widely recommended in the treatment of refractory pleural effusion or pulmonary air leak of different etiologies. Although several agents have been used, many questions have remained unanswered about their toxicity. Talc is the most commonly used agent for the treatment, with rare, serious complications reported. Oxytetracycline pleurodesis in clinical practice has been described in a few studies, but literature reveals no experimental studies using this agent. We performed a prospective, randomized, observer-blinded, controlled study to evaluate the changes in lung histology and systemic response to pleurodesis with oxytetracycline and talc in acute and subacute phases in a rat model.