Pharmacokinetics of medroxyprogesterone acetate after single and multiple injection of cyclofem® in Chinese women

To provide pharmacokinetic data for safety evaluation on prolonged treatment with Cyclofem®, which contains 25 mg medroxyprogesterone acetate (MPA) and 5 mg estradiol cypionate in 0.5 mL microcrystalline aqueous suspension, the pharmacokinetic profiles of MPA after single and multiple administration of this monthly injectable contraceptive were investigated in Chinese women. Nine healthy fertile women received Cyclofem based on a once-a-month regimen for up to 1 year. Blood samples were collected immediately prior to drug administration and on days 1, 3, 5, 7, 14, 21, and 28 after injection. After the 1st, 6th, and 12th injection, the maximum serum concentrations (C_max) of MPA were observed on days 3.4 ± 0.9, 4.3 ± 2.2, and 3.7 ± 2.6, respectively. C_max of serum MPA during the 1st, 6th, and 12th treatment cycles were 3.75 ± 1.27, 5.54 ± 1.79, and 5.55 ± 1.80 nmol/L, whereas the areas under the curve (AUC_{0–28 days}) were 55.84 ± 28.15, 95.45 ± 26.56, and 98.81 ± 21.84 nmol/L·day, respectively. There was significant interindividual variation in the pharmacokinetics of MPA after intramuscular injection of Cyclofem. No significant change was demonstrated in mean residence time (MRT) of MPA after single and multiple injection. There was a tendency of increase in C_max and AUC_{0–28 days} of MPA during the first 6 months of treatment, whereas no further enhancement was found between the 6th and 12th injection (p > 0.05). Peak levels of estradiol (E₂) observed in Cyclofem users were within the normal range of the preovulatory phase. Results of this long-term study suggest that no drug accumulation occurred after repeated administration of Cyclofem in the Chinese women.     

治伤巴布剂对大鼠急性软组织损伤模型P38MAPK、AKT信号通路的影响＊

目的 观察治伤巴布剂对急性软组织损伤（acute soft tissue injury， ASTI）模型p38丝裂原活化蛋白激酶（mitogen-activated protein kinase，MAPK）、丝/苏氨酸蛋白激酶（AKT）信号通路的影响，探讨治伤巴布剂干预ASTI的可能作用机制。方法 将40只雄性SD大鼠按照随机数字表法分为正常对照组、模型对照组、治伤巴布剂组、p38MAPK信号通路抑制剂组、AKT信号通路抑制剂组，每组8只。除正常对照组外，其余四组均予以左侧后肢小腿ASTI造模。造模成功后，治伤巴布剂组于标记部位立即予治伤巴布剂（修剪成1.5x3cm大小）外敷，并用胶布固定；其余四组均予等剂量赋形剂（修剪成1.5×3 cm大小）外敷处理，胶布固定；持续外敷，共持续24 h。p38MAPK信号通路抑制剂组在造模前30 min予腹腔注射p38MAPK信号通路抑制剂SB203580（400 μg/kg/天）1次；AKT信号通路抑制剂组在造模前30 min予腹腔注射AKT信号通路抑制剂perifosine（20 mg/kg/天）1次。分别于0（造模前）、2h、4h、8h、12h、24h测量受伤小腿肌肉处的周长，并计算肌肉肿胀率（muscle swelling rate，MSR）。24 h药物干预结束后，采用颈椎脱臼法处死大鼠。后将左侧后肢小腿损伤中心部位进行取材，分成三份。一部分用于观察组织病理学形态变化；一部分用于逆转录聚合酶链反应（RT-PCR）检测核因子-κB（nuclear factor kappa-B，NF-κB）p65 mRNA、肿瘤坏死因子-α（TNF-α）mRNA、白细胞介素-1β（IL-1β）mRNA表达水平；剩下部分用酶联免疫吸附试验（ELISA）法检测骨骼肌组织TNF-α、IL-1β含量水平及蛋白质免疫印迹（Western-blot）法测定p38MAPK、AKT、NF-κB p65、核因子抑制蛋白α（inhibitor kappa B alpha， IκBα）表达水平。结果 与正常对照组相比，模型对照组MSR显著增加（P<0.01）；病理形态学上，骨骼肌组织可见大面积肌细胞排列紊乱，肌细胞变性坏死，间质内可见红细胞聚集及大量炎症细胞浸润；骨骼肌组织TNF-α、IL-1β含量水平显著升高（P<0.01）；磷酸化p38MAPK（p-p38）/总p38MAPK（t-p38），磷酸化-AKT（p-AKT）/总-AKT（t-AKT）明显升高（P<0.01），NF-κB p65及NF-κB p65mRNA表达水平明显升高（P<0.01）。与模型对照组相比，治伤巴布剂组MSR在治疗第8 h、12 h、24 h显著下降（P<0.01），且在治疗第24 h，其MSR较p38MAPK、AKT信号通路抑制剂组下降更明显（P<0.05）；病理学评分显著下降（P<0.01），且较p38MAPK、AKT信号通路抑制剂组下降更显著（P<0.05）；骨骼肌组织TNF-α、IL-1β含量水平明显下降（P<0.01），且较p38MAPK、AKT信号通路抑制剂组更显著（P<0.05）；p-p38/t-p38及p-AKT/t-AKT明显下降（P<0.01），NF-κB p65及NF-κB p65 mRNA表达水平显著下降（P<0.01），且较p38MAPK、AKT信号通路抑制剂组在降低NF-κB p65及NF-κB p65 mRNA相对表达值方面更显著（P<0.01）。结论 治伤巴布剂可能同时对p38MAPK、AKT信号通路产生了一定的抑制作用，引起NF-κB活性下调，NF-κB p65蛋白的表达下调，进而引起骨骼肌组织TNF-α、IL-1β炎性细胞因子含量水平下调，减轻ASTI炎症反应，从而改善ASTI。     

Anal Sex Role, Circumcision Status, and HIV Infection Among Men Who Have Sex with Men in Chongqing, China

Men who have sex with men (MSM) in China face a rapidly expanding HIV epidemic. Anal sex role plays a significant role in HIV infection. Research has already begun in China investigating the potential for circumcision-based interventions to slow the rise of HIV among Chinese MSM. Using peer referral recruitment, we sampled 491 men who reported anal sex role preference. We analyzed preferred anal sex role, enacted sex role during recent sexual behavior, and circumcision status and HIV infection among MSM in one Chinese city. Men reported on their anal sex role preference and reported on up to three male sexual partners. Men were asked to report on whether they were “top” or “bottom” with each of the partners. Those that preferred being bottom and versatile were significantly younger than those who preferred being top. Men who preferred bottoming and those that preferred the versatile role were significantly more likely to be HIV-infected than those who preferred to be tops. There was no significant association between circumcision and HIV infection among men who maintained their preferred top role. In terms of anal sex role behavior, prevalence was not statistically different across anal sex roles. Circumcision conferred no additional protection to men who preferred and who engaged the top role during anal sex. HIV interventions will need to address anal sex roles in more sophisticated ways than perhaps originally thought. Simplistic assumptions that anal sex role is a fixed behavior undermines interventions such as circumcision among MSM.     

2008～2013年武汉地区32家医院喹诺酮类药应用分析

目的:评价近6年武汉地区喹诺酮类药应用状况及发展趋势进行分析评价。方法:采用限定日剂量法,对2008~2013年武汉地区32家医院喹诺酮类药的用药频度(DDDs)、总消耗金额、限定日费用等进行统计分析。结果:武汉地区医院近6年喹诺酮类药销售总金额分别为11 519.92、11 507.52、12 565.62、11 412.57、11 032.24、11 906.78万元,其中左氧氟沙星、莫西沙星名列前茅,二者的销售金额总和占总份额的70%~80%,并持续增长;帕珠沙星、加替沙星、司帕沙星、洛美沙星的销售金额和DDDs大幅下降;普卢利沙星、巴洛沙星、吉米沙星、芦氟沙星、妥舒沙星已逐渐退出该地区。结论:受几年来抗菌药专项整治的影响,该地区临床使用喹诺酮类药品种减少显著,药品的用量变化较大。     

美国药品审评制度改革对我国的启示

本文概述了我国药品审评现状,介绍了美国药品审评制度改革经验,探讨如何提升我国药品审评的质量和效率。研究认为,我国应完善审评法规体系,增加资源投入,规范审评程序、细化时限规定、制定审评模板,进行质量管理,构建制度评价体系。     

OIC-A006 promotes osteogenesis in vitro and in vivo

Bone morphogenesis proteins (BMPs) are one of the potent bone-forming factors. However, the safety, utility, and cost effectiveness of BMPs must be considered. Nowadays, there has been substantial interest in developing a chemical compound that safely promotes bone formation and facilitates fracture repair. Based on previous research with high throughout screening assay, we found one potent osteogenic inductive compound, named as OIC-A006 (Osteogenic inducible compound-active 006), which is classified in the amine family. In this study, we aimed to investigate the inducing effects of OIC-A006 on osteogenesis by bone marrow stem cells (BMSCs) in vitro and in vivo. We demonstrated that OIC-A006, at different concentrations, especially at optimal concentration of 6.25 microM, could stimulate BMSCs to express alkaline phosphatase (ALP), core-binding factor a1 (Cbfa1), osteopontin (OPN) and osteocalcin (OC), and to form calcified nodules in vitro. Under the bone tissue culture conditions, OIC-A006 also stimulated new bone formation of murine calvarial and metatarsal bone, indicating that OIC-A006 may exert positive effects on osteogenesis. Furthermore, to elucidate the in vivo osteogenic potential of OIC-A006, we used a rabbit skull defect model treated with sustained release microcapsules (OIC-A006/PLGA-MC) injected s.c. adjacent to the defect. These results revealed, for the first time, that OIC-A006 has the potential to promote osteogenesis in vitro and in vivo. This new compound may provide a new alterative agent for growth factors to promote bone healing and bone regeneration.     

原发性肝癌TACE治疗后的影像学评价

原发性肝癌是严重威胁人类健康及寿命的恶性肿瘤之一,经动脉导管化疗栓塞术(TACE)是治疗原发性肝癌应用较为广泛的非外科手术治疗方法,准确地判断肝癌TACE治疗术后的疗效直接关系到临床治疗方案的选择及预后。目前,临床上对肝癌TACE术后的影像学检查方法众多,本文主要针对超声、CT、MR、DSA及PET/CT等影像学检查方法在肝癌TACE治疗后疗效评估中应用的现状进行综述。     

ICP-AES法同时测定碳酸锂原料药中6种杂质元素

目的：建立电感耦合等离子体发射光谱（ICP-AES)同时测定碳酸锂原料药中6种杂质元素（钙、钠、钾、镁、铁和铝）的分析方法,并分析不同厂商碳酸锂原料药的杂质含量。方法：用硝酸溶解样品, ICP-AES法分析样品中6种杂质元素的含量。结果：6种元素标准曲线的相关系数均高于0.999,加标回收率为93%～99%,检出限为0.0003～0.1275μg·mL-1,RSD值均小于2%;利用本法对5个厂家使用的碳酸锂原料药进行测定,结果表明C厂的原料药中钙、钠、镁、铁和铝元素含量均高于其余4个厂家,其中钠超出了药典规定限度。结论：与《中国药典》中碳酸锂原料药杂质测定方法进行比对,本试验所建立的方法测定结果与药典方法一致,且方法专属性强、灵敏度高、操作简单,可以用于碳酸锂原料药中6种杂质元素的测定。     

Enediyne anticancer antibiotic lidamycin: chemistry, biology and pharmacology

The enediyne antibiotics, the potent anticancer agents that contain diyne-ene functional groups, are appreciated for their novel molecular architecture, their remarkable biological activity and their fascinating mechanism of action. Their anticancer activity is apparently due to their ability to damage DNA through radical-mediated hydrogen abstraction. The enediyne antibiotics show markedly cytotoxicities against cancers in vitro and in vivo. Lidamycin is a member of the enediyne anticancer antibiotic family. This review examines lidamycin with particular emphasis on the discovery, the biological properties and its structure-activity relationships. In addition, the possible mechanisms of action of lidamycin are described. Recent progress, particularly in the areas of biosynthesis, and immunoconjugates are highlighted. Finally, the pharmacological applications of lidamycin in cancer therapy and its potential use as anticancer agents are also discussed.     

卡介苗多糖核酸联合异维A酸治疗扁平疣疗效观察

目的：：观察卡介苗多糖核酸联合异维A酸治疗扁平疣的临床疗效和安全性。方法：70例扁平疣患者随机分为观察组和对照组各35例。对照组口服异维A酸软胶囊10 mg,bid,4周后改为10 mg,qd。观察组在对照组基础上加用卡介苗多糖核酸1 ml,im,隔日一次。治疗8周后,比较两组患者治疗前后T淋巴细胞群和免疫球蛋白水平变化,评价两组临床疗效及不良反应情况。结果：治疗后,两组患者的T细胞群水平、IgG、IgA均得到明显改善(P<0.01),且观察组除IgM外的各项指标改善效果均明显优于对照组(P<0.05)。观察组患者的起效时间明显短于对照组(P<0.01),总有效率明显高于对照组(P<0.05)。两组药品不良反应发生率差异无统计学意义(P>0.05)。结论：卡介苗多糖核酸联合异维A酸软胶囊治疗扁平疣,可显著改善患者的免疫功能状况,提高临床疗效,明显优于单独使用异维A酸。且安全性较高。