Steady‐state amprenavir and tenofovir pharmacokinetics after coadministration of unboosted or ritonavir‐boosted fosamprenavir with tenofovir disoproxil fumarate in healthy volunteers

Objective

An open‐label, three‐period pharmacokinetic study was conducted to investigate the drug interaction potential between fosamprenavir (FPV) and tenofovir disoproxil fumarate (TDF).

Methods

Thirty‐six healthy subjects received TDF 300 mg once daily (qd) for 7 days (period 1), and then were randomized to 14 days of either FPV 1400 mg twice daily (bid) or FPV/ritonavir (RTV) 700/100 mg bid alone or with TDF (period 2). Subjects continued their randomized dose of FPV for 14 more days, adding or removing TDF based upon its receipt in period 2 (period 3). Twenty‐four‐hour pharmacokinetic sampling was carried out on day 7 of period 1 and on day 14 of periods 2 and 3. Steady‐state plasma amprenavir (APV) and tenofovir (TFV) pharmacokinetics were assessed by noncompartmental analysis and parameter values observed with each regimen were compared using geometric mean ratios with 90% confidence intervals.

Results

After TDF coadministration, APV geometric mean minimum concentration (C_min), maximum concentration (C_max), and area under the plasma concentration–time curve (AUC) increased by 31, 3 and 7% above values observed with unboosted FPV alone; they also increased by 31, 4 and 16% above values observed with FPV/RTV alone. TFV C_min, C_max and AUC decreased by 12, 25 and 15% after FPV coadministration and by 9, 18 and 7% after FPV/RTV coadministration. No significant changes in RTV pharmacokinetics were observed. No differences were noted in adverse events among dosing periods.

Conclusions

In this evaluation of the interaction between FPV and TDF, increases in APV exposures and modest decreases in TFV exposures were observed. These were unlikely to be clinically significant.

     

关节镜手术治疗踝关节骨折后创伤性关节炎17例

目的 观察关节镜手术治疗踝关节骨折后创伤性关节炎的近期效果.方法 2007年12月～2009年4月我院对17例踝关节骨折术后创伤性关节炎进行踝关节镜手术治疗,并运用关节镜观察踝关节病变情况.结果 术中踝关节镜下见慢性滑膜炎性增生17例,胫骨下端前缘骨赘6例,距骨颈部骨赘4例,距骨关节软骨损伤11例,胫骨关节软骨损伤4例,游离体2例.术后48 h 5例有关节疼痛、轻度肿胀,1周后好转,余无明显关节疼痛.16例随访12～25个月,平均18.2个月.根据Baird等踝关节评分系统评定疗效,优4例,良10例,可2例,优良率87.5%.结论 踝关节镜手术治疗踝关节骨折后创伤性关节炎近期效果满意.     

Preliminary Evaluation of the Wound Healing Effect of Vitex Doniana Sweet (Verbenaceae) in Mice

Vitex doniana is traditionally used in Togo to treat various diseases including wounds. The aim of this work was to evaluate the efficiency of Vitex doniana on cutaneous wound healing. Wounds were induced in ICR mice divided into four groups as following: Group I received carbopol 974P NF empty gel, Groups II and III were treated topically with carbopol gel containing 2.5% and 5% of Vitex doniana extract. Group IV received Betadine® 10% as standard drug. The efficacy of treatment was evaluated by planimetry and histological analysis. We secondary used the gel containing Vitex doniana at 2.5% and the pure extract at 10 mg/ml on the model of ear edema induced by xylene. Skin toxicity test was performed with the gel containing Vitex doniana at 5% and the pure extract at 30 mg/ml. Vitex doniana at 5% and 2.5% provided better wound contraction (91.14% and 86.38%) at day 12 post-excision when compared to control (51.15%). The results of histological evaluation supported the outcome of excision wound model. Moreover Vitex doniana inhibited significantly edema induced by xylene when compared to control (p< 0.05). In skin toxicity test, no abnormal symptoms were developed over 14 day-time period. Vitex doniana inhibits the topical inflammation and accelerate cutaneous wound repair.     

外固定器结合可吸收缝线治疗桡骨远端骨折

目的探讨外固定架结合可吸收缝线治疗桡骨远端粉碎性骨折的临床疗效。方法 2006年9月至2008年5月,运用万向式骨外固定器结合可吸收线治疗桡骨远端不稳定骨折42例,男性26例,女性16例,并对关节功能按Dienst标准进行评定。结果 42例均获随访,时间6~18个月（平均10个月）,骨折均骨性愈合,愈合时间6~8周。关节功能评定：优23例,良14例,可5例。结论万向式外固定架结合可吸收线治疗桡骨远端粉碎性骨折操作简单、固定可靠、疗效满意。     

Bupropion in the treatment of pathological gambling: a randomized, double-blind, placebo-controlled, flexible-dose study

We tested the efficacy of bupropion in the treatment of persons with pathological gambling (PG). Nondepressed, healthy subjects with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition PG were randomly assigned to placebo or flexibly dosed bupropion in a 12-week double-blind trial. Outcome measures included the Yale-Brown Obsessive-Compulsive Scale modified for PG, the Gambling Severity Assessment Scale, the Clinical Global Impression Improvement and Severity Scales, the Global Assessment Scale, the Timeline Follow Back, the Attention-Deficit/Hyperactivity Disorder Rating Scale, and the Sheehan Disability Scale. Thirty-nine subjects (28 men, 11 women) were randomized to bupropion (n = 18) or placebo (n = 21). The 2 groups were similar on demographic and clinical measures. There were few differences between the treatment groups on any primary or secondary outcome measure, although subjects in each cell experienced significant improvement. Of subjects with at least 1 postrandomization visit, 35.7% of bupropion and 47.1% of placebo recipients experienced "much" or "very much" improvement on the Clinical Global Impression Improvement Scale. The trial was complicated by a high noncompletion rate (43.6%). Bupropion was well tolerated. Bupropion and placebo recipients did equally well in a short-term trial, with improvement seen as early as the first week of treatment. The high placebo response rate and the high noncompletion rate each reflect the challenge inherent in treating persons with PG.     

损伤性癫痫模型大鼠海马和额叶突触蛋白的动态表达

目的 通过观察FeCl2皮层注射致损伤性癫痫(PTE)模型大鼠海马、额叶突触蛋白P38的表达变化.探讨突触可塑性在PTE发病机制中的作用. 方法 健康成年雄性SD大鼠采用随机数字表法分为正常对照组(n=5)、假手术组(n=12)、模型组(n=20).采取立体定向皮层注射FeCl2(0.1 moL/L,10μL)建立PTE模型,假手术组注入等量生理盐水,正常对照组不做处理.观察各组大鼠EEG的变化并应用免疫组织化学方法 检测大鼠造模后不同时间点(1 h、7 d、14 d、30 d)海马、额叶P38的表达. 结果大多数模型组大鼠在注射FeCl2后不久记录到癫痫样放电;与假手术组比较,模型组不同时间点右侧额叶P38表达减少.差异有统计学意义(P<0.05);与正常对照组和假手术组比较,致痫1h后,CA3区多形层、辐射层、腔隙层和齿状回(DG)分子层P38表达均无明显变化,7 d后P38表达增加,维持到30d,差异均有统计学意义(P<0.05). 结论 与突触蛋白P38表达相关的突触可塑性变化在PTE的发病机制中可能起重要作用.     

金藤清痹颗粒治疗急性痛风性关节炎的作用机制研究

目的 应用网络药理学分析金藤清痹颗粒治疗急性痛风性关节炎（acute gouty arthritis，AGA）的作用机制，并建立AGA大鼠模型进行验证。方法 在清热解毒、活血止痛治法指导下，通过TCMSP数据库搜集金藤清痹颗粒的活性成分及靶点，利用GeneCards、NCBI数据库等搜集AGA相关靶点，与金藤清痹颗粒作用靶点整合后，构建共有靶点蛋白质-蛋白质相互作用（protein-protein interaction，PPI）网络和“金藤清痹颗粒-中药-活性成分-靶点-AGA”网络，并进行基因本体（gene ontology，GO）功能及京都基因与基因组百科全书（Kyoto encyclopedia of genes and genomes，KEGG）通路富集分析。雄性SD大鼠随机分为空白组、模型组、秋水仙碱（0.3 mg/kg）组和金藤清痹颗粒低、中、高剂量（1.05、2.10、4.20 g/kg）组，每组6只，踝关节注射单钠尿酸盐（monosodium urate，MSU）晶体建立AGA大鼠模型。采用游标卡尺测量大鼠踝关节直径，计算踝关节肿胀度；采用全自动生化仪检测血清尿酸（serum uric acid，SUA）、C反应蛋白（C-reactive protein，CRP）水平；采用苏木素-伊红（HE）染色观察踝关节组织病理变化；采用qRT-PCR、ELISA和Western blotting检测踝关节组织及血清中关键靶点和信号通路的表达。结果 共检索到金藤清痹颗粒110种活性成分、212个作用靶点，272个AGA治疗靶点，共有靶点29个，关键靶点有白细胞介素-1β（interleukin-1β，IL-1β）、肿瘤坏死因子（tumor necrosis factor，TNF）及IL-6，涉及TNF信号通路、IL-17信号通路和NOD样受体信号通路等。大鼠踝关节注射MSU晶体后明显肿胀（P<0.01），SUA及CRP显著升高（P<0.05、0.01），滑膜组织增生明显、结构紊乱，有大量炎症细胞浸润，NOD样受体热蛋白结构域相关蛋白3（NOD-like receptor thermal protein domain associated protein 3，NLRP3）、NIMA相关蛋白激酶7（NIMA-related kinases 7，NEK7）、凋亡相关斑点样蛋白（apoptosis-associated speck-like protein containing a CARD，ASC）、半胱氨酸天冬氨酸蛋白酶-1（cystein-asparate protease-1，Caspase-1）、消皮素D（gasdermin D，GSDMD）、IL-18、IL-1β、IL-6及TNF-α表达水平明显升高（P<0.01）；秋水仙碱或金藤清痹颗粒治疗后，有效缓解踝关节肿胀（P<0.05、0.01），SUA及CRP均显著降低（P<0.05、0.01），关节滑膜增生、炎症细胞浸润均得到改善，同时显著抑制IL-1β、TNF-α及IL-6等靶点和NOD样受体信号通路的表达（P<0.05、0.01）。结论 金藤清痹颗粒对AGA大鼠具有明显的保护作用，其机制可能与抑制NOD样受体信号通路的异常激活，降低炎症因子水平，改善关节滑膜增生、炎症细胞浸润有关。     

The erroneous perception of a clinical sign: Cholestasis preceding sepsis mimicking hepatitis in an adolescent patient

Jaundice should be considered as a first clinical sign preceding severe invasive bacterial infection or sepsis in patients of all ages including childhood and adolescence. Early laboratory investigations and MR imaging studies for osteomyelitis or myositis are paramount to avoid progression to life‐threatening sepsis and significant morbidity and mortality.     

生物碱类天然药物抗痛风作用及作用机制的研究进展

痛风是由于机体嘌呤代谢异常和(或)尿酸排泄障碍所致的一组异质性疾病。生物碱是一类含有氮的有机化合物,广泛存在于植物中,用于痛风等多种疾病引起的炎症反应。通过查阅国内外最新相关文献报道,对生物碱抗痛风作用及作用机制的研究进展进行综述,以期为生物碱的进一步研究和临床应用提供科学依据和理论指导。