卡铂-乳酸/羟基乙酸共聚物微球的制备和体外性质

目的制备卡铂-乳酸/羟基乙酸共聚物(PLGA)微球,比较不同方法所得微球的形态、载药量和体外释药特点。方法采用相分离法和溶剂挥发法制备卡铂-PLGA微球,显微镜下测定微球的粒径和粒径分布,电子扫描显微镜观察微球表面形态。用电感耦合等离子体发射光谱法(ICP-AES)测定微球含药量,计算包封率,考察微球体外释药行为。结果两种方法所得微球球形较好,相分离法制得的卡铂-PLGA微球,平均粒径为22~31μm,含药量为42~61μg·mg-1、包封率21%~31%;体外释放试验中药物于24h完全溶出。溶剂挥发法所得微球平均粒径为38~54μm,含药量为7.2μg·mg-1、包封率约为20%;体外药物突释率约为39%,缓释期药物释放符合Higuchi模型,PLGA75/25、η=0.19和PLGA50/50、η=0.18的微球药物释放速度常数分别为2.40h-1/2和0.85h-1/2;体外14d累计释药分别达到71%和54%。结论相分离法制备卡铂-PLGA微球含药量高,但体外释药快,没有缓释作用;溶剂挥发法所得微球药物突释率较低,体外能控制药物缓慢释放。     

5-FU纳米微粒的制备及其释药特性研究

目的 制备一种新型的载氟尿嘧啶(5-FU)纳米微粒并对其体内释药特性进行研究.方法 运用聚合物交联法制备出壳聚糖载氟尿嘧啶纳米粒,通过扫描电镜、激光粒度分析仪对其表征进行检测,紫外分光光度法测定载药量,高效液相色谱法检测体内的释药特性.结果 壳聚糖载氟尿嘧啶纳米粒呈圆形或椭圆形,分散性良好,粒径在120～150nm;载药量为31.000%±0.001%;壳聚糖-5-FU纳米粒注射入兔体内后,初期突释相约在1.5h,峰浓度为5 069.6μg/L,随即进入缓释相,浓度维持在76μg/L,时间长达48h.结论 壳聚糖纳米药物载体可改变5-FU在体内的药代动力学行为,延长其循环时间,具有良好的缓释作用.     

依他硝唑纳米粒对乏氧肿瘤细胞辐射增敏作用的研究

目的 制备出具有生物活性并可控制释放的依他硝唑纳米粒,探讨其对乏氧人乳腺癌细胞(MCF-7)和人子宫颈癌细胞(HeLa)的辐射增敏作用。方法 采用复乳溶剂挥发法制备聚乳酸-聚羟基乙酸共聚物(PLGA)包裹的依他硝唑纳米粒,高效液相色谱分析纳米粒的载药率、包封率和模拟体外释药,透射电镜研究纳米粒的形态,激光衍射粒度分析仪检测纳米粒的粒径分布。经乏氧处理的MCF-7和HeLa细胞与依他硝唑纳米粒和药物单体共培养,采用平板克隆形成实验检验其辐射增敏作用。结果 成功制备依他硝唑纳米粒,呈光滑球形,粒径分布在90～190 nm之间,载药率为1.66％,包封率为18.02％,模拟体外释药曲线呈双相,即在爆发释放之后为缓慢释放。同依他硝唑纳米粒和药物单体共培养的乏氧MCF-7和HeLa细胞克隆形成能力照射后明显降低,依他硝唑纳米粒作用更为显著。结论 具有生物活性的依他硝唑从纳米粒中以可控的方式被释放,有效地增加了乏氧肿瘤细胞的辐射敏感性,为辐射增敏剂的临床应用提供了一种新的给药方式。     

载阿霉素-全氟溴辛烷纳米级聚乳酸超声造影剂体外显像和抗肿瘤效果实验研究

目的制备以聚乳酸羟基乙酸(PLGA)为成膜材料,内载阿霉素(DOX)-全氟溴辛烷(PFOB)的纳米级超声造影剂,并评价其体外超声显像效果及体外抗肿瘤疗效。方法应用改进的单乳化水包油(O/W)溶剂挥发法制备DOXPFOB@PLGA纳米粒子,检测其一般特性及DOX体外释放行为;应用超声成像仪观察其体外超声显像效果;用细胞计数试剂盒(CCK-8)法评估其体外癌细胞杀伤效果。结果成功制备DOX-PFOB@PLGA纳米粒子,平均粒径(236. 7±45. 9)nm,分散性好; DOX的包封率为(53. 52±1. 72)%,载药量为(4. 28±0. 61)%,DOX体外释放具有PH响应性(24h累计释放量(%):PH5. 7,40%; PH7. 4,15%);体外超声显像显示纳米粒子具有造影增强效果;体外细胞实验显示其具有良好抗肿瘤效果。结论成功制备集成像与化疗功能为一体的PFOB-DOX@PLGA超声造影剂,具有良好的体外超声成像效果和体外抗肿瘤疗效。     

重组人骨形态发生蛋白-2缓释凝胶微球的研制及其溶胀、降解、载药、释药特征

目的制备载人骨形态发生蛋白-2(rhBMP-2)的甲基丙烯酸缩水甘油酯右旋糖酐(dex-GMA)凝胶微球并初步考察其体外溶胀、降解、载药与释药特征。方法以液体石蜡为油相,Span-80为乳化剂,采用乳化化学交联技术制备载rhBMP-2的凝胶微球(BMP-HMs)并通过正交设计法优化其制备工艺;观察BMP-HMs形态和粒径,测定其包封率与载药量;用微球的吸水能力表示微球的溶胀率(Rs),扫描电镜观察微球的体外降解,动态观察体外释药特征及其与微球溶胀、降解的关系。结果所制备的BMP-HMs形态规整,粒径40～50μm,分布均匀;rhBMP-2载药量(10.6±4.8)%,包封率(88.9±1.0)%,BMP-HMs冻干剂4℃以下存放6个月性能稳定,但在磷酸盐缓冲液(PBS)中20～40d内可以完全降解。微球Rs随反应促进剂四甲基乙二胺(TEMED)用量的增大而减小,0.3mlTEMED制备的BMP-HMs体外释药实验表明80%的rhBMP-2在前20d左右释放。结论BMP-HMs对rhBMP-2具有确定的缓释作用,并可以通过制备工艺的改变控制其释药。     

基于普朗尼克双配体修饰的载药纳米靶向聚合物胶束制备工艺的筛选及靶向性评价

目的 优选载多柔比星(阿霉素,DOX)纳米靶向聚合物胶束的制备工艺,并对其体外释放行为和体外靶向性进行考察.方法 以琥珀酰亚胺法合成靶向聚合物材料,以包封率、载药量和总评归一化值为评价指标,利用星点设计-响应面法优化薄膜水化法设计考察投药量、有机溶剂体积、水化体积对纳米胶束制备的影响,并优选处方.以与羟基磷灰石(HA)和离体骨片共同孵育考察骨靶向性;以乳腺癌细胞(MDA-MB-231)为模型做体外细胞摄取考察肿瘤细胞靶向性.结果 成功合成靶向聚合物材料P123-ALN和P123-DP-8,优选纳米胶束最佳制备工艺为:DOX投药量5.48 mg,有机溶剂体积7.28 ml,水化体积8.58 ml.根据筛选出的最佳制备工艺,确定混合载体材料的比例为4∶1时,制备的双配体修饰的纳米靶向聚合物胶束P123-ALN/P123-DP-8@DOX符合纳米制剂的制备要求,包封率为76.97％,载药量3.70％,粒径122.97 nm,ζ电位-12.60 mV,缓释和体外靶向性良好.结论 用最优处方制备的纳米靶向聚合物胶束可为后续骨靶向给药奠定基础.     

氟尿嘧啶纳米乳剂的制备与性质

目的研究氟尿嘧啶大豆油纳米乳剂的相图、稳定性、载药量及药物的体外释放特点。方法在三元相图的基础上优选出制备纳米乳剂的最佳处方,用透射电子显微镜观测纳米乳剂粒径的大小,HPLC法测定纳米乳剂中氟尿嘧啶的含量及体外释放性能。结果纳米乳剂颗粒为圆形或椭圆形,粒径范围20±10nm,药物包裹率85.06%,体外11h药物释放50%,50h缓释95%。结论本实验制备的纳米乳剂性质稳定,与游离的药物相比有明显的缓释性能。     

双氯芬酸钠壳聚糖-海藻酸钠微球的制备和性质简

目的制备双氯芬酸钠微球,获得理想的释药行为。方法以微球的载药量、包封率及体外释药行为评价指标,采用单因素考察确立了最佳处方;结果最佳处方为：壳聚糖分子量为150kD,海藻酸钠：壳聚糖=3：1,药物：空白微球=1：4,吸附时间为12h,吸附温度为37℃,得到药物浓度为5．0mg·ml-1结论以该最佳处方制备的微球,具有均匀的粒径和理想的释药行为。     

聚乳酸羟基乙酸CXCR4-miRNA纳米微粒抑制人肾癌细胞生长的研究

目的探讨聚乳酸羟基乙酸CXCR4-miRNA纳米复合微粒在体外对人肾癌细胞增殖的抑制作用。方法运用二次超声乳化和溶剂挥发法制备聚乳酸羟基乙酸CXCR4-miRNA纳米粒;通过MTT法观察纳米微粒对肾癌细胞A498增殖的抑制作用;并运用流式细胞术检测纳米微粒作用后A498细胞的凋亡情况。结果制备的聚乳酸羟基乙酸CXCR4-miRNA纳米粒外观呈圆型,平均粒径为280 nm,平均载药量为(0.515±0.023)%,平均包封率为50.2%。通过MTT实验证明纳米微粒可以较好的抑制人肾癌细胞(A498)的增殖,随着聚乳酸羟基乙酸CXCR4-miRNA纳米微球浓度的增加,药物作用时间越长,细胞增殖受到抑制的效果越明显。流式细胞术检测可见凋亡峰出现,细胞周期阻滞在S+G2/M期。结论聚乳酸羟基乙酸CXCR4-miRNA纳米粒具有抑制肾癌细胞A498增殖的作用,其效果与药物浓度及作用时间长短有关。     

克拉霉素胃漂浮小丸的制备及其体外释药研究

目的 制备克拉霉素胃漂浮小丸，考察其漂浮性，包封率和体外释药行为。方法以海藻酸钠为材料，液体石蜡为起漂剂，两者乳化后经钙离子交联制备可漂浮小丸，考察不同药物含量、不同比例起漂剂和包衣对小丸形态及释药行为的影响。结果液体石蜡-2％海藻酸钠水溶液=2：10（v／v）的载药海藻酸钙小丸可在pH=1的HCl溶液中漂浮超过12h，包封率在90％左右，乙基纤维亲包衣增重10％的小丸（克拉霉素：海藻酸钠=2：1）可持续释放药物达5h。结论含液体石蜡的海藻酸钙小丸经包衣处理可以达到胃内漂浮和局部缓释药物的目的。     

Knee injury and Osteoarthritis Outcome Score (KOOS) - validation of a Swedish version

The Knee injury and Osteoarthritis Outcome Score (KOOS) is a self-administered instrument measuring outcome after knee injury at impairment, disability, and handicap level in five subscales. Reliability, validity, and responsiveness of a Swedish version was assessed in 142 patients who underwent arthroscopy because of injury to the menisci, anterior cruciate ligament, or cartilage of the knee. The clinimetric properties were found to be good and comparable to the American version of the KOOS. Comparison to the Short Form-36 and the Lysholm knee scoring scale revealed expected correlations and construct validity. Item by item, symptoms and functional limitations were compared between diagnostic groups. High responsiveness was found three months after arthroscopic partial meniscectomy for all subscales but Activities of Daily Living.     

The acutely limping child

Acute limping may be the result of multiple pathologies in children. The differential diagnosis varies based on the age of the child. Irrespective of age, the initial imaging work-up includes AP and frog leg radiographs of the pelvis and ultrasound; MRI may sometimes be helpful. In children less than 3 years, infections and trauma are most frequent. MRI is the imaging modality of choice when osteomyelitis is clinically suspected. Between the ages of 3 and 10 years, transient synovitis of the hip and Legg-Calvé-Perthes disease are main considerations but infection, inflammation and focal bony lesions are also considered. In children over 10 years, slipped capital femoral epiphysis also is considered.     

Do Balance Board Training Programs Reduce the Risk of Ankle Sprains in Athletes?

Introduction Ankle sprains are the most common musculo-skeletal injury that occurs in athletes,particularly in sports that require jumping and landing on one foot such as soccer,and basketball(1-4).These injuries often result in significant time loss from participation,long-term disability,and have a major impact on health care costs and resources(5-8).     

High Intensity Interval Training:New Insights

KEY POINTS ·High-intensity interval training(HIT)is characterized by repeated sessions of relatively brief，intermittent exercise.often performed with an“a11 out”effort or at an intensity close to that which elicits peak oxygen uptake(i.e.，≥90%of VO2 peak).     

Endovascular management of carotid-cavernous fistulas

Objective To investigate endovascular treatment of traumatic direct carotid-cavernous fistulas （CCF） and their complications such as pseudoaneurysms. Methods： Over a five-year period, 22 patients with traumatic direct CCFs were treated endovascularly in our institution. Thirteen patients were treated once with the result of CCF occluded, 8 twice and 1 three times. Treatment modalities included balloon occlusion of the CCF, sacrifice of the ipsilateral internal carotid artery with detachable balloon, coll embolization of the cavernous sinus and secondary pseudoaneurysms, and covered-stem management of the pseudoaneurysms. Results All the direct CCFs were successfully managed endovascularly. Four patients developed a pseudoaneurysm after the occlusion of the CCF with an incidence of pseudoaneurysm formation of 18.2% （4/22）. A total number of 8 patients experienced permanent occlusion of the ICA with a rate of ICA occlusion reaching 36.4% （8/22）. Followed up through telephone consultation from 6 months to 5 years, all did well with no recurrence of CCF symptoms and signs. Conclusion Traumatic direct CCFs can be successfully managed with endovascular means. The pseudoaneurysms secondary to the occlusion of the CCFs can be occluded with stent-assisted coiling and implantation of covered stents.     

Developmental validation of the PowerPlex(®) ESI 16 and PowerPlex(®) ESI 17 Systems: STR multiplexes for the new European standard

In response to the ENFSI and EDNAP groups’ call for new STR multiplexes for Europe, Promega^® developed a suite of four new DNA profiling kits. This paper describes the developmental validation study performed on the PowerPlex^® ESI 16 (European Standard Investigator 16) and the PowerPlex^® ESI 17 Systems. The PowerPlex^® ESI 16 System combines the 11 loci compatible with the UK National DNA Database^®, contained within the AmpFlSTR^® SGM Plus^® PCR Amplification Kit, with five additional loci: D2S441, D10S1248, D22S1045, D1S1656 and D12S391. The multiplex was designed to reduce the amplicon size of the loci found in the AmpFlSTR^® SGM Plus^® kit. This design facilitates increased robustness and amplification success for the loci used in the national DNA databases created in many countries, when analyzing degraded DNA samples. The PowerPlex^® ESI 17 System amplifies the same loci as the PowerPlex^® ESI 16 System, but with the addition of a primer pair for the SE33 locus. Tests were designed to address the developmental validation guidelines issued by the Scientific Working Group on DNA Analysis Methods (SWGDAM), and those of the DNA Advisory Board (DAB). Samples processed include DNA mixtures, PCR reactions spiked with inhibitors, a sensitivity series, and 306 United Kingdom donor samples to determine concordance with data generated with the AmpFlSTR^® SGM Plus^® kit. Allele frequencies from 242 white Caucasian samples collected in the United Kingdom are also presented. The PowerPlex^® ESI 16 and ESI 17 Systems are robust and sensitive tools, suitable for the analysis of forensic DNA samples. Full profiles were routinely observed with 62.5 pg of a fully heterozygous single source DNA template. This high level of sensitivity was found to impact on mixture analyses, where 54–86% of unique minor contributor alleles were routinely observed in a 1:19 mixture ratio. Improved sensitivity combined with the robustness afforded by smaller amplicons has substantially improved the quantity of data obtained from degraded samples, and the improved chemistry confers exceptional tolerance to high levels of laboratory prepared inhibitors.     

Bronchial stump fistula :treatment with covered retrievable hinged metallic stents-preliminary clinical experience

Objective To evaluate the preliminaily clinical efficacy and retrievability of a retrievable hinged covered metallic stent in the treatment of the bronchial stump fistula （BSF）. Methods Between April 2003 and March 2005, 8 patients with bronchial stump fistula after pneumonectomy or lobectomy were treated with two types （A and B） of retrievable hinged covered metallic stents. Type A stent was placed in 6 patients and type B in 2 under fluoroscopic guidance. The stent was removed with a retrieval set when BSF was healed or complications occurred. Results Stent placement in the bronchial tree was technically successful in all patients, without procedure-related complications. Immediate closure of the BSF was achieved in all patients after the procedure. Stents were removed from all patients but one. Removal of the stents was difficult in two patients due to tissue hyperplasia. Patients were followed up for 6 - 21 months. Placement of the stents remained stable in all patients except one due to severe cough. Permanent closure of BSF was achieved in 7 （87.5%） of 8 patients. Conclusion Use of a retrievable hinged covered expandable metallic stent is a simple, safe, and effective procedure for closure of the BSF. Retrieval of the stent seems to be feasible. （J Intervent Radiol, 2007, 16： 253-257）     

Prevalence and severity of hip and groin pain in sub‐elite male football: a cross‐sectional cohort study of 695 players

The purpose of this study was twofold: (a) to investigate the prevalence of hip and groin pain in sub‐elite male adult football in Denmark and (b) to explore the association between prevalence and duration of hip and groin pain in the previous season with the Copenhagen Hip and Groin Outcome Score (HAGOS) in the beginning of the new season. In total 695 respondents from 40 teams (Division 1–4) were included. Players completed in the beginning of the new season (July–Sept 2011) a self‐reported paper questionnaire on hip and/or groin pain during the previous season and HAGOS. In total 49% (95% CI: 45–52%) reported hip and/or groin pain during the previous season. Of these, 31% (95% CI: 26–36%) reported pain for >6 weeks. Players with the longest duration of pain during the previous season had the lowest HAGOS scores, when assessed at the beginning of the new season, P < 0.001. This study documents that half of sub‐elite male adult football players report pain in the hip and/or groin during a football season. The football players with the longest duration of pain in previous season displayed the lowest HAGOS scores in the beginning of the new season.