骨水泥中抗癌药的释放、活性及抗肿瘤效应的实验研究

目的:确定化疗药丝裂霉素、长春新碱和5F-尿嘧啶掺入骨水泥后的释放及活性,评价其掺入骨水泥后经皮介入治疗小鼠移植瘤模型的抗肿瘤效应。材料和方法:采用洗提法和MTT法测量药物的释放及活性。60只昆明种小鼠,每只小鼠皮下注射,S180肉瘤细胞1×106,7天后随机分为4组,每组15只。3组为治疗组,每一组各以上述一种抗癌药骨水泥0.5ml瘤块内注入;另1组为对照组,仅注入单纯骨水泥0.5ml。记录每组10只荷瘤小鼠肿瘤大小变化,余5只作病理检查。结果:三种药物均可从骨水泥中释放并具有杀伤肿瘤细胞效应;3组治疗组中,肿瘤体积在1～10天内逐日缩小或不增大;而对照组中肿瘤体积持续增大。病理检查见治疗组水泥块周边肿瘤组织片状坏死。结论:骨水泥携带常用抗癌药具有抗肿瘤效应。     

骨水泥中表阿霉素的释放及活性研究

目的：为了确定表阿霉素从骨水泥中释放及活性情况。方法：用洗提方法研究药物的释放；用ＭＴＴ方法和活体实验研究释放药物的抗癌活性及作病理学检查。结果：表阿霉素可自骨水泥释放，周期约９～１５ｄ。ＭＴＴ方法发现洗提液中抗癌药的活性见于１２ｈ和２４ｈ两个时间点；活体实验则显示肿瘤内注射表阿霉素骨水泥后瘤块在２～１０ｄ各时间点逐渐缩小。病理检查证实在表阿霉素水泥块周围肿瘤组织有大片坏死。结论：本实验结果提示表阿霉素骨水泥可用于介入治疗椎体转移瘤。     

聚甲基丙烯酸甲酯骨水泥作为抗肿瘤药物缓释载体的实验研究

骨水泥作为抗生素类的缓释载体用于人工全髋关节置换及骨髓炎的治疗早已应用于临床,对于骨水泥是否可以作为抗肿瘤药物的缓释载体,文献报道较少.笔者将抗肿瘤药物与聚甲基丙烯酸甲酯(PMMA)骨水泥混合,与抗生素骨水泥做阳性对照,检测其骨水泥的物理和力学性能以及药物的释放情况.     

兔Vx2肿瘤对表阿霉素骨水泥介入治疗反应的^31P磁共振频谱监测

目的：用３１Ｐ ＭＲＳ监测表阿霉素骨水泥介入兔Ｖｘ２ 肿瘤的治疗反应。　方法：对５ 个皮下Ｖｘ２ 实体瘤作表阿霉素骨水泥经皮介入治疗;对另５ 个肿瘤仅作单纯骨水泥注入以作对照。对二组肿瘤均作治疗前后３１Ｐ ＭＲＳ检查。　结果：表阿霉素骨水泥治疗早期出现ＰＯＥ和Ｐｉ峰值升高,ＰＭＥ和ＡＴＰ信号峰减低的改变,提示良好的治疗反应。　结论：表阿霉素骨水泥可从骨水泥中释放并具有抗肿瘤效应;３１ＰＭＲＳ具有早期监测肿瘤化疗反应的作用。     

阿霉素异体脱钙骨基质骨粒骨水泥缓释体的制备及体内释药实验

为研究阿霉素异体脱钙骨基质骨粒骨水泥缓释体，并研究分析其体内药物释放特性，按Urist等的方法制备异体脱钙骨基质骨粒，通过冻干、真空吸附等处理，将阿霉素载入其中并与骨水泥按1：1比例复合，制得阿霉素异体脱钙骨基质骨粒骨水泥缓释体，植入家兔股骨粗隆部进行体内药物释放实验。该缓释体可使阿霉素在局部骨组织中缓慢释放达12周以上，4周内维持相对稳定的水平。骨组织中最高浓度是静注相同剂量阿霉素时的29倍，但血浆峰值浓度仅为静注组的1／10；局部骨组织早期浓度高，以后为稳定的低浓度释放。提示该缓释体具有良好的缓释功能，能较好地满足骨肿瘤保肢术后局部化疗的要求。     

跟骨创伤性骨髓炎的手术及非手术治疗进展

高能量跟骨损伤带来的后续创伤感染发生率逐年升高,原因在于跟骨大部分为松质骨,受伤后血液在松质骨内部淤积,导致细菌滋生,而跟骨皮肤软组织较薄,受创后易出现软组织损伤现象.跟骨创伤性骨髓炎非手术治疗主要根据药敏长疗程抗感染治疗.手术治疗原则为清除病灶、空腔内填充局部药物释放系统、软组织重建以及骨缺损修复;局部药物(抗生素)释放载体包括骨水泥、硫酸钙等,骨缺损可采用膜诱导成骨、植入带抗生素人工骨、开放植骨等.本文就跟骨创伤性骨髓炎的手术及非手术治疗方式进行阐述,为临床治疗提供参考.     

多孔聚乳酸-聚乙醇酸共聚物作为缓释重组人骨形态发生蛋白-2载体的实验研究

目的 探讨多孔聚乳酸-聚乙醇酸共聚物(PLGA)作为重组人骨形态发生蛋白-2(rhBMP-2)的载体，通过体外释放试验和体内活性试验来评价rhBMP-2释放的动力学过程及活性。方法 采用乳液冷冻干燥法制作含rhBMP-2缓释系统的PLGA支架，支架进行扫描电镜观察；采用高效液相色谱分析仪检测不同时间点释放液中rhBMP-2的含量，进行累积释放量的动态观察；将缓释rhBMP-2支架植入SD大鼠大腿股部肌袋内，分别在不同时间点进行组织学观察。结果 支架材料的形态学观察显示，材料表面呈多孔状；rhBMP-2从支架中释放的动力学过程为第1天表现为爆发性释放(30.0％)，以后缓慢持续释放，至1个月左右释放量达80.6％；活性评价结果显示，rhBMP-2缓释支架组可见新生骨组织形成伴较多的骨母细胞排列，无rhBMP-2支架组则无成骨现象。结论 多孔PLGA可作为rhBMP-2的缓释载体，并具有良好的生物活性，可作为骨组织工程研究中的新型支架，同时具有临床应用的可行性。     

钛表面TiO2纳米管抗菌覆膜药物释放动力学表征及其抗菌活性体外研究

 目的 明确钛表面TiO₂纳米管抗菌覆膜药物释放动力学特征,并通过体外试验测试其抗菌活性。方法 电化学氧化法在钛金属表面构建TiO₂纳米管表层,利用冻干法加载庆大霉素,在磷酸盐缓冲液中进行药物释放动力学研究。选择标准表皮葡萄球菌菌株,分别在负载和未负载药物纳米管及纯钛3种钛表面进行培养,通过观察细菌粘附和活性菌落存活情况进行表面抗菌活性对比研究。结果 NTS-G庆大霉素药物释放可分为两部分:初始突发释放和后期缓慢释放,初始释放浓度为51.50 μg/mL,第6 h为73.13 μg/ml,大多数负载的庆大霉素大约在9 h内释放。经过一个爆发性初始释放后,庆大霉素从纳米管释放呈现一个平台期,释放量几乎保持不变,维持在89.10 μg/ml水平。3种钛表面体外抗菌活性检测发现,TiO₂纳米管抗菌覆膜假体表面死亡细菌菌落显著增加(P<0.05)。结论 钛表面TiO₂纳米管抗菌覆膜为人工关节相关感染预防提供了新途径,骨科植入材料表面纳米管抗生素覆膜具有广泛的应用潜力。     

RBX-庆大霉素药物释放系统的研制及体内释放效应

研制复合bBMP的异种骨庆大霉素局部药物释放系统 ,为治疗开放性骨折提供简便有效的方法。复合bBMP的异种骨为核心载体 ,采用明胶包裹法和聚己内酯 (Poly ε caprolacton ,PCL)多重包裹法分别制成庆大霉素复合体与RBX 庆大霉素药物释放系统 ,对其进行体内释放实验研究。两种方法制成的植骨材料均在 2 4h内有一暴发释放 ,并能维持一定时间的缓慢释放。其中RBX 庆大霉素药物释放系统在 30天时仍能达到 2 84mg/L的释放浓度 ,高于庆大霉素对金黄色葡萄球菌的MIC(2mg/L)。提示RBX 庆大霉素药物释放系统具有良好的体内缓释特性 ,结合RBX的诱导成骨作用 ,能成为一种理想的开放性骨缺损修复材料。     

α粒子放射性药物在骨转移瘤治疗中的应用进展

骨骼是晚期恶性肿瘤的常见转移部位之一,骨转移瘤不仅会导致顽固性骨痛、病理性骨折等骨相关事件（SRE）的发生,还会导致医疗费用的增加和死亡风险的上升。放射性药物内放射治疗具有疗效好、靶向性好和毒性低等优点。常用于治疗骨转移瘤的放射性药物主要是释放β粒子和α粒子的药物,其中释放β粒子的放射性药物的临床应用较成熟,但也具有一定的局限性。近年来,释放α粒子的放射性药物越来越多地用于骨转移瘤的治疗,其在缓解骨痛、降低SRE发生率、延长总生存期等方面具有更大的优势。笔者仅就α粒子放射性药物在骨转移瘤治疗中的应用进展进行综述。     

诺福素对MCF-7人乳腺癌细胞的体内外抗癌药效学研究

目的 研究评价诺福素在体内体外对MCF-7人乳腺癌细胞的生长抑制作用.方法 按照抗癌药物临床前药效学评价原则,体外评价试验用MTT法,体内评价通过观察受试药物对MCF-7裸鼠移植瘤生长的影响,并与阳性药紫杉醇进行比较.结果 两批体外MTT法显示,诺福素抑制MCF-7细胞生长的半效抑制浓度分别为1.7762 nmol/L...     

Diffusion of radon through varying depths of cement.

Portland cement was mixed with different concentrations of radium chloride (1200, 2400 and 3600 Bq) to produce radioactive sources. These sources were surrounded with cement of different thickness (1, 2 and 4cm). The release of radon from these sources (before and after being surrounded) was studied. The results showed that radon release from the sources itself was less then its release from the same source after being surrounded by cement, and the release did not change with the thickness of cement. Samples were covered with a thin layer of polyethylene before being surrounded with cement. It was found that this additional layer reduced the radon exhalation. This thin layer stopped any reaction between the source and the surrounding cement during solidification of the cement layers. These reactions are thought to be the reason for the increase of radon exhalation from the sources surrounded by cement.     

Development of a signal‐inducing bone cement for magnetic resonance imaging

Purpose:

To develop a signal‐inducing bone cement for musculoskeletal procedures in magnetic resonance imaging (MRI).

Materials and Methods:

Acrylic resins were mixed with contrast agents (CAs) and water. We determined the ideal concentration of the components and assessed feasibility in cadaveric bones in an open high‐field MR scanner. The contrast‐to‐noise ratio (CNR) in air and bone was evaluated and mechanical tests were achieved. We determined the amount of water that was not incorporated and measured the amount of CA released with photometric analysis. The cement was analyzed microscopically.

Results:

Preparation and application of the CA‐water‐cement compound was feasible and its differentiation in MRI was clear. The maximal CNR^air had a value of 157.5 (SD 18.3) in an interventional fast T1W turbo‐spin echo (TSE) sequence. The compressive strength decreased with the amount of water added. Although nearly 50% of the water added was not incorporated in the cement, the CNR was sufficient for cement detection. The threshold for systemic toxicity of delivered CA was not reached and the microscopic analysis showed water bubbles in the cement.

Conclusion:

A signal‐inducing bone cement is feasible for the use in MRI. J. Magn. Reson. Imaging 2010;31:636–644. © 2010 Wiley‐Liss, Inc.     

用国产骨水泥行经皮椎体成形术的临床应用

目的　探讨用国产骨水泥行经皮椎体成形术 (PVP)的临床疗效和应用价值。方法　在C臂X线机或CT机引导下 ,采用经皮穿刺向患椎注射国产骨水泥 (PMMA)治疗椎体的骨质疏松性压缩骨折、血管瘤和溶骨性转移瘤患者 2 2例 ,观察其临床疗效及并发症。结果　 2 2例共行PVP治疗 3 0个椎体 ,技术操作成功率为 10 0 % ,其中 2 1例疼痛症状明显缓解 ,临床有效率达到 95 .5 % ;术中有 2 3 .3 %的治疗椎体有骨水泥外溢 ,但均未出现严重不良反应。结论　用国产骨水泥行PVP同样具有微创、安全和疗效显著等特点 ,能有效缓解疼痛和加固椎体 ,且易推广 ,临床应用前景广阔     

Effects of barium concentration on the radiopacity and biomechanics of bone cement: experimental study

Purpose  This study was undertaken to evaluate the changes in the radiopacity and mechanics of polymethylmethacrylate (PMMA) bone cement with the addition of barium. Materials and methods  Barium sulfate powder was added to a PMMA bone cement with an initial 10% barium concentration. The changes in radiopacity and strength were evaluated by testing cement blocks containing four barium concentrations (10%, 20%, 30%, 40%). Radiopacity was evaluated by measuring the computed tomography (CT) values of the bone cement, and strength was evaluated by compressive, three-point bending, and impact load tests. Results  CT values increased in proportion to the barium concentration. The compressive load test showed that cement with a 40% barium concentration was significantly more fragile than cement with lower barium concentrations. The three-point bending load test showed that the cement became more fragile in proportion to the barium concentration. The impact load test showed that cement with 30% and 40% barium concentrations was significantly more fragile than cement with 10% and 20% barium concentrations. Conclusion  Radiopacity is increased and strength is reduced by adding increasing concentrations of barium powder to bone cement. The results of the present study suggest that adding barium permits the radiopacity and strength of bone cement to be adjusted in clinical practice.     

碱性成纤维细胞生长因子缓释微球对成骨细胞作用的实验研究

目的 旨在探讨碱性成纤维细胞生长因了(bFGF)缓释做球生物活性保存情况及其对于成骨细胞的作用。方法 将bFGF、bFGF-聚乳酸-聚乙二醇共聚物(PELA)做球和bFGF-聚乳酸-羟基乙酸共聚物(PLGA)微球加入成骨细胞培养液中．用细胞计数法、四甲基偶氮唑盐微量反应比色法(MTT法)、流式细胞仪观察细胞增殖情况，并检测成骨细胞上清液中骨钙素(BGP)含量。结果 培养1d后．四组细胞计数、吸光度(A)值差异均无显著性意义；4，6d时PLGA做球组细胞计数和A值明显优于其余三组；培养6．8d后．bFGF组值仍然高丁PELA做球组，但差异无显著性意义。流式细胞仪检测显示，培养2b后，bFGF组的G2／M s期百分数最高，4，8d后PLGA微球组G2／M S期百分数最高。成骨细胞上清液中BGP含量．PLGA做球组最高，其次为PELA做球组。结论 bFGF—PELA微球效果不佳．制备工艺需要改进；bFGF-PLGA微球通过较长时间持续释放活性bFGF，明显促进成骨细胞增殖和分化     

Selective intra-arterial chemoembolization of pelvic and spine bone metastases

The purpose of this study was to determine the effect of interventional palliative therapy by using chemoembolization on metastatic bone pain and tumor bulk in inoperable metastases where chemotherapy and radiotherapy had failed. Twenty-five patients (mean age: 59 years) underwent chemoembolization of symptomatic lytic lesions involving the spinal column (n=10), iliac bone and sacrum (n=15). The study design consisted of at least three procedures based on combined chemoembolization performed under analog-sedation. Therapeutic agents were carboplatin for selective chemotherapy and pirarubicin mixed with polyvinyl alcohol foam for chemoembolization. Fifteen of 18 (83%) patients had significant pain relief, as shown by the decrease of analgesic drug use. Mean clinical response duration was 12 months. Radiologically, ten patients were stable. A partial response was observed in four patients, while a complete response was seen in two others. Selective intra-arterial chemoembolization gives longer pain relief than embolization, compared to the literature data, probably because of partial response with local anti-cancer drugs.