白蛋白毫微囊的化学表面修饰

本文以靶向制剂白蛋白毫微囊为研究对象,选择人体内的正常血浆糖蛋白转铁蛋白为蛋白毫微囊的表面修饰剂,双功能偶联剂戊二醛为偶联剂,通过对白蛋白微囊表面进行修饰,改变毫微囊的靶向特性,提高毫微囊制剂在体内的靶向效果。研究结果表明:采用中文方法对白蛋白毫微囊表面进行修饰,所修饰的转铁蛋白保持了其免疫原性(反应原性),形成的免疫毫微囊具有主动靶向的特性,同时本文还对修饰后的毫微囊的孔径分布要求、靶向特性、载药量等进行了理论上的探讨。     

表面修饰人工晶状体的表面特性研究

目的采用低温等离子体联合离子束技术对硅凝胶人工晶状体进行钛及钛基复合材料表面修饰，以提高人工晶状体的生物相容性。方法通过紫外光谱、接触角、化学分析用电子能谱（ESCA）对人工晶状体进行表面特性检测。结果修饰后人工晶状体对紫外光的吸收有所增加，其表面亲水性有所提高，人工晶状体表面获得适宜的化学组成。结论修饰后人工晶状体的表面特性得到改善。     

金纳米棒制备、修饰及与寡核苷酸适配子的耦联

目的金纳米棒的制备、修饰及与寡核苷酸适配子的耦联。方法利用种子调制生长法制备了金纳米棒,采用化学桥联方法对金纳米棒进行m-SH-PEG修饰及与靶向定位乳腺癌细胞的寡核苷酸适配子的耦联。结果成功制备了金纳米棒,以CTAB包裹的金纳米棒表面光滑、尺寸均一、分散性和稳定性良好;Zeta电位检测表明m-SH-PEG已成功修饰金纳米棒,琼脂糖电泳证实寡核苷酸适配子与金纳米棒成功耦联。结论成功地进行了金纳米棒的制备、修饰及与寡核苷酸适配子的耦联。     

内生型转铁蛋白-金纳米簇探针的合成及其对前列腺癌的靶向成像研究

目的 以转铁蛋白(transferrin,Tf)为模板,氯金酸为原料,原位合成靶向荧光探针-内生型转铁蛋白-金纳米簇(gold nanoclusters,AuNCs),并以前列腺癌(prostate cancer,PCa)为模型,探讨该荧光探针的靶向成像效果.方法 利用场发射透射电子显微镜及粒度分析仪分析所合成的荧光探针的形貌、水合粒径及分布;利用紫外-可见分光光度计及荧光分光光度计对其光学性能进行表征;MTT法检测细胞毒性;并通过细胞荧光成像及竞争抑制实验表征其肿瘤的特异性靶向效果;静脉注射Tf-AuNCs至PC-3种植瘤鼠体内,进行连续荧光成像,评价其肿瘤靶向成像效果;通过组织病理学明确其活体毒性.结果 本研究制备的Tf-AuNCs粒径约为3 nm,荧光发射峰为700 nm,保留了Tf及金纳米簇的性能;细胞成像结果显示Tf-AuNCs对前列腺肿瘤细胞(PC-3)特异性靶向效果好;小动物活体成像结果显示Tf-AuNCs探针仅需15 min即可准确显示肿瘤部位,至2h时肿瘤区荧光强度达峰值,表明其具有良好的活体肿瘤成像能力;病理学结果表明Tf-AuNCs具有良好的生物相容性.结论 Tf-AuNCs荧光探针具有良好的光学性能、特异靶向能力,并具有优异的荧光成像能力及良好的生物相容性,将有望应用于PCa的早期影像学分析.     

活性炭纳米粒子对5-Fu抗肿瘤作用的影响

目的：观察活性炭纳米粒子（activated carbonna noparticles,ACNP）吸附5-Fu在体内外对5-Fu肿瘤作用的影响,探讨ACNP的作用机制。方法：用紫外分光光度法检测ACNP对5-Fu的吸附性能;分别采用MTT实验和S180小鼠、H22小鼠动物肿瘤模型观察了ACNP在体外和体内对5-Fu抗肿瘤作用的影响;采用流式细胞术测定ACNP对细胞周期的影响;采用甲基绿-派洛宁染色法观察ACNP对细胞凋亡的影响。结果：ACNP在常温下对5-Fu有良好的吸附性能,符合经验公式M=0.295C1.919;ACNP吸附5-Fu后对BGC-823的抑制生长作用显著高于相等浓度的5-Fu组,有良好的量效及时效关系;ACNP吸附5-Fu后对S180小鼠的抑瘤率及对H22小鼠的生命延长率均显著高于含药量相等的5-Fu组;ACNP可以将BGC-823细胞阻滞在S期、与5-Fu合用可以诱导BGC-823的早期凋亡。结论：ACNP吸附5-Fu具有显著的体内外抗肿瘤活性,与5-Fu合用诱导细胞早期凋亡,将细胞周期阻滞在S期,ACNP的载体效应可能是增强5-Fu药理学作用的机制之一。     

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。     

表面修饰在神经介入治疗材料中应用和进展

【摘要】 随着神经介入治疗技术和新材料不断发展,其在脑血管疾病诊疗中的地位显著提高。与外科手术治疗相比,这些新型金属材料植入后仍会出现一些并发症,如内皮化延迟、血栓事件和再狭窄等,亟待解决。目前,通过表面修饰改善这些金属材料的生物学行为和功能,是提高临床安全性和疗效的可靠途径。该文主要就表面修饰在神经介入治疗材料,如弹簧圈和支架（药物洗脱支架、覆膜支架和血流导向装置）中的应用,以及各种靶向治疗药物、中药等研究进展作一综述。     

缺血修饰白蛋白对心肌缺血早期诊断的意义

血清白蛋白（HSA）氨基末端序列为人类所特有,易受烃自由基损害,使N-末端序列的2~3个氨基酸发生改变,从而形成缺血修饰白蛋白（IMA）。目前,IMA测定方法是采用白蛋白结合钴试验（ACB试验）。第一代ACB试验为手工操作的分光光度法,方便简易,适合基层单位使用;第二代ACB试验为全自动分光光度法。IMA的临川意义不仅可作为急性心肌缺血的早期诊断指标,同时可用于ACS早期诊断及危险程度分级,而且更可用于AMI早期诊断及危险程度分级。总之IMA作为一种新的心肌缺血标志物。     

5例颅底囊性脑膜瘤的MRI表现

囊性脑膜瘤多见于儿童,约占儿童颅内肿瘤的10%～19%,而成人发病率为2%～4%[1].肿瘤多发生于大脑半球凸面、镰旁或矢状窦旁,而位于颅底部较为少见[2～7].本研究搜集1996-02～2004-05手术病理及免疫组化检查证实颅底囊性脑膜瘤5例,分析其MRI表现,并结合文献探讨其MRI特点和鉴别点,以期提高其MRI诊断水平.     

表面麻醉与表面麻醉联合结膜下浸润麻醉在小切口白内障囊外摘除手术中的效果比较

目的观察表面麻醉与表面麻醉联合结膜下浸润麻醉在小切口白内障囊外摘除手术中的效果。方法A组361例(361只眼)采用表面麻醉的方法;B组298例(298只眼)采用表面麻醉联合结膜下浸润麻醉的方法对白内障进行小切口白内障囊外摘除及人工晶体植入术。结果A组在表面麻醉下325例顺利完成手术,36例术中追加表面麻醉或加用结膜下浸润麻醉后完成手术。B组表面麻醉联合结膜下浸润麻醉的298例全部顺利完成手术。结论表面麻醉在小切口白内障囊外摘除及人工晶体植入术中是一种简便、安全、有效的麻醉方法。     

Classification of transferrin (Tf) subtypes by isoelectric focusing

Summary A sample of 450 sera from unrelated individuals from Southern Germany was examined by isoelectric focusing on polyacrylamide gels. Three common subtypes, TfC1, C2-1, and C2, were differentiated. In addition, the rare variants TfB1, B1-2, B2, D1, D1-2, D2, and D3 were observed. The frequencies of the Tf alleles in our sample were found to be: Tf^C1=0.8544, Tf^C2=0.1367, Tf^B1=0.0011, Tf^B1-2=0.0022, Tf^B2=0.0045, and Tf^D1=0.0011. Analysis of 73 parents with 73 children did not show deviations from the expected mode of inheritance. Modification of the method by addition of 0.01 M FeCl₃ to the sera prior to examination did, however, reveal further variation and permitted the distinction of six subtypes, C1, C2-1, C2, C3, C3-1, and C3-2.This paper is dedicated to Fritz Hartmann, MD, Professor of Medicine, Hannover Medical School, FRG, on the occasion of his 60th birthday     

Differentiation between human and chimpanzee in bloodstains by enzyme-linked immunosorbent assay (ELISA) using antihuman serum

Summary An enzyme-linked immunosorbent assay (ELISA) for species identification of human bloodstains using two commercially available antisera against human serum is described. Human bloodstains were to be distinguished from those of chimpanzees and other animals using raw antisera, and the differentiation between human and chimpanzee became more evident when those antisera were absorbed with a small amount of chimpanzee plasma. Human bloodstains could clearly be identified by the present method even after 4 weeks of aging at room temperature.Supported in part by the Cooperation Research Program of the Primate Research Institute     

Radiation response of plasma protein and albumin of peripheral blood and its modification by MPG (2-Mercaptopropionylglycine) in mice

Changes in the total protein and albumin level in the blood of six week and three week old Swiss albino mice exposed to a sublethal dose of 2.2 Gy of gamma rays after an intraperitoneal injection of 20 mg/kg body weight of the radioprotector drug MPG (2-Mercaptopropionylglycine) were studied. The results were compared with those obtained from animals irradiated with the same dose of gamma rays in the absence of the drug. Animals were sacrificed at one, three, five, seven and 14 days after irradiation. The drug has been found to modify the levels of plasma protein and albumin in the blood of the irradiated animals. The depletion observed was less marked in the drug treated animals than their respective controls. The observations have been discussed in light of relevant literature.     

Preparation and radiolabeling of human serum albumin (HSA)-coated magnetite nanoparticles for magnetically targeted therapy

In this paper, we describe the preparation of human serum albumin-coated magnetic particles of about 200 nm in diameter with narrow size distribution radiolabeled with ¹⁸⁸Re for the purpose of magnetically targeted therapy. The optimum radiolabeling conditions are: SnCl₂·2H₂O 8 mg/ml, citric acid 20 mg/ml, vitamin C 8 mg/ml, labeling volume 500 μl and a reaction time of 3 h. The stability of the radiolabeled particles is suitable for in vivo study.     

Experimental biodistribution studies of 99mTc-recombinant human serum albumin (rHSA): a new generation of radiopharmaceutical

Recombinant human serum albumin (rHSA) produced by cultured fermentation has been prepared in the form of microcapsules nominally 3–5 m in diameter and radiolabelled with technetium-99m following reduction with stannous chloride. Radiochemical purity was assessed by chromatography on instant thin-layer chromatography and found to be greater than 90%. No evidence of aggregation was seen by microscopic examination. Imaging biodistribution studies in New Zealand white rabbits demonstrated targeting to the liver or lung, respectively, depending upon the size and surfactant properties of the microcapsules. This communication is the first to show scintigraphic studies using ^99m-Tc-labelled rHSA with the potential for lung, liver and cardiovascular imaging and demonstrates that recombinant DNA technology offers an important new source of materials suitable for use as radiopharmaceuticals without the need for pooled human blood products.     

静态负荷诱发肌肉疲劳时表面肌电信号(sEMG)变化与主观疲劳感之间的关系

目的 探讨静态负荷诱发肌肉疲劳时肌电信号指标与主观疲劳感之间的数量关系。方法 记录11名被试持续负重时主观疲劳感量表得分及肱二头肌相应表面肌电信号,分析MPF、MF和Lempel-ziv复杂度以及持续时间与主观疲劳感量表分数之间的相关,并对其间的数量关系进行拟合。结果 主观疲劳评定分数与持续时间成显著正相关,而与各肌电信号指标成不同程度的显著负相关。以主观疲劳评定分数为因变量,以持续时间及各肌电信号指标为自变量的对数函数和幂函数的拟合均具有统计学意义。结论 主观疲劳感得分与表面肌电信号指标及持续时间对反映肌肉疲劳状态具有较高一致性;其间的数量关系比较符合心理物理学中Stevens幂定律。     

Targeting of ultrasmall superparamagnetic iron oxide (USPIO) particles to tumor cells in Vivo by using transferrin receptor pathways

Human transferrin was covalently coupled to ultrasmall superparamagnetic iron oxide (USPIO) particles, and the trans-ferrin-USPIO obtained was investigated in vivo in experimental SMT/2A tumor-bearing rats (rat mammary carcinoma). Physicochemical characterization showed an overall size of 36 nm (DLS) with a core size of 5 nm (TEM). Relaxivities were R,₁ = 23.6 and R₂ = 52.1 liter/mmol · s (0.47 T). Bound transferrin was 280 μg/mg of iron. Pharmacokinetic investigations revealed a half-life of 17 min in normal rats. The MR evaluation of tumor signal intensity over time showed a 40% (range 25–55%) signal reduction 150 min after injection with the reduction persisting for at least 8 h. Control experiments using the parent USPIO compound or USPIO labeled with a nonspecific human serum albumin (HSA-USPIO) showed a change of only 10% (range 5–15%) in tumor signal intensity over time. The results demonstrate that a combination of the USPIO relaxivity properties with the specificity of transferrin-medi-ated endocytosis allows in vivo detection of tumors by MR imaging.