富勒烯对斑马鱼60Coγ辐射生物效应修饰作用的研究

目的 研究富勒烯化合物对斑马鱼受到γ射线照射后的存活率、畸形发生率的影响及其机制,以了解富勒烯类化合物对辐射生物效应的修饰作用。方法 ⁶⁰Coγ射线照射下富勒烯母体纳米颗粒对斑马鱼成鱼存活率的改变,同时利用斑马鱼胚胎-幼体比较该化合物对不同照射条件下斑马鱼鱼卵及幼体畸形发生率的影响,并从活性氧(ROS)生成的改变及DNA链断裂形成探讨了其可能的作用机制。结果 光照期给药500×10^－9的富勒烯母体(nano-C₆₀)能增强γ射线照射对成鱼的杀伤作用,在此条件下活性氧生成和DNA损伤增加,且抑制胚胎的孵出率和导致畸形的发生率增加;但避光期用药对射线效应没有明显的增强作用,除了高浓度5000×10^－9会抑制幼鱼的孵出率,并导致发育畸形增加。结论 富勒烯母体对斑马鱼的辐射损伤效应有增强作用,其机制可能是在光照期用药后活化并导致活性氧生成增加,并导致DNA氧化损伤增强。     

富勒烯衍生物对自由基的清除作用及其生物学效应

富勒烯及其衍生物因其独特的化学结构和理化性质,尤其是它们强大的清除自由基的能力,引起了生物医学界研究者的极大关注,开展了大量生物学效应研究,近年来取得较大进展.在此重点探讨多种富勒烯衍生物的生物学效应,特别是对自由基清除效应的应用意义及应用前景.     

富勒烯C_(60)/C_(70)的分离与应用

富勒烯Ｃ６０／Ｃ７０的分离与应用谷贵文刘兵①②林阳①关键词富勒烯Ｃ６０／Ｃ７０中图法分类号Ｏ６５８日本科学家小泽于１９７０年预言碳元素除了已知的两种同素异形体金刚石、石墨外，在自然界中还应该有第三种同素异形体存在。经过各国科学家１５年的不懈努力和艰苦...     

富勒烯亮肤精华液对小鼠皮肤光老化的抑制作用

目的观察富勒烯亮肤精华液对小鼠皮肤光老化的防护作用。方法用UVA和UVB照射小鼠诱导光老化。选取60只小鼠,随机均分为三组,每组小鼠20只。对照组(A组),不进行任何处理。抗氧化组(B组),每次紫外线照射前30 min备皮并外涂富勒烯亮肤精华液1次。光老化组(C组),紫外线照射前,不进行富勒烯亮肤精华液外涂。14周后,对小鼠背部皮肤进行肉眼观察,并进行谷胱甘肽氧化酶(Glutathione peroxidase,GSH-Px)及超氧化物歧化酶(Superoxide dismutase,SOD)的活性以及羟脯氨酸(Hydroxyproline,HYP)含量的检测。结果肉眼观察小鼠背部皮肤,C组小鼠皮肤褶皱伴粗糙,A组和B组小鼠皮肤外观未出现明显变化。B组小鼠皮肤SOD、GSH-Px活性和HPY的含量高于C组;A组SOD、GSH-Px和HPY的含量无明显变化。结论富勒烯亮肤精华液可减少皮肤内与老化相关的酶物质含量的消耗,使其活性明显增强最终抑制氧自由基的形成,从而减少紫外线照射对皮肤造成的伤害。     

第11届全国放射性药物与标记化合物学术会议征文通知

第11届全国放射性药物与标记化合物学术会议将于2011年11月在广州召开。本次会议将进行大会论文交流,评选优秀论文,并特邀国内外著名专家、学者做报告。会议征文范围：单光子放射性药物制备,放射性治疗药物制备,正电子放射性药物合成,放射性药物的质量控制,放射性药物的生物学评价及应用,标记化合物研究、制备及应用,放射性药物与标记化合物相关的其他研究。     

纳米富勒烯钆制剂实现短距离放疗及纵向成像:脑肿瘤原位异种移植小鼠模型的研究

目的采用脑肿瘤原位异种移植小鼠模型,验证功能化富勒烯钆(f-Gd3N@C80)纵向MR成像功能以及标记放射性同位素177镥(177Lu)-四氮杂环十二烷-四乙酸(DOTA)     

环状双硫化物的辐射防护研究 Ⅰ.5,8-二硫辛酸衍生物和相关化合物的合成及其抗放作用

1949年Patt等发现半胱氨酸在哺乳动物有明显的辐射防护作用以来,在这方面,国内外许多学者筛选研究了各种类型的药物和化合物。其中以含碱性基的巯基化合物及其衍生物通常称氨巯基化合物研究得最广泛。在氨巯基化合物中半胱胺、胱胺、S-(2-氨乙基)异硫脲盐(AET)、氨乙基硫代磷酸(Gyslaphos)和S-2-(3-氨基丙胺基)乙基硫代磷酸(WR2721)等是高效防护剂的代表,特别是WR2721是目前应用于预防放疗反应最有希望的药物。然而这些化合物在有效剂量时都具有一定的毒副作用,而且在照射后给药,表现不出辐射防护作用,这就限制了它们预防急性放射病实际应用的可能性。     

推进剂中硝基类化合物定量检测方法的研究进展

推进剂中硝基化合物对推进剂职业工作环境造成严重危害,严重威胁职业工作人员健康,硝基化合物污染痕迹的准确检测显得至关重要。本文对国内外推进剂中硝基类化合物的定量检测方法进行了综述,介绍了目前常用检测方法的优缺点及其在体内外检测中的应用,对推进剂中硝基类化合物定量检测的研究发展趋势进行了展望。     

稀土对受照射小鼠辐射损伤影响的实验研究

稀土化合物因具有其特殊的物理特性，在医学领域的应用也已引起广泛关注。有文献报道，稀土化合物能增强机体免疫功能和抑制肿瘤作用，能诱导某些抑癌基因的表达，对癌基因有抑制作用。但稀土及其化合物在辐射损伤中的作用，尤其是对电离辐射诱导细胞DNA损伤的影响报道较少。笔者重点研究柠檬酸镧在电离辐射引起动物骨髓细胞DNA损伤中的作用。     

富勒烯衍生物C3对AHH-1细胞电离辐射的防护效应

目的 研究富勒烯衍生物C3(以下简称C3)对AHH-1细胞电离辐射的防护效应,探讨该类化合物作为新型辐射防护剂的发展前景.方法 通过化学合成制备C3,用台盼兰拒染试验检测C3对AHH-1细胞的毒性作用.在此基础上于AHH-1细胞培养体系中加入不同浓度C3,以不同剂量60Coγ射线照射细胞,通过台盼兰拒染试验检测C3化合物对细胞的毒性作用,用Annexin-V/PI染色、Facscalibur流式细胞术等,分析C3化合物对γ射线照射细胞增殖活力和细胞凋亡的变化.结果 在细胞培养体系中,终浓度范围0～400 mg/L的C3对培养的对数生长期AHH-1细胞活力几乎无影响,AHH-1细胞台盼兰拒染率无明显变化(P＞0.05).C3对1～8 Gy γ射线照射的AHH-1细胞具有良好的辐射防护效应,终浓度在10 mg/L时即显示其对4 Gy60Co γ照射的细胞有保护效应,且随浓度增加而增加;终浓度达200～400 mg/L时,照射细胞存活率已接近未照射的正常细胞(P＞0.05),辐射诱导的细胞调亡率和细胞死亡率用药组均显著低于未用药的对照组(P＜0.01).研究结果还显示,C3提高照射细胞存活率的作用还与给药时间有关,照前24 h至照前即刻给药最为有效.结论 C3对不同剂量60Co γ射线照射的AHH-1细胞具有较好的电离辐射防护作用,该防护效应与用药浓度有关,C3浓度越高,防护作用越好;且在本实验产生辐射防护作用的浓度范围内,C3对培养的对数生长期AHH-1细胞存活率几乎无影响,提示该类化合物有作为新型辐射防护剂的研究前景.     

硼中子俘获治疗的生物学机制及临床研究进展

硼中子俘获治疗(boron neutron capture therapy，BNCT)是一种新型且高度精准的肿瘤放疗手段。BNCT可依赖高效靶向的含硼药物，在细胞级别同时实现对肿瘤细胞的精准打击和对正常细胞的精准防护。含硼药物研发正在深入进行，新型高效的制剂层出不穷，这为充分发挥BNCT优势和疗效带来新的曙光。由于BNCT过程中产生复合射线，其对肿瘤细胞的杀伤机制较为复杂，相关研究仍相对匮乏，具体分子机制有待阐明和完善。世界范围内，BNCT已用于恶性脑瘤、头颈部肿瘤、恶性黑色素瘤等临床治疗，并取得良好疗效。本文主要针对BNCT药物研究、生物学机制、潜在优势、临床应用进行综述。     

Protection of Tissue-culture Cells against Ionizing Radiation

Summary

The radioprotective activity of a number of biological amines, disulphide compounds and thiols at various concentrations was tested in an in vitro system, based on the cloning technique devised by Puck et al.

It was found that none of the biological amines (histamine, adrenaline, noradrenaline and serotonin) or disulphide compounds (cystamine and cystine) showed a protective activity. A defininitive protection on the other hand was observed with the thiol compounds (cysteamine, cysteine and AET).

The protective activity of the latter compounds depended on the concentration which was used. Concentrations of 2–4 mM gave dose–reduction factors (DRF) between 1 and 2. At higher concentrations (cysteamine 32 mM and cysteine 128 mM) DRF's approaching 4 were obtained. The best protection with AET was observed at a concentration of 128 mM (DRF 2·2). The protection by AET was meliorated if higher serum concentrations in the culture medium were used. The best protection on a mM basis was provided by cysteamine. None of the compounds protected when applied after irradiation.     

生物样品中吗啡类药物的检测进展

介绍了气相色谱法、气－质联用法，高效液相色谱法和放射免疫法在检测生物样品中吗啡类药物衣其代谢物中的应用。     

Biological studies of radiolabeled glucose analogues iodinated in positions 3, 4 or 6

The aim of this study was to assess the biological behavior of new radiolabeled glucose analogues proposed as tracers of glucose uptake in vivo and iodinated in position 3, 4, or 6. Biological results obtained in vitro on adipocytes and erythrocytes and in vivo in mice were compared to those obtained with the gold-standard tracer of glucose uptake, 2-deoxy-D-glucose. None of these molecules had the same biological behavior than 2-deoxy-D-glucose. Therefore, these compounds cannot be considered as tracers of glucose uptake.     

Development and testing of new hypoxic cell radiosensitizers.

Several new electron-affinic compounds have been shown to possess radiosensitizing ability in hypoxic mammalian cells. The correlation between chemical structure and biological activity can aid in the design and synthesis of new agents with potentially greater hypoxic cell radiosensitizing ability.     

Aurora激酶抑制剂ZM447439的合成及生物活性研究

目的优化Aurora激酶抑制剂ZM447439的合成路线,并对其体外生物活性进行评价。方法以4-羟基-3-甲氧基苯甲酸为起始原料,通过酯化、取代、硝化、还原、关环等反应合成ZM447439,涉及到的中间体及目标产物结构经1H-NMR,MS及IR确证。以MTT法研究其体外抗肿瘤活性(U937,K562,A549,LoVo及HT29细胞株),同时评价其体外AuroraA/B激酶抑制活性。结果合成了Aurora A/B激酶抑制剂ZM447439并进行相关生物活性研究。结论新合成路线总收率约34%,目标化合物具有较好的Aurora A/B激酶活性及肿瘤细胞增殖抑制活性。     

The Mechanism of Radiation Protection by Histamine and Other Biological Amines

Summary

The radioprotective activity of a number of biological amines, amongst them histamine and epinephrine, has been shown to be related to their pharmacological activity in mice. Pharmacological antagonists were found to counteract the protective activity of these compounds. The protective effect could not be correlated with the effects of the amines on the blood pressure.

By the use of a polarographic technique it could be shown that the protective compounds cause a decrease of the oxygen tension in the spleen, the magnitude and duration of which is correlated to the degree of radioprotection.

Similarly a reduction of the oxygen content of the inspiratory air reduces the oxygen tension in the spleen and affords protection against irradiation.

It is concluded that histamine, epinephrine and a number of other biological amines protect against irradiation by reducing the oxygen tension in the spleen and possibly in other blood forming organs.     

Fundamentals of positron emission tomography

Positron emission tomography is a modern radionuclide method of measuring physiological quantities or metabolic parameters in vivo. The method is based on: (1) radioactive labelling with positron emitters; (2) the coincidence technique for the measurement of the annihilation radiation following positron decay; (3) analysis of the data measured using biological models. The basic aspects and problems of the method are discussed. The main fields of future research are the synthesis of new labelled compounds and the development of mathematical models of the biological processes to be investigated.     

Synthesis, in vitro binding and biodistribution in B16 melanoma-bearing mice of new iodine-125 spermidine benzamide derivatives

In the course of our investigations aimed at improving the biological characteristics of iodobenzamides for melanoma therapeutic applications, four new derivatives containing a spermidine chain have been prepared and radiolabeled with (125)I. In vitro studies showed that all compounds displayed high affinity for melanin superior to the reference compound BZA, thus validating our experimental approach. In vivo biodistribution was investigated in B16 melanoma-bearing mice. All four compounds, particularly benzamide 3, showed accumulation in the tumor, but lower, however, than that of BZA. Moreover, high concentrations of radioactivity in other organs, namely, the liver and lung, demonstrated nonspecific tumoral uptake. In view of these results, compounds 1 2 3 4 do not appear to be suitable radiopharmaceuticals for melanoma radionuclide therapy.