Enhanced dual contrast agent,Co-doped NaYF4:Yb,Tm nanorods,for near infrared-to-near infrared upconversion luminescence and magnetic resonance imaging

Dual-modality imaging with magnetic resonance (MR) and upconversion luminescence (UCL) is a promising technique for molecular imaging in biomedical research. Multifunctional lanthanide-based nanoparticles have been widely investigated as agents for contrast enhanced MR and fluorescence imaging. However, the use of rare earth fluoride nanoparticles for dual-modality imaging of T2-weighted MR and UCL is rarely reported. We find that NaYF₄:Yb³⁺,Tm³⁺,Co²⁺ (MUC) nanorods can be applied as a high-performance dual contrast agent for both T2-weighted MR and UCL dual-modality imaging. After modification with 6-O-carboxymethyl chitosan (OCC), MUC nanorods can be endocytosed by cells without showing signs of cytotoxicity. High-quality UCL images of living cells incubated with MUC-OCC nanorods were acquired on a near-infrared (NIR) confocal microscopy under the excitation at 980 nm. Moreover, MUC-OCC nanorods display high transverse (r2) relaxivities in vitro. The application of low-dose MUC-OCC nanorods for NIR-to-NIR UCL and MR dual-modality in vivo imaging was also carried out successfully. In addition, the toxicity of MUC-OCC nanorods was evaluated by MTT assay, serological tests and histological analysis of visceral organs.     

Electrochemical and Raman spectroscopic studies of the effect of lanthanide ions on the activity of mitochondrial malate dehydrogenase

Chronoamperometry based on the ‘diffusion’ layer concept of the convective system was used to assay the activity of mitochondrial malate dehydrogenase (MDH). When the enzyme-catalysed reaction was initiated by adding the enzyme MDH into a well-stirred nicotinamide adenine dinucleotide (NADH, coenzyme) solution, the enzyme activity could be indicated by the continuous in-situ decrease in the limiting steady-state oxidation current of NADH. The effects of some lanthanide ions on the MDH activity were monitored. The La³⁺, Ce³⁺ and Eu³⁺ ions could activate markedly the enzyme MDH as the concentrations were lower. The activation mechanism would be that the lanthanide ions could interrupt the binding of NAD⁺ to MDH by combining preferentially to NAD⁺. This mechanism was proposed on the basis of voltammetric and Raman spectroscopic studies.     

Gadolinium block of calcium channels: influence of bicarbonate

The selectivity of block of voltage-activated barium (Ba⁺) currents by lanthanide ions was studied in a rat dorsal root ganglion (DRG) cell line (F11-B9), rat and frog peripheral neurons, and rat cardiac myocytes using the whole-cell patch clamp technique. Gadolinium (Gd³⁺) produced a dose-dependent and complete inhibition of whole-cell Ba²⁺ current in all cells studied, including cells expressing identified dihydropyridine-sensitive L-type currents and ω-conotoxin-sensitive N-type currents. Like Gd³⁺, lutetium (Lu³⁺) and lanthanum (La³⁺) blocked all Ba²⁺ current with little selectivity for different components of the whole-cell current. Gd³⁺ block of Ba²⁺ currents was incomplete, however, when sodium bicarbonate (5–22.6 mM) was added to the standard HEPES-buffered external Ba⁺ solution. In rat DRG neurons and F11-B9 cells, a fraction of the whole-cell Ba²⁺ current recorded in the presence of bicarbonate was resistant to block by saturating concentrations of Gd³⁺ (50–100 μM). The resistant current inactivated more rapidly than the original current giving the appearance that, under these conditions, Gd³⁺ block is more selective for the slowly inactivating component of the whole-cell current. Bicarbonate modification of Gd³⁺ block occurred both before and after ω-conotoxin block of N-type currents in rat DRG neurons, suggesting that even in the presence of bicarbonate, Gd³⁺ block was not selective for N-type currents.     

镧离子对大鼠腹腔巨噬细胞生长过程影响的研究

目的 :研究镧离子对腹腔巨噬细胞功能的影响。方法 :用 LKB- 2 2 77量热活性检测仪测定 3 7°C时细胞在加和不加 La3 + 的介质中的产热过程的差异 ;用亚硝酸盐分光光度法及电子自旋捕获法检测稀土离子存在下大鼠巨噬细胞产生的氧自由基· O-2 及·OH的变化。结论 :La3 + 在较低浓度时都能抑制活性氧自由基的生成。较高浓度时 ,作用相反 ,另外 La3 + 在初始时可促进细胞产热。     

镧系元素由土壤向人体转移及其分布

目的 计算14种镧系元素从土壤经膳食向人体的转移系数和在10种器官、组织中的分布。方法 依据我国4个不同膳食类型地区镧系元素膳食摄入量和10种主要器官、组织负荷量研究结果及土壤元素背景值文献资料,采用UNSCEA R陆地转移模式计算土壤、膳食、关键器官或全身三隔室间转移系数,采用LREE HREE作为分异评价指标。结果 镧系元素从土壤向膳食和从膳食向全身的总转移系数分别为0.131 ga^-1/gkg^-1和0.176 g/ga^-1。从膳食向骨骼转移系数比向肝大1个数量级;从土壤向膳食转移中轻稀土组稍有富集,而从膳食向骨骼转移中轻稀土组趋于向骨骼,重稀土组趋于向肝;器官、组织分布以骨骼最高(36.5%),其后依次为肌肉、肺和肝。结论 获得了14种镧系元素从我国土壤经膳食向人体的转移系数、分异状况和在10种器官、组织中分布。本文结果在辐射防护领域为镧系放射性核素内剂量估算、相关卫生标准制定和生物动力学模型及参数的确定提供了直接人体依据,对其他领域广泛研究也有重要意义。     

时间分辨荧光分析技术的研究进展及应用

时间分辨荧光分析(TRFA)技术是一种以镧系元素螫合物为标记物,测量其发射荧光的超灵敏的无放射性污染的标记分析技术,在生物分析中得到了广泛的应用。在近些年,研究发展了酶放大时间分辨荧光分析、时间分辨猝灭分析和分子信标等分析系统,其灵敏度更高,满足了不同的需求,使TRFA技术在临床诊断和科学研究中得到了更广泛的应用。     

Modulation of water exchange in Eu(III) DOTA–tetraamide complexes: considerations for in vivo imaging of PARACEST agents

Modulation of water exchange in lanthanide(III)–DOTA type complexes has drawn considerable attention over the past two decades, particularly because of their application as contrast agents for magnetic resonance imaging. LnDOTA–tetraamide complexes display unusually slow water exchange kinetics and this chemical property offers an opportunity to use these complexes as a new type of contrast agent based upon the chemical exchange saturation transfer (CEST) mechanism. Six new DOTA–tetraamide ligands having side‐chain amide arms with varying hydrophobicity and polarity were prepared and the water exchange characteristic of complexes formed with europium(III) complexes were investigated. The results show that introduction of steric bulk into the amide side‐chain arms of the europium(III) complexes not only favors formation of the mono‐capped twisted square antiprism coordination isomers, the isomer that is generally less favourable for CEST, but also accelerates water exchange in the mono‐capped square antiprism isomers. However, converting single methyl groups on these bulky arms to carboxyl or carboxyl ethyl esters results in a rather dramatic decrease in water exchange rates, about 50‐fold. Thus, steric bulk, polarity and hydrophobicity of the amide side‐chains each contribute to organization of water molecules in the second hydration sphere of the europium(III) ion and this in turn controls water exchange in these complexes. Copyright © 2009 John Wiley & Sons, Ltd.     

中国人镧系元素膳食摄入量和主要器官及组织负荷量研究

目的 测定我国成年男子膳食食品和主要器官、组织中镧系元素浓度和估算其膳食日摄入量和器官、组织负荷量。方法 在我国不同膳食类型4地区采集21例急死正常尸体10种主要器官、组织样品，连同过去所采当地食品和31例尸体6种器官、组织样品，采用ICP—MS或INAA法及必要的质量控制措施，分别测定了11和14种镧系元素浓度。按当地膳食组成和中同参考人器官组织重量估算了摄入量和器官、组织负荷量。结果 获得了我国12类食品和10种主要器官、组织样品中14种镧系元素浓度、摄入量和相应器官、组织负荷量。结论 本研究首次获得我国各类食品和成年男子10种器官组织中11种镧系元素浓度、相应膳食口摄入量和负荷量。所获结果为确定中国参考人镧系元素相应参数提供较前更为系统的依据，也为不同镧系元素、食品和器官组织提供了比较和背景值的国情资料。     

Low molecular weight lanthanide contrast agents: In vitro studies of mechanisms of action

The MR contrast properties of a series of structurally dissimilar low molecular weight (LMW) gadolinium (Gd) and dysprosium (Dy) chelates have been investigated under controlled experimental conditions in various in vitro test systems. Relaxation analysis (water, pH = 5.8, 37°C, .47 T) demonstrated the high dipolar relaxation efficacy of the tested Gd chelates. The T1 and T2 relaxivities of both metal chelate series decreased with decreasing hydration number, confirming the strong correlation between metal chelate structure and dipolar relaxivity. Susceptibility-induced T2 relaxation, commonly known as the susceptibility effect, is modulated primarily by the magnetic susceptibility and compartmentalization of the contrast agent. The influence of these parameters on the susceptibility effect of Dy diethylenetriamine pentaacetic acid bis-methylamide (DTPA-BMA) and GdDTPA-BMA was investigated in two-compartment in vitro models. In red blood cell suspensions (45% hematocrit, 37°C, .47 T, 2 and 3 mM metal ion concentration), the T2 relaxation efficacy of DyDTPA-BMA was markedly improved due to susceptibility effects that were shown to depend on compartmentalization. As the relaxation ability of GdDTPA-BMA was modulated by the dipolar interactions, compartmentalization was not a prerequisite for its T2 relaxation efficacy. In a coaxial glass system with no intercompartmental water exchange, which eliminated the dipolar relaxation mechanism, DyDTPABMA was shown to be the most efficient susceptibility agent because of its higher magnetic susceptibility. The reported one- and two-compartment model studies have demonstrated the different mechanism of action of LMW Gd- and Dy-based contrast agents. Gd chelates are predominantly dipolar relaxation enhancers, whereas Dy chelates are efficient susceptibility agents only in compartmentalized systems.     

人血清B2—mG BAS—时间分辨免疫荧光分析法的建立

本文报告将BAS引入时间分辨免疫荧光测量法(TRIFMA),成功地在国内首次建立人血清B_2-mG固相夹心BAS—TRIFMA。本法批内平均CV8.0%,批间平均CV11.7%,最小检出值为0.6μg/ml,平均回收率为101.2%,42例血清样品分别用TRIFMA和RLA测量B_2-mG水平,相关性良好,γ=0.9614,P<0.001。研究结果表明:采用戊二醛活化微量滴定条,多次包被抗体,每次中间用戊二醛固定,提高了IgG包被含量,使本方法的检测剂量范围可达1.25～40μg/mL,超过任何一种标记免疫分析法的最大检出值。