Synthesis and characterisation of a novel tubulin-directed DO3A-colchicine conjugate with potential theranostic features

Colchicine is a known tubulin binding agent enabling necrosis in tumors. A novel tubulin-directed DO3A-colchicine conjugate and its Gd(III) complex were prepared from N-deacetylcolchicine, coupling alkaloid and polyaza-alicyclic functions via a peptide coupling methodology. The longitudinal proton relaxivity of the Gd(III) complex in water at 4.7 T is 2.86 mM⁻¹ s⁻¹ and a similar efficacy as colchicine towards ovarian carcinoma cells in vitro.     

抗人精子蛋白17磁性纳米探针靶向的卵巢癌体内外磁共振成像

用MRI(magnetic resonance imaging)技术探索连接抗人精子蛋白17单克隆抗体(anti-Sp17 mAb)的磁性纳米探针对体外培养及动物体内Sp17+卵巢癌的靶向性。将anti-Sp17mAb连接到表面包覆壳聚糖的超顺磁性氧化铁纳米颗粒上,制成磁性纳米探针anti-Sp17-MNP,用作MRI阴性对比剂。将磁性纳米探针与Sp17+和Sp17-培养的肿瘤细胞共育,进行一系列体外磁共振成像实验。荷瘤小鼠尾静脉注射磁性纳米颗粒,用7T磁共振仪在体成像,观察肿瘤部位的信号变化,并用普鲁士蓝染色肿瘤组织切片,观察有无铁粒子聚集。体外MRI数据显示,anti-Sp17-MNP与细胞靶向结合,并与细胞共育2 h后,Sp17+HO-8910的T2*信号强度比Sp17-HepG2低2倍;anti-Sp17-MNP对肿瘤细胞的靶向作用可被重组人Sp17阻断。7T磁共振仪对动物在体肿瘤成像结果显示,感兴趣区因磁性纳米探针靶向聚集而导致信号降低,并经组织切片普鲁士蓝染色证实。本研究结果表明,用anti-Sp17抗体和新的合成路线制备的纳米探针具有用作MR对比剂进行分子成像的潜能。     

Bicuspid stenotic aortic valves: clinical characteristics and morphological assessment using MRI and echocardiography

Background

Bicuspid aortic valve (BAV) is one of the most common congenital heart defects with a population prevalence of 0.5% to 1.3%. Identifying patients with BAV is clinically relevant because BAV is associated with aortic stenosis, endocarditis and ascending aorta pathology.

Methods and Results

Patients with severe aortic stenosis necessitating aortic valve replacement surgery were included in this study. All dissected aortic valves were stored in the biobank of the University Medical Centre Utrecht. Additionally to the morphological assessment of the aortic valve by the surgeon and pathologist, echocardiographic and magnetic resonance imaging (MRI) images were evaluated. A total of 80 patients were included of whom 32 (40%) were diagnosed with BAV by the surgeon (gold standard). Patients with BAV were significantly younger (55 vs 71 years) and were more frequently male. Notably, a significant difference was found between the surgeon and pathologist in determining valve morphology. MRI was performed in 33% of patients. MRI could assess valve morphology in 96% vs 73% with echocardiography. The sensitivity of MRI for BAV in a population of patients with severe aortic stenosis was higher than echocardiography (75% vs 55%), whereas specificity was better with the latter (91% vs 79%). Typically, the ascending aorta was larger in patients with BAV.

Conclusion

Among unselected patients with severe aortic valve stenosis, a high percentage of patients with BAV were found. Imaging and assessment of the aortic valve morphology when stenotic is challenging.     

Recovery of lysozyme from hen egg white by selective magnetic cake filtration

A new concept for the improvement of the downstream processing and purification is the so‐called magnetic separation. By using surface functionalized magnetic substrate particles, which selectively adsorb the target product, it can be directly separated out of a crude bioprocess stream. These methods are already used for analytical purposes, where only small amounts of functionalized particles are necessary. To apply the same concept at a larger scale, effective and economical procedures have to be provided. First, suitable process equipment has to be developed. Second, the magnetic particles have to be manufactured with a stable surface functionalization and long‐term stability for their reuse. Up to now mainly high‐gradient magnetic separation filter devices are applied for selective magnetic separation. They consist of a magnetic matrix in which the magnetic particles are trapped. In this work, a new magnetic filter is introduced that overcomes the capacity limitations of the current high‐gradient magnetic separation technology. The principle is demonstrated by selective recovery of lysozyme from hen egg white. Prior to the separation experiments magnetic beads with a strong acid cation‐exchange surface functionalization are synthesized. The separation procedure is implemented in only one unit operation. With the implementation of the displacement elution sequence lysozyme can be separated out of a hen egg white solution with a purification factor of PF=36 and a purity P=0.83.     

颅内静脉系统血栓形成6 例临床分析

目的:探讨颅内静脉系统血栓形成(CVT)的临床表现、影像学特征以及治疗方法对临床诊断的意义。方法:回顾性分析首都医科大学宣武医院收治的6例CVT患者的临床表现及影像学特征与治疗方法。结果:6例临床表现无特殊,4例经MRI+MRV确诊,3例DSA检查确诊,1例介入治疗,4例抗凝治疗,2例保守,无死亡患者。结论:静脉系统血栓形成临床症状缺乏特异性,临床遇到急性起病的头痛、呕吐,伴或不伴有局灶性神经功能缺损或癫痫发作、意识障碍的青中年人,应高度怀疑CVT。早期应用抗凝、溶栓等治疗方法,对改善预后具有较高的临床应用价值。     

磁性氧化铁纳米药物载体的研究进展

近年来,磁性氧化铁靶向纳米载体作为载药系统引起了人们的关注。磁性靶向载药系统和靶向药物治疗的目的是药物载体载药后,在外部磁场的作用下直接靶向富集在肿瘤或病损组织,杀伤病损细胞,对人体无害或减少毒副作用。本文介绍了影响磁纳米颗粒在体内作用的设计参数,并总结了被广泛应用于氧化铁纳米颗粒的制备,表面修饰,功能化的方法及氧化铁纳米载体在靶向载药体系中的应用。     

Water uptake and oil distribution during imbibition of seeds of western white pine (<Emphasis Type="Italic">Pinus monticola</Emphasis> Dougl. ex D. Don) monitored in vivo using magnetic resonance imaging

Dry or fully imbibed seeds of western white pine (Pinus monticola Dougl. ex D. Don) were studied using high-resolution magnetic resonance imaging (MRI). Analyses of the dry seed revealed many of the gross anatomical features of seed structure. Furthermore, the non-invasive nature of MRI allowed for a study of the dynamics of water and oil distribution during in situ imbibition of a single seed with time-lapse chemical shift selective MRI. During soaking of the dry seed, water penetrated through the seed coat and megagametophyte. The cotyledons of the embryo (located in the chalazal end of the seed) were the first to show hydration followed by the hypocotyl and later the radicle. After penetrating the seed coat, water in the micropylar end of the seed likely also contributed to further hydration of the embryo; however, the micropyle itself did not appear to be a site for water entry into the seed. A model that describes the kinetics of the earlier stages of imbibition is proposed. Non-viable pine seeds captured with MRI displayed atypical imbibition kinetics and were distinguished by their rapid and uncontrolled water uptake. The potential of MR microimaging for detailed studies of water uptake and distribution during the soaking, moist chilling (stratification), and germination of conifer seeds is discussed.Electronic Supplementary Material Supplementary material is available for this article if you access the article at . A link in the frame on the left on that page takes you directly to the supplementary material.     

Bis(2-methyltetrazole)dichlorocopper(II) is a layered coordination polymer built from dinuclear chloro-bridged Cu units linked by bridging tetrazoles. The first structurally and magnetically characterized complex of 2-monosubstituted tetrazoles

The data on synthesis, crystal structure, magnetic susceptibility and thermal properties of coordination compound of copper(II) chloride with 2-methyltetrazole (2mtet) of Cu(2mtet)₂Cl₂ composition are reported. The Cu atom environment forms an elongated octahedron, with two 2-methyltetrazole ligands (N4 bound) and two Cl atoms in the equatorial positions. Symmetry related 2-methyltetrazole ligand and Cl atom are in the axial positions. One of the two 2-methyltetrazole molecules of the asymmetric unit exhibits bridging properties being linked to two Cu atoms through two N atoms (i.e., N4 and N1) of the tetrazole ring, while the other ligand molecule is coordinated in monodentate fashion via one tetrazole N4 atom. The Cu-octahedra form dinuclear building bricks by sharing edges with equatorial and axial Cl atoms. These dinuclear units are linked together via bridging 2-methyltetrazole ligands to form infinite layers parallel to the plane. Magnetic properties of Cu(2mtet)₂Cl₂ and the data of quantum-chemical calculations of molecular electrostatic potential and energies of hydronation of nitrogen atoms for 2mtet using B3LYP/6-31G^* level of theory are in agreement with the structural data obtained.     

Hydrogen-bonded supramolecular manganese(II) complexes with network and sheet structures bridged by terephthalate unit

Two 1D complexes [Mn(4- methylpyrazole)₃(H₂O)(tp)]_n (2) and [Mn(4-methylpyrazole)₄(tp)]_n (3) (tp = terephthalate) were synthesized and characterized by means of X-ray analysis and magnetic studies. The molecular structure of 2 reveals that Mn(II) centers with asymmetric coordination surroundings are bridged by crystallographically different tp ligands, forming a 1D chain. The 1D coordination chains are interconnected by hydrogen bonds between free carboxylate oxygen atoms in a chain and hydrogens of pyrazole nitrogen atoms in neighboring chains, leading to a 3D framework. Compound 3 also exhibits a 1D coordination chain which is hydrogen-bonded to adjacent chains, providing a 2D sheet structure. Interestingly, the structures include intra- and interchain hydrogen bonds contributed from N-H groups of the capping 4-methylpyrazole ligands. Magnetic measurements show weak antiferromagnetic interactions with exchange coupling parameters of J = −0.018 cm⁻¹ for 2 and J = −0.062 cm⁻¹ for 3 through the extended tp ligand on the basis of an infinite chain model (H = −J∑S_i · S_i + 1).     

Synthesis, structure, and magnetic properties of dinuclear nickel(II) complexes with a phenol-based dinucleating ligand with four methoxyethyl chelating arms

Dinuclear nickel(II) complexes [Ni₂(bomp)(MeCO₂)₂]BPh₄ (1) and [Ni₂(bomp)(PhCO₂)₂]BPh₄ (2) were synthesized with the dinucleating ligand 2,6-bis[bis(2-methoxyethyl)aminomethyl]-4-methylphenol [H(bomp)]. X-Ray analysis revealed that the complex 1 · 0.5CHCl₃ contains two nickel(II) ions bridged by phenolic oxygen and two acetate groups, forming a μ-phenoxo-bis(μ-acetato)dinickel(II) core. Electronic spectra were investigated for 1 and 2 in the range of 400-1800 nm, and the data were typical for the octahedral high-spin nickel(II) complexes. Obtained spectral components were well simulated based on the angular overlap model assuming the trigonally distorted octahedral geometry. Magnetic susceptibility was measured for 1 and 2 over a temperature range of 4.5-300 K. The optimized magnetic data were J = 1.75 cm⁻¹, zJ′ = −0.234 cm⁻¹, g = 2.21, D = 15.1 cm⁻¹, and TIP = 370 × 10⁻⁶ cm⁻¹ for complex 1 and J = 3.55 cm⁻¹, zJ′ = −0.238 cm⁻¹, g = 2.23, D = 21.8 cm⁻¹, and TIP = 470 × 10⁻⁶ cm⁻¹ for complex 2. The data revealed ferromagnetic interactions between the two nickel(II) ions.