Binary and ternary mixed metal complexes of terminally free peptides containing two different histidyl binding sites

Copper(II), nickel(II) and zinc(II) complexes of the terminally free peptides AHAAAHG and AAHAAAHG have been studied by combined applications of potentiometric and various spectroscopic techniques, including UV-visible, CD and EPR for copper(II) and UV-visible, CD and NMR for nickel(II). It was found that the octapeptide AAHAAAHG can easily bind two equivalents of copper(II) or nickel(II) ions and the amino terminus was identified as the primary ligating site of the molecule. On the other hand, this peptide has a relatively low zinc(II) binding affinity. Mono- and di-nuclear copper(II) and nickel(II) complexes were also formed with the heptapeptide AHAAAHG but this peptide can effectively bind one equivalent of zinc(II) ions, too, with the involvement of the deprotonated amide nitrogen in zinc(II) binding. The enhanced stability of the [MH-1L] species of AHAAAHG was explained by the tridentate (NH2,N-,Nim) coordination of the amino terminus supported by the macrochelation of the internal histidyl residue. Mixed metal copper(II)-nickel(II) complexes were also formed with both peptides and copper(II) ions were coordinated to the amino terminal, while nickel(II) ions to the internal histidyl sites. © 2013 Elsevier Inc

In Vivo Preclinical Assessment of β-Amyloid–Affine [11C]C-PIB Accumulation in Aluminium-Induced Alzheimer’s Disease-Resembling Hypercholesterinaemic Rat Model

Aluminum (Al) excess and hypercholesterinaemia are established risks of Alzheimer’s disease (AD). The aim of this study was to establish an AD-resembling hypercholesterinaemic animal model—with the involvement of 8 week and 48 week-old Fischer-344 rats—by Al administration for the safe and rapid verification of β-amyloid-targeted positron emission tomography (PET) radiopharmaceuticals. Measurement of lipid parameters and β-amyloid–affine [11C]C-Pittsburgh Compound B ([11C]C-PIB) PET examinations were performed. Compared with the control, the significantly elevated cholesterol and LDL levels of the rats receiving the cholesterol-rich diet support the development of hypercholesterinaemia (p ≤ 0.01). In the older cohort, a notably increased age-related radiopharmaceutical accumulation was registered compared to in the young (p ≤ 0.05; p ≤ 0.01). A monotherapy-induced slight elevation of mean standardised uptake values (SUVmean) was statistically not significant; however, adult rats administered a combined diet expressed remarkable SUVmean increment compared to the adult control (SUVmean: from 0.78 ± 0.16 to 1.99 ± 0.28). One and two months after restoration to normal diet, the cerebral [11C]C-PIB accumulation of AD-mimicking animals decreased by half and a third, respectively, to the baseline value. The proposed in vivo Al-induced AD-resembling animal system seems to be adequate for the understanding of AD neuropathology and future drug testing and radiopharmaceutical development

PET Probes for Preclinical Imaging of GRPR-Positive Prostate Cancer: Comparative Preclinical Study of [68Ga]Ga-NODAGA-AMBA and [44Sc]Sc-NODAGA-AMBA

Gastrin-releasing peptide receptors (GRPR) are overexpressed in prostate cancer (PCa). Since bombesin analogue aminobenzoic-acid (AMBA) binds to GRPR with high affinity, scandium-44 conjugated AMBA is a promising radiotracer in the PET diagnostics of GRPR positive tumors. Herein, the GRPR specificity of the newly synthetized [44Sc]Sc-NODAGA-AMBA was investigated in vitro and in vivo applying PCa PC-3 xenograft. After the in-vitro assessment of receptor binding, PC-3 tumor-bearing mice were injected with [44Sc]Sc/[68Ga]Ga-NODAGA-AMBA (in blocking studies with bombesin) and in-vivo PET examinations were performed to determine the radiotracer uptake in standardized uptake values (SUV). 44Sc/68Ga-labelled NODAGA-AMBA was produced with high molar activity (approx. 20 GBq/µmoL) and excellent radiochemical purity. The in-vitro accumulation of [44Sc]Sc-NODAGA-AMBA in PC-3 cells was approximately 25-fold higher than that of the control HaCaT cells. Relatively higher uptake was found in vitro, ex vivo, and in vivo in the same tumor with the 44Sc-labelled probe compared to [68Ga]Ga-NODAGA-AMBA. The GRPR specificity of [44Sc]Sc-NODAGA-AMBA was confirmed by significantly (p ≤ 0.01) decreased %ID and SUV values in PC-3 tumors after bombesin pretreatment. The outstanding binding properties of the novel [44Sc]Sc-NODAGA-AMBA to GRPR outlines its potential to be a valuable radiotracer in the imaging of GRPR-positive PCa

A regionális struktúra kialakítása Magyarországon az uniós csatlakozás tükrében

INST: L_11

Az apa jelentősége és hiányának következményei a gyermeki fejlődésre

Dolgozatom témájából kitűnik, az apa hiánya már kora gyerekkorban pszichés nehézségeket vonhat maga után, majd később a pubertás idején és a felnőttkorban a lelki problémák mellett oka lehet párválasztási kudarcoknak, illetve akár kriminalitáshoz is vezethet. Mi lehet a magyarázata, hogy az apa nélkül felnőni kényszerülők problémákkal küzdenek? Dolgozatommal szeretnék betekintést nyújtani a német nyelvterületen e témában végzett kutatásokba, természetesen a teljesség igénye nélkül. A dolgozat a pozitív, „elég jó” apaság jellemzőire, azok hatásaira a gyermek, ifjú, és fiatal felnőtt korra, valamint a pozitív apa hiányára világít rá