In Vivo Detection of Amyloid-β Deposits Using Heavy Chain Antibody Fragments in a Transgenic Mouse Model for Alzheimer's Disease

This study investigated the in vivo properties of two heavy chain antibody fragments (VHH), ni3A and pa2H, to differentially detect vascular or parenchymal amyloid-β deposits characteristic for Alzheimer's disease and cerebral amyloid angiopathy. Blood clearance and biodistribution including brain uptake were assessed by bolus injection of radiolabeled VHH in APP/PS1 mice or wildtype littermates. In addition, in vivo specificity for Aβ was examined in more detail with fluorescently labeled VHH by circumventing the blood-brain barrier via direct application or intracarotid co-injection with mannitol. All VHH showed rapid renal clearance (10–20 min). Twenty-four hours post-injection 99mTc-pa2H resulted in a small yet significant higher cerebral uptake in the APP/PS1 animals. No difference in brain uptake were observed for 99mTc-ni3A or DTPA(111In)-pa2H, which lacked additional peptide tags to investigate further clinical applicability. In vivo specificity for Aβ was confirmed for both fluorescently labeled VHH, where pa2H remained readily detectable for 24 hours or more after injection. Furthermore, both VHH showed affinity for parenchymal and vascular deposits, this in contrast to human tissue, where ni3A specifically targeted only vascular Aβ. Despite a brain uptake that is as yet too low for in vivo imaging, this study provides evidence that VHH detect Aβ deposits in vivo, with high selectivity and favorable in vivo characteristics, making them promising tools for further development as diagnostic agents for the distinctive detection of different Aβ deposits

Mobile ion transport pathways in (LiBr) x[(Li 2O) 0.6(P 2O 5) 0.4] (1-x) glasses

10.1007/s10008-010-1005-0Journal of Solid State Electrochemistry14101781-178

Intermediate species detection in a morpholine flame: contributions to fuel-bound nitrogen conversion from a model biofuel

Nau P, Seipel A, Lucassen A, Brockhinke A, Kohse-Höinghaus K. Intermediate species detection in a morpholine flame: contributions to fuel-bound nitrogen conversion from a model biofuel. EXPERIMENTS IN FLUIDS. 2010;49(4):761-773.A slightly fuel-rich (I broken vertical bar = 1.3) premixed laminar flat morpholine/oxygen/argon flame at 40 mbar was studied with cavity ring-down spectroscopy (CRDS). Morpholine as a secondary amine was considered as a prototypical nitrogenated biofuel. To contribute to the investigation of fuel-nitrogen conversion chemistry in this flame, absolute mole fraction profiles of CH, CN, and NH2 were determined. To our knowledge, this is the first study reporting quantitative mole fractions of these radicals from CRDS in a low-pressure flame of a model biofuel. The species profiles are discussed in combination with some relevant intermediates from molecular beam mass spectrometry, determined in this flame very recently (Lucassen et al., Proc Combust Inst 32(1):1269-1276, 2009). Some relative species profiles were also determined in flames of further amines to facilitate comparison. The results demonstrate that NH3- and HCN-related chemistry occurs in different regions of this flame. HCN production is considerable, and NO is found in the exhaust gases in percent-level concentrations. To monitor the combustion status, chemiluminescence is increasingly being applied as an intrinsic low-cost sensor. We believe to present the first chemiluminescence measurements in a flame of a prototypical nitrogenated biofuel, reporting relative emission intensities for five excited-state species. The shapes and maximum positions of the ground- and excited-state profiles show interesting differences, especially for the CN radical, which must be the consequence of different reaction pathways