Philipp Schmidt

Feasibility and Limits of Magnetically Labeling Primary Cultured Rat T Cells with Ferumoxides Coupled with Commonly Used Transfection Agents

Visualization and quantification of inflammatory processes is of high importance for early diagnosis of a multitude of diseases. Magnetic resonance imaging (MRI) using iron oxide (FeO) nanoparticles as contrast agents allows the study of macrophage infiltration during inflammation in a variety of tissues. Macrophages are effectors of the immune response, their appearance being orchestrated by activated T lymphocytes. Therefore, tracking of labeled T lymphocytes, which initiate the immune process, should enable earlier detection of tissue inflammation. In this study, we investigate the feasibility of specifically labeling harvested T cells by using dextran-coated FeO nanoparticles and commonly available transfection agents (TAs). Physicochemical properties of the newly formed FeO/TA vesicles were determined as well as their cell toxicity and their T cell activation potential. The labeling efficiency of each FeO/TA combination was evaluated by measuring the transverse MRI relaxation rate R2 by X-ray spectroscopy and magnetic selection. Toxicity and labeling efficacy differed significantly among TAs. The best results were achieved by using polyamine TAs and in particular by using poly-l-lysine at a concentration of 1.5 µg/mL administered in combination with 22.5 µg iron/mL. By using this protocol, up to 60% of harvested T cells could be labeled. Microscopic investigation revealed FeO/TA nanoparticles not only localized within the cytoplasma of the cells but also sticking to the outer membrane surface.

In vivo assessments of mucus dynamics in the rat lung using a Gd-Cy5.5-bilabeled contrast agent for magnetic resonance and optical imaging

Dysfunctions in mucociliary clearance are associated with the accelerated loss of lung function in several respiratory diseases. Approaches enabling the in vivo visualization of mucus dynamics in rodents at high resolution and sensitivity would be beneficial for experimental lung research. We describe the synthesis and characterization of two bilabeled amino dextran–based probes binding specifically to mucin. Labeling of secreted mucus and of mucin in goblet cells in the lungs of lipopolysaccharide‐challenged rats has been demonstrated in vivo with near‐infrared fluorescence and MRI and confirmed by histology. The effects of uridine triphosphate were then studied in lipopolysaccharide‐challenged rats by simultaneously administering the imaging probe and the compound. The data suggest that uridine triphosphate increased the mucociliary clearance, but at the same time induced a release of mucin from goblet cells, thus not contributing to the overall reduction of mucus in the lung. The approach outlined here enables one to derive information on mucus clearance, as well as secretion. Such a global view on mucus dynamics may prove invaluable when testing new pharmacological agents aimed at improving mucociliary clearance. Magn Reson Med, 2009.

cis-(3R,5R)-3-Bromo-2,2-di­methyl-5-phenyl­tetra­hydro­pyran

The heterocyclic ring in the title compound, C13H17BrO, adopts a 1C4 conformation, with the phenyl and bromo substituents located in equatorial positions.

A radical version of the bromine cyclization of alkenols

Abstract The scope of an alkoxyl radical version of the classical bromine cyclization was explored. Oxygen-centered radicals were generated in photochemically initiated radical chain reactions from N-alkenoxy-4-(p-chlorophenyl)thiazole-2(3H)-thiones 5a–c, N-alkenoxy-4-methylthiazole-2(3H)-thiones 13, 14, 21, rac-23, and N-alkenoxypyridine-2(1H)-thiones 6d–f, 16, rac-25. Thus, 2-(2-bromopropyl)-substituted tetrahydrofurans 4a–c, which are minor compounds (