No abstract

Abstract-Human atrial fibrillation (AF) has been associated with increased atrial oxidative stress. In animal models, inhibition of reactive oxygen species prevents atrial remodeling induced by rapid pacing, suggesting that oxidative stress may play an important role in the pathophysiology of AF. NAD(P)H oxidase is a major source of superoxide in the cardiovascular system; however, whether this enzyme contributes to atrial oxidative stress in AF remains to be elucidated. We investigated the sources of superoxide production (using inhibitors and substrates of a range of oxidases, RT-PCR, immunofluorescence, and immunoblotting) in tissue homogenates and isolated atrial myocytes from the right atrial appendage (RAA) of patients undergoing cardiac surgery (nϭ54 in sinus rhythm [SR] and 15 in AF). A membrane-bound gp91phox containing NAD(P)H oxidase in atrial myocytes was the main source of atrial superoxide production in SR and in AF. NADPH-stimulated superoxide release from RAA homogenates was significantly increased in patients with AF in the absence of changes in mRNA expression of the p22phox and gp91phox subunits of the NAD(P)H oxidase. In contrast with findings in SR patients, NO synthases (NOSs) contributed significantly to atrial superoxide production in fibrillating atria, suggesting that increased oxidative stress in AF may lead to NOS "uncoupling." These findings indicate that a myocardial NAD(P)H oxidase and, to a lesser extent, dysfunctional NOS contribute significantly to superoxide production in the fibrillating human atrial myocardium and may play an important role in the atrial oxidative injury and electrophysiological remodeling observed in patients with AF.

The origin of ferromagnetism in ZnO-based systems was investigated using Co-doped ZnO thin films as prototypical examples of II–VI-based diluted magnetic semiconductors. In spite of the atomic-scale dissolution of Co ions in wurtzite ZnO, both the magnetization-temperature curve and the magnetization-field curve demonstrated that Zn1−xCoxO thin films were paramagnetic for x⩽0.12. On the other hand, Zn1−xCoxO films with x greater than 0.12 were characterized by the Co-metal clustering and apparently showed room-temperature ferromagnetism. The discrepancy between the zero-field cooling and the field cooling curves further indicates that Co-doped ZnO films (for x>0.12) are superparamagnetic and the observed ferromagnetism originates from the nanometer-sized Co clusters.

Inorganic nanocrystals have attracted much attention for therapeutic and diagnostic applications due to their unique optical, magnetic, and fluorescent properties.[1] Among these various nanocrystals, colloidal superparamagnetic iron oxide (e.g., γ-Fe 2 O 3 and Fe 3 O 4 ) have been extensively highlighted for many biomedical applications such as contrast agents for magnetic-resonance (MR) imaging, therapeutic gene carriers, protein purification, and sensors for nucleic-acid and virus detection. [2] In principle, it is of utmost importance to prepare highly stable magnetic nanocrystals in aqueous solutions to maximize in vivo half-life and tissuespecificity. However, the fabrication of such stable, bioactive magnetic nanocolloids has proven to be nontrivial.Methods for hydrophilic surface modification include addition of surface-active small molecules or polymeric stabilizers [3] and synthesis of magneto-composites via encapsulation.

Gadolinium-labeled magnetite nanoparticles (GMNPs) were synthesized via a bioinspired manner to use as dual contrast agents for T1- and T2-weighted magnetic resonance imaging. A mussel-derived adhesive moiety, 3,4-dihydroxy-l-phenylalanine (DOPA), was utilized as a robust anchor to form a mixed layer of poly(ethylene glycol) (PEG) chains and dopamine molecules on the surface of iron oxide nanoparticles. Gadolinium ions were subsequently complexed at the distal end of the dopamine molecules that were prefunctionalized with a chelating ligand for gadolinium. The resultant GMNPs exhibited high dispersion stability in aqueous solution. Crystal structure and superparamagnetic properties of magnetite nanocrystals were also maintained after the complexation of gadolinium. The potential of GMNPs as dual contrast agents for T1 and T2-weighted magnetic resonance imaging was demonstrated by conducting in vitro and in vivo imaging and relaxivity measurements.