Radiosynthesis and in vivo evaluation of a 18F-labelled styryl-benzoxazole derivative for β-amyloid targeting

The formation of β-amyloid deposits is considered a histopathological feature of Alzheimer′s disease (AD). In vivo molecular imaging by means of amyloid-avid radiotracers will allow for an early and conclusive diagnostic of AD. Herein, we describe the radiosynthesis of the radiofluorinated styryl benzoxazole derivative [18F]-[2-[N-methyl-N-(2′-fluoroethyl)-4′-aminostyryl]benzoxazole] ([18F]-1) and its pre-clinical evaluation, including metabolic and biodistribution studies in male Wistar rats. The in vivo biological evaluation of [18F]-1 showed that this new radiotracer has a moderate brain uptake with a slow brain washout and a poor in vivo stability

Outcomes to Objectives: Learning About Quality Assessment

Recently assessment has become an important component of student affairs and higher education to assist in determining the effect and impact of programs and educational initiatives. To embrace this trend, the Office of Housing and Residence Life at Ball State University (IN) created learning outcomes for students living in residence halls. Through reflective questioning, discussion, and assessment, the Residence Life program strives to further the development and learning experience of students

Outcomes to Objectives: Learning About Quality Assessment

Recently assessment has become an important component of student affairs and higher education to assist in determining the effect and impact of programs and educational initiatives. To embrace this trend, the Office of Housing and Residence Life at Ball State University (IN) created learning outcomes for students living in residence halls. Through reflective questioning, discussion, and assessment, the Residence Life program strives to further the development and learning experience of students

KCNMA1 Encoded Cardiac BK Channels Afford Protection against Ischemia-Reperfusion Injury

Mitochondrial potassium channels have been implicated in myocardial protection mediated through pre-/postconditioning. Compounds that open the Ca2+-and voltage-activated potassium channel of big-conductance (BK) have a pre-conditioninglike effect on survival of cardiomyocytes after ischemia/reperfusion injury. Recently, mitochondrial BK channels (mitoBKs) in cardiomyocytes were implicated as infarct-limiting factors that derive directly from the KCNMA1 gene encoding for canonical BKs usually present at the plasma membrane of cells. However, some studies challenged these cardio-protective roles of mitoBKs. Herein, we present electrophysiological evidence for paxilline- and NS11021-sensitive BK-mediated currents of 190 pS conductance in mitoplasts from wild-type but not BK-/- cardiomyocytes. Transmission electron microscopy of BK-/- ventricular muscles fibres showed normal ultra-structures and matrix dimension, but oxidative phosphorylation capacities at normoxia and upon re-oxygenation after anoxia were significantly attenuated in BK-/- permeabilized cardiomyocytes. In the absence of BK, post-anoxic reactive oxygen species (ROS) production from cardiomyocyte mitochondria was elevated indicating that mitoBK fine-tune the oxidative state at hypoxia and reoxygenation. Because ROS and the capacity of the myocardium for oxidative metabolism are important determinants of cellular survival, we tested BK-/- hearts for their response in an ex-vivo model of ischemia/reperfusion (I/R) injury. Infarct areas, coronary flow and heart rates were not different between wild-type and BK-/- hearts upon I/R injury in the absence of ischemic pre-conditioning (IP),but differed upon IP. While the area of infarction comprised 28 +/- 3% of the area at risk in wild-type, it was increased to 58 +/- 5% in BK-/- hearts suggesting that BK mediates the beneficial effects of IP. These findings suggest that cardiac BK channels are important for proper oxidative energy supply of cardiomyocytes at normoxia and upon re-oxygenation after prolonged anoxia and that IP might indeed favor survival of the myocardium upon I/R injury in a BK-dependent mode stemming from both mitochondrial post-anoxic ROS modulation and non-mitochondrial localizations