The activity of [(18)F]WC-II-89 was also compared with [(99m)Tc]mebrofenin. The effect of pan-caspase inhibition with quinolyl-valyl-O-methylaspartyl[2,6-difluorophenoxy]-methyl ketone (Q-VD-OPh) on [(18)F]WC-II-89 uptake was studied. Caspase-3 activity was confirmed by a fluorometric enzyme assay.

Results: All three tracers behaved similarly in microPET

and biodistribution studies. Increased retention of all tracers was observed in the livers of treated animals and several other organs, all of which demonstrated increased caspase-3 enzyme activity; however, impaired hepatobiliary excretion made attribution of these findings to caspase-3 activity difficult. The isatin [(18)F]WC-II-89 Selleck Veliparib was retained at statistically significantly higher levels in the organs after anti-Fas antibody treatment while [(99m)Tc]mebrofenin activity cleared, suggesting specific binding to activated caspase-3, but the magnitude of increased binding vas still relatively low. Caspase inhibition with Q-VD-OPh partially blocked [(18)F]WC-II-89 retention but completely blocked caspase-3 enzyme activity in the liver.

Conclusions: The racholabeled isatins appear to bind specifically to caspase-3 in vivo, but their sensitivity is limited. Further optimization is required for these tracers to be useful for clinical applications. (C) 2012 Elsevier Inc. All rights reserved.”
“Intermediate

filament (IF) E7080 proteins belong to a large and diverse gene family with broad representation in vertebrate tissues. Although considered the ‘toughest’ cytoskeletal fibers, studies in cultured cells have revealed

that IF can be surprisingly dynamic and highly regulated. This review examines the diversity of IF assembly behaviors, and considers the ideas that IF proteins are co- or post-translationally PDE4B assembled into oligomeric precursors, which can be delivered to different subcellular compartments by microtubulles or actomyosin and associated motor proteins. Their interaction with other cellular elements via IF associated proteins (IFAPs) affects IF dynamics and also results in cellular networks with properties that transcend those of individual components. We end by discussing how mutations leading to defects in IF assembly, network formation or IF-IFAP association compromise in vivo functions of IF as protectors against environmental stress.”
“Objectives: We hypothesize that concomitant tricuspid annuloplasty in patients with tricuspid annular dilatation who undergo mitral valve repair could prevent progression of tricuspid regurgitation and right ventricular remodeling.

Methods: In 2002, 80 patients underwent mitral valve repair. Concomitant tricuspid annuloplasty was performed in 13 patients with grade 3 or 4 tricuspid regurgitation.