Objective-The cytosolic form of Cu/Zn-containing superoxide dismutase (SOD1) has peroxidase activity, with H 2 O 2 used as a substrate to oxidize other molecules. We examined peroxidase properties of the extracellular form of SOD (SOD3), a major isoform of SOD in the vessel wall, by using recombinant SOD3 and an in vivo model of atherosclerosis. Methods and Results-In the presence of HCO 3 Ϫ , SOD3 reacted with H 2 O 2 to produce a hydroxyl radical adduct of the spin trap 5-diethoxyphosphoryl-5methyl-1-pyrroline N-oxide (DEMPO). SOD1 and SOD3 were inactivated by H 2 O 2 in a dose-and time-dependent fashion, and this was prevented by physiological levels of uric acid. To examine the in vivo role of uric acid on SOD1 and SOD3, control and apolipoprotein E-deficient (ApoE Ϫ/Ϫ ) mice were treated with oxonic acid, which inhibits urate metabolism. This treatment increased plasma levels of uric acid in control and ApoE Ϫ/Ϫ mice by Ϸ3-fold. Although increasing uric acid levels did not alter aortic SOD1 and SOD3 protein expression, aortic SOD1 and SOD3 activities were increased by 2-to 3-fold in aortas from ApoE Ϫ/Ϫ mice but not in aortas from control mice. Conclusions-These studies show that SOD1 and SOD3 are partially inactivated in atherosclerotic vessels of ApoE See page 1367Extracellular SOD (SOD3) is also a Cu/Zu-containing SOD that shares Ϸ50% sequence homology with SOD1 within its catalytic region. 7 Compared with the x-ray crystallography structure data for SOD1, 8 all ligands to the copper and zinc atoms can be identified in SOD3, as can the cysteines forming the intramolecular disulfide bond. 7 Thus, these findings suggest that the conformation of the active copper-binding site of SOD3 may resemble the active site of SOD1. The rate constants for dismutation of O 2 ⅐Ϫ by SOD1 and SOD3 are similar, and both enzymes are inhibited by cyanide, azide, and diethyldithiocarbamate. 9 Because SOD3 constitutes 30% to 50% of the total SOD in vascular tissues 10 and is localized in the extracellular space, it would be of considerable importance to determine whether SOD3 also has peroxidase activity and to determine which small molecule reductants can preserve its dismutase activity.Although peroxidase properties of SOD1 have been studied extensively in vitro, evidence is lacking to prove that either SOD1 or SOD3 activities are affected by H 2 O 2 in vivo. In the present study, we sought to determine whether SOD3 has peroxidase activities that are similar to those of SOD1 and to examine small molecules that might prevent the inactivation of SOD3 by using recombinant SOD3 expressed in Pichia pastoris. In these experiments, we found that physiological levels of uric acid completely prevented the inactivation of SOD1 and SOD3 by H 2 O 2 . In additional experiments, we provide evidence for peroxidase activity of SOD1 and SOD3 in vivo, by showing that these enzymes seem to be partially inactivated in the aortas of apolipoprotein E-deficient (ApoE Ϫ/Ϫ ) mice and that the activity of these

In this randomized trial of TAVR procedural pharmacotherapy, bivalirudin did not reduce rates of major bleeding at 48 h or net adverse cardiovascular events within 30 days compared with heparin. Although superiority was not shown, the noninferiority hypothesis was met with respect to the latter factor. Given the lower cost, heparin should remain the standard of care, and bivalirudin can be an alternative anticoagulant option in patients unable to receive heparin in TAVR. (International, Multi-center, Open-label, Randomized Controlled Trial in Patients Undergoing TAVR to Determine the Treatment Effect [Both Safety and Efficacy] of Using Bivalirudin Instead of UFH [BRAVO-2/3]; NCT01651780).

No abstract

No abstract

Although RM in CIEDs may be a clinically valuable technological armamentarium, its activation does not reflect patients' clinical profile. In fact, RM is often not activated, most probably because it is still recognized as a source of increased workload in a reality where reimbursement plans for dedicated human resources are not yet optimized.