It remains uncertain whether the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) reduce cardiovascular risk.OBJECTIVE To determine the effects on cardiovascular outcomes of a carboxylic acid formulation of EPA and DHA (omega-3 CA) with documented favorable effects on lipid and inflammatory markers in patients with atherogenic dyslipidemia and high cardiovascular risk.

Objectives-Nebivolol, in contrast to other selective ␤ 1 -adrenergic receptor antagonists like atenolol, improves endothelial function in patients with oxidative stress within vascular tissue. With the present studies we sought to determine whether ␤ receptor blockade with nebivolol may improve endothelial function in hyperlipidemia and whether this is attributable to reductions in vascular oxidative stress. Methods and Results-Watanabe heritable hyperlipidemic rabbits (WHHL) were treated with nebivolol (10 mg/kg per day for 8 weeks). New Zealand white rabbits (NZWR) served as controls. Nebivolol improved endothelial function, reduced vascular superoxide and vascular macrophage infiltration, and prevented NO synthase uncoupling in WHHL. Nebivolol treatment did not modify the expression of sGC or cGK-I but improved cGK-I activity (assessed by the phosphorylation state of the VAsodilator Stimulated Phosphoprotein at serine 239 , P-VASP). NAD(P)H oxidase activity in whole blood and isolated neutrophils was dose-dependently inhibited by nebivolol, whereas atenolol, metoprolol, and carvedilol were markedly less effective. Key Words: nebivolol Ⅲ NO synthase Ⅲ superoxide Ⅲ neutrophils Ⅲ NADPH oxidase ␤ -Adrenergic receptor blockers have become a mainstay in the management of unstable and stable angina and acute myocardial infarction as well as in the treatment of patients with hypertension and chronic congestive heart failure. Third-generation ␤ receptor blockers comprise substances that block selectively the ␤ 1 -receptor and that also have vasodilator properties attributable to simultaneous ␣-receptor blocking effects. Interestingly, the vasodilatory properties of the third-generation ␤-blocker nebivolol revealed to be mediated by the release of the endotheliumderived relaxing factor NO. Nebivolol-induced vasodilation was almost completely blocked by the inhibitors of the NO synthase L-NMMA. 1 In vitro studies revealed that this phenomenon is at least in part attributable to stimulation of ␤ 2 receptors on endothelial cells by nebivolol metabolites, leading to an increase in endothelial [Ca 2ϩ ] levels and subsequently to NO synthase (NOS) III activation. 2 Chronic treatment with nebivolol has also been shown to improve endothelial function in patients with essential hypertension. 3 Interestingly, endothelial function in the setting of hypertension has recently been shown to be improved by the antioxidant vitamin C, suggesting that this phenomenon may be partly attributable to increased production of superoxide. 4 The beneficial effects on endothelial function in hypertensive patients may therefore indicate that nebivolol treatment inhibits vascular superoxide production. Indeed, recent studies revealed that antihypertensive doses of nebivolol decreased oxidative stress in healthy volunteers, reflected by a decrease in the formation of the isoprostane 8-iso-PGF 2␣ . 5 Indirect evidence for antioxidative properties of nebivolol was recently provided by in vitro experiments. Incubation of cultured endothelial as well...

Cinaciguat unloaded the heart in patients with ADHF. However, high doses were associated with hypotension.

In this contribution, a spotlight is given to Janus nanoparticles, which offer a promising future for interfacial applications, such as catalysis, and different biomedical purposes ranging from drug delivery to tissue regeneration. Here, we briefly describe different chemical strategies to design Janus particles with targeted functionalization and physicochemical attributes. A special focus is given on the interfacial activity of Janus nanoparticles, which helps to use them for emulsion stabilization, catalysis, compatibilizer, etc. As the Janus nanoparticles have different chemical functionality on different sides, they can be used for loading multiple drugs and drugs in combination with contrast agents. This makes them suitable for drug delivery and cell imaging. Additionally, we review recent developments in using Janus architecture for tissue regeneration. We also pay special attention to a much overlooked aspect of understanding the interaction of Janus particles, having surface anisotropy with the biological environment, which in turn can be used to adjust the responses as desired. Finally, we discuss different milestones that need to be mastered in order to achieve their desired fate.