Nitric oxide synthesis and biological functions of nitric oxide released from ruthenium compounds

During three decades, an enormous number of studies have demonstrated the critical role of nitric oxide (NO) as a second messenger engaged in the activation of many systems including vascular smooth muscle relaxation. The underlying cellular mechanisms involved in vasodilatation are essentially due to soluble guanylyl-cyclase (sGC) modulation in the cytoplasm of vascular smooth cells. sGC activation culminates in cyclic GMP (cGMP) production, which in turn leads to protein kinase G (PKG) activation. NO binds to the sGC heme moiety, thereby activating this enzyme. Activation of the NO-sGC-cGMP-PKG pathway entails Ca2+ signaling reduction and vasodilatation. Endothelium dysfunction leads to decreased production or bioavailability of endogenous NO that could contribute to vascular diseases. Nitrosyl ruthenium complexes have been studied as a new class of NO donors with potential therapeutic use in order to supply the NO deficiency. In this context, this article shall provide a brief review of the effects exerted by the NO that is enzymatically produced via endothelial NO-synthase (eNOS) activation and by the NO released from NO donor compounds in the vascular smooth muscle cells on both conduit and resistance arteries, as well as veins. In addition, the involvement of the nitrite molecule as an endogenous NO reservoir engaged in vasodilatation will be described

Specific heat of quasi-2D antiferromagnetic Heisenberg models with varying inter-planar couplings

We have used the stochastic series expansion (SSE) quantum Monte Carlo (QMC) method to study the three-dimensional (3D) antiferromagnetic Heisenberg model on cubic lattices with in-plane coupling J and varying inter-plane coupling J_perp < J. The specific heat curves exhibit a 3D ordering peak as well as a broad maximum arising from short-range 2D order. For J_perp << J, there is a clear separation of the two peaks. In the simulations, the contributions to the total specific heat from the ordering across and within the layers can be separated, and this enables us to study in detail the 3D peak around T_c (which otherwise typically is dominated by statistical noise). We find that the peak height decreases with decreasing J_perp, becoming nearly linear below J_perp = 0.2J. The relevance of these results to the lack of observed specific heat anomaly at the ordering transition of some quasi-2D antiferromagnets is discussed.Comment: 7 pages, 8 figure

Growth inhibitory effects of 3′-nitro-3-phenylamino nor-beta-lapachone against HL-60: A redox-dependent mechanism

AbstractIn this study, the cytotoxicity, genotoxicity and early ROS generation of 2,2-dimethyl-(3H)-3-(N-3′-nitrophenylamino)naphtho[1,2-b]furan-4,5-dione (QPhNO2) were investigated and compared with those of its precursor, nor-beta-lapachone (nor-beta), with the main goal of proposing a mechanism of antitumor action. The results were correlated with those obtained from electrochemical experiments held in protic (acetate buffer pH 4.5) and aprotic (DMF/TBABF4) media in the presence and absence of oxygen and with those from dsDNA biosensors and ssDNA in solution, which provided evidence of a positive interaction with DNA in the case of QPhNO2. QPhNO2 caused DNA fragmentation and mitochondrial depolarization and induced apoptosis/necrosis in HL-60 cells. Pre-treatment with N-acetyl-l-cysteine partially abolished the observed effects related to the QPhNO2 treatment, including those involving apoptosis induction, indicating a partially redox-dependent mechanism. These findings point to the potential use of the combination of pharmacology and electrochemistry in medicinal chemistry