Objective-Hyperglycemia is the main determinant of long-term diabetic complications, mainly through induction of oxidative stress. NAD(P)H oxidase is a major source of glucose-induced oxidative stress. In this study, we tested the hypothesis that rosiglitazone (RSG) is able to quench oxidative stress initiated by high glucose through prevention of NAD(P)H oxidase activation. Methods and Results-Intracellular ROS were measured using the fluoroprobe TEMPO-9-AC in HUVECs exposed to control (5 mmol/L) and moderately high (10 mmol/L) glucose concentrations. NAD(P)H oxidase and AMPK activities were determined by Western blot. We found that 10 mmol/L glucose increased significantly ROS production in comparison with 5 mmol/L glucose, and that this effect was completely abolished by RSG. Interestingly, inhibition of AMPK, but not PPAR␥, prevented this effect of RSG. AMPK phosphorylation by RSG was necessary for its ability to hamper NAD(P)H oxidase activation, which was indispensable for glucose-induced oxidative stress. Downstream of AMPK activation, RSG exerts antioxidative effects by inhibiting PKC. Conclusions-This study demonstrates that RSG activates AMPK which, in turn, prevents hyperactivity of NAD(P)H oxidase induced by high glucose, possibly through PKC inhibition. Therefore, RSG protects endothelial cells against glucose-induced oxidative stress with an AMPK-dependent and a PPAR␥-independent mechanism. (Arterioscler

Time-resolved electron paramagnetic resonance (TREPR) spectroscopy was used to study two functionalized fullerenes consisting of a C60 moiety covalently linked to TEMPO radical via spacers of different length. Photoinduced electron spin polarization (ESP) reflecting a non-Boltzmann population within the energy levels of the spin system was observed in the electronic ground and excited states. Both fullerenes are characterized by a sign inversion of their TREPR spectra. A new mechanism of ESP generation was suggested to explain the experimental results. This mechanism, termed as the reversed quartet mechanism (RQM), includes the intersystem crossing process, which generates ESP in the excited trip-doublet and trip-quartet (2T1 and 4T1) states. This ISC is accompanied by ESP transfer to the ground state (2S0) by either electron-transfer reaction (in our case via charge transfer state, 2CT, i.e., 2T1--> 2CT --> 2S0 or internal conversion, 2T1--> 2S0.

The reactions of pyrazole (Hpz) with some copper(II) carboxylates in the presence of water yield trinuclear copper derivatives characterized by the triangular core [Cu3mu3-OH)(mu-pz)3(RCOO)2] (R = H, C2H5, C3H7). Copper(II) formate gives [Cu3(mu3-OH)(mu-pz)3(HCOO)2(Hpz)2] (1), whereas copper propionate and butyrate afford [Cu3(mu3-OH)(mu-pz)3(C2H5COO)2(EtOH)] (2) and [Cu3(mu3-OH)(mu-pz)3(C3H7COO)2(MeOH)(H2O)] (3), respectively, both containing solvent molecules coordinated to copper atoms. Magnetic susceptibilities are consistent with a single unpaired electron for each trinuclear unit of 1-3, and EPR measurements indicate that higher spin states, generated by exchange coupling between copper atoms, may be populated at room temperature. Density-functional calculations provide the description of the electronic structures of 1-3, allowing, at the same time, the assignment of their UV-vis absorption spectra. X-ray molecular structure determinations show that triangular trinuclear units of 1 are connected to each other through single formate bridges, forming one-dimensional (1D) zigzag coordination polymers, whereas in 2 and 3, two oxygen atoms of two carboxylate ions doubly bridge two copper atoms of different triangles, thus generating hexanuclear units. Moreover, in 2, two other propionate ions link together two hexanuclear units yielding a 12-membered cycle and giving rise to 1D coordination polymers. The supramolecular assemblies of 1-3 are compared to that of the previously reported trinuclear triangular copper(II) derivative [Cu3(mu3-OH)(mu-pz)3(CH3COO)2(Hpz)] (A), where a two-dimensional (2D) coordination polymer is present. The reactions of 3,5-dimethylpyrazole (Hpz) with copper(II) carboxylates in the same conditions yield 1:2 Cu(RCOO)2/Hpz adducts.

BackgroundThe biological and clinical significance of multifocal and multicentric (MF/MC) breast cancers and the choice of appropriate surgical treatment for these tumors are still debated.Methods1158 women operated on for a stage I-III breast cancer were included in this retrospective study; clinical and pathological data were obtained from the institutional database of the Department of Oncology of the University of Siena, Italy. The impact of MF/MC breast cancers on patterns of recurrence and breast cancer specific survival (BCSS) was investigated in relation to the type of surgical treatment.ResultsMF and MC cancers were present in 131 cases (11.3%) and 60 cases (5.2%) respectively and were more frequently treated with mastectomy (55 MF and 60 MC cancers, 81.2%) than with breast conserving surgery (36 MF cancers, 18.9%; p < 0.001). MF and MC breast cancers were associated with a worse prognosis with a BCSS of 154 months compared to 204 months of unicentric cancers (p < 0.001). In multivariate analysis, MF/MC cancers were independent prognostic factors for BCSS together with higher number of metastatic axillary nodes, absence of estrogen receptors and high proliferative activity. MF and MC cancers were related to a significantly shorter BCSS in patients submitted to mastectomy as well as those submitted to breast conserving surgery. Relapse at any site was higher in the subgroup of MF and MC cancers but the incidence of loco-regional and distant recurrences did not differ between patients treated with mastectomy or breast conserving surgery.ConclusionsOur results indicate that MF/MC cancers have a negative impact on prognosis and are related to higher loregional and distant relapse independently from the type of surgery performed. Adjuvant therapies did not modify the poorer outcome, but in patients receiving adjuvant anthacyclines, the differences with unicentric tumors were reduced. Our data support the hypothesis that MF/MC tumors may have a worse biological behavior and that the presence of multiple foci should be considered in planning adjuvant treatments.