Enantioselective organocatalytic conjugate addition of aldehydes to nitrodienes

The asymmetric organocatalyzed Michael addition of aldehydes to alpha,beta-gamma,delta-unsaturated nitro compounds has been accomplished using only 5 mol % of (S)-diphenylprolinol silyl ether and 2 equiv of aldehyde in a mixture of ethanol and water (5% v/v). The Michael adducts were obtained in good yields, diastereoselectivities up to 94/6, and ee's up to 99%. This process provides synthetically useful compounds which can easily lead to more complex molecules, as exemplified with substituted tetrahydropyran or cyclohexene

Discovery of a New Class of Potent MMP Inhibitors by Structure-Based Optimization of the Arylsulfonamide Scaffold

A new class of potent matrix metalloproteinase (MMP) inhibitors designed by structure-based optimization of the well-known arylsulfonamide scaffold is presented. Molecules show an ethylene linker connecting the sulfonamide group with the P1′ aromatic portion and a d-proline residue bearing the zinc-binding group. The affinity improvement provided by these modifications led us to discover a nanomolar MMP inhibitor bearing a carboxylate moiety as zinc-binding group, which might be a promising lead molecule. Notably, a significant selectivity for MMP-8, MMP-12, and MMP-13 was observed with respect to MMP-1 and MMP-7

Telemedicina applicata:il caso di studio di "Telemeliolab"

Il progetto telemeliolab,in sperimentazione nella Regione Puglia,rappresenta un chiaro esempio di telemedicina applicata ai processi di deospetalizzazione in ambito oncologico.La piattaforma software progettuale consente di mettere in comunicazione la control room del policlinico di Bari con i pazienti affetti da gammapatia monoclonale sia MGUS (monoclonal component of undetermined signifiance) che mieloma multiplo potendo controllare a distanza l'evoluzione della patologia gestendo e pianificando gli esami ematochimici da effettuare nei laboratori di analisi aderenti al progett

Homocysteine induces VCAM-1 gene expression through NF-κB and NAD(P)H oxidase activation: Protective role of Mediterranean diet polyphenolic antioxidants

Hyperhomocysteinemia is a recognized risk factor for vascular disease, but pathogenetic mechanisms involved in its vascular actions are largely unknown. Because VCAM-1 expression is crucial in monocyte adhesion and early atherogenesis, we evaluated the NF-κB-related induction of VCAM-1 by homocysteine (Hcy) and the possible inhibitory effect of dietary polyphenolic antioxidants, such as trans-resveratrol (RSV) and hydroxytyrosol (HT), which are known inhibitors of NF-κB-mediated VCAM-1 induction. In human umbilical vein endothelial cells (HUVEC), Hcy, at 100 μmol/l, but not cysteine, induced VCAM-1 expression at the protein and mRNA levels, as shown by enzyme immunoassay and Northern analysis, respectively. Transfection studies with deletional VCAM-1 promoter constructs demonstrated that the two tandem NF-κB motifs in the VCAM-1 promoter are necessary for Hcy-induced VCAM-1 gene expression. Hcy-induced NF-κB activation was confirmed by EMSA, as shown by the nuclear translocation of its p65 (RelA) subunit and the degradation of the inhibitors IκB-α and IκB-β by Western analysis. Hcy also increased intracellular reactive oxygen species by NAD(P)H oxidase activation, as shown by the membrane translocation of its p47 phox subunit. NF-κB inhibitors decreased Hcy-induced intracellular reactive oxygen species and VCAM-1 expression. Finally, we found that nutritionally relevant concentrations of RSV and HT, but not folate and vitamin B6, reduce (by >60% at 10 -6 mol/l) Hcy-induced VCAM-1 expression and monocytoid cell adhesion to the endothelium. These data indicate that pathophysiologically relevant Hcy concentrations induce VCAM-1 expression through a prooxidant mechanism involving NF-κB. Natural Mediterranean diet antioxidants can inhibit such activation, suggesting their possible therapeutic role in Hcy-induced vascular damage