SGLT2is and Renal Protection: From Biological Mechanisms to Real-World Clinical Benefits

In recent years, following the publication of results from several RCTs, first on cardiovascular and more recently on renal outcomes, SGLT2is have become the standard of care to prevent diabetic kidney disease and slow its progression. This narrative review focuses on biological mechanisms, both renal and extrarenal, underlying kidney protection with SGLT2is. Furthermore, data from cardiovascular as well as renal outcome trials, mostly conducted in diabetic patients, are presented and discussed to provide an overview of current uses as well as the future therapeutic potential of these drugs.     

Adhesion of resin cements to contaminated zirconia resin cements on zirconia: effect saliva-contamination and surface conditioning

This study evaluated the adhesion of resin cements to zirconia after saliva contamination using resin cements with different chemistries. Zirconia discs (N?=?240, n?=?10 per group) were randomly divided into three groups: (a) C: No contamination (Control), (b) S: Contamination with saliva, (c) S?+?AA: Contamination with saliva followed by air-abrasion (CoJet). While half of the specimens were not conditioned, the other half were conditioned with 37.5% H₃PO₄ for 60?s. After rinsing, all specimen surfaces were silanized (Monobond Plus). Resin cements based on either methacrylate (Variolink II–VL) or MDP monomer (Panavia 21-PN) were polymerized on the substrates. The specimens were randomly divided into two further groups to be tested either after (a) 24?h dry storage at 37?°C or (b) thermocycling (×5000, 5–55?°C). Microshear bond (MSB) tests were conducted in a Universal Testing Machine and failure types were analyzed. Data were analyzed using Univariate analysis and Tukey’s tests (alpha = 0.05). While saliva contamination, 37.5% H₃PO₄ application (p?<?.001) and aging (p?<?.05) significantly affected the bond results, cement type did not show significant difference after aging (p?>?.05). Adhesive strength of PN (1.2–4.4?MPa) on saliva contaminated and etched zirconia was more stable than that of VL (0–2.8?MPa). After aging, bond strength results decreased the most with VL (3–100%) compared to PN (32–71%) but the decrease was less in the air-abraded groups after aging (VL: 3%; PN: 32%). Exclusively adhesive failures were experienced in all groups.     

A2B Adenosine Receptors: When Outsiders May Become an Attractive Target to Treat Brain Ischemia or Demyelination

Adenosine is a signaling molecule, which, by activating its receptors, acts as an important player after cerebral ischemia. Here, we review data in the literature describing A_2BR-mediated effects in models of cerebral ischemia obtained in vivo by the occlusion of the middle cerebral artery (MCAo) or in vitro by oxygen-glucose deprivation (OGD) in hippocampal slices. Adenosine plays an apparently contradictory role in this receptor subtype depending on whether it is activated on neuro-glial cells or peripheral blood vessels and/or inflammatory cells after ischemia. Indeed, A_2BRs participate in the early glutamate-mediated excitotoxicity responsible for neuronal and synaptic loss in the CA1 hippocampus. On the contrary, later after ischemia, the same receptors have a protective role in tissue damage and functional impairments, reducing inflammatory cell infiltration and neuroinflammation by central and/or peripheral mechanisms. Of note, demyelination following brain ischemia, or autoimmune neuroinflammatory reactions, are also profoundly affected by A_2BRs since they are expressed by oligodendroglia where their activation inhibits cell maturation and expression of myelin-related proteins. In conclusion, data in the literature indicate the A_2BRs as putative therapeutic targets for the still unmet treatment of stroke or demyelinating diseases.     

Nanostructured TiO2-based mixed metal oxides prepared using microemulsions for carbon monoxide detection

Nanostructured powders of Nb-doped TiO₂ (TN) and SnO₂ mixed with Nb-doped TiO₂ in two different atomic ratios—10 to 1 (TSN 101) and 1 to 1 (TSN 11)—were synthesized using the reverse micelle microemulsion of a nonionic surfactant (brine solution/1-hexanol/Triton X-100/cyclohexane). The powders were characterized by transmission electron microscopy (TEM) and X-ray diffraction (XRD). Thick films were fabricated for gas sensors and characterized by XRD analysis and field emission scanning electron microscopy (FE-SEM). The effects of the film morphology and firing temperature in the range 650–850 °C on CO sensitivity were studied. The best gas response, expressed as the ratio between the resistance in air and the resistance under gas exposure (R _air/R _gas), was measured for TSN 11 at 11 for 1,000 ppm CO exposure. All types of sensors showed good thermal stability. The electrochemical impedance spectroscopy (EIS) measurements were performed in different gas atmospheres (air, O₂, CO and NO₂) to better understand the electrical properties of the nanostructured mixed metal oxides.     

A Birkhoff interpolation problem and application

A Birkhoff interpolation problem is studied. The explicit solution and estimation of remainder is given. The cases of equidistant and Chebyshev nodes are considered. This problem is of interest in collocation methods of boundary value problem (Costabile and Napoli in Far East J. Appl. Math. 25(3):289–305, 2006; Costabile and Longo in Applied and Industrial Mathematics in Italy III, 2009, in press). In addition an application to quadrature is given.     

Apoptotic DNA fragmentation can be revealed in situ: An ultrastructural approach

A common pattern of apoptotic death is DNA cleavage, initially producing large fragments (50 kbp), followed by the production of nucleosomic/oligonucleosomic fragments. Nevertheless, apoptosis without DNA fragmentation, at least of the nucleosomic type, has been reported. To investigate the spatial relationship between DNA cleavage and chromatin condensation, we applied the TUNEL technique to the ultrastructural analysis of apoptotic cells. A modified method, utilizing a gold‐conjugated antidigoxigenin antibody, was carried out on U937 versus Molt‐4 cells, both exposed to UVB radiation or staurosporine treatment. Gold particle density in the different domains of apoptotic cells was evaluated by a four‐way ANOVA test. Gold labelling was more strongly localised in condensed chromatin than in the diffuse chromatin. U937 cells, which evidenced in vitro oligonucleosomic fragmentation after both UVB and staurosporine treatments, revealed a significantly higher gold particle density, when compared with Molt‐4, which did not show, on the other hand, oligonucleosomic cleavage even in the presence of ≤50 kbp cleavage. Thus, a correlation between DNA fragment sizes and gold particle density appears. TUNEL applied to electron microscopy is an effective approach to study the relationship between apoptotic chromatin condensation and DNA cleavage. Both these events indeed appear in the apoptotic nucleus, but their reciprocal correlation is still greatly unknown. Microsc. Res. Tech. 2009. © 2009 Wiley‐Liss, Inc.