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Abstract A new bismuth-based CT agent was synthesized through a facile synthesis strategy. The in vitro stability, toxicity and CT performance were evaluated. The in vivo imaging performance was investigated using three different doses (0.5, 1.2 and 5 mmol/kg) and the result obtained at 1.2 mmol/kg was compared with the clinically approved CT agent iopamidol at the same dosage.

Nuclear Magnetic Resonance allows the non-invasive detection and quantitation of metabolites to be carried out in cells and tissues. This means that that metabolic changes can be revealed without the need for sample processing and the destruction of the biological matrix. The main limitation to the application of this method to biological studies is its intrinsic low sensitivity. The introduction of hyperpolarization techniques and, in particular, of dissolution-Dynamic Nuclear Polarization (d-DNP) and ParaHydrogen Induced Polarization (PHIP) is a significant breakthrough for the field as the MR signals of molecules and, most importantly, metabolites, can be increased by some orders of magnitude. Hyperpolarized pyruvate is the metabolite that has been most widely used for the investigation of metabolic alterations in cancer and other diseases. Although d-DNP is currently the gold-standard hyperpolarization method, its high costs and intrinsically slow hyperpolarization procedure are a hurdle to the application of this tool. However, PHIP is cost effective and fast and hyperpolarized pyruvate can be obtained using the so-called Side Arm Hydrogenation approach (PHIP-SAH). The potential toxicity of a solution of the hyperpolarized metabolite that is obtained in this way is presented herein. HP pyruvate has then been used for metabolic studies on different prostate cancer cells lines (DU145, PC3, and LnCap). The results obtained using the HP metabolite have been compared with those from conventional biochemical assays.

Nowadays, magnetic resonance imaging (MRI) is one of the key, noninvasive modalities to detect and stage cancer which benefits from contrast agents (CA) to differentiate healthy from tumor tissue. An innovative class of MRI CAs is represented by Gd-loaded gold nanoparticles. The size, shape and chemical functionalization of Gd-loaded gold nanoparticles appear to affect the observed relaxation enhancement of water protons in their suspensions. The herein reported results shed more light on the determinants of the relaxation enhancement brought by Gd-loaded concave cube gold nanoparticles (CCGNPs). It has been found that, in the case of nanoparticles endowed with concave surfaces, the relaxivity is remarkably higher compared to the corresponding spherical (i.e., convex) gold nanoparticles (SPhGNPs). The main determinant for the observed relaxation enhancement is represented by the occurrence of a large contribution from second sphere water molecules which can be exploited in the design of high-efficiency MRI CA.

Hyperpolarization of 13C carboxylate signals of metabolicallyrelevant molecules, such as acetate and pyruvate, was recently obtainedby means of ParaHydrogen Induced Polarization by Side Arm Hydrogenation(PHIP-SAH). This method relies on functionalization of the carboxylicacid with an unsaturated alcohol (side arm), hydrogenation of theunsaturated alcohol using parahydrogen, and polarization transferto the target 13C signal. In this case, parahydrogen protonsare added three to four bonds away from the target 13Cnucleus, while biologically relevant molecules had been hyperpolarized,using parahydrogen, through hydrogenation of an unsaturated bond adjacentto the target 13C signal. The herein reported results showthat the same polarization level can be obtained on the 13C carboxylate signal of an ester by means of addition of parahydrogento the acidic or to the alcoholic moiety and successive applicationof magnetic field cycle (MFC). Experimental results are supportedby calculations that allow one to predict that, upon accurate controlof magnetic field strength and speed of the passages, more than 20%polarization can be achieved on the 13C-carboxylate resonanceof the esters by means of side arm hydrogenation and MFC. [ABSTRACT FROM AUTHOR]

A novel Gd(iii) complex with a modified DO3A-like chelating cage has been synthesized and characterized as a candidate contrast agent responsive to the concentration of free thiols in tissues (essentially represented by reduced glutathione, GSH). The novel compound (called Gd-DO3AS-Act) bears a flexible linker ending with a 2-pyridyl-dithio group, that can promptly react with free thiols (XSH) to form mixed disulfides of the form Gd-DO3AS-SX. Compound Gd-DO3AS-Act is characterized by a millimolar relaxivity as high as 8.1 mM−1 s−1 (at 20 MHz, 25 °C and pH 7.4). Upon reaction with GSH, the Gd-DO3AS-SG covalent adduct is formed and the millimolar relaxivity drops to 4.1 mM−1 s−1. Such a decrease in relaxivity is explained on the basis of the formation of an intramolecular coordinative bond between one of the glutathionyl carboxyl groups and the Gd(iii) centre, lowering the hydration state of the paramagnetic centre. 1H-NMR dispersion profiles together with 17O-NMR transverse relaxation time versus temperature profiles confirm that the hydration of the Gd(iii) centre is strongly reduced ongoing from Gd-DO3AS-Act to the Gd-DO3AS-SG adduct. The relaxivity difference brought about by the reaction of Gd-DO3AS-Act with GSH can be enhanced up to 60% in the presence of poly-β-cyclodextrin. [ABSTRACT FROM AUTHOR]

En Dewey, filosofia i educació són indestriables. Sovint s’oblida que la concepció deweyana de l’escola i de l’educació només ha estat possible perquè Dewey concebia el pensament en termes d’experiència viscuda, d’experiència constantment posada a prova, de recerca sempre posada en qüestió; en altres termes, de «recerca contínua» de «vies d’acció efectives». Però a més, per Dewey, la vertadera educació és una educació per a la democràcia, i significa apostar per una educació que s’ocupi del fet de pensar. El servei al progrés democràtic es fa precisament a través d’una educació en la raonabilitat i tenint en compte l’experiència. Paraules clau: Dewey, democràcia, educació, experiència, mètode científic.