The involvement of the receptor for advanced glycation end products (RAGE)-ligand axis in liver transplantation: hepatic RAGE expression, soluble RAGE and RAGE-ligand levels

BACKGROUND. In animal testing the blockade of the receptor for advanced glycation end products (RAGE) attenuates the liver injury extent induced by RAGE-ligands. Likewise circulating truncated soluble isoforms of RAGE (sRAGE), acting as decoy of RAGE-ligands, protects by injury. AIM. The primary objective of this study was to investigate the association between tissue RAGE isoform (both full-length and truncated) mRNA expression with both recipient liver disease and early outcomes after liver transplantation. Secondarily, to evaluate trends of circulating RAGE-ligands and of protective sRAGE in the immediate period following transplantation and their association with the development of early organ dysfunction METHODS. We prospectively included 28 adult LT recipients (53±8.7 years) of primary whole-size grafts by deceased donors (62.1±17.3 years). In liver biopsies of both donor and LT recipients, we measured the transcriptional expression of full-length RAGE and its truncated isoform, the endogenous secreted RAGE (esRAGE). The RAGE-ligands — N(epsilon)-carboxymethyllysine (CML) and high-mobility group protein 1 (HMGB-1) — and the circulating sRAGE were measured in plasma specimens before LT, after graft reperfusion, 1 and 7 days after LT. RESULTS. In LT recipients the hepatic RAGE mRNA levels were higher than in healthy donors (p<0.01). In LT recipients the tissue full-length RAGE inversely correlated with antithrombin III (β= -0.58, p = 0.013) and cholinesterase plasma levels (β= -0.717, p= 0.0018) and directly correlated with MELD score before LT, likewise to basal HMGB-1 plasma levels (β=0.425, p=0.043 and β=0.448, p<0.05 respectively). Basal CML levels were higher in LT recipient than donors (p=0.02), decreased after graft reperfusion (p<0.0001) but returned progressively to basal values at 7 days after LT. HMGB-1 levels increased after graft reperfusion (p<0.0001) and returned suddenly to basal values one day after LT while circulating sRAGE did not change soon after LT but decreased significantly 7 days after LT (p<0.0001). The MELD score 7 days after LT inversely correlated with graft esRAGE mRNA expression (β= -0.487, p=0.029) and tended to correlate directly with the peak values of HMGB-1 after reperfusion (β = 0.42, p = 0.07), with recipient age (β = 0.38, p = 0.07) and recipient gender (β = 0.49, p = 0.015). Multivariate analysis showed that, after adjustment for gender, donor age, recipient age, only graft esRAGE mRNA expression was a significant determinant of MELD score 7 days after LT (β= -0.788, p=0.0005). CONCLUSIONS. The inverse correlation between graft esRAGE mRNA expression and the MELD score 7 days after LT underline the importance of this protective factor for graft survival and patient outcomes. CML accumulation and rapid increase of HMGB-1 followed by remarkable decline of protective sRAGE could have deleterious consequences on graft survival and long term outcomes in LT recipients

Protective role of adiponectin on endothelial dysfunction induced by AGEs: A clinical and experimental approach

Objective: Obesity is characterized by low levels of adiponectin, an adipocytes derived hormone, and by an inflammatory component. Endothelial dysfunction is often found in overweight/obesity, diabetes, and atherosclerosis. Advanced glycation end products (AGEs) induce endothelial dysfunction and are linked to diabetes and increased atherogenicity and inflammation. The aim of the study was to investigate the possible link between adiponectin and N(epsilon)-(carboxymethyl) lysine (CML), the predominant adduct of circulating AGEs in overweight patients, and, in an in vitro model, to test the hypothesis that adiponectin acts as modulator of endothelial dysfunction, induced by AGEs. Results: In 108 overweight patients, plasma levels of CML correlated inversely with adiponectin levels. Preincubation of human vein endothelial cells (HUVECs) with physiological concentrations of adiponectin, followed by stimulation with AGEs, reduced vascular adhesion molecule-1 (VCAM-1) and E-selectin expression, as assessed by surface enzyme immunoassay. Conclusions: Taken together, these findings demonstrate an inverse correlation between CML and adiponectin levels in overweight patients and a protective role of adiponectin on endothelial dysfunction induced by AGEs, suggesting its key role in the treatment of the vascular complications of obesity/metabolic syndrome

Protective role of adiponectin on endothelial dysfunction induced by AGEs: a clinical and experimental approach

OBJECTIVE: Obesity is characterized by low levels of adiponectin, an adipocytes derived hormone, and by an inflammatory component. Endothelial dysfunction is often found in overweight/obesity, diabetes, and atherosclerosis. Advanced glycation end products (AGEs) induce endothelial dysfunction and are linked to diabetes and increased atherogenicity and inflammation. The aim of the study was to investigate the possible link between adiponectin and N(epsilon)-(carboxymethyl) lysine (CML), the predominant adduct of circulating AGEs in overweight patients, and, in an in vitro model, to test the hypothesis that adiponectin acts as modulator of endothelial dysfunction, induced by AGEs. RESULTS: In 108 overweight patients, plasma levels of CML correlated inversely with adiponectin levels. Pre-incubation of human vein endothelial cells (HUVECs) with physiological concentrations of adiponectin, followed by stimulation with AGEs, reduced vascular adhesion molecule-1 (VCAM-1) and E-selectin expression, as assessed by surface enzyme immunoassay. CONCLUSIONS: Taken together, these findings demonstrate an inverse correlation between CML and adiponectin levels in overweight patients and a protective role of adiponectin on endothelial dysfunction induced by AGEs, suggesting its key role in the treatment of the vascular complications of obesity/metabolic syndrom

Elevated soluble receptor for advanced glycation end product levels in patients with acute coronary syndrome and positive cardiac troponin I

Objectives High levels of soluble receptor for advanced glycation end products (sRAGE) have been shown to have an atheroprotective role; however, no data are available on this molecule in acute coronary syndromes (ACS). We evaluated sRAGE levels in patients with non-ST segment elevation ACS (NSTE-ACS) or with chronic stable angina. Methods We studied 265 patients, 190 of whom had NSTE-ACS and 75 had chronic stable angina. Results Plasma sRAGE values were comparable in the two groups (P= 0.19). However, in the patients with NSTEACS,sRAGE levels were significantly higher in patients with cardiac troponin-I (cTnI) of more than or equal to 0.04 lg/l compared with those with cTnI of less than 0.04 lg/l [758 pg/ml (493-1536 pg/ml) vs. 454 pg/ml (167-899 pg/ml); P = 0.0037]. A significant correlation(r= 0.323, P = 0.0045) was found between sRAGE and cTnI levels in patients with NSTE-ACS.Conclusion Plasma sRAGE levels are elevated in patients with NSTE-ACS with positive cTnI, suggesting that they could be related to myocardial cell damage

Occult hepatitis B virus infection predicts non-alcoholic steatohepatitis in severely obese individuals from Italy

Obesity is associated with\ua0non-alcoholic fatty liver (NAFL), which may progress towards non-alcoholic steatohepatitis (NASH), cirrhosis and hepatocellular carcinoma (HCC). Occult hepatitis B virus infection (OBI) may contribute to hepatic damage in patients with\ua0chronic liver disease\ua0of different aetiologies (eg\ua0HCV, alcohol). However, information on the prevalence and clinical impact of OBI in obese individuals is lacking. The aims of this study were to investigate NASH prevalence and risk factors in obese people who underwent bariatric surgery

Measurement of the cosmic ray spectrum above 4×10184{\times}10^{18} eV using inclined events detected with the Pierre Auger Observatory

A measurement of the cosmic-ray spectrum for energies exceeding $4{\times}10^{18}$ eV is presented, which is based on the analysis of showers with zenith angles greater than $60^{\circ}$ detected with the Pierre Auger Observatory between 1 January 2004 and 31 December 2013. The measured spectrum confirms a flux suppression at the highest energies. Above $5.3{\times}10^{18}$ eV, the "ankle", the flux can be described by a power law $E^{-\gamma}$ with index $\gamma=2.70 \pm 0.02 \,\text{(stat)} \pm 0.1\,\text{(sys)}$ followed by a smooth suppression region. For the energy ($E_\text{s}$) at which the spectral flux has fallen to one-half of its extrapolated value in the absence of suppression, we find $E_\text{s}=(5.12\pm0.25\,\text{(stat)}^{+1.0}_{-1.2}\,\text{(sys)}){\times}10^{19}$ eV.Comment: Replaced with published version. Added journal reference and DO

XXII Setmana Internacional de Cinema Fomatiu. L’Educació Lliure i el Cinema Formatiu

XXII Setmana Internacional de Cinema Fomatiu: L’Educació Lliure i el Cinema Formatiu. 21 al 25 de novembre de 2016. Sala d'actes. Palau de les heures. Campus Mundet, Universitat de Barcelona.Fa 22 anys vàrem iniciar, arrel de la celebració del centenari del naixement del cinema, una activitat que encara avui mantenim: la SETMANA DE CINEMA FORMATIU. Una activitat per a aprofundir en una estratègia didàctica a partir del model ORA, dissenyat per un col·lectiu de professorat pertanyent al grup GIAD, concretament Saturnino de la Torre, Maria de Borja, Núria Rajadell i Maria Dolors Millan. Després d‟haver superat ja dues dècades seguim oferint aquest punt de trobada entre professorat i estudiants de diferents ensenyaments, amb la finalitat de debatre i reflexionar al voltant d‟una temàtica concreta, i, depenent de la temàtica seleccionada, i eixamplant la col·laboració amb altres institucions i professionals que treballen de manera específica amb la temàtica seleccionada. El Seminari de Cinema Formatiu, depenent del GIAD (Grup d‟Investigació i Assessorament Didàctic) de la Facultat d‟Educació de la Universitat de Barcelona, promou aquesta activitat però és un seminari de treball i de recerca obert a totes aquelles persones que estiguin interessades en el cinema, i puntualment a aquelles persones que estan interessades per la temàtica específica que es tracta al llarg de la Setmana. Alguns estudiants s‟han implicat i han passat a formar part del Seminari que l‟organitza. Aquest és l‟èxit i la raó d‟aquesta activitat, la implicació i la participació, el diàleg i l‟expressió de totes les persones que participen. Aquest any, arrel de l‟interessant debat que existeix en la nostra societat sobre la importància, necessitat i eficiència de l‟actual Sistema Educatiu, i amb la incorporació d‟entitats que es troben més enllà de l‟Administració i que han creat col·lectius per a aprofundir i visibilitzar la innovació educativa a les aules,hem considerat que podria ser interessant conèixer experiències més aviat trencadores del sistema escolar en què ens trobem immersos. Considerem interessant conèixer i reflexionar al voltant de propostes innovadores en el marc de l‟educació i la formació en un escenari complex, obert i global, com és en el que ens trobem immersos en aquests moments. Aquesta setmana comptem amb la col·laboració d‟un equip de professionals de diferents universitats i de diferents escoles catalanes que ens aportaran el seu coneixement des d‟un escenari privilegiat del nostre petit país com és Catalunya. Comptem, a més, amb una sèrie de pel·lícules que es visionaran i debatran en algunes de les classes, i amb una conferenciant que ha estat investigant en el marc de l‟educació lliure a Itàlia i a Catalunya, la Dra. Aurora Bosna