Visfatin Impairs Endothelium-Dependent Relaxation in Rat and Human Mesenteric Microvessels through Nicotinamide Phosphoribosyltransferase Activity

Visfatin, also known as extracellular pre–B-cell colony–enhancing factor (PBEF) and nicotinamide phosphoribosyltransferase (Nampt), is an adipocytokine whose circulating levels are enhanced in metabolic disorders, such as type 2 diabetes mellitus and obesity. Circulating visfatin levels have been positively associated with vascular damage and endothelial dysfunction. Here, we investigated the ability of visfatin to directly impair vascular reactivity in mesenteric microvessels from both male Sprague-Dawley rats and patients undergoing non-urgent, non-septic abdominal surgery. The pre-incubation of rat microvessels with visfatin (50 and 100 ng/mL) did not modify the contractile response to noradrenaline (1 pmol/L to 30 µmol/L), as determined using a small vessel myograph. However, visfatin (10 to 100 ng/mL) concentration-dependently impaired the relaxation to acetylcholine (ACh; 100 pmol/L to 3 µmol/L), without interfering with the endothelium-independent relaxation to sodium nitroprusside (1 nmol/L to 3 µmol/L). In both cultured human umbilical vein endothelial cells and rat microvascular preparations, visfatin (50 ng/mL) stimulated nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity, as determined by lucigenin-derived chemiluminiscence. The relaxation to ACh impaired by visfatin was restored by the NADPH oxidase inhibitor apocynin (10 µmol/L). Additionally, the Nampt inhibitor APO866 (10 mmol/L to 10 µmol/L), but not an insulin receptor-blocking antibody, also prevented the stimulation of NADPH oxidase and the relaxation impairment elicited by visfatin. Accordingly, the product of Nampt activity nicotinamide mononucleotide (100 nmol/L to 1 mmol/L) stimulated endothelial NADPH oxidase activity and concentration-dependently impaired ACh-induced vasorelaxation. In human mesenteric microvessels pre-contracted with 35 mmol/L potassium chloride, the endothelium-dependent vasodilation to bradykinin (1 nmol/L to 3 µmol/L) was equally impaired by visfatin and restored upon co-incubation with APO866. In conclusion, visfatin impairs endothelium-dependent relaxation through a mechanism involving NADPH oxidase stimulation and relying on Nampt enzymatic activity, and therefore arises as a potential new player in the development of endothelial dysfunction

Il ritorno a casa secondo Primo Levi

Primo Levi recounts two journeys: a real one in La Tregua, and a fictitious one in Se non ora, quando? In both cases he has to deal with the romance’s structure and its stereotypes, which tend to negate realism. For this reason the writer adopts proceedings to defuse romance and happy ending

Emerging trends in reassessing translation, conflict, and memory

New Approaches on Translation, Conflict, and Memory: Narratives of the Spanish Civil War and the Dictatorship is a collection of essays that endeavours to establish a new dialogue between translation, conflict, and memory studies. Focusing on cultural representations of the Spanish Civil War and the Franco Dictatorship, it explores the significance and the effect of translation within Spain and beyond. Drawing on fictional and non-fictional texts, reports from war zones, and audiovisual productions, the contributors to this volume examine the scope of translation in transmitting the conflict and the dictatorship from a contemporary perspective. Narratives produced during and after the Civil War and the dictatorship both in Spain and abroad have led to new debates arising from the reassessment of a conflict that continues to resonate

The vision and the path (Volume 11)

What is Europe? A continent fragmented through the centuries by wars, border conflicts and cultural diversity. As Europeans, we do not have a common language or a common history, but we do have common roots, needs and ambitions. These similarities led us to fulfil what at the end of the Second World War could have been called a “reasonable utopia” — the European Union. The Spanish writer Javier Cercas investigates Europe and Europeans, our past, the conflicts, the ideologies and the people who forged Europe as we know it today. Though no final answer to all the questions can be found, the conclusion seems inevitable: Europe will be unified, naturally, sooner or later, despite all the hostility. This is the eleventh essay in the Big Ideas series created by the European Investment Bank. The EIB has invited international thought leaders to write about the most important issues of the day. These essays are a reminder that we need new thinking to protect the environment, promote equality and improve people’s lives around the globe

The vision and the path (Volume 11)

What is Europe? A continent fragmented through the centuries by wars, border conflicts and cultural diversity. As Europeans, we do not have a common language or a common history, but we do have common roots, needs and ambitions. These similarities led us to fulfil what at the end of the Second World War could have been called a “reasonable utopia” — the European Union. The Spanish writer Javier Cercas investigates Europe and Europeans, our past, the conflicts, the ideologies and the people who forged Europe as we know it today. Though no final answer to all the questions can be found, the conclusion seems inevitable: Europe will be unified, naturally, sooner or later, despite all the hostility. This is the eleventh essay in the Big Ideas series created by the European Investment Bank. The EIB has invited international thought leaders to write about the most important issues of the day. These essays are a reminder that we need new thinking to protect the environment, promote equality and improve people’s lives around the globe

"Los escritores somos recicladores de basura": conversación Sergio del Molino, Javier Cercas

El ganador del último premio Eñe, Javier Cercas, conversa con el director literario de la undécima edición del Festival, el escritor Sergio del Molino, acerca de los territorios fronterizos por los que transitan sus novelas, en las que va en busca de la persona que se esconde tras el héroe. El autor de “Soldados de Salamina (2001), “Anatomía de un instante” (2009) o “Terra alta” (Premio Planeta 2019) asegura que en esa búsqueda solo sigue el mandato de Cervantes

De l'any vuit i el dia. Joan Ferraté en persona

Taula rodona sobre Joan Ferraté, amb la intervenció del poeta i traductor Salvador Oliva; del poeta, assagista i editor literari, Jordi Cornudella i de l'escriptor i professor de Literatura espanyola de la Universitat de Girona, Javier Cerca