Search

La relation établie par Jean Abélanet entre les toponymes « arabes » et les sites archéologiques, souvent évidente, pose néanmoins un problème à l’historien. Ces noms Jurent attribués à des lieux dont les vestiges, connus mais incompris des contemporains, étaient expliqués par un passé mythique. En relation avec un corpus légendaire bien attesté sur l’ensemble de l’arc pyrénéen (Roland, Charlemagne, etc.) leur naissance est, pour les plus précoces d’entre eux, à rapprocher de la diffusion populaire de légendes attachées à l’idéologie de la Reconquête. Mais la fabrication vernaculaire de ces toponymes ne s’est pas limitée à la période médiévale. Elle a largement débordé sur l’époque moderne, voire contemporaine, mêlant l’histoire immédiate — car la proximité de la piraterie sarrasine a pu entretenir l’image du musulman comme celle du malfaisant par excellence — au goût pour les contes fantastiques que les premiers folkloristes ont recensés, parfois aussi embellis, voire forgés. Pourtant, aujourd’hui encore, des historiens catalans continuent à chercher par l’étude de certaines associations de noms dérivés, selon eux, de la langue arabe, des informations sur l’occupation musulmane de la Catalogne Vieille. La relació establerta per Jean Abelanet entre els topònims «arabs» i els sites arqueològics, sovint evident, posa tanmateix un problema a l’historiador. Aquests noms van ser atribuïts a llocs els vestigis dels quais, coneguts però incompressos dels contemporanis, eren explicats per un passai mític. En relació amb un corpus llegendari ben atestat sobre el conjunt de l’arc pirinenc (Rotllà, Carlemany, etc.) llur naixement és, pels més precoços d’entre ells, a apropar de la difusió popular de llegendes lligades a la ideologia de la Reconquesta. Però la fabricació vernacular d’aquests topònims no s’ha limitat al període medieval. Ha sobreposat amplament l’època moderna, fins i tot contempàrania, i tot mesclant la història immediata - perquè la proximitat de la pirateria saraína ha pogut mantenir la imatge del musulmà com la del malfactor per excel, lència - al gust pels contes fantàstics que els primers folkloristes han compilat, a vegades també embellits i tot forjats. Tanmateix, avuidia encara, historiadors catalans continuen a cercar, segons ells, mitjançant l’estudi de certes associacions de noms derivais de la llengua àrab, informacions sobre l’occupació musulmana de la Catalunya Vella. The link established by Jean Abélanet between the «Arab» toponyms and the archaeological sites, though often obvious, raises a problem to the historian. Those names were given to places whose vestiges, known but not understood by the contemporaries, were explained by a mythical past. Having relations with a legendary corpus well attested on the whole Pyrenean (Roland, Charlemagne), their birth is, for the earliest ones, to be connected with the popular circulation of legends linked to the Reconquest ideology. The vernacular making of those toponyms is not limited to the Middle Ages. It has largely overflown modern and even contemporary periods, mingling immediate history — for the nearness of Saracenic piracy could foster the image of the Moslem as the Villain in the highest sens of the word-with a taste for fantastic tales that the first folklorists inventoried, sometimes embellished or even invented. And yet, today, some Catalan historians are still searching information on the Mohammedan occupation of Old Catalonia, by means of the study of some associations of words which, according to them, derived from the Arabic.

Jean Abélanet peut être considéré comme le pionnier de l'archéologie actuelle sur les terres nord-catalanes. Ce rôle de précurseur dans la découverte de sites majeurs, mais aussi sa contribution savante à l'avancée des études préhistoriques, tant sur le mégalithisme en Pyrénées que sur l'art rupestre post-glaciaire en Europe occidentale, justifient l'hommage qui lui est rendu par la communauté des chercheurs. Cet hommage a pris la forme d'un colloque placé sous l'égide de l'Association Archéologique des Pyrénées-Orientales, dont il fut membre fondateur, et de l'Université de Perpignan, dont il fut le premier enseignant en Préhistoire. Sont rassemblées dans cet ouvrage les contributions de 74 auteurs et co-auteurs. Ces 576 pages, abondamment illustrées par près de 300 figures, abordent des sujets très divers qui reflètent les différents champs d'études balayés par son insatiable et humaniste curiosité. Une première partie, remontant aux sources des arts et des mythes, éclaire certains aspects de l'art rupestre et du mégalithisme, depuis leurs origines jusqu'à nos jours, à partir de recherches récentes menées dans l'Ancien monde, des terres australes d'Afrique jusqu'en Europe de l'Ouest. Le second thème, tout en laissant une large place à l'étude des arts et des traditions funéraires, rassemble des travaux pluridisciplinaires menés à l'orient des Pyrénées, travaux d'historiographie, de palynologie, de géologie, d'archéologie préhistorique et historique, d'histoire ou d'ethnologie.

Cold storage of organs in preservation solutions, such as Institute George Lopez 1 (IGL-1) or histidine-tryptophan-ketoglutarate (HTK), is a mandatory step for organ transplantation. This preservation leads to an ischemic injury that affects the outcome of the organ. This article studies the liver graft eluate after organ recovery using IGL-1 or HTK solutions. We explore the influence of the volume used for washing out the liver and the consequences in the graft preservation when both solutions are used. Livers were washed out with different volumes of HTK and IGL-1 according to manufacturers' instructions and then preserved in both solutions for 24 hours at 4°C. Tissue and eluates were collected for subsequent analyses. We measured transaminases (aspartate aminotransferase and alanine aminotransferase), histology by hematoxylin/eosin staining, and red blood cell and hemoglobin counts, respectively. After washing out and cold storage, the IGL-1 processed livers showed better preservation than those with HTK solution; however, in this latter case, an important accumulation of erythrocytes was found when compared to IGL-1. These data were consistent with the higher hemoglobin and red blood cell counts observed for IGL-1 eluates after 24 hours. The volume used for washing out the organ depends on the composition and properties of the organ preservation solutions (ie, IGL-1 and HTK); this is an important factor for the graft cold preservation. The total volume used for washing out the graft should be considered because it has a direct impact on the total cost for clinical transplantations., Supported by Instituto de Salud Carlos III (ISCIII) through the FIS project PI12/0056 cofunded by FEDER from Regional Development European Funds (European Union). Sravan Bellogi was fellowship-holder from project FOIE GRAS, from the European Union's Horizon 2020 Research and Innovation programme under the Marie Sklodowska-Curie Grant Agreement No. 722619.

Institute Goeorges Lopez 1 (IGL-1) and Histidine-Tryptophan-Ketoglutarate (HTK) preservation solutions are regularly used in clinical for liver transplantation besides University of Wisconsin (UW) solution and Celsior. Several clinical trials and experimental works have been carried out comparing all the solutions, however the comparative IGL-1 and HTK appraisals are poor; especially when they deal with the underlying protection mechanisms of the fatty liver graft during cold storage. Fatty livers from male obese Zücker rats were conserved for 24 h at 4 ◦C in IGL-1 or HTK preservation solutions. After organ recovery and rinsing of fatty liver grafts with Ringer Lactate solution, we measured the changes in mechanistic target of rapamycin (mTOR) signaling activation, liver autophagy markers (Beclin-1, Beclin-2, LC3B and ATG7) and apoptotic markers (caspase 3, caspase 9 and TUNEL). These determinations were correlated with the prevention of liver injury (aspartate and alanine aminostransferase (AST/ALT), histology) and mitochondrial damage (glutamate dehydrogenase (GLDH) and confocal microscopy findings). Liver grafts preserved in IGL-1 solution showed a marked reduction on p-TOR/mTOR ratio when compared to HTK. This was concomitant with significant increased cyto-protective autophagy and prevention of liver apoptosis, including inflammatory cytokines such as HMGB1. Together, our results revealed that IGL-1 preservation solution better protected fatty liver grafts against cold ischemia damage than HTK solution. IGL-1 protection was associated with a reduced liver damage, higher induced autophagy and decreased apoptosis. All these effects would contribute to limit the subsequent extension of reperfusion injury after graft revascularization in liver transplantation procedures., This work was supported by Instituto de Salud Carlos III through FIS project PI 12/0056 co-funded by FEDER from Regional Development European Funds (European Union) and the FOIE GRAS project, which has received funding from the European Union’s Horizon 2020 Research and Innovation programme under the Marie Sklodowska-Curie Grant (Agreement No. 722619).

In the Roussillon area, several scheduled archaeological digs were conducted in the heart of villages between 2010 and 2015. These operations were part of a collective research project entitled “ Villages of yesteryear, villages of today” whose objective was to determine the contribution of planning, history, social occurrences and religious events to the shape and template of current villages. The results presented, stemming from three archaeological digs, provide new data on the origin of village forms set in place by fortifications in the 12th to 13th centuries and which are the fruit of a constant and critical dialogue between historians, archaeologists and geomorphologists. They also highlight the role of the environmental conditions specific to the alluvial plain in the transformation of village topography., En Roussillon, plusieurs fouilles archéologiques programmées ont été menées au coeur de villages, entre 2010 et 2015. Ces opérations s’inscrivaient dans le cadre d’un Projet Collectif de Recherches intitulé «Villages d’hier, villages d’aujourd’hui » qui avait pour objectif de déterminer la part de l’urbanisme, de l’histoire, des événements sociaux et religieux dans la forme et la trame actuelle du village. Les résultats présentés ici, issus de trois fouilles archéologiques, offrent des données nouvelles sur la genèse de la forme villageoise fixée par les mises en fortification des XIIe-XIIIe siècles et sont le fruit d’un dialogue constant et critique entre historien, archéologue et géomorphologue. Ils mettent également en lumière le rôle des conditions environnementales, propres à la plaine alluvionnaire, dans la transformation de la topographie villageoise., Entre 2010 y 2015 se realizaron varias excavaciones arqueológicas programadas en el corazón de algunos pueblos del Roseelón. Estas operaciones formaban parte de un proyecto de investigación colectiva titulado «Aldeas de ayer, aldeas de hoy » , que tenía por objetivo determinar la influencia de la planificación urbana, la historia y los acontecimientos sociales y religiosos en la forma y estructura actuales de los pueblos. Los resultados que aquí se presentan, fruto de tres excavaciones arqueológicas, aportan nuevos datos sobre la génesis de la forma del pueblo definidas por las fortificaciones de los siglos XII-XIII y son el fruto de un diálogo constante y crítico entre historiador, arqueólogo y geomorfólogo. También destacan el papel de las condiciones ambientales, específicas de la llanura aluvial, en la transformación de la topografía de las aldeas., Passarrius Olivier,Catafau Aymat,Bénézet Jérôme,Carozza Jean-Michel,Illes Pauline,Lambert Sylvain. Autour de quelques villages du Roussillon : le cadastre et les textes à l’épreuve de l’archéologie. In: Archéologie du Midi médiéval. Tome 36, 2018. Numéro spécial. L'archéologie au village. Le village et ses transformations, du Moyen Âge au premier cadastre. Actes du colloque de Perpignan, 20-22 septembre 2017 - Travaux réunis par Olivier Passarrius et Aymat Catafau. pp. 253-265.

International audience

As a biomarker of beta-amyloid, positron emission tomography (PET) amyloid imaging offers a unique opportunity to detect the presence of this protein in the human body during life. Besides Alzheimer’s disease (AD), deposits of beta-amyloid in the brain are also present in other neurodegenerative diseases associated to dementia, such as Parkinson’s disease and dementia with Lewy bodies, as well as in other processes affecting brain function, such as cerebral amyloid angiopathy, brain trauma, Down’s syndrome and meningiomas, as shown by post-mortem pathology studies. Furthermore, in systemic amyloidosis other organs besides the brain are affected, and amyloid PET imaging may be suitable for the identification of these extra-cerebral amyloid depositions. Finally, the potential use of amyloid PET tracer accumulation in cerebral white matter (WM) as a marker of myelin is being investigated, leading to some promising results in patients with WM lesions and multiple sclerosis. In this article, a review of the ongoing research pointing to a broader application of amyloid PET imaging in clinical practice beyond AD is provided.

Objective: To investigate brain β-amyloid binding in subjects with Down syndrome (DS) using [ 18 F]florbetaben PET imaging. Methods: Thirty-nine subjects with DS (46.3 ± 4.7 years) were assessed with [ 18 F]florbetaben PET imaging. Three blinded independent readers assessed the scans to provide a visual analysis. The primary quantitative imaging outcome was a standardized uptake value ratio (SUVR) obtained for 6 brain regions. Cognitive status was evaluated using the Dementia Screening Questionnaire for Individuals with Intellectual Disabilities (DSQIID). Results: [ 18 F]Florbetaben uptake was correlated with age ( p R 2 = 0.39); 90% of scans in subjects with DS aged 50 years or older (SUVR = 1.62 ± 0.26), 53% in those aged 45 to 49 years (SUVR = 1.43 ± 0.16), and 7% in those aged 40 to 45 years (SUVR = 1.27 ± 0.11) were visually assessed as positive. Visual and quantitative assessments were highly related (χ 2 = 11.3823, p = 0.0007; Cohen κ = 0.58). Only 2 of 34 participants were considered to have dementia by the DSQIID. Conclusions: Brain β-amyloid binding, as measured by [ 18 F]florbetaben, increases with age in DS. Subjects with DS who have no evidence of dementia demonstrate brain β-amyloid binding in vivo, suggesting that [ 18 F]florbetaben PET imaging may detect β-amyloid in this at-risk population.

Melatonin (Mel) is widely used to attenuate ischemia/reperfusion (I/R) injury in several organs. Nevertheless, the underlying mechanisms remain unclear. This study was conducted to explore the effect of Mel on endoplasmic reticulum (ER) stress, Akt and MAPK cascades after renal warm I/R. Eighteen Wistar rats were randomized into three groups: Sham, I/R, and Mel + I/R. The ischemia period was 60 min followed by 120 min of reperfusion. Mel (10 mg/kg) was administrated 30 min prior to ischemia. The creatinine clearance, MDA, LDH levels, and histopathological changes were evaluated. In addition, Western blot was performed to study ER stress and its downstream apoptosis as well as phosphorylation of Akt, GSK-3β, VDAC, ERK, and P38. Mel decreased cytolysis and lipid peroxidation and improved renal function and morphology compared to I/R group. Parallely, it significantly reduced the ER stress parameters including GRP 78, p-PERK, XBP 1, ATF 6, CHOP, and JNK. Simultaneously, p-Akt level was significantly enhanced and its target molecules GSK-3βand VDAC were inhibited. Furthermore, the ERK and P38 phosphorylation were evidently augmented after Mel administration in comparison to I/R group. In conclusion, Mel improves the recovery of renal function by decreasing ER stress and stimulating Akt pathway after renal I/R injury.

Les médiévistes, historiens ou archéologues, s’intéressent, ce n’est pas nouveau, à l’histoire du peuplement et de ses structures. Les origines du village ont ainsi été l’objet de recherches variées, ainsi que de premières synthèses ou confrontations d’expériences. Il ne nous semble pas inutile d’apporter ici un élément de réflexion à ce débat, tiré de l’exemple particulier des villages concentrés nés en Roussillon autour d’une cellera, le groupement de celliers, dépôts des récoltes, dans le ...

Aux lisières de l’Occident chrétien et d’al-Andalus, parcourue par les Pyrénées et bordée par la mer, la Catalogne fut, tout au long du Moyen Age, un carrefour de civilisations, une terre de frontières. Non pas une Catalogne, mais plusieurs. C’est à ces terres et aux hommes qui y vécurent que sont consacrées les dix-huit contributions que regroupe cet ouvrage.

De nos jours, violences et insécurité occupent une place importante dans les médias et semblent la préoccupation majeure de la société. Qu'en était-il autrefois ? Les violences étaient-elles omniprésentes ? Une évolution des notions de normes sociales et d'infraction à celles-ci s'est-elle produite ? Cet ouvrage, publication d'un colloque tenu à l'université de Perpignan, regroupe les points de vue d'historiens, d'archéologues et de juristes. Ceux-ci proposent diverses interprétations des sources narratives, normatives, des traités juridiques, des archives judiciaires qui permettent d'approcher violences individuelles et violences collectives. Quelques communications traitent des rapports entre l'État et la violence, rapports qui peuvent être éclairés par le droit pénal, la répression des violences, les lois d'exception. Les pratiques actuelles de l'État fixant des limites juridiques au travail des historiens sont aussi abordées. Colloque subventionné par l'Université de Perpignan Via Domitia, le département d'histoire, le CRHISM, l'école Doctorale, la mairie de Perpignan, la région Languedoc-Roussillon. Ouvrage publié avec le concours du CRHISM.

En quoi consiste la violence aristocratique au Moyen Âge central ? Quelles formes prend-elle, qui sont les coupables et les victimes ? Les sources qui nous permettent de les connaître varient selon les époques et les auteurs. Je me suis intéressé ici à la manière dont des documents très différents, distants de deux siècles, parlent de la violence. L’un de ces documents est le célèbre sermon du moine Garsias de Cuxa, non daté, sans doute des années 1043-1046. Il a suscité l’attention des histo...

The 26S proteasome is the central proteolytic machinery of the ubiquitin proteasome system (UPS), which is involved in the degradation of ubiquitinated protein substrates. Recently, UPS inhibition has been shown to be a key factor in fatty liver graft preservation during organ cold storage using University of Wisconsin solution (UW) and Institute Georges Lopez (IGL-1) solutions. However, the merits of IGL-1 and histidine-tryptophan-ketoglutarate (HTK) solutions for fatty liver preservation have not been compared. Fatty liver grafts from obese Zücker rats were preserved for 24 h at 4 ◦C. Aspartate aminotransferase and alanine aminotransferase (AST/ALT), glutamate dehydrogenase (GLDH), ATP, adenosine monophosphate protein kinase (AMPK), e-NOS, proteasome activity and liver polyubiquitinated proteins were determined. IGL-1 solution prevented ATP breakdown during cold-storage preservation of steatotic livers to a greater extent than HTK solution. There were concomitant increases in AMPK activation, e-NOS (endothelial NOS (NO synthase)) expression and UPS inhibition. UPS activity is closely related to the composition of the solution used to preserve the organ. IGL-1 solution provided significantly better protection against ischemia-reperfusion for cold-stored fatty liver grafts than HTK solution. The effect is exerted through the activation of the protective AMPK signaling pathway, an increase in e-NOS expression and a dysregulation of the UPS., This work was supported by Instituto de Salud Carlos III (ISCIII) through the FIS project PI12/0056 co-funded by FEDER from Regional Development European Funds (European Union).

We assessed the clinical utility of β-amyloid (Aβ) imaging with (18)F-florbetaben (FBB) in mild cognitive impairment (MCI) by evaluating its prognostic accuracy for progression to Alzheimer's disease (AD), comparing semiquantitative with visual scan assessment, and exploring the relationships among Aβ, hippocampal volume (HV) and memory over time.45 MCI underwent FBB positron emission tomography, MRI and neuropsychological assessment at baseline and 2 years and clinical follow-up at 4 years. Positive FBB (FBB+), defined by a cortical to cerebellar cortex standardised uptake value ratio (SUVR) ≥ 1.45, was compared with visual assessment by five readers. Amnestic MCI (aMCI) was defined by a composite episodic memory (EM) Z-score of-1.5.At baseline, 24 (53%) MCI were FBB+. Majority reads agreed with SUVR classification (κ 0.96). In 2 years, 18 (75%) FBB+ progressed to AD compared with 2 (9.5%) FBB-, yielding a predictive accuracy of 83% (95% CI 61% to 94%). Four FBB- developed non-AD dementia. Predictive accuracies of HV (58% (95% CI 42% to 73%)) and aMCI status (73% (95% CI 58% to 81%)) were lower. Combinations did not improve accuracy. By 4 years, 21 (87.5%) FBB+ had AD whereas 5 (24%) FBB- had non-AD dementia yielding a predictive accuracy of 94% (95% CI 74% to 99%). While the strong baseline association between FBB SUVR and EM declined over 2 years, the association between EM and HV became stronger. FBB SUVR increased 2.2%/year in FBB+ with no change in FBB-.(18)F-florbetaben Aβ imaging facilitates accurate detection of prodromal AD. As neurodegeneration progresses, and in contrast with the early stages of the disease, hippocampal atrophy and not Aβ, seems to drive memory decline.NCT01138111.

We investigated the involvement of glycogen synthase kinase-3β (GSK3β) and the voltage-dependent anion channel (VDAC) in livers subjected to cold ischemia–reperfusion injury (I/R) associated with orthotopic liver transplantation (OLT). Rat livers were preserved in University of Wisconsin (UW) and Institute Georges Lopez (IGL-1) solution, the latter enriched or not with trimetazidine, and then subjected to OLT. Transaminase (ALT) and HMGB1 protein levels, glutamate dehydrogenase (GLDH), and oxidative stress (MDA) were measured. The AKT protein kinase and its direct substrates, GSK3β and VDAC, as well as caspases 3, 9, and cytochrome C and reticulum endoplasmic stress-related proteins (GRP78, pPERK, ATF4, and CHOP), were determined by Western blot. IGL-1+TMZ significantly reduced liver injury. We also observed a significant phosphorylation of AKT, which in turn induced the phosphorylation and inhibition of GSK3β. In addition, TMZ protected the mitochondria since, in comparison with IGL-1 alone, we found reductions in VDAC phosphorylation, apoptosis, and GLDH release. All these results were correlated with decreased ER stress. Addition of TMZ to IGL-1 solution increased the tolerance of the liver graft to I/R injury through inhibition of GSK3β and VDAC, contributing to ER stress reduction and cell death prevention., The authors would like to thank Michael Maudsley at the Language Advisory Service of the University of Barcelona for revising the English text. This work was supported by Instituto de Salud Carlos III (ISCIII) through the FIS project PI12/0056 co-funded by FEDER from Regional Development European Funds (European Union)., We acknowledge support by the CSIC Open Access Publication Initiative through its Unit of Information Resources for Research (URICI).

International audience

Resumen del póster presentado al OCC World Congress and Annual SFRR-E Conference: "Metabolic Stress and Redox Regulation", celebrados en Berlin (Alemania) del 21 la 23 de junio de 2017., Liver steatosis is associated with mitochondrial dysfunction and elevated Reactive Oxygen Species (ROS) levels together with enhanced sensitivity to IR injury and limited response to preconditioning protocols. Here, we sought to determine whether the downregulation in the steatotic liver of PGC-1a, a master regulator of mitochondrial metabolism and ROSl, could be responsible for the sensitivity of steatotic liver to ischemic damage. PGC-1a was induced in normal liver following exposure to an IR protocol concomitant with an increase in the levels of antioxidant proteins. By contrast, its induction was severely blunted in steatotic liver, resulting in a modest induction of antioxidant proteins. Livers of PGC-1a-/- mice on chow diet were normal, but they exhibited an enhanced sensitivity to IR injury and also a lack of response to ischemic preconditioning, a phenotype that recapitulated the features of steatotic liver in terms of liver damage. Utilizing an in vitro model of IPC, we found that PGC-1a expression was downregulated in hepatic cells cultured at 1% O2 whereas it was induced following reoxygenation (3% O2), and was responsible for the recovery of antioxidant gene expression following the ischemic period. We concluded that PGC-1a plays an important role in the protection against IR injury in the liver, which is likely associated with its capacity to induce antioxidant gene expression., Funding was provided by MINEICO, FEDER Funds, Comunidad Autónoma de Madrid, ISCIII.

[AIM] To compare liver proteolysis and proteasome activation in steatotic liver grafts conserved in University of Wisconsin (UW) and Institut Georges Lopez-1 (IGL-1) solutions, [METHODS] Fatty liver grafts from male obese Zücker rats were conserved in UW and IGL-1 solutions for 24 h at 4 ℃ and subjected to “ex vivo ” normo-thermic perfusion (2 h; 37 ℃). Liver proteolysis in tissue specimens and perfusate was measured by reverse-phase high performance liquid chromatography. Total free amino acid release was correlated with the activation of the ubiquitin proteasome system (UPS: measured as chymotryptic-like activity and 20S and 19S proteasome), the prevention of liver injury (transaminases), mitochondrial injury (confocal microscopy) and inflammation markers (TNF 1 alpha, high mobility group box-1 (HGMB-1) and PPAR gamma), and liver apoptosis (TUNEL assay, cytochrome c and caspase 3)., [RESULTS] Profiles of free AA (alanine, proline, leucine, isoleucine, methionine, lysine, ornithine, and threonine, among others) were similar for tissue and reperfusion effluent. In all cases, the IGL-1 solution showed a significantly higher prevention of proteolysis than UW (p < 0.05) after cold ischemia reperfusion. Livers conserved in IGL-1 presented more effective prevention of ATP-breakdown and more inhibition of UPS activity (measured as chymotryptic-like activity). In addition, the prevention of liver proteolysis and UPS activation correlated with the prevention of liver injury (AST/ ALT) and mitochondrial damage (revealed by confocal microscopy findings) as well as with the prevention of inflammatory markers (TNF1alpha and HMGB) after reperfusion. In addition, the liver grafts preserved in IGL-1 showed a significant decrease in liver apoptosis, as shown by TUNEL assay and the reduction of cytochrome c, caspase 3 and P62 levels., [CONCLUSION] Our comparison of these two preservation solutions suggests that IGL-1 helps to prevent ATP breakdown more effectively than UW and subsequently achieves a higher UPS inhibition and reduced liver proteolysis., Supported by Instituto de Salud Carlos III (ISCIII) through the FIS project PI12/0056, co-funded by FEDER from Regional Development European Funds (European Union).

[Background] Sirtuin 1 (SIRT1) is a nicotinamide adenine dinucleotide +–dependent histone deacetylase that regulates various pathways involved in ischemia-reperfusion injury (IRI). Moreover, high-mobility group box 1 protein (HMGB1) has also been involved in inflammatory processes during IRI. However, the roles of both SIRT1 and HMGB1 in liver preservation is poorly understood. In this communication, we evaluated the potential relationship between SIRT1 and HMGB1 in steatotic and non-steatotic liver grafts preserved in Institute Georges Lopez solution (IGL-1) preservation solution enriched or not enriched with trimetazidine (TMZ)., [Methods] Steatotic and non-steatotic livers were preserved in IGL-1 preservation solution (24 hours, 4°C), enriched or not enriched with TMZ (10 μmol/L), and then submitted to ex vivo reperfusion (2 hours; 37°C). Liver injury (AST/ALT) and function (bile output, vascular resistance) were evaluated. SIRT1, HMGB1, autophagy parameters (beclin-1, LC3B), PPAR-γ, and heat-shock protein (HO-1, HSP70) expression were determined by means of Western blot. Also, we assessed oxidative stress, mitochondrial damage (glutamate dehydrogenase), and TNF-α levels., [Results] Elevated SIRT1 and enhanced autophagy were found after reperfusion in steatotic livers preserved in IGL-1+TMZ when compared with IGL-1. However, these changes were not seen in the case of non-steatotic livers. Also, HO-1 increases in the IGL-1 + TMZ group were evident only in the case of steatotic livers, whereas HSP70 and PPAR-γ protein expression were enhanced only in non-steatotic livers. All reported changes were consistent with decreased liver injury diminution, ameliorated hepatic function, and decreased TNF-α and HMGB levels. In addition, the oxidative stress and mitochondrial damage were efficiently prevented by the IGL-1 + TMZ use., [Conclusions] SIRT1 is associated with HMGB1 decreases and increased autophagy in steatotic livers, contributing to increased tolerance to cold IRI., This work was supported by Instituto de Salud Carlos III (ISCIII) through the FIS project PI12/0056, co-funded by FEDER from Regional Development European Funds (European Union).

The need for innovation in research is leading to an increased use of imaging biomarkers, which have shown to reduce timings and increase productivity, thus saving costs. PET and SPECT neurotransmission imaging has shown usefulness in the discovery and development of drugs for the central nervous system, providing unique information on drug-target interactions in the living human brain. Among the different therapeutic areas, antipsychotic drugs pioneered the application of these technologies in early phases of development. PET and SPECT radioligands for the most commonly targeted neurotransmission systems in the development of these drugs, such as the dopaminergic and serotoninergic systems are available, thus fostering the inclusion of PET and SPECT studies in the antipsychotic drug development plans. Radioligands for other neurotransmission systems more recently implicated in the pathophysiology of schizophrenia, such as the glutamatergic system, are being currently investigated. This review focuses on neurotransmission PET and SPECT aiming to serve as guidance for procedure requirements and methodology choices to be applied in antipsychotic drug development, through specific examples. Cutting-edge study designs and quantification approaches will be reviewed. Finally, some clues to get the most out of the PET and SPECT studies in the development of antipsychotic drugs will be provided.