Fatty acids, eicosanoids, and hypolipidemic agents identified as ligands of peroxisome proliferator-activated receptors by coactivator-dependent receptor ligand assay.

Peroxisome proliferator-activated receptors (PPARs) are nuclear hormone receptors controlling the expression of genes involved in lipid homeostasis. PPARs activate gene transcription in response to a variety of compounds including hypolipidemic drugs as well as natural fatty acids. From the plethora of PPAR activators, Scatchard analysis of receptor-ligand interactions has thus far identified only four ligands. These are the chemotactic agent leukotriene B4 and the hypolipidemic drug Wy 14,643 for the alpha-subtype and a prostaglandin J2 metabolite and synthetic antidiabetic thiazolidinediones for the gamma-subtype. Based on the hypothesis that ligand binding to PPAR would induce interactions of the receptor with transcriptional coactivators, we have developed a novel ligand sensor assay, termed coactivator-dependent receptor ligand assay (CARLA). With CARLA we have screened several natural and synthetic candidate ligands and have identified naturally occurring fatty acids and metabolites as well as hypolipidemic drugs as bona fide ligands of the three PPAR subtypes from Xenopus laevis. Our results suggest that PPARs, by their ability to interact with a number of structurally diverse compounds, have acquired unique ligand-binding properties among the superfamily of nuclear receptors that are compatible with their biological activity.

Integrating novel agents into multiple myeloma treatment - current status in Switzerland and treatment recommendations.

The treatment of multiple myeloma has undergone significant changes in the recent past. The arrival of novel agents, especially thalidomide, bortezomib and lenalidomide, has expanded treatment options and patient outcomes are improving significantly. This article summarises the discussions of an expert meeting which was held to debate current treatment practices for multiple myeloma in Switzerland concerning the role of the novel agents and to provide recommendations for their use in different treatment stages based on currently available clinical data. Novel agent combinations for the treatment of newly diagnosed, as well as relapsed multiple myeloma are examined. In addition, the role of novel agents in patients with cytogenetic abnormalities and renal impairment, as well as the management of the most frequent side effects of the novel agents are discussed. The aim of this article is to assist in treatment decisions in daily clinical practice to achieve the best possible outcome for patients with multiple myeloma.

Adverse reactions to biologic agents and their medical management.

Biologic agents have substantially advanced the treatment of immunological disorders, including chronic inflammatory and autoimmune diseases. However, these drugs are often associated with adverse events (AEs), including allergic, immunological and other unwanted reactions. AEs can affect almost any organ or system in the body and can occur immediately, within minutes to hours, or with a delay of several days or more after initiation of biologic therapy. Although some AEs are a direct consequence of the functional inhibition of biologic-agent-targeted antigens, the pathogenesis of other AEs results from a drug-induced imbalance of the immune system, intermediary factors and cofactors, a complexity that complicates their prediction. Herein, we review the AEs associated with biologic therapy most relevant to rheumatic and immunological diseases, and discuss their underlying pathogenesis. We also include our recommendations for the medical management of such AEs. Increased understanding and improved risk management of AEs induced by biologic agents will enable better use of these versatile immune-response modifiers.

Intangible Capital: An opportunity for PhD students and junior researchers

El objetivo de esta editorial es exponer los hitos más importantes acontecidos durante el año 2008, en el que se publicó el volumen 4, los datos de visibilidad y por primera vez los resultados de una encuesta de satisfacción realizada a los autores que han enviado durante 2008 alguna publicación a evaluación. Además, en el anexo se expone la relación de revisores y miembros del Editorial Board que han hecho posible el cuarto volumen de Intangible Capital. También se informa sobre los aspectos que indican el principio de una consolidación de la revista, y la importancia de mantener los principios básicos que dieron origen a esta publicación. Concluimos la editorial animando a directores de tesis, estudiantes de doctorado y autores noveles a enviar sus primeros trabajos a evaluación.The aim of this editorial is to present the most important Intangible Capital milestones of 2008. During the last year, the intangible Capital published its 4th volume, together with information regarding the journal’s visibility and the first results of a satisfaction survey conducted among the authors, who submitted a paper for evaluation. In addition, the annex presents the list of reviewers and the Editorial Board members who have enabled the publication of the fourth volume of the Intangible Capital. This editorial also provides information regarding the aspects that indicate the beginning of the journal’s consolidation, and the importance of maintaining the basic principles that gave rise to this publication. The editorial concludes by encouraging PhD advisors, doctoral students and junior researchers the Intangible Capital a potential outlet for their work.

Intangible Capital: four years of growth as an open-access scientific publication

Con este nuevo número, la revista Intangible Capital, inicia el cuarto volumen avanzando hacia el quinto año de publicación. Como ya es tradición en la revista, iniciamos este nuevo volumen evaluando el anterior y presentando las nuevas direcciones. Como principales aportaciones del 2007, se destacan hechos relevantes como la renovación de convenios para la indexación científica de la revista, el cambio de plataforma a OJS, la inclusión de un nuevo editor, la nueva composición del editorial board, el equipo de revisores, el cambio a un modelo bilingüe de revista, la nueva financiación obtenida y el trabajo que estamos realizando gran número de editores científicos de acceso abierto en España para el reconocimiento por parte de la Comisión Nacional Evaluadora de la Actividad Investigadora.This issue opens the fourth volume of the Intangible Capital journal, which makes its way towards the fifth year of publication. As usually, we start this volume by evaluating the previous one and tracing new directions. Among the main contributions during the year 2007, we consider important to highlight the following aspects: the renewal of the scientific indexation agreements, the platform change to OJS, the appointment of a new editor, new members included in the editorial board, the board of reviewers, the change towards a bilingual model, the new financing obtained and, the last but not the least, the work undertaken together with many scientific editors of open access Spanish journals for obtaining the positive evaluation of the CNEAI (National Commission for the Evaluation of the Research Activity) and thus, being a proof of scientific excellence

El sistema de gestió documental de la Universitat de Barcelona: una funció de suport a la creació de patrimoni intangible?.

Es descriu el Projecte del Sistema de Gestió Documental de la Universitat de Barcelona (PSGD UB) destacant-ne la funció de creació, gestió, preservació i difusió del capital intel·lectual de la institució, alhora que s¿introdueixen els conceptes de recurs tangible, tot referint-se al patrimoni documental, i de patrimoni intangible per definir el conjuntdels recursos i activitats associats al coneixement. Per dur a terme aquest projecte es marquen tres grans línies estratègiques: la implantació del Sistema de Gestió Documental, la valorització del patrimoni documental i el foment de les aliances i de les relacions institucionals.

Development of an erythropoietin prescription simulator to improve abilities for the prescription of erythropoietin stimulating agents: is it feasible?

BACKGROUND: The increasing use of erythropoietins with long half-lives and the tendency to lengthen the administration interval to monthly injections call for raising awareness on the pharmacokinetics and risks of new erythropoietin stimulating agents (ESA). Their pharmacodynamic complexity and individual variability limit the possibility of attaining comprehensive clinical experience. In order to help physicians acquiring prescription abilities, we have built a prescription computer model to be used both as a simulator and education tool. METHODS: The pharmacokinetic computer model was developed using Visual Basic on Excel and tested with 3 different ESA half-lives (24, 48 and 138 hours) and 2 administration intervals (weekly vs. monthly). Two groups of 25 nephrologists were exposed to the six randomised combinations of half-life and administration interval. They were asked to achieve and maintain, as precisely as possible, the haemoglobin target of 11-12 g/dL in a simulated naïve patient. Each simulation was repeated twice, with or without randomly generated bleeding episodes. RESULTS: The simulation using an ESA with a half-life of 138 hours, administered monthly, compared to the other combinations of half-lives and administration intervals, showed an overshooting tendency (percentages of Hb values > 13 g/dL 15.8 ± 18.3 vs. 6.9 ± 12.2; P < 0.01), which was quickly corrected with experience. The prescription ability appeared to be optimal with a 24 hour half-life and weekly administration (ability score indexing values in the target 1.52 ± 0.70 vs. 1.24 ± 0.37; P < 0.05). The monthly prescription interval, as suggested in the literature, was accompanied by less therapeutic adjustments (4.9 ± 2.2 vs. 8.2 ± 4.9; P < 0.001); a direct correlation between haemoglobin variability and number of therapy modifications was found (P < 0.01). CONCLUSIONS: Computer-based simulations can be a useful tool for improving ESA prescription abilities among nephrologists by raising awareness about the pharmacokinetic characteristics of the various ESAs and recognizing the factors that influence haemoglobin variability.

Organometallic anticancer agents that interfere with cellular energy processes: a subtle approach to inducing cancer cell death.

Two hybrid compounds comprising an antimetastatic ruthenium-arene fragment tethered to an indazole-3-carboxylic acid derivative that inhibits aerobic glycolysis in cancer cells have been prepared and evaluated in a variety of cancer cell lines, including highly relevant human glioblastoma cells, with an apparent synergistic action between the two components observed.