Light and Shadows in cardiac regeneration.

Given that the adult human heart has an extremely limited regenerative capacity, diseases characterized by contractile cell loss, as myocardial infarction and cardiomyopathies, lead to ventricular remodeling and heart failure. Hence, diverse strategies to promote myocardial regeneration have been proposed and assessed in animals and humans with ischemic heart disease. Of these, gene transfer and especially stem cell therapy have been used. So far, the overall main outcome is a gross disparity between the promising results obtained in mammalian models and the poor, if any, benefit observed in randomized,controlled clinical trials. Many reasons may account for this disappointing scenario.Some, including flawed trial design and methodology, differences in cell type and dosing as well as in route of administration, erroneous end points selection and heterogeneous patient populations have been extensively discussed in comprehensive reviews. Others,more recently addressed, signal the use of inadequate or non-precise laboratorytechniques in cell identification and fate, this leading to precarious or misleadingconclusions. We hereby summarize part of the work done and quote some newapproaches, like the use of induced pluripotent stem cells and the promotion of selfregeneration by targeting the adult cardiomyocyte cell cycle, that may cast some light inthe otherwise shadowy field of cardiac regeneration.Fil: Giménez, Carlos Sebastián. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional, Trasplante y Bioingeniería. Fundación Favaloro. Instituto de Medicina Traslacional, Trasplante y Bioingeniería; Argentin

Lights and shadows in cardiac regeneration

Given that the adult human heart has an extremely limited regenerative capacity, diseases characterized by contractile cell loss, as myocardial infarction and cardiomyopathies, lead to ventricular remodeling and heart failure. Hence, diverse strategies to promote myocardial regeneration have been proposed and assessed in animals and humans with ischemic heart disease. Of these, gene transfer and especially stem cell therapy have been used. So far, the overall main outcome is a gross disparity between the promising results obtained in mammalian models and the poor, if any, benefit observed in randomized, controlled clinical trials. Many reasons may account for this disappointing scenario. Some, including flawed trial design and methodology, differences in cell type and dosing as well as in route of administration, erroneous end points selection and heterogeneous patient populations have been extensively discussed in comprehensive reviews. Others, more recently addressed, signal the use of inadequate or non-precise laboratory techniques in cell identification and fate, this leading to precarious or misleading conclusions. We hereby summarize part of the work done and quote some new approaches, like the use of induced pluripotent stem cells and the promotion of selfregeneration by targeting the adult cardiomyocyte cell cycle, that may cast some light in the otherwise shadowy field of cardiac regeneration.Dada la limitadísima capacidad regenerativa del corazón humano adulto, las enfermedades caracterizadas por pérdida de tejido contráctil, como el infarto de miocardio y las miocardiopatías, conducen al remodelamiento ventricular y la insuficiencia cardíaca. Por ello, diversas estrategias cardiorregenerativas han sido propuestas y evaluadas en modelos animales y pacientes con cardiopatía isquémica. De ellas, las más usadas han sido la transferencia génica y, especialmente, la terapia con células madre. Hasta aquí, el resultado global es una gran disparidad entre los prometedores resultados obtenidos en modelos animales y los pobres o nulos beneficios observados en los ensayos clínicos. Muchas razones explican este decepcionante escenario. Algunas, tales como imperfecciones de diseño y metodología, diferencias en el tipo y dosis de células así como en la vía de administración, puntos finales erróneamente elegidos, y heterogeneidad en las poblaciones de pacientes, han sido ampliamente discutidos en muy completas revisiones. Otros, más recientemente abordados, señalan el uso de inadecuadas o imprecisas técnicas de laboratorio para identificar el tipo de célula y su destino, conducentes a conclusiones precarias o engañosas. En este artículo resumimos parte del trabajo realizado y citamos algunos nuevos abordajes, tales como el uso de células pluripotentes inducidas y la auto- regeneración por manipulación del ciclo celular del miocardiocito adulto, que podrían arrojar algo de luz al sombrío campo de la regeneración cardíaca.Sociedad Argentina de Fisiologí

Allogeneic mesenchymal stromal cells overexpressing mutant human Hypoxia-inducible factor 1-α (HIF1-α) in an ovine model of acute myocardial infarction

Background-Bone marrow mesenchymal stromal cells (BMMSCs) are cardioprotective in acute myocardial infarction (AMI) because of release of paracrine angiogenic and prosurvival factors. Hypoxia-inducible factor 1-α (HIF1-α), rapidly degraded during normoxia, is stabilized during ischemia and upregulates various cardioprotective genes. We hypothesized that BMMSCs engineered to overexpress mutant, oxygen-resistant HIF1-α would confer greater cardioprotection than nontransfected BMMSCs in sheep with AMI. Methods and Results-Allogeneic BMMSCs transfected with a minicircle vector encoding mutant HIF1-α (BMMSC-HIF) were injected in the peri-infarct of sheep (n=6) undergoing coronary occlusion. Over 2 months, infarct volume measured by cardiac magnetic resonance (CMR) imaging decreased by 71.7±1.3% (P < 0.001), and left ventricular (LV) percent ejection fraction (%EF) increased near 2-fold (P < 0.001) in the presence of markedly decreased end-systolic volume. Sheep receiving nontransfected BMMSCs (BMMSC; n=6) displayed less infarct size limitation and percent LVEF improvement, whereas in placebo-treated animals (n=6), neither parameters changed over time. HIF1-α-transfected BMMSCs (BMMSC-HIF) induced angio-/arteriogenesis and decreased apoptosis by HIF1-mediated overexpression of erythropoietin, inducible nitrous oxide synthase, vascular endothelial growth factor, and angiopoietin-1. Cell tracking using paramagnetic iron nanoparticles in 12 additional sheep revealed enhanced long-term retention of BMMSC-HIF. Conclusions-Intramyocardial delivery of BMMSC-HIF reduced infarct size and improved LV systolic performance compared to BMMSC, attributed to increased neovascularization and cardioprotective effects induced by HIF1-mediated overexpression of paracrine factors and enhanced retention of injected cells. Given the safety of the minicircle vector and the feasibility of BMMSCs for allogeneic application, this treatment may be potentially useful in the clinic.Fil: Hnatiuk, Anna. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional, Trasplante y Bioingeniería. Fundación Favaloro. Instituto de Medicina Traslacional, Trasplante y Bioingeniería; ArgentinaFil: Ong, Sang-Ging. Stanford University School of Medicine; Estados UnidosFil: Olea, Fernanda Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional, Trasplante y Bioingeniería. Fundación Favaloro. Instituto de Medicina Traslacional, Trasplante y Bioingeniería; ArgentinaFil: Locatelli, Paola. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional, Trasplante y Bioingeniería. Fundación Favaloro. Instituto de Medicina Traslacional, Trasplante y Bioingeniería; ArgentinaFil: Riegler, Johannes. Stanford University School of Medicine; Estados UnidosFil: Lee, Won Hee. Stanford University School of Medicine; Estados UnidosFil: Jen, Cheng Hao. University of London; Reino UnidoFil: De Lorenzi, Andrea. Fundación Favaloro; ArgentinaFil: Giménez, Carlos Sebastián. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional, Trasplante y Bioingeniería. Fundación Favaloro. Instituto de Medicina Traslacional, Trasplante y Bioingeniería; ArgentinaFil: Laguens, Rubén. Universidad Favaloro; ArgentinaFil: Wu, Joseph C.. Stanford University School of Medicine; Estados UnidosFil: Crottogini, Alberto José. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional, Trasplante y Bioingeniería. Fundación Favaloro. Instituto de Medicina Traslacional, Trasplante y Bioingeniería; Argentin

Mechanism of photooxidation of folic acid sensitized by unconjugated pterins

Folic acid, or pteroyl-L-glutamic acid (PteGlu), is a precursor of coenzymes involved in the metabolism of nucleotides and amino acids. PteGlu is composed of three moieties: a 6-methylpterin (Mep) residue, a p-aminobenzoic acid (PABA) residue, and a glutamic acid (Glu) residue. Accumulated evidence indicates that photolysis of PteGlu leads to increased risk of several pathologies. Thus, a study of PteGlu photodegradation can have significant ramifications. When an air-equilibrated aqueous solution of PteGlu is exposed to UV-A radiation, the rate of the degradation increases with irradiation time. The mechanism involved in this “auto-photo-catalytic” effect was investigated in aqueous solutions using a variety of tools. Whereas PteGlu is photostable under anaerobic conditions, it is converted into 6-formylpterin (Fop) and p-aminobenzoyl-L-glutamic acid (PABA-Glu) in the presence of oxygen. As the reaction proceeds and enough Fop accumulates in the solution, a photosensitized electron-transfer process starts, where Fop photoinduces the oxidation of PteGlu to Fop, and H₂O₂ is formed. This process also takes place with other pterins as photosensitizers. The results are discussed with the context of previous mechanisms for processes photosensitized by pterins, and their biological implications are evaluated.Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicada

Mechanism of photooxidation of folic acid sensitized by unconjugated pterins

Folic acid, or pteroyl-L-glutamic acid (PteGlu), is a precursor of coenzymes involved in the metabolism of nucleotides and amino acids. PteGlu is composed of three moieties: a 6-methylpterin (Mep) residue, a p-aminobenzoic acid (PABA) residue, and a glutamic acid (Glu) residue. Accumulated evidence indicates that photolysis of PteGlu leads to increased risk of several pathologies. Thus, a study of PteGlu photodegradation can have significant ramifications. When an air-equilibrated aqueous solution of PteGlu is exposed to UV-A radiation, the rate of the degradation increases with irradiation time. The mechanism involved in this “auto-photo-catalytic” effect was investigated in aqueous solutions using a variety of tools. Whereas PteGlu is photostable under anaerobic conditions, it is converted into 6-formylpterin (Fop) and p-aminobenzoyl-L-glutamic acid (PABA-Glu) in the presence of oxygen. As the reaction proceeds and enough Fop accumulates in the solution, a photosensitized electron-transfer process starts, where Fop photoinduces the oxidation of PteGlu to Fop, and H₂O₂ is formed. This process also takes place with other pterins as photosensitizers. The results are discussed with the context of previous mechanisms for processes photosensitized by pterins, and their biological implications are evaluated.Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicada

Difusión y visibilidad del conocimiento producido en las Ciencias Económicas en ambientes virtuales en la Argentina 2010-2011

En la actualidad, y desde al menos desde los últimos cinco años a esta parte, ha cobrado una preponderante relevancia y peso significativo el uso de los ambientes virtuales como ámbitos de comunicación y difusión del conocimiento producido en los distintos campos de la ciencia, y en particular de las Ciencias Económicas, área en la cual se ha ocupado esta investigación. Los objetivos propuestos se orientan a establecer un relevamiento de los principales recursos de información disponibles en sitios web locales producidos y/o mantenidos por organismos de educación superior, consejos profesionales y organizaciones intermedias vinculadas al quehacer de las Ciencias Económicas. La metodología de exploración y recolección de datos ha sido llevada a cabo a través de herramientas de cibermetría aplicadas a la información de sitios web que brindan información en Ciencias Económicas relevados por profesionales en Ciencias Económicas, y la información resultante de los sitios web mencionados por alumnos de las carreras de Ciencias Económicas a través de una encuesta presencial. Los resultados obtenidos indican que es escasa o baja la visibilidad de los recursos web de información en Ciencias Económicas de carácter académico-universitario para los alumnos, destacándose el uso de sitios de información general, buscados, y sitios gubernamentales relacionados con la operatoria económica financiera.Fil: Ezeiza Pohl, Carlos Enrique. Universidad Nacional de La Matanza; Argentina.Fil: Bidiña, Ana Marcela. Universidad Nacional de La Matanza; Argentina.Fil: Ferrero, Eduardo Daniel. Universidad Nacional de La Matanza; Argentina.Fil: Céspedes, Diego Andrés. Universidad Nacional de La Matanza; Argentina.Fil: Vera, Pablo Sebastián. Universidad Nacional de La Matanza; Argentina.Fil: Giménez, Diego Gabriel. Universidad Nacional de La Matanza; Argentina.Fil: Estrada, Verónica Ruth. Universidad Nacional de La Matanza; Argentina

Estado de las poblaciones de Caimanes en seis Localidades del Paraguay

El objetivo general del trabajo es determinar la densidad poblacional, estructura etaria y uso de hábitat de caimanes en el sur del departamento de Boquerón, Paraguay. Se adjuntan poster y presentación con el mismo título y contenido.CONACYT – Consejo Nacional de Ciencia y TecnologíaPROCIENCI

Aligned ovine diaphragmatic myoblasts overexpressing human connexin-43 seeded on poly (L-lactic acid) scaffolds for potential use in cardiac regeneration

Diaphragmatic myoblasts (DMs) are precursors of type-1 muscle cells displaying high exhaustion threshold on account that they contract and relax 20 times/min over a lifespan, making them potentially useful in cardiac regeneration strategies. Besides, it has been shown that biomaterials for stem cell delivery improve cell retention and viability in the target organ. In the present study, we aimed at developing a novel approach based on the use of poly (L-lactic acid) (PLLA) scaffolds seeded with DMs overexpressing connexin-43 (cx43), a gap junction protein that promotes inter-cell connectivity. DMs isolated from ovine diaphragm biopsies were characterized by immunohistochemistry and ability to differentiate into myotubes (MTs) and transduced with a lentiviral vector encoding cx43. After confirming cx43 expression (RT-qPCR and Western blot) and its effect on inter-cell connectivity (fluorescence recovery after photobleaching), DMs were grown on fiberaligned or random PLLA scaffolds. DMs were successfully isolated and characterized. Cx43 mRNA and protein were overexpressed and favored inter-cell connectivity. Alignment of the scaffold fibers not only aligned but also elongated the cells, increasing the contact surface between them. This novel approach is feasible and combines the advantages of bioresorbable scaffolds as delivery method and a cell type that on account of its features may be suitable for cardiac regeneration. Future studies on animal models of myocardial infarction are needed to establish its usefulness on scar reduction and cardiac function.Centro de Investigaciones Cardiovasculare

ATLAS search for a heavy gauge boson decaying to a charged lepton and a neutrino in pp collisions at root s=7 TeV

The ATLAS detector at the LHC is used to search for high-mass states, such as heavy charged gauge bosons (W'), decaying to a charged lepton (electron or muon) and a neutrino. Results are presented based on the analysis of pp collisions at a center-of-mass energy of 7 TeV corresponding to an integrated luminosity of 4.7 fb(-1). No excess beyond Standard Model expectations is observed. A W' with Sequential Standard Model couplings is excluded at the 95 % credibility level for masses up to 2.55 TeV. Excited chiral bosons (W*) with equivalent coupling strength are excluded for masses up to 2.42 TeV