Examinando por Autor "Morales, Paola"

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    Gold nanorods/siRNA complex administration for knockdown of PARP-1: A potential treatment for perinatal asphyxia
    (Dove Medical Press Ltd., 2018) Vio, Valentina; Riveros, Ana L.; Tapia-Bustos, Andrea; Lespay-Rebolledo, Carolyne; Pérez-Lobos, Ronald; Muñoz, Luis; Pismante, Paola; Morales, Paola; Araya, Eyleen; Hassan, Natalia; Herrera-Marschitz, Mario; Kogan, Marcelo J.
    Background: Perinatal asphyxia interferes with neonatal development, resulting in long-term deficits associated with systemic and neurological diseases. Despite the important role of poly (ADP-ribose) polymerase 1 (PARP-1) in the regulation of gene expression and DNA repair, overactivation of PARP-1 in asphyxia-exposed animals worsens the ATP-dependent energetic crisis. Inhibition of PARP-1 offers a therapeutic strategy for diminishing the effects of perinatal asphyxia. Methods: We designed a nanosystem that incorporates a specific siRNA for PARP-1 knockdown. The siRNA was complexed with gold nanorods (AuNR) conjugated to the peptide CLPFFD for brain targeting. Results: The siRNA was efficiently delivered into PC12 cells, resulting in gene silencing. The complex was administered intraperitoneally in vivo to asphyxia-exposed rat pups, and the ability of the AuNR-CLPFFD/siRNA complex to reach the brain was demonstrated. Conclusion: The combination of a nanosystem for delivery and a specific siRNA for gene silencing resulted in effective inhibition of PARP-1 in vivo. © 2018 Vio et al.
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    Ítem
    El impacto del coaching en el desempeño laboral
    (Universidad Andrés Bello, 2007) Acevedo, Nicole; Barra, Gloria; Morales, Paola; Nicolaievsky, Gabriel; Facultad de Educación y Ciencias Sociales
    Este trabajo aborda la técnica de desarrollo personal llamada "coaching", para esto se realizó un estudio en organizaciones coacheadas, evaluando el impacto que ejerce éste en el desempeño laboral del capital humano que integra una organización. Explica cómo coach y la persona o grupo implicados en dicho proceso buscan el camino más eficaz para alcanzar los objetivos fijados usando sus propios recursos y habilidades, implica el recorrido entre dos puntos: aquel donde el coachee está y aquel otro en el que quiere estar. Señala el concepto de coaching y sus principales enfoques que determinan el tipo de intervención a ejecutar, facilitando el proceso de mejoramiento del cambio organizacional de las empresas. Como parte del contenido se presentan resultados que sustentan la efectividad de la intervención aplicada en organizaciones. Este estudio aporta a los escenarios del presente que requieren de un personal calificado, capaz de interpretar los requerimientos que actualmente la competitividad demanda, producto de esa gran apertura que es la globalización.
  • Miniatura
    Ítem
    Targeting Sentinel Proteins and Extrasynaptic Glutamate Receptors: a Therapeutic Strategy for Preventing the Effects Elicited by Perinatal Asphyxia?
    (Springer New York LLC, 2018-02) Herrera-Marschitz, Mario; Perez-Lobos, Ronald; Lespay-Rebolledo, Carolyne; Tapia-Bustos, Andrea; Casanova-Ortiz, Emmanuel; Morales, Paola; Valdés, José-Luis; Bustamante, Diego; Cassels, Bruce K.
    Perinatal asphyxia (PA) is a relevant cause of death at the time of labour, and when survival is stabilised, associated with short- and long-term developmental disabilities, requiring inordinate care by health systems and families. Its prevalence is high (1 to 10/1000 live births) worldwide. At present, there are few therapeutic options, apart from hypothermia, that regrettably provides only limited protection if applied shortly after the insult. PA implies a primary and a secondary insult. The primary insult relates to the lack of oxygen, and the secondary one to the oxidative stress triggered by re-oxygenation, formation of reactive oxygen (ROS) and reactive nitrogen (RNS) species, and overactivation of glutamate receptors and mitochondrial deficiencies. PA induces overactivation of a number of sentinel proteins, including hypoxia-induced factor-1α (HIF-1α) and the genome-protecting poly(ADP-ribose) polymerase-1 (PARP-1). Upon activation, PARP-1 consumes high amounts of ATP at a time when this metabolite is scarce, worsening in turn the energy crisis elicited by asphyxia. The energy crisis also impairs ATP-dependent transport, including glutamate re-uptake by astroglia. Nicotinamide, a PARP-1 inhibitor, protects against the metabolic cascade elicited by the primary stage, avoiding NAD+ exhaustion and the energetic crisis. Upon re-oxygenation, however, oxidative stress leads to nuclear translocation of the NF-κB subunit p65, overexpression of the pro-inflammatory cytokines IL-1β and TNF-α, and glutamate-excitotoxicity, due to impairment of glial-glutamate transport, extracellular glutamate overflow, and overactivation of NMDA receptors, mainly of the extrasynaptic type. This leads to calcium influx, mitochondrial impairment, and inactivation of antioxidant enzymes, increasing further the activity of pro-oxidant enzymes, thereby making the surviving neonate vulnerable to recurrent metabolic insults whenever oxidative stress is involved. Here, we discuss evidence showing that (i) inhibition of PARP-1 overactivation by nicotinamide and (ii) inhibition of extrasynaptic NMDA receptor overactivation by memantine can prevent the short- and long-term consequences of PA. These hypotheses have been evaluated in a rat preclinical model of PA, aiming to identify the metabolic cascades responsible for the long-term consequences induced by the insult, also assessing postnatal vulnerability to recurrent oxidative insults. Thus, we present and discuss evidence demonstrating that PA induces long-term changes in metabolic pathways related to energy and oxidative stress, priming vulnerability of cells with both the neuronal and the glial phenotype. The effects induced by PA are region dependent, the substantia nigra being particularly prone to cell death. The issue of short- and long-term consequences of PA provides a framework for addressing a fundamental issue referred to plasticity of the CNS, since the perinatal insult triggers a domino-like sequence of events making the developing individual vulnerable to recurrent adverse conditions, decreasing his/her coping repertoire because of a relevant insult occurring at birth. © 2017, The Author(s).