ABSTRACT
Mitochondria are highly dynamic organelles that in response to the cell's bio-energetic state continuously undergo structural remodeling fission and fusion processes. This mitochondrial dynamic activity has been implicated in cell cycle, autophagy, and age-related diseases. Adult tissue-derived mesenchymal stromal/stem cells present a therapeutic potential. However, to obtain an adequate mesenchymal stromal/stem cell number for clinical use, extensive in vitro expansion is required. Unfortunately, these cells undergo replicative senescence rapidly by mechanisms that are not well understood. Senescence has been associated with metabolic changes in the oxidative state of the cell, a process that has been also linked to mitochondrial fission and fusion events, suggesting an association between mitochondrial dynamics and senescence. In the present work, we studied the mitochondrial structural remodeling process of mesenchymal stromal/stem cells isolated from adipose tissue in vitro to determine if mitochondrial phenotypic changes were associated with mesenchymal stromal/stem cell senescence. For this purpose, mitochondrial dynamics and oxidative state of stromal/stem cell were compared between young and old cells. With increased cell passage, we observed a significant change in cell morphology that was associated with an increase in ß-galactosidase activity. In addition, old cells (population doubling seven) also showed increased mitochondrial mass, augmented superoxide production, and decreased mitochondrial membrane potential. These changes in morphology were related to slightly levels increases in mitochondrial fusion proteins, Mitofusion 1 (MFN1), and Dynamin-related GTPase (OPA1). Collectively, our results showed that adipose tissue-derived MSCs at population doubling seven developed a senescent phenotype that was characterized by metabolic cell changes that can lead to mitochondrial fusion.
ABSTRACT
The use-dependent regulation of the GABAA receptor occurs under physiological, pathological, and pharmacological conditions. Tolerance induced by prolonged administration of benzodiazepines is associated with changes in GABAA receptor function. Chronic exposure of neurons to GABA for 48 hr induces a downregulation of the GABAA receptor number and an uncoupling of the GABA/benzodiazepine site interactions. A single brief exposure ((t1/2) = 3 min) of rat neocortical neurons to the neurotransmitter initiates a process that results in uncoupling hours later (t(1/2) = 12 hr) without alterations in the number of GABAA receptors and provides a paradigm to study the uncoupling mechanism selectively. Here we report that uncoupling induced by a brief GABAA receptor activation is blocked by the coincubation with inhibitors of protein kinases A and C, indicating that the uncoupling is mediated by the activation of a phosphorylation cascade. GABA-induced uncoupling is accompanied by subunit-selective changes in the GABAA receptor mRNA levels. However, the GABA-induced downregulation of the α3 subunit mRNA level is not altered by the kinase inhibitors, suggesting that the uncoupling is the result of a posttranscriptional regulatory process. GABA exposure also produces an increase in the serine phosphorylation on the GABAA receptor γ2 subunit. Taken together, our results suggest that the GABA-induced uncoupling is mediated by a posttranscriptional mechanism involving an increase in the phosphorylation of GABAA receptors. The uncoupling of the GABAA receptor may represent a compensatory mechanism to control GABAergic neurotransmission under conditions in which receptors are persistently activated.
Subject(s)
Hippocampus/drug effects , Neurons/drug effects , Protein Subunits/metabolism , Receptors, GABA-A/metabolism , gamma-Aminobutyric Acid/pharmacology , Animals , Cells, Cultured , Hippocampus/cytology , Hippocampus/metabolism , Neurons/cytology , Neurons/metabolism , Phosphorylation , Rats , Rats, Sprague-DawleyABSTRACT
This report describes findings from epidemiological surveillance of influenza virus in two cities in Argentina (Mar del Plata and Córdoba) from 1987 to 1993. It includes information on reporting and serologic characterization of isolated influenza viruses. In addition, determination was made of the nucleotide sequences of the HA1 subunits of five type A (subtype H3) viral strains isolated in the epidemics of 1990 and 1993. The incidence of illness, type of viruses isolated, and H gene sequences were similar to what has been reported from other parts of the world during the same period. The H3 strains isolated in the 1990 and 1993 seasons were somewhat removed in their molecular characteristics from the strains the World Health Organization recommended for vaccines for those years, and appeared closer to the strains recommended for vaccination in subsequent seasons
En este informe se describen los resultados de la vigilancia epidemiológica de virus de gripe en dos ciudades de la Argentina (Mar del Plata y Córdoba) de 1987 a 1993. Se incluye información acerca de la notificación y la caracterización serológica de los virus aisaldos. Además, se determinaron las secuencias de nucleótidos de las subunidades HA1 de cinco cepas tipo A (subtipo H3) aisladas durante las epidemias de 1990 y 1993. La incidencia de enfermedad, los tipos de virus aislados y las secuencias genéticas H fueron similares a las notificaciones del mismo período en otras partes del mundo. En sus características moleculares, las cepas H3 aisladas en las estaciones de 1990 y 1993 se distinguían un poco de las cepas que la Organización Mundial de la Salud recomendó incluir en las vacunas de esos años y se parecían más a las cepas recomendadas para vacunación en estaciones subsecuentes
Subject(s)
Serotyping , Influenza, Human , Epidemiological Monitoring , ArgentinaABSTRACT
El fenómeno del maltrato al menor es universal, tiene relación muy directa con lo que acontece en el mundo en torno a la economía, el manejo político de la economía y de las relaciones internacionales que influyen en los índices de pobreza colombiana con todas sus consecuencias deprivatorias. Desencadena trastornos familiares en donde el menor recibe una descarga permanente de agresividad tanto física como emocional que se refleja a diario en este hospital pediátrico.
Subject(s)
Humans , Child , Child Abuse/classification , Child Abuse/diagnosis , Child Abuse/statistics & numerical data , Child Abuse/mortality , Child Abuse/prevention & controlABSTRACT
Se presentan los resultados del Proyecto de Investigación para Vigilancia Epidemiológica de Influenza, realizado durante la temporada gripal de 1983.Se estudiaron los soldados de la clase 1964 que aquejaron síndrome gripal. Sobre 34 muestras de sueros pareados se obtubieron 24 conversiones serológicas, 14 de las cuales correspondieron a la cepa A/England/333/80 con títulos significativos que podrían señalar la presencia de un brote originado por la misma y otra similar
Subject(s)
Child , Adolescent , Humans , Male , History, 20th Century , Influenza, Human/epidemiology , ArgentinaABSTRACT
Se presentan los resultados del Proyecto de Investigación para Vigilancia Epidemiológica de Influenza, realizado durante la temporada gripal de 1983.Se estudiaron los soldados de la clase 1964 que aquejaron síndrome gripal. Sobre 34 muestras de sueros pareados se obtubieron 24 conversiones serológicas, 14 de las cuales correspondieron a la cepa A/England/333/80 con títulos significativos que podrían señalar la presencia de un brote originado por la misma y otra similar (AU)