ABSTRACT
BACKGROUND: The FDA approved drug granulocyte-colony stimulating factor (G-CSF) displays anti-apoptotic and immunomodulatory properties with neurogenesis and angiogenic functions. It is known to demonstrate neuroprotective mechanisms against ischemic global stroke. Autophagy is a method for the degradation of intracellular components and in particular, unrestrained autophagy may lead to uncontrolled digestion of affected neurons as well as neuronal death in cerebral ischemia. Mitochondrial dynamics is vital for the regulation of cell survival and death after cerebral ischemia and an early upstream event in neuronal death is mitochondrial fission. We examined the pro-survival mechanisms of G-CSF against apoptosis resulting from autophagy, mitochondrial stress and endoplasmic reticulum (ER) stress. METHODS: Male Swiss Webster mice (20 weeks of age) were subjected to bilateral common carotid artery occlusion (BCAO) for 30 min. After occlusion, mice were injected with G-CSF (50 µg/kg) subcutaneously for 4 days. Behavioral analysis was carried out using the corner test and locomotor activity test before animals were sacrificed on day 4 or day 7. Key proteins in ER stress, autophagy and mitochondrial stress induced apoptosis were analyzed by immunoblotting. RESULTS: G-CSF improved neurological deficits and improved behavioral performance on corner and locomotor test. G-CSF binds to G-CSF receptors and its activation leads to upregulation of Akt phosphorylation (P-Akt) which in turn decreases levels of the ER stress sensor, GRP 78 and expression of proteins involved in ER stress apoptosis pathway; ATF6, ATF4, eIF2α, XBP1, Caspase 12 and CHOP. G-CSF treatment significantly decreased Beclin-1, an autophagy marker, and decreased mitochondrial stress biomarkers DRP1 and P53. G-CSF also up-regulated the mitochondrial fusion protein, OPA1 and anti-apoptotic protein Bcl-2 while down-regulating the pro-apoptotic proteins Bax, Bak and PUMA. CONCLUSIONS: G-CSF is an endogenous ligand in the CNS that has a dual activity that is beneficial both in reducing acute neuronal degeneration and adding to long-term plasticity after cerebral ischemia. G-CSF treatment exerts neuroprotective effects on damaged neurons through the suppression of the ER stress and mitochondrial stress and maintains cellular homeostasis by decreasing pro-apoptotic proteins and increasing of anti-apoptotic proteins.
Subject(s)
Endoplasmic Reticulum Stress/drug effects , Granulocyte Colony-Stimulating Factor/pharmacology , Stroke , Animals , Apoptosis/drug effects , Apoptosis Regulatory Proteins/biosynthesis , Behavior, Animal/drug effects , Disease Models, Animal , Gene Expression Regulation/drug effects , Humans , Male , Mice , Mitochondrial Dynamics/drug effects , Phosphorylation/drug effects , Proto-Oncogene Proteins c-akt/metabolism , Receptors, Granulocyte Colony-Stimulating Factor/metabolism , Signal Transduction/drug effects , Stroke/drug therapy , Stroke/metabolism , Stroke/pathologyABSTRACT
Antecedentes. Las úlceras por presión representan una complicación del cuidado de la salud que no debe ser atribuible exclusivamente al cuidado de enfermería. Deterioran la calidad de vida de los pacientes y su familia, aumentando los costos sociales y en salud. En Colombia los indicadores epidemiológicos son escasos. El estudio expone una visión preliminar de la situación de las úlceras por presión por regiones en el país. Objetivo. Establecer la prevalencia de las úlceras por presión a nivel nacional. Materiales y métodos. Estudio descriptivo, transversal, de prevalencia cruda de periodo que utiliza, como instrumento, una encuesta elaborada a partir de las directrices del Grupo Nacional para el Estudio y Asesoramiento de Úlceras por Presión y Heridas Crónicas. La encuesta fue diligenciada online por enfermeros entre septiembre y noviembre de 2013. Resultados. Se respondieron 111 encuestas, de 800 correos electrónicos enviados a enfermeros de todas las regiones de Colombia. Se encontró: el 68% de úlceras por presión en hombres, 64% en instituciones públicas, el 44% en el primer nivel, el 65% de la información proviene de personas afiliadas al régimen subsidiado de Salud. La causa principal en el 98% de los casos es la presión, seguido por cizalla, humedad e incontinencia. Se destaca el desconocimiento de los ácidos grasos hiperoxigenados y el escaso uso de superficies especiales para el manejo de la presión; el 43% no utiliza escalas para medir el riesgo. Conclusiones. Estos resultados son el preámbulo de una investigación nacional que permita establecer indicadores propios, encaminados a estrategias de prevención reales.
Background. Pressure ulcers represent a healthcare complication which should not be solely attributable to nursing care. They lead to patients and their families' quality of life becoming deteriorated and increased social and healthcare costs. There are few pertinent epidemiological indicators in Colombia so this study was aimed at providing a preliminary overview of the status of pressure ulcers by region in Colombia. Objective. Establishing the prevalence of pressure ulcers nationwide. Materials and methods. This was a descriptive, cross-sectional study of crude period prevalence regarding pressure ulcer, this being defined as a localised injury to the skin and/or underlying tissue usually over a bony prominence, as a result of pressure, or pressure in combination with shear. The study involved using a survey instrument developed from the guidelines provided by the Colombian Study and Advisory Group for Pressure Ulcers and Chronic Wounds which was filled out online by nurses between September and November 2013. Results. 800 e-mails were sent to nurses in all regions of Colombia and 111 surveys (13.9%) were answered. Men suffered 68% of all pressure ulcers, 64% occurred in public institutions, 44% were detected by first level attention nurses and 65% of the information came from people affiliated to Colombia's subsidised healthcare regime. Pressure was the main cause in 98% of the cases reported in the questionnaire, followed by shear, moisture and incontinence. Ignorance regarding hyperoxygenated fatty acids and the limited use of special surfaces for managing pressure was noted and 43% of the nurses did not use a scale for measuring/estimating risk. Conclusions. These results represent the prelude to national research aimed at establishing Colombian indicators aimed at real/effective prevention strategies.
ABSTRACT
Introducción: el síndrome de ovario poliquístico es un trastorno endocrino metabólico de etiología incierta, que afecta a mujeres en edad reproductiva con una prevalencia del 5-10 %, y se caracteriza por oligo o anovulación, oligomenorrea e hiperandrogenismo clínico o bioquímico. Su presentación clínica está sujeta a la presencia de una predisposición genética, sometida a diferentes influencias externas tales como la obesidad, entre otras.Objetivo: revisar la literatura disponible acerca de las diferencias fisiopatológicas entre pacientes obesas y no obesas con el síndrome. Metodología: se realizó una búsqueda de los artículos disponibles en Ovid, Pubmed y Medline usando las palabras clave: polycystic ovary syndrome, obese and nonobese.Resultados: aunque la resistencia la insulina no es un hallazgo universal en mujeres con el síndrome, su papel en los cambios metabólicos de estas pacientes es evidente. Hay gran variabilidad en cuanto a la sensibilidad a la insulina en cada paciente, con una respuesta ovárica androgénica variable. Se observa un aumento de los andrógenos, inhibición de la acción de la insulina y disminución de la captación de glucosa por parte del órgano blanco. También hay alteración de las lipoproteínas y del metabolismo lipídico. En las pacientes no obesas predomina una alteración del eje hipotálamo - hipófisis- ovario; mientras que en las obesas, predomina una alteración en la sensibilidad a la insulina.
Objetive: To review the literature available about the difference between obese and non obese women with polycystic ovary syndrome (POS) Background: POS is characterized by endocrine and metabolic abnormalities. The etiology of POS remains uncertain and its prevalence is 5-10 % in reproductive-age women. POS is diagnosed by the presence of oligovulation or anovulation, oligomenorrhea and hyperandrogenemia or hyperandrogenism. Clinical presentation depends on a genetic predisposition (associated with metabolic abnormalities) influenced by external factors such as obesity. Methods: Pubmed, Ovid and Medline databases were searched up using polycystic ovary syndrome, obese, nonobese as key words. Results: Insulin resistance is not a universal finding in women with POS (it is onlypresent in 60 % of them), its role in metabolic changes is evident. There is a great variability in insulin resistance levels in each patient with variable response to androgens production from ovaries. There is an increase in androgens, inhibition of insulin action and decrease in glucose uptake in the target organ. It is associated with lipid and lipoprotein abnormalities. In nonobese women with POS predominates an alteration in the hypothalamo-pituitary-adrenal axis while in obese women with POS there is more marked dysregulationin insulin sensitivity. In the obese women with POS plasmatic levels of sex hormonebinding globulin (SHBG) are significantly low.
