ABSTRACT
Resumen: En los últimos años se ha intentado comprender la etiología del Trastorno del Espectro Autista (TEA), evidenciandose que existe una compleja interacción entre factores genéticos y ambientales. Estudios epidemiológicos y en modelos animales sugieren que la activación inmune de la madre durante el embarazo puede asociarse un mayor riesgo de desarrollar TEA en los hijos, destacando el rol de las citoquinas proinflamatorias, los auto-anticuerpos y el rol de la microglia activada en la poda sináptica durante el desarrollo embrionario. Comprender mejor los factores asociados con los Trastornos del Neurodesarrollo permitirá en el futuro desarrollar estrategias de manejo y detección precoz en población de riesgo.
Abstract: Autism Spectrum Disorder (ASD) etiology has been related whit complex interaction between ge netic and environmental factors. In the last years, numerous studies have suggested that maternal immune activation during pregnancy could be related to ASD in the offspring. This relation could be explained by the effects of pro-inflammatory cytokines, autoantibodies and microglial synap tic pruning during early embryonic development. Better understanding of Neurodevelopmental Disorders risk factors will support appropriate strategies of screening and management of risk population.
Subject(s)
Humans , Female , Pregnancy , Pregnancy Complications/immunology , Prenatal Exposure Delayed Effects/immunology , Autism Spectrum Disorder/immunology , Autoantibodies/immunology , Risk Factors , Cytokines/immunology , Microglia/immunology , Autism Spectrum Disorder/etiologyABSTRACT
INTRODUÇÃO: O absenteísmo-doença, enquanto falta ao trabalho justificada por licença médica, é um importante indicador das condições de saúde dos trabalhadores. Em geral, características sociodemográficas e ocupacionais situam-se entre os principais fatores associados ao absenteísmo-doença. A administração pública é responsável por 21,8% dos empregos formais no Brasil. Esta população permite o estudo de uma grande variedade de categorias profissionais. OBJETIVO: Analisar o perfil e os indicadores de absenteísmo-doença entre servidores municipais de Goiânia, no Estado de Goiás, Brasil. Métodos: Estudo transversal das licenças certificadas para tratamento de saúde superiores a três dias, de todos os servidores, desde janeiro de 2005 a dezembro de 2010. Foram calculadas as prevalências, utilizando como critérios o número de indivíduos, os episódios e os dias de afastamento. RESULTADOS: Foram concedidas 40.578 licenças certificadas para tratamento de saúde a 13.408 servidores numa população média anual de 17.270 pessoas, o que resultou em 944.722 dias de absenteísmo. A prevalência acumulada de licença no período foi de 143,7%, com média anual de 39,2% e duração de 23 dias por episódio. A prevalência acumulada de absenteísmo-doença foi maior entre mulheres (52,0%) com idade superior a 40 anos (55,9%), com companheiro (49,9%), de baixa escolaridade (54,4%), profissionais de educação (54,7%), > 10 anos de serviço (61,9%) e múltiplos vínculos profissionais (53,7%). Os grupos de diagnósticos (CID-10) com as maiores prevalências acumuladas de licenças foram os do capítulo de transtornos mentais (26,5%), doenças osteomusculares (25,1%) e lesões (23,6%). CONCLUSÕES: Os indicadores de absenteísmo-doença expressam a magnitude desse fenômeno no serviço público e podem auxiliar no planejamento das ações de saúde do trabalhador, priorizando os grupos ocupacionais mais vulneráveis. .
BACKGROUND: Sickness absence, as work absenteeism justified by medical certificate, is an important health status indicator of the employees and, overall, sociodemographic and occupational characteristics are among the main factors associated with sickness absence. Public administration accounts for 21.8% of the formal job positions in Brazil. This population allows the study of a wide range of professional categories. OBJECTIVE: To assess the profile and indicators of sickness absence among public workers from the municipality of Goiania, in the State of Goiás, Brazil. METHODS: A cross-sectional study on certified sick leaves, lasting longer than three days, of all civil servants from January 2005 to December 2010. Prevalence rates were calculated using as main criteria the number of individuals, episodes and sick days. RESULTS: 40,578 certified sick leaves were granted for health treatment among 13,408 public workers, in an annual average population of 17,270 people, which resulted in 944,722 days of absenteeism. The cumulative prevalence of sick leave for the period was of 143.7%, with annual average of 39.2% and duration of 23 days per episode. The cumulative prevalence of sickness absence was higher among women (52.0%), older than 40 years old (55.9%), with a partner (49.9%), low schooling (54.4%), education professionals (54.7%), > 10 years of service (61.9%), and with multiple work contracts (53.7%). Diagnoses groups (ICD-10) with higher cumulative prevalence of sick leaves were those with mental disorders (26.5%), musculoskeletal diseases (25.1%), and injuries (23.6%). CONCLUSIONS: Indicators of sickness absence express the magnitude of this phenomenon in the public sector and can assist in planning health actions for the worker, prioritizing the most vulnerable occupational groups. .
Subject(s)
Animals , Male , Rats , Complement Factor H , Cytokines/immunology , Neuroglia/immunology , Seizures/immunology , Age Factors , Amino Acid Transport System X-AG/immunology , Amino Acid Transport System X-AG/physiology , Astrocytes/drug effects , Astrocytes/immunology , Astrocytes/physiology , Blotting, Western , Clusterin/immunology , Cytokines/drug effects , Cytokines/physiology , Disease Models, Animal , Disease Susceptibility/immunology , Fluorescent Antibody Technique , Hippocampus/immunology , Hippocampus/physiology , Immunohistochemistry , Inflammation/immunology , Kainic Acid , Microglia/drug effects , Microglia/immunology , Microglia/physiology , Neuroglia/drug effects , Random Allocation , Rats, Sprague-Dawley , Severity of Illness Index , Seizures/chemically induced , Seizures/physiopathology , Up-Regulation/drug effects , Up-Regulation/immunology , Up-Regulation/physiologyABSTRACT
Polyinosinic:polycytidylic acid (Poly I:C; 5 mg/kg body weight, ip) and lipopolysaccharide (LPS; 0.3 mg/kg body weight, ip) induced microglial and astrocytic activation in Sprague Dawley rats. Higher microglial and astrocytic activities were noticed in Poly I:C infused rats throughout the hippocampus till postnatal day 21 with a comparatively weaker response in LPS group. However, LPS induced inflammation persisted even after postnatal day 21, indicating thereby, that the Poly I:C (viral mimic) produces an acute inflammation, while LPS (bacterial endotoxin) produces chronic inflammation when exposed during early neonatal life.
Subject(s)
Acute Disease , Animals , Animals, Newborn , Antiviral Agents/pharmacology , Astrocytes/drug effects , Astrocytes/immunology , Astrocytes/metabolism , Chronic Disease , Female , Glial Fibrillary Acidic Protein/metabolism , Hippocampus/drug effects , Hippocampus/immunology , Hippocampus/metabolism , Immunoenzyme Techniques , Inflammation/chemically induced , Inflammation/immunology , Inflammation/pathology , Lipopolysaccharides/pharmacology , Microglia/drug effects , Microglia/immunology , Microglia/metabolism , Poly I-C/pharmacology , Rats , Rats, Sprague-DawleyABSTRACT
The progressive increase in life expectancy of the world population has fostered a major concern in order to find effective avenues for diagnosis of treatment of Alzheimer's disease (AD). Even tough AD pathogenesis is still unclear, new advances have allowed to understand that exposure of individuals to a series of environmental risk factors, named to as damage signals, play a main role in triggering the disease. This is important for AD prevention but also for the search of new treatment approaches. Activation of innate immunity in the central nervous system (CNS), essentially microglial cells, appears to be a key element in the neurodegenerative pathway As a matter of fact, when microglia cells are exposed continuously to damage signals such as metabolites from conditions of hyperlipidemia, hyperglycemia, oxidative stress, head injury and trauma, recurrent infections, in addition to supramolecular aggregates such as tau filaments or b-amyloid oligomers, among other anomalous protein filaments, they respond by triggering the inflammatory cascade. On this basis, we have postulated the neuroimmunomodulation hypothesis for Alzheimer's Disease. Therefore, we postulates that a long-term activation of brain innate immunity by a converging set of damage signals constitute a unifying mechanism that triggers the inflammatory cascade, thus leading to irreversible alteration in the neuronal cytoskeleton. These concerted alterations in signaling mechanisms will lead in neuronal cells to a final common pathway, tau hyperphosphorylations, with the consequent self-aggregation of modified tau and formation of paired helical filaments (PHFs), as the main triggering event for neurodegenration in AD.
El constante aumento en la expectativa de vida en la población mundial ha incrementado la preocupación hacia la búsqueda de la comprensión de la Enfermedad de Alzheimer (EA), así como de su diagnóstico temprano y tratamiento. Actualmente la etiopatogenia que conduce al desarrollo de la EA es aún difusa, pero se ha llegado a comprender que la exposición a una serie de distintos factores de riesgo, o señales de daño, está asociada al desencadenamiento de la EA. Esto es muy importante no solo para la prevención de esta devastadora enfermedad sino también para la búsqueda de avenidas efectivas para su tratamiento. En efecto, la activación de la inmunidad innata en el sistema nervioso central (SNC), esencialmente por las células microgliales, son un elemento clave en el proceso neurodegenerativo, cuando éstas son expuestas por períodos prolongados a señales de daño. Entre éstas están la hiperlipidemia, hiperglicemia, estrés oxidativo, traumatismos, infecciones recurrentes, oligomeros de -amiloide, agregados de tau, entre otros factores, los que desencadenarían una respuesta pro-inflamatoria persistente que conduce a la cascada neurodegenerativa. En base a esto, hemos postulado la teoría de la neuroinmunomodulación en la EA, y proponemos que la activación a largo plazo del sistema inmune innato por un conjunto de señales de daño constituye un mecanismo unificado que gatillo, una cascada inflamatoria que conduce a alteraciones irreversibles en el citoesqueleto. Estos mecanismos anómalos de señalización molecular llevarían a una vía final común que es la hiperfosforilación de la proteína tau, su autoagregación y formación de los PHFs, como desencadenantes claves en la neurodegeneración y desarrollo de la EA.
Subject(s)
Humans , Alzheimer Disease/immunology , Inflammation/immunology , Central Nervous System/immunology , Cytokines , Immunity, Innate/immunology , Microglia/immunology , Neuroimmunomodulation , Neurofibrillary Tangles/immunology , Precipitating Factors , Risk Factors , tau ProteinsABSTRACT
Inflammation, a self-defensive reaction against various pathogenic stimuli, may become harmful self-damaging process. Increasing evidence has linked chronic inflammation to a number of neurodegenerative disorders including Alzheimer's disease (AD), Parkinson's disease (PD), and multiple sclerosis. In the central nervous system, microglia, the resident innate immune cells play major role in the inflammatory process. Although they form the first line of defense for the neural parenchyma, uncontrolled activation of microglia may directly toxic to neurons by releasing various substances such as inflammatory cytokines (IL-1beta, TNF-alpha, IL-6), NO, PGE