Low-Level Primary Blast Induces Neuroinflammation and Neurodegeneration in Rats.

OBJECTIVE: Mild blast traumatic brain injury is commonly prevalent in modern combat casualty care and has been associated with the development of neurodegenerative conditions. However, whether primary lower level blast overpressure (LBOP) causes neurodegeneration and neuroinflammation remains largely unknown. The aim of our present study was to determine whether LBOP can cause neuroinflammation and neurodegeneration. METHODS: Anesthetized rats were randomly assigned to LBOP group (70 kPa, n = 5) or sham group (without blast, n = 5). Histopathological and cytokine changes in brain tissue at 5 days post-injury were evaluated by hematoxylin-eosin staining and Bioplex assay, respectively. RESULTS: Histopathological assessment revealed neuronal degeneration and increased density of inflammatory cells in frontal and parietal cortex, hippocampus and thalamus in rats exposed to LBOP. LBOP exposure significantly elevated levels of pro-inflammatory cytokines (EPO, IL-1ß, IL-6, IL-12, IL-18, and TNF-α) and chemokines (GRO and RANTES) as well as of an anti-inflammatory cytokine (IL-13) in the frontal cortex. CONCLUSIONS: This study reveals a role of neuroinflammation in neurodegeneration after mild blast traumatic brain injury. Therapies that target this process might in warfighters might function either by attenuating the development of post-traumatic stress disorder, chronic traumatic encephalopathy and Alzheimer's disease, or by slowing their progression.

Metabolomic profiling of schizophrenia patients at risk for metabolic syndrome.

Second-generation antipsychotics (SGAs) are commonly used to treat schizophrenia. However, SGAs cause metabolic disturbances that can manifest as metabolic syndrome (MetS) in a subset of patients. The causes for these metabolic disturbances remain unclear. We performed a comprehensive metabolomic profiling of 60 schizophrenia patients undergoing treatment with SGAs that puts them at high (clozapine, olanzapine), medium (quetiapine, risperidone), or low (ziprasidone, aripiprazole) risk for developing MetS, compared to a cohort of 20 healthy controls. Multiplex immunoassays were used to measure 13 metabolic hormones and adipokines in plasma. Mass spectrometry was used to determine levels of lipids and polar metabolites in 29 patients and 10 controls. We found that levels of insulin and tumor necrosis factor alpha (TNF-α) were significantly higher (p < 0.005) in patients at medium and high risk for MetS, compared to controls. These molecules are known to be increased in individuals with high body fat content and obesity. On the other hand, adiponectin, a molecule responsible for control of food intake and body weight, was significantly decreased in patients at medium and high risk for MetS (p < 0.005). Further, levels of dyacylglycerides (DG), tryacylglycerides (TG) and cholestenone were increased, whereas α-Ketoglutarate and malate, important mediators of the tricarboxylic acid (TCA) cycle, were significantly decreased in patients compared to controls. Our studies suggest that high- and medium-risk SGAs are associated with disruption of energy metabolism pathways. These findings may shed light on the molecular underpinnings of antipsychotic-induced MetS and aid in design of novel therapeutic approaches to reduce the side effects associated with these drugs.

Differential correlations between inflammatory cytokines and psychopathology in veterans with schizophrenia: potential role for IL-17 pathway.

Pro-inflammatory cytokines have been consistently reported to be elevated in schizophrenia patients. However, it is not known whether cytokines influence the presentation of psychotic symptoms. To address this issue, we evaluated the relationship between levels of inflammatory molecules and psychopathological parameters in patients with schizophrenia. We hypothesized that severity of symptoms would correlate with increased levels of inflammatory cytokines. Serum samples from 47 veterans with a diagnosis of schizophrenia and 20 healthy controls were tested for levels of 38 cytokines/chemokines involved in regulation of immune/inflammatory reactions using a Millipore multiplex bead array in a Luminex 100 system. We found significantly increased levels of GRO, MCP-1, MDC, and sCD40L, and significantly decreased levels of IFN-γ, IL-2, IL-12p70, and IL-17, in schizophrenia patients compared to controls. In addition, we observed positive correlations between levels of cytokines and the Positive and Negative Symptoms Scale (PANSS) scores in subjects with schizophrenia for G-CSF, IL-1ß, IL1ra, IL-3, IL-6, IL-9, IL-10, sCD40L and TNF-ß. Pathway analyses showed these cytokines to be part of the IL17 pathway. Using principal component analyses, we found the factor that included these cytokines and IL-17 to be associated with positive, general and total PANSS scores. These results suggest that alterations in this pathway may play a role in development of psychotic symptoms in schizophrenia.

Evaluación de los procesos gerenciales y calidad del servicio médico / Evaluation of the management processes and medical quality of the service

Al revisar los problemas gerenciales y el rendimiento de los Servicios de Atención en el Sector Salud en Venezuela, enfocamos nuestra investigación para: Identificar las características de los Procesos Gerenciales y describir el Nivel de la Calidad del Servicio Médico del Ambulatorio Urbano I de Villa Rosa. Municipio García. Distrito Sanitario Nº 1. Estado Nueva Esparta. Primer Semestre Año 2003. Utilizando 2 cuestionarios uno dirigido al Personal y otro al usuario. Estos datos fueron recolectados, codificados y transferidos a una matriz y analizados por un paquete estadístico: SPSS. Obteniéndose que: el 50 por ciento no participa en la planificación y determinación de metas y objetivos; un 50 por ciento siempre organiza con su superior el trabajo; el 45,8 por ciento consideró que algunas veces la información de los planes anuales es adecuada; en el 62,5 por ciento y 54,1 por ciento el superior siempre delega la toma de decisiones e indica la forma como desarrollar las actividades; el 100 por ciento del personal conoce sus funciones y atribuciones; en dirección y control la mayoría respondió siempre y/o algunas veces; en Calidad de Servicio predominó las respuestas buena y/o excelente. Los Procesos Organizacionales y la Calidad del Servicio Médico presentan marcadas fortalezas estructurales, influyendo positivamente en establecimientos con características similares al caso en estudio.