CD163-Macrophages Are Involved in Rhabdomyolysis-Induced Kidney Injury and May Be Detected by MRI with Targeted Gold-Coated Iron Oxide Nanoparticles.

Macrophages play an important role in rhabdomyolysis-acute kidney injury (AKI), although the molecular mechanisms involved in macrophage differentiation are poorly understood. We analyzed the expression and regulation of CD163, a membrane receptor mainly expressed by anti-inflammatory M2 macrophages, in rhabdomyolysis-AKI and developed targeted probes for its specific detection in vivo by MRI. Intramuscular injection of glycerol in mice promoted an early inflammatory response, with elevated proportion of M1 macrophages, and partial differentiation towards a M2 phenotype in later stages, where increased CD163 expression was observed. Immunohistological studies confirmed the presence of CD163-macrophages in human rhabdomyolysis-AKI. In cultured macrophages, myoglobin upregulated CD163 expression via HO-1/IL-10 axis. Moreover, we developed gold-coated iron oxide nanoparticles vectorized with an anti-CD163 antibody that specifically targeted CD163 in kidneys from glycerol-injected mice, as determined by MRI studies, and confirmed by electron microscopy and immunological analysis. Our findings are the first to demonstrate that CD163 is present in both human and experimental rhabdomyolysis-induced AKI, suggesting an important role of this molecule in this pathological condition. Therefore, the use of probes targeting CD163-macrophages by MRI may provide important information about the cellular composition of renal lesion in rhabdomyolysis.

In vivo PET imaging of the α4ß2 nicotinic acetylcholine receptor as a marker for brain inflammation after cerebral ischemia.

PET imaging of nicotinic acetylcholine receptors (nAChRs) could become an effective tool for the diagnosis and therapy evaluation of neurologic diseases. Despite this, the role of nAChRs α4ß2 receptors after brain diseases such as cerebral ischemia and its involvement in inflammatory reaction is still largely unknown. To investigate this, we performed in parallel in vivo magnetic resonance imaging (MRI) and positron emission tomography (PET) with 2[(18)F]-fluoro-A85380 and [(11)C]PK11195 at 1, 3, 7, 14, 21, and 28 d after middle cerebral artery occlusion (MCAO) in rats. In the ischemic territory, PET with 2[(18)F]-fluoro-A85380 and [(11)C]PK11195 showed a progressive binding increase from days 3-7, followed by a progressive decrease from days 14-28 after cerebral ischemia onset. Ex vivo immunohistochemistry for the nicotinic α4ß2 receptor and the mitochondrial translocator protein (18 kDa) (TSPO) confirmed the PET findings and demonstrated the overexpression of α4ß2 receptors in both microglia/macrophages and astrocytes from days 7-28 after experimental ischemic stroke. Likewise, the role played by α4ß2 receptors on neuroinflammation was supported by the increase of [(11)C]PK11195 binding in ischemic rats treated with the α4ß2 antagonist dihydro-ß-erythroidine hydrobromide (DHBE) at day 7 after MCAO. Finally, both functional and behavioral testing showed major impaired outcome at day 1 after ischemia onset, followed by a recovery of the sensorimotor function and dexterity from days 21-28 after experimental stroke. Together, these results suggest that the nicotinic α4ß2 receptor could have a key role in the inflammatory reaction underlying cerebral ischemia in rats.

PET imaging of serotoninergic neurotransmission with [(11)C]DASB and [(18)F]altanserin after focal cerebral ischemia in rats.

The use of selective serotonin reuptake inhibitors has shown functional improvement after stroke. Despite this, the role of serotoninergic neurotransmission after cerebral ischemia evolution and its involvement in functional recovery processes are still largely unknown. For this purpose, we performed in parallel in vivo magnetic resonance imaging and positron emission tomography (PET) with [(11)C]DASB and [(18)F]altanserin at 1, 3, 7, 14, 21, and 28 days after middle cerebral artery occlusion (MCAO) in rats. In the ischemic territory, PET with [(11)C]DASB and [(18)F]altanserin showed a dramatic decline in serotonin transporter (SERT) and 5-HT2A binding potential in the cortex and striatum after cerebral ischemia. Interestingly, a slight increase in [(11)C]DASB binding was observed from days 7 to 21 followed by the uppermost binding at day 28 in the ipsilateral midbrain. In contrast, no changes were observed in the contralateral hemisphere by using both radiotracers. Likewise, both functional and behavior testing showed major impaired outcome at day 1 after ischemia onset followed by a recovery of the sensorimotor function and dexterity from day 21 to day 28 after cerebral ischemia. Taken together, these results might evidence that SERT changes in the midbrain could have a key role in the functional recovery process after cerebral ischemia.

El estrés en personal sanitario hospitalario; estado actual / The stress in the hospital sanitary personnel; current status

Introducción: Los riesgos psicosociales y en particular el estrés se han convertido en uno de los principales problemas para la salud y la seguridad laboral. Se ha realizado una revisión de la literatura científica actual sobre el estrés debido a su importancia como riesgo emergente, y la repercusión de este problema en la productividad y el deterioro de la calidad de vida en el personal sanitario que desarrolla su actividad profesional en medio hospitalario, así como intentar identificar los principales métodos de evaluación del estrés actualmente utilizados. Objetivos: Conocer el estado actual del estrés en el personal hospitalario e identificar los principales métodos de evaluación. Metodología: Se realizo una búsqueda bibliográfica exploratoria utilizando las bases de datos Medline, Embase, Scirus, Wok, Psicoinfo, OSH update, Cisdoc, IBECS y LILACS, así como en repositorios como Dialnet, SciELO y Google académico. El periodo de estudio de la bibliografía publicada fue el comprendido entre el año 2009 y 2012 realizándose la última búsqueda el 10 de diciembre de 2012. Resultados: Los niveles de estrés encontrados en los artículos revisados fueron moderados-altos, con diferencias entre las distintas áreas y especialidades. Factores individuales tanto objetivos como subjetivos parecen influir en los grados de estrés. Existe diversidad de métodos utilizados para la evaluación del estrés, la mayoría tienen un nivel de fiabilidad elevado. La producción bibliográfica encontrada es mayor en Asia y Europa. Conclusiones: Los niveles de estrés son elevados en el personal sanitario del hospital ,sobre todo en algunas areas y especialidades, existen una serie de moderadores del grado de estrés como los factores individuales y el ambiente físico y no existe un consenso internacional en el método utilizado para su evaluación (AU)

Introduction: Psychosocial risks and stress in particular have become one of the major problems for health and safety. There has been a review of the current scientific literature on stress due to its importance as an emerging risk, and the impact of this problem on productivity and impaired quality of life in personnel hospital and try to identify the main stress assessment methods currently used. Objective: To determine the current state of stress in personnel hospital and identify the main evaluation methods. Methods: A Bibliography review using Medline, Embase, Scirus, Wok, Psicoinfo, OSH update, CISDOC IBECS and LILACS as well as repositories as Dialnet, SciELO and Google Scholar. The study period of the published literature was between 2009 and 2012 carried the last search December 10, 2012. Results: Stress levels found in the articles reviewed were moderate-high, with differences between different areas and specialties. Individual factors both objective and subjective appear to influence the degree of stress. There is variety of methods used for the evaluation of stress; most have a high reliability level. The literature found production is higher in Asia and Europe. Conclusion: Stress levels are high in the sanitary personnel hospital, especially in some areas and specialties. There are a number of moderators of the degree of stress as individual factors and the physical environment , and there is no international consensus on the method used for evaluation (AU)