Función de las tetraspaninas y proteínas del citoesqueleto cortical de actina en la entradadel virus de la inmunodeficiencia humana (VIH-1)

Tesis doctoral inédita leida en la Universidad Autónoma de Madrid. Facultad de Medicina. Departamento de Bioquímica. Fecha de lectura: 23 de Noviembre de 200

Centro de Arte y Cultura Tumbaco

Due to the transformation that the parish of Tumbaco has undergone in recent years, there is evidence of uncontrolled growth within. This is not only reflected at a level of growth but also in the construction of its blocks. There is a problem in the distribution of free space and many of these areas have been segregated inside the built blocks...Debido a la transformación que ha sufrido la parroquia de Tumbaco en los últimos años se evidencia un crecimiento descontrolado en la misma. Esto no se refleja únicamente a nivel de crecimiento sino a la vez dentro de la edificación de las cuadras del sector..

Diagnosing external ventricular drain-related ventriculitis by means of local inflammatory response: soluble triggering receptor expressed on myeloid cells-1.

INTRODUCTION: External ventricular drainage (EVD)-related ventriculitis is one of the most severe complications associated with the use of EVDs. Establishing an early and certain diagnosis can be difficult in critically ill patients. We performed this prospective study to evaluate the usefulness of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) determination in cerebrospinal fluid (CSF) in the diagnosis of ventriculitis. METHODS: A prospective observational study was conducted of 73 consecutive patients with EVD. Samples of CSF for culture, cytobiochemical analysis and sTREM-1 determination were extracted three times a week. Ventriculitis diagnosis required a combination of microbiological, cytobiochemical and clinical criteria. RESULTS: Seventy-three consecutive patients were included. EVD-related ventriculitis was diagnosed in six patients and EVD-colonization in ten patients. Patients without clinical or microbiological findings were considered controls. The median CSF sTREM-1 was 4,320 pg/ml (interquartile range (IQR): 2,987 to 4,886) versus 266 pg/ml (118 to 689); P <0.001. There were no differences when comparing colonized-patients and controls. The best cut-off sTREM-1 value for the diagnosis of ventriculitis was 2,388.79 pg/ml (sensitivity 100%, specificity 98.5%, positive predictive value 85.71%, negative predictive value 100%). CSF proteins, glucose and the ratio CSF/serum glucose were also significantly different (P = 0.001). Serum biomarkers were not useful to diagnose EVD-related infection. These results were confirmed by a case-control study with ventriculitis patients (cases) and non-ventriculitis (control subjects) matched by age, comorbidities, severity scales and EVD duration (P = 0.004). CONCLUSIONS: CSF sTREM-1 was useful in the diagnosis of ventriculitis, in a similar measure to classical CSF parameters. Furthermore, CSF sTREM-1 could prove the diagnosis in uncertain cases and discriminate between EVD-colonization and infectio

MTOC translocation modulates IS formation and controls sustained T cell signaling

The translocation of the microtubule-organizing center (MTOC) toward the nascent immune synapse (IS) is an early step in lymphocyte activation initiated by T cell receptor (TCR) signaling. The molecular mechanisms that control the physical movement of the lymphocyte MTOC remain largely unknown. We have studied the role of the dynein–dynactin complex, a microtubule-based molecular motor, in the process of T cell activation during T cell antigen–presenting cell cognate immune interactions. Impairment of dynein–dynactin complex activity, either by overexpressing the p50-dynamitin component of dynactin to disrupt the complex or by knocking down dynein heavy chain expression to prevent its formation, inhibited MTOC translocation after TCR antigen priming. This resulted in a strong reduction in the phosphorylation of molecules such as ζ chain–associated protein kinase 70 (ZAP70), linker of activated T cells (LAT), and Vav1; prevented the supply of molecules to the IS from intracellular pools, resulting in a disorganized and dysfunctional IS architecture; and impaired interleukin-2 production. Together, these data reveal MTOC translocation as an important mechanism underlying IS formation and sustained T cell signaling

The PDZ-adaptor protein syntenin-1 regulates HIV-1 entry

Syntenin-1 is a cytosolic adaptor protein involved in several cellular processes requiring polarization. Human immunodeficiency virus type 1 (HIV-1) attachment to target CD4(+) T-cells induces polarization of the viral receptor and coreceptor, CD4/CXCR4, and cellular structures toward the virus contact area, and triggers local actin polymerization and phosphatidylinositol 4,5-bisphosphate (PIP(2)) production, which are needed for successful HIV infection. We show that syntenin-1 is recruited to the plasma membrane during HIV-1 attachment and associates with CD4, the main HIV-1 receptor. Syntenin-1 overexpression inhibits HIV-1 production and HIV-mediated cell fusion, while syntenin depletion specifically increases HIV-1 entry. Down-regulation of syntenin-1 expression reduces F-actin polymerization in response to HIV-1. Moreover, HIV-induced PIP(2) accumulation is increased in syntenin-1–depleted cells. Once the virus has entered the target cell, syntenin-1 polarization toward the viral nucleocapsid is lost, suggesting a spatiotemporal regulatory role of syntenin-1 in actin remodeling, PIP(2) production, and the dynamics of HIV-1 entry

Host adaptive immunity deficiency in severe pandemic influenza

INTRODUCTION: Pandemic A/H1N1/2009 influenza causes severe lower respiratory complications in rare cases. The association between host immune responses and clinical outcome in severe cases is unknown. METHODS: We utilized gene expression, cytokine profiles and generation of antibody responses following hospitalization in 19 critically ill patients with primary pandemic A/H1N1/2009 influenza pneumonia for identifying host immune responses associated with clinical outcome. Ingenuity pathway analysis 8.5 (IPA) (Ingenuity Systems, Redwood City, CA) was used to select, annotate and visualize genes by function and pathway (gene ontology). IPA analysis identified those canonical pathways differentially expressed (P < 0.05) between comparison groups. Hierarchical clustering of those genes differentially expressed between groups by IPA analysis was performed using BRB-Array Tools v.3.8.1. RESULTS: The majority of patients were characterized by the presence of comorbidities and the absence of immunosuppressive conditions. pH1N1 specific antibody production was observed around day 9 from disease onset and defined an early period of innate immune response and a late period of adaptive immune response to the virus. The most severe patients (n = 12) showed persistence of viral secretion. Seven of the most severe patients died. During the late phase, the most severe patient group had impaired expression of a number of genes participating in adaptive immune responses when compared to less severe patients. These genes were involved in antigen presentation, B-cell development, T-helper cell differentiation, CD28, granzyme B signaling, apoptosis and protein ubiquitination. Patients with the poorest outcomes were characterized by proinflammatory hypercytokinemia, along with elevated levels of immunosuppressory cytokines (interleukin (IL)-10 and IL-1ra) in serum. CONCLUSIONS: Our findings suggest an impaired development of adaptive immunity in the most severe cases of pandemic influenza, leading to an unremitting cycle of viral replication and innate cytokine-chemokine release. Interruption of this deleterious cycle may improve disease outcome.The study was scientifically sponsored by the Spanish Society for Critical Care Medicine (SEMICYUC). Funding: MICCIN-FIS/JCYL-IECSCYL-SACYL (Spain): Programa de Investigación Comisionada en Gripe, GR09/0021-EMER07/050- PI081236-RD07/0067. CIHR-NIH-Sardinia Recherché-LKSF Canada support DJK.S

Th1 and Th17 hypercytokinemia as early host response signature in severe pandemic influenza

Abstract Introduction Human host immune response following infection with the new variant of A/H1N1 pandemic influenza virus (nvH1N1) is poorly understood. We utilize here systemic cytokine and antibody levels in evaluating differences in early immune response in both mild and severe patients infected with nvH1N1. Methods We profiled 29 cytokines and chemokines and evaluated the haemagglutination inhibition activity as quantitative and qualitative measurements of host immune responses in serum obtained during the first five days after symptoms onset, in two cohorts of nvH1N1 infected patients. Severe patients required hospitalization (n = 20), due to respiratory insufficiency (10 of them were admitted to the intensive care unit), while mild patients had exclusively flu-like symptoms (n = 15). A group of healthy donors was included as control (n = 15). Differences in levels of mediators between groups were assessed by using the non parametric U-Mann Whitney test. Association between variables was determined by calculating the Spearman correlation coefficient. Viral load was performed in serum by using real-time PCR targeting the neuraminidase gene. Results Increased levels of innate-immunity mediators (IP-10, MCP-1, MIP-1β), and the absence of anti-nvH1N1 antibodies, characterized the early response to nvH1N1 infection in both hospitalized and mild patients. High systemic levels of type-II interferon (IFN-γ) and also of a group of mediators involved in the development of T-helper 17 (IL-8, IL-9, IL-17, IL-6) and T-helper 1 (TNF-α, IL-15, IL-12p70) responses were exclusively found in hospitalized patients. IL-15, IL-12p70, IL-6 constituted a hallmark of critical illness in our study. A significant inverse association was found between IL-6, IL-8 and PaO2 in critical patients. Conclusions While infection with the nvH1N1 induces a typical innate response in both mild and severe patients, severe disease with respiratory involvement is characterized by early secretion of Th17 and Th1 cytokines usually associated with cell mediated immunity but also commonly linked to the pathogenesis of autoimmune/inflammatory diseases. The exact role of Th1 and Th17 mediators in the evolution of nvH1N1 mild and severe disease merits further investigation as to the detrimental or beneficial role these cytokines play in severe illness

Direct association between pharyngeal viral secretion and host cytokine response in severe pandemic influenza

<p>Abstract</p> <p>Background</p> <p>Severe disease caused by 2009 pandemic influenza A/H1N1virus is characterized by the presence of hypercytokinemia. The origin of the exacerbated cytokine response is unclear. As observed previously, uncontrolled influenza virus replication could strongly influence cytokine production. The objective of the present study was to evaluate the relationship between host cytokine responses and viral levels in pandemic influenza critically ill patients.</p> <p>Methods</p> <p>Twenty three patients admitted to the ICU with primary viral pneumonia were included in this study. A quantitative PCR based method targeting the M1 influenza gene was developed to quantify pharyngeal viral load. In addition, by using a multiplex based assay, we systematically evaluated host cytokine responses to the viral infection at admission to the ICU. Correlation studies between cytokine levels and viral load were done by calculating the Spearman correlation coefficient.</p> <p>Results</p> <p>Fifteen patients needed of intubation and ventilation, while eight did not need of mechanical ventilation during ICU hospitalization. Viral load in pharyngeal swabs was 300 fold higher in the group of patients with the worst respiratory condition at admission to the ICU. Pharyngeal viral load directly correlated with plasma levels of the pro-inflammatory cytokines IL-6, IL-12p70, IFN-γ, the chemotactic factors MIP-1β, GM-CSF, the angiogenic mediator VEGF and also of the immuno-modulatory cytokine IL-1ra (p < 0.05). Correlation studies demonstrated also the existence of a significant positive association between the levels of these mediators, evidencing that they are simultaneously regulated in response to the virus.</p> <p>Conclusions</p> <p>Severe respiratory disease caused by the 2009 pandemic influenza virus is characterized by the existence of a direct association between viral replication and host cytokine response, revealing a potential pathogenic link with the severe disease caused by other influenza subtypes such as H5N1.</p

Ecos de la academia: Revista de la Facultad de Educación, Ciencia y Tecnología - FECYT Nro 5

Ecos de la academia, Revista de la Facultad de Educación Ciencia y Tecnología es una publicación científica de la Universidad Técnica del Norte, con revisión por pares a doble ciego que publica artículos en idioma español, quichua, portugués e inglés. Se edita con una frecuencia semestral con dos números por año.En ella se divulgan trabajos originales e inéditos generados por los investigadores, docentes y estudiantes de la FECYT, y contribuciones de profesionales de instituciones docentes e investigativas dentro y fuera del país, con calidad, originalidad y relevancia en las áreas de ciencias sociales y tecnología aplicada.Realidad socioinclusiva del adulto mayor del grupo etario mayor a los 70 años en las parroquias urbanas de Ibarra. Orientación vocacional y personalidad en el Sistema Nacional de Nivelación y Admisión en la Universidad Técnica de Ambato. Las primeras tarjetas postales de Ibarra, Ecuador: 1906-1914. Aprendizaje móvil en el aula. Aproximación a la Concepción Etnomatemática. La ética en la investigación educativa: ¿condición indispensable?. Inteligencia sociocultural para la inclusión. Atención al alumnado inmigrante: la visión de una profesora francesa en Galicia. Análisis crítico de la dimensión ambiental del ecosistema montañoso Guamuhaya, Cuba (1995-2014). La adaptación curricular inclusiva en la educación regular. El arte en la provincia de Imbabura de mediados del siglo XIX en torno a las escuelas de arte. Formación integral: un estudio de algunos logros y carencias. Experiencias en la publicidad online en la ciudad de Ibarra, Ecuador. Estudio exploratorio de la incidencia de los hogares disfuncionales en la iniciación sexual temprana de los adolescentes. Etnografía Virtual como aplicación metodológica: Caso Chevron en Ecuador. Alfabetización y calidad de vida: percepción de los alfabetizados. Elaboración de un manual mediante el método Delphi para la enseñanza de patronaje. Pertinencia de la Carrera de Turismo de la UTN, en el contexto de la Región 1 del Ecuador, 2016-2020. Preferencias por doble titulación de bachilleres de la Zona 1 de Ecuador y Nariño de Colombia. “Mucha Publicidad”, II Simposio de Diseño, Publicidad y Sociedad, de la UTN. Normas de presentación de artículos en la revista Ecos de la Academia

Estudio de la trascendencia clínica de la colonización por Acinetobacter baumannii en una Unidad de Cuidados Intensivos (UCI) médica. Utilidad de los programas de cribado semanal y medidas de vigilancia y control de la infección nosocomial

Acinetobacter baumannii forma parte de la flora cutánea saprófita en un 25-40% de sujetos sanos. La trascendencia clínica de la colonización de los pacientes críticos por este microorganismo es un aspecto discutido y que sigue abierto en un debate no aclarado. Lejos de la virulencia propia de otras bacterias, A. baumannii se caracteriza por su persistencia en las mucosas del paciente colonizado y en diversos fómites, su difícil erradicación y su compleja pero fácil capacidad para desarrollar resistencias a múltiples antibióticos. Nuestro objetivo es analizar la correlación entre la presión de colonización (PC) por A. baumannii y la tasa de infecciones nosocomiales por dicho microorganismo. El estudio se ha llevado a cabo a lo largo de dos años (diciembre 2012 – diciembre 2014) en la Unidad de Cuidados Intensivos (UCI) del Hospital Universitario y Politécnico la Fe (Valencia). Con una periodicidad semanal se realiza un cribado para la detección de microorganismos multirresistentes (MMR), mediante torunda para frotis rectal y orofaríngeo, además de broncoaspirado (BAS) en caso de ventilación mecánica invasiva, en aquellos pacientes ingresados durante ≥48 h en la UCI. En todos los pacientes ingresados se aplican las medidas generales de control de la infección nosocomial y, en el caso de pacientes con factores de riesgo para la colonización por MMR, se realiza además un aislamiento de contacto preventivo hasta confirmar o descartar la sospecha de colonización. De forma diaria se realiza un seguimiento de todos los pacientes para detectar precozmente posibles infecciones nosocomiales, confirmar su diagnóstico e iniciar un tratamiento antimicrobiano precoz. Para la realización del presente trabajo, se calculó la PCS (PCS= relación de pacientes colonizados en una semana / total de pacientes en riesgo esa semana), como variable individual (PCSi) y como variable global corregida por la estancia (PCSe). Las infecciones por A. baumannii se diagnosticaron según los criterios de los Centros para el control y prevención de las enfermedades (CDC) de Atlanta y se calculó una variable semanal ajustada por estancia: tasa de infección semanal (TIS= relación de pacientes diagnosticados de infección por A. baumannii en una semana / total de pacientes colonizados esa misma semana). Se elaboró una base de datos con variables demográficas, clínicas, analíticas y microbiológicas. La relación entre PCS y la TIS de cada semana se analizó mediante la correlación de Pearson