ABSTRACT
Air pollution (gases and particulate matter -PM) and child undernutrition are globally recognized stressors with significant consequences. PM and its components breach the respiratory alveolar-capillary barrier, entering the vasculature transporting not only harmful particles and its mediators but, altering vascular paracrine and autocrine functions. The aim of this study was to investigate the effects of Residual Oil Fly Ash (ROFA), on the vasculature of young animals with nutritional growth retardation (NGR). Weanling rats were fed a diet restricted 20% (NGR) compared to ad libitum intake (control-C) for 4 weeks. Rats were intranasally instilled with 1 mg/kg BW of ROFA. After 24h exposure, histological and immunohistochemical, biochemical and contractile response to NA/ACh were evaluated in aortas. ROFA induced changes in the tunica media of the aorta in all groups regarding thickness, muscular cells and expression of Connexin-43. ROFA increased TGF-ß1 and decreased eNOs levels and calcium channels in C and NGR animals. An increment in cytokines IL-6 and IL-10 was observed in C, with no changes in NGR. ROFA exposure altered the vascular contractile capacity. In conclusion, ROFA exposure could increase the risk for CVD through the alteration of vascular biochemical parameters, a possible step of the endothelial dysfunction.
Subject(s)
Air Pollution , Malnutrition , Animals , Rats , Male , Malnutrition/physiopathology , Malnutrition/complications , Air Pollution/adverse effects , Nitric Oxide Synthase Type III/metabolism , Coal Ash/toxicity , Rats, Wistar , Connexin 43/metabolism , Particulate Matter/toxicity , Aorta/drug effects , Transforming Growth Factor beta1/metabolism , Air Pollutants/toxicityABSTRACT
Introducción: la diabetes mellitus autoinmune (DMA) y la enfermedad celíaca (EC) son enfermedades crónicas, poligénicas y multifactoriales vinculadas con la disfunción del sistema inmune. Dado que es frecuente que un mismo paciente presente ambas patologías, la detección simultánea de los marcadores de autoinmunidad de DMA y EC sería una estrategia racional para mejorar el diagnóstico. Objetivos: desarrollar un inmunoensayo basado en citometría de flujo (FloCMIA multiplex) para la detección simultánea y discriminativa de marcadores de DMA (GADA e IA-2A) y de EC (tTgA). Materiales y métodos: las muestras analizadas consistieron en sueros provenientes de 35 individuos controles normales y 21 pacientes con diabetes mellitus tipo 1 (DM1). Se empleó un modelo de "doble paratope" incubando los sueros con una mezcla de microesferas de diferente fluorescencia interna, cada una adsorbida con un autoantígeno: TrxGAD, TrxIA-2 o H6-tTg, y una mezcla de dichos autoantígenos biotinilados. Los inmunocomplejos se detectaron con estreptavidina-ficoeritrina y se adquirió en un citómetro de flujo. Resultados: FloCMIA multiplex detectó GADA en el 76,2% de los pacientes e IA-2A en el 52,38% (sensibilidad analítica: 88,24 y 56,25% respectivamente,y especificidad: 85,71%) y tTgA en el 42,86% (sensibilidad analítica: 50,0%, y especificidad: 80,0%). Estos resultados se contrastaron con el ensayo de unión de radioligando para GADA e IA-2A y se detectaron 80,95 y 76,19% de los sueros respectivamente (especificidad: 100%), y con un ELISA para tTgA se detectó un 38,1% (especificidad: 97,1%). Conclusiones: FloCMIA multiplex permitió detectar y discriminar GADA, IA-2A y/o tTgA, -en un único acto analítico- en sueros de pacientes con DMA y/o EC. El novedoso inmunoensayo desarrollado simplifica el screening de la población a gran escala
Introduction: autoimmune diabetes mellitus (ADM) and celiac disease (CD) are chronic, polygenic and multifactorial diseases associated with immune system dysfunction. As it is frequent that a patient presents both pathologies, the simultaneous detection of autoimmunity markers of ADM and CD would be a rational strategy to improve the diagnosis. Objectives: to develop an immunoassay based on Flow Cytometry (FloCMIA multiplex) for the simultaneous and discriminative detection of markers for ADM (GADA and IA-2A) and CD (tTgA). Materials and methods: thirty five serum samples of control individuals and 21 type 1 diabetes mellitus (T1DM) patients were assayed. A "double bridge" model was used for the assay, incubating the serum samples with a mixture of microspheres containing different amount of internal fluorescence, each one adsorbed with an autoantigen: TrxGAD, TrxIA-2 or H6-tTg, and a mixture of the same biotinilated autoantigens. The immunocomplexes were detected using streptavidinphycoerytrin and then acquired in a flow cytometer. Results: FloCMIA multiplex detected GADA in 76.2% of the patients; IA-2A in 52.38% (analytical sensitivity: 88.24% and 56.25% respectively, and specificity: 85.71%) and tTgA in 42.86% (analytical sensitivity: 50.0%, and specificity: 80.0%). These results were compared with the radioligand binding assay for GADA and IA-2A, detecting 80.95% and 76.19% of the serum samples respectively (100% specificity), and with an ELISA for tTgA detecting 38.1% (97.1% specificity). Conclusions: FloCMIA multiplex allowed detecting and discriminating GADA, IA-2A and/or tTgA, -in a single assay- in serum samples of ADM and/or CD. The novel developed immunoassay simplifies the screening of the large scale population