8 results on '"Fandos, Marta"'
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2. Diabetes mellitus y barrera hematorretiniana. Análisis in vitro de la expresión de proteínas de tight junction y su traducción funcional. Implicaciones terapéuticas
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Villarroel Fandos, Marta, Simó Canonge, Rafael, Hernández Pascual, Cristina, Garcia-Ramírez, Marta, and Universitat Autònoma de Barcelona. Departament de Bioquímica i Biologia Molecular
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Barrera hematorretiniana ,Ciències Experimentals ,Retinopatía diabética ,Diabetic retinopathy ,Retinopatia diabètica ,Blood-retinal ,Tinght junction - Abstract
El edema macular diabético (DME) es una de las primeras causas de disminución de la agudeza visual en pacientes con retinopatía diabética (DR). La rotura de la barrera hematorretiniana (BHR) debido a la disrupción de las tight junctions (TJ) es el principal factor causante del DME. Además, el incremento de las citoquinas proinflamatorias como la IL-1β juega un papel importante en la patogénesis del DME y la retinopatía diabética proliferativa (PDR). Mientras que la alteración de las proteínas implicadas en la disrupción de las TJ de la BHR interna ha sido ampliamente estudiada, existe poca información sobre este proceso en la BHR externa. En el estudio FIELD sobre DR, el tratamiento con fenofibrato redujo en un 30% la necesidad de tratamiento con láser en pacientes diabéticos. Además, en el estudio ACCORD-Eye se observó una reducción del 40% en la progresión de la DR en el grupo de pacientes diabéticos a los que se les administró fenofibrato. Sin embargo, los mecanismos a través de los cuales el fenofibrato ejerce sus efectos beneficiosos en pacientes con DR se desconocen. En base a lo explicado anteriormente, los objetivos de esta tesis han sido: 1. Estudiar el efecto de la hiperglicemia sobre la funcionalidad de la BHR externa y la expresión de las proteínas de TJ en una línea celular humana de RPE (ARPE-19). 2. Estudiar el efecto protector del ácido fenofíbrico (el metabolito activo del fenofibrato) sobre la funcionalidad y la expresión de las proteínas de TJ en células ARPE-19 cultivadas bajo diferentes concentraciones de glucosa, con o sin IL-1β. Además se evaluó la implicación de la vía de la AMPK en la hiperpermeabilidad inducida por la IL-1β y el efecto del ácido fenofíbrico sobre la activación de la AMPK. En nuestro primer trabajo observamos una disminución de la permeabilidad y un aumento de los niveles de claudina-1 en condiciones de hiperglicemia. Sin embargo, después de bloquear la expresión de claudina-1 no se detectaron cambios en la resistencia transepitelial (TER) ni en la permeabilidad. Estos resultados sugieren que la sobreexpresión de claudina-1 inducida por la hiperglicemia no está relacionada con los mecanismos a través de los cuales la glucosa aumenta la función oclusiva de las TJ en las células ARPE-19. Se demuestra que es la combinación de los diferentes factores presentes en el medio diabético, y no la hiperglicemia por sí sola, los que producen una alteración de la funcionalidad de la BHR externa y la disrupción de las TJ. En el segundo trabajo utilizamos una combinación de IL-1β + hiperglicemia con el fin de simular en las células ARPE-19 la lesión producida por el medio diabético. El tratamiento con ácido fenofíbrico redujo (a 25 μmol/l) o previno (a 100 μmol/l) de manera dosis dependiente, el aumento de permeabilidad y la desorganización de las TJ inducida por la IL-1β + 25 mmol/l D-Glucosa, hecho que se asoció a una mayor preservación de la función de sellado de las células del RPE. Este efecto no está relacionado con cambios en la expresión de las proteínas de TJ y sugiere que para el correcto funcionamiento de la BHR externa es más importante una adecuada distribución y estructura de las TJ que un aumento en el contenido neto de éstas. Además, demostramos que el efecto protector del ácido fenofíbrico se debe a su capacidad para suprimir la activación de la AMPK inducida por la IL-1β, previniendo así la hiperpermeabilidad inducida por el medio diabético. Nuestros resultados contribuyen significativamente a aumentar el conocimiento sobre los mecanismos de acción a través de los cuales el fenofibrato ejerce sus efectos beneficiosos en el desarrollo y la progresión del DME., Diabetic macular edema (DME) is one of the primary causes of poor visual acuity in patients with diabetic retinopathy (DR). The breakdown of the blood-retinal barrier (BRB) due to the disruption of tight junctions (TJ) is the main factor accounting for DME. In addition, the increase of proinflammatory cytokines such as IL-1β plays a key role in the pathogenesis of DME and proliferative diabetic retinopathy (PDR). While extensive work has been carried out to identify the factors involved in the disruption of TJ of the inner BRB, the mechanisms implicated in the outer BRB regulation have been poorly explored. In the FIELD study on DR, treatment with fenofibrate reduced the need for laser treatment for DME and PDR by 30% in diabetic patients. In addition, the ACCORD Eye Study showed a 40% reduction in DR progression in the group of patients receiving fenofibrate. However, the mechanisms by which fenofibrate exerts its beneficial effects in DR remain to be elucidated. With all this background, the main points of this thesis were: 1. To study the effects of high glucose concentration on the outer BRB function and the expression of TJ proteins in a human RPE cell line (ARPE-19). 2. To study the effect of fenofibric acid (the active metabolite of fenofibrate) on the barrier function and the levels of TJ proteins in ARPE-19 cells cultured under different glucose concentrations with and without IL-1β. In addition, we evaluated the role of AMPK in mediating the hyperpermeability induced by IL-1β and the effect of fenofibric acid on AMPK activation. Our first study showed a reduction of permeability and an increment of claudin-1 levels under hyperglycemic conditions. However, after blocking claudin-1 expression no changes in transepithelial electrical resistance (TER) and permeability were observed. These results suggest that the overexpression of claudin-1 induced by high glucose concentration is not involved in the mechanisms by which glucose increases the TJ sealing function in ARPE-19 cells. In addition, our findings demonstrate that hyperglycemia per se is not the only cause responsible for the breakdown of the outer BRB in patients with DR. It is the combination of different factors present in the diabetic milieu with hyperglycemia, the one responsible for the impairment of the outer BRB and TJ disruption. In our second study we used a combination of IL-1β + hyperglycemia to mimic the diabetic milieu and induce the breakdown of ARPE-19 monolayer. Treatment with fenofibric acid was able to reduce (at 25 μmol/l) or prevent (at 100 μmol/l) in a dose-dependent manner, the increment of permeability and the disorganization of TJ induced by IL-1β + 25 mmol/l D-Glucose, which was associated with the preservation of the sealing function of RPE cells. This effect was unrelated to changes in the content of TJ proteins, suggesting that an ordered distribution, rather than a crude assortment, of TJ proteins is essential for the efficient functioning of the outer BRB barrier. In addition, we demonstrated that the protective effect of fenofibric acid was mainly mediated by its ability to lower AMPK activation induced by IL-1β, which prevented the hypermermeability induced by the diabetic milieu. These findings contribute significantly to increasing our knowledge about the mechanisms involved in the beneficial effects of fenofibrate on the development and progression of DME.
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- 2015
3. Insulin resistance and oxidative stress in familial combined hyperlipidemia
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Martinez-Hervas, Sergio, primary, Fandos, Marta, additional, Real, Jose T., additional, Espinosa, Olga, additional, Chaves, F. Javier, additional, Saez, Guillermo T., additional, Salvador, Amparo, additional, Cerdá, Concha, additional, Carmena, Rafael, additional, and Ascaso, Juan F., additional
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- 2008
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4. Estudio de los valores de 8-oxo-7,8-dihidro-2’-desoxiguanosina como marcador de estrés oxidativo del ADN en pacientes con hiperlipemia familiar combinada
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Ferri, Jordi, primary, Martínez-Hervás, Sergio, additional, Espinosa, Olga, additional, Fandos, Marta, additional, Pedro, Teresa, additional, Tomás Real, José, additional, Javier Chaves, Felipe, additional, Cerdá, Concha, additional, Sáez, Guillermo, additional, and Francisco Ascaso, Juan, additional
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- 2008
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5. Urinary 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxo-dG), a reliable oxidative stress marker in hypertension
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Espinosa, Olga, primary, Jiménez-Almazán, Jorge, additional, Chaves, Felipe J., additional, Tormos, M. Carmen, additional, Clapes, Sonia, additional, Iradi, Antonio, additional, Salvador, Amparo, additional, Fandos, Marta, additional, Redón, Josep, additional, and Sáez, Guillermo T., additional
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- 2007
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6. Impairment of antioxidant enzymes, lipid peroxidation and 8-oxo-2′-deoxyguanosine in advanced epithelial ovarian carcinoma of a Spanish community
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Sanchez, Maria, primary, Torres, José Vicente, additional, Tormos, Carmen, additional, Iradi, Antonio, additional, Muñiz, Pilar, additional, Espinosa, Olga, additional, Salvador, Amparo, additional, Rodriguez-Delgado, Juana, additional, Fandos, Marta, additional, and Sáez, Guillermo T., additional
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- 2006
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7. Impact of cardiovascular risk factors on oxidative stress and DNA damage in a high risk Mediterranean population.
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Fandos, Marta, Corella, Dolores, Guillén, Marisa, Portolés, Olga, Carrasco, Paula, Iradi, Antonio, Martínez-González, Miguel A., Estruch, Ramón, Covas, Maria I., Lamuela-Raventós, Rosa María, Michavilla, Maria Teresa, Cerdá, Concha, Torregrosa, Rafael, Redón, Josep, Chaves, Francisco Felipe, Tormos, M. Carmen, Ocete, Dolores, and Sáez, Guillermo T.
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OXIDATIVE stress , *DNA damage , *CARDIOVASCULAR diseases risk factors , *HYPERTENSION , *MALONDIALDEHYDE , *SUPEROXIDE dismutase , *CATALASE - Abstract
The impact of classic cardiovascular risk factors on oxidative stress status in a high-risk cardiovascular Mediterranean population of 527 subjects was estimated. Oxidative stress markers (malondialdehyde, 8-oxo-7′8′-dihydro-2′-deoxyguanosine, oxidized/reduced glutathione ratio) together with the activity of antioxidant enzyme triad (superoxide dismutase, catalase, glutathione peroxidase) were analysed in circulating mononuclear blood cells. Malondialdehyde, oxidized glutathione and the ratio of oxidized to reduced glutathione were significantly higher while catalase and glutathione peroxidase activities were significantly lower in high cardiovascular risk participants than in controls. Statistically significant differences were obtained after additional multivariate control for sex, age, obesity, diabetes, lipids and medications. Among the main cardiovascular risk factors, hypertension was the strongest determinant of oxidative stress in high risk subjects studied at a primary prevention stage. [ABSTRACT FROM AUTHOR]
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- 2009
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8. [8-oxo-7,8-dihydro-2'-deoxyguanosine as a marker of DNA oxidative stress in individuals with combined familiar hyperlipidemia].
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Ferri J, Martínez-Hervás S, Espinosa O, Fandos M, Pedro T, Real JT, Chaves FJ, Cerdá C, Sáez G, and Ascaso JF
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- 8-Hydroxy-2'-Deoxyguanosine, Adult, Biomarkers blood, Case-Control Studies, Deoxyguanosine blood, Female, Humans, Hyperlipidemia, Familial Combined metabolism, Male, Middle Aged, DNA metabolism, Deoxyguanosine analogs & derivatives, Hyperlipidemia, Familial Combined blood, Hyperlipidemia, Familial Combined genetics, Oxidative Stress
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Background and Objective: To compare 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG) value as an indicator of oxidative stress situation between healthy and familial combined hyperlipidemic (FCH) subjects as a mixed dislipidemia with insulin resistance model and early coronary heart disease, and to study its relationship with clinical-biologic parameters of insulin resistance., Subjects and Method: 40 non-related FCH patients (15 women) and 20 normolipidemic and nondiabetic healthy subjects (8 women) were studied. Clinical, anthropometric and biochemical parameters (lipidic profile, glucemia, insulinemia and 8-oxo-dG) were measured in fasting state in all., Results: Both groups had similar age, body mass index blood pressure and waist perimeter values. Insulin and 8-oxo-dG values were significantly higher in FHC subjects. These differences were maintained after correcting by waist perimeter. 8-oxo-dG correlated positively with insulin and trygliceride; and negatively with high density lipoprotein cholesterol in FCH subjects., Conclusions: Insulin values are independently correlated with oxidative stress degree measured as 8-oxo-dG.
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- 2008
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