11 results on '"Fernández-Villegas, Ana"'
Search Results
2. Intramitochondrial proteostasis is directly coupled to α-synuclein and amyloid β1-42 pathologies
- Author
-
Lautenschläger, Janin, primary, Wagner-Valladolid, Sara, additional, Stephens, Amberley D., additional, Fernández-Villegas, Ana, additional, Hockings, Colin, additional, Mishra, Ajay, additional, Manton, James D., additional, Fantham, Marcus J., additional, Lu, Meng, additional, Rees, Eric J., additional, Kaminski, Clemens F., additional, and Kaminski Schierle, Gabriele S., additional
- Published
- 2020
- Full Text
- View/download PDF
3. A Parasite Biomarker Set for Evaluating Benznidazole Treatment Efficacy in Patients with Chronic Asymptomatic Trypanosoma cruzi Infection
- Author
-
Egui, Adriana, primary, Thomas, M. Carmen, additional, Fernández-Villegas, Ana, additional, Pérez-Antón, Elena, additional, Gómez, Inmaculada, additional, Carrilero, Bartolomé, additional, del Pozo, Ángel, additional, Ceballos, Maialen, additional, Andrés-León, Eduardo, additional, López-Ruz, Miguel Ángel, additional, Gainza, Eusebio, additional, Oquiñena, Enrique, additional, Segovia, Manuel, additional, and López, Manuel Carlos, additional
- Published
- 2019
- Full Text
- View/download PDF
4. Intra-mitochondrial proteostasis is directly coupled to alpha-synuclein and Amyloid β 1-42 pathology
- Author
-
Lautenschläger, Janin, primary, Wagner-Valladolid, Sara, additional, Stephens, Amberley D., additional, Fernández-Villegas, Ana, additional, Hockings, Colin, additional, Mishra, Ajay, additional, Manton, James D., additional, Fantham, Marcus J., additional, Lu, Meng, additional, Rees, Eric J., additional, Kaminski, Clemens F., additional, and Schierle, Gabriele S. Kaminski, additional
- Published
- 2019
- Full Text
- View/download PDF
5. Short-term follow-up of chagasic patients after benznidazole treatment using multiple serological markers
- Author
-
Fernández-Villegas Ana, Pinazo María, Marañón Concepción, Thomas M Carmen, Posada Elizabeth, Carrilero Bartolomé, Segovia Manuel, Gascon Joaquim, and López Manuel C
- Subjects
Infectious and parasitic diseases ,RC109-216 - Abstract
Abstract Background Conventional serological tests, using total soluble proteins or a cocktail of recombinant proteins from T. cruzi as antigens, are highly sensitive for Chagas disease diagnosis. This type of tests, however, does not seem to be reliable tools for short- and medium-term monitoring of the evolution of patients after antiparasitic treatment. The aim of the present study was to search for immunological markers that could be altered in the sera from Chagas disease patients after benznidazole treatment, and therefore have a potential predictive diagnostic value. Methods We analyzed the reactivity of sera from chagasic patients during different clinical phases of the disease against a series of immunodominant antigens, known as KMP11, PFR2, HSP70 and Tgp63. The reactivity of the sera from 46 adult Chronic Chagas disease patients living in a non-endemic country without vector transmission of T. cruzi (15 patients in the indeterminate stage, 16 in the cardiomiopathy stage and 16 in the digestive stage) and 22 control sera from non-infected subjects was analyzed. We also analyzed the response dynamics of sera from those patients who had been treated with benznidazole. Results Regardless of the stage of the sickness, the sera from chagasic patients reacted against KMP11, HSP70, PFR2 and Tgp63 recombinant proteins with statistical significance relative to the reactivity against the same antigens by the sera from healthy donors, patients with autoimmune diseases or patients suffering from tuberculosis, leprosy or malaria. Shortly after benznidazole treatment, a statistically significant decrease in reactivity against KMP11, HSP70 and PFR2 was observed (six or nine month). It was also observed that, following benznidazole treatment, the differential reactivity against these antigens co-relates with the clinical status of the patients. Conclusions The recombinant antigens KMP11, PFR2, Tgp63 and HSP70 are recognized by Chagas disease patients' sera at any clinical stage of the disease. Shortly after benznidazole treatment, a drop in reactivity against three of these antigens is produced in an antigen-specific manner. Most likely, analysis of the reactivity against these recombinant antigens may be useful for monitoring the effectiveness of benznidazole treatment.
- Published
- 2011
- Full Text
- View/download PDF
6. Identificación y caracterización de biomarcadores de patología de la enfermedad de Chagas y de eficacia del tratamiento con benznidazol
- Author
-
Fernández Villegas, Ana Isabel, Universidad de Granada. Departamento de Bioquímica y Biología Molecular III e Inmunología, Thomas Carazo, María del Carmen, Marañón Lizana, Concepción, and López López, Manuel Carlos
- Subjects
Marcadores (Biología) ,Enfermedad de chagas ,616.9 ,Trypanosoma cruzi ,Benznidazole ,576.8 ,577.15 ,3207.10 - Abstract
La enfermedad de Chagas, o tripanosomiasis americana es causada por el protozoo flagelado hematófilo Trypanosoma cruzi. Esta zoonosis es endémica del continente americano. Se estima que existen entre 8 y 10 millones de personas infectadas en el mundo y que cerca de 40 millones están en riesgo de infectarse (Coura and Dias, 2009; Schofield and Galvao, 2009). La enfermedad presenta unos elevados índices de mortalidad y morbilidad asociados con trastornos cardiacos y digestivos. Actualmente, debido a los movimientos migratorios, la enfermedad de Chagas está presente en zonas no endémicas, donde la transmisión por transfusión sanguínea, transplantes de órganos y vía transplacentaria resultan en un alto número de nuevos casos (Wendel, 2010; Barcan et al., 2005; Carrilero et al., 2009). La enfermedad cursa con diferentes fases; una fase aguda subclínica en la mayoría de los casos, que ocasiona la muerte en el 10% de los pacientes. A la fase aguda le sigue una fase indeterminada inaparente y una fase crónica (40% de los pacientes) en la que el parásito persiste en tejidos profundos y a la que se le asocian altas tasas de mortalidad y morbilidad. A lo largo de la fase crónica, puede aparecer sintomatología cardiaca y/o trastornos digestivos. En fases avanzadas, la enfermedad crónica de Chagas puede causar la muerte (Prata, 2001; Punukollu et al., 2007). Los dos medicamentos disponibles para el tratamiento de la enfermedad de Chagas son el Benznidazol y el Nifurtimox. Ambos fármacos presentan diversos efectos secundarios, como fiebres, dolores musculares, pérdida de peso y reacciones cutáneas. En la fase inicial aguda, la administración de estos medicamentos ayuda a controlar la enfermedad y disminuye la probabilidad de cronicidad (Jannin and Villa, 2007), pero en fases crónicas su efectividad no está firmemente demostrada. Estudios previos han indicado que el tratamiento con benznidazol en pacientes asintomáticos retrasa la aparición de daños cardiacos (Gallerano and Sosa, 2000; Viotti et al., 1994). Actualmente, las pruebas serológicas más utilizadas para el diagnóstico de Chagas son el ensayo de hemaglutinación (IHA), el ensayo de inmunofluorescencia (Woolley and Merrifield) y el ensayo por inmunoabsorción ligado a enzimas (ELISA). Los antígenos que contienen estos tests son extractos de proteínas totales del parásito o una combinación de proteínas recombinantes del mismo (Britto et al., 2001; Viotti et al., 2006). Estas técnicas son capaces de detectar la respuesta de anticuerpos producida frente a las proteínas de parásitos en sueros de pacientes de Chagas, aunque no son útiles para diferenciar si el paciente se encuentra en fase indeterminada o en fase crónica de la enfermedad, resultan poco útiles para evaluar la progresión de pacientes bajo tratamiento, ya que los anticuerpos son muy estables y persisten durante mucho tiempo (WHO, 2002). Por tanto, las pruebas serológicas convencionales no permiten detectar la evolución de respuesta tras el tratamiento y por tanto reconocer fallos terapéuticos. Debido a la importancia y necesidad de evaluar el estado de la enfermedad de pacientes de Chagas, tanto la fase de la enfermedad como durante el seguimiento tras el tratamiento con benznidazol, se han propuesto como objetivos, por una parte la búsqueda de moléculas capaces de discernir entre fases de la enfermedad de Chagas y, por otra parte, encontrar marcadores susceptibles de ser sensibles al tratamiento con benznidazol con valor predictivo del estado clínico del paciente. Con los resultados descritos a lo largo de este trabajo hemos podido establecer un biomarcador serológico de la enfermedad de Chagas capaz de distinguir entra la fase crónica asintomática y fase crónica sintomática (manifestaciones cardiacas o trastornos digestivos). Por otra parte, se han identificado un sistema de marcadores serológicos útiles para evaluar la modificación de la respuesta inmunitaria adaptativa en pacientes de Chagas tratados con benznidazol. Y, por último, se presenta la aplicación de los marcadores serológicos anteriormente mencionados en un caso clínico de dos mellizos infectados con Trypanosoma cruzi vía congénita en una zona no endémica como es España., Tesis Univ. Granada. Departamento de Bioquímica y Biología Molecular III e Inmunología
- Published
- 2013
7. The innate immune response status correlates with a divergent clinical course in congenital Chagas disease of twins born in a non-endemic country
- Author
-
Fernández-Villegas, Ana, primary, Thomas, M. Carmen, additional, Carrilero, Bartolomé, additional, Téllez, Cinta, additional, Marañón, Concepción, additional, Murcia, Laura, additional, Moralo, Sara, additional, Alonso, Carlos, additional, Segovia, Manuel, additional, and López, Manuel Carlos, additional
- Published
- 2014
- Full Text
- View/download PDF
8. Characterization of an Immunodominant Antigenic Epitope from Trypanosoma cruzi as a Biomarker of Chronic Chagas' Disease Pathology
- Author
-
Thomas, M. Carmen, primary, Fernández-Villegas, Ana, additional, Carrilero, Bartolomé, additional, Marañón, Concepción, additional, Saura, Daniel, additional, Noya, Oscar, additional, Segovia, Manuel, additional, Alarcón de Noya, Belkisyolé, additional, Alonso, Carlos, additional, and López, Manuel Carlos, additional
- Published
- 2012
- Full Text
- View/download PDF
9. Characterization of an Immunodominant Antigenic Epitope from Trypanosoma cruzias a Biomarker of Chronic Chagas' Disease Pathology
- Author
-
Thomas, M. Carmen, Fernández-Villegas, Ana, Carrilero, Bartolomé, Marañón, Concepción, Saura, Daniel, Noya, Oscar, Segovia, Manuel, Alarcón de Noya, Belkisyolé, Alonso, Carlos, and López, Manuel Carlos
- Abstract
ABSTRACTNowadays, the techniques available for chronic Chagas' disease diagnosis are very sensitive; however, they do not allow discrimination of the patient's clinical stages of the disease. The present paper describes that three out of the five different repeats contained in the Trypanosoma cruziTcCA-2 membrane protein (3972-FGQAAAGDKPPP, 6303-FGQAAAGDKPAP, and 3973-FGQAAAGDKPSL) are recognized with high sensitivity (>90%) by sera from chronic Chagas' disease patients and that they are not recognized by sera from patients in the acute phase of the disease. A total of 133 serum samples from chagasic patients and 50 serum samples from healthy donors were tested. In addition, sera from 15 patients with different autoimmune diseases, 43 serum samples from patients suffering an infectious disease other than Chagas' disease, and 38 serum samples from patients with nonchagasic cardiac disorders were also included in this study. The residue 3973 peptide shows a specificity of >98%, as it is not recognized by individuals with autoimmune and inflammatory processes or by patients with a nonchagasic cardiomyopathy. Remarkably, the levels of antibody against the 3973 epitope detected by the sera from Chagas' disease patients in the symptomatic chronic phase, involving cardiac or digestive alterations, are higher than those detected by the sera from Chagas' disease patients in the indeterminate phase of the disease. It is suggested that the diagnostic technique described could also be used to indicate the degree of pathology. The amino acids F, Q, and DKP located in the peptide at positions 1, 3, and 8 to 10, respectively, are essential to conform to the immunodominant antigenic epitope.
- Published
- 2011
- Full Text
- View/download PDF
10. Intramitochondrial proteostasis is directly coupled to α-synuclein and amyloid β1-42 pathologies
- Author
-
Lautenschläger, Janin, Wagner-Valladolid, Sara, Stephens, Amberley D, Fernández-Villegas, Ana, Hockings, Colin, Mishra, Ajay, Manton, James D, Fantham, Marcus J, Lu, Meng, Rees, Eric J, Kaminski, Clemens F, and Kaminski Schierle, Gabriele S
- Subjects
amyloid-β (Aβ,) ,HtrA2/Omi ,Nerve Tissue Proteins ,protein aggregation ,Rats, Sprague-Dawley ,neurodegenerative disease ,α-synuclein ,amyloid-β (AB) ,Cell Line, Tumor ,Animals ,Humans ,Lon peptidase 1 mitochondrial ,protein homeostasis ,Amyloid beta-Peptides ,Serine-Arginine Splicing Factors ,neurodegeneration ,HtrA serine peptidase 2 ,Lon protease ,Parkinson Disease ,High-Temperature Requirement A Serine Peptidase 2 ,Peptide Fragments ,3. Good health ,Mitochondria ,Rats ,α-synuclein (a-synuclein) ,Proteostasis ,alpha-Synuclein ,Female - Abstract
Mitochondrial dysfunction has long been implicated in the neurodegenerative disorder Parkinson's disease (PD); however, it is unclear how mitochondrial impairment and α-synuclein pathology are coupled. Using specific mitochondrial inhibitors, EM analysis, and biochemical assays, we report here that intramitochondrial protein homeostasis plays a major role in α-synuclein aggregation. We found that interference with intramitochondrial proteases, such as HtrA2 and Lon protease, and mitochondrial protein import significantly aggravates α-synuclein seeding. In contrast, direct inhibition of mitochondrial complex I, an increase in intracellular calcium concentration, or formation of reactive oxygen species, all of which have been associated with mitochondrial stress, did not affect α-synuclein pathology. We further demonstrate that similar mechanisms are involved in amyloid-β 1-42 (Aβ42) aggregation. Our results suggest that, in addition to other protein quality control pathways, such as the ubiquitin-proteasome system, mitochondria per se can influence protein homeostasis of cytosolic aggregation-prone proteins. We propose that approaches that seek to maintain mitochondrial fitness, rather than target downstream mitochondrial dysfunction, may aid in the search for therapeutic strategies to manage PD and related neuropathologies.
11. Short-term follow-up of chagasic patients after benznidazole treatment using multiple serological markers
- Author
-
Joaquim Gascon, Ana Fernández-Villegas, M. Carmen Thomas, Manuel Carlos López, Concepción Marañón, María-Jesús Pinazo, Bartolomé Carrilero, Manuel Segovia, Elizabeth Posada, Fernández-Villegas, Ana [0000-0002-9766-8722], Pinazo, María Jesús [0000-0002-4237-1075], Marañón, Concepción [0000-0002-7827-6301], Thomas, M Carmen [0000-0003-3586-9657], Carrilero, Bartolomé [0000-0002-0110-603X], Gascon, Joaquim [0000-0002-5045-1585], López, Manuel C [0000-0003-0002-3678], and Apollo - University of Cambridge Repository
- Subjects
Chagas disease ,Adult ,Male ,medicine.medical_specialty ,Tuberculosis ,Adolescent ,Antiprotozoal Agents ,Antibodies, Protozoan ,Antigens, Protozoan ,Disease ,Biology ,Serology ,lcsh:Infectious and parasitic diseases ,Young Adult ,Medical microbiology ,Antigen ,medicine ,Humans ,Chagas Disease ,lcsh:RC109-216 ,Aged ,Middle Aged ,medicine.disease ,Recombinant Proteins ,Infectious Diseases ,Treatment Outcome ,Benznidazole ,Nitroimidazoles ,Immunology ,Female ,Leprosy ,Drug Monitoring ,Biomarkers ,Research Article ,medicine.drug ,Follow-Up Studies - Abstract
Background Conventional serological tests, using total soluble proteins or a cocktail of recombinant proteins from T. cruzi as antigens, are highly sensitive for Chagas disease diagnosis. This type of tests, however, does not seem to be reliable tools for short- and medium-term monitoring of the evolution of patients after antiparasitic treatment. The aim of the present study was to search for immunological markers that could be altered in the sera from Chagas disease patients after benznidazole treatment, and therefore have a potential predictive diagnostic value. Methods We analyzed the reactivity of sera from chagasic patients during different clinical phases of the disease against a series of immunodominant antigens, known as KMP11, PFR2, HSP70 and Tgp63. The reactivity of the sera from 46 adult Chronic Chagas disease patients living in a non-endemic country without vector transmission of T. cruzi (15 patients in the indeterminate stage, 16 in the cardiomiopathy stage and 16 in the digestive stage) and 22 control sera from non-infected subjects was analyzed. We also analyzed the response dynamics of sera from those patients who had been treated with benznidazole. Results Regardless of the stage of the sickness, the sera from chagasic patients reacted against KMP11, HSP70, PFR2 and Tgp63 recombinant proteins with statistical significance relative to the reactivity against the same antigens by the sera from healthy donors, patients with autoimmune diseases or patients suffering from tuberculosis, leprosy or malaria. Shortly after benznidazole treatment, a statistically significant decrease in reactivity against KMP11, HSP70 and PFR2 was observed (six or nine month). It was also observed that, following benznidazole treatment, the differential reactivity against these antigens co-relates with the clinical status of the patients. Conclusions The recombinant antigens KMP11, PFR2, Tgp63 and HSP70 are recognized by Chagas disease patients' sera at any clinical stage of the disease. Shortly after benznidazole treatment, a drop in reactivity against three of these antigens is produced in an antigen-specific manner. Most likely, analysis of the reactivity against these recombinant antigens may be useful for monitoring the effectiveness of benznidazole treatment., We thank Fundacion Mundo Sano España for supporting Chagas research in CRESIB. This study was supported by grants P08-CVI-04037PAI (Junta de Andalucía), BFU2010-1670 from Plan Nacional I+D+i (MICINN), RD06/0021/0014 - ISCIII-RETIC (MICINN, Spain) and FEDER. MJP, EP and JG were supported by grant 2009SGR385 from the Department d'Universitats, Recerca i Societat de la Informació de la Generalitat de Catalunya, Spain.
- Published
- 2011
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.