43 results on '"Pais MA"'
Search Results
2. Species and biotypes of Streptococcus bovis causing infective endocarditis
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Corredoira, Juan, Grau, Inma, Garcia-Rodriguez, Jose Francisco, Romay, Eva, Cuervo, Guillermo, Berbel, Damaris, Ayuso, Blanca, García-Pais, Mª José, Rabuñal, Román, García-Garrote, Fernando, Alonso, Mª Pilar, and Pallarés, Román
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- 2023
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3. Alumnado con diversidad funcional en la universidad: necesidades y dificultades/Students with functional diversity at the university: needs and difficulties
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Pais, Ma Emma Mayo
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- 2022
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4. Discapacidade visual
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Mayo Pais, Mª Emma, primary
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- 2024
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5. Species and biotypes of Streptococcus bovis causing infective endocarditis
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Corredoira, Juan, Grau, Inma, Garcia-Rodriguez, Jose Francisco, Romay, Eva, Cuervo, Guillermo, Berbel, Damaris, Ayuso, Blanca, García-Pais, Mª José, Rabuñal, Ramón, García-Garrote, Fernando, Alonso, Mª Pilar, and Pallarés, Ramón
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- 2021
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6. What is university success? Graduates with disabilities define it
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Universidad de Sevilla. Departamento de Didáctica y Organización Educativa, Universidad de Sevilla. HUM-423: I.D.E.A. (nnovación, Desarrollo, Evaluación y Asesoramiento, Mayo Pais, Mª Emma, Moriña Díez, Anabel, Morgado Camacho, Beatriz María, Universidad de Sevilla. Departamento de Didáctica y Organización Educativa, Universidad de Sevilla. HUM-423: I.D.E.A. (nnovación, Desarrollo, Evaluación y Asesoramiento, Mayo Pais, Mª Emma, Moriña Díez, Anabel, and Morgado Camacho, Beatriz María
- Abstract
This article explores the concept of university success from the perspective of 95 Spanish graduates (62.1% women and 37.9% men) with different types of disabilities, identifying situations in which the participants felt that they were successful at university. The data of this qualitative study were gathered through a semi-structured interview and analyzed with an emerging and progressive system of categories and codes. According to the obtained results, university success is a dynamic and multidimensional concept that consists of dif ferent elements, and it is defined through eight components: graduating, attaining the set goal, learning process, social experience, personal growth, professional success, obtaining good marks, and recognition. These results must be considered by universities to promote success among students with disabilities, by fostering their participation in the univer sity experiences and offering them opportunities to attain their academic and professional goals. Future research on university success must delve further into the concept of univer sity success from a holistic perspective that contemplates all these elements
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- 2024
7. Flashbulb Memories in the Communication of the Diagnosis of Visual Impairment: The Effect of Context and Content
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Mayo Pais, Mª Emma, primary, Real Deus, José Eulogio, additional, Iglesias-Souto, Patricia Mª, additional, and Taboada-Ares, Eva Mª, additional
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- 2023
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8. Perceived social support and self-regulated learning: A systematic review and meta-analysis
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Universidade de Santiago de Compostela. Departamento de Psicoloxía Evolutiva e da Educación, Martínez-López, Zeltia, Sousa Monteiro Nouws, Sónia Maria de, Villar, Eva, Mayo Pais, Mª Emma, Tinajero Vacas, Carolina, Universidade de Santiago de Compostela. Departamento de Psicoloxía Evolutiva e da Educación, Martínez-López, Zeltia, Sousa Monteiro Nouws, Sónia Maria de, Villar, Eva, Mayo Pais, Mª Emma, and Tinajero Vacas, Carolina
- Abstract
Self-regulated learning (SRL) is conceived as an active, constructive process aimed at the attainment of personal learning goals. It is considered essential for academic achievement and life-long learning. Distal and proximal social influences, among which perceived social support (PSS) has been receiving increasing attention, are thought to play a key role in the development and display of SRL. In this paper, we aim to summarize the available data on the relationship between PSS and SRL by reviewing published studies that include samples comprising students at different stages of education, ranging from elementary school to university. We conducted a systematic literature review and meta-analysis, seeking to examine the association between PSS and SRL, by considering the possible moderating effects of different support provisions and sources. In addition, we tentatively propose explanations for the relationship based on broadly supported theoretical models of PSS and SRL
- Published
- 2023
9. Perceived social support and its relationship with self‑regulated learning, goal orientation self‑management, and academic achievement
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Universidade de Santiago de Compostela. Departamento de Psicoloxía Evolutiva e da Educación, Martínez-López, Zeltia, Moran, Valeria, Mayo Pais, Mª Emma, Villar, Eva, Tinajero, Carolina, Universidade de Santiago de Compostela. Departamento de Psicoloxía Evolutiva e da Educación, Martínez-López, Zeltia, Moran, Valeria, Mayo Pais, Mª Emma, Villar, Eva, and Tinajero, Carolina
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Self-regulated learning is recognized as a core competence for academic success and lifelong formation. The social context in which self-regulated learning develops and takes place is attracting growing interest. Using cross-sectional data from secondary education students (n = 561), we aimed to formulate explanatory arguments regarding the effect of social support on metacognitive knowledge, metacognitive and cognitive learning strategies, and academic achievement, considering the potential mediating role of goal orientation self-management. Structural Equation Modelling yielded a conceptually consistent and statistically satisfactory empirical model, explaining a moderate-high percentage of the variance in self-regulated learning and academic achievement. The results showed that perceived support from teachers and family positively predicted metacognitive knowledge, metacognitive and cognitive learning strategies, and mastery self-talk and negatively predicted work-avoidance self-talk. Moreover, mastery self-talk and work-avoidance self-talk directly and indirectly (through metacognitive knowledge) predicted academic achievement. Perceived social support is proposed as a marker of vulnerability/protection and as a resource for facing challenges in the academic context
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- 2023
10. Las prácticas externas en títulos universitarios de formación del profesorado
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Belmonte Otero, Isabel, primary, Castro Pais, Mª Dolores, additional, and Mallo Rey, Marta Mª, additional
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- 2022
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11. Alumnado con diversidad funcional en la universidad: necesidades y dificultades
- Author
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Universidade de Santiago de Compostela. Departamento de Psicoloxía Clínica e Psicobioloxía, Mayo Pais, Mª Emma, Universidade de Santiago de Compostela. Departamento de Psicoloxía Clínica e Psicobioloxía, and Mayo Pais, Mª Emma
- Abstract
Introducción. La presente investigación se plantea con el objetivo de conocer cuáles son las necesidades y dificultades que presentan los estudiantes con diversidad funcional en la universidad. Método. Se utilizó un cuestionario para la recopilación de datos. Participaron 73 estudiantes con diversidad funcional, que cursan sus estudios en una universidad pública española. Resultados. Los resultados obtenidos indican que este colectivo presenta dificultades para seguir las explicaciones del profesorado, realizar las prácticas y/o los exámenes. Asimismo, un porcentaje importante considera que el profesorado tendría que recibir formación para saber cómo atender a la diversidad y que las medidas educativas puestas en marcha por la institución no responden a sus necesidades. Conclusión. Como conclusión podemos afirmar que se hace necesaria la eliminación de barreras arquitectónicas e instaurar programas de formación docente para mejorar la atención a la diversidad, pues no hacerlo contribuirá a generar barreras que impiden la inclusión, al no garantizar la igualdad de oportunidades, Introduction. The aim of this research is to find out what are the needs and difficulties that students with functional diversity present at the university. Method. A questionnaire was used for data collection. Seventy-three students with functional diversity who are studying at a Spanish public university participated. Results. The results obtained indicate that this group presents difficulties in following the explanations of the professors, doing the practicals and/or exams. Likewise, a significant percentage considers that the teaching staff should receive training to know how to deal with diversity and that the educational measures implemented by the institution do not respond to their needs. Conclusion. In conclusion, we can affirm that it is necessary to eliminate architectural barriers and establish teacher training programs to improve attention to diversity, since not doing so will contribute to generating barriers that prevent inclusion, by not guaranteeing equal opportunities
- Published
- 2022
12. Criterios para la selección de imágenes sin estereotipos vinculadas con la práctica de actividad físico-deportiva en la edición de libros de texto
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Rey-Cao, Ana, Táboas-Pais, Ma. Inés, and González-Palomares, Alba
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- 2014
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13. Alumnado con diversidad funcional en la universidad: necesidades y dificultades
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Mayo Pais, Mª Emma, primary
- Published
- 2021
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14. Las bibliotecas escolares en la Comunidad Autónoma de Galicia: análisis de los recursos documentales, personales y tecnológicos
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Barreiro Fernández, Felicidad, primary, Castro Pais, Mª Dolores, additional, Zamora Rodríguez, Elisa Teresa, additional, and Mosteiro García, Mª Josefa, additional
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- 2021
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15. Students with functional diversity at the university: needs and difficulties
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Mayo Pais, Mª Emma and Mayo Pais, Mª Emma
- Abstract
Introduction. The aim of this research is to find out what are the needs and difficulties that students with functional diversity present at the university. Method. A questionnaire was used for data collection. Seventy-three students with functional diversity who are studying at a Spanish public university participated. Results. The results obtained indicate that this group presents difficulties in following the explanations of the professors, doing the practicals and/or exams. Likewise, a significant percentage considers that the teaching staff should receive training to know how to deal with diversity and that the educational measures implemented by the institution do not respond to their needs. Conclusion. In conclusion, we can affirm that it is necessary to eliminate architectural barriers and establish teacher training programs to improve attention to diversity, since not doing so will contribute to generating barriers that prevent inclusion, by not guaranteeing equal opportunities., Introducción. La presente investigación se plantea con el objetivo de conocer cuáles son las necesidades y dificultades que presentan los estudiantes con diversidad funcional en la universidad. Método. Se utilizó un cuestionario para la recopilación de datos. Participaron 73 estudiantes con diversidad funcional, que cursan sus estudios en una universidad pública española. Resultados. Los resultados obtenidos indican que este colectivo presenta dificultades para seguir las explicaciones del profesorado, realizar las prácticas y/o los exámenes. Asimismo, un porcentaje importante considera que el profesorado tendría que recibir formación para saber cómo atender a la diversidad y que las medidas educativas puestas en marcha por la institución no responden a sus necesidades. Conclusión. Como conclusión podemos afirmar que se hace necesaria la eliminación de barreras arquitectónicas e instaurar programas de formación docente para mejorar la atención a la diversidad, pues no hacerlo contribuirá a generar barreras que impiden la inclusión, al no garantizar la igualdad de oportunidades.
- Published
- 2021
16. Los estudiantes de la Universidad de Santiago de Compostela ante la diversidad funcional de sus compañeros y compañeras
- Author
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Universidade de Santiago de Compostela. Departamento de Psicoloxía Evolutiva e da Educación, Mayo Pais, Mª Emma, Universidade de Santiago de Compostela. Departamento de Psicoloxía Evolutiva e da Educación, and Mayo Pais, Mª Emma
- Abstract
Para dar continuidad a investigaciones previas, la presente investigación se plantea con el objetivo general de conocer las ideas y actitudes de los estudiantes de la Universidad de Santiago de Compostela (USC) hacia sus iguales con diversidad funcional (discapacidad). El método de recogida de información seleccionado ha sido la encuesta, utilizando un cuestionario como instrumento para la recopilación de datos. Participaron un total de 400 estudiantes sin discapacidad de la USC, que cursan sus estudios en las diferentes áreas de conocimiento. Los resultados indican que los estudiantes de la USC manifiestan unas ideas y actitudes positivas, de aceptación hacia la integración en la universidad de sus compañeros y compañeras con diversidad funcional. A diferencia de lo que ocurre en otras investigaciones, la edad, el género y el curso académico en el que están matriculados no introdujeron diferencias estadísticamente significativas en cuanto a las ideas y actitudes manifestadas, To continue previous research, this research is proposed in order to know the ideas and attitudes of students of the University of Santiago de Compostela (USC) towards their peers with functional diversity (disability). The method selected for collecting information has been the survey, using a questionnaire as a tool for data collection. A total of 400 non-disabled students from the USC participated, studying in the different areas of knowledge. The results indicate that USC students express positive ideas and attitudes, of acceptance towards the integration into the university of their peers with functional diversity. Unlike other research, the age, gender and academic year in which they are enrolled did not introduce statistically significant differences in the ideas and attitudes expressed
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- 2021
17. La atención a la diversidad en el aula: dificultades y necesidades del profesorado de educación secundaria y universidad
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Mayo Pais, Mª Emma, primary, Fernández de la Iglesia, Josefa del Carmen, additional, and Roget Salgado, Felipe, additional
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- 2020
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18. LAS BIBLIOTECAS ESCOLARES EN LA COMUNIDAD AUTÓNOMA DE GALICIA: ANÁLISIS DE LOS RECURSOS DOCUMENTALES, PERSONALES Y TECNOLÓGICOS.
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Fernández, Felicidad Barreiro, Castro Pais, Ma Dolores, Zamora Rodríguez, Elisa Teresa, and Mosteiro García, Ma Josefa
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- 2021
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19. THE FUNCTIONING OF THE SCHOOL LIBRARY: IMPORTANCE OF ITS HUMAN AND MATERIAL RESOURCES
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Barreiro Fernández, Felicidad, primary, Castro Pais, Mª Dolores, additional, Mosteiro García, Mª Josefa, additional, and Zamora Rodríguez, Elisa Teresa, additional
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- 2018
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20. The voice of students with disabilities: reasons for going to university and criteria for choosing the institution.
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Fernández-Menor, Isabel, Doménech, Ana, Mayo Pais, Mª Emma, and Aguirre, Arecia
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STUDENTS with disabilities , *VOCATIONAL guidance , *COLLEGE choice , *PRESTIGE , *HIGHER education , *SEMI-structured interviews - Abstract
Abstract\nPoints of interestThis article describes the factors and criteria that affect graduates with disabilities when deciding to pursue higher education and choosing a university. The study involved 95 graduate students from 27 Spanish universities, with whom semi-structured interviews were conducted. The results show intrinsic and extrinsic factors in choosing to study at university, as well as personal and university-related criteria. Personal motivations, impairment as a conditioning factor and previous experiences are part of the intrinsic factors referred to by the students. Extrinsic factors include socially expected trajectories, influences from different agents and improved job and/or career opportunities. In the choice of university, students pointed to personal criteria such as independence or the influence of others. As criteria related to the university, they mentioned the proximity, the academic offer, the structure and services, and the prestige of the institution. The university can and must consider strategies and actions that favour the access and inclusion.This study explores the factors that motivate students with disabilities to go to university, as well as their institution selection criteria.Students with disabilities show intrinsic factors (originating in oneself) and extrinsic factors (originating from the context) in choosing to study at university.The selection of university depends on both personal issues and the characteristics of the university.This study shows that a variety of factors influence the decision to go to university and the criteria used in their choice. [ABSTRACT FROM AUTHOR]
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- 2024
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21. ANSIEDAD ANTE LOS EXÁMENES EN LA UNIVERSIDAD: ESTUDIO DE CASO ÚNICO.
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Emma Mayo Pais, Mª, González-Freire, Beatriz, and Trillo, Vanesa Moreira
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PSYCHOLOGY of college students , *TEST anxiety , *MENTAL health of college students , *TEST-taking skills , *COGNITIVE therapy , *QUESTIONNAIRES , *SELF-esteem , *PSYCHOEDUCATION - Abstract
This study presents a cognitive-behavioral therapy applied to a 20 year old female college student with high levels of test anxiety. In addition to the clinical interview, the following questionnaires were administered: Self-Assessment Questionnaire, Achievement Anxiety Test, Study Habits Self Report, State-Trait Anxiety Inventory, and Self-Esteem Scale. Based on this assessment, the main objective was to reduce anxiety levels prior to exams and the specific objectives were the removal of distorted thoughts and avoidance behaviors, as well as improving studying skills and increasing self-esteem. The intervention was carried out in thirteen treatment sessions in which several cognitive-behavioral techniques were used: psychoeducation, cognitive restructuring, systematic desensitization, problem solving strategies and assertiveness. On completion of the treatment, a notable reduction of anxiety levels and a successful academic performance were found. In addition, patient scores improved throughout the follow-up. These results support the efficacy of cognitive-behavioral therapy in the treatment of test anxiety. [ABSTRACT FROM AUTHOR]
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- 2015
22. Species and biotypes of Streptococcus boviscausing infective endocarditis
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Corredoira, Juan, Grau, Inma, Garcia-Rodriguez, Jose Francisco, Romay, Eva, Cuervo, Guillermo, Berbel, Damaris, Ayuso, Blanca, García-Pais, Mª José, Rabuñal, Ramón, García-Garrote, Fernando, Alonso, Mª Pilar, and Pallarés, Ramón
- Abstract
Streptococcus bovis/equinuscomplex (SBEC) is a major cause of infective endocarditis (IE), although its incidence varies greatly depending on the geographical area. The characteristics of IE caused by Streptococcus gallolyticusare well known; there are hardly any descriptions of IE caused by other species or biotypes.
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- 2021
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23. Variation in plant defenses of Didymopanax vinosum (Cham. & Schltdl.) Seem. (Apiaceae) across a vegetation gradient in a Brazilian cerrado
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Pais Mara Patrícia and Varanda Elenice Mouro
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cerrado ,plant defenses ,tannins ,vegetation gradient ,water stress ,Botany ,QK1-989 - Abstract
Cerrado vegetation is composed of a mosaic of vegetation types, from campo sujo, dominated by herbs; campo cerrado and cerrado sensu stricto, with shrubby vegetation; to cerradão, with trees forming a denser forest. This physiognomic mosaic is related to differences in the water availability in the soil. Cerrado plants are considered physically and chemically well defended against herbivores, but there are no studies showing how plants allocate investment to various types of defensive mechanisms in different habitat physiognomies. The defensive mechanisms and the nutritional traits of a cerrado plant, Didymopanax vinosum (Cham. & Schltdl.) Seem. (Apiaceae), were compared along a vegetation gradient. Toughness, as well as water, nitrogen, cellulose, lignin, and tannin contents were measured in young and mature leaves of D. vinosum collected in campo cerrado, cerrado sensu stricto (s.s.) and cerradão. Plants from cerrado s.s. and cerradão were of better nutritional quality but also had higher tannin contents than campo cerrado plants. Some type of compensation mechanism could have been selected to provide an optimum investment in defense, according to limitations imposed by water deficits in the habitat.
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- 2003
24. Organogenic nodule formation from hop internodes. Reactive oxygen species and expression of lipoxygenase and extracellular-regulated kinases
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Pais Maria S, Risueco Maria, Testillano Pilar S, Coronado Maria, Costa Joana, Silva Marta, and Fortes Ana M
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Botany ,QK1-989 - Published
- 2005
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25. Transcript and metabolite analysis in Trincadeira cultivar reveals novel information regarding the dynamics of grape ripening
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Martinez- Zapater José M, Grimplet Jerome, Choi Young H, Maltese Federica, Sousa Lisete, Ali Kashif, Silva Marta S, Agudelo-Romero Patricia, Fortes Ana M, Verpoorte Robert, and Pais Maria S
- Subjects
Botany ,QK1-989 - Abstract
Abstract Background Grapes (Vitis vinifera L.) are economically the most important fruit crop worldwide. However, the complexity of molecular and biochemical events that lead to the onset of ripening of nonclimacteric fruits is not fully understood which is further complicated in grapes due to seasonal and cultivar specific variation. The Portuguese wine variety Trincadeira gives rise to high quality wines but presents extremely irregular berry ripening among seasons probably due to high susceptibility to abiotic and biotic stresses. Results Ripening of Trincadeira grapes was studied taking into account the transcriptional and metabolic profilings complemented with biochemical data. The mRNA expression profiles of four time points spanning developmental stages from pea size green berries, through véraison and mature berries (EL 32, EL 34, EL 35 and EL 36) and in two seasons (2007 and 2008) were compared using the Affymetrix GrapeGen® genome array containing 23096 probesets corresponding to 18726 unique sequences. Over 50% of these probesets were significantly differentially expressed (1.5 fold) between at least two developmental stages. A common set of modulated transcripts corresponding to 5877 unigenes indicates the activation of common pathways between years despite the irregular development of Trincadeira grapes. These unigenes were assigned to the functional categories of "metabolism", "development", "cellular process", "diverse/miscellanenous functions", "regulation overview", "response to stimulus, stress", "signaling", "transport overview", "xenoprotein, transposable element" and "unknown". Quantitative RT-PCR validated microarrays results being carried out for eight selected genes and five developmental stages (EL 32, EL 34, EL 35, EL 36 and EL 38). Metabolic profiling using 1H NMR spectroscopy associated to two-dimensional techniques showed the importance of metabolites related to oxidative stress response, amino acid and sugar metabolism as well as secondary metabolism. These results were integrated with transcriptional profiling obtained using genome array to provide new information regarding the network of events leading to grape ripening. Conclusions Altogether the data obtained provides the most extensive survey obtained so far for gene expression and metabolites accumulated during grape ripening. Moreover, it highlighted information obtained in a poorly known variety exhibiting particular characteristics that may be cultivar specific or dependent upon climatic conditions. Several genes were identified that had not been previously reported in the context of grape ripening namely genes involved in carbohydrate and amino acid metabolisms as well as in growth regulators; metabolism, epigenetic factors and signaling pathways. Some of these genes were annotated as receptors, transcription factors, and kinases and constitute good candidates for functional analysis in order to establish a model for ripening control of a non-climacteric fruit.
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- 2011
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26. Accumulation of neutral lipids in peripheral blood mononuclear cells as a distinctive trait of Alzheimer patients and asymptomatic subjects at risk of disease
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Palmas Manuela, Zaru Cristina, Barberini Luigi, Saba Antonio, Pais Maria, Muçaka Nico, Brundu Annalisa, Angius Fabrizio, Cocco Pier, Abete Claudia, Diaz Giacomo, Mandas Antonella, Pani Alessandra, Putzu Paolo F, Mocali Alessandra, Paoletti Francesco, La Colla Paolo, and Dessì Sandra
- Subjects
Medicine - Abstract
Abstract Background Alzheimer's disease is the most common progressive neurodegenerative disease. In recent years, numerous progresses in the discovery of novel Alzheimer's disease molecular biomarkers in brain as well as in biological fluids have been made. Among them, those involving lipid metabolism are emerging as potential candidates. In particular, an accumulation of neutral lipids was recently found by us in skin fibroblasts from Alzheimer's disease patients. Therefore, with the aim to assess whether peripheral alterations in cholesterol homeostasis might be relevant in Alzheimer's disease development and progression, in the present study we analyzed lipid metabolism in plasma and peripheral blood mononuclear cells from Alzheimer's disease patients and from their first-degree relatives. Methods Blood samples were obtained from 93 patients with probable Alzheimer's disease and from 91 of their first-degree relatives. As controls we utilized 57, cognitively normal, over-65 year-old volunteers and 113 blood donors aged 21-66 years, respectively. Data are reported as mean ± standard error. Statistical calculations were performed using the statistical analysis software Origin 8.0 version. Data analysis was done using the Student t-test and the Pearson test. Results Data reported here show high neutral lipid levels and increased ACAT-1 protein in about 85% of peripheral blood mononuclear cells freshly isolated (ex vivo) from patients with probable sporadic Alzheimer's disease compared to about 7% of cognitively normal age-matched controls. A significant reduction in high density lipoprotein-cholesterol levels in plasma from Alzheimer's disease blood samples was also observed. Additionally, correlation analyses reveal a negative correlation between high density lipoprotein-cholesterol and cognitive capacity, as determined by Mini Mental State Examination, as well as between high density lipoprotein-cholesterol and neutral lipid accumulation. We observed great variability in the neutral lipid-peripheral blood mononuclear cells data and in plasma lipid analysis of the subjects enrolled as Alzheimer's disease-first-degree relatives. However, about 30% of them tend to display a peripheral metabolic cholesterol pattern similar to that exhibited by Alzheimer's disease patients. Conclusion We suggest that neutral lipid-peripheral blood mononuclear cells and plasma high density lipoprotein-cholesterol determinations might be of interest to outline a distinctive metabolic profile applying to both Alzheimer's disease patients and asymptomatic subjects at higher risk of disease.
- Published
- 2009
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27. Organogenic nodule development in hop (Humulus lupulus L.): Transcript and metabolic responses
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Santos Bartolomeu A, Pessoa Fernando, Sousa Lisete, Figueiredo Andreia, Silva Marta S, Choi Young H, Santos Filipa, Fortes Ana M, Sebastiana Mónica, Palme Klaus, Malhó Rui, Verpoorte Rob, and Pais Maria S
- Subjects
Biotechnology ,TP248.13-248.65 ,Genetics ,QH426-470 - Abstract
Abstract Background Hop (Humulus lupulus L.) is an economically important plant forming organogenic nodules which can be used for genetic transformation and micropropagation. We are interested in the mechanisms underlying reprogramming of cells through stress and hormone treatments. Results An integrated molecular and metabolomic approach was used to investigate global gene expression and metabolic responses during development of hop's organogenic nodules. Transcript profiling using a 3,324-cDNA clone array revealed differential regulation of 133 unigenes, classified into 11 functional categories. Several pathways seem to be determinant in organogenic nodule formation, namely defense and stress response, sugar and lipid metabolism, synthesis of secondary metabolites and hormone signaling. Metabolic profiling using 1H NMR spectroscopy associated to two-dimensional techniques showed the importance of metabolites related to oxidative stress response, lipid and sugar metabolism and secondary metabolism in organogenic nodule formation. Conclusion The expression profile of genes pivotal for energy metabolism, together with metabolites profile, suggested that these morphogenic structures gain energy through a heterotrophic, transport-dependent and sugar-degrading anaerobic metabolism. Polyamines and auxins are likely to be involved in the regulation of expression of many genes related to organogenic nodule formation. These results represent substantial progress toward a better understanding of this complex developmental program and reveal novel information regarding morphogenesis in plants.
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- 2008
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28. Contribució a l'Estudi dels Receptors de Serotonina. Molècules Basades en Indens i Indans
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López Pérez, Sara, Alcaide Pais, Mª Ermitas, Mesquida Estévez, Ma. Neus, Universitat de Barcelona. Departament de Farmacologia i Química Terapèutica, and Alcalde Pais, Ma. Ermitas (María de las Ermitas)
- Subjects
Serotonin receptors ,Indens ,Indans ,Receptor de serotonina ,Ciències de la Salut ,Receptors de serotonina - Abstract
El punt de partida de la present Tesi Doctoral se situa entorn a l'estudi d'estructures basades en (Z)-estilbens: disseny, síntesi i examen de quimioteques dirigides a l'obtenció de nous compostos bioactius a nivell de sistema nerviós central (SNC), en el marc d'una col·laboració amb la indústria farmacèutica. Així, el projecte es va iniciar amb una recerca bibliogràfica per la selecció del scaffold, la qual ens posà de manifest com els (Z)-arilmetilidenindens constituïen un conjunt de compostos amb diferents perfils farmacològics.Valorant aquests antecedents, la dificultat radicava en l'elecció de l'estructura prototipus. Els (Z) arilmetilidenindens podien ésser un inici ja que el fragment estructural cis estilbè s'integra en el scaffold. A més, la química de sistemes basats en indens i l'estudi de les seves propietats biològiques estaven menys explorats que la d'altres famílies de compostos, la qual cosa permetria desenvolupar temes específics d'investigació amb probabilitat raonable d'èxit.Concretament, se sintetitzaren els cis-indens I i les seves formes reduïdes II, basats en una selecció estructural, a partir de les indolilsulfonamides per substitució de l'indol per l'indè, i que incorporaven el grup sulfonamido en la posició 5. L'accés a les indenilsulfonamides II es portà a terme inicialment mitjançant una via específica, de cinc etapes, on els àcids (sulfonilamino)indenilacètics eren els intermedis claus, els quals es prepararen, després d'examinar diferents alternatives sintètiques, per reacció aldòlica.Els assajos d'afinitats pel receptor 5-HT6 mostraren valors diferents, sent moderats pels compostos I i augmentant de forma important per les indenilsulfonamides II. A més, cal destacar la funcionalitat agonista d'aquests derivats, ja que en els darrers anys, la majoria de lligands descoberts per aquest receptor havien estat identificats com antagonistes. Per aquesta raó, i tenint en compte que els canvis responsables de l'augment d'afinitat enfront el receptor 5-HT6 venien limitats per la química de l'indè, ens plantejàrem la síntesi d'altres estructures mitjançant una ruta més general de quatre etapes, on la sulfonilació es duia en la darrera etapa, sent les inden-5-amines els precursors de nous lligands II diversificats en la posició 5.Les noves indenilsulfonamides II exhibiren afinitats variables pel receptor 5 HT6, destacant dos compostos que s'identificaren com a potents agonistes selectius amb excel·lents perfils farmacològics in vitro (Ki ≥ 4,5 nM).Alhora, s'ha estudiat la influència de la cadena N,N-dimetilaminoetil de la posició 3 sobre l'indè, amb a la preparació d'indenilsulfonamides restringides III i derivats simplificats, en base als requeriments estructurals establerts prèviament per augmentar l'afinitat dels lligands pel receptor 5 HT6. La síntesi d'aquests compostos es portà a terme mitjançant una via de tres etapes, a partir de les indanones convenientment substituïdes per preparar les indenamines precursores, aplicant la reacció aldòlica anteriorment emprada, adaptada a les lactames.Aquestes indenilsulfonamides restringides III exhibiren elevades afinitats pel receptor 5-HT6 actuant com antagonistes, tot i que amb potències moderades a nivell micromolar. D'altra banda, l'absència de la amina bàsica en els compostos estructuralment simplicats no implicava pèrdua d'afinitat, indicant com els grups N,N aminoetil o l'amina restringida sobre la posició 3 de l'indè no eren necessàris per mantenir l'afinitat pel receptor.Finalment, també s'ha portat a terme el canvi de la cadena aminoetílica per un grup guanilhidrazona rígid, que ens ha permès la identificació de les indanilguanilhidrazones sulfonamides IV com a potents i selectius antagonistes del receptor 5-HT6 amb elevades afinitats, a nivell nanomolar.Aquest conjunt de nous lligands basats en indens podrien ser útils eines d'elucidació d'aspectes funcionals i usos terapèutics d'altres lligands del receptor 5-HT6 en el tractament de malalties del SNC tals com l'ansietat, depressió o altres desordres mentals. Així, com l'interès que representen els agonistes enfront alteracions alimentàries tals com l'obesitat o la bulímia., The background of this thesis is the study of structures based on (Z)-stilbenes: design, synthesis and testing of libraries designed to obtain new bioactive compounds in central nervous system, in collaboration with the pharmaceutical industry. So the structure proptotype, the (Z)-arylmethylideneindenes were chosen as the structural fragment cis-stilbenes integrated into the scaffold could form a set of compounds with different pharmacological profiles. In addition, chemical-based systems indenes such as I and the study of their biological properties were less explored than other families of compounds, which permit the development of specific topics of research with responsible likelihood of success.By developing an indole-to-indene core change, we have synthesized the cis indenes I and their reduced forms II, which incorporate the sulfonamido group in 5 position. These compounds have presented affinity for serotonin 5-HT6 receptor (Ki ≥ 20 nM). The novel indenylsulfonamides II exhibited variable binding affinities for the 5-HT6 receptor and the in vitro profiles of the most active compounds revealed them to be selective 5 HT6 receptor agonists in the low-nanomolar range (Ki ≥ 4.5 nM).Moreover, we have studied the influence of the N,N-dimethylaminoethyl side chain on the indene 3-position. Preparation of a few examples of ring-constrained III type indenylsulfonamides and the structurally simplified counterparts, based on previously established structural requirements for enhancing the affinity of indene based ligands towards the 5-HT6 receptor, gave access compounds which exhibited a high binding affinity and functioned as antagonists, although with moderate potency at the micromolar level. Finally, changing the N,N-(dimethylamino)ethyl side chain for a conformationally rigid guanylhydrazone moiety on the indene 3 position led to the identification of novel indanylguanylhydrazone sulfonamides IV with excellent binding affinities and an antagonistic response at the 5-HT6 receptor in the nanomolar range.The ensemble of indene-based frameworks constituted by the (aminoethyl)indenylsulfonamide agonists II, the conformationally rigid antagonists III and the structurally simplified counterparts, as well as the indanylsulfonamide guanylhydrazone antagonists IV (see Figure 1) resulted in a range of compounds which may be useful biological tools for the fundamental understanding of the 5-HT6 receptor.
- Published
- 2010
29. Entramats moleculars d'imidazoli-calix[4]arè
- Author
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García de Miguel, Cristina, Alcaide Pais, Mª Ermitas, Dinarès Milà, M. Immaculada, Universitat de Barcelona. Departament de Farmacologia i Química Terapèutica, and Alcalde Pais, Ma. Ermitas (María de las Ermitas)
- Subjects
Compostos heterocíclics ,Imidazoli ,Sistemes oligocatiònics ,Imidazoles ,Química farmacèutica ,Heterocyclic compounds ,Pharmaceutical chemistry ,Ciències de la Salut ,Reacció de Suzuki-Miyaura - Abstract
Els entramats moleculars d'imidazoli-calix[4]arè constitueixen sistemes oligocatiònics macrocíclics amb un potencial atractiu en l'estudi de propietats a nivell supramolecular.Des de fa més de 20 anys la investigació en el nostre grup de reserca gira entorn de l'estudi de la química dels sistemes catiònics i oligocatiònics basats en sals d'imidazoli. Concretament, en la present Tesi Doctoral s'ha accedit a entramats moleculares d'imidazoli-calix[4]arè, la particular estructura química dels quals ha permés la formació de carbens N-heterocíclics (NHC), accedint, així, als nous complexos organometàl·lics de bis(carbè N-heterocíclic)-pal·ladi, a més, aquests darrers i els corresponents precursors, han estat valorats en reaccions d'acoblament creuat, essent la reacció de Suzuki-Miyaura seleccionada com a model, mostrant la seva eficiencia en front de cloro i bromoarens.Anàlogament, s'ha mostrat la seva capacitat en el reconeixement molecular d'anions, mitjançant el mètode de les titriacions per RMN de protó, i parells iònics, observant-se la cooperació en l'associació del parell iònic potassi-benzoat.Paral·lelament, s'ha sintetitzat una petita col·lecció de líquids iònics a temperatura ambient (RTILs) mitjançant un procediment innovador, basat en la utilització d'una resina de bescanvi iònic amb l'anió seleccionat mitjançant dos metodologies. Aquest estudi s'ha extès a altres sitemes catiònics i dicatiònics com són els derivats de bis(n-butilimidazoli)-calix[4]arè., "IMIDAZOLIUM-CALIX[4]ARENE AS MOLECULAR FRAMEWORKS"TEXT:Imidazolium-calix[4]arene molecular scaffolds constitute oligocationics and macrocyclic compounds with a great potential towards the study of their own properties in Supramolecular Chemistry.For more than twenty years Prof. Ermitas Alcalde's research group has been working on the study of the chemistry of imidazolium-based frameworks. Specifically, in this Thesis we provide the synthesis of imidazolium-calix[4]arene molecular frameworks. Thanks to its own particular chemical structure, we have reported the synthesis of the bis(N-heterociclic carbenes) (NHC) as new bidentated ligands, carring out the preparation of the new bidentate palladium (II) complexes from the bis(imidazolium)-calix[4]arene salts. The Suzuki-Miyaura reaction was used to study their activity as catalyst, when they were prepared either in situ or from a well-defined complex, showing their effectiveness with chloro and bromoarenes.Analogously, as part of our ongoing research, we have described the anion binding properties of the dicationic bis(imidazolium) salts directly bonded to the upper rim of the calixarene structure then were studied by 1H NMR spectroscopic methods. In paralel, the hability of bis(imidazolium)-calixarene-crown-5 scaffold was examined in ion-pair binding. Remarkably, the cooperation effect in potassium-benzoate ion-pair binding of dicationic calix[4]arene-crown-5 was showed. On the other hand, a series of room temperature ionic liquids have been prepared by using an ion exchange resin with the anionic species selected by two methodologies. This study has been extended to another cationic and dicationic imidazolium frameworks as the bis(n-butylimidazolium)-calix[4]arene scaffold.
- Published
- 2008
30. Sistemes moleculars catiònics i dicatiònics: Estructures basades en sals d'imidazoli
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Rodríguez Gómez, Sandra, Alcaide Pais, Mª Ermitas, Dinarès Milà, M. Immaculada, Universitat de Barcelona. Departament de Farmacologia i Química Terapèutica, and Alcalde Pais, Ma. Ermitas (María de las Ermitas)
- Subjects
Complexes organometàl·lics ,Catalysts ,Catalitzadors ,Complexes organometàl.lics ,Imidazoles ,Sals ,Salts ,Organometallic compounds ,Compostos organometàl·lics ,Ciències de la Salut ,Catalitzadors homogenis ,Sals d'imidazoli - Abstract
La investigació s'ha centrat en la preparació d'estructures basades en sals d'imidazoli que per tractament en medi bàsic puguin transformar-se en carbens N-heterocíclics (NHCs) i complexar metalls de transició proporcionant complexes organometàl·lics amb potencial aplicació com a catalitzadors homogenis. D'altra banda, els sistemes moleculars que incorporen sals d'imidazoli poden presentar capacitat per al reconeixement molecular d'anions d'interès en el camp biològic. Inicialment, es prepararen blocs fonamentals i mòduls moleculars de N-arilazoles, impedits estèricament, mitjançant reaccions d'acoblament catalitzades per coure entre halogenurs d'aril i imidazole, optimitzant-se els protocols sintètics pel 1,3-bis(imidazolil)benzè i alguns N-arilimidazoles descrits a la literatura. A partir d'aquests, s'han sintetitzat sals de bis(imidazoli). En primer lloc, es quaternitzaren els anells heteroaromàtics del 1,3-di(N-imidazolil)benzè incorporant altres funcionalitzacions que poguessin aportar punts d'ancoratge addicionals per a la formació de complexos organometàl·lics. Així, s'han sintetitzat les sals de bis(fosfino-imidazoli) i de bis(piridil-imidazoli) amb bons rendiments. Paral·lelament, es va plantejar augmentar la distància entre l'anell d'imidazoli i l'espaiador interanular aromàtic, inserint cadenes alquíliques de metilè, etilè i propilè, que proporcionen certa flexibilitat a la molècula. Es seleccionà com a espaiador el mesitilè donat que pot condicionar la disposició de les cadenes laterals de forma perpendicular al pla de l'anell aromàtic i aportar els electrons necessaris per a l'estabilització dels complexos formats amb metalls de transició. En aquest sentit, s'han preparat les sals de bis(metilen-, etilen i propilen-imidazoli) per quaternització de N-alquil o N-arilimidazoles amb bons rendiments. Seguint amb la investigació de nous sistemes basats en sals d'imidazoli, s'han sintetitzat estructures en les que coexisteixen una unitat d'imidazoli i una unitat d'oxazolina, capaç d'aportar parells d'electrons per cedir al metall al formar complexos organometàl·lics i introduir estereocentres a la molècula. La preparació d'aquestes sals no fou fàcil donada la dificultat que representa la incorporació de dos heterocicles diferents a la mateixa molècula, tot i així s'ha desenvolupat una ruta sintètica eficient per a la seva preparació la qual ens permet obtenir sistemes d'oxazolina-imidazoli amb bons rendiments. El protocol sintètic utilitzat pot aplicar-se a altres sistemes quirals de potencial aplicació en síntesi asimètrica. Amb les sals d'oxazolinil-imidazoli, i altres bis(oxazolines) preparades, s'ha procedit a l'avaluació de la seva capacitat d'actuació com a lligands en sistemes catalítics front la reacció de Suzuki-Miyaura, generant el sistema catalític in situ amb acetat de pal·ladi. Els resultats mostren que els cations impedits estèricament són eficaços tant amb bromurs com amb clorurs d'aril, fins i tot utilitzant baixes proporcions de catalitzador. Per altra banda, també s'ha estudiat el comportament de les sals de bis(fosfino-imidazoli) i bis(piridil-imidazoli) en la reacció de Suzuki-Miyaura, però cap d'elles ha mostrat una activitat catalítica remarcable. També, s'han intentat preparar complexes de NHC-Ag i NHC-Pd d'algunes de les sals de bis(imidazoli) preparades. Així mateix, s'ha realitzat l'estudi estructural en estat gas per ESI-MS, i en dissolució per RMN-1H. A més, s'ha estudiat la velocitat d'intercanvi protó/deuteri del protó del C-2 de l'anell d'imidazoli en metanol deuterat, calculant-se la constant d'intercanvi sempre que el compost ho ha permès. El valor d'aquesta constant és indicativa de la facilitat que presenten els compostos estudiats per a formar carbens i de la influència que exerceix l'anió que acompanya a les sals d'imidazoli. La preparació i estudi de nous complexos organometàl·lics, així com l'avaluació de la capacitat d'aquests sistemes en el reconeixement molecular d'anions serà objecte d'estudis posteriors. La present Tesi Doctoral ha donat lloc, fins al moment de la seva defensa, a dues publicacions en revistes internacionals (Eur. J. Org. Chem., 2005, 1637-1643; Synthesis, 2007, en premsa) i a altres dues pendents d'enviament, a més dels resultats que s'obtinguin amb la profundització d'alguns aspectes inacabats., Our investigation has been focused on imidazolium-based molecular structures, potential precursors of N-heterocyclic carbenes (NHCs) which have emerged as a relevant family of ancillary ligands in organometallic chemistry due to their practical applications in homogeneous catalysis, and in anion recognition chemistry which is of revelant interest to field of biology. Firstly, we pursued the synthesis of more or less sterically hindered N-arylazoles using a mild protocol for a Cu-catalyzed coupling reactions between aryl halides and imidazole optimizing the synthesis of 1,3-bis(imidazolyl)benzene and other N-arylimidazoles described in literature. Subsequently, 1,3-bis(N-imidazolyl)benzene heteroaromatic ring quaternization and incorporation of other funcionalizations that contribute additional anchorage points for the formation of organometallic complex afforded bis(phosphine-imidazolium) and bis(pyridyl-imidazolium) salts in good yields. Moreover, bis(methylene-, ethylene- and propylene-imidazolium) salts were prepared in good yields from quaternization with N-alkyl or N-arylimidazoles. In this case, a mesitylene spacer was selected because it can orientate lateral chain arrangement perpendicular in respect to the aromatic ring plane and contribute to organometallic complex stabilization. In addition, oxazolinyl-imidazolium salts were prepared using an efficient multistep sequence, which can be adapted to a variety of chiral frameworks with catalytic performance in asymmetric reactions. A Suzuki-Miyaura reaction was used to illustrate the activity of the catalyst systems produced in situ from these salts and palladium(II)acetate. Also, it has been studied the behaviour of bis(phosphine-imidazolium) and bis(pyridyl-imidazolium) salts as a polidentate ligand precursors. Finally, the structural study in the gas phase using ESI-MS and in solution by 1H-NMR has been carried out. Additionally, it has been observed the proton/deuterium exchange rate of imidazolium C-2 proton in methanol-d4, which indicates its acidity and the suitability of NHC formation. This Doctoral Thesis has resulted in the publication of two articles in international journals (Eur. J. Org. Chem.,2005, 1637-1643; Synthesis, 2007, in press) and also two further articles subject to acceptance.
- Published
- 2007
31. Betaïnes d'azolat piridini (azoli) i derivats amb diversos agrupaments interanulars
- Author
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Pérez García, M. Lluïsa (Maria Lluïsa), Alcaide Pais, Mª Ermitas, Universitat de Barcelona. Departament de Farmacologia i Química Terapèutica, and Alcalde Pais, Ma. Ermitas (María de las Ermitas)
- Subjects
Betaine ,Compostos heterocíclics ,Betaïna ,Química farmacèutica ,Heterocyclic compounds ,Pharmaceutical chemistry ,Ciències de la Salut - Abstract
En l'actualitat, la Química Heterocíclica ofereix la possibilitat de ser utilitzada com un bon mitjà de transferència entre els camps que presenten major futur en Química: aquells camps situats en la frontera amb la Biologia -presència d'una gran varietat d'estructures en els éssers vius i en els fàrmacs- i amb la Física -materials avançats-. L'examen d'una obra actualitzada en Química Heterocíclica241 mostra que unes de les estructures més captivants són les betaïnes heterocícliques i els compostos mesoiònics.Les betaïnes heterocícliques d'azolat azini i azolat azoli, formen un conjunt de compostos heterocíclics, l'originalitat de les estructures dels quals brinda un excel·lent potencial investigador. El nombre de compostos possible és força elevat i el nostre esforç inicial s'ha orientat cap a l'estudi de molècules model.Dins de l'àmplia i variada gamma d'estructures que poden presentar les betaïnes mesòmeres heterocícliques es troba el ciclopentadienur de piridini 1 -azaanàleg de la forma dipolar del sesquifulvalè 2B- i altres azaderivats, tais com les sals internes d'azolat piridini UI i d'azolat azoli V, les quals, juntament amb les 4-azoliden-l,4-dihidropiridines VI, són desenvolupades pel nostre grup de treball en els darrers anys, amb l'objectiu d'aprofundir en les seves propietats estructurals i de reactivitat química, com també en les seves possibles apücacions. Així mateix, s'ha ampliat l'estudi a les betaïnes d'azolat vinilenpiridini VII, azolat etilenpiridini i azolat etilenimidazoli VIII, azolat metilenpiridini IX (Sèrie C-N), azolat metilenimidazoli X (Sèrie C-N) i azolat metilenpiridini XI (Sèrie C-C). Aquestes darreres estructures IX-XI han estat un dels principals objectius de la present Tesi Doctoral.
- Published
- 1991
32. Betaïnes d'azolat piridini(azoli) i derivats amb diversos agrupaments interanulars
- Author
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Pérez García, M. Lluïsa (Maria Lluïsa), Alcalde Pais, Ma. Ermitas (María de las Ermitas), and Universitat de Barcelona. Departament de Farmacologia i Química Terapèutica
- Subjects
Betaïna ,Compostos heterocíclics ,Betaine ,Química farmacèutica ,Heterocyclic compounds ,Pharmaceutical chemistry - Abstract
En l'actualitat, la Química Heterocíclica ofereix la possibilitat de ser utilitzada com un bon mitjà de transferència entre els camps que presenten major futur en Química: aquells camps situats en la frontera amb la Biologia -presència d'una gran varietat d'estructures en els éssers vius i en els fàrmacs- i amb la Física -materials avançats-. L'examen d'una obra actualitzada en Química Heterocíclica241 mostra que unes de les estructures més captivants són les betaïnes heterocícliques i els compostos mesoiònics. Les betaïnes heterocícliques d'azolat azini i azolat azoli, formen un conjunt de compostos heterocíclics, l'originalitat de les estructures dels quals brinda un excel·lent potencial investigador. El nombre de compostos possible és força elevat i el nostre esforç inicial s'ha orientat cap a l'estudi de molècules model. Dins de l'àmplia i variada gamma d'estructures que poden presentar les betaïnes mesòmeres heterocícliques es troba el ciclopentadienur de piridini 1 -azaanàleg de la forma dipolar del sesquifulvalè 2B- i altres azaderivats, tais com les sals internes d'azolat piridini UI i d'azolat azoli V, les quals, juntament amb les 4-azoliden-l,4-dihidropiridines VI, són desenvolupades pel nostre grup de treball en els darrers anys, amb l'objectiu d'aprofundir en les seves propietats estructurals i de reactivitat química, com també en les seves possibles apücacions. Així mateix, s'ha ampliat l'estudi a les betaïnes d'azolat vinilenpiridini VII, azolat etilenpiridini i azolat etilenimidazoli VIII, azolat metilenpiridini IX (Sèrie C-N), azolat metilenimidazoli X (Sèrie C-N) i azolat metilenpiridini XI (Sèrie C-C). Aquestes darreres estructures IX-XI han estat un dels principals objectius de la present Tesi Doctoral.
- Published
- 1991
33. Compost de N-azolilpidridini amb possible activitat antiparasitària: síntesi i propietats
- Author
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Dinarès Milà, M. Immaculada and Alcalde Pais, Ma. Ermitas (María de las Ermitas)
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Parasitologia ,Tesis de Llicenciatura (Tesines) ,Drugs ,Parasitology ,Medicaments - Abstract
Tesi de Llicenciatura per a la obtenció del Grau de Farmàcia. Facultat de Farmàcia. Universitat de Barcelona. Director: Ma. Ermitas Alcalde Pais. 1984., Donades les conseqüències incalculables en el domini de la salut, i els enormes interessos financers en joc , el tema dels antiparasitaris, humans i animals, ha estat objecte de nombrossos treballs per part de poderoses empreses farmacèutiques multinacionals. Dades recents assenyalen que la infecció per Trichomonas vaginalis té una incidència mundial del 10 al 90 % de la població. Per la seva part, la malaltia de Chagas, causada per Tripanosoma cruzi, afecta 7 milions de persones a Sudamèrica, i que uns 35 milions més estan amenaçats d'agafar-la.
- Published
- 1984
34. Betaínas heterocíclicas y derivados: una nueva clase de agentes antiprotozoarios: síntesis, estructura y propiedades
- Author
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Dinarès Milà, M. Immaculada, Alcalde Pais, Ma. Ermitas (María de las Ermitas), and Universitat de Barcelona. Departament de Farmacologia i Química Terapèutica
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Compostos heterocíclics ,Química farmacéutica ,Compuestos heterocíclicos ,Química farmacèutica ,Heterocyclic compounds ,Ciències de la Salut ,Pharmaceutical chemistry - Abstract
La tesis doctoral constituye la prospección previa realizada de un programa de investigación sobre la química de las betaínas heterocíclicas, cuyas ideas generales giran fundamentalmente alrededor del eje formado por la química heterocíclica y la química terapéutica. Las betaínas heterocíclicas forman un conjunto de compuestos en los que la originalidad de las estructuras moleculares ofrece un excelente potencial investigador. Se describe la síntesis de una serie de betaínas heterocíclicas de azolato piridinio, azolato azolio y 1-alquil-4-azoliden-1,4- dihidropiridinas, y sus derivados, conjunto de compuestos prácticamente desconocido en la literatura química y que pueden considerarse de manera formal como azaanálogos del sesquifulvaleno. Se han realizado ensayos de su actividad biológica frente a diversos parásitos, y se observa que son particularmente activos frente Leishmania donovani y Trypanosoma cruzi, y se pueden considerar las sales de N-aziolilpiridinio como una nueva clase de agentes antiprotozoarios. Asimismo, se ha llevado a cabo un minucioso estudio estructural de los nuevos compuestos sintetizados. La estructura de las betaínas heterocíclicas se analiza en base a los resultados de los cálculos teóricos (MNDO), datos espectroscópicos, momentos dipolares experimentales y análisis por difracción de rayos X. La estructura altamente dipolar de las betaínas heterocíclicas se refleja en sus elevados momentos dipolares experimentales (los mas altos para moléculas orgánicas sencillas). Por otra parte se ha iniciado el estudio de su reactividad frente a electrófilos y frente a dipolarófilos, describiéndose por primera vez una reacción de cicloadición dipolar de una betaína mesomera heterocíclica, azaderivada de la forma dipolar del N-iluro del ciclopentadienuro de piridinio.
- Published
- 1989
35. Protein Aggregation on Metal Oxides Governs Catalytic Activity and Cellular Uptake.
- Author
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Nißler R, Dennebouy L, Gogos A, Gerken LRH, Dommke M, Zimmermann M, Pais MA, Neuer AL, Matter MT, Kissling VM, de Brot S, Lese I, and Herrmann IK
- Subjects
- Animals, Catalysis, Protein Aggregates, Macrophages metabolism, Mice, Metals chemistry, Humans, RAW 264.7 Cells, Oxides chemistry, Protein Corona chemistry, Protein Corona metabolism
- Abstract
Engineering of catalytically active inorganic nanomaterials holds promising prospects for biomedicine. Catalytically active metal oxides show applications in enhancing wound healing but have also been employed to induce cell death in photodynamic or radiation therapy. Upon introduction into a biological system, nanomaterials are exposed to complex fluids, causing interaction and adsorption of ions and proteins. While protein corona formation on nanomaterials is acknowledged, its modulation of nanomaterial catalytic efficacy is less understood. In this study, proteomic analyses and nano-analytic methodologies quantify and characterize adsorbed proteins, correlating this protein layer with metal oxide catalytic activity in vitro and in vivo. The protein corona comprises up to 280 different proteins, constituting up to 38% by weight. Enhanced complement factors and other opsonins on nanocatalyst surfaces lead to their uptake into macrophages when applied topically, localizing >99% of the nanomaterials in tissue-resident macrophages. Initially, the formation of the protein corona significantly reduces the nanocatalysts' activity, but this activity can be partially recovered in endosomal conditions due to the proteolytic degradation of the corona. Overall, the research reveals the complex relationship between physisorbed proteins and the catalytic characteristics of specific metal oxide nanoparticles, providing design parameters for optimizing nanocatalysts in complex biological environments., (© 2024 The Authors. Small published by Wiley‐VCH GmbH.)
- Published
- 2024
- Full Text
- View/download PDF
36. Bioglass/ceria nanoparticle hybrids for the treatment of seroma: a comparative long-term study in rats.
- Author
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Pais MA, Papanikolaou A, Hoyos IA, Nißler R, De Brot S, Gogos A, Rieben R, Constantinescu MA, Matter MT, Herrmann IK, and Lese I
- Abstract
Background: Seroma formation is a common postoperative complication. Fibrin-based glues are typically employed in an attempt to seal the cavity. Recently, the first nanoparticle (NP)-based treatment approaches have emerged. Nanoparticle dispersions can be used as tissue glues, capitalizing on a phenomenon known as 'nanobridging'. In this process, macromolecules such as proteins physically adsorb onto the NP surface, leading to macroscopic adhesion. Although significant early seroma reduction has been shown, little is known about long-term efficacy of NPs. The aim of this study was to assess the long-term effects of NPs in reducing seroma formation, and to understand their underlying mechanism. Methods: Seroma was surgically induced bilaterally in 20 Lewis rats. On postoperative day (POD) 7, seromas were aspirated on both sides. In 10 rats, one side was treated with NPs, while the contralateral side received only NP carrier solution. In the other 10 rats, one side was treated with fibrin glue, while the other was left untreated. Seroma fluid, blood and tissue samples were obtained at defined time points. Biochemical, histopathological and immunohistochemical assessments were made. Results: NP-treated sides showed no macroscopically visible seroma formation after application on POD 7, in stark contrast to the fibrin-treated sides, where 60% of the rats had seromas on POD 14, and 50% on POD 21. At the endpoint (POD 42), sides treated with nanoparticles (NPs) exhibited significant macroscopic differences compared to other groups, including the absence of a cavity, and increased fibrous adhesions. Histologically, there were more macrophage groupings and collagen type 1 (COL1) deposits in the superficial capsule on NP-treated sides. Conclusion: NPs not only significantly reduced early manifestations of seroma and demonstrated an anti-inflammatory response, but they also led to increased adhesion formation over the long term, suggesting a decreased risk of seroma recurrence. These findings highlight both the adhesive properties of NPs and their potential for clinical therapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Pais, Papanikolaou, Hoyos, Nißler, De Brot, Gogos, Rieben, Constantinescu, Matter, Herrmann and Lese.)
- Published
- 2024
- Full Text
- View/download PDF
37. Flap Reconstruction Outcome Following Surgical Resection of Soft Tissue and Bone Sarcoma in the Setting of (Neo)adjuvant Therapy: A Sarcoma Center Experience.
- Author
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Lese I, Baesu C, Hoyos IA, Pais MA, Klenke F, Kollar A, Ionescu C, Constantinescu M, and Olariu R
- Abstract
Background: Soft tissue and bone sarcomas are heterogeneous groups of malignant tumors. The shift in their management, with an emphasis on limb salvage, has deemed the involvement of reconstructive surgeons an integral part of their multidisciplinary treatment. We present our experience with free and pedicled flaps in the reconstruction of sarcomas at a tertiary referral university hospital and major sarcoma center., Materials and Methods: All patients undergoing flap reconstruction after sarcoma resection over a 5-year period have been included in the study. Patient-related data and postoperative complications were collected retrospectively, ensuring a minimum follow-up of 3 years., Results: A total of 90 patients underwent treatment with 26 free flaps and 64 pedicled flaps. Postoperative complications occurred in 37.7% of patients, and the flap failure rate was 4.4%. Diabetes, alcohol consumption and male gender were associated with increased early necrosis of the flap. Preoperative chemotherapy significantly increased the occurrence of early infection and late dehiscence, while preoperative radiotherapy was associated with a higher incidence of lymphedema. Intraoperative radiotherapy was associated with late seromas and lymphedema., Conclusions: Reconstructive surgery with either pedicled or free flaps is reliable, but it can be demanding in the setting of sarcoma surgery. A higher complication rate is to be expected with neoadjuvant therapy and with certain comorbidities.
- Published
- 2023
- Full Text
- View/download PDF
38. Management of Postoperative Seroma: Recommendations Based on a 12-Year Retrospective Study.
- Author
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Papanikolaou A, Minger E, Pais MA, Constantinescu M, Olariu R, Grobbelaar A, and Lese I
- Abstract
Introduction: Seroma formation is a serious postoperative complication. Since the management algorithms available in the literature are scarce, we aimed to analyze our experience with postoperative seroma in order to identify indicators for revisional surgery and propose recommendations for management. Methods: This retrospective study included all patients with postoperative seroma treated in a tertiary university hospital from 2008 to 2020. Patients’ demographics, medical history, and seroma treatment details were recorded and analyzed. Results: Overall, 156 patients were included: 41% were initially treated through needle aspiration, with 61% eventually undergoing surgical treatment for postoperative seroma. Comorbidities, such as heart failure and coronary heart disease, were significantly associated with an increased need for revisional surgery (p < 0.05). Both a duration of >40 days of repeated needle aspirations and drain re-insertions were significantly correlated with an increased risk for revisional surgery (p < 0.05). Conclusion: Patients requiring seroma aspiration should be counseled on surgical treatment sooner rather than later, as prolonged aspiration time (over 40 days) greatly increases the risk of surgical revision. Moreover, the reinsertion of a drain should only be used as a temporizing measure, at most, and patients requiring a drain to control the size of the seroma should promptly be scheduled for a surgical revision.
- Published
- 2022
- Full Text
- View/download PDF
39. Preclinical assessment of antiviral combination therapy in a genetically humanized mouse model for hepatitis delta virus infection.
- Author
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Winer BY, Shirvani-Dastgerdi E, Bram Y, Sellau J, Low BE, Johnson H, Huang T, Hrebikova G, Heller B, Sharon Y, Giersch K, Gerges S, Seneca K, Pais MA, Frankel AS, Chiriboga L, Cullen J, Nahass RG, Lutgehetmann M, Toettcher JE, Wiles MV, Schwartz RE, and Ploss A
- Subjects
- Adaptive Immunity drug effects, Animals, Disease Models, Animal, Drug Therapy, Combination, Genome, Viral, Glycoproteins metabolism, Hepatitis B virus genetics, Hepatitis B virus physiology, Hepatitis D immunology, Hepatitis Delta Virus drug effects, Hepatocytes metabolism, Hepatocytes virology, Humans, Immunity, Innate drug effects, Immunocompetence, Lipopeptides pharmacology, Lipopeptides therapeutic use, Mice, Inbred C57BL, Mice, Transgenic, Organic Anion Transporters, Sodium-Dependent metabolism, Piperidines pharmacology, Piperidines therapeutic use, Pyridines pharmacology, Pyridines therapeutic use, Symporters metabolism, Transgenes, Viremia drug therapy, Viremia pathology, Hepatitis D drug therapy, Hepatitis D virology, Hepatitis Delta Virus physiology
- Abstract
Chronic delta hepatitis, caused by hepatitis delta virus (HDV), is the most severe form of viral hepatitis, affecting at least 20 million hepatitis B virus (HBV)-infected patients worldwide. HDV/HBV co- or superinfections are major drivers for hepatocarcinogenesis. Antiviral treatments exist only for HBV and can only suppress but not cure infection. Development of more effective therapies has been impeded by the scarcity of suitable small-animal models. We created a transgenic (tg) mouse model for HDV expressing the functional receptor for HBV and HDV, the human sodium taurocholate cotransporting peptide NTCP. Both HBV and HDV entered hepatocytes in these mice in a glycoprotein-dependent manner, but one or more postentry blocks prevented HBV replication. In contrast, HDV persistently infected hNTCP tg mice coexpressing the HBV envelope, consistent with HDV dependency on the HBV surface antigen (HBsAg) for packaging and spread. In immunocompromised mice lacking functional B, T, and natural killer cells, viremia lasted at least 80 days but resolved within 14 days in immunocompetent animals, demonstrating that lymphocytes are critical for controlling HDV infection. Although acute HDV infection did not cause overt liver damage in this model, cell-intrinsic and cellular innate immune responses were induced. We further demonstrated that single and dual treatment with myrcludex B and lonafarnib efficiently suppressed viremia but failed to cure HDV infection at the doses tested. This small-animal model with inheritable susceptibility to HDV opens opportunities for studying viral pathogenesis and immune responses and for testing novel HDV therapeutics., (Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)
- Published
- 2018
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40. Recapitulation of treatment response patterns in a novel humanized mouse model for chronic hepatitis B virus infection.
- Author
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Winer BY, Huang T, Low BE, Avery C, Pais MA, Hrebikova G, Siu E, Chiriboga L, Wiles MV, and Ploss A
- Subjects
- Animals, Female, Hepatitis B virus genetics, Hepatitis B virus physiology, Hepatitis B, Chronic genetics, Hepatitis B, Chronic metabolism, Hepatitis B, Chronic virology, Hepatocytes virology, Homeodomain Proteins genetics, Homeodomain Proteins metabolism, Humans, Interleukin Receptor Common gamma Subunit genetics, Interleukin Receptor Common gamma Subunit metabolism, Liver virology, Male, Mice, Mice, Inbred NOD, Mice, Knockout, Virus Replication, Antiviral Agents administration & dosage, Disease Models, Animal, Hepatitis B virus drug effects, Hepatitis B, Chronic drug therapy
- Abstract
There are ~350 million chronic carriers of hepatitis B (HBV). While a prophylactic vaccine and drug regimens to suppress viremia are available, chronic HBV infection is rarely cured. HBV's limited host tropism leads to a scarcity of susceptible small animal models and is a hurdle to developing curative therapies. Mice that support engraftment with human hepatoctyes have traditionally been generated through crosses of murine liver injury models to immunodeficient backgrounds. Here, we describe the disruption of fumarylacetoacetate hydrolase directly in the NOD Rag1
-/- IL2RγNULL (NRG) background using zinc finger nucleases. The resultant human liver chimeric mice sustain persistent HBV viremia for >90 days. When treated with standard of care therapy, HBV DNA levels decrease below detection but rebound when drug suppression is released, mimicking treatment response observed in patients. Our study highlights the utility of directed gene targeting approaches in zygotes to create new humanized mouse models for human diseases., (Copyright © 2016 Elsevier Inc. All rights reserved.)- Published
- 2017
- Full Text
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41. [Complete atrioventricular block in Kearns-Sayre syndrome].
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Villacorta H, Catharina CV, Nogueira AS, Duarte MM, Roma CC, Pais MA, and Victer HJ
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- Adult, Electrocardiography, Female, Heart Block diagnosis, Heart Block therapy, Humans, Kearns-Sayre Syndrome therapy, Pacemaker, Artificial, Syncope diagnosis, Syncope therapy, Heart Block complications, Kearns-Sayre Syndrome complications, Syncope etiology
- Abstract
A thirty-three year old woman, known to have Kearns-Sayre syndrome for eight years, had an ECG pattern of right bundle branch block and left anterior fascicular block that evolved to complete atrioventricular block, leading her to a syncopal episode. A temporary pacemaker and a permanent one were installed. The patient has been asymptomatic so far.
- Published
- 1996
42. [Multicenter study of isolated micro-organisms resistant to antimicrobials in 10 Portuguese hospitals in 1994].
- Author
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Cristino JM, Calado E, Calheiros IM, Costa D, Costa MN, Diogo J, Felicio ML, Ferro ML, Da Fonseca JC, Guimarães MA, Lito L, Marques J, Marques MT, Martins F, Pais MA, Pinto M, Ramos MH, Ribeiro G, Rodrigues LA, Salgado MJ, Simões J, Sobral MD, and Toscano C
- Subjects
- Bacteria isolation & purification, Hospitals statistics & numerical data, Humans, Microbial Sensitivity Tests, Anti-Bacterial Agents pharmacology, Bacteria drug effects
- Abstract
In 1994, Microbiology Laboratories of ten Portuguese hospitals analysed isolated microorganisms found in blood and urine samples and studied antimicrobial susceptibilities of the most frequent bacterial pathogens. From 63780 blood samples, the most frequent were Staphylococcus spp. and from 69189 urine samples significant numbers of Escherichia coli, Enterococcus spp., Pseudomonas aeruginosa and Candida spp. were isolated. Escherichia coli strains (c.7000) revealed a low percentage of resistance to antibiotics with the exceptions of ampicillin (48%) and co-trimoxazol (25%). Klebsiella pneumoniae isolates (c.2000) revealed important resistance to ampicillin (98%), cephalotin (31%), co-trimoxazol (38%) and gentamicin (28%), while values for 3rd generation cephalosporins varied among hospitals, with several strains showing phenotype of extended-spectrum beta-lactamase. A great variation in resistance values of P. aeruginosa (c.4000) was found in relation to the antibiotics as well as to the hospitals. Resistance to methicillin in S. aureus (c.6000) was high, reaching an average of 47%, and it was even higher with S. epidermidis (c.3000) and S. haemolyticus (c.650). Only vancomycin was always active against these strains. In E. faecalis (c.2500) resistance was of 2% to ampicillin, 35% to gentamicin, 45% to streptomycin and 1% to vancomycin. E. faecium isolates (c.300) showed the most worrying results with 70% resistance to ampicillin, 42% to gentamicin, 59% to streptomycin and 9% (30 strains isolated in 5 hospitals) to vancomycin. Vancomycin resistant strains were also resistant to all other antibiotics.
- Published
- 1996
43. Description of Pratylenchoides camachoi n. sp. (Tylenchida: Pratylenchidae) from Spain.
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Gomez Barcina A, Castillo P, and Gonzalez Pais MA
- Abstract
Pratylenchoides camachoi n. sp. from rosemary (Rosmarinus officinalis L.) in Sierra De Cazorla in southeastern Spain is described and illustrated. Pratylenchoides camachoi n. sp. is a bisexual species characterized by a cylindroid, sometimes clavate-shaped, male tail with a uniquely shaped smooth, rounded terminus. Females are characterized by a short esophageal overlap and six lines in the lateral field, which reduce to four in the tail region; not areolated except outer bands in the esophageal and tail regions.
- Published
- 1990
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