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1. Periodic gastroenterology and hepatology meetings with primary care: reasons for consultation

Author

Laura Mata-Román, Lourdes del Olmo-Martínez, Raquel Briso-Montiano, Agustina García-Pascual, Manuela Catón-Valdés, Manuel Jiménez-Rodríguez-Vila, María José Castellanos-Alonso, Lucinio Laso, Pilar Gómez-Gómez, Antonio Otero, José Ignacio Pinilla-Gimeno, Juan del Río-Hortega, Juan Pradera-Leonardo, Rosario Vallelado, Fernando Villuela-González, Elisa Ibañes-Jalón, Soledad Sañudo, Agustín Mayo, Agustín Caro-Patón, and Ana Almaraz-Gómez

Subjects
Consultas compartidas, Intervención educativa, Gastroenterología, Hepatología, Atención primaria, Urbano, Rural, Derivaciones, Diseases of the digestive system. Gastroenterology, RC799-869
Abstract

Introduction: care overload, aging of population, and increased chronic diseases lead to increased referrals from primary care, which may sometimes overload the health system. Thus, different interventions have been carried out attempting to improve these aspects. Objectives: to assess the most frequent causes of consultation of general physicians, both in joint consultations and clinical sessions held jointly with specialist consultant in primary care, in the urban and rural setting, and the influence on referrals to first consultations of gastroenterology. Material and methods: a mainly training type of intervention was carried out, consisting of regular meetings in both urban and rural primary care center, to perform joint consultations and clinical sessions on patients and topics related to the specialty of gastroenterology. The intervention period (divided in two subperiods) was compared with a control period. Results: most reasons for consultation were those corresponding to lower gastrointestinal tract, followed by liver disease and upper gastrointestinal tract. Significant differences were only found in distribution of diagnoses between the two centers in joint consultations. There was a relative (percent) decrease in referrals at the global level in both subperiods, only significant in the first (51.45%), as well as in rural setting (45.24%). Conclusion: common consultations motifs were similar in urban and rural settings, with some relevance of lower gastrointestinal tract disease. Most of them can be solved at primary care, with the help of consultant specialist. There is impact on referrals to the outpatient first consultations of gastroenterology, mainly in rural setting.

Published
2013
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2. Reduced expression of NO-sensitive guanylyl cyclase in reactive astrocytes of Alzheimer disease, Creutzfeldt–Jakob disease, and multiple sclerosis brains

Author

María Antonia Baltrons, Paula Pifarré, Isidre Ferrer, José Miguel Carot, and Agustina García

Subjects
Astroglia, Cyclic GMP, Soluble guanylyl cyclase, Nitric oxide, Alzheimer's disease, Creutzfeldt–Jakob disease, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

In Alzheimer's disease (AD) brains increased NO synthase (NOS) expression is found in reactive astrocytes surrounding amyloid plaques. We have recently shown that treatment with β-amyloid peptides or IL-1β down-regulates NO-sensitive soluble guanylyl cyclase (sGC) in cultured astrocytes and in adult rat brain. In this work, we have examined sGC activity and expression in postmortem brain tissue of AD patients and matched controls. No significant alteration was observed in basal or NO-stimulated sGC activity, nor in sGC β1 and α1 subunit levels in cortical extracts of AD brains. Immunohistochemistry showed intense and widespread labeling of sGC β1 in cortical and hippocampal neurons and white matter fibrillar astrocytes, while grey matter astrocytes were faintly stained. In AD, expression of sGC in neurons and fibrillar astrocytes is not altered but is markedly reduced in reactive astrocytes surrounding amyloid plaques. Immunostaining for sGC β1 was also lacking in reactive astrocytes in cortex and subcortical white matter in Creutzfeldt–Jakob disease brains and in subacute and chronic plaques in multiple sclerosis (MS) brains. Thus, induction of astrocyte reactivity is associated with decreased capacity to generate cGMP in response to NO both in vitro and in vivo. This effect may be related to the development of the astroglial inflammatory response.

Published
2004
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3. Taping en rizartrosis

Author

Veronica De cellis, Agustina García, Adriana Pérez Dávila, Analía Bohr, and Eduardo Scheines

Subjects
rizartrosis, rehabilitación, taping, Medicine
Abstract

Introducción: la osteoartritis (OA) de manos es una de las patologías particulares más frecuentes en la consulta diaria. Una de las localizaciones de la OA comúnmente afectada es la articulación trapecio 1° metacarpiana (TPM), denominada rizartrosis, que puede traer, además del dolor, alteraciones funcionales. Respecto al tratamiento, guías nacionales e internacionales recomiendan el uso de ortesis y ejercicios. El taping o vendaje neuromuscular actúa sobre estímulos propioceptivos generando analgesia sin limitación de la movilidad articular. Objetivo: evaluar los efectos de la aplicación de taping, comparado con el tratamiento ortésico convencional, en un programa de rehabilitación de rizartrosis. Material y métodos: fueron incluidos pacientes de ambos sexos, mayores de 45 años con OA primaria que cumplían los criterios clínicos grado II-III de Eaton, y radiológicos grado 2-3 de Kellgren y Lawrence. Fueron divididos aleatoriamente en dos grupos, el GRUPO TAPING (GT) en donde se realizó un vendaje para la TPM y el GRUPO FÉRULA (GF) a quienes se les realizó una ortesis tipo Spica corta en termomoldeable. Todos iniciaron un programa de ejercicios específicos y fueron instruidos en principios de protección articular (PPA). Fueron evaluados al inicio y al mes del tratamiento: dolor (VAS), fuerza muscular (dinamómetro Jamar), habilidad y destreza (picking up test), capacidad funcional (Australian Canadian Osteoarthritis Hand Index: AUSCAN). Para el análisis estadístico se utilizó la prueba T Student, del programa Excel versión 2010. Resultados: fueron ingresados 40 pacientes, 20 en el grupo GF y 20 en el GT. Ambos grupos mejoraron significativamente el dolor al mes de tratamiento con respecto a la evaluación basal: GF= Xi: 5,8 - Xf: 4,2 (p.0013) y GT Xi= 6,1 - Xf= 3,5 (p.0003); y el AUSCAN total GF: Xi: 40 Xf: 35 (p.0028) y GT: Xi: 39 - Xf: 29 (p.007). En cuanto a las subescalas del AUSCAN ambos grupos mejoraron significativamente el dolor y función, solo se encontró una mejoría estadísticamente significativa en la rigidez en el grupo taping GT: Xi 2,65 - Xf: 1,95 (p.004). Conclusiones: en la población estudiada encontramos que ambas modalidades terapéuticas son recomendadas en el tratamiento de rehabilitación conservador de la rizartrosis; observándose mejoría en los parámetros de dolor y función. Sin embargo, el presente estudio indica que se obtienen mejores resultados en la evaluación de la rigidez en el grupo taping comparado con el grupo férula.

Published
2014
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4. Characterization of albendazole-randomly methylated-β-cyclodextrin inclusion complex and in vivo evaluation of its antihelmitic activity in a murine model of Trichinellosis.

Author

Agustina García, Darío Leonardi, María D Vasconi, Lucila I Hinrichsen, and María C Lamas

Subjects
Medicine, Science
Abstract

Albendazole is a benzimidazole carbamate extensively used in oral chemotherapy against intestinal parasites, due to its broad spectrum activity, good tolerance and low cost. However, the drug has the disadvantage of poor bioavailability due to its very low solubility in water; as a consequence, a very active area of research focuses on the development of new pharmaceutical formulations to increase its solubility, dissolution rate, and bioavailability. The primary objective of this study was to prepare randomly methylated β-cyclodextrins inclusion complexes to increase albendazole dissolution rate, in order to enhance its antiparasitic activity. This formulation therapeutic efficacy was contrasted with that of the pure drug by treating Trichinella spiralis infected mice during the intestinal phase of the parasite cycle, on days five and six post-infection. This protocol significantly decreased muscle larval burden measured in the parenteral stage on day 30 post-infection, when compared with the untreated control. Thus, it could be demonstrated that the inclusion complexes improve the in vivo therapeutic activity of albendazole.

Published
2014
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5. Modified β-cyclodextrin inclusion complex to improve the physicochemical properties of albendazole. complete in vitro evaluation and characterization.

Author

Agustina García, Darío Leonardi, Mario Oscar Salazar, and María Celina Lamas

Subjects
Medicine, Science
Abstract

The potential use of natural cyclodextrins and their synthetic derivatives have been studied extensively in pharmaceutical research and development to modify certain properties of hydrophobic drugs. The ability of these host molecules of including guest molecules within their cavities improves notably the physicochemical properties of poorly soluble drugs, such as albendazole, the first chosen drug to treat gastrointestinal helminthic infections. Thus, the aim of this work was to synthesize a beta cyclodextrin citrate derivative, to analyze its ability to form complexes with albendazole and to evaluate its solubility and dissolution rate. The synthesis progress of the cyclodextrin derivative was followed by electrospray mass spectrometry and the acid-base titration of the product. The derivative exhibited an important drug affinity. Nuclear magnetic resonance experiments demonstrated that the tail and the aromatic ring of the drug were inside the cavity of the cyclodextrin derivative. The inclusion complex was prepared by spray drying and full characterized. The drug dissolution rate displayed exceptional results, achieving 100% drug release after 20 minutes. The studies indicated that the inclusion complex with the cyclodextrin derivative improved remarkably the physicochemical properties of albendazole, being a suitable excipient to design oral dosage forms.

Published
2014
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6. Contextual aspects of the emergence of occupational therapy in Argentina

Author

Julieta Briglia and Agustina García

Subjects
Industrial medicine. Industrial hygiene, RC963-969, Industrial hygiene. Industrial welfare, HD7260-7780.8
Abstract

This paper aims to characterize some contextual aspects before and after the opening of the first educational institution for Occupational Therapy in Argentina, the National School of Occupational Therapy in the historical period that runs from 1946-1965. This article was written based on our work as scholars in the framework of a research project led by Mariela Nabergoi and comprised by a team of teacher researchers from the Institute of Rehabilitation Sciences and the Movement of The National University of San Martín. To meet the proposed objective we performed an analysis of secondary sources which describe the political-economic, social, educational and health contexts in Argentina during the period studied and which address the issue of the emergence of Occupational Therapy in Argentina. Re!ecting on the contextual factors that allowed the emergence of OT in the country, we can state that the polio epidemic of 1956 was, as pointed out in much of the literature on the history of OT relieved in our country, a situation triggering the need for social care to form human resources to attend to the effects of the disease. However, we emphasize the importance of avoiding conceiving the epidemic in terms of cause and effect with respect to the creation of vocational training in OT, because it cannot be isolated from the broader political-economic, social, educational and health contexts.

Published
2013
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7. Delitos de cuello blanco: ejecución de las sentencias

Author

María Agustina García, Tiago Oscar Chabeuf, Pablo Jesús Bur Ahumada, Nelson Alú, Juan Ignacio Acosta, and Juan Martin Degano

Subjects
Delitos de cuello blanco, delincuencia de cuello blanco, ejecución de sentencias, sociología de la desviación, teoría de la asociación diferencial, teoría del etiquetaje, Social sciences (General), H1-99
Abstract

Los delitos de cuello blanco, caracterizados por su comisión por individuos de alto estatus social y económico, representan una problemática significativa en la justicia moderna. A diferencia de los delitos convencionales, los de cuello blanco impactan ampliamente en la estructura social y económica, implicando no sólo a individuos aislados, sino a la sociedad en su conjunto. Este estudio emplea un enfoque cualitativo-descriptivo para examinar la incidencia, características y repercusiones de estos delitos, utilizando como fuentes primarias artículos científicos recientes de países latinoamericanos y España. Las palabras clave incluyen términos como: medios de comunicación, perfil del delincuente y teorías sociológicas, y el análisis se enriquece con contribuciones de teóricos clásicos como Becker, Foucault y Zaffaroni. Además, se examinan casos mediáticos, como la tragedia de Once en Argentina, que ilustran la complejidad de atribuir y sancionar efectivamente estas conductas delictivas. Los hallazgos indican que existe una gran dificultad en establecer un vínculo claro entre la acción delictiva y sus consecuencias, lo que, sumado a la representación mediática que frecuentemente minimiza estos actos, resulta en una escasa frecuencia de condenas. El estudio concluye que la falta de reconocimiento de la gravedad de estos delitos y su tratamiento diferenciado debido a la influencia y el poder de los delincuentes perpetúan la disparidad en la aplicación de la justicia, subrayando la necesidad de reformas en la percepción y enfoques legales hacia los delitos de cuello blanco.

Published
2024
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8. Impact of protein conformational diversity on AlphaFold predictions.

Author

Tadeo E. Saldaño, Nahuel Escobedo, Julia Marchetti, Diego Javier Zea, Juan Mac Donagh, Ana Julia Velez Rueda, Eduardo Gonik, Agustina García Melani, Julieta Novomisky Nechcoff, Martín N. Salas, Tomás Peters, Nicolás Demitroff, Sebastian Fernandez Alberti, Nicolas Palopoli, María Silvina Fornasari, and Gustavo D. Parisi

Published
2022
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9. Impact of protein conformational diversity on AlphaFold predictions

Author

María Silvina Fornasari, Nahuel Escobedo, Agustina García Melani, Sebastian Fernandez Alberti, Tomás Peters, Gustavo Parisi, Nicolás Demitroff, Ana Julia Velez Rueda, Juan Mac Donagh, Eduardo Gonik, Nicolas Palopoli, Diego Javier Zea, Julieta Novomisky Nechcoff, Tadeo E. Saldaño, Julia Marchetti, and Martín N. Salas

Subjects
Statistics and Probability, Protein Conformation, Chemistry, Proteins, A protein, 3d model, Computational biology, Biochemistry, Single sequence, Computer Science Applications, Computational Mathematics, Computational Theory and Mathematics, Prediction methods, Model quality, Molecular Biology, Conformational isomerism, Protein Binding, Diversity (business)
Abstract

Motivation After the outstanding breakthrough of AlphaFold in predicting protein 3D models, new questions appeared and remain unanswered. The ensemble nature of proteins, for example, challenges the structural prediction methods because the models should represent a set of conformers instead of single structures. The evolutionary and structural features captured by effective deep learning techniques may unveil the information to generate several diverse conformations from a single sequence. Here, we address the performance of AlphaFold2 predictions obtained through ColabFold under this ensemble paradigm. Results Using a curated collection of apo–holo pairs of conformers, we found that AlphaFold2 predicts the holo form of a protein in ∼70% of the cases, being unable to reproduce the observed conformational diversity with the same error for both conformers. More importantly, we found that AlphaFold2's performance worsens with the increasing conformational diversity of the studied protein. This impairment is related to the heterogeneity in the degree of conformational diversity found between different members of the homologous family of the protein under study. Finally, we found that main-chain flexibility associated with apo–holo pairs of conformers negatively correlates with the predicted local model quality score plDDT, indicating that plDDT values in a single 3D model could be used to infer local conformational changes linked to ligand binding transitions. Availability and implementation Data and code used in this manuscript are publicly available at https://gitlab.com/sbgunq/publications/af2confdiv-oct2021. Supplementary information Supplementary data are available at Bioinformatics online.

Published
2021

10. Impact of protein conformational diversity on AlphaFold predictions

Author

Saldaño, Tadeo, primary, Escobedo, Nahuel, additional, Marchetti, Julia, additional, Zea, Diego Javier, additional, Mac Donagh, Juan, additional, Velez Rueda, Ana Julia, additional, Gonik, Eduardo, additional, Melani, Agustina García, additional, Novomisky Nechcoff, Julieta, additional, Salas, Martín N., additional, Peters, Tomás, additional, Demitroff, Nicolás, additional, Fernandez Alberti, Sebastian, additional, Palopoli, Nicolas, additional, Fornasari, Maria Silvina, additional, and Parisi, Gustavo, additional

Published
2021
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11. Ordenamiento Territorial de Bosques Nativos: Resultados de la Zonificación realizada por provincias del Norte argentino

Author

María Agustina García Collazo, Amalia Panizza, and José María Paruelo

Subjects
Ley de bosques nativos, Plan de ordenamiento territorial, criterios de sustentabilidad ambiental, categorías de conservación, Environmental sciences, GE1-350, Ecology, QH540-549.5
Abstract

Argentina cuenta con varias experiencias de ordenamiento territorial (OT) pero hasta el momento no ha sancionado una ley integral. Uno de los principales antecedentes es el ordenamiento territorial de los bosques nativos (OTBN) a través de la ley 26331, sancionada en 2007. El objetivo de este trabajo fue evaluar las experiencias de zonificación en el marco de esta ley de las provincias de Santiago del Estero, Chaco, Formosa y Salta. Se analizó la aplicación de los 10 criterios de sustentabilidad ambiental contemplados por la ley y se compararon cuantitativamente los mapas de zonificación resultantes del proceso de OTBN en las áreas limítrofes. La interpretación de los criterios de sustentabilidad ambiental ha sido dispar entre provincias debido, en parte, a que la información de base utilizada no tiene el mismo nivel de detalle. Salta y Chaco consideraron mayor detalle en estos criterios mientras que Santiago del Estero y Formosa utilizaron información con un nivel de detalle menor. La comparación de la categorización de bosques entre provincias colindantes muestra que la mayor concordancia en las categorías asignadas se observa en los límites de Santiago del Estero y Chaco (58.3%). El grado de concordancia entre los restantes pares de provincias colindantes resultó considerablemente menor: 24.76% entre Chaco y Salta; 20.65% entre Formosa y Salta; 10.54% entre Chaco y Formosa y 1.28% entre Salta y Santiago del Estero. Los resultados sugieren que las zonificaciones no han resultado consistentes debido al bajo nivel de concordancia en la categorización de sus bosques.

Published
2013
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12. Circuitos de Fluidos. Suspensión y Dirección

Author

Agustina García, Iván, Canales Leiva, Joaquim, and Universitat Jaume I. Departament d'Enginyeria Mecànica i Construcció

Subjects
Máster Universitario en Profesor/a de Educación Secundaria Obligatoria y Bachillerato, Formación Profesional y Enseñanzas de Idiomas, Master's Degree in Secondary Education, Vocational Training and Language Teaching, Suspensión y Dirección, TFM, Programación didáctica, Unidades Didácticas, Formación Profesional, Circuito de Fluidos, Màster Universitari en Professor/a d'Educació Secundària Obligatòria i Batxillerat, Formació Professional i Ensenyaments d'Idiomes
Abstract

Treball Final de Màster Universitari en Professor/a d'Educació Secundària Obligatòria i Batxillerat, Formació Professional i Ensenyaments d'Idiomes. Codi SAP129. Curs: 2019/2020 El trabajo de fin de máster presentado se clasifica dentro de la modalidad de Planificación y/o programación curriculares corresponde a una programación curricular del módulo profesional Circuitos de Fluidos. Suspensión y Dirección, perteneciente al Ciclo Formativo de Técnico en Electromecánica de Vehículos Automóviles de Formación Profesional de Grado Medio. El módulo profesional Circuitos de Fluidos. Suspensión y Dirección se divide en 3 grandes bloques; el primer bloque, sobre circuitos neumáticos e hidráulicos donde el alumno aprenderá sobre las leyes de hidráulica y neumática, sus elementos y diseño de circuitos. En el segundo bloque, el sistema de suspensión, se explica todos los elementos que conforman un sistema de suspensión, los tipos de sistemas existentes en el mercado y así como todas las intervenciones que se realizan sobre los sistemas de suspensión. Y finalmente, el tercer bloque, corresponde el sistema de dirección, al igual que en el anterior, el alumno conocerá todos los elementos que intervienen en el sistema de dirección, tipos y todas las operaciones que se realizan en los sistemas de dirección. IES Politècnic de Castellón constituye el centro que se ha elegido para hacer este trabajo, y la programación es diseñada para una clase de 25 alumnos. A lo largo de este documento se han desarrollado las unidades didácticas que serán aplicadas dentro del aula, para su diseño se ha tenido en cuenta la normativa específica donde se define desde los contenidos, los resultados de aprendizaje y los criterios de evaluación. Las unidades están divididas en dos partes; una parte teórica y una parte práctica. En la parte teórica, el profesor explicaría el contenido, durante las sesiones se realizarían actividades y test con la finalidad de asentar los contenidos explicados. Y en la parte practica, formada por un conjunto de actividades en el aula taller donde los alumnos realizaran intervenciones sobre los vehículos o en componentes del vehículo. La evaluación de las actividades practicas se realizara mediante un listado de control y rubricas. Y al finalizar la unidad didáctica, se realizará la evaluación del alumno por medio de una prueba escrita.

Published
2020

13. Impact of protein conformational diversity on AlphaFold predictions.

Author

Saldaño, Tadeo, Escobedo, Nahuel, Marchetti, Julia, Zea, Diego Javier, Donagh, Juan Mac, Rueda, Ana Julia Velez, Gonik, Eduardo, Melani, Agustina García, Nechcoff, Julieta Novomisky, Salas, Martín N, Peters, Tomás, Demitroff, Nicolás, Alberti, Sebastian Fernandez, Palopoli, Nicolas, Fornasari, Maria Silvina, and Parisi, Gustavo

Subjects
PROTEIN models, DEEP learning, PROTEINS, FORECASTING
Abstract

Motivation After the outstanding breakthrough of AlphaFold in predicting protein 3D models, new questions appeared and remain unanswered. The ensemble nature of proteins, for example, challenges the structural prediction methods because the models should represent a set of conformers instead of single structures. The evolutionary and structural features captured by effective deep learning techniques may unveil the information to generate several diverse conformations from a single sequence. Here, we address the performance of AlphaFold2 predictions obtained through ColabFold under this ensemble paradigm. Results Using a curated collection of apo–holo pairs of conformers, we found that AlphaFold2 predicts the holo form of a protein in ∼70% of the cases, being unable to reproduce the observed conformational diversity with the same error for both conformers. More importantly, we found that AlphaFold2's performance worsens with the increasing conformational diversity of the studied protein. This impairment is related to the heterogeneity in the degree of conformational diversity found between different members of the homologous family of the protein under study. Finally, we found that main-chain flexibility associated with apo–holo pairs of conformers negatively correlates with the predicted local model quality score plDDT, indicating that plDDT values in a single 3D model could be used to infer local conformational changes linked to ligand binding transitions. Availability and implementation Data and code used in this manuscript are publicly available at https://gitlab.com/sbgunq/publications/af2confdiv-oct2021. Supplementary information Supplementary data are available at Bioinformatics online. [ABSTRACT FROM AUTHOR]

Published
2022
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14. Synthesis and characterization of a new cyclodextrin derivative with improved properties to design oral dosage forms

Author

María D. Vasconi, Lucila Isabel Hinrichsen, Maria Celina Lamas, Ana Victoria Codina, Josefina Priotti, Ariel D. Quiroga, Darío Leonardi, and Agustina García

Subjects
CYCLODEXTRINS, Farmacología y Farmacia, CIENCIAS MÉDICAS Y DE LA SALUD, Otras Ciencias Biológicas, Administration, Oral, Pharmaceutical Science, 02 engineering and technology, SYNTHESIS, Albendazole, 030226 pharmacology & pharmacy, Dosage form, Ciencias Biológicas, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Differential scanning calorimetry, Animals, Solubility, Dissolution, Trichinella spiralis, Anthelmintics, chemistry.chemical_classification, PHYSICOCHEMICAL CHARACTERIZATION, Calorimetry, Differential Scanning, Molecular Structure, Cyclodextrin, beta-Cyclodextrins, Nuclear magnetic resonance spectroscopy, 021001 nanoscience & nanotechnology, Medicina Básica, chemistry, Stability constants of complexes, Drug Design, Microscopy, Electron, Scanning, ALBENDAZOLE, 0210 nano-technology, POORLY WATER-SOLUBLE DRUG, Derivative (chemistry), CIENCIAS NATURALES Y EXACTAS, Nuclear chemistry
Abstract

This work aimed to synthesize a novel β-cyclodextrin derivative, itaconyl-β-cyclodextrin to evaluate whether albendazole inclusion complexes with the new β-cyclodextrin derivative-improved albendazole dissolution efficiency and its anthelminthic activity. The new derivative was thoroughly evaluated and characterized, and an average degree of substitution of 1.4 per cyclodextrin molecule was observed. Albendazole:itaconyl-β-cyclodextrin complexes were prepared by spray drying procedures and investigated using phase solubility diagrams, dissolution efficiency, X-ray diffraction, differential scanning calorimetry, Fourier transform infrared, scanning electronic microscopy, mass spectrometry, and nuclear magnetic resonance spectroscopy. Phase solubility diagrams and mass spectrometry studies showed that the inclusion complex was formed in an equimolar ratio. Stability constant values were 602 M −1 in water, and 149 M −1 in HCl 0.1 N. Nuclear magnetic resonance experiments of the inclusion complex showed correlation signals between the aromatic and propyl protons of albendazole and the itaconyl-β-cyclodextrin inner protons. The studies indicated solid structure changes of albendazole included in itaconyl-β-cyclodextrin. The maximum drug release was reached at 15 min, and the inclusion complex solubility was 88-fold higher than that of the pure drug. The in vitro anthelmintic activity assay showed that the complex was significantly more effective than pure albendazole. Fil: García, Agustina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; Argentina Fil: Priotti, Josefina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; Argentina Fil: Codina, Ana Victoria. Universidad Nacional de Rosario. Facultad de Ciencias Medicas. Instituto de Genetica Experimental; Argentina Fil: Vasconi, María Delia. Universidad Nacional de Rosario. Facultad de Ciencias Medicas. Instituto de Genetica Experimental; Argentina Fil: Quiroga, Ariel Dario. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Fisiología Experimental. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Fisiología Experimental; Argentina Fil: Hinrichsen, Lucila Isabel. Universidad Nacional de Rosario. Facultad de Ciencias Medicas. Instituto de Genetica Experimental; Argentina Fil: Leonardi, Darío. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; Argentina Fil: Lamas, Maria Celina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; Argentina

Published
2019
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15. Succinyl-β-cyclodextrin: Influence of the substitution degree on albendazole inclusion complexes probed by NMR

Author

Agustina García, Josefina Priotti, M. J. Ferreira, Teresa G. Nunes, Maria Celina Lamas, and Darío Leonardi

Subjects
Materials science, Bioengineering, 02 engineering and technology, Albendazole, 010402 general chemistry, 01 natural sciences, Biomaterials, purl.org/becyt/ford/1 [https], Phase (matter), medicine, purl.org/becyt/ford/1.4 [https], Aromatic moiety, Solubility, Nuclear Magnetic Resonance, Biomolecular, chemistry.chemical_classification, SUCCINYL SUBSTITUENT, Aqueous solution, Cyclodextrin, Otras Ciencias Químicas, beta-Cyclodextrins, Ciencias Químicas, 021001 nanoscience & nanotechnology, CYCLODEXTRIN, SOLUTION NMR, 0104 chemical sciences, SOLID-STATE NMR, Crystallography, Solid-state nuclear magnetic resonance, chemistry, Mechanics of Materials, Stability constants of complexes, ALBENDAZOLE, 0210 nano-technology, CIENCIAS NATURALES Y EXACTAS, medicine.drug
Abstract

Succinyl-β-CD derivatives were obtained by green synthesis with degrees of substitution (DS) 1.3 and 2.9. The spray-drying technique was used to obtain albendazole (ABZ):succinyl-β-CD inclusion complexes. Phase solubility diagrams indicated that both succinyl-β-CD derivatives formed 1:1 molar ratio ABZ complexes, but the complex with DS 2.9 has a lower formation constant. The presence of stable inclusion complexes in aqueous solution was confirmed by NMR. For both complexes the aromatic moiety is encapsulated into the host cavity. In the solid-state, 13C and 15N NMR spectral differences between ABZ and ABZ included in spray-dried systems showed that strong structural changes occurred in the systems. At least two different ABZ amorphous species were identified based on DS. ABZ species were stable over more than six months based on spectral data. Finally, the influence of DS in the number and type of the inclusion complexes was elucidated. Fil: Priotti, Josefina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; Argentina Fil: García, Agustina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; Argentina Fil: Leonardi, Darío. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; Argentina Fil: Ferreira, M. J.. Instituto Superior Tecnico; Portugal Fil: Lamas, Maria Celina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; Argentina Fil: Nunes, T. G.. Instituto Superior Tecnico; Portugal

Published
2018

16. ¿Cuál es la situación de la Ley de Bosques en la Región Chaqueña a diez años de su sanción? Revisando su pasado para discutir su futuro

Author

Mariana Andrea Schmidt, Lorenzo Langbehn, Matías E. Mastrangelo, Lucas Seghezzo, Marcos Texeira, José Norberto Volante, Gabriela Merlinsky, Santiago R. Verón, José M. Paruelo, Miguel Marcelo Brassiolo, Clara E. Mosso, Sebastián Aguiar, María Vallejos, Daniel Cáceres, Luciana Staiano, Lucía Ciuffoli, Gonzalo H. Camba Sans, and María Agustina García Collazo

Subjects
bosque nativo, equidad, Forests, Legislación, EQUIDAD, lcsh:Environmental sciences, efectividad, lcsh:GE1-350, Ecology, purl.org/becyt/ford/5 [https], ZONIFICACIÓN, EFFECTIVENESS, Bosques, Ordenación Territorial, Otras Agricultura, Silvicultura y Pesca, NATIVE FOREST, zonificación, Primary Forests, EQUITY, CHACO, LEGITIMIDAD, Legislation, Argentina, BOSQUES NATIVOS, bosques nativos, LEY DE BOSQUES, purl.org/becyt/ford/5.4 [https], chaco, OTBN, CIENCIAS SOCIALES, Otras Sociología, lcsh:QH540-549.5, ordenamiento territorial, Región Chaqueña, argentina, Ecology, Evolution, Behavior and Systematics, Bosque Primario, ORDENAMIENTO TERRITORIAL, legitimidad, CIENCIAS AGRÍCOLAS, LEGITIMACY, purl.org/becyt/ford/4.1 [https], ZONATION, lcsh:Ecology, LAND USE PLANNING, otbn, EFECTIVIDAD, Agricultura, Silvicultura y Pesca, Sociología, purl.org/becyt/ford/4 [https]
Abstract

En un complejo escenario ambiental, productivo y socioeconómico, el 28 de noviembre de 2007 fue sancionada en Argentina la Ley Nacional Nº 26.331 de “Presupuestos Mínimos de Protección Ambiental de los Bosques Nativos" (conocida como "Ley de bosques") con el propósito de proteger los bosques nativos a escala nacional. En este artículo nos proponemos realizar una síntesis crítica de la información disponible acerca de esta ley a diez años de su sanción, con una aproximación que toma en cuenta aspectos ambientales, económicos y sociales. Caracterizamos el desempeño de esta ley en la Región Chaqueña en cuanto a diferentes dimensiones, identificamos sus principales desafíos y describimos una serie de propuestas que desde el sector de Ciencia y Técnica pueden contribuir a su (re)diseño e implementación en el contexto de las actualizaciones de los Ordenamientos Territoriales de Bosques Nativos provinciales. Para ello, integramos información disponible proveniente de distintas fuentes, tales como normativas (nacionales y provinciales), literatura científica, informes de organismos estatales y de ONG y artículos periodísticos. La Ley de Bosques instaló en la opinión pública de nuestro país la problemática vinculada a la pérdida de bosques nativos y se ha posicionado como el principal instrumento de política forestal nacional para su protección. Si bien hubo una reducción en las tasas de deforestación en la región Chaqueña, no existen evidencias certeras de que esta reducción se deba a su aplicación. La Ley de Bosques en la Región Chaqueña presenta una serie de desafíos para mejorar su desempeño en cuanto a su efectividad, equidad y legitimidad social. En este trabajo se presentan diez observaciones que emergen de la revisión realizada. Por otro lado, se esbozan una serie de propuestas de investigación y acción en torno a la ley vinculadas a esas observaciones. In a complex environmental, productive and socioeconomic scenario, on November 28th, 2007, the National Act N°26.331 of “Minimum Standards for the Environmental Protection of Native Forests” (known as the “Forest Law”) was sanctioned in Argentina with the purpose of protecting native forests at the national scale. In this article, we aim to critically synthesize the available information about this law ten years after its sanction from an approach that takes into account environmental, economic and social aspects. In particular, we characterize the performance of this law in the Chaco Region in different dimensions, identify its main challenges and describe a series of proposals that from the science and technology sector can contribute to its (re)design and implementation in the context of the revisions of the Provincial Native Forest Land Use Planning Programs. In order to accomplish these objectives, we integrated information available from different sources, such as laws and regulations (national and provincial), scientific literature, reports from government agencies and NGOs and newspaper articles. The Forest Law installed in the public opinion of our country the problems related to the loss of native forests and has positioned itself as the main national instrument for forest conservation. Although deforestation rates lowered in the Chaco Region, there is no clear evidence that this reduction was due to its application. The Forest Law in the Chaco Region presents a series of challenges to improve its performance in terms of its effectiveness, equity and social legitimacy. In this paper, we present ten observations that emerge from the review carried out. On the other hand, linked to these observations, we outline a series of research and action proposals for enhancing the performance of the law. EEA Balcarce Fil: Aguiar, Sebastián. Universidad de Buenos Aires. Facultad de Agronomia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Fisiológicas y Ecológicas Vinculadas a la Agricultura. Universidad de Buenos Aires. Facultad de Agronomía. Instituto de Investigaciones Fisiológicas y Ecológicas Vinculadas a la Agricultura; Argentina Fil: Mastrangelo, Matias Enrique. Universidad Nacional de Mar del Plata. Facultad de Ciencias Agrarias. Grupo de Estudio de Agroecosistemas y Paisajes Rurales; Argentina. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Balcarce; Argentina Fil: García Collazo, María A. Ministerio de Ambiente y Desarrollo Sustentable de la Nación. Dirección Nacional de Bosques; Argentina. Universidad de Buenos Aires. Facultad de Agronomía. Departamento de Métodos Cuantitativos y Sistemas de Información; Argentina Fil: Camba Sans, Gonzalo H. Universidad de Buenos Aires. Facultad de Agronomia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Fisiológicas y Ecológicas Vinculadas a la Agricultura. Universidad de Buenos Aires. Facultad de Agronomía. Instituto de Investigaciones Fisiológicas y Ecológicas Vinculadas a la Agricultura; Argentina. Universidad de Buenos Aires. Facultad de Agronomía. Departamento de Métodos Cuantitativos y Sistemas de Información; Argentina Fil: Mosso, Clara E. Universidad de Buenos Aires. Facultad de Agronomía. Licenciatura en Ciencias Ambientales; Argentina Fil: Ciuffoli, Lucía. Ministerio de Ambiente y Desarrollo Sustentable de la Nación. Dirección Nacional de Bosques; Argentina. Fil: Schmidt, Mariana. Universidad de Buenos Aires. Facultad de Ciencias Sociales. Instituto de Investigaciones Gino Germani. Grupo de Estudios Ambientales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Vallejos, María. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Fisiológicas y Ecológicas Vinculadas a la Agricultura. Universidad de Buenos Aires. Facultad de Agronomía. Instituto de Investigaciones Fisiológicas y Ecológicas Vinculadas a la Agricultura; Argentina. Universidad de Buenos Aires. Facultad de Agronomía. Departamento de Métodos Cuantitativos y Sistemas de Información; Argentina Fil: Langbehn, Lorenzo. Universidad Nacional de Santiago del Estero. Facultad de Humanidades, Ciencias Sociales y de la Salud; Argentina Fil: Brassiolo, Miguel. Universidad Nacional de Santiago del Estero. Facultad de Ciencias Forestales; Argentina Fil: Cáceres, Daniel. Universidad Nacional de Córdoba. Facultad de Ciencias Agropecuarias; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Merlinsky, Gabriela. Universidad de Buenos Aires. Facultad de Ciencias Sociales. Instituto de Investigaciones Gino Germani. Grupo de Estudios Ambientales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Paruelo, José María. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Fisiológicas y Ecológicas Vinculadas a la Agricultura. Universidad de Buenos Aires. Facultad de Agronomía. Instituto de Investigaciones Fisiológicas y Ecológicas Vinculadas a la Agricultura; Argentina. Universidad de Buenos Aires. Facultad de Agronomía. Departamento de Métodos Cuantitativos y Sistemas de Información; Argentina. Instituto Nacional de Investigaciones Agropecuarias. INIA La Estanzuela; Uruguay Fil: Seghezzo, Lucas. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Investigaciones en Energía no Convencional. Universidad Nacional de Salta. Facultad de Ciencias Exactas. Departamento de Física. Instituto de Investigaciones en Energía no Convencional; Argentina Fil: Staiano, Luciana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Fisiológicas y Ecológicas Vinculadas a la Agricultura. Universidad de Buenos Aires. Facultad de Agronomía. Instituto de Investigaciones Fisiológicas y Ecológicas Vinculadas a la Agricultura; Argentina. Universidad de Buenos Aires. Facultad de Agronomía. Departamento de Métodos Cuantitativos y Sistemas de Información; Argentina Fil: Texeira González, Marcos Alexis. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Fisiológicas y Ecológicas Vinculadas a la Agricultura. Universidad de Buenos Aires. Facultad de Agronomía. Instituto de Investigaciones Fisiológicas y Ecológicas Vinculadas a la Agricultura; Argentina. Universidad de Buenos Aires. Facultad de Agronomía. Departamento de Métodos Cuantitativos y Sistemas de Información; Argentina Fil: Volante, Jose Norberto. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Salta; Argentina Fil: Veron, Santiago Ramón. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Clima y Agua; Argentina. Universidad de Buenos Aires. Facultad de Agronomía. Departamento de Métodos Cuantitativos y Sistemas de Información; Argentina

Published
2018

17. Repositioning of Anti-parasitic Drugs in Cyclodextrin Inclusion Complexes for Treatment of Triple-Negative Breast Cancer

Author

Agustina García, Mauricio Ariel Menacho Márquez, María Virginia Baglioni, Maria Celina Lamas, María José Rico, Josefina Priotti, and Darío Leonardi

Subjects
Pharmaceutical Science, Triple Negative Breast Neoplasms, Pharmacology, 030226 pharmacology & pharmacy, Mice, Random Allocation, 0302 clinical medicine, X-Ray Diffraction, Drug Discovery, Medicine, Triple-negative breast cancer, media_common, Mice, Inbred BALB C, Ecology, Antiparasitic Agents, Biopharmaceutics, beta-Cyclodextrins, Ciencias Químicas, General Medicine, Drug repositioning, Treatment Outcome, 030220 oncology & carcinogenesis, MCF-7 Cells, Female, ALBENDAZOLE, CIENCIAS NATURALES Y EXACTAS, medicine.drug, Drug, media_common.quotation_subject, REPOSITIONING, Biological Availability, Aquatic Science, Albendazole, 03 medical and health sciences, In vivo, BREAST CANCER CELL LINE, Animals, Humans, Ecology, Evolution, Behavior and Systematics, Cell Proliferation, Cyclodextrins, business.industry, Otras Ciencias Químicas, Drug Repositioning, CYCLODEXTRIN, In vitro, Bioavailability, business, Agronomy and Crop Science
Abstract

Drug repositioning refers to the identification of new therapeutic indications for drugs already approved. Albendazole and ricobendazole have been used as anti-parasitic drugs for many years; their therapeutic action is based on the inhibition of microtubule formation. Therefore, the study of their properties as antitumor compounds and the design of an appropriate formulation for cancer therapy is an interesting issue to investigate. The selected compounds are poorly soluble in water, and consequently, they have low and erratic bioavailability. In order to improve their biopharmaceutics properties, several formulations employing cyclodextrin inclusion complexes were developed. To carefully evaluate the in vitro and in vivo antitumor activity of these drugs and their complexes, several studies were performed on a breast cancer cell line (4T1) and BALB/c mice. In vitro studies showed that albendazole presented improved antitumor activity compared with ricobendazole. Furthermore, albendazole:citrate-β-cyclodextrin complex decreased significantly 4T1 cell growth both in in vitro and in vivo experiments. Thus, new formulations for anti-parasitic drugs could help to reposition them for new therapeutic indications, offering safer and more effective treatments by using a well-known drug. Fil: Priotti, Josefina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; Argentina Fil: Baglioni, María Virginia. Universidad Nacional de Rosario. Facultad de Ciencias Medicas. Instituto de Genetica Experimental; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: García, Agustina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; Argentina Fil: Rico, Maria Jose. Universidad Nacional de Rosario. Facultad de Ciencias Medicas. Instituto de Genetica Experimental; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Leonardi, Darío. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; Argentina Fil: Lamas, Maria Celina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; Argentina Fil: Menacho Márquez, Mauricio Ariel. Universidad Nacional de Rosario. Facultad de Ciencias Medicas. Instituto de Genetica Experimental; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Investigaciones para el Descubrimiento de Fármacos de Rosario. Universidad Nacional de Rosario. Instituto de Investigaciones para el Descubrimiento de Fármacos de Rosario; Argentina

Published
2018

18. Promising applications in drug delivery systems of a novel β-cyclodextrin derivative obtained by green synthesis

Author

Darío Leonardi, Agustina García, and Maria Celina Lamas

Subjects
Models, Molecular, Spectrometry, Mass, Electrospray Ionization, INCLUSION COMPLEX, Magnetic Resonance Spectroscopy, Clinical Biochemistry, Succinic Acid, Pharmaceutical Science, Excipient, 02 engineering and technology, Albendazole, 030226 pharmacology & pharmacy, Biochemistry, Dosage form, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, X-Ray Diffraction, Drug Discovery, medicine, Solubility, Molecular Biology, Anthelmintics, Drug Carriers, Chromatography, Calorimetry, Differential Scanning, Otras Ciencias Químicas, beta-Cyclodextrins, Organic Chemistry, Ciencias Químicas, Green Chemistry Technology, Nuclear magnetic resonance spectroscopy, Carbon-13 NMR, 021001 nanoscience & nanotechnology, CYCLODEXTRIN DERIVATIVES, Combinatorial chemistry, chemistry, Proton NMR, Molecular Medicine, 0210 nano-technology, Drug carrier, CIENCIAS NATURALES Y EXACTAS, Derivative (chemistry), GREEN SYNTHESIS, medicine.drug
Abstract

An efficient and green method has been developed for the synthesis of succinyl-β-cyclodextrin in aqueous media obtaining very good yield. Acidic groups have been introduced in the synthesized carrier molecule to improve the guest-host affinity. To evaluate the suitability of the novel excipient focused to develop oral dosage forms, albendazole, a BSC class II compound, was chosen as a model drug. The β-cyclodextrin derivative and the inclusion complex were thoroughly characterized in solution and solid state by phase solubility studies, FT-IR spectroscopy, SEM, XRD, ESI-MS, DSC, 1D 1H NMR, 1D 13C NMR, selective 1D TOCSY, 2D COSY, 2D HSQC, 2D HMBC and ROESY NMR spectroscopy. Phase solubility studies indicated that both of them β-cyclodextrin and succinyl-β-cyclodextrin formed 1:1 inclusion complexes with albendazole, and the stability constants were 68 M-1 (β-cyclodextrin), 437 M-1 (succinyl-β-cyclodextrin), respectively. Water solubility and dissolution rate of albendazole were significantly improved in complex forms. Thus, the succinyl-β-cyclodextrin derivative could be a promising excipient to design oral dosage forms. Fil: García, Agustina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; Argentina Fil: Leonardi, Darío. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; Argentina Fil: Lamas, Maria Celina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; Argentina

Published
2016
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19. Consultas compartidas entre Gastroenterología y atención primaria: influencia en las derivaciones a las consultas externas del hospital

Author

Soledad Sañudo García, Agustina García Pascual, Lourdes del Olmo Martínez, Fernando Villuela González, Juan del Río Hortega, Raquel Briso Montiano, Pilar Gomez, Manuela Catón Valdés, Juan Pradera Leonardo, Laura Mata Román, Agustín Caro-Patón Gómez, Elisa María Ibáñes Jalón, Agustín Mayo Íscar, Rosario Vallelado Cuéllar, Gómez A, José Ignacio Pinilla Gimeno, María José Castellanos Alonso, Manuel Jiménez Rodríguez-Vila, Lucinio Laso Santos, and Antonio Otero Rodríguez

Abstract

Resumen Objetivo Evaluar la influencia de una intervencion formativa en las derivaciones a consultas hospitalarias, su adecuacion y motivos de derivacion, y analizar diferencias entre medio urbano y rural. Material y metodos Estudio prospectivo de una intervencion fundamentalmente de tipo formativo (consultas compartidas y sesiones clinicas) entre Gastroenterologia y atencion primaria, realizada mensualmente en un centro de salud urbano y otro rural, comparandolos con 2 correspondientes centros control. El periodo de estudio fue de noviembre de 2004 a junio de 2008, con un periodo de referencia de 12 meses y uno de intervencion de 30 meses, dividido en 2 subperiodos (1 y 2). Los parametros (cambios en las derivaciones, y sus motivos y pertinencia) se evaluaron en 1.449 derivaciones realizadas desde atencion primaria a las consultas externas de aparato digestivo. Resultados En relacion con el periodo de referencia, descendio significativamente el porcentaje de derivaciones en los centros de intervencion: 51 y 57 % en los subperiodos 1 y 2, respectivamente. Analizando las diferencias entre los centros de intervencion y los centros control, el descenso en la proporcion de derivaciones fue de aproximadamente un 30 % en ambos periodos, que fue solo significativo en el medio rural. No se encontraron cambios significativos en la pertinencia ni en los motivos de las derivaciones. Conclusiones La intervencion resulto en conjunto eficaz en disminuir derivaciones a las consultas hospitalarias de gastroenterologia, aunque sugerimos medidas que mejoren su pertinencia.

Published
2015
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20. 13C and 15N solid-state NMR studies on albendazole and cyclodextrin albendazole complexes

Author

Agustina García, M. Celina Lamas, Darío Leonardi, M. João Ferreira, Teresa G. Nunes, and Claudio J. Salomon

Subjects
CYCLODEXTRINS, Magnetic Resonance Spectroscopy, Polymers and Plastics, Físico-Química, Ciencia de los Polímeros, Electroquímica, Substituent, Chemical interaction, Albendazole, chemistry.chemical_compound, X-Ray Diffraction, Materials Chemistry, medicine, chemistry.chemical_classification, Cyclodextrins, Cyclodextrin, Chemistry, Organic Chemistry, Ciencias Químicas, Nmr data, Crystallography, Solubility, Solid-state nuclear magnetic resonance, ALBENDAZOLE, SOLID STATE NMR, CIENCIAS NATURALES Y EXACTAS, Powder Diffraction, Nuclear chemistry, medicine.drug
Abstract

13C and 15N solid-state nuclear magnetic resonance (NMR) spectra were recorded from albendazole (ABZ) and from ABZ:β-cyclodextrin, ABZ:methyl-β-cyclodextrin, ABZ:hydroxypropyl-β-cyclodextrin and ABZ:citrate-β-cyclodextrin, which were prepared by the spray-drying technique. ABZ signals were typical of a crystalline solid for the pure drug and of an amorphous compound obtained from ABZ:cyclodextrin samples. Relevant spectral differences were correlated with chemical interaction between ABZ and cyclodextrins. The number and type of complexes revealed a strong dependence on the cyclodextrin group substituent. Solid-state NMR data were consistent with the presence of stable inclusion complexes. Fil: Ferreira, M. João G.. Universidade de Lisboa. Instituto Superior Técnico; Portugal Fil: García, Agustina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Química Rosario; Argentina Fil: Leonardi, Darío. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Química Rosario; Argentina Fil: Salomon, Claudio Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Química Rosario; Argentina Fil: Lamas, Maria Celina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Química Rosario; Argentina Fil: Nunes, T. G.. Universidade de Lisboa. Instituto Superior Técnico; Portugal

Published
2015
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21. Trabajo cooperativo en la asignatura de Tecnología

Author

Agustina García, Óscar, Canales Leiva, Joaquim, and Universitat Jaume I. Departament d'Enginyeria Mecànica i Construcció

Subjects
Máster Universitario en Profesor/a de Educación Secundaria Obligatoria y Bachillerato, Formación Profesional y Enseñanzas de Idiomas, Master's Degree in Secondary Education, Vocational Training and Language Teaching, Màster Universitari en Professor/a d'Educació Secundària Obligatòria i Batxillerat, Formació Professional i Ensenyaments d'Idiomes
Abstract

Treball Final de Màster Universitari en Professor/a d'Educació Secundària Obligatòria i Batxillerat, Formació Professional i Ensenyaments d'Idiomes. Codi SAP129. Curs: 2017/2018 El presente Trabajo Final de Máster (TFM) se inscribe en la modalidad 1: Mejora educativa, según la normativa de los trabajos de Final de Máster de la Universidad Jaume I, relativa al Máster universitario de Profesorado de Educación Secundaria Obligatoria, Bachillerato, Formación Profesional y Enseñanza de Idiomas. Esta modalidad corresponde a la experiencia de investigación sobre la propia práctica del docente a través de la metodología de investigación-acción. Aprovechando mi estancia de prácticas, se pone en funcionamiento la clase cooperativa en la asignatura de Tecnología en los grupos de 1º ESO del instituto IES Politécnico de Castellón, se centra en mejorar la falta de motivación hacia la asignatura a través de la metodología del aprendizaje cooperativo con el fin también de mejorar el rendimiento académico. Para conseguir estos objetivos se ha propuesto un plan de acción que consiste en un cambio en la metodología de la asignatura, de tal manera que los alumnos trabajen cooperativamente en la realización de una serie de actividades propuestas por el profesorado. Durante la puesta en práctica de las diferentes actividades se recoge información utilizando diferentes herramientas como el diario del profesor, libro de notas, observación del tutor, análisis de documentación, libreta del alumno, registros virtuales y encuestas a los alumnos. Toda esta información se ha organizado mediante unos indicadores a partir de los objetivos que se pretenden conseguir con el trabajo de investigación-acción. El posterior análisis de los resultados demuestra que el enfoque metodológico utilizado ha mejorado la cooperatividad de los grupos de trabajo y la visión de los alumnos hacia la asignatura. Todos los alumnos han realizado las diferentes actividades cooperando con los compañeros de grupo, aprendiendo, compartiendo sus conocimientos y ayudándose entre ellos. Con ello han conseguido aumentar la interacción entre compañeros, divertirse, trabajar en equipo, respetar la opinión de sus compañeros, valorar el esfuerzo individual y grupal. Se ha demostrado que el rendimiento académico ha mejorado como su comportamiento en clase, a excepción de un grupo que ha empeorado en todos los aspectos.

Published
2018

22. Mechanisms Involved in the Remyelinating Effect of Sildenafil

Author

Paula Pifarré, Maria Gutierrez-Mecinas, Daniela Díaz-Lucena, Agustina García, Beatriz Moreno, and José Lupicinio Martínez-Sánchez

Subjects
0301 basic medicine, Encephalomyelitis, Autoimmune, Experimental, medicine.drug_mechanism_of_action, Immunology, Neuroscience (miscellaneous), Bone Marrow Cells, Esclerosi múltiple, Ciliary neurotrophic factor, Pharmacology, Neuroprotection, Sildenafil Citrate, Myelin oligodendrocyte glycoprotein, Multiple sclerosis, 03 medical and health sciences, Myelin, Mice, 0302 clinical medicine, Cerebellum, medicine, Immunology and Allergy, Animals, Remyelination, biology, Microglia, business.industry, Macrophages, Experimental autoimmune encephalomyelitis, Phosphodiesterase 5 Inhibitors, medicine.disease, Mice, Inbred C57BL, Mielina, Oligodendroglia, 030104 developmental biology, medicine.anatomical_structure, Spinal Cord, biology.protein, Female, business, Phosphodiesterase 5 inhibitor, 030217 neurology & neurosurgery
Abstract

Remyelination occurs in demyelinated lesions in multiple sclerosis (MS) and pharmacological treatments that enhance this process will critically impact the long term functional outcome in the disease. Sildenafil, a cyclic GMP (cGMP)-specific phosphodiesterase 5 inhibitor (PDE5-I), is an oral vasodilator drug extensively used in humans for treatment of erectile dysfunction and pulmonary arterial hypertension. PDE5 is expressed in central nervous system (CNS) neuronal and glial populations and in endothelial cells and numerous studies in rodent models of neurological disease have evidenced the neuroprotective potential of PDE5-Is. Using myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE) as a MS model, we previously showed that daily administration of sildenafil starting at peak disease rapidly ameliorates clinical symptoms while administration at symptoms onset prevents disease progression. These beneficial effects of the drug involved down-regulation of adaptive and innate immune responses, protection of axons and oligodendrocytes (OLs) and promotion of remyelination. In this work we have investigated mechanisms involved in the remyelinating effect of sildenafil. Using demyelinated organotypic cerebellar slice cultures we demonstrate that sildenafil stimulates remyelination by direct effects on CNS cells in a nitric oxide (NO)-cGMP-protein kinase G (PKG)-dependent manner. We also show that sildenafil treatment enhances OL maturation and induces expression of the promyelinating factor ciliary neurotrophic factor (CNTF) in spinal cord of EAE mice and in cerebellar slice cultures. Furthermore, we demonstrate that sildenafil promotes a M2 phenotype in bone marrow derived macrophages (BMDM) and increases myelin phagocytosis in these cells and in M2 microglia/macrophages in the spinal cord of EAE mice. Taken together these data indicate that promotion of OL maturation directly or through induction of growth factor expression, regulation of microglia/macrophage inflammatory phenotype and clearance of myelin debris may be relevant mechanisms involved in sildenafil enhancement of remyelination in demyelinated tissue and further support the contention that this well tolerated drug could be useful for ameliorating MS pathology.

Published
2018

24. Spray drying formulation of albendazole microspheres by experimental design.In vitro–in vivostudies

Author

María Eugenia Mamprin, Maria Celina Lamas, Alejandro C. Olivieri, Gisela Noemi Piccirilli, Darío Leonardi, and Agustina García

Subjects
Male, food.ingredient, Pectin, Chemistry, Pharmaceutical, Administration, Oral, Biological Availability, Pharmaceutical Science, Nanotechnology, macromolecular substances, In Vitro Techniques, Albendazole, Microsphere, Chitosan, chemistry.chemical_compound, Drug Delivery Systems, food, Drug Stability, Drug Discovery, medicine, Animals, Rats, Wistar, In vitro in vivo, Dissolution, Pharmacology, Chromatography, Chemistry, Organic Chemistry, Microspheres, Rats, Bioavailability, Area Under Curve, Carboxymethylcellulose Sodium, Spray drying, Microscopy, Electron, Scanning, Pectins, medicine.drug
Abstract

Both an experimental design and optimization techniques were carried out for the development of chitosan-pectin-carboxymethylcellulose microspheres to improve the oral absorption of albendazole as a model drug. The effect of three different factors (chitosan, pectin and carboxy methyl cellulose concentrations) was studied on five responses: yield, morphology, dissolution rate at 30 and 60 min, and encapsulation efficiency of the microspheres. During the screening phase, the factors were evaluated in order to identify those which exert a significant effect. Simultaneous multiple response optimizations were then used to find out experimental conditions where the system shows the most adequate results. The optimal conditions were found to be: chitosan concentration, 1.00% w/v, pectin concentration 0.10% w/v and carboxymethylcellulose concentration 0.20% w/v. The bioavailability of the loaded drug in the optimized microspheres was evaluated in Wistar rats which showed an area under curve (AUC) almost 10 times higher than the pure drug.

Published
2013
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25. Metallothioneins I/II are involved in the neuroprotective effect of sildenafil in focal brain injury

Author

M. Giralt, Judith Prado, Juan Hidalgo, Paula Pifarré, and Agustina García

Subjects
medicine.medical_specialty, Programmed cell death, Purinones, Phosphodiesterase Inhibitors, Angiogenesis, Blotting, Western, Neovascularization, Physiologic, Apoptosis, Enzyme-Linked Immunosorbent Assay, medicine.disease_cause, Neuroprotection, Piperazines, Sildenafil Citrate, Neovascularization, Lesion, Mice, Cellular and Molecular Neuroscience, chemistry.chemical_compound, Internal medicine, medicine, Animals, Gliosis, Sulfones, Cerebral Cortex, Cyclic Nucleotide Phosphodiesterases, Type 5, Mice, Knockout, business.industry, Cell Biology, Macrophage Activation, medicine.disease, Immunohistochemistry, Up-Regulation, Astrogliosis, Cold Temperature, Oxidative Stress, Neuroprotective Agents, Endocrinology, chemistry, Purines, Brain Injuries, Metallothionein, Microglia, medicine.symptom, Zaprinast, business, Oxidative stress
Abstract

We recently reported that administration of the non-selective cyclic GMP-phosphodiesterase (cGMP-PDE) inhibitor zaprinast to cortically cryoinjured rats results three days post-lesion in reduced neuronal cell death that was associated to decreased macrophage/microglial activation and oxidative stress and increased astrogliosis and angiogenesis. Similar effects have been observed in cryoinjured animals overexpressing metallothioneins I/II (MT-I/II), metal-binding cysteine-rich proteins that are up-regulated in response to injury. In this work we have examined the effect of administration of the selective PDE5 inhibitor sildenafil (10mg/kg, sc) 2h before and 24 and 48h after induction of cortical cryolesion in wild-type and MT-I/II-deficient mice. Our results show that in wild-type animals sildenafil induces similar changes in glial reactivity, angiogenesis and antioxidant and antiapoptotic effects in the cryolesioned cortex as those observed in rats with zaprinast, indicating that inhibition of PDE5 is responsible for the neuroprotective actions. However, these effects were not observed in mice deficient in MT-I/II. We further show that sildenafil significantly increases MT-I/II protein levels in homogenates of lesioned cortex and MT-I/II immunostaining in glial cells around the lesion. Taken together these results indicate that cGMP-mediated pathways regulate expression of MT-I/II and support the involvement of these proteins in the neuroprotective effects of sildenafil in focal brain lesion.

Published
2013
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26. Secretase-Independent and RhoGTPase/PAK/ERK-Dependent Regulation of Cytoskeleton Dynamics in Astrocytes by NSAIDs and Derivatives

Author

Jeffrey R. Peterson, Mathieu P. Lichtenstein, Elena Galea, Paulina Carriba, Beata Wojciak-Stothard, María Antonia Baltrons, and Agustina García

Subjects
Cyclopropanes, rho GTP-Binding Proteins, MAPK/ERK pathway, RHOA, Blotting, Western, Ibuprofen, macromolecular substances, CDC42, Pharmacology, Rats, Sprague-Dawley, Cerebellum, medicine, Animals, Extracellular Signal-Regulated MAP Kinases, Cytoskeleton, Cells, Cultured, Cerebral Cortex, Analysis of Variance, Dose-Response Relationship, Drug, biology, General Neuroscience, Anti-Inflammatory Agents, Non-Steroidal, Neurodegeneration, General Medicine, medicine.disease, Immunohistochemistry, Rats, Cell biology, Psychiatry and Mental health, Clinical Psychology, medicine.anatomical_structure, Flurbiprofen, Cyclooxygenase 2, Astrocytes, Stellation, biology.protein, Amyloid Precursor Protein Secretases, Geriatrics and Gerontology, Amyloid precursor protein secretase, Signal Transduction, Astrocyte
Abstract

Profens like ibuprofen, R-flurbiprofen, or CHF5074 are being considered for the treatment of Alzheimer's disease because epidemiological data indicates that non-steroidal anti-inflammatory drugs are protective against neurodegeneration. Rho-GTPases are small G proteins, including RhoA, Cdc42, and Rac1, which control cytoskeleton dynamics. Because ibuprofen promotes axon growth via RhoA in neurons, we examined whether profens modulate astrocyte plasticity via Rho-GTPases. We report that ibuprofen (100-500 μM), R-flurbiprofen (100-500 μM), and CHF5074 (10-30 μM) caused a concentration-dependent stellation of astrocytes in primary cultures, associated with the reorganization of GFAP and actin filaments. The stellation was independent of COX2, α-, β- or γ-secretase as judged by the lack of effect of inhibitors of these enzymes. RhoA, PAK, and Cdc42, but not Rac1, accounted for the profen-mediated stellation, as concluded from the joint analyses of activities and reversal experiments with adenoviral or pharmacological manipulations. Ibuprofen accelerated migration in a scratch-wound assay, while R-flurbiprofen had no effect and CHF5074 caused deceleration. Cell polarity regulation by Cdc42 and ERK1/2 may underlie the paradoxical effects of profens on migration. We conclude that profens regulate cytoskeleton dynamics in astrocytes via Rho-GTPases, PAK, and ERK1/2. Since migration is a hallmark of astrocyte response during inflammation we propose that, in addition to (or instead of) lowering amyloid-β42 via secretases, ibuprofen and its derivatives may prevent Alzheimer's disease instead of AD by modulating astrocyte reactivity through Rho-GTPase/PAK/ERK-dependent signaling.

Published
2011
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27. NO-sensitive guanylyl cyclase β1 subunit is peripherally associated to chromosomes during mitosis. Novel role in chromatin condensation and cell cycle progression

Author

Agustina García, María Antonia Baltrons, Paula Pifarré, and Istvan Földi

Subjects
Protein subunit, Mitosis, Receptors, Cytoplasmic and Nuclear, Biology, Nitric Oxide, Transfection, Biochemistry, Gene Expression Regulation, Enzymologic, Rats, Sprague-Dawley, Soluble Guanylyl Cyclase, Prophase, Cell Line, Tumor, Animals, RNA, Messenger, RNA, Small Interfering, Cell Proliferation, Cell Nucleus, Cell growth, Cell Cycle, Cell Biology, Cell cycle, Molecular biology, Chromatin, Rats, Cell biology, Protein Subunits, Protein Transport, Guanylate Cyclase, Cytoplasm, Astrocytes, Microglia, Soluble guanylyl cyclase, Protein Binding
Abstract

NO-sensitive guanylyl cyclase (GC(NO)), the major NO target, is involved in important regulatory functions in the cardiovascular, gastrointestinal and central nervous systems. GC(NO) exists as heterodimers of alpha(1/2) and beta1 subunits. Deletion of the obligate beta1 dimerizing partner abrogates NO/cGMP signaling and shortens the life span of KO mice. Localization studies in the CNS have shown that beta1 is more widespread than alpha subunits and in some areas is the only GC(NO) subunit expressed, suggesting that beta1 may have GC(NO)-independent functions. GC(NO) is predominantly cytosolic, but association to membranes and other intracellular structures has been described. Here, we show localization of beta1 in cytoplasm and nucleus of cells expressing alpha subunits and GC(NO) activity (astrocytes, C6 cells), as well as in cells devoid of alpha subunits and GC(NO) activity (microglia). In both cell types beta1 associates peripherally to chromosomes in all phases of mitosis. Immunodepletion of beta1 in C6 cells enhances chromatin condensation in an in vitro assay. Moreover, silencing beta1 by siRNA induces cell cycle re-entry as determined by flow cytometry, and increases proliferation rate in a MTT-assay, whereas infection with beta1-containing adenovirus has the opposite effect. These actions are independent of cGMP formation. We postulate that beta1 is a multifunctional protein that regulates chromatin condensation and cell cycle progression, in addition to being an obligate monomer in functional GC(NO) heterodimers.

Published
2009
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28. Cuantificación de agua y carbono en plantaciones de teca (Tectona grandis, L.F.) en Bahía de Banderas, Nayarit, México

Author

S Bernardino Parada, O Agustina García, S Juan de Dios Benavides, R Agustín Gallegos, José Aguilar, and A Efrén Hernández

Abstract

Los servicios ambientales son aquellos procesos y funciones de los ecosistemas que, además de influir directamente en el mantenimiento de la vida, generan beneficios y bienestar para las personas y las comunidades, pero es necesario evaluarlos para conocer el efecto real que tienen los bosques y plantaciones en su preservación. En este trabajo se presentan los resultados de la cuantificación del agua y carbono en una plantación de Teca

Published
2009
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29. Regulation and Function of Cyclic GMP-Mediated Pathways in Glial Cells

Author

Agustina García, Paula Pifarré, Mariela Susana Borán, and María Antonia Baltrons

Subjects
Cell physiology, Neuronal Plasticity, Microglia, Kinase, Cell migration, General Medicine, Biology, Neurotransmission, Synaptic Transmission, Biochemistry, Neuroprotection, Cell biology, Nitric oxide synthase, Cellular and Molecular Neuroscience, medicine.anatomical_structure, Natriuretic Peptide, Brain, medicine, biology.protein, Animals, Humans, Cyclic GMP, Neuroglia, Neuroscience, Neuroinflammation
Abstract

A large body of evidence supports a role for the NO-cGMP-protein kinase G pathway in the regulation of synaptic transmission and plasticity, brain development and neuroprotection. Circumstantial evidence implicates natriuretic peptide-stimulated cGMP formation in the same CNS functions. In addition to neurons, both cGMP-mediated pathways are functional in glial cells and an increasing number of reports indicate that they may control important aspects of glial cell physiology relevant to neuronal function. In this article we briefly review the regulation of cGMP formation in glial cells and summarize recent evidence indicating that cGMP-mediated pathways can play important roles in astroglial and microglial function in normal and diseased brain.

Published
2008
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30. The ANP-cGMP-protein kinase G pathway induces a phagocytic phenotype but decreases inflammatory gene expression in microglial cells

Author

Mariela Susana Borán, María Antonia Baltrons, and Agustina García

Subjects
Lipopolysaccharides, RHOA, Nitric Oxide Synthase Type II, RAC1, Biology, Nitric Oxide, Transfection, Cell morphology, Rats, Sprague-Dawley, Cellular and Molecular Neuroscience, Organ Culture Techniques, Atrial natriuretic peptide, Cyclic GMP-Dependent Protein Kinases, Dibutyryl Cyclic GMP, medicine, Animals, Enzyme Inhibitors, Cyclic GMP, Cells, Cultured, Neuroinflammation, Phagocytes, Dose-Response Relationship, Drug, Microglia, Tumor Necrosis Factor-alpha, Brain, Actin cytoskeleton, Rats, Cell biology, medicine.anatomical_structure, Animals, Newborn, Gene Expression Regulation, Neurology, cardiovascular system, biology.protein, cGMP-dependent protein kinase, Atrial Natriuretic Factor, Signal Transduction
Abstract

Reactive gliosis is a prominent feature of CNS injury that involves dramatic changes in glial cell morphology together with increased motility, phagocytic activity, and release of inflammatory mediators. We have recently demonstrated that stimulation of the cGMP-protein kinase G (PKG) pathway by NO or atrial natriuretic peptide (ANP) regulates cytoskeleton dynamics and motility in rat astrocytes in culture. In this work, we show that the cGMP-PKG pathway stimulated by ANP, but not by NO, regulates microglial cell morphology by inducing a dramatic reorganization in the actin cytoskeleton. Both ANP (0.01-1.0 microM) and the permeable cGMP analog, dibutyryl-cGMP (1-100 microM), promote a rapid (maximal at 30 min) and concentration-dependent increase in size, rounding, and lamellipodia and filopodia formation in rat brain cultured microglia. These morphological changes involve an augment and redistribution of F-actin and result in increased phagocytic activity. ANP-induced rearrangements in actin cytoskeleton and inert particle phagocytosis are prevented by the PKG inhibitor, Rp-8-Br-PET-cGMPS (0.5 microM), and involve inhibition of RhoA GTPase and activation of Rac1 and Cdc42. However, ANP does not induce NO synthase Type 2 (NOS-2) or tumor necrosis factor-alpha expression and is able to decrease lipopolysaccharide (LPS)-elicited induction of these inflammatory genes. The morphological changes and the decrease of LPS-induced NOS-2 expression produced by ANP in cultured microglia are also observed by immunostaining in organotypic cultures from rat hippocampus. These results suggest that stimulation of the ANP-cGMP-PKG pathway in microglia could play a beneficial role in the resolution of neuroinflammation by removing dead cells and decreasing levels of proinflammatory mediators.

Published
2008
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31. The cyclic GMP-protein kinase G pathway regulates cytoskeleton dynamics and motility in astrocytes

Author

Agustina García and Mariela Susana Borán

Subjects
Lipopolysaccharides, Indoles, RHOA, Antimetabolites, Blotting, Western, Biology, Nitric Oxide, Transfection, Biochemistry, Rats, Sprague-Dawley, Cellular and Molecular Neuroscience, Cell Movement, Glial Fibrillary Acidic Protein, Cyclic GMP-Dependent Protein Kinases, medicine, Animals, Cytoskeleton, Cells, Cultured, Fluorescent Dyes, Inflammation, Glial fibrillary acidic protein, Kinase, Actins, Rats, Cell biology, Nitric oxide synthase, Phenotype, medicine.anatomical_structure, Bromodeoxyuridine, Bucladesine, Astrocytes, biology.protein, Wounds and Injuries, Neuroglia, rhoA GTP-Binding Protein, cGMP-dependent protein kinase, Atrial Natriuretic Factor, Signal Transduction, Astrocyte
Abstract

We have previously demonstrated that inflammatory compounds that increase nitric oxide (NO) synthase expression have a biphasic effect on the level of the NO messenger cGMP in astrocytes. In this work, we demonstrate that NO-dependent cGMP formation is involved in the morphological change induced by lipopolysaccharide (LPS) in cultured rat cerebellar astroglia. In agreement with this, dibutyryl-cGMP, a permeable cGMP analogue, and atrial natriuretic peptide, a ligand for particulate guanylyl cyclase, are both able to induce process elongation and branching in astrocytes resulting from a rapid, reversible and concentration-dependent redistribution of glial fibrillary acidic protein (GFAP) and actin filaments without significant change in protein levels. These effects are also observed in astrocytes co-cultured with neurons. The cytoskeleton rearrangement induced by cGMP is prevented by the specific protein kinase G inhibitor Rp-8Br-PET-cGMPS and involves downstream inhibition of RhoA GTPase since is not observed in cells transfected with constitutively active RhoA. Furthermore, dibutyryl-cGMP prevents RhoA-membrane association, a step necessary for its interaction with effectors. Stimulation of the cGMP-protein kinase G pathway also leads to increased astrocyte migration in an in vitro scratch-wound assay resulting in accelerated wound closure, as seen in reactive gliosis following brain injury. These results indicate that cGMP-mediated pathways may regulate physio-pathologically relevant responses in astroglial cells.

Published
2007
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32. Cuadro de instrumentos para un automóvil

Author

Agustina García, Iván, Universitat Jaume I. Departament d'Enginyeria Mecànica i Construcció, and Company Calleja, Pedro Pablo

Subjects
Diseño, Automóvil, Master's Degree in Design and Manufacturing, Máster Universitario en Diseño y Fabricación, Cuadro de instrumentos, Màster Universitari en Disseny i Fabricació
Abstract

Treball final de Màster Universitari en Disseny i Fabricació (Pla de 2013). Codi: SIX500. Curs acadèmic 2014-2015 El objeto de este proyecto es diseñar un cuadro de instrumentos de última generación para un automóvil. En este proyecto se incluye el diseño exterior del cuadro de instrumentos para poder ser montado sobre un automóvil, todos los componentes internos y el diseño de la forma y el posicionamiento de los indicadores para conseguir que la lectura de los parámetros sea rápida y fácil. El cuadro de instrumentos a diseñar debe combinar con el uso de los nuevos ordenadores de abordo multimedia (navegador, control de climatización, música, etc.). Los componentes mínimos que debe incluir son el velocímetro, cuentarrevoluciones, temperatura de motor, nivel de combustible y los indicadores necesarios para la correcta transmisión de información al conductor.

Published
2015

33. The in vivo behaviour of a sol–gel glass and a glass-ceramic during critical diaphyseal bone defects healing

Author

Agustina García-Barea, Jorge Gil-Albarova, Milena Fini, Antonio L. Bueno-Lozano, J. Román, María Vallet-Regí, Antonio J. Salinas, Nicolo Aldini-Nicolo, Gianluca Giavaresi, Roberto Giardino, Gil-Albarova J., Salinas A.J., Bueno-Lozano A.L., Roman J., Nicoli Aldini N., Garcia-Barea A., Giavaresi G., Fini M., Giardino R., and Vallet-Regi M.

Subjects
Ceramics, Materials science, Simulated body fluid, Biophysics, Dentistry, Bioengineering, Bone healing, Phase Transition, Osseointegration, Bone remodeling, Biomaterials, Materials Testing, Animals, Kirschner wire, Fracture Healing, Osteosynthesis, business.industry, Resorption, Treatment Outcome, Mechanics of Materials, Bone Substitutes, Ceramics and Composites, Glass, Rabbits, Implant, business, Femoral Fractures, Biomedical engineering
Abstract

The in vivo evaluation, in New Zealand rabbits, of a sol-gel glass 70% CaO-30% SiO2 (in mol%) and a glass-ceramic obtained from thermal treatment of the glass, both bioactive in Kokubo's simulated body fluid (SBF), is presented. Femoral bone diaphyseal critical defects were filled with: (i) sol-gel glass cylinders, (ii) glass-ceramic cylinders, or (iii) no material (control group). Osteosynthesis was done by means of anterior screwed plates with an associate intramedullar Kirschner wire. Each group included 10 mature rabbits, 9 months old. Follow-up was 6 months. After sacrifice, macroscopic study showed healing of bone defects, with bone coating over the cylinders, but without evidence of satisfactory repair in control group. Radiographic study showed good implant stability and periosteal growth and bone remodelling around and over the filled bone defect. The morphometric study showed minimum evidences of degradation or resorption in glass-ceramic cylinders, maintaining its original shape, but sol-gel glass cylinders showed abundant fragmentation and surface resorption. An intimate union of the new-formed bone to both materials was observed. Mechanical study showed the higher results in the glass-ceramic group, whereas sol-gel glass and control group showed no differences. The minimum degradation of glass-ceramic cylinders suggests their application in critical bone defects locations of transmission forces or load bearing. The performance of sol-gel glass cylinders suggests their usefulness in locations where a quick resorption should be preferable, considering the possibility of serving as drug or cells vehicle for both of them.

Published
2005
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34. Novel albendazole formulations given during the intestinal phase of Trichinella spiralis infection reduce effectively parasitic muscle burden in mice

Author

María D. Vasconi, Agustina García, Lucila Isabel Hinrichsen, María G. Barrera, Ricardo José Di Masso, Gisela Noemi Piccirilli, Maria Celina Lamas, and Darío Leonardi

Subjects
Male, Drug, Farmacología y Farmacia, Benzimidazole, CIENCIAS MÉDICAS Y DE LA SALUD, Antiparasitic, medicine.drug_class, Chemistry, Pharmaceutical, media_common.quotation_subject, Ciencias de la Salud, Absorption (skin), TRICHINELLOSIS, Pharmacology, Biology, Albendazole, IN VIVO ANTIPARASITIC ASSAY, Mice, chemistry.chemical_compound, In vivo, medicine, Animals, Helminths, Parasitología, MCROPARTICULATE FORMULATIONS, Trichinella spiralis, media_common, Anthelmintics, Muscles, Trichinellosis, Bioavailability, Intestines, Solutions, Medicina Básica, Disease Models, Animal, Infectious Diseases, chemistry, Larva, Immunology, Parasitology, ALBENDAZOLE, medicine.drug
Abstract

Trichinellosis is a zoonotic disease affecting people all over the world, for which there is no speedy and reliable treatment. Albendazole (ABZ), an inexpensive benzimidazole used in oral chemotherapy against helminthic diseases, has a broad spectrum activity and iswell tolerated. However, the low absorption and variable bioavailability of the drug due to its low aqueous solubility are serious disadvantages for a successful therapy. In this study, we evaluated the in vivo antiparasitic activity of three novel solid microencapsulated formulations, designed to improve ABZ dissolution rate, in amurinemodel of trichinellosis. Both ABZ and the microparticulate formulations were administered during the intestinal phase of the parasite cycle, on days 5 and 6 post-infection. This protocol significantly decreased muscle larval burden measured in the parenteral phase, on day 30 post-infection, when compared with the untreated control. Moreover, two of the three microencapsulated formulations both strongly and consistently reduced worm burden. Fil: García, Agustina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Química Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; Argentina Fil: Barrera, María G.. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; Argentina Fil: Piccirilli, Gisela Noemi. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Química Rosario; Argentina Fil: Vasconi, María D.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Química Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Medicas. Instituto de Genetica Experimental; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; Argentina Fil: Di Masso, Ricardo Jose. Universidad Nacional de Rosario. Facultad de Ciencias Medicas. Instituto de Genetica Experimental; Argentina Fil: Leonardi, Darío. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Química Rosario; Argentina Fil: Hinrichsen, Lucila Isabel. Universidad Nacional de Rosario. Facultad de Ciencias Medicas. Instituto de Genetica Experimental; Argentina. Universidad Nacional de Rosario; Argentina Fil: Lamas, Maria Celina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Química Rosario; Argentina

Published
2013
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35. Reduced expression of NO-sensitive guanylyl cyclase in reactive astrocytes of Alzheimer disease, Creutzfeldt–Jakob disease, and multiple sclerosis brains

Author

Agustina García, José Miguel Carot, María Antonia Baltrons, Paula Pifarré, and Isidre Ferrer

Subjects
Male, inorganic chemicals, Pathology, medicine.medical_specialty, Multiple Sclerosis, Amyloid, Creutzfeldt–Jakob disease, Grey matter, Biology, Hippocampal formation, Creutzfeldt-Jakob Syndrome, lcsh:RC321-571, White matter, Astroglia, Soluble guanylyl cyclase, medicine, Humans, heterocyclic compounds, Cyclic GMP, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, Aged, Aged, 80 and over, Brain, Nitric oxide, Middle Aged, Alzheimer's disease, medicine.disease, Kinetics, medicine.anatomical_structure, Neurology, Guanylate Cyclase, Astrocytes, Postmortem Changes, cardiovascular system, Female, Immunostaining, Astrocyte
Abstract

In Alzheimer's disease (AD) brains increased NO synthase (NOS) expression is found in reactive astrocytes surrounding amyloid plaques. We have recently shown that treatment with β -amyloid peptides or IL-1 β down-regulates NO-sensitive soluble guanylyl cyclase (sGC) in cultured astrocytes and in adult rat brain. In this work, we have examined sGC activity and expression in postmortem brain tissue of AD patients and matched controls. No significant alteration was observed in basal or NO-stimulated sGC activity, nor in sGC β 1 and α 1 subunit levels in cortical extracts of AD brains. Immunohistochemistry showed intense and widespread labeling of sGC β 1 in cortical and hippocampal neurons and white matter fibrillar astrocytes, while grey matter astrocytes were faintly stained. In AD, expression of sGC in neurons and fibrillar astrocytes is not altered but is markedly reduced in reactive astrocytes surrounding amyloid plaques. Immunostaining for sGC β 1 was also lacking in reactive astrocytes in cortex and subcortical white matter in Creutzfeldt–Jakob disease brains and in subacute and chronic plaques in multiple sclerosis (MS) brains. Thus, induction of astrocyte reactivity is associated with decreased capacity to generate cGMP in response to NO both in vitro and in vivo. This effect may be related to the development of the astroglial inflammatory response.

Published
2004

36. Nitric oxide-dependent and independent down-regulation of NO-sensitive guanylyl cyclase in neural cells

Author

María Antonia Baltrons, Teresa Sardón, and Agustina García

Subjects
Central Nervous System, medicine.medical_specialty, Down-Regulation, Endogeny, Vasodilation, Inflammation, Biology, Nitric Oxide, Toxicology, Gene Expression Regulation, Enzymologic, Nitric oxide, chemistry.chemical_compound, Mediator, Downregulation and upregulation, Internal medicine, medicine, Animals, Humans, Neuroinflammation, Neurons, General Medicine, Rats, Cell biology, Enzyme Activation, Endocrinology, chemistry, Guanylate Cyclase, Astrocytes, medicine.symptom, Soluble guanylyl cyclase
Abstract

NO-sensitive guanylyl cyclase or soluble guanylyl cyclase (sGC) is the major target for NO and cyclic GMP the mediator of its vasodilating and neuromodulatory actions. Studies on the mechanism of nitrovasodilator-induced tolerance have shown that in smooth muscle cells sGC is down-regulated by prolonged exposure to exogenous or endogenous NO. Increased expression of NO synthase (NOS) in CNS glial cells is a landmark of acute and chronic neuroinflammation. Our studies in cultured astroglial cells demonstrate that exposure to neuroinflammatory agents leads to a long-lasting down-regulation of sGC that occurs by NO-dependent and independent mechanisms. Decreased expression of the enzyme at the protein and mRNA level is evident in the brain of adult rats after intracerebral injection of inflammatory compounds. A decreased cGMP synthesizing capacity may contribute to the neurodegenerative process associated to neuroinflammation.

Published
2004
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37. Interleukin-1β and lipopolysaccharide decrease soluble guanylyl cyclase in brain cells: NO-independent destabilization of protein and NO-dependent decrease of mRNA

Author

Agustina García, María Antonia Baltrons, Carlos E Pedraza, and Michael T. Heneka

Subjects
Lipopolysaccharides, inorganic chemicals, Transcription, Genetic, medicine.medical_treatment, Protein subunit, Immunology, Down-Regulation, Nitric Oxide, Nitric oxide, Rats, Sprague-Dawley, chemistry.chemical_compound, Cerebellum, Enzyme Stability, medicine, Animals, Immunology and Allergy, heterocyclic compounds, RNA, Messenger, Cyclic GMP, Cells, Cultured, biology, Brain, Interleukin, Phosphodiesterase, Molecular biology, Rats, Nitric oxide synthase, Protein Subunits, Cytokine, Solubility, Neurology, chemistry, Guanylate Cyclase, Astrocytes, Protein Biosynthesis, cardiovascular system, biology.protein, Tumor necrosis factor alpha, Neurology (clinical), Mitogen-Activated Protein Kinases, Soluble guanylyl cyclase, Half-Life, Interleukin-1
Abstract

We previously showed that soluble guanylyl cyclase (sGC) is down-regulated in astroglial cells after exposure to LPS. Here, we show that this effect is not mediated by released IL-1beta but that this cytokine is also able to decrease NO-dependent cGMP accumulation in a time- and concentration-dependent manner. The effect of IL-1beta is receptor-mediated, mimicked by tumor necrosis factor-alpha and involves a decrease in sGC activity and protein. IL-1beta and LPS decrease the half-life of the sGC beta1 subunit by a NO-independent but transcription- and translation-dependent mechanism. Additionally, both agents induce a NO-dependent decrease of sGC subunit mRNA. Decreased sGC subunit protein and mRNA levels are also observed in adult rat brain after focal injection of IL-1beta or LPS.

Published
2003
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38. Interferon-γ Regulates Oxidative Stress during Experimental Autoimmune Encephalomyelitis

Author

Carmen Espejo, Agustina García, Xavier Montalban, Irene Sáez-Torres, Juan Hidalgo, Eva Martínez-Cáceres, and Milena Penkowa

Subjects
Male, Encephalomyelitis, Autoimmune, Experimental, Encephalomyelitis, medicine.medical_treatment, Nitric Oxide Synthase Type II, Apoptosis, medicine.disease_cause, Antioxidants, Myelin oligodendrocyte glycoprotein, Proinflammatory cytokine, Interferon-gamma, Mice, chemistry.chemical_compound, Developmental Neuroscience, medicine, Demyelinating disease, Animals, Mice, Knockout, biology, Nitrotyrosine, Experimental autoimmune encephalomyelitis, medicine.disease, Rats, Oxidative Stress, Cytokine, Neurology, chemistry, Immunology, biology.protein, Female, Nitric Oxide Synthase, Oxidative stress, Brain Stem
Abstract

Experimental autoimmune encephalomyelitis (EAE) is an induced inflammatory and demyelinating disease of the central nervous system which shares many clinical and pathological features with and is considered the animal model of multiple sclerosis. There is extensive evidence that EAE is a Th1 disease eliciting secretion of proinflammatory cytokines like IFN-gamma or TNF-alpha, and it has been suggested that cytokine-induced oxidative stress could have a role in EAE neuropathology. However, the individual roles of these and other cytokines in the pathogenesis of the disease are still uncertain. Here we analyze the role of IFN-gamma during EAE by using both IFN-gamma receptor-knockout (IFN-gamma R(-/-)) and wild-type mice, both strains immunized with peptide 40-55 from rat myelin oligodendrocyte glycoprotein. The levels of oxidative stress were determined through the analysis of immunoreactivity for inducible NO synthase, nitrotyrosine, and malondialdehyde, as well as through the expression of the tissue-protective antioxidant factors metallothionein I+II (MT-I+II). We also examined the number of cells undergoing apoptosis as judged by using the TUNEL technique. The levels of oxidative stress, MT-I+II, and apoptotic cell death by EAE were significantly increased in all mice, though more so in IFN-gamma R(-/-) mice compared with wild-type mice. These data support the notion that IFN-gamma has a protective role against EAE.

Published
2002
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39. β-Amyloid Peptides Decrease Soluble Guanylyl Cyclase Expression in Astroglial Cells

Author

María Antonia Baltrons, Carlos E Pedraza, Michael T. Heneka, and Agustina García

Subjects
Nitroprusside, medicine.medical_specialty, Cerebellum, Receptors, Cytoplasmic and Nuclear, Hippocampus, Nerve Tissue Proteins, Cycloheximide, Biology, β-amyloid peptides, Nitric oxide, lcsh:RC321-571, Rats, Sprague-Dawley, chemistry.chemical_compound, 3',5'-Cyclic-GMP Phosphodiesterases, nitric oxide, Internal medicine, medicine, Animals, Nitric Oxide Donors, RNA, Messenger, astroglial, Cyclic GMP, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, Cells, Cultured, Nitrites, Protein Synthesis Inhibitors, Amyloid beta-Peptides, Protein synthesis inhibitor, soluble guanylyl cyclase, Long-term potentiation, Phenotype, Peptide Fragments, Rats, Cell biology, Isoenzymes, Protein Subunits, medicine.anatomical_structure, Endocrinology, Solubility, Neurology, chemistry, Guanylate Cyclase, Astrocytes, Enzyme Induction, Soluble guanylyl cyclase
Abstract

In astroglial cells beta-amyloid peptides (betaA) induce a reactive phenotype and increase expression of NO synthase. Here we show that treatment of rat brain astrocytes with betaA decreases their capacity to accumulate cyclic GMP (cGMP) in response to NO as a result of a decreased expression of soluble guanylyl cyclase (sGC) at the protein and mRNA levels. Potentiation of betaA-induced NO formation by interferon-gamma did not result in a larger decrease in cGMP formation and inhibition of NO synthase failed to reverse down-regulation of sGC, indicating that NO is not involved. The betaA effect was prevented by the protein synthesis inhibitor cycloheximide. Intracerebral betaA injection also decreased sGC beta1 subunit mRNA levels in adult rat hippocampus and cerebellum. A loss of sGC in reactive astrocytes surrounding beta-amyloid plaques could be a mechanism to prevent excess signalling via cGMP at sites of high NO production.

Published
2002

40. Efficacy of albendazole:β-cyclodextrin citrate in the parenteral stage of Trichinella spiralis infection

Author

María D. Vasconi, Ana Victoria Codina, Darío Leonardi, Lucila Isabel Hinrichsen, Agustina García, Maria Celina Lamas, and Ricardo José Di Masso

Subjects
Male, Trichinella, Biology, Pharmacology, Albendazole, Biochemistry, Citric Acid, purl.org/becyt/ford/1 [https], Ciencias Biológicas, Mice, Structural Biology, In vivo, medicine, Parasite hosting, Animals, Dissolution testing, purl.org/becyt/ford/1.6 [https], Molecular Biology, Trichinella spiralis, chemistry.chemical_classification, TRIQUINELLOSIS, Cyclodextrin, Antiparasitic Agents, fungi, beta-Cyclodextrins, Trichinella spiralis infection, MURINE MODEL, General Medicine, Bioquímica y Biología Molecular, biology.organism_classification, Bioavailability, chemistry, Immunology, ALBENDAZOLE, CIENCIAS NATURALES Y EXACTAS, medicine.drug
Abstract

Albendazole–β-cyclodextrin citrate (ABZ:C-β-CD) inclusion complex in vivo antiparasitic activity was evaluated in the parenteral phase of Trichinella spiralis infection in mice. An equimolar complex of ABZ:C-β-CD was prepared by spray-drying and tested in CBi–IGE male mice orally infected with L1 infective larvae. Infected animals were treated with 50 or 30 mg/kg albendazole, (ABZ) equivalent amounts of the ABZ:C-β-CD complex and non treated (controls). Mice received a daily dose on days 28, 29 and 30 post-infection. A week later, larval burden and percentage of encysted dead larvae were assessed in the host by counting viable and non-viable larvae in the tongue. Complexation of ABZ with C-β-CD increased the drug dissolution efficiency nearly eightfold. At 37 days p-i, the reduction percentage in muscle larval load was 35% in mice treated with 50 mg/kg/day ABZ and 68% in those given the complex. Treatment with the lower dose showed a similar decrease in parasite burden. Treated animals showed a high percentage of nonviable larvae, the proportion being significantly higher in mice receiving the complex than in control animals (72–88% vs. 11%, P = 0.0032). These data indicate that ABZ:C-β-CD increases bioavailability and effectiveness of ABZ against encapsulated Trichinella larvae, thus allowing the use of small doses. Fil: Codina, Ana Victoria. Universidad Nacional de Rosario. Facultad de Ciencias Medicas. Instituto de Genetica Experimental; Argentina Fil: García, Agustina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Química Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; Argentina Fil: Leonardi, Darío. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Química Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; Argentina Fil: Vasconi, María D.. Universidad Nacional de Rosario. Facultad de Ciencias Medicas. Instituto de Genetica Experimental; Argentina Fil: Di Masso, Ricardo Jose. Universidad Nacional de Rosario. Facultad de Ciencias Medicas. Instituto de Genetica Experimental; Argentina Fil: Lamas, Maria Celina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Química Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; Argentina Fil: Hinrichsen, Lucila Isabel. Universidad Nacional de Rosario. Facultad de Ciencias Medicas. Instituto de Genetica Experimental; Argentina

Published
2014

41. Diseño de un asiento de un automóvil

Author

Agustina García, Óscar, Universitat Jaume I. Departament d'Enginyeria Mecànica i Construcció, and Pérez González, Antonio

Subjects
Master's Degree in Design and Manufacturing, Máster Universitario en Diseño y Fabricación, Màster Universitari en Disseny i Fabricació
Abstract

Treball Final de Màster Universitari en Disseny i Fabricació. Codi: SDF500. Curs acadèmic: 2013-2014

Published
2014

42. Propiedades físicas de jugos de pitaya secados por aspersión

Author

Karina Agustina García Lucas

Subjects
colorantes naturales, Stenocereus pruinosus, 6 [cti], Industria de alimentos, pigmentos vegetales, Stenocereus griseus
Abstract

En este trabajo se determinaron las condiciones de secado por aspersión para obtener polvos a partir de jugos de pitaya de las especies Stenocereus griseus y Stenocereus pruinosus. Jugos, suspensiones alimentadas al secador y polvos encapsulados fueron caracterizados. El contenido de humedad, rendimiento, color, isoterma de adsorción, temperatura de transición vítrea y morfología de los polvos fueron determinados. El color se midió con un colorímetro MiniScan, el ángulo de tono y el croma fueron calculados. Las isotermas de adsorción se obtuvieron con un VTI-SA+ y la temperatura de transición vítrea (Tg) se determinó empleando un calorímetro diferencial de barrido (DSC). La morfología de las partículas se analizó con un microscopio electrónico de barrido (SEM) y finalmente el contenido de humedad y el rendimiento fueron determinados por diferencia de peso y por la relación de masa recuperada/masa alimentada, respectivamente. Un diseño factorial 23fue usado para evaluar el efecto de las condiciones de secado sobre las propiedades físicas. En general, no se encontraron diferencias importantes en las propiedades de los polvos de las dos especies de pitaya. Se encontró que el % de encapsulantes tuvo un efecto significativo en el rendimiento, mientras que el contenido de humedad y el color fueron afectados por todas las condiciones de secado. Los datos experimentales de isotermas de adsorción fueron ajustados a los modelos de GAB y BET y los datos de Tgse ajustaron al modelo de Gordon-Taylor. Las isotermas de adsorción tuvieron un comportamiento tipo III, comúnmente observadas en alimentos ricos en azúcares. Los parámetros del modelo de GAB fueron calculadas con un valor deR2> 0.99 y los del modelo de Gordon-Taylor con un valor de R2> 0.95. El factor que tuvo mayor efecto en la adsorción de agua y Tgfue el % de encapsulantes. Para calcular las condiciones críticas(actividad de agua y contenido de humedad críticos)de almacenamiento a 25 °C para los polvos se emplearon los ajustes de los modelos de GAB y Gordon-Taylor. La morfología de las partículas fue esférica con una superficie lisa sin colapsos. El tratamiento P7 (150 °C, 2 L/h y 90% de encapsulantes) presentó las mejores características físicas, a estas condiciones de secado se asegura la obtención de polvos estables con una vida de anaquel prolongada y una menor pérdida del color, sugiriendo una mejor retención de las betalaínas. La actividad de agua crítica y contenido de humedad crítico para una temperatura de almacenamiento de 25 °C para polvos PG, OG y OA (tratamiento P7) fueron: 0.210 y 0.036 g H2O/g s.s., 0.252 y 0.043 g H2O/g s.s. y 0.247 y 0.043 g H2O/g s.s., respectivamente.

Published
2014

43. Modified β-Cyclodextrin Inclusion Complex to Improve the Physicochemical Properties of Albendazole. Complete In Vitro Evaluation and Characterization

Author

Mario O. Salazar, Maria Celina Lamas, Darío Leonardi, and Agustina García

Subjects
INCLUSION COMPLEX, Magnetic Resonance Spectroscopy, Chemical Phenomena, lcsh:Medicine, Beta-Cyclodextrins, Dosage form, purl.org/becyt/ford/1 [https], chemistry.chemical_compound, X-Ray Diffraction, Drug Discovery, Spectroscopy, Fourier Transform Infrared, Dissolution testing, Citrates, Solubility, lcsh:Science, media_common, chemistry.chemical_classification, Multidisciplinary, Cyclodextrin, Calorimetry, Differential Scanning, Chemistry, MODIFIED CYCLODEXTRINS, beta-Cyclodextrins, Ciencias Químicas, Infectious Diseases, Microtechnology, Medicine, ALBENDAZOLE, CIENCIAS NATURALES Y EXACTAS, medicine.drug, Research Article, Biotechnology, Drug, Drugs and Devices, Spectrometry, Mass, Electrospray Ionization, Drug Research and Development, media_common.quotation_subject, Materials Science, Excipient, Albendazole, Phase Transition, Biomaterials, medicine, purl.org/becyt/ford/1.4 [https], Biology, Chemical Physics, Otras Ciencias Químicas, lcsh:R, Organic Chemistry, Tropical Diseases (Non-Neglected), Polymer Chemistry, Combinatorial chemistry, lcsh:Q, Derivative (chemistry)
Abstract

The potential use of natural cyclodextrins and their synthetic derivatives have been studied extensively in pharmaceutical research and development to modify certain properties of hydrophobic drugs. The ability of these host molecules of including guest molecules within their cavities improves notably the physicochemical properties of poorly soluble drugs, such as albendazole, the first chosen drug to treat gastrointestinal helminthic infections. Thus, the aim of this work was to synthesize a beta cyclodextrin citrate derivative, to analyze its ability to form complexes with albendazole and to evaluate its solubility and dissolution rate. The synthesis progress of the cyclodextrin derivative was followed by electrospray mass spectrometry and the acid-base titration of the product. The derivative exhibited an important drug affinity. Nuclear magnetic resonance experiments demonstrated that the tail and the aromatic ring of the drug were inside the cavity of the cyclodextrin derivative. The inclusion complex was prepared by spray drying and full characterized. The drug dissolution rate displayed exceptional results, achieving 100% drug release after 20 minutes. The studies indicated that the inclusion complex with the cyclodextrin derivative improved remarkably the physicochemical properties of albendazole, being a suitable excipient to design oral dosage forms. Fil: García, Agustina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Química Rosario; Argentina Fil: Leonardi, Darío. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Química Rosario; Argentina Fil: Salazar, Mario Oscar. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; Argentina Fil: Lamas, Maria Celina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Química Rosario; Argentina

Published
2014

45. Periodic gastroenterology and hepatology meetings with primary care. Reasons for consultation

Author

Agustín Caro-Patón, Juan del Río-Hortega, Antonio Otero, Juan Pradera-Leonardo, Raquel Briso-Montiano, Manuel Jiménez-Rodríguez-Vila, Agustín Mayo, Fernando Villuela-González, Lourdes del Olmo-Martínez, Elisa Ibañes-Jalón, Agustina García-Pascual, María José Castellanos-Alonso, Ana Almaraz-Gómez, Laura Mata-Román, Soledad Sañudo, José Ignacio Pinilla-Gimeno, Manuela Catón-Valdés, Pilar Gómez-Gómez, Lucinio Laso, and Rosario Vallelado

Subjects
Adult, Male, Rural Population, medicine.medical_specialty, Urban Population, Population, Specialty, Psychological intervention, Disease, Primary care, Derivaciones, Gastroenterology, Urbano, Internal medicine, Intervention (counseling), Intervención educativa, medicine, Urban, Humans, Gastroenterología, Rural, Prospective Studies, Medical diagnosis, lcsh:RC799-869, education, Referral and Consultation, Aged, education.field_of_study, Hepatología, Hepatology, Primary Health Care, business.industry, Consultas compartidas, General Medicine, Referrals, Middle Aged, Atención primaria, Joint consultation, lcsh:Diseases of the digestive system. Gastroenterology, Female, Training intervention, business
Abstract

Introduction: care overload, aging of population, and increased chronic diseases lead to increased referrals from primary care, which may sometimes overload the health system. Thus, different interventions have been carried out attempting to improve these aspects. Objectives: to assess the most frequent causes of consultation of general physicians, both in joint consultations and clinical sessions held jointly with specialist consultant in primary care, in the urban and rural setting, and the influence on referrals to first consultations of gastroenterology. Material and methods: a mainly training type of intervention was carried out, consisting of regular meetings in both urban and rural primary care center, to perform joint consultations and clinical sessions on patients and topics related to the specialty of gastroenterology. The intervention period (divided in two subperiods) was compared with a control period. Results: most reasons for consultation were those corresponding to lower gastrointestinal tract, followed by liver disease and upper gastrointestinal tract. Significant differences were only found in distribution of diagnoses between the two centers in joint consultations. There was a relative (percent) decrease in referrals at the global level in both subperiods, only significant in the first (51.45 %), as well as in rural setting (45.24 %). Conclusion: common consultations motifs were similar in urban and rural settings, with some relevance of lower gastrointestinal tract disease. Most of them can be solved at primary care, with the help of consultant specialist. There is impact on referrals to the outpatient first consultations of gastroenterology, mainly in rural setting.

Published
2014

46. Phosphodiesterase 5 inhibition at disease onset prevents experimental autoimmune encephalomyelitis progression through immunoregulatory and neuroprotective actions

Author

María Gutierrez-Mecinas, Agustina García, Lorena Usero, Judith Prado, Mercedes Giralt, Juan Hidalgo, Paula Pifarré, and Carme Roura-Mir

Subjects
Encephalomyelitis, Autoimmune, Experimental, Time Factors, T-Lymphocytes, Freund's Adjuvant, Neuroprotection, Severity of Illness Index, Piperazines, Sildenafil Citrate, Myelin oligodendrocyte glycoprotein, Myelin, Mice, Developmental Neuroscience, Neurotrophic factors, medicine, Animals, Humans, Sulfones, biology, Multiple sclerosis, Experimental autoimmune encephalomyelitis, FOXP3, Brain, Myelin Basic Protein, Phosphodiesterase 5 Inhibitors, medicine.disease, Axons, respiratory tract diseases, Mice, Inbred C57BL, Disease Models, Animal, Oligodendroglia, medicine.anatomical_structure, Neurology, Gene Expression Regulation, Purines, cGMP-specific phosphodiesterase type 5, Immunology, cardiovascular system, biology.protein, Disease Progression, Cytokines, Female, Myelin-Oligodendrocyte Glycoprotein
Abstract

In addition to detrimental inflammation, widespread axon degeneration is an important feature of multiple sclerosis (MS) pathology and a major correlate for permanent clinical deficits. Thus, treatments that combine immunomodulatory and neuroprotective effects are beneficial for MS. Using myelin oligodendrocyte glycoprotein peptide 35-55 (MOG)-induced experimental autoimmune encephalomyelitis (EAE) as a model of MS, we recently showed that daily treatment with the phosphodiesterase 5 (PDE5) inhibitor sildenafil at peak disease rapidly ameliorates clinical symptoms and neuropathology (Pifarre et al., 2011). We have now investigated the immunomodulatory and neuroprotective actions of sildenafil treatment from the onset of EAE when the immune response prevails and show that early administration of the drug prevents disease progression. Ultrastructural analysis of spinal cord evidenced that sildenafil treatment preserves axons and myelin and increases the number of remyelinating axons. Immunostaining of oligodendrocytes at different stages of differentiation showed that sildenafil protects immature and mature myelinating oligodendrocytes. Brain-derived neurotrophic factor (BDNF), a recognized neuroprotectant in EAE, was up-regulated by sildenafil in immune and neural cells suggesting its implication in the beneficial effects of the drug. RNA microarray analysis of spinal cord revealed that sildenafil up-regulates YM-1, a marker of the alternative macrophage/microglial M2 phenotype that has neuroprotective and regenerative properties. Immunostaining confirmed up-regulation of YM-1 while the classical macrophage/microglial activation marker Iba-1 was down-regulated. Microarray analysis also showed a notable up-regulation of several members of the granzyme B cluster (GrBs). Immunostaining revealed expression of GrBs in Foxp3+-T regulatory cells (Tregs) suggesting a role for these proteases in sildenafil-induced suppression of T effector cells (Teffs). In vitro analysis of splenocytes from sildenafil-treated animals showed down-regulation of Th1/Th2/Th17 responses while Tregs were up-regulated. Additionally, sildenafil treatment prevented MOG-specific IgG2b accumulation in serum. Taken together these data demonstrates that daily sildenafil treatment from the initiation of EAE symptoms prevents further clinical deterioration by stimulating immunomodulatory and neuroprotective mechanisms. Importantly, we also show here that sildenafil enhances the ability of human Tregs from healthy donors to down-regulate the proliferation of Teffs in vitro, strongly supporting the potential of sildenafil for therapeutic intervention in MS.

Published
2013

47. Aspectos contextuales del surgimiento de terapia ocupacional en la Argentina

Author

Agustina García and Julieta Briglia

Subjects
General Medicine
Abstract

El presente trabajo pretende caracterizar algunos aspectos contextuales previos y posteriores a la apertura del primer centro de enseñanza de Terapia Ocupacional en la Argentina, la Escuela Nacional de Terapia Ocupacional en el periodo histórico que va desde 1946 a 1965. Este artículo fue escrito a partir de nuestra actividad como becarias3 en el marco de un proyecto de investigación dirigido por Lic. TO Mariela Nabergoi y conformado por un equipo de docentes investigadores del Instituto de las Ciencias de Rehabilitación y el Movimiento de la Universidad Nacional de San Martín.Para cumplir con el objetivo propuesto realizamos un análisis de fuentes secundarias que describan el contexto políticoeconómico, social, educativo y sanitario en Argentina durante el periodo estudiado y que traten el tema del surgimiento de Terapia Ocupacional en la Argentina.Al reflexionar sobre los factores contextuales que permitieron el surgimiento de la TO en el país, podemos afirmar que la epidemia de poliomielitis de 1956 fue, tal como señala buena parte de la bibliografía relevada sobre la historia de TO en nuestro país, una situación desencadenante de la necesidad socio-sanitaria de formar recursos humanos para atender las secuelas de la enfermedad. No obstante, remarcamos la importancia de evitar concebir a la epidemia en términos de causa-efecto con respecto a la creación de la formación profesional en TO, debido a que no puede ser aislada de los contextos político-económico, social, educativo y sanitario.

Published
2013
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48. Native forest land management : zoning results performed by north Argentinean provinces

Author

Amalia Panizza, José M. Paruelo, and María Agustina García Collazo

Subjects
plan de ordenamiento territorial, Categorías de conservación, Native forests act, PROTECCION AMBIENTAL, Land management, land use planning, categorías de conservación, Context (language use), Native forest, Environmental protection, lcsh:QH540-549.5, Silvicultura, ORDENACION TERRITORIAL, lcsh:Environmental sciences, Ecology, Evolution, Behavior and Systematics, ORDENACION FORESTAL, lcsh:GE1-350, ARGENTINA, native forests act, Criterios de sustentabilidad ambiental, Ecology, Forestry, Land-use planning, Plan de ordenamiento territorial, environmental sustainability criteria, ley de bosques nativos, LEGISLACION MEDIOAMBIENTAL, DESARROLLO SOSTENIBLE, Geography, CIENCIAS AGRÍCOLAS, BOSQUE VIRGEN, conservation categories, criterios de sustentabilidad ambiental, Sustainability, purl.org/becyt/ford/4.1 [https], lcsh:Ecology, Ley de Bosques Nativos, Agricultura, Silvicultura y Pesca, Zoning, purl.org/becyt/ford/4 [https]
Abstract

Argentina cuenta con varias experiencias de ordenamiento territorial (OT) pero hasta el momento no ha sancionado una ley integral. Uno de los principales antecedentes es el ordenamiento territorial de los bosques nativos (OTBN) a través de la ley 26331, sancionada en 2007. El objetivo de este trabajo fue evaluar las experiencias de zonificación en el marco de esta ley de las provincias de Santiago del Estero, Chaco, Formosa y Salta. Se analizó la aplicación de los 10 criterios de sustentabilidad ambiental contemplados por la ley y se compararon cuantitativamente los mapas de zonificación resultantes del proceso de OTBN en las áreas limítrofes. La interpretación de los criterios de sustentabilidad ambiental ha sido dispar entre provincias debido, en parte, a que la información de base utilizada no tiene el mismo nivel de detalle. Salta y Chaco consideraron mayor detalle en estos criterios mientras que Santiago del Estero y Formosa utilizaron información con un nivel de detalle menor. La comparación de la categorización de bosques entre provincias colindantes muestra que la mayor concordancia en las categorías asignadas se observa en los límites de Santiago del Estero y Chaco (58.3%). El grado de concordancia entre los restantes pares de provincias colindantes resultó considerablemente menor:24.76% entre Chaco y Salta; 20.65% entre Formosa y Salta; 10.54% entre Chaco y Formosa y 1.28% entre Salta y Santiago del Estero. Los resultados sugieren que las zonificaciones no han resultado consistentes debido al bajo nivel de concordancia en la categorización de sus bosques. Argentina has several experiences on Land Planning, but so far there is not an integral normative. A key background experience is the land use planning of native forest act (26331) from 2007.The aim of this study was to evaluate the experiences of zoning of the provinces of Santiago del Estero, Chaco, Formosa and Salta in the context of this act. We characterize the way the 10 criteria of environmental sustainability were considered by the four provinces, and we quantitatively compared the zoning maps on the provincial boundaries. The interpretation of the criteria of environmental sustainability differed, in part, because the different provinces did not use the same level of detail. Salta and Chaco considered a higher level of detail on these criteria than the rest. The comparison of the way forests were categorized showed that the highest concordance corresponded to the Santiago del Estero - Chaco border (58.3%). All the other pairs of neighbor provinces presented a significantly lower concordance: 24.76% between Chaco and Salta, 20.65% between Formosa and Salta, 10.54% between Chaco and Formosa and 1.28% between Salta and Santiago del Estero. Our results suggest that the zoning has not been consistent due to the low agreement on the categorization of forests among provinces. Fil: García Collazo, María Agustina. Universidad de Buenos Aires. Facultad de Agronomía. Departamento de Métodos Cuantitativos y Sistemas de Información; Argentina Fil: Panizza, Amalia. Universidad de Buenos Aires. Facultad de Agronomía. Departamento de Métodos Cuantitativos y Sistemas de Información; Argentina Fil: Paruelo, José. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Fisiológicas y Ecológicas Vinculadas a la Agricultura; Argentina

Published
2013

49. Characteristics of nitric oxide synthase type I of rat cerebellar astrocytes

Author

Joan Ribera, Maria Lourdes Arbonés, Valentina Riveros‐Moreno, María Antonia Baltrons, Anna Casanovas, Agustina García, and Luis Agulló

Subjects
education.field_of_study, Cerebellum, biology, medicine.diagnostic_test, Population, Molecular biology, Nitric oxide synthase, Cellular and Molecular Neuroscience, chemistry.chemical_compound, medicine.anatomical_structure, Neurology, chemistry, Western blot, Biochemistry, Citrulline, biology.protein, medicine, Neuroglia, education, Immunostaining, Astrocyte
Abstract

We have previously reported that stimulation of astrocyte cultures by particular agonists and calcium ionophores induces cyclic GMP formation through activation of a constitutive nitric oxide synthase (NOS) and that astrocytes from cerebellum show the largest response. In the present work we have used rat cerebellar astrocyteenriched primary cultures to identify and characterise the isoform of NOS expressed in these cells. The specific NOS activity in astrocyte homogenates, determined by conversion of [3H]arginine to [3H]citrulline, was ten times lower than in homogenates from cerebellar granule neurons. Upon centrifugation at 100,000 g, the astroglial activity was recovered in the supernatant, whereas in neurons around 30% of the activity remained particulate. The cytosolic NOS activities of both astrocytes and granule neurons displayed the same Km for L-arginine, dependency of calcium, and sensitivity to NOS inhibitors. Expression of NOS-I in astrocyte cytosolic fractions was revealed by Western blot with a specific polyclonal antiserum against recombinant NOS-I. Double immunofluorescence labelling using anti-glial fibrillary acidic protein (GFAP) and anti-NOS-I antibodies revealed that a minor population of the GFAP-positive cells, usually in clusters, presented a strong NOS-I immunostaining that was predominantly located around the nuclei and had a granular appearance, indicating association with the endoplasmic reticulum-Golgi system. Astrocytes of stellate morphology also showed immunoreactivity in the processes. Similar staining was observed with the avidin-biotin-peroxidase complex using different anti-NOS-I antisera. With this method the majority of cells showed a weak NOS-I immunoreactivity around the nuclei and cytosol. A similar pattern was observed with the NADPH-diaphorase reaction. These results demonstrate that the NOS-I expressed in astrocytes presents the same biochemical characteristics as the predominant neuronal isoform but may differ in intracellular location.

Published
1996
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50. Induction of atypical EAE mediated by transgenic production of IL-6 in astrocytes in the absence of systemic IL-6

Author

Iain L. Campbell, Agustina García, Elisenda Sanz, Juan Hidalgo, Mercedes Giralt, Maria Erta, Marco Castro-Freire, Mercedes Unzeta, Raquel Ramos, Paula Pifarré, Beatriz Ferrer, Albert Quintana, and Gemma Comes

Subjects
Genetically modified mouse, Male, Encephalomyelitis, Autoimmune, Experimental, Transgene, Encephalomyelitis, Central nervous system, Mice, Transgenic, Biology, Cellular and Molecular Neuroscience, Mice, immune system diseases, medicine, Animals, Cells, Cultured, Mice, Knockout, Microglia, Interleukin-6, Experimental autoimmune encephalomyelitis, Interleukin, medicine.disease, Mice, Inbred C57BL, medicine.anatomical_structure, Neurology, Astrocytes, Immunology, Female, Astrocyte
Abstract

Interleukin (IL)-6 is crucial for the induction of many murine models of autoimmunity including experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. While IL-6-deficient mice (IL-6 KO) are resistant to EAE, we showed previously that in transgenic mice with astrocyte-targeted production of IL-6-restricted to the cerebellum (GFAP-IL6), EAE induced with MOG(35-55) was redirected away from the spinal cord to the cerebellum. To further establish the importance of IL-6 produced in the central nervous system, we have generated mice producing IL-6 essentially only in the brain by crossing the GFAP-IL6 mice with IL-6 KO mice. Interestingly, GFAP-IL6-IL-6 KO mice showed a milder but almost identical phenotype as the GFAP-IL6 mice, which correlated with a lower load of inflammatory cells and decreased microglial reactivity. These results indicate that not only is cerebellar IL-6 production and eventual leakage into the peripheral compartment the dominating factor controlling this type of EAE but that it can also facilitate induction of autoimmunity in the absence of normal systemic IL-6 production.

Published
2012

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