Una mirada comparativa sobre la edición y circulación de historietas en España y Argentina en el Siglo XXI Gago, Sebastian Horacio En las últimas décadas, la historieta ha ganado reconocimiento entre el público general, instituciones del Estado, medios de comunicación masiva, el ámbito académico y el campo cultural. Este cambio de estatus puede ser entendido en correlación con un proceso de renovación económica y cultural. En España y Argentina, la tradicional industria editorial de historietas desapareció en los años noventa del siglo XX. En el país europeo, el medio se ha tornado una renovada industria que experimentó un crecimiento creativo y una progresiva consolidación editorial. En la nación sudamericana, han proliferado pequeños emprendimientos editoriales autogestivos que revitalizaron un mercado drásticamente reducido desde la crisis de 2001. Este texto busca examinar las condiciones que produjeron cambios estructurales en la circulación de historietas en España y la Argentina durante las últimas dos décadas. Nuestra hipótesis es que los usos sociales, las prácticas lectoras, los mecanismos de legitimación y las estrategias editoriales son mediaciones culturales entre las historietas y sus lectores. Sin esas mediaciones no puede entenderse que el medio actualmente sea considerado un producto cultural con una legitimidad y visibilidad que no había tenido en el siglo pasado, cuando aún revestía un carácter masivo y popular.; Currently comics have gained recognition within readers, public institutions, journalism and intellectual and cultural fields. This change can be understood in correlation with a process of social and economic renewal. In box the Spanish and Argentine cases, the traditional comic publishing industry disappeared in the nineties. In the European country, comics became a renewed industry that is facing an increase in sales and a progressive consolidation within the publishing world. In the South American country, following the Argentinean Crisis of December 2001, small self-managed publishing enterprises have proliferated and they revitalized a small market. The objective of this research is to examine the social conditions that produced structural changes in the circulation of comics in Spain and Argentina over the last two decades. Our hypothesis is that social uses, reading practices, mechanisms of legitimacy and publishing strategies are cultural mediations between comics and readers. This reorganization in the forms of production and circulation of symbolic goods changed its way of insertion in social life. Therefore, cultural mediations made the Spanish and Argentine comic to be considered as a cultural product with a kind of legitimacy and visibility that it did not have before.

Trabajo no remunerado y uso del tiempo en la Argentina de principios del siglo XXI Delfino, María Andrea; Herzfeld, Claudia Lorena; Arrillaga, Hugo Este artículo presenta y analiza las tendencias centrales surgidas de la ?Encuesta sobre trabajo no remunerado y uso del tiempo?, realizada por primera vez en Argentina en el último trimestre de 2013, como módulo de la Encuesta Anual de Hogares Urbanos. La encuesta recogió respuestas de 65.000 personas mayores de 18 años en localidades de dos mil o más habitantes en todo el país; en este sentido es representativa de 80% del territorio argentino. Las tendencias que se analizan corresponden a los datos relativos a dos tipos de trabajo no remune-rado: el doméstico (quehaceres del hogar) y los cuidados a miembros del hogar (actividades de cuidado de ni-ños, enfermos o adultos mayores, y actividades de apoyo escolar y/o de aprendizaje); y el trabajo voluntario, es decir, aquellas actividades no remuneradas hechas libremente para el beneficio de personas ajenas a la familia.

Circadian rhythms of factors involved in luteal regression are modified in p55 tumour necrosis factor receptor (TNFRp55)-deficient mice de la Vega, Magali del Carmen; Delsouc, María Belén; Ponce, Ivana Tamara; Ragusa, Juan Antonio Vicente; Vallcaneras, Sandra; Anzulovich Miranda, Ana Cecilia; Casais, Marilina The rhythm of factors involved in luteal regression is crucial in determining the physiological duration of the oestrous cycle. Given the role of tumour necrosis factor (TNF)-α in luteal function and circadian regulation and that most of the effects of TNF-α are mediated by p55 TNF receptor (TNFRp55), the aims of the present study were to analyse the following during the luteal regression phase in the ovary of mice: (1) whether the pattern of expression of progesterone (P4) and the enzymes involved in the synthesis and degradation of P4 is circadian and endogenous (the rhythm persists in constant conditions, (i.e., constant darkness) with a period of about 24 hours); (2) circadian oscillations in clock gene expression; (3) whether there are daily variations in the expression of key genes involved in apoptosis and antioxidant mechanisms; and (4) the consequences of TNFRp55 deficiency. P4 was found to oscillate circadianally following endogenous rhythms of clock factors. Of note, TNFRp55 deficiency modified the circadian oscillation in P4 concentrations and its enzymes involved in the synthesis and degradation of P4, probably as a consequence of changes in the circadian oscillations of brain and muscle ARNT-Like protein 1 (Bmal1) and Cryptochrome 1 (Cry1). Furthermore, TNFRp55 deficiency modified the circadian rhythms of apoptosis genes, as well as antioxidant enzymes and peroxidation levels in the ovary in dioestrus. The findings of the present study strengthen the hypothesis that dysregulation of TNF-α signalling may be a potential cause for altered circadian and menstrual cycling in some gynaecological diseases.

Spectrum of J-frame operators Giribet, Juan Ignacio; Langer, Matthias; Leben, Leslie; Maestripieri, Alejandra Laura; Martinez Peria, Francisco Dardo; Trunk, Carsten Joachim A J-frame is a frame F for a Krein space (H, [⋯, ⋯]) which is compatible with the indefinite inner product [⋯, ⋯] in the sense that it induces an indefinite reconstruction formula that resembles those produced by orthonormal bases in H. With every J-frame the so-called J-frame operator is associated, which is a self-adjoint operator in the Krein space H. The J-frame operator plays an essential role in the indefinite reconstruction formula. In this paper we characterize the class of J-frame operators in a Krein space by a 2 × 2 block operator representation. The J-frame bounds of F are then recovered as the suprema and infima of the numerical ranges of some uniformly positive operators which are build from the entries of the 2 × 2 block representation. Moreover, this 2 × 2 block representation is utilized to obtain enclosures for the spectrum of J-frame operators, which finally leads to the construction of a square root. This square root allows a complete description of all J-frames associated with a given J-frame operator.

Evaluation of Water Activity in H2O-PEG400-PEG6000 Solutions between 318.15 and 348.15 K Paulazzo, Micaela G.; Passamonti, Francisco Javier The vapor pressure of H2O(1)-polyethylene glycol 400(2)-polyethylene glycol 6000(3) solutions was evaluated experimentally in a temperature range between 318.15 and 348.15 K and in a broad range of concentrations. The dependence of the solvent activity on composition was evaluated and correlated by means of a polynomial expression, in terms of concentrations, volumetric and mass fractions, and temperature, obtaining in all cases standard deviations less than 0.0086 and 0.0106 for a1(φ2,φ3,T) and a1(w2,w3,T), respectively.

Virtual prototype of a low-cost vacuum baffle based on thermoelectric cooling Conde Garrido, Juan Manuel; Silveyra, Josefina María Contaminants can enter vacuum systems from two main sources: backstreaming of oil vapors from the diffusion and mechanical pumps, and vapors generated as byproducts in the process chamber. Both sources can be hindered by using an appropriate baffle. We developed a virtual prototype of a low-cost baffle for vacuum systems that is cooled down with thermoelectric coolers (TECs). Compared to compressor cooling systems, TECs have useful advantages for this application: they are compact, silent, vibration-free, almost maintenance-free, inexpensive, widely commercially available, and capable of providing a precise temperature control. The baffle is partly built inside a tee vacuum fitting. A refrigerated cooper helix provides the trapping surfaces for contaminants flowing between the process chamber and the vacuum pumps. The cost of the baffle is below USD 250. The proof-of-concept model, implemented by the finite element method, showed that, when using TEC1-12706 modules, the helix can reach temperatures as low as −50 °C. According to our analysis, this temperature is more than enough for trapping the contaminants described above.

The peri-urban interface: hydrological effects of anthropogenic pressure Delgado, María Isabel; Carol, Eleonora Silvina; Casco, Maria Adela; Mac Donagh, María Elicia The province of Buenos Aires (Argentina) is one of the main productive areas of the country. In the These days of the province landscape is shaped by a mosaic of rural and urban sectors; here is placed the Cinturón Hortícola Platens integrated by a set of watersheds with different level of anthropogenic modification. The aim of this work was to evaluate how land use covers change process, derived from anthropogenic pressure, affects the hydrological and environmental characteristics of flat land watersheds; for this purpose, it was chosen as case study the peri-urban watershed of El Pesaro Creek, located in Argentina s Pampas region. This watershed has historically presented the least anthropogenic impact, but nowadays shows evident productive and real estate expansion. Land use change was evaluated with satellite images; current land use mainly includes urbanization, cattle raising and intensive agriculture. Surface water chemistry was determined by sampling different sections of the creek, groundwater sampling was based on groundwater monitoring wells distributed along the watershed. Physical-chemical water parameters were determined in situ, major ions were determined in laboratory under standardized methods. Results were compared with hydro chemical previous studies (when the whole watershed was characterized as rural, with extensive livestock farming), allowing to conclude that the most important quantifiable modifications from an ecohydrological perspective are being registered in the upper watershed. In this area is where land use is turning to intensive horticulture (greenhouses), with no planning and minimal precautions about its possible impact on natural resources. Results obtained constitutes a valuable tool for the generation of management strategies not only for this particular watershed, but could also be extrapolated to areas with similar territorial dynamics.

“discamus naturales incurvationes rectificare”: De ludo globi I. Un diálogo entre el hombre y la naturaleza; “discamus naturales incurvationes rectificare”: De ludo globi I. A dialog between man and nature Rusconi, Maria Cecilia Como lo indica su título, el diálogo De ludo globi está construido en torno a un juego. Este juego consta de dos elementos: una bocha de madera levemente ahuecada y una superficie sobre la que están dibujados diez círculos concéntricos. El significado de cada uno de los círculos es detallado en el Libro II. Por su parte, el Libro I se ocupa de la forma de la bocha y su movimiento. El desafío al que se enfrenta el presente trabajo reside en encontrar una unidad sistemática, que sirva de hilo conductor del diálogo De ludo globi, en el marco del Libro I. Esta sistematización del texto deberá mostrar que el diálogo tiene como trasfondo otra dimensión dialógica, que muestra al texto como un diálogo del individuo con la naturaleza. Con esta intención, el presente trabajo está articulado en tres partes. En primer lugar (1) me concentraré en la bocha y su movimiento. En segundo lugar (2) abordaré el planteo cusano del alma y el cuerpo. Éste deberá dirigirnos, por último, a (3) una distinción entre la libertad y la naturaleza.; As its title indicates, Cusanus’ dialogue De ludo globi is built around a game. This game is composed of two elements: a slightly concave wooden ball and a surface on which nine concentric circles are drawn. The meaning of each circle is detailed in Book II of De ludo globi. For its part, Book I deals with the ball and its movement. My paper seeks to find a systematic unity that can become a guiding interpretive framework for the dialogue, in the context of Book I. This systematic unity must also show that the work incorporates in the background another, dialogical dimension, in which we can read De ludo globi as a dialogue between man and nature. With this in mind, I’ve divided the paper into three parts. First, (1) I will focus on the ball itself and its movement. Secondly, (2) I will present Cusanus’ approach to soul and body. This approach will then lead us to (3) a distinction between freedom and nature.

Cartografía analógica y digital para la delimitación regional y el análisis temático: aplicación a la cuenca del río Luján (Argentina); Analogue and digital cartography for regional delimitation and thematic analysis: Application to the Luján river basin (Argentina) Buzai, Gustavo Daniel; Lanzelotti, Sonia Laura; Paso Viola, Fernando; Principi, Noelia El paso inicial del proyecto “Análisis espacial y evaluación de zonas de potenciales conflictos ambientales, productivos y patrimoniales ante la expansión urbana en la cuenca del río Luján (Provincia de Buenos Aires, Argentina)” consistió en realizar la actualización de la delimitación del área de estudio. Para llevar a cabo esta tarea fue trazada una secuencia teórico-metodológica que implicó el análisis de cartografía histórica, confección de mapas mediante cartografía asistida por computador (CAC), definición de límites mediante el procesamiento digital de imágenes satelitales (PDI) utilizando modelos digitales de elevación y realización de la base de datos geográfica a través de Sistemas de Información Geográfica (SIG) vinculados con los globos terráqueos virtuales. El presente trabajo presenta aspectos teórico-metodológicos que permiten ejemplificar la secuencia con detalle en la alta cuenca, tanto en aspectos cartográficos como en imágenes logradas en el trabajo de campo y uso de GPS. El total de la tarea presenta claros aspectos de la vinculación entre procedimientos tradicionales y las actuales tecnologías de la información geográfica (TIG) utilizadas en la construcción regional y la representación temática de los resultados.; The initial step of the research project “Spatial analysis and evaluation of areas of environmental, productive and patrimonial potential conflicts before the urban expansion in the Luján river basin (Province of Buenos Aires, Argentina)” consisted in updating the delimitation of the study area. In order to carry out this task a theoretical-methodological sequence was drawn up, which involved the analysis of historical cartography, mapping using computer-aided cartography (CAC), definition of boundaries using digital image processing (DIP) through digital elevation models (DEM) and realization of the geographic database through Geographical Information Systems (GIS) linked to Virtual Earth and Digital Globes. The present work presents theoretical and methodological aspects that allow to exemplify the sequence with detail in the high basin area, as much in cartographic aspects as in images obtained in the field work with GPS. The total of the task presents clear aspects of the link between traditional procedures and the current Geographical Information Technologies (GIT) used in the regional construction and thematic representation of the results.

Collection of alkenylcoumarin derivatives as Taq DNA polymerase inhibitors: SAR and in silico simulations Bruna Haupt, Ezequiel Fabricio; Garro, Hugo Alejandro; Gutierrez, Lucas Joel; Pungitore, Carlos Rodolfo Using a feasible method, we generated a small focused library of structurally related alkenylcoumarins. These compounds were evaluated as potential antitumoral agents against Taq DNA polymerase. 6-(pent-4-enyloxy)-coumarin (7) IC50 = 48.33 ± 2.85 μM was defined as a small molecule able to disturb DNA replication. Docking and Molecular Dynamic Simulations suggest an active-site binding. Structure/activity relationship was reasonably established. Compound 7 represents a potential structure for further studies in the development of new anti-cancer DNA/polymerase binding agents.

Knowledge, attitudes and practices (KAP) regarding leptospirosis among residents of riverside settlements of Santa Fe, Argentina Ricardo, Tamara; Bergero, Laura; Bulgarella, Esteban; Previtali, Maria Andrea Background: Leptospirosis is a global and re-emerging zoonotic disease caused by Leptospira spirochetes that are shed into the environment by infected animals. Humans can get infected via contact with animal hosts or contaminated environment. In Argentina, the highest annual incidences were reported in the province of Santa Fe, where epidemic outbreaks occurred during flooding events. This study examined the knowledge, attitudes and practices (KAP) regarding leptospirosis among residents of riverside slum settlements from Santa Fe after a major flood. Methods and findings: A cross-sectional questionnaire was administered to 113 residents of 3 riverside settlements from Santa Fe. The influence of knowledge and attitudes regarding leptospirosis on the likelihood that an individual will use preventive practices were evaluated using linear mixed-effects models. The majority of respondents (83.2%) had previously heard about leptospirosis; however specific knowledge about leptospirosis was limited. The results of the modeling efforts, show that the likelihood of using preventive practices was associated with having greater knowledge score, but not with more positive attitudes. We also found that females were more likely to use safer practices than males. Conclusions: Even though the majority of respondents had heard about leptospirosis, a high percentage of them had limited knowledge regarding the severity of the disease and its prevalence in the region. Our results suggest that public health interventions in these riverside communities should focus on educating the public on the multiple dimensions of leptospirosis in order to attain greater adherence to preventive practices instead of intending to change the perceptions or attitudes towards the disease, which did not have a significant influence. The key challenge lies in identifying effective strategies to reach the high risk group for leptospirosis here that is male fishermen, who spend most of the time in precarious campsites on the river islands.

Contrasting consequences of different defence strategies in a natural multihost-parasite system Manzoli, Darío Ezequiel; Saravia Pietropaolo, María José; Antoniazzi, Leandro Raúl; Barengo, Emilce; Arce, Sofía Irene; Quiroga, Martin Anibal; Beldomenico, Pablo Martín Hosts counteract infections using two distinct defence strategies, resistance (reduction in pathogen fitness) and tolerance (limitation of infection damage). These strategies have been minimally investigated in multi-host systems, where they may vary across host species, entailing consequences both for hosts (virulence) and parasites (transmission). Comprehending the interplay among resistance, tolerance, virulence and parasite success is highly relevant for our understanding of the ecology and evolution of infectious and parasitic diseases. Our work investigated the interaction between an insect parasite and its most common bird host species, focusing on two relevant questions: (i) are defence strategies different between main and alternative hosts and, (ii) what are the consequences (virulence and parasite success) of different defence strategies? We conducted a matched field experiment and longitudinal studies at the host and the parasite levels under natural conditions, using a system comprising Philornis torquans flies and three bird hosts – the main host and two of the most frequently used alternative hosts. We found that main and alternative hosts have contrasting defence strategies, which gave rise in turn to contrasting virulence and parasite success. In the main bird host, minor loss of fitness, no detectable immune response, and high parasite success suggest a strategy of high tolerance and negligible resistance. Alternative hosts, on the contrary, resisted by mounting inflammatory responses, although with very different efficiency, which resulted in highly dissimilar parasite success and virulence. These results show clearly distinct defence strategies between main and alternative hosts in a natural multi-host system. They also highlight the importance of defence strategies in determining virulence and infection dynamics, and hint that defence efficiency is a crucial intervening element in these processes.

Ambivalenza della vita umana. Tra la materialità corporale e l'ontologia del «vulnerabile» nel pensiero di Judith Butler; The ambivalence of human life. The corporeal materialization and the ontology of vulnerability in Judith Butler’s thought Rosenzweig, Esteban The present work is aimed at establishing a conceptual correspondence between the notions of body and corporal materialization proposed by Judith Butler, until they converge on the theoretical core of that concept the philosopher designates as «common human vulnerability». In what way do we think of human life? What value do we have to give life, without turning and ontologically transforming it into something essential? These questions will trigger the following reflexions.

Erratum: Signals of strong electronic correlation in ion scattering processes (Physical Review B (2016) 93 (195439) DOI: 10.1103/PhysRevB.93.195439) Tacca, Marcos Sebastian; Bonetto, Fernando Jose; Gonzalez, C.; Goldberg, Edith Catalina We found an error in the mathematical formulation of the finite-U model [19] that we used in our paper to describe the neutral fractions measured when Sr+ ions collide with a gold surface [4,5]. The error is connected to boundary conditions, such as the following one: (Formula Presented) where the correct minus sign was dismissed. This correction introduces changes of sign in the integral terms (Formula Presented) The above-described amendment of the finite-U model introduces slight modifications in Figs. 6(c) and 7 of the published paper. These figures should be replaced by the figures below.

Synthesis and characterization of a waterborne polyurethane made from castor oil and tartaric acid Hormaiztegui, Maria Eugenia Victoria; Aranguren, Mirta Ines; Mucci, Veronica Lujan Waterborne polyurethanes (WBPUs) based on the reaction of unmodified castor oil (CO) with isophorone diisocyanate (IPDI) were synthesized using dimethylolpropionic acid (DMPA) or tartaric acid (TA) as internal emulsifiers. The effect of the incorporation of TA, a bio-based carboxylic acid, in the synthesis of castor oil-based WBPU was carefully investigated. For comparison, two WBPUs were synthesized using DMPA. The chemical changes that took place during the reaction were followed using FTIR. The raw materials and the final polymeric films were characterized by this technique as well as 1H NMR, XRD, DSC, DMA and TGA. Results indicated that in the case of the sample prepared with TA, the isocyanate reacts with the hydroxyls of the acyl groups of the acid additionally to the alcoholic ones. In all cases, the films prepared by casting were translucent and showed glass transition temperatures above room temperature, although comparatively lower for the WBPU formulated with TA. Differences were also observed in the thermal degradation performance of the films. The observed differences were tracked to those in the molecular structures of the WBPUs.

Population and reproductive patterns of the Neotropical planarian Girardia capacivasa (Platyhelminthes, Tricladida), and the influence of seasonality on its life history Lenguas Francavilla, Marina Matilde; Negrete, Lisandro Hector Luis; Delevati Colpo, Karine; Brusa, Francisco The biology of Neotropical freshwater planarians (Platyhelminthes) is almost unknown compared with that of their Holarctic relatives. In this paper, we 1) studied the sequence of development of the reproductive system of Girardia capacivasa Sluys & Kawakatsu, 2005 (Dugesiidae), to estimate the onset of sexual maturity, applying the logistic regressions for the first time in flatworms; and 2) assessed reproductive and population patterns of this freshwater flatworm, and their responses to water temperature variation in a temperate Neotropical stream. These appraisals allowed us to test if the life history traits of freshwater planarians are similar in regions with marked temperature seasonality. According to the degree of development of the gonads and copulatory apparatus the development of the reproductive system was classified in five stages. The estimated size at the onset of sexual maturity was 12 mm. We found no relationship between the density of G. capacivasa and temperature, but planarians were more gregarious in warmer months. The largest planarians were recorded in cold months. The reproductive effort during the warm season was higher, but cocoons and juveniles were found throughout the study period, indicating continuous reproduction. Hence, the temperature variation recorded in the study area was not a limiting factor for breeding but influenced the body size and spatial distribution pattern of G. capacivasa.

Quality and yield of Ricotta cheese as affected by milk fat content and coagulant type Ortiz Araque, Leidy Carolina; Darré, Magalí; Ortiz, Cristian Matias; Massolo, Juan Facundo; Vicente, Ariel Roberto Milk processing conditions can exert a large influence on the quality of acid-coagulated cheeses. Herein, we evaluated the influence of milk fat content and coagulant type on Ricotta yield and physical, chemical and sensory properties. Fat-free Ricotta was hard and whiter than reduced-fat or full-fat Ricotta. Ricotta produced from low-fat and whole milk showed no differences in acceptability, indicating that fat content could be substantially reduced without impairing quality. Milk coagulation by citric acid decreased Ricotta moisture, firmness and yield, whereas calcium chloride produced a white Ricotta with desired firmness and high consumer acceptability.

Development of the layered structure in a double-gated glass fiber-reinforced polypropylene injection molding: Experimental and simulated results Quintana, María Camila; Frontini, Patricia Maria The present study aims to experimentally validate numerical simulation of fiber orientation distribution performed by molding simulation software Moldex3D in a double-gated injection-molded glass fiber-filled (40 wt%) polypropylene box, by making a detailed comparison of predicted and experimentally measured fiber orientation distribution data. The modeling approach evaluated in this work consists in the implementation of the Folgar–Tucker rotary diffusion model with the invariant-based optimal fitting closure approximation for the fourth-order orientation tensor. The specimen used has a weld line in the center and sharp corners. This investigation characterizes in detail the development of the through-thickness layered structure at distinctive locations of the specimen. The sensitivity of fiber orientation distribution and the layered structure to changes upon injection time and melt temperature is also evaluated. The boxes display the typical layered laminate structure, with fibers aligned in the main flow direction near the walls (shell layer) and less oriented in the middle plane (core layer). The boxes injected at the lowest melt temperature display an additional skin layer. Unfortunately, simulation fails in predicting the five layers structure developed under these latter conditions. The grade of fiber orientation is deemed to be independent of process parameters but not the layered structure.

Sunshine Duration Analysis as a First Step to Estimate Solar Resource for Photovoltaic Electricity Production in Middle Latitudes Fernández, María Eugenia; Gentili, Jorge Osvaldo; Campo, Alicia María This paper analyzes the spatio-temporal variability of sunshine duration in the south of the Pampeana region as a first approach to solar climatic analysis, main input for the use of this resource. Hourly sunshine duration records from 1991 to 2015 in eight Argentine cities were analyzed using statistics and geospatial techniques. In addition, we analyzed the frequency of clear sky and overcast days in order to relate it to the sunshine duration variability. Sunshine duration in the Pampeana region presented a linear gradient increasing in an east-west direction. An inverse relationship between the mean sunshine duration and coefficients of variation was found in all the cities. The highest mean values of sunshine duration were recorded located between 62°W and 65°W, where the lowest variability was also registered. The city of Mar del Plata showed the lowest mean values of sunshine duration (4.5 h) and the highest percentage of variability (78.1%), whereas Río Colorado recorded the highest mean values of sunshine duration (7.5 h) and the lowest variability (51.1%) over the observation period. During the warm season, it was recorded a difference of 3.7 h in the mean SD values between the stations Río Colorado and Mar del Plata. The spatial distribution of the solar resource in the Pampena region is markedly affected by weather systems playing at the regional scale of South America. In the cold season, the west-east movement of the high pressure cells promotes the occurrence of Sudestadas, which explain the variability of sunshine duration over the coastal areas.

Síntesis, caracterización fisicoquímica, determinaciones biológicas (in vitro) y estudios teóricos de complejos de Cu(II) y VO(IV) con ligandos antioxidantes y/o antimicrobianos Martínez Medina, Juan José La Química Bioinorgánica constituye la intersección entre la Química Inorgánica y la Bioquímica. Se sabe que los elementos inorgánicos (incluidos los iones metálicos y los compuestos de coordinación) son necesarios para la vida en muchos organismos, ya que funcionan en el transporte de moléculas y son un componente clave de las enzimas. Además, la coordinación de moléculas orgánicas con metales permite potenciar las propiedades biológicas de las mismas. En este contexto, se decidió sintetizar y caracterizar complejos de coordinación para estudiar sus propiedades biológicas y toxicológicas en el marco de este trabajo de tesis doctoral. A continuación se presenta una reseña de las principales conclusiones arribadas luego del estudio de la química bioinorgánica de los compuestos sintetizados.En concordancia con los objetivos propuestos en el plan de tesis, se sintetizaron tres complejos de coordinación nuevos (VO/Baic, VO/Api y Cu/5-HTP). Los mismos se caracterizaron experimentalmente como Na4[VO(Baic)2].6H2O, [VO(Api)(H2O)2]Cl y [Cu(5-HTP)2].H2O. La optimización de los complejos empleando herramientas del DFT sugiere que el complejo VO/Baic es un complejo pentacoordinado con geometría piramidal cuadrada VO(O4), el VO/Api es un complejo pentacoordinado con geometría piramidal cuadrada distorsionada VO(O4) y que el confórmero más estable del Cu/5HTP tiene una geometría cuadrado-plana CuN2O2 con una disposición trans de los aminoácidos en el plano ecuatorial. Las geometrías optimizadas de los mismos concuerdan con las esferas de coordinación propuestas teniendo en cuenta la caracterización estructural realizada por métodos químicos y fisicoquímicos.La determinación de las propiedades biológicas in vitro de las moléculas nuevas y el estudio de su perfil toxicológico constituyen los pilares fundamentales del descubrimiento de fármacos (drug discovery). En este sentido, se estudiaron las características biológicas y toxicológicas de los complejos sintetizados. Los complejos en estudio mostraron buenas propiedades antioxidantes en ensayos in vitro con el siguiente orden de actividad Cu/5-HTP > VO/Baic > VO/Api. En todos los casos la complejación con el metal mejoró las propiedades antioxidantes del ligando libre. En lo que respecta a las demás propiedades biológicas, el complejo Cu/5-HTP fue el único que mostró actividad antimicrobiana moderada (frente a S. aureus ATCC 25923 y E. faecalis ATCC 29212). Asimismo, este complejo fue el único que mostró una fuerte actividad inhibitoria de la enzima fosfatasa alcalina, mucho mayor que las actividades medidas para el ligando y el metal libre. Los estudios toxicológicos indican que los complejos sintetizados son seguros ya que no mostraron toxicidad aguda ni genotoxicidad. Estos hallazgos permiten concluir que la complejación mejora las propiedades biológicas de los mismos permitiendo la obtención de nuevas moléculas farmacológicamente activas.Existen numerosos reportes sobre complejos de iones metálicos que ejercen efectos inhibitorios a nivel de la promoción del tumor. Los complejos de coordinación sintetizados durante este trabajo de tesis doctoral mostraron actividad antitumoral frente a las líneas de cáncer ensayadas. La complejación mejoró la actividad antitumoral de los ligandos (efecto sinérgico). La disminución en la viabilidad celular y los cambios morfológicos observados ponen en evidencia la actividad antitumoral de los complejos sintetizados. En líneas generales la actividad es dependiente de la dosis de los compuestos y del tiempo de incubación. Los resultados de los ensayos de generación intracelular de ROS (con y sin agregado de los agentes antioxidantes) sugieren que el mecanismo de acción antitumoral en todos los casos está asociado al estrés oxidativo generado por el agregado de los compuestos, los que mostraron actividad pro-oxidante en las células tumorales. Estos hallazgos sugieren que los complejos sintetizados podrían ser candidatos para el tratamiento del cáncer.Además de las propiedades biológicas y toxicológicas, es necesario estudiar la biodisponibilidad de las moléculas nuevas. Como la albúmina sérica es la proteína más abundante en el plasma sanguíneo e interviene en el transporte y disposición de fármacos, se estudió la interacción de los complejos VO/Baic y VO/Api con la ASB. Dicha interacción se produce de manera espontánea y al mismo tiempo reversible indicando que los dos complejos podrían ser transportados por la ASB hasta el sitio de acción en el que van a ejercer su actividad farmacológica (antioxidante, antitumoral, etc). Para el complejo de Cu/5-HTP no pudo medirse la interacción por técnicas fluorométricas debido a la interferencia que el espectro de fluorescencia del ligando produce sobre la banda caraterística de la albúmina.Tomados en conjunto, los resultados indican que la modificación estructural de compuestos antioxidantes por complejación con iones metálicos de transición resultó en la generación de candidatos prometedores como nuevos agentes con potencial actividad anticancerígena. Los aportes al conocimiento científico de la química bioinorgánica generados durante el desarrollo de esta tesis doctoral pueden dar lugar a nuevas líneas de investigación.