Simulation Model of Benthic Antarctic Assemblages (SIMBAA), link to PC-executable

SIMBAA is a spatially explicit, individual-based simulation model. It was developed to analyse the response of populations of Antarctic benthic species and their diversity to iceberg scouring. This disturbance is causing a high local mortality providing potential space for new colonisation. Traits can be attributed to model species, e.g. in terms of reproduction, dispersal, and life span. Physical disturbances can be designed in space and time, e.g. in terms of size, shape, and frequency. Environmental heterogeneity can be considered by cell-specific capacities to host a certain number of individuals. When grid cells become empty (after a disturbance event or due to natural mortality of of an individual), a lottery decides which individual from which species stored in a pool of candidates (for this cell) will recruit in that cell. After a defined period the individuals become mature and their offspring are dispersed and stored in the pool of candidates. The biological parameters and disturbance regimes decide on how long an individual lives. Temporal development of single populations of species as well as Shannon diversity are depicted in the main window graphically and primary values are listed. Examples for simulations can be loaded and saved as sgf-files. The results are also shown in an additional window in a dimensionless area with 50 x 50 cells, which contain single individuals depicted as circles; their colour indicates the assignment to the self-designed model species and the size represents their age. Dominant species per cell and disturbed areas can also be depicted. Output of simulation runs can be saved as images, which can be assembled to video-clips by standard computer programs (see GIF-examples of which "Demo 1" represents the response of the Antarctic benthos to iceberg scouring and "Demo 2" represents a simulation of a deep-sea benthic habitat).

Modelización de la respuesta de elementos estructurales lineales de vidrio plano : vigas y pilares pretensados

El vidrio se trata de un material muy apreciado en la arquitectura debido a la transparencia, característica que pocos materiales tienen. Pero, también es un material frágil, con una rotura inmediata cuando alcanza su límite elástico, sin disponer de un período plástico, que advierta de su futura rotura y permita un margen de seguridad. Por ambas razones, el vidrio se ha utilizado en arquitectura como elemento de plementería o relleno, desde tiempos antiguos, pero no como elemento estructural o portante, pese a que es un material interesante para los arquitectos para ese uso, por su característica de transparencia, ya que conseguiría la desmaterialización visual de la estructura, logrando espacios más ligeros y livianos. En cambio, si se tienen en cuenta las propiedades mecánicas del material se puede comprobar que dispone de unas características apropiadas para su uso estructural, ya que su Módulo elástico es similar al del aluminio, elemento muy utilizado en la arquitectura principalmente en las fachadas desde los últimos años, y su resistencia a compresión es muy superior incluso al hormigón armado; aunque su principal problema es su resistencia a tracción que es muy inferior a su resistencia a compresión, lo que penaliza su resistencia a flexión. En la actualidad se empieza a utilizar el vidrio como elemento portante o estructural, pero debido a su peor resistencia a flexión, se utilizan con grandes dimensiones que, a pesar de su transparencia, tienen una gran presencia. Por ello, la presente investigación pretende conseguir una reducción de las secciones de estos elementos estructurales de vidrio. Entonces, para el desarrollo de la investigación es necesario responder a una serie de preguntas fundamentales, cuyas respuestas serán el cuerpo de la investigación: 1. ¿Cuál es la finalidad de la investigación? El objetivo de esta investigación es la optimización de elementos estructurales de vidrio para su utilización en arquitectura. 2. ¿Cómo se va a realizar esa optimización? ¿Qué sistemas se van a utilizar? El sistema para realizar la optimización será la pretensión de los elementos estructurales de vidrio 3. ¿Por qué se va a utilizar la precompresión? Porque el vidrio tiene un buen comportamiento a compresión y un mal comportamiento a tracción lo que penaliza su utilización a flexión. Por medio de la precompresión se puede incrementar esta resistencia a tracción, ya que los primeros esfuerzos reducirán la compresión inicial hasta comenzar a funcionar a tracción, y por tanto aumentará su capacidad de carga. 4. ¿Con qué medios se va a comprobar y justificar ese comportamiento? Mediante simulaciones informáticas con programas de elementos finitos. 5. ¿Por qué se utilizará este método? Porque es una herramienta que arroja ventajas sobre otros métodos como los experimentales, debido a su fiabilidad, economía, rapidez y facilidad para establecer distintos casos. 6. ¿Cómo se garantiza su fiabilidad? Mediante el contraste de resultados obtenidos con ensayos físicos realizados, garantizando de ésta manera el buen comportamiento de los programas utilizados. El presente estudio tratará de responder a todas estas preguntas, para concluir y conseguir elementos estructurales de vidrio con secciones más reducidas gracias a la introducción de la precompresión, todo ello a través de las simulaciones informáticas por medio de elementos finitos. Dentro de estas simulaciones, también se realizarán comprobaciones y comparaciones entre distintas tipologías de programas para comprobar y contrastar los resultados obtenidos, intentando analizar cuál de ellos es el más idóneo para la simulación de elementos estructurales de vidrio. ABSTRACT Glass is a material very appreciated in architecture due to its transparency, feature that just a few materials share. But it is also a brittle material with an immediate breakage when it reaches its elastic limit, without having a plastic period that provides warning of future breakage allowing a safety period. For both reasons, glass has been used in architecture as infill panels, from old times. However, it has never been used as a structural or load‐bearing element, although it is an interesting material for architects for that use: because of its transparency, structural glass makes possible the visual dematerialization of the structure, achieving lighter spaces. However, taking into account the mechanical properties of the material, it is possible to check that it has appropriate conditions for structural use: its elastic modulus is similar to that of aluminium, element widely used in architecture, especially in facades from recent years; and its compressive strength is much higher than even the one of concrete. However, its main problem consists in its tensile strength that is much lower than its compressive strength, penalizing its resistance to bending. Nowadays glass is starting to be used as a bearing or structural element, but due to its worse bending strength, elements with large dimensions must be used, with a large presence despite its transparency. Therefore this research aims to get smaller sections of these structural glass elements. For the development of this thesis, it is necessary to answer a number of fundamental questions. The answers will be the core of this work: 1. What is the purpose of the investigation? The objective of this research is the optimization of structural glass elements for its use in architecture. 2. How are you going to perform this optimization? What systems will be implemented? The system for optimization is the pre‐stress of the structural elements of glass 3. Why are you going to use the pre‐compression? Because glass has a good resistance to compression and a poor tensile behaviour, which penalizes its use in bending elements. Through the pre‐compression it is possible to increase this tensile strength, due to the initial tensile efforts reducing the pre‐stress and increasing its load capacity. 4. What are the means that you will use in order to verify and justify this behaviour? The means are based on computer simulations with finite element programs (FEM) 5. Why do you use this method? Because it is a tool which gives advantages over other methods such as experimental: its reliability, economy, quick and easy to set different cases. 6. How the reliability is guaranteed? It’s guaranteed comparing the results of the simulation with the performed physical tests, ensuring the good performance of the software. This thesis will attempt to answer all these questions, to obtain glass structural elements with smaller sections thanks to the introduction of the pre‐compression, all through computer simulations using finite elements methods. In these simulations, tests and comparisons between different types of programs will also be implemented, in order to test and compare the obtained results, trying to analyse which one is the most suitable for the simulation of structural glass elements.

Efeito da cirurgia bariátrica sobre parâmetros clínicos, laboratoriais e fatores de risco cardiovascular

Introdução - Na prevenção primária das doenças cardiovasculares, a adoção de estilo de vida saudável representa uma das estratégias mais importantes. Entretanto, baixos índices de adesão e o abandono da dieta constituem obstáculo importante ao tratamento. Neste sentido, as intervenções cirúrgicas surgiram como um mecanismo promotor da restrição alimentar e têm ganhado importância não só pelo tratamento da obesidade como também no controle dos fatores de risco cardiovascular e na possível redução da mortalidade. Através de estudos clínicos foi possível observar que estas estratégias cirúrgicas promovem profundas modificações estruturais no trato gastrointestinal gerando aumento da saciedade e da sensibilidade à insulina. Em especial para os pacientes diabéticos, por si só associados a maior risco cardiovascular, as cirurgias bariátricas seriam capazes de promover um efeito muito intenso e agudo sobre os marcadores relacionados ao desenvolvimento da aterosclerose. Um evento muito definido no tempo como uma intervenção cirúrgica pode ser muito útil para o estudo e identificação de mecanismos que ainda não estão completamente estabelecidos no processo aterosclerótico. Objetivos - Analisar o comportamento das variáveis laboratoriais, clínicas e estruturais relacionadas ao desenvolvimento e progressão da aterosclerose em indivíduos diabéticos submetidos à cirurgia bariátrica. Métodos - Foram incluídos vinte voluntários diabéticos refratários ao tratamento clínico e que apresentavam obesidade abdominal. Deste grupo, metade foi aleatoriamente selecionada para realização da cirurgia bariátrica e metade foi mantida em tratamento clínico otimizado. Todos os participantes foram submetidos a exames clínicos e bioquímicos nas mesmas ocasiões, até trinta dias antes da cirurgia, três e vinte e quatro meses após a cirurgia. Nestas ocasiões além do perfil lipídico e da glicemia, determinamos os hormônios incretínicos, adipocinas. A avaliação da quantidade de gordura epicárdica e a presença de esteatose hepática será realizada somente após dois anos de seguimento em conjunto com as demais variáveis,. Foram incluídos também 10 indivíduos saudáveis e com IMC dentro da normalidade, como parte do grupo controle. Estes indivíduos foram submetidos à coleta de sangue em dois momentos para avaliação dos mesmos metabólitos. Resultados - No momento pré-intervenção os indivíduos do grupo cirúrgico e clinico eram diferentes em relação ao IMC, Glicemia e Triglicérides, sendo assim, os resultados obtidos foram ajustados minimizando o impacto destas diferenças. Após o seguimento de 3 meses, o grupo cirúrgico apresentou redução significativa nos valores de peso, IMC (33,4 ± 2,6 vs. 27,4±2,8 kg/m2, p < 0,001), HbA1c (9,26 ± 2,12 vs. 6,18±0,63%, p < 0,001), CT (182,9 ± 45,4 vs. 139,8 ± 13 mg/dl, p < 0,001), HDL (33,1 ± 7,7 vs. 38,4 ± 10,6 mg/dL, p < 0,001), TG (369,5 ± 324,6 vs. 130,8 ± 43,1 mg/dL, p < 0,001), Pro-insulina (12.72±9,11 vs. 1,76±1,14 pM, p < 0,001), RBP-4 (9,85±2,53 vs. 7,3±1,35 ng/ml, p < 0,001) e CCK (84,8±33,2 vs. 79,9 ± 31,1, ng/ml, p < 0,001), houve também aumento significativo nos níveis de HDL-colesterol (33,1 ± 7,7 vs. 38,4 ± 10,6 mg/dL, p < 0,001), Glucagon (7,4 ± 7,9 vs. 10,2±9,7 pg/ml, p < 0,001) e FGF- 19 (74,1 ± 45,8 vs. 237,3 ± 234 pg/ml, p=0,001). Um dado interessante foi que os valores de Pro-insulina, RBP-4, HbA1c e HDL- colesterol no grupo cirúrgico atingiram valores similares àqueles do grupo controle três meses após a intervenção, sendo que o FGF-19 apresentava valor duas vezes maior do que o encontrado no grupo de indivíduos saudáveis (237 ± 234 vs. 98 ± 102,1 pg/ml). O grupo clínico não apresentou variação nas variáveis clinicas, apenas nos valores de glucagon com redução significativa no período pós-intervenção (18,1 ± 20,7 vs. 16,8 ± 18,4 pg/ml, p < 0,001). Conclusão - Concluímos que indivíduos diabéticos descompensados e refratários ao tratamento clínico, quando submetidos à cirurgia bariátrica, apresentam uma alteração profunda do ponto de vista clínico, metabólico e hormonal, em relação ao indivíduos de mesmo perfil mantidos em tratamento clínico otimizado. Esta importante alteração, observada já com três meses após a intervenção, pode representar uma importante redução do risco cardiovascular nestes indivíduos. Individualmente, a notável modificação dos valores de FGF-19 associadas à intervenção devem ser estudadas com maior profundidade para compreensão de seu significado e sua potencial utilidade como marcador ou como um dos protagonistas no mecanismo de prevenção cardiovascular

Proposta de Balanced Scorecard para auxílio ao processo de gestão estratégica da internacionalização do ensino superior: um estudo de caso em universidades públicas

A intensificação da globalização tem afetado diretamente organizações e pessoas, não é diferente quando se trata das instituições de ensino superior. Desta forma, a internacionalização do ensino superior vem se intensificando e os impulsionadores destes esforços vêm se tornado cada vez mais fortes nos últimos anos. Diante das demandas que surgem neste contexto de intensa globalização, esforços realizados em resposta a este fenômeno são empreendidos, mas muitas vezes sem o alcance dos resultados esperados. O propósito deste estudo é adaptar e propor o Balanced Scorecard (BSC) como ferramenta de auxílio ao processo de gestão da internacionalização do ensino superior às universidades públicas brasileiras. O estudo se justifica pela compreensão de que organizações precisam monitorar seus processos e resultados. Devem se esforçar para conhecer seus pontos fracos e fortes, bem como as possibilidades de correção de desvios e maximização de resultados, assim contribuindo para o alcance de seus objetivos, entende-se que uma ferramenta voltada ao auxílio das atividades relacionadas a internacionalização do ensino superior pode contribuir diretamente para a melhoria do processo. A metodologia adotada para a condução do estudo foi o estudo de caso, desenvolvido em cinco instituições públicas de ensino superior brasileiras de melhor reputação internacional, em acordo com cinco rankings internacionais. A análise dos resultados proporcionou a identificação de seis perspectivas a serem utilizadas no BSC proposto: 1. Perspectiva da mudança organizacional; 2. Perspectiva dos recursos materiais, financeiros e estruturais; 3. Perspectiva do desenvolvimento de pessoas; 4. Perspectiva da inovação curricular; 5. Perspectiva da mobilidade acadêmica e 6. Perspectiva dos stakeholders. A partir da definição destas perspectivas, apresentou-se o mapa estratégico a ser utilizado pelas universidades.

Violencia estructural: una ilustración del concepto

El término violencia estructural es aplicable en aquellas situaciones en las que se produce un daño en la satisfacción de las necesidades humanas básicas (supervivencia, bienestar, identidad o libertad) como resultado de los procesos de estratificación social, es decir, sin necesidad de formas de violencia directa. El término violencia estructural remite a la existencia de un conflicto entre dos o más grupos de una sociedad (normalmente caracterizados en términos de género, etnia, clase, nacionalidad, edad u otros) en el que el reparto, acceso o posibilidad de uso de los recursos es resuelto sistemáticamente a favor de alguna de las partes y en perjuicio de las demás, debido a los mecanismos de estratificación social. La utilidad del término violencia estructural radica en el reconocimiento de la existencia de conflicto en el uso de los recursos materiales y sociales y, como tal, es útil para entender y relacionarlo con manifestaciones de violencia directa (cuando alguno de los grupos quiere cambiar o reforzar su posición en la situación conflictiva por la vía de la fuerza) o de violencia cultural (legitimizaciones de las otras dos formas de violencia, como, por ejemplo, el racismo, sexismo, clasismo o eurocentrismo).

Europe's economic challenges and the importance of ideas and innovation. CHALLENGE EUROPE Issue 22 - Challenges and new beginnings: Priorities for the EU's new leadership, September 2014.

How will we Europeans earn our living in 20 or 30 years' time? And how can it be done, while remaining true to our values of fairness, freedom and solidarity? These fundamental questions predate the financial crisis and will still be with us once we have fully overcome it. Of all the groups in society, business leaders are probably most keenly aware of the challenge posed by globalisation. They have their finger on the pulse of global economic activity and keep alerting me that Europe is losing out. The trade unions, generally more focused on the economy's demand side, regularly call for more (public) investment. Their leadership remains highly committed to Europe but they can sense a rise of Euro-scepticism among their members. We must, and can bring these two narratives together. Yes, global change is relentless and our societies must adapt, but we can also preserve what makes Europe such a special place: a unique combination of relative prosperity, solidarity, individual freedoms, and security. This challenge was always on my mind.

Educar para a cidadania através de práticas de igualdade de género na educação pré-escolar

O presente relatório desenvolveu-se sob um trajeto de investigação-ação e consiste na descrição e reflexão de todo percurso traçado e experienciado numa sala de Jardim de Infância da rede pública da cidade de Portalegre, no âmbito do mestrado em Educação Pré-Escolar. A opção temática incidiu na Igualdade de Género, cujo interesse e curiosidade surgiram após observadas as atitudes e os comportamentos de género por parte das crianças da sala do jardim de infância. Fomentar nas crianças a igualdade de género e a mudança das representações, atitudes e comportamentos que, de alguma forma, se revelem estereotipados em função do género, implica o desenvolvimento de várias atividades com as crianças, a partir do conhecimento do grupo em articulação com o conhecimento das conceções das/os encarregados de educação e das educadoras de infância. No âmbito da metodologia utilizada, investigação-ação, o percurso vivido caracterizou-se por momentos de discussão onde valorizámos a intervenção, a pesquisa e a inovação. Alguns procedimentos serviram para a construção de saberes, incrementando o desenvolvimento profissional e pessoal, conducentes a uma ação educativa de qualidade.

Engineering stable peptide toxins by means of backbone cyclization: Stabilization of the alpha-conotoxin MII

Conotoxins (CTXs), with their exquisite specificity and potency, have recently created much excitement as drug leads. However, like most peptides, their beneficial activities may potentially be undermined by susceptibility to proteolysis in vivo. By cyclizing the alpha-CTX MII by using a range of linkers, we have engineered peptides that preserve their full activity but have greatly improved resistance to proteolytic degradation. The cyclic MII analogue containing a seven-residue linker joining the N and C termini was as active and selective as the native peptide for native and recombinant neuronal nicotinic acetylcholine receptor subtypes present in bovine chromaffin cells and expressed in Xerl oocytes, respectively. Furthermore, its resistance to proteolysis against a specific protease and in human plasma was significantly improved. More generally, to our knowledge, this report is the first on the cyclization of disulfide-rich toxins. Cyclization strategies represent an approach for stabilizing bioactive peptides while keeping their full potencies and should boost applications of peptide-based drugs in human medicine.

Language and peace

This study seeks to demonstrate how critical discourse analysis can elucidate the relationship between language and peace. It provides a view on the notion of peace put forward by peace researchers, namely that peace includes not only the absence of war or physical violence, but also the absence of structural violence. Approaching the topic from various perspectives, the volume argues that language is a factor to be considered together with social and economic factors in any examination of the social conditions and institutions that prevent the achievement of a comprehensive peace. It illustrates a framework of concepts and methodologies that offer to help guide future linguistic research in this area, and also calls for foreign language, second language and peace educators to include critical linguistic education into their curricula and describes an approach for doing so.

The environmental impacts of technical change

The thesis is concerned with relationships between profit, technology and environmental change. Existing work has concentrated on only a few questions, treated at either micro or macro levels of analysis. And there has been something of an impasse since the neoclassical and neomarxist approaches are either in direct conflict (macro level), or hardly interact (micro level). The aim of the thesis was to bypass this impasse by starting to develop a meso level of analysis that focusses on issues largely ignored in the traditional approaches - on questions about distribution. The first questions looked at were descriptive - what were the patterns of distribution over time of the variability in types and rates of environmental change, and in particular, was there any evidence of periodization? Two case studies were used to examine these issues. The first looked at environmental change in the iron and steel industry since 1700, and the second studied pollution in five industries in the basic processing sector. It was established that environmental change has been markedly periodized, with an apparently fairly regular `cycle length' of about fifty years. The second questions considered were explanatory - whether and how this periodization could be accounted for by reference to variations in aspects of profitability and technical change. In the iron and steel industry, it was found that diffusion rates and the rate of nature of innovation were periodized on the same pattern as was environmental change. And the same sort of variation was also present in the realm of profits, as evidenced by cyclical changes in output growth. Simple theoretical accounts could be given for all the empirically demonstrable links, and it was suggested that the most useful models at this meso level of analysis are provided by structural change models of economic development.

Obstacles and solutions to maximising urban biodiversity throughout the lifecycles of major developments in England

Thus far, achieving net biodiversity gains through major urban developments has been neither common nor straightforward - despite the presence of incentives, regulatory contexts, and ubiquitous practical guidance tools. A diverse set of obstructions, occurring within different spatial, temporal and actor hierarchies, are experienced by practitioners and render the realisation of maximised biodiversity, a rarity. This research aims to illuminate why this is so, and what needs to be changed to rectify the situation. To determine meaningful findings and conclusions, capable of assisting applied contexts and accommodating a diverse range of influences, a ‘systems approach’ was adopted. This approach led to the use of a multi-strategy research methodology, to identify the key obstructions and solutions to protecting and enhancing biodiversity - incorporating the following methods: action research, a questionnaire to local government ecologists, interviews and personal communications with leading players, and literature reviews. Nevertheless, ‘case studies’ are the predominant research method, the focus being a ‘nested’ case study looking at strategic issues of the largest regeneration area in Europe ‘the Thames Gateway’, and the largest individual mixeduse mega-development in the UK (at the time of planning consent) ‘Eastern Quarry 2’ - set within the Gateway. A further key case study, focussing on the Central Riverside development in Sheffield, identifies the merits of competition and partnership. The nested cases, theories and findings show that the strategic scale - generally relating to governance and prioritisation - impacts heavily upon individual development sites. It also enables the identification of various processes, mechanisms and issues at play on the individual development sites, which primarily relate to project management, planning processes, skills and transdisciplinary working, innovative urban biodiversity design capabilities, incentives, organisational cultures, and socio-ecological resilience. From these findings a way forward is mapped, spanning aspects from strategic governance to detailed project management.

Financial Inclusion of The Small and Marginal Farmers by the Banking Sector in Kerala

Financial inclusion for inclusive growth is central to the developmental philosophy of most of the nations over the past decade. It has been a priority for policy makers and regulators in financial sector development for improving access and usage of financial services to achieve comprehensive financial inclusion. The initiatives taken towards financial inclusion can promote a more effective and efficient process to achieve significant improvements in financial inclusion are to establish and achieve shared and sustainable development and growth. Realising this, an increasing number of countries are committing to promote financial inclusion, encouraged by the growing body of country level experiences (World Bank, 2012). Financial inclusion basically means, broad based growth through participation as well as sharing the benefits from the growth process along with the under privileged and marginal segments of the economy. Evidence suggests that it has substantial benefits for equitable and sustainable growth. Inclusive growth ensures that while economy grows rapidly, all segments of society are involved in this growth process, ensuring equal opportunities, devoid of any regional or sectoral disparitiesIt is widely acknowledged that the objective ofinclusive growth is accomplished through the process of financial inclusion. Financial inclusion envisages bringing everyone, irrespective of financial status, into the banking fold for the individual progress and development and thereby achieving comprehensive growth with equity

Developmental Neural Correlates of Social Interaction

Children develop in a sea of reciprocal social interaction, but their brain development is predominately studied in non-interactive contexts (e.g., viewing photographs of faces). This dissertation investigated how the developing brain supports social interaction. Specifically, novel paradigms were used to target two facets of social experience—social communication and social motivation—across three studies in children and adults. In Study 1, adults listened to short vignettes—which contained no social information—that they believed to be either prerecorded or presented over an audio-feed by a live social partner. Simply believing that speech was from a live social partner increased activation in the brain’s mentalizing network—a network involved in thinking about others’ thoughts. Study 2 extended this paradigm to middle childhood, a time of increasing social competence and social network complexity, as well as structural and functional social brain development. Results showed that, as in adults, regions of the mentalizing network were engaged by live speech. Taken together, these findings indicate that the mentalizing network may support the processing of interactive communicative cues across development. Given this established importance of social-interactive context, Study 3 examined children’s social motivation when they believed they were engaged in a computer-based chat with a peer. Children initiated interaction via sharing information about their likes and hobbies and received responses from the peer. Compared to a non-social control, in which children chatted with a computer, peer interaction increased activation in mentalizing regions and reward circuitry. Further, within mentalizing regions, responsivity to the peer increased with age. Thus, across all three studies, social cognitive regions associated with mentalizing supported real-time social interaction. In contrast, the specific social context appeared to influence both reward circuitry involvement and age-related changes in neural activity. Future studies should continue to examine how the brain supports interaction across varied real-world social contexts. In addition to illuminating typical development, understanding the neural bases of interaction will offer insight into social disabilities such as autism, where social difficulties are often most acute in interactive situations. Ultimately, to best capture human experience, social neuroscience ought to be embedded in the social world.

Potencial terapêutico de um heparinóide isolado do invertebrado marinho Litopenaeus vannamei

The occurrence of bioactive compounds in marine organisms comes awaking the interest of the pharmaceutical industry. Heparin, a sulfated polysaccharide which presence was already identified in several marine invertebrates, is very attractive due its remarkable functional versatility. Besides to intervene in blood coagulation, this molecule has a great anti-inflammatory potential. However, its strong anticoagulant activity difficult the clinical exploitation of its anti-inflammatory properties. Thus, the aims of this work were to evaluate the effect of a heparin-like compound (heparinoid), isolated from the cephalotorax of the Litopenaeus vannamei shrimp, on the inflammatory response, hemostasia and synthesis of antithrombotic heparan sulfate by endothelial cells, besides studying some aspects concerning its structure. The purified heparinoid was structurally characterized following an analytical boarding, involving electrophoresis and chromatography. The structural analysis have shown that this compound possess a high content of glucuronic acid residues and disulfated disaccharide units. In contrast to mammalian heparin, the heparinoid was incapable to stimulate the synthesis of heparan sulfate by endothelial cells in the tested concentrations, beyond to show reduced anticoagulant activity and hemorrhagic effect. In a model of acute inflammation, the compound isolated from the shrimp reduced more than 50% of the cellular infiltration. Besides reduce the activity of MMP-9 and proMMP-2 of the peritoneal lavage of inflamed animals, the heparinoid also reduced the activity of MMP-9 secreted by activated human leukocytes. These results demonstrate the potential of heparinoid from L. vannamei to intervene in the inflammatory response. For possessing reduced anticoagulant activity and hemorrhagic effect, this compound can serve as a structural model to direct the development of more specific therapeutical agents to the treatment of inflammatory diseases

Efeito anti-inflamatório do heparinóide isolado do camarão Litopenaeus vannamei sobre a peritonite aguda

In recent years the heparin has been the subject of several studies that aim to expand its use as a therapeutic agent, due to its ability to modulate the activity of various proteins that play important roles in the regulation of pathophysiological processes. In several experiments and preclinical trials, heparin has demonstrated an anti-inflammatory role. However, its clinical use is limited, due to its strong anticoagulant activity and hemorrhagic complications. For this reason, considerable efforts have been employed in discovery of heparin analogous (heparinoid) with reduced side effects, that retain the anti-inflammatory properties of heparin. In this context, a heparinoid obtained from the head of Litopenaeus vannamei shrimp, which presents a structural similarity to heparin, showed, in previous studies, anti-inflammatory activity in a model of acute peritonitis with reduced anticoagulant effect in vitro and low hemorrhagic activity. Thus, the present work had as objective to evaluate the effect the heparinoid of the cephalothorax of gray shrimp on the acute inflammatory response in different times (3 or 6 hours after the induction of inflammatory stimulus), using the model of acute peritonitis induced in mice. It was also analyzed the HL effect over the activity of elastase, an enzyme involved in leukocyte recruitment. Furthermore to check if the different doses of heparin and heparinoid change the hemostatic balance in vivo, was assessed the effect of these compounds on the plasma clotting time in animals submitted to inflammation. The results show that in 3 hours, all doses of heparinoid were able to prevent efficiently in the acute inflammatory process without any anticoagulant effects, unlike the extrapolation dose of heparin, which has induced a large hemorrhage due its high anticoagulant activity. However, 6 hours after induction of inflammation, only the dosages of 0.1 and 1.0 μg/Kg of heparin and 1.0 μg/Kg of heparinoid kept anti-migratory effect, without changing of the hemostatic balance. These results indicate that the anti-migratory effect of theses compounds depends on the dosage and time of inflammatory stimulus. The HL and heparin were also able to inhibit the activity of the enzyme elastase. The discovery of this bioactive compound in the cephalothorax of shrimps can arouse great interest in biotechnology, since this compound could be useful as a structural model interesting for the development of new therapeutic agents for peritonitis