Tonin in rat heart with experimental hypertrophy

The present study was undertaken to determine tonin expression and activity in rat heart presenting isoproterenol-induced hypertrophy. Renin, angiotensin-converting enzyme (ACE), and angiotensinogen (AG) expression were also determined. Wistar rats were treated with isoproterenol for 7 days (5 mg.kg(-1).day(-1) sc). for untreated animals, the levels of tonin-specific activity in the atrium were 2.6- and 5.5-fold higher than those of the left and right ventricle, respectively. After treatment, the levels of tonin-specific activity increased twofold in the atrium but did not change in the ventricles. Renin expression was not detectable in these structures, and ACE expression levels did not change with treatment. AG expression was detected in the left ventricle at very low levels compared with the atrium and increased significantly only in the hypertrophied atrium (1.8-fold). Tonin mRNA was not detected in the ventricle but was found at low levels in the atrium, which increased after isoproterenol treatment. Our results permit us to conclude that tonin may play a role in the process of heart hypertrophy in the rat.Univ Fed Minas Gerais, Inst Biol Sci, Dept Physiol & Biophys, BR-31270901 Belo Horizonte, MG, BrazilUniv Fed Minas Gerais, Inst Biol Sci, Dept Parasitol, BR-31270901 Belo Horizonte, MG, BrazilUniversidade Federal de São Paulo, Dept Biophys, BR-04023062 São Paulo, BrazilUniv Mogi das Cruzes, BR-08789091 Mogi Das Cruzes, BrazilMax Delbruck Ctr Mol Med, D-13092 Berlin, GermanyUniversidade Federal de São Paulo, Dept Biophys, BR-04023062 São Paulo, BrazilWeb of Scienc

Kinin B2 receptor regulates chemokines CCL2 and CCL5 expression and modulates leukocyte recruitment and pathology in experimental autoimmune encephalomyelitis (EAE) in mice

BACKGROUND: Kinins are important mediators of inflammation and act through stimulation of two receptor subtypes, B1 and B2. Leukocyte infiltration contributes to the pathogenesis of autoimmune inflammation in the central nervous system (CNS), occurring not only in multiple sclerosis (MS) but also in experimental autoimmune encephalomyelitis (EAE). We have previously shown that the chemokines CCL2 and CCL5 play an important role in the adhesion of leukocytes to the brain microcirculation in EAE. The aim of the present study was to evaluate the relevance of B2 receptors to leukocyte-endothelium interactions in the cerebral microcirculation, and its participation in CNS inflammation in the experimental model of myelin-oligodendrocyte-glycoprotein (MOG)35-55-induced EAE in mice. METHODS: In order to evaluate the role of B2 receptor in the cerebral microvasculature we used wild-type (WT) and kinin B2 receptor knockout (B2-/-) mice subjected to MOG35-55-induced EAE. Intravital microscopy was used to investigate leukocyte recruitment on pial matter vessels in B2-/- and WT EAE mice. Histological documentation of inflammatory infiltrates in brain and spinal cords was correlated with intravital findings. The expression of CCL5 and CCL2 in cerebral tissue was assessed by ELISA. RESULTS: Clinical parameters of disease were reduced in B2-/- mice in comparison to wild type EAE mice. At day 14 after EAE induction, there was a significant decrease in the number of adherent leukocytes, a reduction of cerebral CCL5 and CCL2 expressions, and smaller inflammatory and degenerative changes in B2-/- mice when compared to WT. CONCLUSION: Our results suggest that B2 receptors have two major effects in the control of EAE severity: (i) B2 regulates the expression of chemokines, including CCL2 and CCL5, and (ii) B2 modulates leukocyte recruitment and inflammatory lesions in the CNS

Leucurogin, a new recombinant disintegrin cloned from Bothrops leucurus (white-tailed-jararaca) with potent activity upon platelet aggregation and tumor growth

Disintegrins and disintegrins-like proteins are able to inhibit platelet aggregation and integrin-mediated cell adhesion. the aim of this study was to produce one disintegrin-like cloned from Bothrops leucurus venom gland and to characterize it regarding biological activity. the recombinant protein was purified by one step procedure involving anion-exchange chromatography (DEAE-cellulose) and presented a molecular mass of 10.4 kDa. the purified protein was able to inhibit platelet aggregation induced by collagen (IC(50) = 0.65 mu M) and to inhibit growth of Ehrlich tumor implanted in mice by more than 50% after 7 days administration of 10 mu g/day. No effects were observed upon adenosine 5'diphosphate (ADP)-and arachidonic acid (AA)-induced platelet aggregation. the recombinant protein was recognized by an antibody specific for jararhagin one metalloproteinase isolated from Bothrops jararaca venom, and therefore it was named leucurogin. Anti-angiogenesis effect of leucurogin was evaluated by the sponge implant model. After 7 days administration leucurogin inhibited, in a dose dependent way, the vascularization process in the sponge. Leucurogin represents a new biotechnological tool to understand biological processes where disintegrins-like are involved and may help to characterize integrins that can be involved in development and progression of malignant cells. (C) 2011 Elsevier B.V. All rights reserved.FAEPFundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Univ Fed Minas Gerais, Inst Ciencias Biol, BR-31270901 Belo Horizonte, MG, BrazilUniv Mogi das Cruzes, Ctr Civ, BR-08780911 São Paulo, BrazilProteobras Desenvolvimento Biotecnol Ltda, BR-13069310 São Paulo, BrazilFundacao Ezequiel Dias, BR-30510010 Belo Horizonte, MG, BrazilUniversidade Federal de São Paulo, Dept Biofis, BR-04023062 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Biofis, BR-04023062 São Paulo, BrazilWeb of Scienc

Dark Tourism in the land of Sunshine: An intercultural business model for the routes of death and disaster in Portugal

The main goal of this dissertation is the creation and subsequent implementation of dark tourism routes in Portugal, following a business model that already exists in other cultures. This typology of tourism is an extension of cultural tourism and is classified by the search for places where once disasters, suffering and death occurred. Thus, concentration camps, inactive prisons, serial killers' homes, cemeteries, and all other places that fit into the patterns of death, tragedy and suffering can be considered dark tourism sites. In Portugal, there are some places associated with the practice of dark tourism, although this type of business is not yet sufficiently explored. Therefore, this dissertation intends to use the country’s heritage, which is one of the levers for promoting tourism and an important factor of development, thus justifying the elaboration of a conceptual map associated with tourism. With the delineation of routes in this dissertation, we intend not only to introduce this market niche in the country, but also to contribute innovatively to the tourist dynamics, in order to blur the existing seasonality, which arises from the demand for sun and sea tourism. With the conception and design of these routes, we intend to make a pioneering contribution to the creation of a platform to promote dark tourism in the country. The creation of a business model and a marketing plan results from the need to assess the viability of the implementation of this project, and to discuss the best strategies for implementing it

Reduced nerve injury-induced neuropathic pain in kinin B1 receptor knock-out mice

Injury to peripheral nerves often results in a persistent neuropathic pain condition that is characterized by spontaneous pain, allodynia, and hyperalgesia. Nerve injury is accompanied by a local inflammatory reaction in which nerve-associated and immune cells release several pronociceptive mediators. Kinin B1 receptors are rarely expressed in nontraumatized tissues, but they can be expressed after tissue injury. Because B1 receptors mediate chronic inflammatory painful processes, we studied their participation in neuropathic pain using receptor gene-deleted mice. In the absence of neuropathy, we found no difference in the paw-withdrawal responses to thermal or mechanical stimulation between B1 receptor knock-out mice and 129/J wild-type mice. Partial ligation of the sciatic nerve in the wild-type mouse produced a profound and long-lasting decrease in thermal and mechanical thresholds in the paw ipsilateral to nerve lesion. Threshold changed neither in the sham-operated animals nor in the paw contralateral to lesion. Ablation of the gene for the B1 receptor resulted in a significant reduction in early stages of mechanical allodynia and thermal hyperalgesia. Furthermore, systemic treatment with the B1 selective receptor antagonist des-Arg9-[Leu8]-bradykinin reduced the established mechanical allodynia observed 7-28 d after nerve lesion in wild-type mice. Partial sciatic nerve ligation induced an upregulation in B1 receptor mRNA in ipsilateral paw, sciatic nerve, and spinal cord of wild-type mice. Together, kinin B1 receptor activation seems to be essential to neuropathic pain development, suggesting that an oral-selective B1 receptor antagonist might have therapeutic potential in the management of chronic pain

The use of the press as a motivating factor to support the work in mathematics

Recogemos en este artículo de forma condensada una síntesis de las posibilidades de aplicación de la prensa en el área de Matemáticas, en el que hacemos un estudio de Matemáticas y Prensa ¿por qué?, analizamos la posibilidad de uso del periódico en el aula, haciendo unas consideraciones sobre la enseñanza del aprendizaje de matemáticas, viendo los recursos que ofrece la prensa. En una segunda fase presentamos nuestra propuesta junto con las pretensiones, desarrollo de capacidades aplicables a la resolución de situaciones problemáticas y el trabajo previo. Finalizamos con el trabajo en el aula, vaciado de un periódico y un ejemplo de interdisciplinariedad con el área de Lenguaje.In this article we summarize a summary of the possibilities of applying the press in the area of Mathematics, in which we do a study of Mathematics and the Press, why?, We analyze the possibility of using the newspaper in the classroom, doing some considerations about the teaching of mathematics learning, seeing the resources offered by the press. In a second phase we present our proposal together with the pretensions, development of capacities applicable to the resolution of problematic situations and the previous work. We finish with the work in the classroom, emptying a newspaper and an example of interdisciplinarity with the area of Language.peerReviewe

Informe de evaluación de Escritura en sexto grado 2013 ¿Qué logros de aprendizaje en Escritura muestran los estudiantes al finalizar la primaria?

Además de evaluar el desempeño de los estudiantes peruanos en comprensión de textos, la Evaluación Muestral (EM), aplicada a fines del 2013, incluyó una prueba de producción de textos escritos, cuyo objetivo es informar cuánto han logrado aprender nuestros estudiantes de sexto grado de primaria en la competencia de escritura. ¿Pueden organizar coherentemente sus ideas en un texto? ¿Pueden producir un cuento proporcionando detalles sobre los personajes y sus acciones? ¿Pueden ajustar sus escritos a las exigencias de la situación comunicativa? A partir de los resultados de la prueba, este informe apunta a responder estas y otras preguntas sobre el desempeño de los estudiantes de sexto grado de primaria al momento de escribir textos narrativos, así como a proporcionar recomendaciones para ayudarlos a mejorar su producción escrita. La prueba de escritura se aplicó a 4327 estudiantes, pertenecientes a 357 escuelas de todo el Perú. Las características de la muestra evaluada permiten proporcionar resultados representativos a nivel nacional y asegurar estimaciones confiables. En otras palabras, los resultados que se reportan en este documento revelan la situación de los niños de sexto de primaria del Perú al escribir textos narrativos, en particular, cuentos. Este informe consta de ocho capítulos. El primero presenta la manera cómo se concibe el aprendizaje de la escritura en la EM. El segundo y tercero señalan las características generales de la evaluación. El cuarto informa cómo se establecieron los niveles de logro para reportar los resultados: Nivel 3, Nivel 2 y Nivel 1. A continuación, el quinto capítulo muestra los resultados nacionales y se describen los niveles de logro. Estas descripciones van acompañadas de ejemplos comentados con el propósito de que el lector pueda tener una aproximación más clara a cada uno de los niveles. El sexto capítulo incluye otros hallazgos importantes obtenidos en la EM, tales como los resultados por área (urbana o rural), gestión (estatal o no estatal) y género. El sétimo presenta información complementaria a los resultados relacionada con el tratamiento que se dio a las diferentes variedades del castellano manejadas por los estudiantes al momento de evaluar sus textos. Finalmente, se presentan conclusiones y recomendaciones pedagógicas

O processo de internacionalização do grupo Casais: sequencial ou irregular?

O fenómeno da globalização, a liberalização dos mercados e a eliminação de “fronteiras” entre países colocaram novos desafios às empresas portuguesas, com muitas delas a encarar esses desafios como oportunidades. Desta forma, estas acabam por ponderar a exploração de mercados externos, iniciando a internacionalização. À medida que o número de empresas que se internacionalizaram aumenta, a relevância dos estudos referentes aos processos de internacionalização também aumenta. Utilizando a metodologia de estudo de caso, procedemos à análise do processo de internacionalização do Grupo Casais, uma empresa portuguesa do setor da Construção e Engenharia. Após estudar o processo, chegamos à conclusão de que o processo de internacionalização do Grupo Casais é sequencial, estando intimamente ligado à Teoria das Redes devido à presença da organização em redes que facilitam o acesso à informação sobre os mercados externos e a entrada nos mesmos.The phenomenon of globalization, the liberalization of markets and the elimination of “borders” between countries have set new challenges for Portuguese companies, with many of them seeing these challenges as opportunities. So they end up considering the exploration of foreign markets, starting the internationalization process. As the number of companies that have internationalized increases, the relevance of studies regarding internationalization processes also increases. Using the case study methodology, we proceeded to analyze the internationalization process of the Grupo Casais, a Portuguese company in the Construction and Engineering sector. After studying the process, we have concluded that the internationalization process of the Grupo Casais Casais is gradual, being closely linked to the Networks Theory due to the presence of the company in networks that facilitate access to and information about foreign markets

Brabykinin B1 Receptor Antagonism Is Beneficial in Renal Ischemia-Reperfusion Injury

Previously we have demonstrated that bradykinin B1 receptor deficient mice (B1KO) were protected against renal ischemia and reperfusion injury (IRI). Here, we aimed to analyze the effect of B1 antagonism on renal IRI and to study whether B1R knockout or antagonism could modulate the renal expression of pro and anti-inflammatory molecules. To this end, mice were subjected to 45 minutes ischemia and reperfused at 4, 24, 48 and 120 hours. Wild-type mice were treated intra-peritoneally with antagonists of either B1 (R-954, 200 µg/kg) or B2 receptor (HOE140, 200 µg/kg) 30 minutes prior to ischemia. Blood samples were collected to ascertain serum creatinine level, and kidneys were harvested for gene transcript analyses by real-time PCR. Herein, B1R antagonism (R-954) was able to decrease serum creatinine levels, whereas B2R antagonism had no effect. The protection seen under B1R deletion or antagonism was associated with an increased expression of GATA-3, IL-4 and IL-10 and a decreased T-bet and IL-1β transcription. Moreover, treatment with R-954 resulted in lower MCP-1, and higher HO-1 expression. Our results demonstrated that bradykinin B1R antagonism is beneficial in renal IRI