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    Museu da Misericórdia, Museu da Cidade?

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    SIAM. Series Iberoamericanas de Museología. Año 3, Vol.

    Impacto da estimulação transcraniana por corrente contínua (ETCC) em ratos wistar machos submetidos a um modelo de dor crônica e / ou exposição ao álcool

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    Dor crônica e o uso nocivo do álcool representam um problema de saúde pública mundial, com altas prevalências, redução da qualidade de vida e elevados custos sociais e econômicos. Ambas as doenças resultam de processos mal adaptativos no sistema nervoso e as inter-relações entre a dor e o consumo de álcool são consideradas de natureza bidirecional. Mecanismos complexos envolvendo processos neuroplásticos são intrinsicamente ligados e a ineficácia das terapias atuais para o tratamento de dor crônica e do uso nocivo do álcool, pelo menos em parte, resulta da pouca compreensão científica para os processos envolvidos em cada uma dessas condições, assim como na associação delas. Por outro lado, as técnicas neuromodulatórias, como a estimulação transcraniana por corrente contínua (ETCC, ou tDCS, da sigla em inglês), atuam por múltiplos mecanismos de ação e apresentam poucos efeitos adversos, sendo promissoras abordagens terapêuticas. Considerando a relevância do tema, esta tese, composta por 3 manuscritos científicos (artigo 1 – publicado, artigo 2 – submetido, artigo 3 – submetido), teve como objetivo avaliar o efeito do tratamento repetido com a ETCC sobre parâmetros comportamentais e neurais em ratos machos adultos submetidos ao modelo animal de dor neuropática crônica e / ou exposição involuntária ou voluntária ao álcool (dependendo do experimento). Foram desenvolvidos 2 experimentos, sendo em ambos, utilizado o modelo de dor neuropática pela constrição do nervo isquiático (CCI, da sigla em inglês). No primeiro experimento (artigos 1 e 2), os animais dos grupos que receberam álcool, foram tratados 1 vez ao dia, durante 15 dias por gavagem e foram divididos em 5 grupos: controle (CT), dor neuropática (NP), dor neuropática + ETCC (NPtDCS), dor neuropática + álcool (NPAL), dor neuropática + álcool + ETCC (NPALtDCS). No segundo experimento (artigo 3), os animais foram expostos ao consumo de álcool de forma voluntaria junto à água de beber, podendo optar por uma de duas garrafas, e foram divididos em 6 grupos: controle (CT), dor neuropática + shamETCC (NP), dor neuropática + álcool (NPAL), álcool + shamETCC (AL), álcool + ETCC Impacto da Estimulação Transcraniana por Corrente Contínua (ETCC) em ratos Wistar machos submetidos a um modelo de dor crônica e/ou à exposição ao álcool. (ALtDCS) , dor neuropática + álcool + ETCC (NPALtDCS). No artigo 1 foram avaliados a hiperalgesia térmica e os níveis de NGF, IL-10, IL-1 α e IL-1 β em córtex e tronco encefálico; no artigo 2 foram avaliados o comportamento do tipo ansioso e os níveis centrais de IL-1 α e IL-1 β (hipocampo, estriado, cerebelo e medula espinhal), RNA mensageiro da Il1a e IL1b em cerebelo, hipocampo e medula espinhal; e imunorreatividade de neuropeptídeo Y (NPY) em hipotálamo; e o artigo 3 avaliou consumo de álcool, imunorreatividade de NPY em córtex pré-frontal (CPF), amígdala e estriado, e BDNF, NGF, IL-10,e IL-6 em cerebelo e estriado. Os ratos com CCI apresentaram hiperalgesia térmica que foi revertida pelo tratamento com ETCC, e a ação da ETCC foi retardada pela abstinência ao álcool. Além disso, a CCI induziu um progressivo aumento no consumo de álcool que foi reduzido ao longo do tempo pelo tratamento com a ETCC. Tanto o CCI quanto a exposição ao álcool induziram a comportamentos do tipo ansioso, que foram revertidos pela ETCC. Dor neuropática crônica, exposição ativa ou passiva ao álcool e o tratamento com ETCC modularam a imunorreatividade central do NPY, os níveis centrais de IL-1α, IL-1ß e IL-10 e de NGF; aumentaram expressão de Il1a e Il1b em medula espinhal e de Il1b em cerebelo. CCI e / ou ETCC reduziram os níveis de BDNF no estriado. ETCC aumentou os níveis cerebelares de IL-6 e IL-10. CCI e / ou exposição ao tDCS reduziram os níveis de IL-1α no estriado e ratos expostos a associação de CCI, álcool e ETCC apresentaram um aumento nos níveis de IL-1α em hipocampo. Concluindo, nossos resultados sugerem a ETCC como uma ferramenta promissora no tratamento de quadros de dor crônica e do uso nocivo do álcool. Neste sentido esta tese aumenta a compreensão neurobiológica relacionada ao paradigma da associação das duas doenças e dos mecanismos envolvidos no tratamento com a ETCC. É importante salientar o aspecto translacional, pois tratamentos não farmacológicos como a ETCC são importantes ferramentas na terapia de transtornos que envolvam neurocircuitos complexos, como processos de dor crônica e abuso de álcool.Chronic pain and harmful use of alcohol represent a worldwide public health problem, with high prevalence, reduced quality of life and high social and economic costs. Both diseases result from maladaptive processes in the nervous system and the interrelationships between pain and alcohol consumption are considered bidirectional in nature. Complex mechanisms involving neuroplastic processes are intricately linked and the ineffectiveness of current therapies for the treatment of chronic pain and the harmful use of alcohol, at least in part, results from little scientific understanding of the processes involved in each of these conditions, as well as in their association. On the other hand, neuromodulatory techniques, such as transcranial direct current stimulation (tDCS), act by multiple mechanisms and have few adverse effects, being promising therapeutic approaches. Considering the relevance of the theme, this doctoral dissertation, composed of 3 scientific manuscripts (article 1 - published, article 2 - in preparation, article 3 - submitted), aimed to evaluate the effect of repeated treatment with tDCS on behavioral and neural parameters in adult male rats submitted to the animal model of chronic neuropathic pain and / or forced or voluntary exposure to alcohol (depending on the experiment). Two experiments were developed, and both used the neuropathic pain model due to sciatic nerve constriction (CCI). In the first experiment (articles 1 and 2), the animals in the groups that received alcohol were treated once a day, during 15 days by gavage and were assigned to one of 5 groups: control (CT), neuropathic pain (NP), neuropathic pain + tDCS (NPtDCS), neuropathic pain + alcohol (NPAL), neuropathic pain + alcohol + tDCS (NPALtDCS). In the second experiment (article 3), the animals were voluntarily exposed to alcohol consumption, in which alcohol and water were offered in separate bottles, and rats were assigned to one of 6 groups: control (CT), neuropathic pain + shamtDCS (NP), neuropathic pain + alcohol (NPAL), alcohol + shamtDCS (AL), alcohol + tDCS (ALtDCS), neuropathic pain + alcohol + tDCS (NPALtDCS). In article 1, thermal hyperalgesia and the levels of NGF, IL-10, IL-1α and IL-1β Impacto da Estimulação Transcraniana por Corrente Contínua (ETCC) em ratos Wistar machos submetidos a um modelo de dor crônica e/ou à exposição ao álcool. in the cortex and brain stem were evaluated. In article 2, anxious-like behavior and central levels of IL-1α and IL-1β (hippocampus, striatum, cerebellum and spinal cord), mRNA of Il1a and Il1b in cerebellum, hippocampus and spinal cord were evaluated, and NPY immunoreactivity in hypothalamus. Finally, in article 3 alcohol consumption, NPY immunoreactivity in PFC, amygdala and striatum, and BDNF, NGF, IL-10, and IL-6 in cerebellum and striatum were assessed. The rats with CCI showed thermal hyperalgesia that was reversed by treatment with tDCS, and the action of tDCS was delayed by alcohol withdrawal. In addition, CCI induced a progressive increase in alcohol consumption that was reduced over time by treatment with tDCS. Both the CCI and exposure to alcohol induced anxiety-like behaviors, which were reversed by the tDCS. Chronic neuropathic pain, active or passive exposure to alcohol and treatment with tDCS modulated the central immunoreactivity of NPY, the central levels of IL-1α, IL-1ß, IL-10 and NGF, and increased the expression of Il1a and Il1b in the spinal cord and Il1b in the cerebellum. CCI and / or tDCS reduced the levels of BDNF in the striatum. tDCS increased the cerebellar levels of IL-6 and IL-10. CCI and / or exposure to tDCS reduced levels of IL-1α in the striatum and rats exposed to the association of CCI, alcohol and tDCS showed an increase in IL-1α levels in the hippocampus. In conclusion, our results suggest tDCS as a promising tool for the treatment of chronic pain and of harmful alcohol use. In this sense, this dissertation increases the neurobiological understanding related to the paradigm of the association of the two diseases and the mechanisms involved in the treatment with tDCS. It is important to highlight the translational aspect, since non-pharmacological treatments such as tDCS are important tools in the treatment of disorders involving complex neurocircuits, such as chronic pain processes and alcohol abuse

    Influence of foot alignment in anticipatory postural adjustments in children with cerebral palsy

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    The difficulty in the organization of anticipatory postural adjustments (APAs) is often associated with lack of postural control (PC) in children/young people with motor spastic hemiplegia, resulting from cerebral palsy (CP). Biomechanical changes of the tibiotarsal and foot characteristics are commonly observed in these children/young people and influence the PC as a wholeinfo:eu-repo/semantics/publishedVersio

    Polyphenol metabolite pyrogallol-o-sulfate decreases microglial activation and vegf in retinal pigment epithelium cells and diabetic mouse retina

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    Funding Information: The authors acknowledge Fundacao para a Ciencia e Tecnologia for funding (PD/BD/114251/2016 scholarship to D.F. Santos; EXPL-BIM-MEC-1433-2013; PTDC/BTM/ORG/28121/2017 grants to G.A.Silva) and iNOVA4Health ? UIDB/Multi/04462/2020, a program financially supported by Funda??o para a Ci?ncia e Tecnologia/Ministerio da Educacao e Ciencia through national funds and co-funded by FEDER under the PT2020 Partnership Agreement, is also acknowledged. C.N.S. also acknowledges the European Research Council (ERC) under the European Union?s Horizon 2020 Research and Innovation Programme under Grant Agreement No. 804229. Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.(Poly)phenol-derived metabolites are small molecules resulting from (poly)phenol metab-olization after ingestion that can be found in circulation. In the last decade, studies on the impact of (poly)phenol properties in health and cellular metabolism accumulated evidence that (poly)phenols are beneficial against human diseases. Diabetic retinopathy (DR) is characterized by inflammation and neovascularization and targeting these is of therapeutic interest. We aimed to study the effect of pyrogallol-O-sulfate (Pyr-s) metabolite in the expression of proteins involved in retinal glial acti-vation, neovascularization, and glucose transport. The expression of PEDF, VEGF, and GLUT-1 were analyzed upon pyrogallol-O-sulfate treatment in RPE cells under high glucose and hypoxia. To test its effect on a diabetic mouse model, Ins2Akita mice were subjected to a single intraocular injection of the metabolite and the expression of PEDF, VEGF, GLUT-1, Iba1, or GFAP measured in the neural retina and/or retinal pigment epithelium (RPE), two weeks after treatment. We observed a significant decrease in the expression of pro-angiogenic VEGF in RPE cells. Moreover, pyrogallol-O-sulfate significantly decreased the expression of microglial marker Iba1 in the diabetic retina at different stages of disease progression. These results highlight the potential pyrogallol-O-sulfate metabolite as a preventive approach towards DR progression, targeting molecules involved in both inflammation and neovascularization.publishersversionpublishe

    An assessment of geotubes performance in coastal protection

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    The Ofir spit is located at the estuary of Cavado River (NW coast of Portugal), and is the natural protection of Esposende city, ensuring also the navigability of the river and preventing from the maritime invasion of its estuary or the flooding of the riverine part of that city. It has been subjected to the actions of nature, especially from the Atlantic Ocean, known for its energetic regime and, more recently, those of human activities. Considering that, in Portugal, the use of geosynthetics on coastal protection is not yet a usual solution, it is relevant to investigate it, especially in this case of high-energy wave agitation. The paper presents a summary on the interventions conducted to the sandbank along time, it refers also the solution implemented as well as the monitoring campaign conducted after December 2015, discussing its results and the viability of the structure itself as a permanent solution.publishersversionpublishe

    Interplay between Erythrocyte Peroxidases and Membrane

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    Red blood cells (RBCs) are continuously exposed to oxidative stress (OS), mainly due to their primary function as oxygen carriers. Since RBC is a unique cell, without nucleus or other organelles, it presents a very special metabolism and a highly efficient antioxidant system to face OS conditions. Hemoglobin and RBC membrane are the major targets of oxidative modifications when RBC antioxidant capacity is overwhelmed. Fortunately, non-enzymatic agents, such as glutathione, and enzymatic agents, namely, several peroxidases, such as catalase, glutathione peroxidase and peroxiredoxin 2, are able to prevent OS damage. Although these peroxidases are mainly cytosolic enzymes, evidence exists about their association to the RBC membrane. So far, it appears that the relative importance of the three enzymes is related to hydrogen peroxide levels within the RBC. In this chapter, we will focus on the importance of these peroxidases in the RBC’s defense against OS mainly in the RBC cytosol and also the interplay between them and the RBC membrane. The potential role of their binding to the membrane will also be addressed
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