279 research outputs found
A novel mechanism of inhibition of high-voltage activated calcium channels by a-conotoxins contributes to relief of nerve injury-induced neuropathic pain
No full textalpha-Conotoxins that are thought to act as antagonists of nicotinic acetylcholine receptors (nAChRs) containing alpha 3-subunits are efficacious in several preclinical models of chronic pain. Potent interactions of Vc1.1 with other targets have suggested that the pain-relieving actions of alpha-conotoxins might be mediated by either alpha 9 alpha 10 nAChRs or a novel GABA(B) receptor-mediated inhibition of N-type calcium channels. Here we establish that three alpha-conotoxins, Vc1.1, AuIB and MII have distinct selectivity profiles for these three potential targets. Their potencies after intramuscular administration were then determined for reversal of allodynia produced by partial nerve ligation in rats. Vc1.1, which potently inhibits alpha 9 alpha 10 nAChRs and GABA(B)/Ca(2+) channels but weakly blocks alpha 3 beta 2 and alpha 3 beta 4 nAChRs, produced potent, long-lasting reversal of allodynia that were prevented by pre-treatment with the GABA(B) receptor antagonist, SCH50911. alpha-Conotoxin AuIB, a weak alpha 3 beta 4 nAChR antagonist, inhibited GABA(B)/Ca(2+) channels but did not act on alpha 9 alpha 10 nAChRs. AuIB also produced reversal of allodynia. These findings suggest that GABA(B) receptor-dependent inhibition of N-type Ca(2+) channels can mediate the sustained anti-allodynic actions of some alpha-conotoxins. However, MII, a potent alpha 3 beta 2 nAChR antagonist but inactive on alpha 9 alpha 10 and alpha 3 beta 4 nAChRs and GABA(B)/Ca(2+) channels, was demonstrated to have short-acting anti-allodynic action. This suggests that alpha 3 beta 2 nAChRs may also contribute to reversal of allodynia. Together, these findings suggest that inhibition of alpha 9 alpha 10 nAChR is neither necessary nor sufficient for relief of allodynia and establish that alpha-conotoxins selective for GABA(B) receptor-dependent inhibition of N-type Ca(2+) channels relieve allodynia, and could therefore be developed to manage chronic pain. (C) 2010 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved
Arte ou não: uma abordagem de aspectos relacionados à formação de paradigmas estéticos do público
No full textDissertação (mestrado) - Universidade Federal de Santa Catarina, Centro Tecnológico. Programa de Pós-Graduação em Engenharia de Produção.A freqüência com que encontramos distribuídas por toda a cidade, em espaços os mais diversos, obras denominadas de 'artes plásticas', fez despertar o interesse quanto a alguns aspectos que se relacionam com esse fenômeno, especialmente o fato de que muitas dessas imagens não são arte, mas aparentam ser. O olhar do público, em sua grande maioria, é despreparado, embora cada vez mais autônomo e aberto; no entanto, totalmente dominado pela cultura de massa, industrializada e mercantilizada, distancia-se cada vez mais dos paradigmas estéticos propostos durante o processo de educação formal, o qual, também, nem sempre é garantia de uma preparação adequada. Caos visual é o que esse fenômeno vem provocando. Conscientes de que a situação é alarmante, dedicamo-nos a desenvolver este estudo. Para delinear nossa pressuposição inicial, buscamos traçar um perfil do público freqüentador de mostras de arte, moderna e contemporânea, realizadas no Museu de Arte de Santa Catarina (MASC), em Florianópolis, entre 2000 e 2002, bem como levantar conceitos de arte contemporânea adotados por esse público a partir de seis amostras. Ao identificar fontes formadoras de conceitos estéticos, verificamos, junto a esses segmentos formadores de opinião, como curadores de espaços públicos, quais os critérios adotados para a seleção de obras de arte a serem expostas ao olhar do público como sendo arte. Para fundamentar a pesquisa, buscamos conhecimentos anteriores relacionados com o problema, quais sejam: a arte como objeto de pesquisa, destacando-se a obra de arte na contemporaneidade; a estética entre o autor e o público; as interpretações, os sentidos e a percepção. Analisamos posturas assumidas por formadores de opinião, selecionando, entre eles, o museu, a crítica, a curadoria, o mercado de arte, o espaço urbano, o uso público dos espaços privados e o papel da mídia. Na pesquisa de campo, mediante questionários, analisamos duas amostras de públicos variados de duas exposições distintas: a primeira em 2000, intitulada "Muito além de Marte: o universo de Meyer Filho", e a segunda em 2002, denominada "Extra I". A necessidade de profissionalização do pessoal envolvido no mercado de arte ou mesmo no meio artístico, em geral, é uma das conclusões
Delta opioid receptors presynaptically regulate cutaneous mechanosensory neuron input to the spinal cord dorsal horn
No full textCutaneous mechanosensory neurons detect mechanical stimuli that generate touch and pain sensation. Although opioids are generally associated only with the control of pain, here we report that the opioid system in fact broadly regulates cutaneous mechanosensation, including touch. This function is predominantly subserved by the delta opioid receptor (DOR), which is expressed by myelinated mechanoreceptors that form Meissner corpuscles, Merkel cell-neurite complexes, and circumferential hair follicle endings. These afferents also include a small population of CGRP-expressing myelinated nociceptors that we now identify as the somatosensory neurons that coexpress mu and delta opioid receptors. We further demonstrate that DOR activation at the central terminals of myelinated mechanoreceptors depresses synaptic input to the spinal dorsal horn, via the inhibition of voltage-gated calcium channels. Collectively our results uncover a molecular mechanism by which opioids modulate cutaneous mechanosensation and provide a rationale for targeting DOR to alleviate injury-induced mechanical hypersensitivity
Plasticity in the airway epithelium
No full text Normal cell turnover as well as the response to injury require cell proliferation and differentiation. The airway epithelium maintains these processes throughout adult life. Controlled homeostatically, cell proliferation and differentiation usually restore, as an end point, the pseudostratified architecture of the normal mucociliary epithelium. After injury, however, cell proliferation and differentiation sometimes establish, as an end point, regions of metaplastic cells. In this brief review, we have tried to summarize research findings that 1) describe the development of metaplastic lesions in morphological terms, 2) identify cells the proliferation of which forms the basis of these lesions, and 3) identify molecular changes within these cells that control development of the metaplastic phenotype. </jats:p
Core outcome domains for chronic pain clinical trials: IMMPACT recommendations
No full textObjective. To provide recommendations for the core outcome domains that should be considered by investigators conducting clinical trials of the efficacy and effectiveness of treatments for chronic pain. Development of a core set of outcome domains would facilitate comparison and pooling of data, encourage more complete reporting of outcomes, simplify the preparation and review of research proposals and manuscripts, and allow clinicians to make informed decisions regarding the risks and benefits of treatment. Methods. Under the auspices of the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT), 27 specialists from academia. governmental agencies, and the pharmaceutical industry participated in a consensus meeting and identified core outcome domains that should be considered in clinical trials of treatments for chronic pain. Conclusions. There was a consensus that chronic pain clinical trials should assess outcomes representing six core domains: (1) pain, (2) physical functioning, (3) emotional functioning, (4) participant ratings of improvement and satisfaction with treatment, (5) symptoms and adverse events, (6) participant disposition (e.g. adherence to the treatment regimen and reasons for premature withdrawal from the trial). Although consideration should be given to the assessment of each of these domains, there may be exceptions to the general recommendation to include all of these domains in chronic pain trials. When this occurs, the rationale for not including domains should be provided. It is not the intention of these recommendations that assessment of the core domains should be considered a requirement for approval of product applications by regulatory agencies or that a treatment must demonstrate statistically significant effects for all of the relevant core domains to establish evidence of its efficacy. (C) 2003 International Association for the Study of Pain
Inter-strain differences of serotonergic inhibitory pain control in inbred mice
No full textBackground: Descending inhibitory pain control contributes to the endogenous defense against chronic pain and involves noradrenergic and serotonergic systems. The clinical efficacy of antidepressants suggests that serotonin may be particularly relevant for neuropathic pain conditions. Serotonergic signaling is regulated by synthesis, metabolisms, reuptake and receptors. To address the complexity, we used inbred mouse strains, C57BL/6J, 129 Sv, DBA/2J and Balb/c, which differ in brain serotonin levels. Results: Serotonin analysis after nerve injury revealed inter-strain differences in the adaptation of descending serotonergic fibers. Upregulation of spinal cord and midbrain serotonin was apparent only in 129 Sv mice and was associated with attenuated nerve injury evoked hyperalgesia and allodynia in this strain. The increase of dorsal horn serotonin was blocked by hemisectioning of descending fibers but not by rhizotomy of primary afferents indicating a midbrain source. Para-chlorophenylalanine-mediated serotonin depletion in spinal cord and midbrain intensified pain hypersensitivity in the nerve injury model. In contrast, chronic inflammation of the hindpaw did not evoke equivalent changes in serotonin levels in the spinal cord and midbrain and nociceptive thresholds dropped in a parallel manner in all strains. Conclusion: The results suggest that chronic nerve injury evoked hypernociception may be contributed by genetic differences of descending serotonergic inhibitory control
Linguagem em carne viva: corpo, percepção, linguagem (rumo a uma semântica aberta do gesto)
No full textO artigo documenta um percurso pedagógico original, com achados, sínteses e intuições importantes na trajetória de pesquisa. Por meio de uma abordagem transdisciplinar, marcada pelo pensamento fenomenológico, descreve-se a descoberta e formalização de uma metodologia para o estudo das relações entre corpo, percepção e inguagem, tendo como atrator uma semântica do gesto. Tomando como preceitos conceituais: a) a primazia da experiência; b) uma opção pela percepção enativa, culturalmente modulada; c) uma definição de gesto; e d) a opção por uma semântica baseada no corpo, reflexões, práticas e exercícios foram propostas, resultando na elaboração de um modelo de Glossário dos Próprios Gestos.
Mentalos: um card game para ajudar na concentração de pacientes com TDAH
No full textEsta pesquisa tem como objetivo geral um jogo analógico para área médica dentro da área de psiquiatria,
contemplando seus principais fundamentos e elementos de jogos de cartas, e o seu processo de
desenvolvimento tendo como base um jogo de mistérios e enigmas. O que justifica essa investigação é
escassez de debate sobre o tema proposto, sob a visão do desenvolvimento de jogos para a saúde, apresenta
carência de jogos lúdicos na área da saúde se comparadas às outras áreas da indústria de jogos,
especialmente no Brasil. O que motiva a realização dessa pesquisa é a possibilidade de investigar alternativas
que possam contribuir para a evolução da indústria de desenvolvimento de jogos sérios no Brasil, no sentido
de incentivar o desenvolvimento de um produto educativo de jogo atualmente usado para treinamento, e que
pode ser explorado fazendo uso em centros de atendimento psiquiátrico. A presente investigação busca
responder a seguinte questão proposta: como desenvolver jogos analógicos focados para pacientes
diagnosticados com TDAH ? Considera-se a hipótese de que jogos analógicos físicos, através de sua
tecnologia antiga, é viável para o desenvolvimento de jogos de cartas no cenário da indústria seria de jogos
digitais e analógica. Optamos pela metodologia de pesquisa científica de natureza qualitativa, do tipo
descritiva, com origem de dados bibliográficos/documentais, com local de realização, uma vez que enfrenta
aspectos teóricos e empíricos, com intuito de cumprir seu objetivo geral. A revisão de estudos anteriores
relacionados ao tema proposto teve foco delimitado o período entre 1798 a 2020, contemplando livros,
artigos científicos, teses e dissertações, considerando pesquisas disponíveis nas seguintes bases online:, a)
Banco de Teses e Dissertações da Capes, b) SBGames – Simpósio Brasileiro de Games, c) Google Scholar.
d) SBEI - Simpósio Brasileiro de Informática na Educação. Também foram considerados para a revisão de
estudos anteriores, os artigos disponíveis na Scientific Electronic Library Online – SciELO, das revistas
científicas classificadas como nível A1 a A3 do Qualis-Capes na área de interdisciplinar e medicina. Os
instrumentos de coleta de dados serão execuções praticas, entrevistas e observação. Os referenciais teóricos
que sustentam esta investigação são os conceitos de jogos de tabuleiro (BELL, 1960); , jogos da área médica
(VASCONSELLOS, 2018),(CARVALHO,2018), (ARAÚJO,2018). O contexto desta investigação envolve
espaços de pesquisa, ensino e extensão das instituições onde pesquisadores parceiros atuam. Os resultados
esperados com essa pesquisa são: 1) Desenvolvimento de um jogo de cartas para TDAH tomando como
referência os estudos anteriores e referenciais teóricas abordadas; 2) O produto possa ser usado em um futuro
próximoThis research has as general objective an analogue game for the medical area within the area of
psychiatry, contemplating its main fundamentals and elements of card games, and its development
process based on a game of mysteries and riddles. What justifies this investigation is the scarcity of
debate on the proposed theme, from the point of view of the development of games for health, it
presents a lack of playful games in the health area when compared to other areas of the games
industry, especially in Brazil. What motivates this research is the possibility of investigating
alternatives that can contribute to the evolution of the serious game development industry in Brazil,
with no sense of incentive for the development of an educational game product currently used for
training, and that can be exploited using psychiatric care centers. This investigation seeks to answer
the following question: how to develop focused analog games for patients diagnosed with ADHD?
It is considered the hypothesis that physical analog games, through its old technology, is feasible for
the development of card games in the industry scenario would be digital and analog games. We
opted for the qualitative descriptive scientific research methodology, with the origin of
bibliographic / documentary data, with place of realization, since it faces theoretical and empirical
aspects, in order to fulfill its general objective. A review of previous studies related to the theme
focused on the period between 1798 to 2020, including books, scientific articles, theses and
dissertations, considering research available in the following online databases:, a) Capes Thesis and
Dissertation Bank, b) SBGames - Simpósio Brasileira de Games, c) Google Scholar. The articles
available in Scientific Electronic Library Online – SciELO,d) SBEI - Simpósio Brasileiro de
Informática na Educação from the scientific journals classified as level A1 to A3 of Qualis-Capes
in the area of interdisciplinary and medicine, were also considered for a review of previous studies.
The instruments of data collection will be practical executions, discovery and observation. The
theoretical references that support this investigation are the concepts of board games (BELL,
1960);, games in the medical field (VASCONSELLOS, 2018), (CARVALHO, 2018), (ARAÚJO,
2018). The context of this investigation involves spaces for research, teaching and extension of the
institutions where research partners work. The expected results with this research are: 1)
Development of a card game for ADHD taking as a reference the previous studies and theoretical
references addressed; 2) The product can be used in the near futur
Regulation of secretion in cultured tracheal serous cells by protein kinases A and C
No full text We recently reported that cultured gland serous cells release chondroitin sulfate proteoglycans (CSPGs) in response to beta-adrenergic agonists. In this study, we analyzed this regulatory pathway and other cellular mechanisms responsible for CSPG secretion. We show the following. 1) Isoproterenol increased CSPG secretion in a concentration-dependent manner, with maximal stimulation (50%) obtained at 10(-5) M; at this concentration, the beta-agonist also stimulated protein kinase A (PKA) by 50%, whereas it increased cellular adenosine 3',5'-cyclic monophosphate (cAMP) content by 300%. 2) Phenylephrine (10(-5) M), 4 beta-phorbol 12 beta-myristate 13 alpha-acetate (1.6 x 10(-7) M), and A23187 (10(-6) M) also stimulated CSPG secretion; this stimulation was concomitant with protein kinase C (PKC) translocation from cytosol to membrane, was blocked by sphingosine (2 x 10(-5) M), and was additive with that elicited by isoproterenol. 3) All PKC activators potentiated the isoproterenol-induced increased in cAMP accumulation without modifying the activation of PKA elicited by the beta-agonist. Our results indicate that although the signaling pathways triggered by alpha- and beta-adrenergic agonists converge at the level of adenylate cyclase in tracheal serous cells, PKA and PKC independently regulate CSPG secretion. </jats:p
Pathophysiology of acute experimental pancreatitis: Lessons from genetically engineered animal models and new molecular approaches
No full textThe incidence of acute pancreatitis is growing and worldwide population-based studies report a doubling or tripling since the 1970s. 25% of acute pancreatitis are severe and associated with histological changes of necrotizing pancreatitis. There is still no specific medical treatment for acute pancreatitis. The average mortality resides around 10%. In order to develop new specific medical treatment strategies for acute pancreatitis, a better understanding of the pathophysiology during the onset of acute pancreatitis is necessary. Since it is difficult to study the early acinar events in human pancreatitis, several animal models of acute pancreatitis have been developed. By this, it is hoped that clues into human pathophysiology become possible. In the last decade, while employing molecular biology techniques, a major progress has been made. The genome of the mouse was recently sequenced. Various strategies are possible to prove a causal effect of a single gene or protein, using either gain-of-function (i.e., overexpression of the protein of interest) or loss-of-function studies (i.e., genetic deletion of the gene of interest). The availability of transgenic mouse models and gene deletion studies has clearly increased our knowledge about the pathophysiology of acute pancreatitis and enables us to study and confirm in vitro findings in animal models. In addition, transgenic models with specific genetic deletion or overexpression of genes help in understanding the role of one specific protein in a cascade of inflammatory processes such as pancreatitis where different proteins interact and co-react. This review summarizes the recent progress in this field. Copyright (c) 2005 S. Karger AG, Basel
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