28 research outputs found

    Exercício físico de baixa intensidade na terapêutica da dor neuropática e regeneração nervosa periférica: efeitos neurobiológicos e estudo dos mecanismos de ação

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    Tese (doutorado) - Universidade Federal de Santa Catarina, Centro de Ciências Biológicas, Programa de Pós-Graduação em Neurociências, Florianópolis, 2015.A dor neuropática que surge em decorrência da lesão de nervos espinais é caracterizada por uma resposta anormal das vias de transmissão da dor. Além disso, as alterações geradas pela desnervação muscular prejudicam a função motora, que juntamente com a dor neuropática diminuem a qualidade de vida dos pacientes. O exercício físico regular é capaz de beneficiar positivamente a saúde física e mental, melhorando a qualidade de vida e diminuindo a incidência de doenças crônicas relacionadas ao estilo de vida sedentário. O exercício físico também é eficaz na reabilitação de pacientes após lesões de nervos espinais, por manter as propriedades musculares e promover a recuperação funcional. No entanto, apesar da grande relevância clínica, poucos estudos identificaram o efeito benéfico do exercício na dor neuropática e recuperação funcional, bem como os seus mecanismos neurobiológicos. O objetivo deste trabalho foi estudar o efeito anti-hiperalgésico e neuroregenerativo do exercício físico de baixa intensidade, realizado na esteira, após a lesão por esmagamento do nervo isquiático em camundongos. Para isto, camundongos Swiss e BALB/cJ selvagens (WT) e BALB/cJ knockouts para IL-4 (IL-4-/-) machos foram submetidos à lesão do nervo isquiático, e, três dias após a lesão, foram submetidos a um programa de exercício físico de baixa intensidade na esteira (30 min/dia, velocidade de 10 m/min, 5 dias/semana), por duas semanas. O exercício físico apresentou importante efeito anti-hiperalgésico reduzindo os comportamentos relacionados à dor neuropática quando avaliados nos testes de von Frey, fuga/esquiva e campo aberto. Parte do efeito neurobiológico do exercício físico é dependente das células do sistema imunológico que migram para o nervo lesionado, pois, a analgesia produzida pelo exercício foi prevenida pela fucoidina (100 µg/animal, i.p.), a qual inibe a migração de leucócitos da circulação sanguínea para o local da lesão. Além disso, o exercício físico promoveu o aumento das concentrações das citocinas anti-inflamatórias, IL-4 e IL-1ra, e das neurotrofinas BDNF e ß-NGF, no nervo isquiático, e IL-4, IL-5 e IL-1ra na medula espinal, bem como, reduziu as concentrações do BDNF e ß-NGF na medula espinal. O efeito anti-hiperalgésico do exercício físico observado em camundongos BALB/cJ WT foi reduzido em camundongos IL-4-/-, confirmando o importante papel da IL-4 neste efeito. Ademais, foi demonstrado que a IL-4 pode modular o perfil fenotípico de macrófagos, pois, camundongos WT exercitados mostraram maior marcação para macrófagos M2a/c, enquanto os camundongos IL-4-/- exercitados apresentaram maior marcação para macrófagos M1. Estes achados fornecem evidências de que o exercício físico promove a alteração fenotípica de macrófagos via liberação da IL-4, o que pode induzir uma resposta das células Th2 e reduzir a dor neuropática, a inflamação e auxiliar no processo de regeneração nervosa. Além disso, foi observado o aumento da expressão da PMP22 no nervo isquiático de animais exercitados, indicando maior concentração de mielina nos axônios em regeneração. O efeito anti-hiperalgésico do exercício físico foi dependente da redução da ativação de astrócitos e microglia na medula espinal. A analgesia causada pelo exercício físico também foi prevenida pelo PCPA (100 mg/kg i.p., um inibidor da síntese de serotonina [5-HT]), mas não pelo AMPT (100 mg/kg i.p., um inibidor da síntese de catecolaminas), sugerindo importante papel do sistema serotoninérgico no efeito do exercício. Ademais, o exercício físico promoveu aumento da concentração de 5-HT e seu metabólito, o ácido 5-hidroxi-indolacético (5-HIAA) no tronco encefálico, e este efeito foi prevenido pelo PCPA. O conteúdo de noradrenalina (NA) foi aumentado com o exercício físico, mas não o de dopamina (DA), e o PCPA também preveniu este aumento, demonstrando a interação entre os sistemas serotoninérgico e noradrenérgico. No entanto, a expressão gênica das enzimas triptofano hidroxilase 2 (Tph2) e dopamina beta hidroxilase (Dbh) não foram alteradas após a lesão, nos animais submetidos ou não ao exercício físico. O exercício também foi capaz de aumentar a expressão gênica dos receptores 5-HT1AR, 5-HT1BR, 5-HT2AR, 5-HT2CR e 5-HT3AR no tronco encefálico. Por fim, o exercício físico reduziu a densidade dos transportadores de serotonina (SERT) nos núcleos da rafe (RPa, RMg e Rob), os quais estavam aumentados após a lesão, sendo este efeito dependente da redução da IL-1ß e do TNF-a, no tronco encefálico. Em conjunto, estes resultados mostram o efeito terapêutico do exercício físico na redução da dor neuropática e regeneração nervosa, através de mecanismos que dependem da ativação do sistema neuroimunológico no local da lesão e na medula espinal, bem como a ativação do sistema endógeno descendente de controle da dor, em especial, da neurotransmissão serotoninérgica no tronco encefálico.Abstract : Neuropathic pain which arises as a result of spinal nerve injury is characterized by an abnormal response of the pain transmission routes. In addition, changes generated by muscle denervation impair motor function, which together with neuropathic pain reduce the quality of life of these patients. Regular physical exercise can positively benefit physical and mental health, improving the quality of life and reducing the incidence of chronic diseases associated with sedentary lifestyle. Physical exercise is also effective in the rehabilitation of patients after spinal nerve injuries through support muscle properties and promotes functional recovery. However, despite the great clinical relevance, few studies have identified the beneficial effect of exercise on neuropathic pain and functional recovery, as well as it neurobiological mechanisms. The aim of this work was to study the anti-hyperalgesic and neuroregenerative effect of low-intensity exercise, performed on the treadmill, after the sciatic nerve crush injury in mice. Then, Swiss and BALB/cJ wild-types (WT) and BALB/cJ IL-4 knockouts (IL-4-/-) males mice were subjected to sciatic nerve injury, after that, three days after injury, mice performed low-intensity exercise on the treadmill (30 min/day, speed of 10 m/min, 5 days/week), for two weeks. Physical exercise showed significant anti-hyperalgesic effect reducing neuropathic pain-related behaviors when assessed by von Frey, escape/avoidance and open field test. Part of the neurobiological effect of physical exercise is dependent on immune cells that migrate to the injured nerve, because the analgesia produced by exercise was prevented by fucoidin (100 µg/mouse, i.p.), that inhibits leukocytes migration from bloodstream to the site of injury. Furthermore, physical exercise promoted increasing concentrations of anti-inflammatory cytokines levels, IL-4 and IL-1ra, and neurotrophins BDNF and ß-NGF, in the sciatic nerve, and IL-4, IL-5 and IL-1ra in the spinal cord, as well as it reduced ß-NGF and BDNF levels in the spinal cord. The noted analgesic effect of physical exercise in BALB/cJ WT mice was reduced in IL-4-/- mice, it confirming the important role of IL-4 on this effect. Furthermore, it was shown that IL-4 can modulate the phenotypic profile of macrophages, because WT exercised mice showed stronger staining for M2a/c macrophages, while IL-4-/- exercised mice presented marked staining for M1 macrophages. These findings provide evidence that physical exercise promotes the phenotypic switch of macrophages by release of IL-4, which can induces Th2 cells response and reducing neuropathic pain, inflammation and helps nerve regeneration process. Furthermore, an increased PMP22 level in the sciatic nerve of exercised animals was observed, indicating higher concentration of myelin in regenerating axons. The anti-hyperalgesic effect of physical exercise was dependent on reduction of astrocytes and microglia activation in the spinal cord. The analgesia caused by physical exercise was also prevented by PCPA (100 mg/kg i.p., an inhibitor of serotonin [5-HT] synthesis), but not by AMPT (100 mg/kg i.p., an inhibitor of catecholamine synthesis), it suggesting the important role of the serotonergic system in the effect of exercise. Furthermore, physical exercise promotes increased 5-HT concentration and its metabolite, the 5-hydroxy-indoleacetic acid (5-HIAA) in the brainstem, and its effect was prevented by the PCPA. The noradrenaline (NA) content was increased by physical exercise, but not the dopamine (DA) content, and the PCPA also prevented this increase, demonstrates the interaction between serotonergic and noradrenergic systems. However, tryptophan hydroxylase 2 (Tph2) and dopamine beta hydroxylase (Dbh) enzymes gene expression were not changed after injury, in the animals submitted or not to physical exercise. The exercise was also able of increasing 5-HT1AR, 5-HT1BR, 5-HT2AR, 5-HT2CR e 5-HT3AR receptors gene expression in the brainstem. Finally, physical exercise reduced serotonin transporter (SERT) density in the raphe nuclei (RPa, RMg and ROb), which were increased after injury, and this effect was dependent of IL-1ß and TNF-a reduced levels in the brainstem. Together, these results demonstrate the therapeutic effect of physical exercise on neuropathic pain reducing and nerve regeneration, through mechanisms that depending on the neuroimmune system activation at the site of injury and spinal cord, as well as the activation of endogenous descending pain control system, especially of serotonergic neurotransmission in the brainstem

    Definição de caso suspeito da COVID-19: uma revisão narrativa dos sinais e sintomas mais frequentes entre os casos confirmados

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    Objective: to describe the most frequent signs and symptoms of infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Methods: this is a narrative literature review carried out in April 2020; the search was performed on electronic databases and complemented with a manual review of the references of the selected papers and Brazilian Ministry of Health publications. Results: the spectrum of clinical disease was wide; fever, coughing and dyspnea were the most frequent signs/symptoms, however, they may not be present, thus hindering case definition. gastrointestinal symptoms and loss of taste or smell have been reported among mild cases; dyspnea was frequent among severe and fatal cases. Conclusion: considering the scarcity of diagnostic tests and the diversity of symptoms, health services should use a sensitive case definition, in order to adopt appropriate surveillance, prevention and treatment actions.Síndrome Respiratorio Agudo Severo Coronavirus 2 (SARS-Cov-2). Métodos: revisión de la literatura narrativa realizada en abril de 2020. La búsqueda se realizó de forma electrónica y se complementó con una revisión manual de las referencias y publicaciones del Ministerio de Salud de Brasil. Resultados: el espectro de la enfermedad clínica fue variado. La fiebre, la tos y la disnea fueron las señales / síntomas más frecuentes, sin embargo, es posible que no estén presentes, lo que dificulta la definición del caso. Se han informado síntomas gastrointestinales y cambios en el olfato o el gusto entre los casos leves. La disnea fue frecuente entre los casos graves y progresó hasta la muerte. Conclusión: teniendo en cuenta la escasez de pruebas diagnósticas y la diversidad de síntomas, los servicios de salud deben utilizar una definición de caso sensible, para adoptar las acciones apropiadas para la vigilancia, prevención y tratamiento.Objetivo: descrever os sinais e sintomas mais frequentes na infecção pelo vírus da síndrome respiratória aguda grave coronavírus 2 (SARS-CoV-2). Métodos: revisão narrativa da literatura realizada em abril de 2020; a busca foi realizada em bases eletrônicas e complementada com revisão manual das referências dos trabalhos selecionados e das publicações do Ministério da Saúde do Brasil. Resultados: o espectro da doença clínica mostrou-se variado; Febre, tosse e dispneia foram os sinais/sintomas mais frequentes, no entanto, podem não estar presentes, dificultando a definição de caso; sintomas gastrointestinais e alteração de olfato ou paladar têm sido relatados entre casos leves; a dispneia foi frequente entre casos graves e com evolução ao óbito. Conclusão: considerando-se a escassez de testes diagnósticos e a diversidade de sintomas, os serviços de saúde devem utilizar uma definição de caso sensível, de forma a serem adotadas ações adequadas de vigilância, prevenção e tratamento

    Jnk And Ikkβ Phosphorylation Is Reduced By Glucocorticoids In Adipose Tissue From Insulin-resistant Rats.

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    Peripheral insulin resistance (IR) is one of the main side effects caused by glucocorticoid (GC)-based therapies, and the molecular mechanisms of GC-induced IR are not yet fully elucidated. Thus, we aimed to investigate the effects of dexamethasone treatment on the main components of insulin and inflammatory signaling in the adipose tissue of rats. Male Wistar rats received daily injections of dexamethasone (1mg/kg body weight (b.w.), intraperitoneally (i.p.)) for 5 days (DEX), whereas control rats received saline (CTL). The metabolic status was investigated, and the epididymal fat fragments were collected for lipolysis and western blot analyses. The DEX rats became hyperglycemic, hyperinsulinemic, insulin resistant and glucose intolerant, compared with the CTL rats (P<0.05). The basal glycerol release in the fat fragments was 1.5-fold higher in the DEX rats (P<0.05). The phosphorylation of protein kinase B (PKB) at ser(473) decreased by 44%, whereas, the phosphorylation of insulin receptor substrate (IRS)-1 at ser(307) increased by 93% in the adipose tissue of the DEX rats after an oral bolus of glucose (P<0.05). The basal phosphorylation of c-jun-N-terminal kinase (JNK) and inhibitor of nuclear factor kappa-B (IKKβ) proteins was reduced by 46% and 58%, respectively, in the adipose tissue of the DEX rats (P<0.05). This was paralleled with a significant reduction (47%) in the glucocorticoid receptor (GR) protein content in the adipose tissue of the DEX rats (P<0.05). The insulin-resistant status of rats induced by dexamethasone administration have PKB and IRS-1 activity attenuated in epididymal fat without increases in the phosphorylation of the proinflammatory signals JNK and IKKβ.1451-1

    Recovery following Rugby Union matches: effects of cold water immersion on markers of fatigue and damage

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    We investigated the effect of post-match cold-water immersion (CWI) on markers of muscle damage, neuromuscular fatigue and perceptual responses within 72 h after a Rugby match. Twenty-two professional male Rugby players were randomized into CWI (10°C/10min; n=11) or Control (CON:30min seated; n=11) groups. Activity profile from Global Positioning Satellite systems and post-match rating of perceived exertion were measured to determined match load. Biochemical (tumor necrosis factor alpha [TNF-α], interleukin-6 [IL-6]), neuromuscular performance (squat and countermovement jump [SJ; CMJ], peak power output [PPO], rate of force development [RFD], stiffness, 10- and 30-m sprint time and perceptual markers (soreness, perceived recovery) were obtained at pre, post, 30 min, 24, 48 and 72 h post-match. Magnitude-based inference and Cohen’s effect size (ES) were used to analyze change over time and between-groups. Changes were unclear for the match loads, sprint times and perceptual markers between-groups. Higher %∆SJ at 24 h (very-likely[ES=0.75]) and in %∆PPO_SJ at 48 h (likely[ES=0.51]) were observed in CWI than in CON. Values in %∆RDF_CMJ were higher at post (likely[ES=0.83]), 30 min (very-likely[ES=0.97]) and 24 h (likely[ES=0.93]) in CWI than in CON. Furthermore, %∆LogTNF-α were lower in CWI than in CON group at post (almost-certainly[ES:-0.76]), 24 h (very-likely[ES:-1.09]) and 72 h (likely[ES:-0.51]) and in ∆stiffness_SJ at 30 min (likely[ES=-0.67]) and 48 h (very-likely[ES=-0.97]), as well as, different within-groups effects throughout post-match were reported. Implementing post-match CWI-based strategies improved the recovery of markers of inflammation and fatigue in Rugby players, despite no change in markers of speed or perceptual recovery.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

    Early fragmentation of polyester urethane sheet neither causes persistent oxidative stress nor alters the outcome of normal tissue healing in rat skin

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    Abstract Silicone breast implant is associated with complications inherent to the surgical procedure. Prosthesis coating with polyurethane, however, commonly reduces the incidence of such complications. In this paper, the authors evaluated the inflammatory histomorphometric profile and oxidative damage associated to the implant of polyester urethane sheets. Forty-eight Wistar rats were divided into Sham or polyester urethane groups (n = 8/group) and underwent a polyester urethane implant in the dorsal skinfold. Tissue samples were collected on days seven, 30, and 90 after surgery and subjected to histomorphometric analysis and biochemical tests. Results were analyzed by one-way ANOVA (p ≤ 0.05). Peri-implant tissue samples exhibited characteristic inflammatory response associated with the biomaterial, with increased vascularization on day seven and augmented levels of IL1-b and TNF-a after 30 days. Peri-implant fibrocystic population was small on day seven, but increased considerably after 90 days. A rise in the carbonyl group levels of skin samples in the polyester urethane group was observed on day seven. Findings suggest that polyester urethane sheets undergo biodegradation at an early stage after implantation, followed by increased vascularity and microencapsulation of biomaterial fragments, without persistent oxidative damage. Fiber arrangement inside the collagen matrix results in a fibrotic scar because of polyester urethane degradation

    Exercício físico aeróbico : melhore sua memória

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    O envelhecimento humano e caracterizado por diversas alterações fisiológicas e funcionais que podem ser influenciadas por fatores genéticos, ambientais e estilo de vida. Dentre as consequências dessas mudanças estão os déficits cognitivos, sobre tudo da memória, afetando as atividades da vida diária dessa população. Intervenções com treino cognitivo, bem como o exercício físico tem sido amplamente indicado como intervenção para promoção da saúde cognitiva, no entanto estudos que investigam exercício físico aliado à estimulação cognitiva, ainda são escassos e inconclusivos. Objetivo: Verificar os efeitos de uma sessão de exercício físico aeróbio conjugado a estimulação cognitiva no desempenho da memória e no aumento do fator neurotrófico derivado do cérebro (BDNF) em idosos. Material e Métodos: O presente estudo caracterizou como quase experimental, com delineamento crossover randomizado, realizado com 30 idosos de ambos os sexos (69,3 ± 5,8 anos de idade; 29,7 ± 3,9 kg.cm-²), foram submetidos a três diferentes sessões, sendo duas de exercício físico (sessão com exercício automático e sessão com estímulos cognitivos) e uma sessão controle, cada sessão teve duração de 50 minutos. A memória foi avaliada com o teste de lista de palavras, realizou-se também uma coleta sanguínea antes e após cada sessão a fim de avaliar a variação da quantidade sérica do BDNF. Após a coleta foi verificado a normalidade e homogeneidade das variâncias. Utilizou-se ANOVA twoway de medidas repetidas para comparação entre e intrasessões das concentrações de BDNF e memória. Adotou-se como nível de significância estatística o p < 5%. Resultados: Na memória, as sessões não foram diferentes entre si (F(2, 89)=0,36, P=0,697, ɳ2p=0,008,), no entanto, houve um efeito significativo no tempo, apontando que houve redução do desempenho pós exercício de memória em todas as sessões, tanto para memória de curto prazo, controle (P=0,002), automático (P<0,001) e exercício com estimulação (P=0,023), quanto para Memoria de trabalho, automático (P=0,012) e exercício com estimulação (P=0,015). Nos níveis de concentração do BDNF, as sessões não foram diferentes entre si (F(2, 90)=0,06, P=0,941, ɳ2 p=0,001), do mesmo modo, não houve significância na interação tempo × sessão (F(2,90)=1,37, P=0,260, ɳ2 p=0,029) e no tempo, F(1, 90)=0,14, P=0,712, ɳ2 p=0,002. Conclusão: O exercício aeróbio simultâneo a estimulação cognitiva com intensidade moderada não é suficiente para aumentar o fator neurotrófico derivado do cérebro, podendo prejudicar o desempenho da memória em tarefas realizadas logo após o exercício.Human aging is characterized by different physiological and functional changes that may be influenced by lifestyle, genetic and environmental factors. Among the consequences of these changes are cognitive deficits, principally memory, affecting the activities of daily life of elderly. Cognitive training intervention combined with exercise has been widely indicated as an alternative to promote cognitive health, however, studies investigating exercise combined with cognitive stimulation are still rare and inconclusive. Objective: To determine the effects of the combination of single session aerobic exercise with cognitive stimulation over memory performance and increased Brain-Derived Neurotrophic Factor (BDNF) in the elderly.Methods: This study was characterized as almost experimental, with randomized and crossover design, fulfill with 30 elderly men and women (69.3 ± 5.8 years; 29.7 ± 3.9 kg.cm-²) who were subjected to three different sessions, including two sessions of physical exercise (one with automatic exercise and other with cognitive stimulation) and a control session, each session lasted 50 minutes. The memory was evaluated using the word list test, also serum BDNF was measured from blood sampling immediately before and immediately after each session. After the collection, was found normality and homogeneity of variances. We used twoway ANOVA to compare repeated measures both the concentration of BDNF and as the memory test between sessions and the session itself. We adopted as statistically significant level p <5%. Results: In relation to memory, the sessions were not diferente from each other (F (2, 89) = 0.36, P = 0.697, ɳ2 p = 0.008,), however, there was a significant effect in relation to time, indicating that there was a reduction of memory performance in post exercise in all sessions for both the short term memory (control – p = 0.002, automatic – p < 0.001 and exercise with stimulation – p = 0.023) and for work memory (automatic – p = 0.012 and exercise with stimulation – p = 0.015). In relation to the levels of concentration of BDNF, the sessions were not different each other (F (2, 90) = 0.06, P = 0.941, ɳ2 p = 0.001), in the same way, there was no significance in interaction time × session (F (2, 90) = 1.37, P = 0.260, ɳ2 p = 0.029) and in time (F (1, 90) = 0.14, P = 0.712, = 0.002 ɳ2 p). Conclusion: Moderate intensity aerobic exercise simultaneously with cognitive stimulation is not enough to increase the brain-derived neurotrophic factor, which may negatively affect the performance of memory in tasks performed soon after exercise

    Effects of far-infrared emitting ceramic materials on recovery during 2-week preseason of elite futsal players

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    We investigated the effects of far-infrared emitting ceramic materials (cFIR) during overnight sleep on neuromuscular, biochemical and perceptual markers in futsal players. Twenty athletes performed a 2-week preseason training program and during sleep wore bioceramic (BIO; n = 10) or placebo pants (PL; n = 10). Performance (countermovement jump [CMJ]; squat jump [SJ]; sprints 5, 10, and 15-m) and biochemical markers (tumor necrosis factor alpha-TNF-α, interleukin 10-IL-10, thiobarbituric acid–reactive species [TBARS], carbonyl, superoxide dismutase [SOD], catalase [CAT]) were obtained at baseline and after the 1st and 2nd week of training. Delayed-onset muscle soreness (DOMS) and training strain were monitored throughout. Changes in ΔCMJ and ΔSJ were possibly (60/36/4 [week-1]) and likely (76/22/2 [week-2]) higher in BIO. Both groups were faster in 5-m sprint in week 2 compared with baseline (p = 0.015), furthermore, BIO was likely faster in 10-m sprint (3/25/72 [week 1]). Significant group × time interaction in %ΔTNF-α were observed (p = 0.024 [week-1]; p = 0.021 [week-2]) with values possibly (53/44/3 [week 1]) and likely (80/19/1 [week 2]) higher in BIO. The %ΔIL-10 decreased across weeks compared with baseline (p = 0.019 [week-1]; p = 0.026 [week-2]), showing values likely higher in BIO (81/16/3 [week-1]; 80/17/3 [week-2]). Significant weekly increases in %ΔTBARS (p = 0.001 [week-1]; p = 0.011 [week-2]) and %ΔCarbonyl (p = 0.002 [week-1]; p < 0.001 [week-2]) were observed compared with baseline, showing likely (91/5/4 [week-1]) and possibly (68/30/2 [week-2]) higher changes in BIO. Significant weekly decreases in %ΔSOD were observed compared with baseline (p = 0.046 [week 1]; p = 0.011 [week-2]), and between week 2 and week 1 (p = 0.021), in addition to significant decreases in %ΔCAT compared with baseline (p = 0.070 [week 1]; p = 0.012 [week 2]). Training strain (p = 0.021; very -likely [0/2/98]; week 1) and DOMS was lower in BIO (likely; 7 sessions) with differences over time (p = 0.001). The results suggest that the daily use of cFIR clothing could facilitate recovery, especially on perceptual markers during the early phases of an intensive training period
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