The use of a pre-workout supplement containing an amphetamine derivative and its effects on physical performance / Uso de suplemento pre-entrenamiento que contiene un derivado anfetamínico y sus efectos sobre el desempeño físico / Uso de suplemento pré-treino que contém um derivado anfetaminico e seus efeitos sobre o desempenho físico

ABSTRACT Introduction: The quest for better sports performance or simply for esthetic ends has led individuals to seek ergogenic resources indiscriminately to attain their goals. It is believed that nutritional supplements promote better strength, power, focus and better reaction time. Nutritional supplements are used to delay fatigue and increase athletic performance. Also, the anorectics, drugs derived from amphetamines and commonly sought for weight loss, act on the central nervous system by releasing substances that transmit the sensation of not being hungry. Supplements that promise quick solutions to these goals may have compounds in their formulas that compromise health. Objectives: In this study, the potential of creatine and Jack 3D® to boost physical performance and delay muscle fatigue was evaluated in animals that were given the supplements. Methods: The animals underwent 10 weeks of swim training at 80% of the maximum load and received creatine and/or Jack 3D. The muscle contractions were recorded by an electrophysiograph for analysis of muscle fatigue. Results: It was observed that the SED+CR group had significantly different values compared to the SED group and NAT+CR group showed significant differences between groups for the SED, SED+JACK, JACK, NAT and NAT+JACK groups (p <0.05). For the two last parameters, the SED group showed a significant difference in relation to the SED+CR, NAT and NAT+CR groups (p <0.05). Conclusions: These results demonstrate a possible positive influence of physical exercise associated with the use of creatine, delaying muscle fatigue and making an increase in sports performance possible. Level of Evidence III; Development of diagnostic criteria in consecutive patients (with "gold" reference standard applied) .

RESUMEN Introducción: La búsqueda por el mejor desempeño deportivo o simplemente para fines estéticos ha inducido a los individuos a buscar indiscriminadamente recursos ergogénicos para alcanzar el éxito. Se cree que la ingestión de suplementos nutricionales puede proporcionar mayor resistencia, potencia, enfoque y mejor tiempo de reacción. Los suplementos nutricionales son empleados para retardar el surgimiento de la fatiga y aumentar el desempeño atlético. También comúnmente buscados para adelgazamiento están los anorexígenos, medicamentos a base de drogas anfetamínicas, que actúan sobre el sistema nervioso central liberando sustancias que transmiten la sensación de ausencia de hambre. Los suplementos que prometen soluciones rápidas para estos objetivos pueden presentar en sus fórmulas, compuestos que comprometen la salud. Objetivo: En este estudio fue evaluado el potencial de la creatina y del Jack3D® para el desempeño físico y la fatiga muscular de los animales que recibieron la suplementación. Métodos: Los animales fueron sometidos a 10 semanas de entrenamiento de natación a 80% de la carga máxima y recibieron creatina y/o Jack3D. Las contracciones musculares fueron registradas por un electrofisiógrafo para análisis de la fatiga muscular. Resultados: Se observó que el grupo SED+CR presentó valores significativamente diferentes en comparación con el grupo SED y el grupo NAT+CR presentó diferencias significativas con relación a los grupos SED, SED+JACK, NAT y NAT+JACK (p < 0,05). En los dos últimos parámetros, el grupo SED presentó diferencia significativa con relación a los grupos SED+CR, NAT y NAT+CR (p < 0,05). Conclusión: Esos resultados demuestran una posible influencia positiva del ejercicio físico asociado al uso de la creatina, retardando la fatiga muscular y posibilitando un aumento en el desempeño deportivo. Nivel de evidencia III; Desarrollo de criterios diagnósticos en pacientes consecutivos (con estándar de referencia "oro" aplicado) .

RESUMO Introdução: A busca pelo melhor rendimento esportivo ou simplesmente para fins estéticos tem induzido indivíduos a procurarem indiscriminadamente recursos ergogênicos para atingir o êxito. Acredita-se que a ingestão de suplementos nutricionais pode proporcionar maior resistência, potência, foco e melhor tempo de reação. Os suplementos nutricionais são empregados afim de retardar o surgimento da fadiga e aumentar o desempenho atlético. Também comumente procuradas para emagrecimento estão os anorexígenos, medicamentos à base de drogas anfetamínicas, que agem sobre o sistema nervoso central liberando substâncias que transmitem a sensação de ausência de fome. Suplementos que prometem soluções rápidas para estes objetivos podem conter em suas fórmulas compostos que comprometem a saúde. Objetivos: Neste estudo foi avaliado o potencial da creatina e do Jack 3D®para o desempenho físico e fadiga muscular dos animais que receberam a suplementação. Métodos: Os animais foram submetidos a 10 semanas de treinamento de natação a 80% da carga máxima e receberam creatina e/ou Jack 3D. As contrações musculares foram registradas por um eletrofisiógrafo para análise da fadiga muscular. Resultados: Observou-se que o grupo SED+CR apresentou valores significativamente diferentes em comparação com o Grupo SED e o Grupo NAT+CR apresentou diferenças significativas com relação aos grupos SED, SED+JACK, NAT e NAT+JACK (p < 0,05). Nos dois últimos parâmetros, o Grupo SED apresentou diferença significativa com relação aos grupos SED+CR, NAT e NAT+CR (p < 0,05). Conclusão: Esses resultados demonstram uma possível influência positiva do exercício físico associado ao uso da creatina, retardando a fadiga muscular e possibilitando um aumento no desempenho esportivo. Nível de Evidência III; Desenvolvimento de critérios diagnósticos em pacientes consecutivos (com padrão de referência "ouro" aplicado) .

Effect of creatine and sildenafil citrate on the physical performance of mice / Efecto de la creatina y del citrato de sildenafil sobre el desempeño físico de ratones / Efeito da creatina e do citrato de sildenafila sobre o desempenho físico de camundongos

ABSTRACT Introduction: The use of substances to enhance sports performance among professional and amateur athletes is increasing. Such substances may either be included in the group of dietary supplements or fall into pharmacological classes. Every substance used for this purpose is called an ergogenic agent. The number of ergogenic options available increases every day, favoring overuse and use without proper guidance. Among the dietary supplements, we highlight the use of creatine, a substance widespread in sports. Among the pharmacological groups, many drugs are used. Recently the use of sildenafil citrate by professional athletes from various predominantly aerobic sports modalities was reported in the media. Objective: To compare and demonstrate the responses caused by physical training associated with the use of creatine and sildenafil citrate in mice. Methods: A swim training protocol was applied and then an electrophysiograph was used in order to obtain parameters related to contraction intensity, the area under the curve and the percentage drop. Results: The responses obtained demonstrated the ergogenic action of creatine because it altered the parameters used for measurement. The use of sildenafil citrate did not yield satisfactory results to frame the drug as an ergogenic agent. Conclusion: Creatine has an ergogenic effect, reducing the percentage drop after 10 seconds, while sildenafil demonstrated no ergogenic potential and, interestingly, resulted in weaker responses when compared to the exercise groups. Evidence level II; Comparative prospective study .

RESUMEN Introducción: El uso de sustancias con el objetivo de aumentar el rendimiento deportivo entre atletas profesionales y amateurs es creciente. Tales sustancias pueden formar parte del grupo de suplementos alimentarios o integrar clases farmacológicas. Toda sustancia empleada para ese fin es denominada agente ergogénico. El número de opciones entre los agentes ergogénicos aumenta cada día, favoreciendo así su uso excesivo y sin la debida orientación. Entre los suplementos alimentarios, se destaca el uso de creatina, sustancia muy difundida en el medio deportivo. Ya entre los grupos farmacológicos, muchas sustancias son usadas. Recientemente, fue divulgado entre los medios de comunicación el uso de citrato de sildenafil por atletas profesionales, de varias modalidades deportivas, predominantemente las aeróbicas. Objetivos: Comparar y demostrar las respuestas ocasionadas por el entrenamiento físico, asociadas al uso de creatina y citrato de sildenafil en ratones. Métodos: Se aplicó un protocolo de entrenamiento de natación y, a continuación, se usó un electrofisiógrafo con el objetivo de obtener parámetros referentes a la intensidad de contracción, al área bajo la curva y a la caída porcentual. Resultados: Las respuestas obtenidas demuestran acción ergogénica de la creatina, visto que alteraron los parámetros empleados para la medición. Ya el uso de citrato de sildenafil no presentó resultados satisfactorios para encuadrar al fármaco como agente ergogénico. Conclusión: La creatina presenta efecto ergogénico porque reduce la caída porcentual después de 10 segundos, mientras que el sildenafil no presentó potencial ergogénico y, curiosamente, demostró respuestas inferiores cuando comparado a los grupos de ejercicio. Nivel de evidencia II; Estudio prospectivo comparativo .

RESUMO Introdução: O uso de substâncias com o objetivo de aumentar o rendimento esportivo entre atletas profissionais e amadores é crescente. Tais substâncias podem fazer parte do grupo de suplementos alimentares ou integrar classes farmacológicas. Toda substância empregada para esse fim é denominada de agente ergogênico. O número de opções entre os agentes ergogênicos aumenta a cada dia, favorecendo assim o uso em demasia e sem a devida orientação. Entre os suplementos alimentares, salientamos a utilização de creatina, substância muito difundida no meio esportivo. Já entre os grupos farmacológicos, muitas substâncias são utilizadas. Recentemente, foi divulgado entre os meios de comunicação o uso de citrato de sildenafila por atletas profissionais de várias modalidades esportivas, predominantemente as aeróbicas. Objetivos: Comparar e demonstrar as repostas ocasionadas pelo treinamento físico, associadas ao uso de creatina e citrato de sildenafila em camundongos. Métodos: Aplicou-se um protocolo de treinamento de natação e, a seguir, empregou-se um eletrofisiógrafo com objetivo de obter parâmetros referentes à intensidade de contração, à área sob a curva e à queda percentual. Resultados: As respostas obtidas demonstram ação ergogênica da creatina, visto que alteraram os parâmetros empregados para a mensuração. Já a utilização de citrato de sildenafila não apresentou resultados satisfatórios para enquadrar o fármaco como agente ergogênico. Conclusão: A creatina apresenta efeito ergogênico porque reduz a queda percentual após 10 segundos, já a sildenafila não apresentou potencial ergogênico e, curiosamente, demonstrou respostas inferiores quando comparado aos grupos de exercício. Nível de evidência II; Estudo prospectivo comparativo .

Aerobic exercise modulates cardiac NAD(P)H oxidase and the NRF2/KEAP1 pathway in a mouse model of chronic fructose consumption.

The present study investigated the effects of exercise on the cardiac nuclear factor (erythroid-derived 2) factor 2 (NRF2)/Kelch-like ECH-associated protein 1 (KEAP1) pathway in an experimental model of chronic fructose consumption. Male C57BL/6 mice were assigned to Control, Fructose (20% fructose in drinking water), Exercise (treadmill exercise at moderate intensity), and Fructose + Exercise groups (n = 10). After 12 wk, the energy intake and body weight in the groups were similar. Maximum exercise testing, resting energy expenditure, resting oxygen consumption, and carbon dioxide production increased in the exercise groups (Exercise and Fructose + Exercise vs. Control and Fructose groups, P < 0.05). Chronic fructose intake induced circulating hypercholesterolemia, hypertriglyceridemia, and hyperleptinemia and increased white adipose tissue depots, with no changes in blood pressure. This metabolic environment increased circulating IL-6, IL-1ß, IL-10, cardiac hypertrophy, and cardiac NF-κB-p65 and TNF-α expression, which were reduced by exercise (P < 0.05). Cardiac ANG II type 1 receptor and NAD(P)H oxidase 2 (NOX2) were increased by fructose intake and exercise decreased this response (P < 0.05). Exercise increased the cardiac expression of the NRF2-to-KEAP1 ratio and phase II antioxidants in fructose-fed mice (P < 0.05). NOX4, glutathione reductase, and catalase protein expression were similar between the groups. These findings suggest that exercise confers modulatory cardiac effects, improving antioxidant defenses through the NRF2/KEAP1 pathway and decreasing oxidative stress, representing a potential nonpharmacological approach to protect against fructose-induced cardiometabolic diseases.NEW & NOTEWORTHY This is the first study to evaluate the cardiac modulation of NAD(P)H oxidase (NOX), the NRF2/Kelch-like ECH-associated protein 1 pathway (KEAP), and the thioredoxin (TRX1) system through exercise in the presence of moderate fructose intake. We demonstrated a novel mechanism by which exercise improves cardiac antioxidant defenses in an experimental model of chronic fructose intake, which involves NRF2-to-KEAP1 ratio modulation, enhancing the local phase II antioxidants hemoxygenase-1, thioredoxin reductase (TXNRD1), and peroxiredoxin1B (PDRX1), and inhibiting cardiac NOX2 overexpression.

Outdoor Endurance Training with Air Pollutant Exposure Versus Sedentary Lifestyle: A Comparison of Airway Immune Responses.

Although regular exercise-training improves immune/inflammatory status, the influence of air pollutants exposure during outdoor endurance training compared to a sedentary lifestyle has not yet been clarified. This study aimed to compare the immune/inflammatory responses in the airways of street runners and sedentary people after acute and chronic particulate matter (PM) exposure. Forty volunteers (street runners (RUN, n = 20); sedentary people (SED, n = 20)) were evaluated 1 (acute) and 10 (chronic) weeks after PM exposure. Cytokines [interferon (IFN)-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-10, IL-13, and IL-17A] in nasal lavage fluid, salivary antibacterial peptides (lactoferrin (LTF), cathelicidin (LL-37), defensin-α 1-3), and secretory immunoglobulin A (SIgA), plasma club cell protein (CC16), and fractional exhaled nitric oxide (FeNO) were analyzed. After acute exposure, the RUN group showed lower levels of IL-13, IL-10, and FeNO, but higher defensin-α than the SED group. After chronic exposure, the RUN group showed elevation of IFN-γ, IL-10, IL-17A, and a decrease of FeNO levels, whereas the SED group showed elevation of TNF-α, IL-6, IL-10, and a decrease of IL-13 levels. Comparing these groups, the RUN group showed higher levels of SIgA and LTF, and lower FeNO levels than the SED group. In relation to the Th immune response analysis after acute and chronic PM exposure, the RUN group showed a pattern associated with Th1, while in the SED group, a Th2 pattern was found. Both groups showed also a Th17 immune response pattern. Our results allow us to suggest that the immune/inflammatory status of the respiratory tract after acute and chronic PM exposure was improved by the long-standing regular practice of outdoor endurance exercise compared to a sedentary lifestyle.

A possible association between fructose consumption and pulmonary emphysema.

Chronic Obstructive Pulmonary Disease (COPD) is a syndrome that comprises several distinct and overlapping phenotypes. In addition to persistent airflow limitation and respiratory symptoms, COPD is also characterized by chronic systemic inflammation. Epidemiological studies have shown that dietary fibers, fruits and vegetables intake protects against the COPD development, while fructose-loading is associated with increased risk of asthma and chronic bronchitis. Since dietary factors might affect susceptibility to COPD by modulating oxidative stress and inflammatory responses, we evaluated how fructose feeding might affect the smoking-induced emphysema in mice. We found that chronic fructose intake induced destruction and remodeling of lung parenchyma and impairment of respiratory mechanics, which are associated with distinctive cytokine profiles in bronchoalveolar lavage fluid, blood plasma and skeletal muscle. The combined effects of chronic fructose intake and cigarette smoking on destruction of lung parenchyma are more pronounced than the effects of either alone. Excessive intake of fructose might directly cause pulmonary emphysema in mice rather than just altering its natural history by facilitating the installation of a low-grade systemic inflammatory milieu.

Myostatin and adipokines: The role of the metabolically unhealthy obese phenotype in muscle function and aerobic capacity in young adults.

Obesity is often associated with metabolic disorders. However, some obese people can present a metabolically healthy phenotype, despite having excessive body fat. Obesity-related cytokines, such as myostatin (MSTN), leptin (LP) and adiponectin (ADP) appear to be key factors for the regulation of muscle and energy metabolism. Our aim was to compare lipid, glucose-insulin and inflammatory (tumor necrosis factor alpha; TNF-α) profiles, muscle function, energy expenditure and aerobic capacity between healthy normal-weight (NW) adults, metabolically healthy obese (MHO) and metabolically unhealthy obese (MUHO) adults; to study the associations between these outcomes and the cytokines MSTN, ADP, LP; and to establish cutoffs for MSTN and LP/ADP to identify the MUHO phenotype. Sixty-one young adults (NW, n = 24; MHO, n = 16; MUHO, n = 21) underwent body composition (body fat -BF and muscle mass - MM), energy expenditure at rest (RER) and aerobic capacity (VO2peak) evaluation, muscle strength and endurance tests and blood profile characterization (glucose-insulin homeostasis and serum MSTN, ADP, LP and TNF-α). MHO and MUHO had a BMI ≥ 30 kg m-2. MUHO was defined as presenting ≥3 criteria for metabolic syndrome (NCEP/ATPIII) in association with insulin resistance (HOMA-IR ≥3.46). MSTN and LP/ADP were associated with MM, MetS and glucose-insulin profile; MSTN was associated with TNF-α and only LP/ADP was associated with parameters of obesity and VO2peak. Neither MSTN nor LP/ADP was associated with muscle functions (p < .05 for adjusted correlations). Both of them were able to discriminate the MUHO phenotype: MSTN [AUC(95%CI) = 0.71(0.55-0.86), MSTN > 517.3 pg/mL] and LP/ADP [AUC(95%CI) = 0.89(0.81-0.97), LP/ADP > 2.14 pg/ng]. In conclusion, high MSTN and LP/ADP are associated with MetS, glucose-insulin homeostasis impairment and low muscle mass. Myostatin is associated with TNF-α and leptin-to-adiponectin ratio is associated with body fatness and aerobic capacity. Neither MSTN nor LP/ADP is associated with energy expenditure, muscle strength and endurance. Myostatin and adipokines cutoffs can identify the metabolically unhealthy obese phenotype in young adults with acceptable accuracy.

Trends in asthma mortality in the 0- to 4-year and 5- to 34-year age groups in Brazil / Tendências da mortalidade da asma nas faixas etárias de 0 a 4 anos e 5 a 34 anos no Brasil

ABSTRACT Objective: To provide an update on trends in asthma mortality in Brazil for two age groups: 0-4 years and 5-34 years. Methods: Data on mortality from asthma, as defined in the International Classification of Diseases, were obtained for the 1980-2014 period from the Mortality Database maintained by the Information Technology Department of the Brazilian Unified Health Care System. To analyze time trends in standardized asthma mortality rates, we conducted an ecological time-series study, using regression models for the 0- to 4-year and 5- to 34-year age groups. Results: There was a linear trend toward a decrease in asthma mortality in both age groups, whereas there was a third-order polynomial fit in the general population. Conclusions: Although asthma mortality showed a consistent, linear decrease in individuals ≤ 34 years of age, the rate of decline was greater in the 0- to 4-year age group. The 5- to 34-year group also showed a linear decline in mortality, and the rate of that decline increased after the year 2004, when treatment with inhaled corticosteroids became more widely available. The linear decrease in asthma mortality found in both age groups contrasts with the nonlinear trend observed in the general population of Brazil. The introduction of inhaled corticosteroid use through public policies to control asthma coincided with a significant decrease in asthma mortality rates in both subsets of individuals over 5 years of age. The causes of this decline in asthma-related mortality in younger age groups continue to constitute a matter of debate.

RESUMO Objetivo: Apresentar uma atualização das tendências da mortalidade da asma no Brasil em duas faixas etárias: 0-4 anos e 5-34 anos Métodos: Dados relativos ao período de 1980 a 2014 referentes à mortalidade da asma, conforme se definiu na Classificação Internacional de Doenças, foram extraídos Sistema de Informação sobre Mortalidade do Departamento de Tecnologia da Informação do Sistema Único de Saúde. Para analisar as tendências temporais das taxas padronizadas de mortalidade da asma, realizou-se um estudo ecológico de séries temporais com modelos de regressão para as faixas etárias de 0 a 4 anos e 5 a 34 anos Resultados: Houve uma tendência linear de redução da mortalidade da asma em ambas as faixas etárias e uma tendência polinomial de terceira ordem na população geral Conclusões: Embora a mortalidade da asma tenha apresentado redução linear consistente em indivíduos com idade ≤ 34 anos, a taxa de declínio foi maior na faixa etária de 0 a 4 anos. A faixa etária de 5 a 34 anos também apresentou redução linear da mortalidade, e essa redução tornou-se mais pronunciada após o ano de 2004, quando o tratamento com corticosteroides inalatórios tornou-se mais amplamente disponível. A redução linear da mortalidade da asma em ambas as faixas etárias contrasta com a tendência não linear observada na população geral do Brasil. A introdução do uso de corticosteroides inalatórios por meio de políticas públicas de controle da asma coincidiu com uma diminuição significativa das taxas de mortalidade da asma em ambos os subgrupos de indivíduos com mais de 5 anos de idade. As causas dessa redução da mortalidade da asma em faixas etárias mais jovens ainda são objeto de debate.

Human Tubal-Derived Mesenchymal Stromal Cells Associated with Low Level Laser Therapy Significantly Reduces Cigarette Smoke-Induced COPD in C57BL/6 mice.

Cigarette smoke-induced chronic obstructive pulmonary disease is a very debilitating disease, with a very high prevalence worldwide, which results in a expressive economic and social burden. Therefore, new therapeutic approaches to treat these patients are of unquestionable relevance. The use of mesenchymal stromal cells (MSCs) is an innovative and yet accessible approach for pulmonary acute and chronic diseases, mainly due to its important immunoregulatory, anti-fibrogenic, anti-apoptotic and pro-angiogenic. Besides, the use of adjuvant therapies, whose aim is to boost or synergize with their function should be tested. Low level laser (LLL) therapy is a relatively new and promising approach, with very low cost, no invasiveness and no side effects. Here, we aimed to study the effectiveness of human tube derived MSCs (htMSCs) cell therapy associated with a 30mW/3J-660 nm LLL irradiation in experimental cigarette smoke-induced chronic obstructive pulmonary disease. Thus, C57BL/6 mice were exposed to cigarette smoke for 75 days (twice a day) and all experiments were performed on day 76. Experimental groups receive htMSCS either intraperitoneally or intranasally and/or LLL irradiation either alone or in association. We show that co-therapy greatly reduces lung inflammation, lowering the cellular infiltrate and pro-inflammatory cytokine secretion (IL-1ß, IL-6, TNF-α and KC), which were followed by decreased mucus production, collagen accumulation and tissue damage. These findings seemed to be secondary to the reduction of both NF-κB and NF-AT activation in lung tissues with a concomitant increase in IL-10. In summary, our data suggests that the concomitant use of MSCs + LLLT may be a promising therapeutic approach for lung inflammatory diseases as COPD.

Effects of High-Intensity Swimming on Lung Inflammation and Oxidative Stress in a Murine Model of DEP-Induced Injury.

Studies have reported that exposure to diesel exhaust particles (DEPs) induces lung inflammation and increases oxidative stress, and both effects are susceptible to changes via regular aerobic exercise in rehabilitation programs. However, the effects of exercise on lungs exposed to DEP after the cessation of exercise are not clear. Therefore, the aim of this study was to evaluate the effects of high-intensity swimming on lung inflammation and oxidative stress in mice exposed to DEP concomitantly and after exercise cessation. Male Swiss mice were divided into 4 groups: Control (n = 12), Swimming (30 min/day) (n = 8), DEP (3 mg/mL-10 µL/mouse) (n = 9) and DEP+Swimming (n = 8). The high-intensity swimming was characterized by an increase in blood lactate levels greater than 1 mmoL/L between 10th and 30th minutes of exercise. Twenty-four hours after the final exposure to DEP, the anesthetized mice were euthanized, and we counted the number of total and differential inflammatory cells in the bronchoalveolar fluid (BALF), measured the lung homogenate levels of IL-1ß, TNF-α, IL-6, INF-Ï«, IL-10, and IL-1ra using ELISA, and measured the levels of glutathione, non-protein thiols (GSH-t and NPSH) and the antioxidant enzymes catalase and glutathione peroxidase (GPx) in the lung. Swimming sessions decreased the number of total cells (p<0.001), neutrophils and lymphocytes (p<0.001; p<0.05) in the BALF, as well as lung levels of IL-1ß (p = 0.002), TNF-α (p = 0.003), IL-6 (p = 0.0001) and IFN-Ï« (p = 0.0001). However, the levels of IL-10 (p = 0.01) and IL-1ra (p = 0.0002) increased in the swimming groups compared with the control groups, as did the CAT lung levels (p = 0.0001). Simultaneously, swimming resulted in an increase in the GSH-t and NPSH lung levels in the DEP group (p = 0.0001 and p<0.002). We concluded that in this experimental model, the high-intensity swimming sessions decreased the lung inflammation and oxidative stress status during DEP-induced lung inflammation in mice.

Effect of pre-irradiation with different doses, wavelengths, and application intervals of low-level laser therapy on cytochrome c oxidase activity in intact skeletal muscle of rats.

Modulation of cytochrome c oxidase activity has been pointed as a possible key mechanism for low-level laser therapy (LLLT) in unhealthy biological tissues. But recent studies by our research group with LLLT in healthy muscles before exercise found delayed skeletal muscle fatigue development and improved biochemical status in muscle tissue. Therefore, the aim of this study was to evaluate effects of different LLLT doses and wavelengths in cytochrome c oxidase activity in intact skeletal muscle. In this animal experiment, we irradiated the tibialis anterior muscle of rats with three different LLLT doses (1, 3, and 10 J) and wavelengths (660, 830, and 905 nm) with 50 mW power output. After irradiation, the analyses of cytochrome c oxidase expression by immunohistochemistry were analyzed at 5, 10, 30 min and at 1, 2, 12, and 24 h. Our results show that LLLT increased (p < 0.05) cytochrome c oxidase expression mainly with the following wavelengths and doses: 660 nm with 1 J, 830 nm with 3 J, and 905 nm with 1 J at all time points. We conclude that LLLT can increase cytochrome c oxidase activity in intact skeletal muscle and that it contributes to our understanding of how LLLT can enhance performance and protect skeletal muscles against fatigue development and tissue damage. Our findings also lead us to think that the combined use of different wavelengths at the same time can enhance LLLT effects in skeletal muscle performance and other conditions, and it can represent a therapeutic advantage in clinical settings.

Methylene blue attenuates ischemia--reperfusion injury in lung transplantation.

BACKGROUND: Ischemia-reperfusion injury (IRI) is one of the principal obstacles for the lung transplantation (LTx) success. Several strategies have been adopted to minimize the effects of IRI in lungs, including ex vivo conditioning of the grafts and the use of antioxidant drugs, such as methylene blue (MB). We hypothesized that MB could minimize the effects of IRI in a LTx rodent model. METHODS: Forty rats were divided into four groups (n = 10) according to treatment (saline solution or MB) and graft cold ischemic time (3 or 6 h). All animals underwent unilateral LTx. Recipients received 2 mL of saline or MB intraperitoneally before transplantation. After 2 h of reperfusion, arterial blood and exhaled nitric oxide samples were collected and bronchoalveolar lavage performed. Then animals were euthanized, and histopathology analysis as well as cell counts and cytokine levels measurements in bronchoalveolar lavage fluid were performed. RESULTS: There was a significant decrease in exhaled nitric oxide, neutrophils, interleukin-6, and tumor necrosis factor-α in MB-treated animals. PaO2 and uric acid levels were higher in MB group. CONCLUSIONS: MB was able in attenuating IRI in this LTx model.

Comparative analysis of low-level laser therapy (660 nm) on inflammatory biomarker expression during the skin wound-repair process in young and aged rats.

The wound-healing process plays an essential role in the protective response to epidermal injury by tissue regeneration. In the elderly, skin functions deteriorate as a consequence of morphological and structural changes. This study aimed to evaluate and compare the effect of low-level laser therapy (LLLT) in cutaneous wound healing in young and aged rats. A total of 60 male rats comprising 30 young (± 30 days) and 30 aged (± 500 days) was used. The animals were divided into four experimental groups and underwent skin wound and/or treatment with LLLT (660 nm, 30 mW, 1.07 W/cm(2), 0.028 cm(2), 72 J/cm(2), and 2 J). Analyses were conducted to verify the effects of LLLT in the tissue repair process, in the gene expression, and protein expression of TNF-α, IL-1ß, and IL-10, obtained in skin wound model. Results showed that there were significant differences between the young control group and the aged control group and their respective treated groups (LLLT young and LLLT aged). We conclude that LLLT has shown to be effective in the treatment of skin wounds in young and aged animals at different stages of the tissue repair process, which suggests that different LLLT dosimetry should be considered in treatment of subjects of different ages. Further clinical trials are needed to confirm these findings in clinical settings.

Comparative analysis of two low-level laser doses on the expression of inflammatory mediators and on neutrophils and macrophages in acute joint inflammation.

Synovial membrane inflammation plays an important role in osteoarthritis (OA) pathophysiology. The synovial tissue of patients with initial OA is characterized by mononuclear cell infiltration and the production of pro-inflammatory cytokines and other mediators of joint injury. The study aims to evaluate the effect of low-level laser therapy (LLLT) at doses of 2 and 4 J on joint inflammation in rats induced by papain through histopathological analysis, differential counts of inflammatory cells; gene expression of IL-1ß, IL-6, and IL-10; and TNF-α protein expression. Male Wistar rats (20) were randomly divided (5 animals each) into a negative control group, an inflammation injury positive control group, a 2-J LLLT group subjected to injury and treated with 2 J of LLLT, and a 4-J LLLT group subjected to injury and treated with 4 J of LLLT. The animals were subjected to joint inflammation (4 % papain solution) and treated with LLLT. On the day of euthanasia, articular lavage was collected and centrifuged. The supernatant was analyzed for TNF-α protein expression by ELISA and IL-1ß, IL-6, and IL-10 mRNA by RT-PCR. The joint tissue was also examined histologically. ANOVA with Tukey's post hoc test was used for comparisons. All data were expressed as means ± S.D. (p < 0.05). Both laser modalities were efficient in reducing cellular inflammation and decreasing the expression of IL-1ß and IL-6. However, the 2-J treatment led to more reduction in TNF-α than the 4-J treatment. A single application of LLLT with 2 J was more efficient in modulating inflammatory mediators and inflammatory cells.

Protective effects of aerobic exercise on acute lung injury induced by LPS in mice.

INTRODUCTION: The regular practice of physical exercise has been associated with beneficial effects on various pulmonary conditions. We investigated the mechanisms involved in the protective effect of exercise in a model of lipopolysaccharide (LPS)-induced acute lung injury (ALI). METHODS: Mice were divided into four groups: Control (CTR), Exercise (Exe), LPS, and Exercise + LPS (Exe + LPS). Exercised mice were trained using low intensity daily exercise for five weeks. LPS and Exe + LPS mice received 200 µg of LPS intratracheally 48 hours after the last physical test. We measured exhaled nitric oxide (eNO); respiratory mechanics; neutrophil density in lung tissue; protein leakage; bronchoalveolar lavage fluid (BALF) cell counts; cytokine levels in BALF, plasma and lung tissue; antioxidant activity in lung tissue; and tissue expression of glucocorticoid receptors (Gre). RESULTS: LPS instillation resulted in increased eNO, neutrophils in BALF and tissue, pulmonary resistance and elastance, protein leakage, TNF-alpha in lung tissue, plasma levels of IL-6 and IL-10, and IL-1beta, IL-6 and KC levels in BALF compared to CTR (P ≤0.02). Aerobic exercise resulted in decreases in eNO levels, neutrophil density and TNF-alpha expression in lung tissue, pulmonary resistance and elastance, and increased the levels of IL-6, IL-10, superoxide dismutase (SOD-2) and Gre in lung tissue and IL-1beta in BALF compared to the LPS group (P ≤0.04). CONCLUSIONS: Aerobic exercise plays important roles in protecting the lungs from the inflammatory effects of LPS-induced ALI. The effects of exercise are mainly mediated by the expression of anti-inflammatory cytokines and antioxidants, suggesting that exercise can modulate the inflammatory-anti-inflammatory and the oxidative-antioxidative balance in the early phase of ALI.

Extracellular ATP exerts opposite effects on activated and regulatory CD4+ T cells via purinergic P2 receptor activation.

It has been reported that ATP inhibits or stimulates lymphoid cell proliferation depending on the cellular subset analyzed. In this study, we show that ATP exerts strikingly opposite effects on anti-CD3/CD28-activated and regulatory CD4(+) T cells (T(regs)), based on nucleotide concentration. We demonstrate that physiological concentrations of extracellular ATP (1-50 nM) do not affect activated CD4(+) T cells and T(regs). Conversely, higher ATP concentrations have a bimodal effect on activated CD4(+) T cells. Whereas 250 nM ATP stimulates proliferation, cytokine release, expression of adhesion molecules, and adhesion, 1 mM ATP induces apoptosis and inhibits activated CD4(+) T cell functions. The expression analysis and pharmacological profile of purinergic P2 receptors for extracellular nucleotides suggest that activated CD4(+) T cells are induced to apoptosis via the upregulation and engagement of P2X7R and P2X4R. On the contrary, 1 mM ATP enhances proliferation, adhesion, migration, via P2Y2R activation, and immunosuppressive ability of T(regs). Similar results were obtained when activated CD4(+) T cells and T(regs) were exposed to ATP released by necrotized leukemic cells. Taken together, our results show that different concentrations of extracellular ATP modulate CD4(+) T cells according to their activated/regulatory status. Because extracellular ATP concentration highly increases in fast-growing tumors or hyperinflamed tissues, the manipulation of purinergic signaling might represent a new therapeutic target to shift the balance between activated CD4(+) T cells and T(regs).

Anti-inflammatory effects of aerobic exercise in mice exposed to air pollution.

PURPOSE: Exposure to diesel exhaust particles (DEP) results in lung inflammation. Regular aerobic exercise improves the inflammatory status in different pulmonary diseases. However, the effects of long-term aerobic exercise on the pulmonary response to DEP have not been investigated. The present study evaluated the effect of aerobic conditioning on the pulmonary inflammatory and oxidative responses of mice exposed to DEP. METHODS: BALB/c mice were subjected to aerobic exercise five times per week for 5 wk, concomitantly with exposure to DEP (3 mg·mL(-1); 10 µL per mouse). The levels of exhaled nitric oxide, reactive oxygen species, cellularity, interleukin 6 (IL-6), and tumor necrosis factor α (TNF-α) were analyzed in bronchoalveolar lavage fluid, and the density of neutrophils and the volume proportion of collagen fibers were measured in the lung parenchyma. The cellular density of leukocytes expressing IL-1ß, keratinocyte chemoattractant (KC), and TNF-α in lung parenchyma was evaluated with immunohistochemistry. The levels of IL-1ß, KC, and TNF-α were also evaluated in the serum. RESULTS: Aerobic exercise inhibited the DEP-induced increase in the levels of reactive oxygen species (P < 0.05); exhaled nitric oxide (P < 0.01); total (P < 0.01) and differential cells (P < 0.01); IL-6 and TNF-α levels in bronchoalveolar lavage fluid (P < 0.05); the level of neutrophils (P < 0.001); collagen density in the lung parenchyma (P < 0.05); the levels of IL-6, KC, and TNF-α in plasma (P < 0.05); and the expression of IL-1ß, KC, and TNF-α by leukocytes in the lung parenchyma (P < 0.01). CONCLUSIONS: We conclude that long-term aerobic exercise presents protective effects in a mouse model of DEP-induced lung inflammation. Our results indicate a need for human studies that evaluate the pulmonary responses to aerobic exercise chronically performed in polluted areas.

Efeitos da suplementação oral com creatina sobre o metabolismo e a morfologia hepática em ratos / Effects of creatine oral supplementation on the hepatic metabolism and morphology of rats

A creatina é uma amina nitrogenada e tem sido utilizada principalmente por atletas e praticantes de atividade física que desejam aumentar a massa muscular e o desempenho físico. Entretanto seu uso não está somente relacionado à prática esportiva, pois inúmeros trabalhos apresentam efeitos benéficos na prática médica. Alguns estudos demonstraram que a suplementação oral com creatina resulta em aumento da sua biodisponibilidade plasmática e também de seus estoques em inúmeros órgãos. Entretanto, estudos sobre possíveis efeitos tóxicos da suplementação com creatina são escassos. Portanto, o objetivo deste trabalho foi avaliar os possíveis efeitos tóxicos da suplementação oral com creatina sobre a função e morfologia hepáticas em ratos após 14 dias de suplementação oral com creatina na dose de 0.5 g/kg/dia. A função hepática foi avaliada através de testes bioquímicos e a estrutura hepática foi avaliada através da massa hepática relativa e da análise histológica. Os resultados demonstraram que 14 dias de suplementação com creatina não alteraram a função hepática quando comparado os grupos controle e suplementado: AST (39.5 x 44.4 U/L), ALT (18.6 x 30.8 U/L), ALP (38.5 x 31.4 U/L), GGT (134.8 x 143.8 U/L), proteínas totais (5.1 x 5.5 g/dl), triglicérides (141.0 x 141.0 mg/dl), colesterol total (130.1 x 126.2 mg/dl), colesterol LDL (36.1 x 36.1 mg/dl), colesterol HDL (65.6 x 62.4 mg/dl), colesterol VLDL (25.0 x 28.0 mg/dl), e também estrutura hepática, exceto nos níveis plasmáticos de albumina (3.0 x 3.5 mg/dl - p<0.02). Nossos resultados demonstraram claramente que, ao menos na dose utilizada, a suplementação oral com creatina não induziu a nenhum tipo de efeito tóxico sobre o fígado.

Creatine is a nitrogenated amine and it has been used mainly by athletes and physical activity practitioners who wish to increase muscle mass and performance. However its use is not just related to sports practice, once several studies have shown beneficial effects on medical practice. Some studies have demonstrated that oral creatine supplementation increases its plasmatic bioavailability and also its concentration in several organs. However, studies about the possible toxic effects followed by creatine supplementation are scarce. Therefore, the aim of this work was to evaluate the hepatic structure and function in rats after 14 days of oral creatine supplementation at dose of 0.5g/kg/day. The hepatic function was evaluated through biochemical assays and the hepatic structure was analyzed through the relative hepatic mass and histological analysis. The results showed that 14 days of creatine supplementation did not alter the hepatic function and structure when compared with the control and supplemented groups, AST (39.5 x 44.4 U/L), ALT (18.6 x 30.8 U/L), ALP (38.5 x 31.4 U/L), GGT (134.8 x 143.8 U/L), total proteins (5.1 x 5.5 g/dl), triglycerides (141.0 x 141.0 mg/dl), total cholesterol (130.1 x 126.2 mg/dl), LDL cholesterol (36.1 x 36.1 mg/dl), HDL cholesterol (65.6 x 62.4 mg/dl), VLDL cholesterol (25.0 x 28.0 mg/dl), and also the hepatic structure, except for the albumin plasmatic levels (3.0 x 3.5 mg/dl - p<0.02). Our results clearly demonstrated that, at least at the used dosage, oral creatine supplementation did not induce any toxic effect on the liver.

Efeitos do treinamento físico aeróbio sobre a inflamação pulmonar alérgica crônica em camundongos / Effects of aerobic physical training on lung allergic: lung inflammation in mice

O presente estudo investigou os efeitos da atividade física aeróbia de intensidade leve e moderada sobre a inflamação e remodelamento pulmonar e também sobre a responsividade brônquica em um modelo experimental de inflamação pulmonar alérgica crônica. Os resultados demonstraram que atividade aeróbia de intensidade leve e moderada inibiram a inflamação e o remodelamento pulmonar (nas vias aéreas, nos vasos e parênquima pulmonares), mas não a responsividade brônquica. Estes efeitos antiinflamatórios da atividade física aeróbia foram atribuídos a uma diminuída expressão de interleucina 4 e 5 pelas células inflamatórias, nos compartimentos pulmonares estudados.O presente estudo investigou os efeitos da atividade física aeróbia de intensidade leve e moderada sobre a inflamação e remodelamento pulmonar e também sobre a responsividade brônquica em um modelo experimental de inflamação pulmonar alérgica crônica. Os resultados demonstraram que atividade aeróbia de intensidade leve e moderada inibiram a inflamação e o remodelamento pulmonar (nas vias aéreas, nos vasos e parênquima pulmonares), mas não a responsividade brônquica. Estes efeitos antiinflamatórios da atividade física aeróbia foram atribuídos a uma diminuída expressão de interleucina 4 e 5 pelas células inflamatórias, nos compartimentos pulmonares estudados.

The present study investigated the effects of aerobic physical activity of low and moderate intensity on the lung inflammation and remodeling and also on the bronchial responsiveness in a model of chronic allergic lung inflammation. The results show that aerobic activity of low and moderate intensity inhibited the lung inflammation and remodeling (in the airways, in the vessels and pulmonary parenchyma), but not the bronchial responsiveness. These anti-inflammatory effects of aerobic physical activity were attributed to decreased expression of interleukin 4 and 5 by inflammatory cells in the pulmonary compartments studied.