Exercise is known to induce changes in the gut, typically referred to as the ‘forgotten organ’, and changes in gut microbiota can also occur with exercise possibly imparting systemic benefits. The question remains whether or not microbiota from an exercised animal can independently affect skeletal muscle morphology. Our first objective was to examine whether an endurance exercise program could modify the microbiota in donor mice. Second, we aimed to elucidate if such an endurance-trained microbiota could be transferred to germ-free mice via fecal inoculation. Finally, we sought to determine how the morphology and functional characteristics of skeletal muscle were influenced as a result of fecal inoculation. We hypothesized that germ-free mice recipients inoculated with the microbiota from endurance trained donors would undergo morphological changes in muscle fibre type composition and physiological changes in skeletal muscle function associated with a more oxidative phenotype. Eight-week-old male C57BL/6NCrl donor mice (n = 20) were randomized into two groups: one group completed an endurance exercise training protocol on a treadmill machine 3x/week for 11 weeks (n = 10) while one group remained cage-bound (n = 10). Ten-week-old male (n = 7) and female (n = 9) germ-free mice were colonized with the cecal microbiota of the donor mice in that, equal numbers of germ-free mice were inoculated with exercised-microbiota as sedentary-microbiota. Glucose metabolism and performance measures were evaluated in the donors as well as the recipients post-inoculation. Muscle tissue was extracted for immunohistochemistry and mitochondrial assays. During the intra-peritoneal glucose tolerance test (IPGTT), significant differences in blood glucose were found at 30min between exercise-inoculated and sedentary-inoculated (23.4 ± 2.2; 29.0 ± 1.9 mmol/L, p<0.05).and change in blood glucose relative to baseline (12.04 ± 2.4; 18.3 ± 1.9 mmol/L, p<0.01). There were significant sex-based differences in the blood glucose response in inoculated animals such that there were significant differences in blood glucose between the exercise-inoculated females and sedentary-inoculated females at 15mins (28.4 ± 2.4; 30.6 ± 1.1 mmol/L, p<0.05) and 30mins (24.7 ± 3.6; 29.9 ± 2.4 mmol/L, p<0.01), however no differences between exercise-inoculated males and sedentary-inoculated males. In addition, there were significant differences in the change in blood glucose relative to baseline between the exercise-inoculated females and sedentary-inoculated females at 15mins (12.3 ± 1.9; 20.6 ± 0.8 mmol/L, p<0.01) and 30mins (10.2 ± 2.6; 19.9 ± 2.1 mmol/L, p<0.001). This novel characterization of a link between gut microbiota and skeletal muscle suggests a transmissible capacity of microbiota to impart properties of ‘healthy’ muscle into compromised populations. / Thesis / Master of Science (MSc) / The gut microbiome or microbiota describes the composition of the human gut – remarkably, over 100 trillion bacterial cells live in symbiosis with the cells of the human body. Research from the past decade has elucidated the salient nature of the human gut microbiome on immunity, metabolic homeostasis, and overall health and disease. Transformative research in the field has demonstrated the ability to transfer these bacterial colonies from one individual to another and elicit change, such as altering body mass and adiposity, respective to their donor. The interaction between gut microbiota and other organ systems i.e. brain, liver, adipose tissue has been the focus of several recent investigations, suggesting that lifestyle changes such as diet and exercise can influence communication between the gut and various other organs and contribute to changes in function. Skeletal muscle is the largest muscle in the human body accounting for 40% of total mass and although the main role of skeletal muscle is locomotion and postural stabilization, it is integral for the regulation of blood glucose as well as a reservoir for other macronutrients. Acute and chronic physical exercise cause a myriad of adaptive responses throughout the human body including in skeletal muscle and the gut. Therefore, the existence and influence of a gut-muscle link or ‘axis’ on human health cannot be ignored. What is unclear exactly, is if exercise-induced adaptations in the gut of an individual can be transferred to elicit change in the gut of a recipient and further induce adaptations at the level of the skeletal muscle.

Duchenne muscular dystrophy (DMD) is a fatal, x-linked disease that causes progressive muscle weakness and susceptibility to damage. DMD is caused by a lack of dystrophin, a large muscle protein that performs both structural and signaling functions. A promising treatment currently in clinical trials is microdystrophin gene therapy, which delivers a truncated version of dystrophin to muscle via a viral vector. Preclinical studies have established efficacy of microdystrophin to improve muscle quality and function. With clinical success of this treatment, patients affected by DMD could become more physically active. However, the effect of exercise on both dystrophic and gene therapy-treated muscles is unclear. Recently, we demonstrated that microdystrophin gene therapy with and without 21 weeks of voluntary wheel running (VWR) improved treadmill time to fatigue and in vivo plantarflexor torque output in young mdx mice, a mouse model of DMD. Although treated mice could run well, diaphragm force and power output were blunted by VWR. A subsequent study tested longevity of two different microdystrophin gene therapy constructs in combination with VWR. Versions of each construct are being tested in clinical trials. Construct 1 contained the nNOS-binding site found in full-length dystrophin, which localizes nNOS to the sarcolemma and reduces functional ischemia of exercising limb muscles, while construct 2 lacked the nNOS-binding site and was the same microdystrophin used in the previous study. Gene- therapy treated mice that were sedentary or performed 52 weeks of VWR demonstrated similar outcomes including increased plantarflexor torque and exceptional treadmill endurance capacity. However, ex vivo diaphragm and soleus force, as well as metabolic enzyme and mitochondrial respiration assays were differentially improved, revealing unique physiological adaptations to each microdystrophin construct. Together, the data demonstrated that response to exercise after gene therapy treatment was variable and dependent on age, microdystrophin construct, and muscle type. / Doctor of Philosophy / Duchenne muscular dystrophy (DMD) is a rare, fatal muscle disease that causes progressive muscle weakness and cardiorespiratory failure. Available treatments, such as corticosteroids, slow progression of the disease but do not address the underlying genetic cause. DMD is caused by a genetic mutation that results in the loss of the muscle protein dystrophin. Microdystrophin gene therapy aims to address the genetic cause of the disease by using a non-pathogenic virus to deliver microdystrophin, a small, functional version of dystrophin, to muscle. This gene therapy is in clinical trials, and, if it is successful, treated patients will likely want to engage in more physical activity than previously possible due to muscle weakness. However, the effects of physical activity on muscles treated with gene therapy are unclear. Therefore, we conducted two studies to test the effects of voluntary wheel running on microdystrophin gene therapy in the mdx mouse, a model of DMD. The first study demonstrated that voluntary wheel running was beneficial to whole-body muscle function in mice treated with microdystrophin gene therapy. However, adaptations to the gene therapy and voluntary wheel running were variable in individual muscles. In the second study, we tested two microdystrophin constructs, which each contain different structural components of full-length dystrophin. In addition, mice ran for 52 weeks, more than twice as long as the first study. The results of the second study found that adaptations in individual muscles depended on microdystrophin construct and activity level. Additionally, we confirmed that voluntary wheel running was beneficial to whole-body function of microdystrophin–treated muscles. Together, these studies demonstrated that adaptations of gene therapy-treated muscles were dependent on microdystrophin structure, activity level, and age.

Insulin resistance (IR), T2DM, and obesity together form a cluster of interrelated metabolic challenges that may be linked by metabolic inflexibility. Metabolic inflexibility is characterized by the resistance to switching substrate oxidation preference based on substrate availability and can be measured in either fasted or insulin-stimulated conditions. As the largest site for glucose disposal and a primary tissue influencing regulation of blood glucose concentrations, skeletal muscle likely plays a central role in regulating substrate oxidation preference based on substrate availability. Skeletal muscle lipotoxicity caused by an impaired regulation of fat uptake and oxidation is postulated to disrupt insulin signaling and lead to skeletal muscle IR. High dietary saturated fat intake results in reduced basal fat oxidation and a resistance to switching to carbohydrate oxidation during insulin-stimulated conditions in susceptible individuals. This metabolic inflexibility may lead to an accumulation of intramyocellular species that impair insulin signaling. Endurance exercise training improves the capacity for fat oxidation in metabolically inflexible individuals. However, relatively little is known about how endurance exercise training influences substrate oxidation preference when paired with a high fat diet (HFD). Therefore, the purpose of this study was to determine the effects of a HFD on substrate metabolism in skeletal muscle of sedentary and endurance trained (ET) males. Healthy, sedentary (n=17) and ET (n=7) males first consumed a 10-day moderate carbohydrate diet (55% carbohydrate, 30% total fat, <10% saturated fat) isocaloric to their individual energy requirements and then underwent a 4- hour high fat challenge testing session. During the session, they consumed a high fat meal (820 kcals; 25% carbohydrate, 63% total fat [26% saturated fat]), and skeletal muscle biopsies were taken in the fasted and 4-hour postprandial conditions. Participants then consumed a 5-day HFD (30% carbohydrate, 55% total fat, 25% saturated fat) and repeated the high fat challenge testing session. Substrate oxidation measures were performed on the collected skeletal muscle tissue, and the meal effect, defined as the percent change from the fasting to 4- hour postprandial condition, for each measure was calculated. There was a HFD by physical activity group interaction on meal effect for metabolic flexibility (P<0.05) and a HFD effect on meal effect for glucose oxidation (P<0.05). Meal effects for metabolic flexibility and glucose oxidation were maintained in the ET (20 ± 4% to 41 ± 21% and 128 ± 92% and 41 ± 15%, respectively; both P>0.05) but decreased in the sedentary (34 ± 7% to 4 ± 5% and 78 ± 26% to -21 ± 6%, respectively; both P<0.01) group. There were trends toward HFD effects on reductions in meal effects for total (P=0.062) and incomplete (P=0.075) fat oxidation, which were driven primarily by an increase in fasting total (12.1 ± 2.6 nmol/mg protein/h to 18.5 ± 2.3 nmol/mg protein/h; P<0.01) and incomplete (11.5 ± 2.5 nmol/mg protein/h to 17.6 ± 2.3 nmol/mg protein/h; P<0.01) fat oxidation in the ET group as a result of the HFD. Fasting total and incomplete fat oxidation did not change in the sedentary group (7.3 ± 0.8 nmol/mg protein/h to 7.8 ± 0.8 nmol/mg protein/h and 6.8 ± 0.7 nmol/mg protein/h to 7.2 ± 0.8 nmol/mg protein/h, respectively; both P>0.05). Overall, these findings suggest the ET state attenuates deleterious effects of a short-term HFD on reduced metabolic flexibility and insulin-stimulated glucose oxidation. In addition, a HFD-induced reduction in fat oxidation during the fasted-to-fed transition may be caused by differing mechanisms in sedentary and ET individuals. These findings provide a basis for future work targeting the elucidation of potential mechanistic differences in substrate oxidation preference between sedentary and ET individuals. / Ph. D. / Type 2 diabetes (T2DM) is a commonly occurring disease worldwide, and treatment of the disease is considerably burdensome for individuals and societies. T2DM is closely related to insulin resistance (IR) and obesity, and in each of these conditions, the characteristic of metabolic inflexibility has been observed. Metabolic inflexibility is a reduced ability to adjust fat or carbohydrate utilization for energy based on the availability of each of these macronutrients. Skeletal muscle may be an important tissue in the regulation of macronutrient utilization since it plays a key role in blood glucose regulation. High dietary saturated fat intake may lead to metabolic inflexibility in skeletal muscle in susceptible individuals. This metabolic inflexibility may result in increased storage of fat within skeletal muscle, which is hypothesized to disrupt insulin signaling. This disruption can lead to IR. Endurance exercise training improves metabolic flexibility. However, little is known about how endurance exercise training influences macronutrient utilization when paired with a high fat diet (HFD). Therefore, the purpose of this study was to determine the effects of a HFD on macronutrient utilization in skeletal muscle of sedentary and endurance trained (ET) males. Seventeen healthy, sedentary males and seven ET males first consumed a 10-day moderate-carbohydrate diet that was provided by the study investigators and designed to keep each participant weight stable. Participants then underwent a high fat challenge testing session in which they consumed a high fat meal and had skeletal muscle biopsies taken both before and after the meal. Participants then consumed a 5-day HFD, also designed to keep them weight stable, and repeated the high fat challenge testing session. Macronutrient utilization measures were performed on the collected skeletal muscle samples. Overall, metabolic flexibility was reduced in the sedentary group but was maintained in the ET group, which suggests that ET individuals may be protected against developing a HFD-induced metabolic inflexibility in skeletal muscle and its associated downstream negative effects on insulin signaling. In addition, fat utilization during the high fat challenge meal decreased in both sedentary and ET individuals as a result of the HFD. However, fat utilization in the fasted state was higher in ET individuals after the HFD compared with baseline, but fat utilization was the same in sedentary individuals before and after the HFD. This suggests there may be differences between sedentary and ET individuals in the mechanisms involved in the adjustment of fat utilization to dietary fat intake. Further research is needed to understand these differences, as they may play important roles in understanding how IR and T2DM develop.

NAND flash-based Solid State Devices (SSDs) provide high performance and energy efficiency and at the same time their capacity continues to grow at an unprecedented rate. As a result, SSDs are increasingly being used in high end computing systems such as supercomputing clusters. However, one of the biggest impediments to large scale deployments is the limited erase cycles in flash devices. The natural skewness in I/O workloads can results in Wear imbalance which has a significant impact on the reliability, performance as well as lifetime of the cluster. Current load balancers for storage systems are designed with a critical goal to optimize performance. Data migration techniques are used to handle wear balancing but they suffer from a huge metadata overhead and extra erasures. To overcome these problems, we propose an endurance-aware write off-loading technique (EWO) for balancing the wear across different flash-based servers with minimal extra cost. Extant wear leveling algorithms are designed for a single flash device. With the use of flash devices in enterprise server storage, the wear leveling algorithms need to take into account the variance of the wear at the cluster level. EWO exploits the out-of-place update feature of flash memory by off- loading the writes across flash servers instead of moving data across flash servers to mitigate extra-wear cost. To evenly distribute erasures to flash servers, EWO off-loads writes from the flash servers with high erase cycles to the ones with low erase cycles by first quantitatively calculating the amount of writes based on the frequency of garbage collection. To reduce metadata overhead caused by write off-loading, EWO employs a hot-slice off-loading policy to explore the trade-offs between extra-wear cost and metadata overhead. Evaluation on a 50 to 200 node SSD cluster shows that EWO outperforms data migration based wear balancing techniques, reducing up to 70% aggregate extra erase cycles while improving the write performance by up to 20% compared to data migration. / Master of Science

Plusieurs études ont démontré que la consommation d’un repas à indice glycémique bas (LGI) avant un exercice physique favorisait l’oxydation des lipides, diminuait les épisodes d’hypoglycémie et améliorait la performance. Par contre, d’autres recherches n’ont pas observé ces bénéfices. Le but de cette étude consiste à démontrer l’impact de l’ingestion de déjeuners avec différents indices glycémiques (IG) sur la performance en endurance de cyclistes de haut niveau. Dix cyclistes masculins ont complété trois protocoles attribués de façon aléatoire, séparés par un intervalle minimal de sept jours. Les trois protocoles consistaient en une épreuve contre la montre, soit trois heures après avoir consommé un déjeuner à indice glycémique bas ou élevé contenant 3 grammes de glucides par kg de poids corporel, soit à compléter l’exercice à jeun. Les résultats obtenus pour le temps de course montrent qu’il n’y pas de différence significative entre les protocoles. Par contre, on observe que le nombre de révolutions par minute (RPM) est significativement plus élevé avec le protocole à indice glycémique élevé (HGI) (94,3 ± 9,9 RPM) comparativement au protocole à jeun (87,7 ± 8,9 RPM) (p<0,005). Au niveau de la glycémie capillaire, on observe que durant l’exercice, au temps 30 minutes, la glycémie est significativement supérieure avec le protocole à jeun (5,47 ± 0,76 mmol/L) comparé à HGI (4,99 ± 0,91 mmol/L) (p<0,002). Notre étude n’a pas permis de confirmer que la consommation d’un repas LGI avant un exercice physique améliorait la performance physique de façon significative. Cependant, notre recherche a démontré que la diversité des protocoles utilisés pour évaluer l’impact de l’indice glycémique sur la performance physique pouvait occasionner des variations positives dans les temps de courses. Par conséquent, il s’avère nécessaire de faire d’autres recherches qui reproduisent les situations de compétition de l’athlète soit la course contre la montre. / Many studies have shown that the consumption of a low glycemic index (LGI) meal before exercise promotes lipid oxidation, thus lowering the amount of hypoglycemic occurrence and improving physical performance. However, other studies have not observed such benefits. The objective of this study is to demonstrate the impact of ingesting various glycemic index (GI) breakfasts on the endurance performance of high-level cyclists. Ten men completed three randomly allocated protocols, and each was separated by a time interval of a minimum of seven days. Each protocol was composed of a time trial, where a measure was taken three hours either after consuming a breakfast of low or high glycemic index containing three grams of glucose per kg of body weight, or after completing exercise while fasting. The race time results demonstrated that there were no significant differences between the protocols. However, the number of revolutions per minutes (RPM) was significantly higher with the high glycemic index level protocol (94,3 ± 9,9) in comparison to the fasting protocol (87,7 ± 8,9) (p<0,005). Furthermore, the capillary glycemic profile showed that, during exercise at 30 minutes, blood glucose level was significantly higher in the fasting protocol (5,47 ± 0,76 mmol/L) in comparison to the high glycemic index (HGI) protocol (4,99 ± 0,91 mmol/L) (p<0,002). Our study did not confirm that the consumption of a LGI meal before physical exercise significantly improves physical performance. Yet it demonstrated that the diversity of protocols used to evaluate the impact of glycemic index on physical performance could generate positive impact during the race time. Therefore, there is a need to conduct further research that can reproduce athletic competition situations, such as time trials.

Submitted by Marcos Anselmo (marcos.anselmo@unipampa.edu.br) on 2018-09-27T17:53:00Z No. of bitstreams: 1 ALVARO SOSA MACHADO.pdf: 1403839 bytes, checksum: ecb430aded30475dee48fa2ac550cd0d (MD5) / Approved for entry into archive by Marcos Anselmo (marcos.anselmo@unipampa.edu.br) on 2018-09-27T17:53:12Z (GMT) No. of bitstreams: 1 ALVARO SOSA MACHADO.pdf: 1403839 bytes, checksum: ecb430aded30475dee48fa2ac550cd0d (MD5) / Made available in DSpace on 2018-09-27T17:53:12Z (GMT). No. of bitstreams: 1 ALVARO SOSA MACHADO.pdf: 1403839 bytes, checksum: ecb430aded30475dee48fa2ac550cd0d (MD5) Previous issue date: 2018-02-23 / A prática regular de exercício intenso é benéfica à saúde, mas quando realizada em dias consecutivos pode intensificar os efeitos deletérios da fadiga muscular, podendo gerar perda de atividade neuromuscular, aumento do dano às fibras musculares e incremento do risco de lesão. Estratégias para inibir ou retardar estes efeitos da fadiga, principalmente o estresse oxidativo, são desejáveis. Nesse contexto, o extrato de chá verde (ECV), derivado da Camellia sinensis, pode ser útil, visto que tem conhecidas propriedades anti-inflamatórias e antioxidantes. Neste estudo, nosso objetivo foi verificar se a suplementação com extrato de chá verde beneficia marcadores de dano muscular, estresse oxidativo e desempenho em condição de fadiga. Dezesseis atletas amadores treinados, todos homens, foram testados durante exercício de 9 ciclismo em duas condições de exercício: sem suplementação sem fadiga; e com suplementação (placebo, n=8; extrato de chá verde 500 mg/dia durante 15 dias, n=8) com fadiga (extensão de joelhos até a exaustão induzida em dois dias consecutivos). Coletas sanguíneas para determinação de marcadores de dano muscular e estresse oxidativo, e medidas de eletromiografia, para determinação da ativação elétrica neuromuscular dos vastos laterais, além de parâmetros de treinamento e frequência cardíaca, foram quantificados e comparados entre os grupos nas diferentes condições. Os valores normalizados de eletromiografia root mean square e mediana da frequência da eletromiografia não diferiram entre a pedalada sem e com fadiga no grupo chá verde, enquanto que o grupo placebo apresentou prejuízo na contratilidade muscular decorrente da fadiga. O maior custo de frequência cardíaca confirma que esse redução na EMG foi combinada por um aumento do esforço na tarefa. O ECV também foi capaz de inibir dano muscular e evitar o estresse oxidativo, ao contrário do grupo placebo na comparação entre as pedaladas sem e com fadiga. Dessa forma, as propriedades antioxidantes do chá verde parecem evitar o dano muscular induzido pelo estresse oxidativo e preservar a contratilidade muscular de atletas submetidos à fadiga em dias consecutivos. Sendo assim, a suplementação com chá verde pode ser considerada como uma estratégia válida para o treinamento físico em tarefas extenuantes. / The regular practice of intense physical exercise benefits health, but when the sessions are accomplished in consecutive day it migh intensify some deleterious effects of muscle fatigue, which can impair efficiency, promote muscle damage and increase injury risk. The interest in strategies to avoid or delay such effects, especially the oxidative stress, are desirable. In this regard, the green tea extract, from Camellia sinesis, can be useful due to its recognized antioxidant and antiinflamatory properties. Here our purpose was to determine whether the supplementation with green tea extract can benefit markers of muscle damage, oxidative stress and performance in exercise under fatigue. Sixteen male athletes trained were evaluted in cycling exercise under two conditions: without supplementation and without fatigue, and supplemented (placebo n=8; extrato de chá verde, n=8, 500 mg/dia durante 15 dias) and with fatigue (knee extension until exhaustion in two consecutive days). Blood 11 samples served to determine markers of muscle damage and oxidative stress. Electromyography was employed to monitore the muscle activation from vastus lateralis, as well as training parameters like heart rate, were quantified and compared between the groups and exercise conditions. Muscle activation did not differ between the cycling with and without fatigue in the green tea group, whereas in the placebo group there a loss of contractility due to fatigue. A higher cost observed by the higher heart rate support that reduction in the activation in the placebo group relies on the effort associated to the performance of the cycling exercise. Green tea supplementation was able to avoid increase in the muscle damage and oxidative stress in response to the exercise compared to the placebo group. Therefore, the properties of green tea seem to delay or avoid the muscle damage resultant of oxidative stress and preserves the contractility in athletes submitted to exercise under a fatigue state. As a conclusion, the supplementation with green tea can be considered a valid strategy in the physical training during extenuant tasks.

Submitted by Marcos Anselmo (marcos.anselmo@unipampa.edu.br) on 2018-09-28T13:49:10Z No. of bitstreams: 1 CRISTINI ESCOBAR VIANA.pdf: 1264568 bytes, checksum: 8c87e6df98a20d981c5e1c739240eae4 (MD5) / Approved for entry into archive by Marcos Anselmo (marcos.anselmo@unipampa.edu.br) on 2018-09-28T13:49:26Z (GMT) No. of bitstreams: 1 CRISTINI ESCOBAR VIANA.pdf: 1264568 bytes, checksum: 8c87e6df98a20d981c5e1c739240eae4 (MD5) / Made available in DSpace on 2018-09-28T13:49:26Z (GMT). No. of bitstreams: 1 CRISTINI ESCOBAR VIANA.pdf: 1264568 bytes, checksum: 8c87e6df98a20d981c5e1c739240eae4 (MD5) Previous issue date: 2018-04-11 / A hipercolesterolemia se caracteriza pela elevação patológica da taxa de colesterol sanguínea aumentando a formação de radicais livres, o qual provoca oxidação e danos nos lipídios celulares causando crescimento da atividade inflamatória e progressão negativa da função cognitiva. O consumo de vinho tinto atua minimizando estes efeitos, inibindo a expressão de citocinas e modulando os níveis do fator neurotrófico derivado do cérebro (BDNF), da proteína cíclica de ligação ao elemento AMPc-resposta (CREB), dos microRNAs (miARN), e a ação da enzima acetilcolinesterase (AChE). Os antioxidantes, os flavonóides e os polifenóis tornaram-se as primeiras substâncias contidas no vinho tinto com efeitos benéficos comprovados em várias doenças, como a inibição da oxidação de LDL e parâmetros envolvidos na resposta inflamatória. A ingestão regular de bebidas ricas em polifenóis demonstra exercer consequências favoráveis à saúde humana, como diminuição da incidência de doenças cardiovasculares, câncer e proteção contra doenças neurodegenerativas, entre outras. Portanto, o presente estudo teve como objetivo investigar o potencial efeito neuroprotetor do vinho Ruby Carbenet em camundongos nocaute para o receptor LDLr-/- expostos à dieta hipercolesterolêmica. O vinho foi submetido a análise em vitro para quantificação de polifenóis, antocianinas, ácido cafeico, ácido gálico, epicatequina e resveratrol. Foram utilizados 40 camundongos adultos com 90 dias, de 20 a 25 gramas. Os animais foram divididos em 4 grupos (n=10) e para a indução da hipercolesterolemia foi borrifado colesterol diluído em álcool puro 96° C, sobre a dieta comercial (Puro Trato PB 22) durante 90 dias. Ao final do tratamento foi realizado teste comportamental de memória, tarefa do labirinto aquático de Morris (MWMT), logo após, o sangue foi coletado por punção cardíaca e o córtex pré-frontal e o hipocampo foram removidos para os ensaios bioquímicos. Foram determinados os níveis de lipídios plasmáticos e as citocinas pró-inflamatórias, interferon gama (IFN-γ), fator de necrose tumoral-α (TNF-α), interleucina-1β (IL-1β) e interleucina-6 (IL-6) no hipocampo e córtex pré-frontal. Também foram avaliadas a atividade da AChE e os níveis das proteínas estruturais BDNF e CREB, e os biomarcadores microRNAs. Nossos resultados mostraram que a dieta hipercolesterolemica causa um aumento nos lipídios plasmáticos, nas citocinas pró-inflamatórias e na atividade da enzima AChE nos camundongos LDLr-/-, o que foi atenuado pelo consumo de vinho tinto através da diminuição do estado inflamatório. A dieta com elevado índice de colesterol diminuiu os níveis de BDNF, CREB e microRNAs cerebrais, e o consumo moderado de vinho tinto foi capaz de reverter estas proteínas estruturais BDNF e CREB, e os biomarcadores miRNA146a e 155, promovendo a neuroproteção e a melhora da memória. O vinho Ruby Cabernet apresentou potencial antioxidante confirmado pelos seus teores de ácido gálico 135, 3 mg/L, ácido caféico 91,2 mg/L, epicatequina 242,2 mg/L e resveratrol 102,2 mg/L. O consumo moderado do vinho proporcionaram aos camundongos melhora no déficit cognitivo e plasticidade, corroborando com o resultado do teste comportamental, no qual o MWMT está relacionado com o sistema de aprendizado e memória. Com isso, verificou-se que o vinho Ruby Carbenet demonstrou efeito neuroprotetor e reduziu os níveis dos lipídios plasmáticos, modulando as citocinas, agindo na manutenção da neuroplasticidade e regulação da atividade da acetilcolinesterase em camundongos hipercolesterolêmicos. Palavras-chave: Compostos fenólicos. Déficit cognitivo. Dieta com elevado índice de colesterol. Camundongos nocaute para receptor LDLr-/-. Neuroplasticidade. / Hypercholesterolemia is characterized by the pathological elevation of the blood cholesterol level, increasing the formation of free radicals, which causes oxidation and damage to the cellular lipids causing inflammatory activity growth and negative progression of cognitive function. Red wine consumption minimizes these effects by inhibiting cytokine expression and modulating levels of brain-derived neurotrophic factor (BDNF), cyclic cAMP-binding element (CREB), microRNAs (miRNA), and the action of the enzyme acetylcholinesterase (AChE). Antioxidants, flavonoids and polyphenols have become the first substances contained in red wine with proven beneficial effects in various diseases, such as the inhibition of LDL oxidation and parameters involved in the inflammatory response. Regular ingestion of polyphenol-rich beverages has a positive effect on human health, such as reducing the incidence of cardiovascular diseases, cancer and protection against neurodegenerative diseases, among others. Therefore, the present study aimed to investigate the potential neuroprotective effect of Ruby Carbenet wine in knockout mice for the Ldlr-/- receptor exposed to the hypercholesterolemic diet. The wine was submitted to in vitro analysis for quantification of polyphenols, anthocyanins, caffeic acid, gallic acid, epicatechin and resveratrol. 40 adult mice with 90 days, from 20 to 25 grams were used. The animals were divided into 4 groups (n=10) and for the induction of hypercholesterolemia cholesterol was diluted in pure alcohol 96 ° C, on the commercial diet (Puro Trato PB 22) for 90 days. At the end of the treatment was performed memory behavioral test, Morris water maze task (MWMT), soon after, blood was collected by cardiac puncture and the prefrontal cortex and hippocampus were removed for biochemical assays. The levels of plasma lipids and proinflammatory cytokines, interferon gamma (IFN-γ), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) in the hippocampus and prefrontal cortex. We also evaluated the activity of AChE and the levels of the structural proteins BDNF and CREB, and the biomarkers microRNAs. Our results showed that the hypercholesterolemic diet causes an increase in plasma lipids, proinflammatory cytokines and AChE enzyme activity in Ldlr-/- mice, which was attenuated by the consumption of red wine through the reduction of the inflammatory state. The high cholesterol diet decreased levels of BDNF, CREB and brain microRNAs, and moderate consumption of red wine was able to revert these structural proteins BDNF and CREB, and the miRNA146a and 155 biomarkers, promoting neuroprotection and the improvement of memory. Ruby Cabernet wine showed antioxidant potential confirmed by its content of gallic acid 135.3 mg/L, caffeic acid 91.2 mg/L, epicatechin 242.2 mg/L and resveratrol 102.2 mg/L. The moderate consumption of wine gave the mice an improvement in cognitive deficit and plasticity, corroborating with the result of the behavioral test, in which MWMT is related to the learning and memory system. Thus, it was verified that Ruby Carbenet wine demonstrated neuroprotective effect and reduced plasma lipid levels, modulating cytokines, acting to maintain neuroplasticity and regulate acetylcholinesterase activity in hypercholesterolemic mice. Keywords: Phenolic compounds. Cognitive deficit. Diet with high cholesterol. Knockout mice for Ldlr-/- receptor. Neuroplasticity.

O objetivo desse estudo foi verificar as repercussões clínicas e na capacidade cardiopulmonar, resultantes das alterações agudas morfofuncionais cardíacas e dos marcadores de injúria miocárdica após a realização de uma maratona, assim como a influência dos polimorfismos da ECA e BNP. Para tanto, 74 maratonistas, que participariam da XIX Maratona Internacional de São Paulo 2013 foram submetidos aos seguintes procedimentos: anamnese, exame físico, avaliação física, ecocardiograma, eletrocardiograma, bem como um teste cardiopulmonar. 24 horas antes da maratona, foi realizada uma coleta de sangue, em jejum. No terceiro momento, imediatamente antes da maratona, os atletas foram submetidos a medida de peso e bioimpedância elétrica a fim de caracterizar a quantidade de água corporal. Imediatamente após a maratona, os atletas foram submetidos a medida de peso, bioimpedância elétrica, coleta de sangue e ecocardiograma. 24 e 72 horas após a maratona, os atletas foram submetidos a coleta de sangue. No sétimo e último momento, entre três e quinze dias apos a maratona, novamente um teste cardiopulmonar. Os principais resultados foram: a) Houveram alterações estatisticamente significativas em todos os marcadores de injúria miocárdica no período após a maratona, sem retorno aos valores basais 72 horas após a maratona, exceto para troponina; b) Não houve correlação linear entre os marcadores relacionados a isquemia e morte celular e o BNP. Porém, houve correlação cúbica entre o BNP e a troponina, além da correlação entre todos os marcadores de injúria relacionados a isquemia e morte, com efeito baixo deles na troponina, na análise de regressão linear; c) Houve influência da idade e experiência de treinamento na liberação de troponina e BNP, e da intensidade de realização da prova nos outros marcadores; d) Houve influência das características ecocardiográficas na liberação de troponina; e) O aumento das capacidades pulmonares na espirometria de repouso, assim como na ventilação do 2º limiar e pico no teste cardiopulmonar correlacionaram-se significativamente com a queda de hemoglobina ocorrida nos dias após a maratona; f) A redução dos níveis de hemoglobina e hematócrito nos maratonistas, 24 e 72 horas após a maratona, caracterizam a anemia do atleta; g) Não houve correlação entre os polimorfismos da ECA e do BNP e as características ecocardiográficas relacionadas ao coração de atleta, porém há correlação com a liberação de BNP após a maratona / The aims of this study was to verify the clinical implications and in the cardiopulmonary capacity resulting from acute cardiac morphofunctional changes and myocardial injury markers after a marathon, as well as the influence of ACE and BNP polymorphisms. Therefore, 74 marathon runners, which participate in the XIX International Marathon of São Paulo in 2013, underwent the following procedures: anamnesis, physical examination, fitness assessment, echocardiogram, electrocardiogram and a cardiopulmonary exercise testing. 24 hours before the marathon, a blood collect was held. Immediately before the marathon, athletes underwent measurement of weight and bioelectrical impedance to characterize the amount of body water. Immediately after the marathon, athletes underwent weight measurement, electrical impedance, blood collect and echocardiogram. 24 and 72 hours after the marathon athletes collected blood. In the seventh and final time between three and fifteen days after the marathon, a cardiopulmonary exercise test was performed. The main results were: a) There were statistically significant changes in all myocardial injury markers in the period after the marathon, which didn\'t return to basal values 72 hours after marathon, except to cardiac troponins; b) There was no linear correlation between the marker related to ischemia and cell death and the BNP. However, there cubic correlation between BNP and troponin, in addition to the correlation between all markers of injury related to cellular ischemia and death, with low effect on troponin in the linear regression analysis; c) Age and training experience affected the release of troponin and BNP, and intensity affected the others markers; d) There was influence of echocardiographic features in the release of troponin; e) The increase in lung capacity in spirometry as well as ventilation of the second threshold and peak in the cardiopulmonary test were significantly correlated with the decrease in haemoglobin occurred after marathon; f) The reduction of haemoglobin and haematocrit levels in marathon runners, 24 and 72 hours after marathon called athletes anaemia; g) There was no correlation between ACE and BNP polymorphisms and echocardiographic features related to the athlete\'s heart, but correlation with the release of BNP after marathon

Contexte: Il n’y a pas de consensus concernant la meilleure activité physique pour réduire le risque cardio-vasculaire (RCV) résultant de l'accumulation du tissu adipeux viscéral dans le syndrome métabolique (SMet). Objectif: analyser les effets de l'activité physique sur le tissu adipeux viscéral et sur le RCV chez des patients SMet. Méthodes: 100 adultes, 50-70 ans, ont été randomisés en trois groupes d’activité physique: mixte (endurance et résistance) résistance modérée + endurance modérée (re), Résistance intense + endurance modérée (Re), résistance modérée + Endurance intense (rE). Une cure de trois semaines (J0 à J20), en institution, a précédé un suivi à domicile d’une année (M12). Nous avons suivi le tissu adipeux viscéral et la composition corporelle par DXA, les paramètres du SMet, les performances en force et en endurance, et le RCV en utilisant le score de Framingham et l’épaisseur intima-média carotidienne. L’observance a été évaluée entre D20 et M12. Résultats: 78 participants (78%) ont terminé l'étude. À J20, la perte de graisse viscérale était la plus élevée pour Re (-18%, p<.0001) et plus élevée pour rE que re (-12% vs 7%, p<.0001). De même, à partir de M3, la graisse viscérale a plus pour Re et rE (p<.05) pour atteindre à M12 une perte de graisse viscérale de -21,5% (Re) et -21,1% (rE) > -13,0% (re) (p<.001). Le RCV, le SMet et les performances physiques ont été améliorées dans tous les groupes. Les principales améliorations ont été obtenues durant la cure et ont ensuite évolué en fonction de l’observance. Particulièrement entre M6 et M12, les non-observants dégradent leurs améliorations alors que les observants restent stables. La perte de tissu adipeux viscéral est corrélée aux améliorations des paramètres du SM. Conclusions: Les 3 modalités d'activité physique induisent une perte de graisse viscérale et améliorent le RCV et le SMet, mais une haute intensité en résistance entraîne une amélioration plus rapide. Une cure avec un encadrement quotidien est indispensable pour aider les patients à atteindre leurs objectifs. L’observance semble être le principal défi dans le succès du traitement du SM. / Background: Opinions differ over the type of physical activity that best limits the cardiovascular risk (CVR) resulting from visceral fat accumulation in the metabolic syndrome (MetS). Aim: To analyze the effects of physical activity on visceral fat and cardiovascular risk (CVR) in patients suffering from MetS. Methods: 100 adults, aged 50-70y, were randomized to three training groups: moderate endurance and resistance (re), dominant resistance (Re), or dominant endurance (rE). A 1-year at-home follow-up (M12) began with a 3-week residential program (Day 0 to Day 20). We measured the change in central fat and body composition by DXA, MetS parameters, fitness and CVR using the Framingham score and carotid-intima-media-thickness. Compliance was assessed between D20 and M12. Results: 78 participants (78%) completed the study. At D20, central fat loss was highest in Re (-18%, p<.0001) and higher in rE than re (-12% vs. -7%, p<.0001). Likewise, from M3, visceral fat decreased more in Re and rE than in re (p<.05) to reach at M12 a central fat loss of -21.5% (Re) and -21.1% (rE) > -13.0% (re) (p<.001). CVR, MetS parameters and fitness improved in all groups. The main improvements were obtained during the residential program and evolved thereafter depending on compliance. Non-compliers had higher values in most outcomes between M6 and M12 whereas compliers maintained improvement. Central fat loss correlated with changes in MetS parameters. Conclusions: The 3 modalities of physical activity induced central fat loss and improvements in CVR and MetS, but high-intensity-resistance resulted in a faster improvement. A residential program with daily coaching is essential to help patients achieve their aims. Compliance appears to be the main challenge in successful Mets treatment.

<p>Försvarsmakten beskriver i Arméns utvecklingsplan 2010-2020 att tre dygns uthållighet på taktisknivå inte är tillräckligt utan bör vara mer flexibelt så att den även passar mindre enheter som skall kunna verka över stora avstånd utan möjlighet till egen logistik. Syftet med uppsatsen är att utreda vad trovärdig uthållighet är. Att utreda om tre dygns uthållighet på taktisk nivå är tillräckligt eller om denna bör utökas till mer än tre dygn. I uppsatsen beskrivs vad som står skrivet i olika dokument från Försvarsmakten vilka styr uthålligheten. Det beskrivs även hur Försvarsmakten avser att uthålligheten skall se ut i framtiden. Detta kopplas sedan mot erfarenhetsvärden från slutrapporter från Afghanistan, rapporter från Försvarets forskningsanstalt och US Marine Corps samt en enkätundersökning genomförd med chefer från FS15, FS16 samt FS17. Uppsatsen visar på att det som står skrivet från Försvarsmakten inte alltid stämmer överens med hurdet ser ut i verkligheten. De flesta chefer som svarat på enkätundersökningen uppger att de tagit med mer förnödenheter avseende mat, vatten och ammunition till personligt eldhandvapen än de inriktningar som Försvarsmakten gett. Detta resultat tyder på att uthålligheten inte är trovärdig utan bör utökas för att i framtiden kunna skapa ytterligare möjligheter för soldatens överlevnad.</p> / <p>The Swedish Armed Forces describes in the document Arméns utvecklingsplan 2010-2020 that three days endurance regarding food, water and ammunition on a tactical level is not enough. It should bemore flexible so that it fits even smaller units which operate over great distances without the possibility of own logistics. The purpose of this paper is to examine what credible endurance is. To investigate whether three days endurance of tactical level is sufficient or whether this should be extended to more than three days. The paper describes what is written in various documents from the Swedish Armed Forces which govern endurance. It also describes how the Swedish Armed Forces relate to endurance in the future. This is then connected to experience values from the final reports from Afghanistan, reports from the Swedish Defence Research Institute and the U.S. Marine Corps and implement a survey of executives from FS15, FS16 and FS17. This paper shows that what is written from the Swedish Armed Forces are not always consistent withhow it looks in reality. Most officers who responded to the survey report that they have included more commodities for food, water and ammunition for personal weapon than the directions given bythe Swedish Armed Forces. These results suggest that endurance is not credible and should be expanded in order to create additional opportunities for the soldier's survival.</p>