Nesta tese é proposto um modelo fenomenológico eletromecânico com relação constitutiva variacional para representar numericamente a resposta ativa/passiva do tecido muscular esquelético, a fadiga muscular de diferentes tipos de fibras e a combinação de contrações. Na literatura não são encontrados modelos que representem esses comportamentos combinados. Para atingir este objetivo são definidos conjuntos de variáveis auxiliares e variáveis internas para desencadear e mapear a evolução das principais características do tecido muscular esquelético. É considerado que o tecido se contrai localmente, através da propagação de um potencial de ação elétrico advindo do sistema nervoso através de uma ou mais unidades motoras. A proposta de propagação do potencial de ação é construída com a criação de critérios de malha e discretização temporal, eliminando o erro dentro desses limites. Com a propagação do potencial de ação é informado ao modelo constitutivo se localmente o tecido está ativo, através de uma variável de acoplamento binária. A relação constitutiva mecânica utiliza este parâmetro para iniciar a contração muscular, que depende da evolução de uma variável interna. A evolução dessa variável substitui a função de ativação encontrada em outros modelos. Também é utilizado um segundo potencial dissipativo para representar a eficiência metabólica do tecido resultando na representação da fadiga muscular. Um conjunto de potenciais elásticos e dissipativos são utilizados para representar diferentes níveis de forças após combinações de contração do tipo isométrica-concêntrica-isométrica e isométrica-excêntrica-isométrica para diferentes velocidades e alterações de comprimento. A proposta é verificada frente ao ajuste de parâmetros de experimentos reais, obtendo boa representação. Através da implementação no método de elementos finitos é possível observar o comportamento do modelo proposto em geometrias tridimensionais. / In this thesis an electromechanical phenomenological model with variational constitutive relation is proposed to numerically represent the active/passive response of skeletal muscle tissue, muscle fatigue of different types of fibers and contraction combination. In the literature there are no models that represent these combined behaviors. To achieve this goal, sets of auxiliary variables and internal variables are defined to trigger and map the evolution of the main characteristics of skeletal muscle tissue. The tissue is considered to contract locally by propagating an electrical action potential from the nervous system through one or more motor units. The proposed propagation of the action potential is defined with the creation of mesh criteria and temporal discretization, eliminating the error within these limits. With the propagation of the action potential it is informed to the constitutive model if the tissue is locally active, through a binary coupling variable. The mechanical constitutive relation uses this parameter to initiate muscle contraction, which depends on the evolution of an internal variable. The evolution of this variable replaces the activation function found in other models. A second dissipative potential is also used to represent the metabolic efficiency of the tissue resulting in the representation of muscle fatigue. A set of elastic and dissipative potentials are used to represent different levels of forces after isometric-concentric-isometric and isometric-eccentric-isometric contraction combinations for different velocities and length changes. The proposed model capabilities are verified with the parameters adjustment to reproduce real experiments, obtaining good representation. The implementation in the finite element method allows to observe the behavior of the proposed model in three-dimensional geometries.

Investigamos o efeito do exercício físico no metabolismo do tecido adiposo e muscular de ratos pinealectomizados tratados ou não com melatonina. Foram retiradas amostras de sangue, tecido adiposo peri epididimal e músculo sóleo para testes biológicos. O treinamento físico mostrou-se eficiente através do aumento da velocidade máxima, atingida no final do treinamento, e da atividade da citrato sintase no músculo. A pinealectomia alterou o padrão de mobilização e utilização dos substratos pelos adipócitos e células musculares tornando menor a adaptação dos animais ao treinamento, causando um desajuste metabólico em vários parâmetros. Quando tratados com melatonina a adaptação funcional recuperou-se plenamente, tanto no tecido adiposo como muscular. Demonstrando que a glândula pineal tem um papel na regulação do metabolismo de lipídeos e carboidratos em resposta ao treinamento físico, a remoção da glândula causa alterações na resposta adaptativa do tecido adiposo e muscular e o tratamento com melatonina reverte o desajuste metabólico instaurado pela pinealectomia. / The current study investigated the effect of exercise on muscle and adipose tissue metabolism melatonin treated or non treated pinealectomized rats. Blood samples, peri-epididymal adipose tissue and soleus muscle were collected for biological tests. The physical training was efficient in increasing the maximum speed reached at the end of training, and the activity of citrate synthase in muscle. Pinealectomy changed the pattern of mobilization and utilization of substrates adipocytes and muscle cells decreasing the adjustment to the training in these animals, causing a mismatch in several metabolic parameters. When treated with melatonin, the functional adaptation is fully recovered both in adipose tissue and muscle. Demonstrating that the pineal gland has a role in regulating the metabolism of lipids and carbohydrates in response to physical training, the removal of the gland caused changes in the adaptive response of adipose tissue and muscle and the treatment with melatonin reversed the metabolic mismatch introduced by pinealectomy.

Title: The influence of different kinds of warm-up on the speed skills of football players from the ontogenetic point of view. Aims: The main objective of this diploma thesis is to compare the results of the times achieved by football players in the U18 youth team with their previous times measured two years ago, and in this way to evaluate their development of speed capabilities. Another aim of the research is to evaluate the progress of these players' flexibility at a chosen time interval (two years) and to inquire into other possible connections of these outcomes. Methods: For the assessment of speed power performance, each player goes through two runs at a distance of 30 meters, with measurements in this section also at distances of 5, 10 and 15 meters. Before the measurement itself, all participants are being prepared by a selected type of stretching. Two standardized tests are used for secondary research dealing with potential connection between the attained speed and the degree of flexibility of lower limbs. Outcomes: Testing revealed that subjects had a deterioration in the average running time with a two-year interval at distances of up to 15 meters (5,10,15 meters). On the contrary, when analyzing the results of measuring the distance of 30 meters, a significant improvement in average...

Skeletal muscle injuries and muscle degenerative diseases pose significant challenges to the healthcare. Surgical interventions are restricted due to tissue availability, donor site morbidity and alterations to tissue biomechanics. Current cell-based therapies are hindered by low survival and long-term engraftment for the transplanted cells due to the lack of appropriate supportive microenvironment (cell niche) in the injured muscle. Therefore, there is a critical need for developing strategies that provide cellular and structural support in the regeneration of functional muscle. In the present work, a bioengineered cell niche mimicking the native skeletal muscle microenvironment has been developed for skeletal muscle regenerative engineering. It is hypothesized that the bioengineered scaffolds with appropriate structural and cell instructive properties will support myoblast alignment and function, as well as promote the myogenic responses in clinically relevant skeletal muscle injuries. The current work utilized a three-pronged approach to design biomaterial scaffolds to aid in skeletal muscle regeneration. In the first part, aligned poly(lactide-co-glycolide) (PLGA) fiber scaffolds mimicking the oriented muscle fiber microenvironment with fiber diameters of 335±154 nm (nanoscale), 1352±225 nm (microscale) and 3013±531 nm (microscale) were fabricated and characterized. Myoblasts were found to respond to fiber diameter as observed from the differences in cell alignment, cell elongation, cell spreading area, proliferation and differentiation. <i>In vivo</i> study demonstrated the potential of using microscale fiber scaffolds to improve myogenic potential in the <i>mdx</i> mouse model. In the second part, we designed, synthesized, and characterized an implantable glycosaminoglycan-based composite hydrogel consisting of hyaluronic acid, chondroitin sulfate and polyethylene glycol (HA-CS) with tailored structural and mechanical properties for skeletal muscle regeneration applications. We demonstrated that HA-CS hydrogels provided a suitable microenvironment for <i>in vitro</i> myoblast proliferation and differentiation. Furthermore, <i>in vivo</i> studies using a volumetric muscle loss model in the mouse quadriceps showed that HA-CS hydrogels integrated with the surrounding host tissue and facilitated <i>de novo</i> myofiber generation, angiogenesis, nerve innervation and minimized scar tissue formation. In the third part, we investigated the effects of PC12 secreted signaling factors in modulating C2C12 myoblast behavior. We showed that PC12 conditioned media modulated myoblast proliferation and differentiation in both 2D culture and 3D aligned electrospun fiber scaffold system in a dose dependent manner. We also demonstrated the biomimetic HA-CS hydrogel system enabled 3D encapsulation of PC12 cells secreting signaling factors and promoted survival and proliferation of myoblasts in co-culture. Further proteomics analysis identified a total of 2088 protein/peptides from the secretome of the encapsulated PC12 cells and revealed the biological role and overlapping functions of nerve secreted proteins for skeletal muscle regeneration, potentially through regulating myoblast behavior, nerve function, and angiogenesis. These set of experiments not only provide critical insight on exploiting the interactions between muscle cells and their microenvironment, but they also open new avenues for developing advanced bioengineered scaffolds for regenerative engineering of skeletal muscle tissues.<br>

Toxoplasma gondii ist weltweit einer der häufigsten zoonotischen Parasiten. Der obligat in-trazelluläre Gewebeparasit hat ein breites Wirtsspektrum als Zwischenwirte. Der Mensch infiziert sich häufig durch orale Aufnahme von Gewebezysten aus rohem oder unzureichend erhitztem Fleisch. Schweine und Hühner als fleischliefernde Tiere stellen eine wichtige Infek-tionsquelle für den Menschen dar. Ziel der Arbeit war die Verteilung und Parasitenbelastung von T. gondii in verschiedenen Geweben von infizierten Schweinen und Hühnern mit Hilfe quantitativer real-time PCR auf Basis des 529-bp-Fragmentes zu bestimmen. Experimentell wurden 10 Schweine und 12 Hühner mit unterschiedlicher Infektionsdosen von Toxoplasma-Oozysten infiziert. Anhand der 529-bp-PCR waren 90% der untersuchten Schweine und >90% der untersuchten Hühner Toxoplasma-DNA-positiv. In Schweinen gelang der Nach-weis von Toxoplasma-DNA in der Oberschenkelmuskulatur mit 70% und Bauchmuskulatur mit 60% am häufigsten. Gehirn und Vorderbeinmuskulatur waren mit jeweils 40%, Herz mit 30% und Zunge mit 10% Toxoplasma-DNA-positiv. In experimentell infizierten Hühnern wur-de T. gondii-DNA am häufigsten in Oberschenkelmuskulatur, Brustmuskulatur und Gehirn mit jeweils 50% und im Herz mit ungefähr 20% nachgewiesen. Die Quantifizierung des Erre-gers in den T. gondii-positiven Gewebeproben ergab eine Parasitenanzahl von 0,1 bis 4,1 in 25 mg Schweinegewebe und von 0,1 bis 4,9 in 25 mg Hühnergewebe, die unabhängig von der Gewebeart war. Es wurde in dieser Arbeit auch eine Reverse Transkriptase real-time PCR zur Bestimmung der Viabilität von Parasiten in den Gewebe infizierter Schweine und Hühner durch Nachweis von T. gondii-mRNA etabliert werden. Die Sensitivität dieser Metho-de war geringer als die der real-time PCR für T. gondii-DNA und konnte in experimentell infi-zierten Schweinen und Hühnern keine lebenden Parasiten detektieren. Die Ergebnisse die-ser Arbeit zeigen, dass Muskulatur von Schweinen und Hühnern bevorzugte Orte für die Persistenz von T. gondii in diesen fleischliefernden Tieren darstellen. Das ist ein wichtiger Hinweis, dass bei Verzehr von rohem oder nicht ausreichend erhitztem Fleisch oder Fleisch-produkten dieser Tiere ein potenzielles Infektionsrisiko für den Menschen besteht.