Oestrogen is believed to be a potent antioxidant, with potential membrane stabilising and gene regulatory effects. Oestrogen has been shown to be an effective cardioprotectant, with for example a lower incidence of atherosclerosis in pre menopausal females compared to age-matched males and in post menopausal females on hormone replacement therapy compared to age-matched males. What has yet to be determined is the extent to which oestrogen can protect skeletal muscle. It has been shown that certain markers of exercise-induced muscle damage (EIMD) are lower in females in both animal and human studies, but as yet no conclusive evidence from human studies has shown that oestrogen provides a protective mechanism against ERvID or whether susceptibility to EIKID varies across the normal menstrual cycle, where oestrogen fluctuations are high. Furthermore, if oestrogen provides a protective mechanism against EIlVID, it is unknown at which phase during the muscle damage and repair cycle this occurs. It is also debatable if the potential inhibitory effects that oestrogen has on the inflammatory response, with regard to repair and regeneration of the skeletal muscle are positive or negative. The thesis is comprised of a critical review of the nature of EIMD and the potential effects that oestrogen has on the muscle damage and repair cycle. This is followed by three empirical studies which were designed to explore this question. These are outlined below: Study 1 Study one was in two parts. The first part of this study aimed at determining if the phase of the menstrual cycle, could in anyway affect eumennorheic (normally 2 menstruating) females in their susceptibility to exercise-induced muscle damage. An eccentric exercise procedure (elbow flexor muscle group) was performed on a randomly assigned arm during either the menses or ovulatory phase of the menstrual cycle. The contra-lateral limb underwent the same procedure during the alternate phase (random assignment determined in which phase the participant was first damaged). Simple markers of EDM were assessed at baseline and every 24 h up to three days post exercise, during both phases. No significant differences were seen in any markers of BIMD across phases of the menstrual cycle. The second part of this study investigated whether prolonged ingestion of exogenous oestrogen, in the form of the combined oral contraceptive pill attenuated any of the symptoms associated with EIMD. The only symptom to show a significant interaction between groups was perceived soreness, with the pill users reporting significantly (P<0.01) less soreness than the eumennorheic females in the days following the exercise protocol. This suggested that oestrogen may modulate the pain associated with EIMD. Study 2 The second study focussed on gender differences in exercise-induced muscle damage, with particular focus on the secondary symptoms and events which occur following ERVID. Male and female participants performed a bout of eccentrically biased exercise. Markers of both EIMD and inflammation were taken prior to the eccentric exercise and across a 7-day follow up period. Gender differences in the response to EIMD were seen in creatine kinase activity and mid-thigh circumference, with males showing a larger response on both variables. In addition to this, males reported significantly less soreness than females following the exercise protocol. 3 Interestingly, with the exception of neutrophil elastase release, there were no differences in other markers of inflammation between men and women. Total elastase concentration, a marker of neutrophil activation, did not differ between genders. However, elastase release per neutrophil was significantly lower in females, which may be indicative of gender differences in the inflammatory response associated with EDvID. Study 3 With the recognition that oestrogen could potentially reduce or inhibit the inflammatory response the third and final study investigated whether female skeletal muscle was more susceptible to exercise-induced muscle damage after a second bout of eccentric exercise, due to poor regeneration and repair following the initial bout. Males and females performed a bout of eccentrically biased exercise. Markers of EEVM included creatine kinase, soreness, isometric strength and isokinetic strength assessment. The procedure was then repeated two weeks later to determine if gender differences existed in terms of the repeated bout effect associated with EIlvID. Only one variable showed a gender x time x bout interaction (P<0.05), that was the fatigue index. It was shown that following the initial bout of damage, males and females responded very differently, with female muscle being less fatiguable in the 48 h following damage compared to the males, but with both groups responding very similarly in the repeated bout. This may be due to differences in gender and their response to EIlVID, or due to differences in fibre type between genders.

No description available.

Ca2+ signals determine smooth muscle contraction and the switch from a contractile to a migratory-proliferative phenotype(s), which requires changes in gene expression. However, the mechanism by which different Ca2+ signals are selective for these processes is enigmatic. In the thesis, I built on the “panjunctional sarcoplasmic reticulum” hypothesis, and described the evidence in support of the view that a variety of Ca2+ pumps and release channels, with different kinetics and affinities for Ca2+, are strategically positioned within the cytoplasmic nanocourses of pulmonary arterial smooth muscle cells (PASMCs), and they serve to demarcate different Ca2+ signalling. Nanocourses of the SR are formed in the perinuclear, extraperinuclear, subplasmalemmal regions and the nucleus. Different subtypes of ryanodine receptors (RyRs) are targeted to those nanocourses. Immunocytochemistry results suggest that RyR1s was preferentially targeted to the subplasmalemmal and nuclear nanocourses of PASMCs, they gave rise to a spatially restricted Ca2+ signal within the nanocourses upon stimulation, without affecting global Ca2+ concentration. The Ca2+ signals in the subplasmalemmal nanocourses were shown to induce arterial smooth muscle cell relaxation. On the other hand, the RyR2 and 3 were shown to target to the perinuclear and extraperinuclear nanocourses. Upon stimulation, they generate propagating Ca2+ waves in the cytoplasmic nanocourses, which trigger arterial smooth muscle cell contraction. However, during this process, no Ca2+ transient was observed within the subplasmalemmal nanocourses, suggesting that the regulation of both contraction and relaxation of smooth muscle cells are achieved by spatially restricted Ca2+ signals within different nanocourses. Invaginations of the nucleoplasmic reticulum in arterial myocytes form trans-nuclear networks of cytoplasmic nanospaces, generate Ca2+ signals by strategically positioned Ca2+ pumps (SERCA1) and release channels (RyR1). Within a subpopulation of nuclear invaginations, evoked Ca2+ signals via ryanodine receptors exhibited spatial and temporal separation from adjacent Ca2+ signals within a single “activated” nuclear invagination, and also from those Ca2+ signals arising within different nuclear invaginations. Moreover, nuclear invaginations provide sites for transcriptional suppression, because lamin A and/or emerin line the entire surface of their inner nuclear membranes and co-localise with nesprin-1 positive puncta. More intriguing still, a subpopulation of these nuclear invaginations harboured punctate regions of colocalisation between lamin A and the suppressive heterochromatin mark H3K9me2, while emerin-positive invaginations harboured puncta of BAF (Barrior to autointegration factor) co-localisation and thus an alternative pathway to the regulation of gene expression. I propose that nuclear invaginations form cytoplasmic nanotubes within which nano-patterning of Ca2+ signals may support stochastic modulation of transcriptional suppressors. Together, the cytoplasmic nanocourses form a cell-wide web for Ca2+ signalling and the regulation of various arterial smooth muscle functions, ranging from the regulation of blood pressure by vasodilation and vasoconstriction to gene expression.

Orientador: Fausto Bérzin / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba / Made available in DSpace on 2018-08-24T16:33:19Z (GMT). No. of bitstreams: 1 CarvalhoFilho_Joao_D.pdf: 1313807 bytes, checksum: 07c697e23cd343e1036e760b59f915e9 (MD5) Previous issue date: 2014 / Resumo: Introdução: A eletromiografia intramuscular (EMG) é uma técnica invasiva que detecta a atividade muscular através de agulhas-eletrodo ou fios inseridos nos músculos, que têm alta seletividade para os diferentes potenciais de ação da unidade motora. O uso clínico atual de sinais EMG intramusculares refere-se ao diagnóstico de miopatias, doenças do neurônio motor alfa e da junção neuromuscular, por meio da análise do sinal de interferência ou da forma de alguns potenciais de ação da unidade motora, geralmente sem uma completa decomposição do sinal. Justificativa: Os escassos trabalhos sobre a cinesiologia dos mm. sartório e tensor da fáscia lata referidos na literatura clássica, foram feitos utilizando-se equipamentos analógicos, que não permitem quantificação matemática do sinal eletromiográfico, produzindo resultados de valor apenas empírico. Por isso, fez-se necessário estudar a cinesiologia dos Mm sartório e tensor da fáscia lata, por meio de equipamento eletromiográfico digital que forneceu resultados mais precisos e confiáveis, passíveis de avaliação matemática, normalizados e submetidos à análise estatística adequada. Objetivo: O presente trabalho objetivou a avaliação eletromiográfica por meio de equipamento digital, da cinesiologia dos músculos sartório e tensor da fáscia lata do lado direito, em indivíduos normais, destros, em repouso e durante diferentes movimentos corporais. Metodologia: Uma amostra de 15 voluntários, de ambos os sexos, independente de etnia, faixa etária de 20 a 30 anos foi estudada a partir de um Eletromiógrafo Data Hominis Ltda. (versão 2.9) e Pré-amplificador da Linx Tecnologia Eletrônica Ltda. Modelo PA1010-VA. Os músculos foram avaliados unilateralmente (lado direito) e a ação muscular foi captada no repouso e durante a execução de vários movimentos corporais. Os dados foram analisados estatisticamente através do teste Scott-Knott e o nível de significância foi de 5% (p<0,05). Resultados obtidos: O músculo sartório se apresentou muito ativo no movimento 1; ativo nos movimentos 3, 5 e 6; atividade moderada nos movimentos 4, 11, 12 e 28, e pouco ativo nos demais; já o músculo tensor da fáscia lata foi muito ativo nos movimentos 3 e 6; ativo no movimento 5; atividade moderada nos movimentos 1, 2 e 4 e pouco ativo nos demais. Conclusão: Conclui-se então a partir dos resultados obtidos que o uso do eletromiógrafo digital, mostrou um sinal muito mais eficiente que o analógico, o que propiciou uma análise matemática e estatística muito mais acurada dos resultados obtidos nas coletas realizadas / Abstract: Introduction: Intramuscular electromyography (EMG), an invasive technique that detects muscle activity through needle electrodes or wires inserted into the muscles, has a high selectivity for different action potentials of the motor unit. Nowadays, the clinical use of intramuscular EMG signals refers to the diagnose of myopathies, alpha-motor neuron and neuromuscular junction diseases by means of analysis of the interference signal or shape of some action potentials of the motor unit, generally without a complete signal decomposition. Justification: the sparse researches on the kinesiology of tensor fasciae latae and sartorius found in classical literature were performed with analogical equipment which does not allow mathematical quantification of EMG signal, resulting only in empirical data. Thus, it was necessary to study the kinesiology of tensor fasciae latae and sartorius through EMG digital equipment that supplies more precise and reliable results which can be mathematically evaluated, normalized and submitted to an adequate statistical analysis. Objective: the present research aimed to perform a digital EMG evaluation of the kinesiology of right tensor fasciae latae and sartorius in dexterous normal individuals at rest and during different body movements. Methods: a sample of 15 non-ethnical volunteers of both sexes, ranging from 20 to 30 years old was studied using a Data Hominis Ltda. (version 2.9) Electromyography set and a PA1010-VA model of Linx Tecnologia Eletrônica Ltda. preamplifier. The right-sided muscles were evaluated and the muscle action taken at rest and during several body movement performance. Data were statistically analyzed through Scott-Knott test and the significance level was of 5% (p<0.05). Results: Sartorius showed to be much active in movement 1; active in movements 3, 5 and 6; moderate active in movements 4, 11, 12 and 28; and less active in the others. Tensor fasciae latae was much active in movements 3 and 6; active in movement 5; moderate active in movements 1, 2 and 4; and less active in the others. Conclusion: the data obtained in the research showed that digital EMG displayed a much more efficient signal than analogical one that allows an even more accurate mathematical and statistical analysis of data taken in our study / Doutorado / Anatomia / Doutor em Biologia Buco-Dental

La dystrophie FacioScapuloHumérale (FSHD), décrite pour la première fois en 1885 par Landouzy Dejerine, est la première dystrophie musculaire de l’adulte en France affectant entre 4000 et 5000 personnes. La destruction progressive des fibres musculaires entraîne une atrophie et une faiblesse musculaires s’aggravant progressivement, avec cependant une grande variabilité intra-familiale du degré des atteintes. Une caractéristique de l’atteinte musculaire est généralement son asymétrie. Les premières manifestations concernent souvent les muscles du visage, les muscles de l’omoplate et des muscles perihuméraux. En progressant la pathologie va toucher d’autres territoires musculaires. Dans environ 10 à 15 % des cas, à un stade évolué, les patients sont contraints d'utiliser un fauteuil roulant. En dépit d’avancées majeures dans la compréhension du locus morbide, les mécanismes exacts responsables des défauts musculaires de la FSHD ne sont toujours pas compris et il n’existe aucune thérapie. Toutefois, il existe de plus en plus de données qui permettent une implication probable du stress oxydant dans cette pathologie. L’hypothèse selon laquelle les réponses antioxydantes sont altérées dans la FSHD s’appuie sur des dérégulations d’enzymes impliqués dans le stress oxydant. Une étude prospective réalisée sur des patients FSHD et des volontaires sains nous a ainsi permis de mettre en évidence une corrélation entre le stress oxydant systémique et musculaire et leurs déficits fonctionnels musculaires. Ces données nous ont conduit à la mise en place d’un essai clinique randomisé, contrôlé, en double aveugle contre placébo, visant à évaluer les effets d’une supplémentation en antioxydants chez 54 patients atteints de FSHD pendant 17 semaines. Cet essai a ainsi permis de montrer une augmentation significative de la force et l’endurance des quadriceps corrélée à une diminution du stress oxydant et une augmentation des défenses antioxydantes chez les patients atteints de FSHD. De nombreuses caractéristiques de la FSHD pourraient être causées et/ou exacerbées par des perturbations de la production des espèces radicalaires ou une réponse non adaptée à cette production. Aussi le premier objectif de ma thèse est de mener une étude comparative des profils d’oxygénation par spectroscopie dans le proche infrarouge de patients atteints de FSHD et sains. Le second objectif est d’évaluer l’effet de la supplémentation en antioxydant sur le volume des quadriceps par IRM et leur qualité musculaire déterminée par le ratio Force/Volume musculaire du quadriceps et d’évaluer les corrélations entre ces variables, la force et le stress oxydant. Les données obtenues ont permis de montrer une réduction de la capacité oxydative lors d’une contraction isométrique volontaire des quadriceps et ont permis d’étudier l’effet de la supplémentation sur les volumes et la qualité musculaire des quadriceps. Ces augmentations sont associées non seulement à une augmentation de la force des quadriceps mais aussi à une diminution du stress oxydant et une augmentation des défenses antioxydantes. L’ensemble de ces données montrent que le stress oxydant pourrait jouer un rôle important dans la FSHD et qu’une approche antioxydante semble adaptée à cette pathologie. Des analyses plus fines sur l’action des espèces réactives de l’oxygène (ROS) et leurs sources pourraient contribuer à une meilleure compréhension des bases physiopathologiques de la FSHD. / Facioscapulohumeral muscular dystrophy (FSHD), first described in 1885 by Landouzy Dejerine, is the most common inherited skeletal muscle disease of adult life affecting 4000 to 5000 persons in France. Progressive evolution of the disease leads to progressive weakness and atrophy of muscle fibers associated to a wide variability. The pattern of muscle weakness is often asymmetrical and the rate and extent of progression may vary considerably with sudden periods of unexplained rapid disease progression. This muscle disorder is characterized by progressive muscle weakness, beginning with facial muscles and the shoulder girdle, followed by the pelvic girdle and the muscles of the lower extremities. In 10 to 15% of cases, patients need to use a wheelchair. Despite major progress in the understanding of the genetic basis of FSHD, the exact mechanisms that lead to FSHD defects are not completely understood and no curative treatment is available. However, there is growing evidence that oxidative stress may contribute to FSHD pathology. The hypothesis that oxidative stress responses might be specifically altered in FSHD is supported by the deregulation of enzymes involved in oxidative stress.A prospective study realized with FSHD patients and healthy subjects unrevealed the correlation between systemic and muscular oxidative stress and functional muscle defects. Based on these data, we organized a randomized, double-blind, placebo-controlled pilot clinical trial in order to evaluate the effects of 17 weeks antioxidant supplementation in 54 FSHD patients. This clinical trial demonstrates a significant increase in muscle force and quadriceps endurance correlated to a decrease in oxidative stress and an increase in antioxidant defense in FSHD patientsFurthermore, many FSHD features may be caused or exacerbated by perturbations in the production of free radicals or inappropriate response to such stressors. Therefore the first objective was planned to investigate muscle oxygenation patterns during and after a MVCQ by near-infrared diffuse optical spectroscopy (NIRS). The second objective is to evaluate the effect of antioxidant supplementation on quadriceps volumes by IRM and determine the muscle quality using Strength/ Volume ratio of quadriceps muscles and correlate this variables with force and oxidative stress parameters.The major findings of this study show a significant decrease in oxidative capacity during voluntary isometric contraction in quadriceps and demonstrate the effect of supplementation on muscle volume and quality. Indeed, vitamin E, vitamin C, zinc and selenium supplementation improves muscle volume and quality of both quadriceps by enhancing the antioxidant defences and reducing oxidative stress.This increase are associated to increase in strength and decrease in oxidative stress and increase in antioxidant defences. Taken together, we show that oxidative stress plays an important role in FSHD and that an anti-oxidant strategy adapted to the FSHD-specific “oxidative stress” may be a relevant therapeutic approach for these patients. Further analyses of ROS production and sources could contribute to a better understanding of the pathophysiological mechanisms implicated in FSHD.

Magister Artium (Sport, Recreation and Exercise Science) - MA(SRES) / Over the years, cricket has progressed into a game of immense physical prowess, and evolved from a traditional and conservative game into a professional sport requiring very high levels of fitness and skill. The ability to throw a ball at high velocity and with great accuracy is critical for successful performance in many ball sports, including cricket. The aim of this study focussed on examining the relationship between isokinetic strength of the shoulder complex and throwing velocity amongst club cricketers in the age group of 18-32 years. The study used a quantitative methodology with a cross-sectional research design. A convenient sample of 40 male cricketers from the University of the Western Cape was tested. Isokinetic strength of external rotators (ER), internal rotators (IR) and ratios were measured using the Biodex Pro System 4 isokinetic dynamometer at two speeds, namely, 60º•sec-¹ and 90º•sec-¹. Throwing velocity was measured using a calibrated Cordless Speed/Radar Gun. The major findings of this study were the significant correlations between IR at 60º•sec-¹ and throwing velocity for the first team (r = 0.72; p = 0.01), second team (r = 0.67; p = 0.03), third team (r = 0.73; p = 0.01) and fourth team (r = 0.69; p = 0.02). The correlation between the strength ratio at 60º•sec-¹ and throwing velocity was significant for the first team (r = 0.76; p = 0.01), second team (r = 0.83; p = 0.002), third team (r = 0.70; p = 0.02) and fourth team (r = 0.94; p = 0.0001). In conclusion, shoulder strength plays a significant role in the throwing velocity amongst club cricketers. Specifically, the shoulder internal rotators were found to be a major influence in throwing velocity. Furthermore, the shoulder strength ratio is a strong predictor of shoulder strength performance.

Muscle strain injuries affect a wide range of physically active people around the world and are reaching epidemic proportions. Despite the variety of treatment options available in rehabilitation, there are no clear guidelines for electrical stimulation that provide effective reproducible results that address the underlying cause of these injuries. For instance, electrotherapy is inefficient at stimulating muscles, because of imprecise parameters and an ability to target particular muscles. The difference between this study and previous research is the precise delivery of electrical stimulation (intramuscular) at two different frequencies (2 Hz and 50 Hz) and comparing it a control group. Objective: To determine the difference on muscle strength and functional status between three treatments modalities for sub acute and chronic hamstring strains. Design: A randomized experimental design was used to compare the effects of low (2 Hz), high (50 Hz) and no-electrical (control) intramuscular stimulation on muscle strength and mental and functional status (AMSMC HEALTH STATUS INDEX). Each group consisted of 18 subjects. Main Outcome: The difference in treatment modalities was evaluated by comparing the muscle strength test (Biodex Dynamometer) results and the AMSMC HEALTH STATUS INDEX results in pretest and post-test conditions. Results: The AMSMC HEALTH STATUS INDEX, but not muscle strength test (Biodex), changed significantly after 2-Hz electrical intramuscular stimulation (pre-test µ = 66.56, Std= 11.92, post-test µ= 92.89, Std= 6.25), whereas no statistically significant changes in health status index and muscle strength test occurred with 50-Hz (pre-test = 69.22, Std= 11.31, post-test µ= 70.22, Std= 12.27)) and no-electrical stimulation groups (pre-test µ= 69.11, post-test µ= 73.39, Std= 13.18). / Education, Faculty of / Kinesiology, School of / Graduate

Statins are the mainstay of cholesterol-lowering therapy and are taken by millions of people worldwide. These drugs are generally well-tolerated but can cause myopathy ranging from mild muscle pain to fatal rhabdomyolysis. The mechanism of statin-induced myopathy (SIM) is not fully understood and there is currently no convenient and reliable marker of SIM, but mitochondrial dysfunction has been implicated. We sought to investigate the effect of statins on mitochondrial DNA (mtDNA) levels in order to gain information on the mechanism of SIM and to explore the possibility of utilizing changing mtDNA levels as a marker of SIM. Several approaches were used. First, mtDNA levels were quantified in skeletal muscle biopsies collected from a previously published 8-week clinical trial of high-dose simvastatin or atorvastatin versus placebo. Forty-eight hypercholesterolemic subjects were randomly assigned to receive placebo (N=16), high dose atorvastatin 40mg/day (N=16), or high dose simvastatin 80mg/day (N=16) for 8 weeks. Muscle mtDNA content was assessed by real-time PCR atbaseline and after 8-weeks on statin treatment and found to be significantly reduced in the groupreceiving simvastatin (P=0.005) but not the other two. In addition, a significant positive correlation was observed between mtDNA and muscle ubiquinone in all groups (R=0.63, P<0.01), with the strongest association found in the simvastatin-treated subjects (R=0.75, P=0.002). Next, in an attempt to determine whether statin-induced muscle pain may be associated with muscle mtDNA depletion, archived muscle biopsies collected from statin users with muscle complaints were sought through a review of a muscle biopsy database and possible study samples were identified; however, this was put on hold as too much information was missing from the pathology reports. Third, a series of cell culture experiments were carried out in which human skeletal muscle myotubes were exposed to various concentrations of simvastatin or atorvastatin, in order to determine an appropriate dose range for subsequent mitochondrial toxicity experiments. Lastly, mtDNA content and expression was quantified in skeletal muscle biopsies collected from 10 patients with statin-induced rhabdomyolysis (SIR) and compared to 8 healthy controls to investigate whether muscle mtDNA is altered in rhabdomyolysis. No differences in mtDNA content or expression were observed between the two study groups, but this may have been be due to the SIR subjects' marked heterogeneity. Statin therapy can be associated with considerable alterations in mtDNA content, which may play a role in the aetiology of SIM. MtDNA levels alterations with statin exposure should be investigated further to explore the involvement of mitochondrial alterations in the mechanism of SIM, and determine whether these may represent a useful clinical tool for assessing statin-induced muscle toxicity. / Medicine, Faculty of / Pathology and Laboratory Medicine, Department of / Graduate

Understanding the regulatory mechanisms controlling utrophin A expression at the sarcolemma of dystrophic muscles will facilitate the development of therapeutic strategies to ameliorate the pathophysiological features of Duchenne Muscular Dystrophy (DMD). The main goal of this study was to characterize the regulation of utrophin A IRES activity using a transgenic mouse model expressing the utrophin A 5’UTR bicistronic reporter and to identify trans-acting factors that could mediate IRES activity and endogenous expression of utrophin A. We found that utrophin A IRES activity is specifically expressed in skeletal muscles. Moreover, we identified eEF1A2 as a muscle-specific trans-acting factor that can interact with utrophin A and mediate IRES-dependent translation of utrophin A. Finally, we showed that eEF1A2 mediates endogenous utrophin A expression and localization in skeletal muscle. Identifying pharmacological compounds that would specifically target eEF1A2 and increase endogenous levels of utrophin A expression could serve as a drug-based therapy to treat DMD.

Since a significantly greater percentage of body weight is supported by the non-paretic limb following stroke, a greater amount of fatigue may be present during daily activities. This may affect the ability of these individuals to maintain a stable upright posture. The presence of falls following a stroke has been attributed in part to this asymmetrical stance post-stroke. Therefore the purpose of this study was to assess the effect of quadriceps muscle fatigue on bi-pedal posture in individuals who had a stroke and an age-matched control group. Although individuals after stroke displayed greater postural sway under the paretic limb than the non-paretic limb or control subjects, results of this study show that sustaining an isometric knee extension of the non-paretic limb induces changes in postural control for individuals after stroke, but that these changes do not markedly differ from those of healthy age-matched controls.