Dissertations / Theses on the topic 'Appendicular skeletal muscle mass'

Evidence is growing that diet, lifestyle factors and chronic inflammation influence sarcopenia. Sarcopenia is the progressive decline of muscle mass, strength and function that occurs with healthy ageing. The ageing process is also associated with a gradual increasing production of pro-inflammatory cytokines, which may potentially enhance the development of sarcopenia. Dietary longitudinal studies have shown associations between protein intake and muscle mass in older people but results of supplementation studies in enhancing muscle mass and strength are equivocal. Additionally, short-term dietary interventions with essential amino acid supplementation have shown promising effects on muscle protein synthesis. Emerging evidence suggests that a number of nutrients may be associated with muscle mass and strength either due to their anti-inflammatory properties or their involvement in muscle biology. However, there are currently few population studies examining the relative importance of specific nutrients in association with muscle mass, muscle strength and muscle quality. Therefore, this thesis aimed to examine associations between the habitual dietary intake of a range of micronutrients, and diet quality (assessed by five predefined diet quality scores) and indexes of muscle mass, strength and muscle quality in female participants aged 18-79 years from the TwinsUK cohort. An additional aim was to examine associations between diet and biomarkers of inflammation and to investigate whether diet could also influence the relationship between muscle mass and inflammation. The results suggested a significant positive association between intakes of vitamins C and E, magnesium, potassium and a range of carotenoids and indexes of muscle mass with scale of associations ranging between 1.5-4.6%. However, no associations were observed for protein and essential amino acid intakes. Higher adherence to the Mediterranean Diet score (MDS), Healthy Diet Indicator (HDI), Diet Quality Index (DQI), Alternate Healthy Eating Index (AHEI), and DASH-style score was significantly associated with measurements of muscle mass, with associations ranging between 1-3% between quintiles. Furthermore, a number of nutrients and the HDI and AHEI scores were inversely associated with plasma levels of the inflammatory marker C-reactive protein (CRP). Interestingly, intakes of magnesium, potassium, vitamin C, carotene, β-carotene, glutamine, and the MDS, HDI and AHEI scores attenuated the association between indexes of muscle mass and CRP by 1-8%, inferring that these components mediate the relationship between muscle mass and inflammation. In conclusion, the findings of this thesis emphasise the importance of consumption of a variety of plant-based nutrients and of overall diet quality for the conservation of muscle mass, and shed new light on the influence of these dietary components on sarcopenia related inflammation.

The loss of muscle mass with age (Sarcopenia) has received growing attention over the past decade. Despite efforts to provide a universal definition with clinically meaningful cut-off points for diagnosis, there is no clear consensus on how to best quantify and assess the impact of loss of muscle mass and function on functional limitations. Whilst most previous studies have used dual energy x-ray absorptiometry (DXA) to quantify this loss, chapter 2 of this thesis shows that DXA underestimates the loss of muscle mass with age in comparison to the gold standard MRI. Muscle mass per se is not enough to determine whether a person has an exceptionally low muscle mass, as it can be readily seen that a healthy tall person will have a larger muscle mass than a small person. Clinicians and researchers thus need an index of muscle mass that takes differences in stature into account and also gives an objective cut off point to define low muscle mass. In Chapter3, we show that femur volume does not significantly differ between young and old. We used this observation to introduce a new index: thigh muscle mass normalised to femur volume, or the muscle to bone ratio. This index allows the examination of the true extent of muscle atrophy within an individual. In previous studies the appendicular lean mass (determined with DXA) divided by height squared appeared to be a relatively poor predictor of functional performance. In Chapter 4, the index introduced in Chapter 3, the muscle to bone ratio, proved to be a somewhat better predictor of functional performance in the overall cohort. This was, however, not true when examining the intra-group relationships. A similar situation applied to the maximal muscle strength. In older adults, the parameter which predicted functional performance best was muscle power per body mass, measured during a counter-movement jump. Chapter 5 shows that part of the larger loss power and force than muscle mass is attributable to a left-ward shift of the torque-frequency relationship, indicative of a slowing of the muscle, and reduction in maximal voluntary activation, as assessed using the interpolated twitch technique in older adults. Chapter 5 also shows that the fatigue resistance during a series of intermittent contractions was similar in young and older adults. However, older adults could sustain a 50% maximal voluntary contraction force longer than young people. Part of this discrepancy maybe due to an age-related slowing of the muscle.

The worldwide prevalence of overweight and obesity continues to rise and will soon place unsustainable demands on the healthcare systems of most developed nations. Sarcopenia, the age-related loss of muscle mass, is commonly exacerbated in overweight/obese individuals causing loss of function and independence. Accordingly, a critical goal for overweight/obese adults is to lose fat mass while preserving lean mass to prevent the deleterious effects of inactivity and age-related metabolic diseases. Although numerous studies have manipulated combinations of diet and/or exercise training to promote weight loss, the optimal diet to improve body composition remains controversial. Furthermore, the composition of tissue losses (i.e. fat versus lean mass) is not always examined and individual responses to weight loss interventions have, to date, received little scientific enquiry. Further, the success of a weight loss intervention should be determined not only acutely, but also in terms of its efficacy in maintaining body composition changes. This thesis comprised a series of independent but related studies that investigated the role of exercise and energy-restricted diets of varying macronutrient composition on the maintenance of skeletal muscle mass and body composition...

Background: To determine the role of muscle mass in sex-dependent differences in power output during flywheel resistance training (FRT). Methods: Twenty recreationally active (≥ 2 resistance exercise bouts per week), subjects (10 M, 10 F) completed 2 bouts of resistance exercise using a flywheel resistance training (FRT) device (Exxentric kbox 4 Pro) separated by at least one week. Each session consisted of 3 sets of 4 exercises (squat, bent-over row, Romanian deadlift, and biceps curl) with varying moments of inertia (0.050, 0.075, and 0.100 kg/m2, respectively) in random order. Each set consisted of 5 maximal effort repetitions with 3-minute recovery between sets. Average power, peak concentric and peak eccentric power were recorded and normalized to whole-body skeletal muscle mass (as calculated from bioelectrical impedence analysis). Additionally, linear regression analysis was used to determine the association between muscle mass and highest power output observed among all three inertial loads. Results: Absolute average, peak concentric and peak eccentric power for all lifts was significantly higher for males compared to females except for peak eccentric power for biceps curl which showed no significant difference. After normalizing to skeletal muscle mass, power output remained significantly higher for men in Row average power and peak concentric power as well as average power for biceps curl. A significant main effect of inertial load was noted for both absolute and relative power output for all exercises except for squat average power and peak concentric power. Regression analysis revealed that power output increases linearly with skeletal muscle mass (R2 = 0.37-0.77). Conclusions: Differences in power output between sexes during resistance exercise can largely be explained by differences in muscle mass. Indeed, muscle mass accounts for approximately 37-77% of the variance in power output during FRT depending on the exercise. Increasing inertial load tends to decrease power output during FRT.

Purpose: To investigate the effects of eccentric exercise on lower body skeletal muscle mass during rapid body mass loss induced by bariatric surgery. Methods: All participants began 6 to 8 weeks after undergoing Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG). Skeletal muscle mass (SMM) in the lower body was measured via magnetic resonance imaging (MRI); additional exercise measurements included muscular strength and functional capacity. Quality of life was measured using Short Form 36 (SF-36). Nineteen females (age = 37.6 ± 9.8 yr, height = 164.4 ± 7.2 cm, mass = 106.9 ± 15.6 kg) were randomly assigned to 1 of 3 groups: eccentric exercise (EEX; n = 6), concentric exercise (CEX; n = 7), or standard-of-care control (CON; n = 6). Exercise groups performed 30-minute lower-body exercise sessions 3 times per week for 16 weeks. Each month the exercise tests were evaluated. At the end of 16 weeks, all participants performed the final exercise tests, received a final MRI scan, and completed the SF-36 questionnaire. Results: Thirteen individuals completed the study. All groups lost mass: CON: 21.4 ± 3.7 kg (p < 0.001), CEX: 19.9 ± 4.0 kg (p = 0.001), and EEX: 21.8 ± 3.3 kg (p < 0.001). SMM decreased in all groups: CON: 0.77 ± 0.5 kg (p = 0.18), CEX: 1.19 ± 0.6 kg (p = 0.06), and EEX: 0.90 ± 0.5 kg (p = 0.09). The skeletal muscle loss in percent of total mass loss was 3.7 ± 4.1%. All measures of muscular strength showed no difference, except for a small decrease in dynamic (60°·sec-1) strength in the eccentric group. Functional capacity and physical quality of life increased significantly in all groups (p < 0.05). Conclusion: SMM loss still occurred in the lower body regardless of resistance training, but the loss was less than what was previously documented. Improved postsurgical functional capacity and physical quality of life may be due to a reduction in fat mass and maintenance of muscular strength during the period of rapid mass loss.

Introduction:  Aging is related to a gradual decline in skeletal muscle mass, which is associated with morphological modifications such as reduced muscle fiber cross-sectional area and satellite cell content. Data also suggest that a short-term strength training period can be an effective instrument to rejuvenate these morphological parameters and to restore muscle mass. Therefore, the aim of this study is to investigate the effects of one year progressive strength training on fiber type-specific morphological parameters (fiber type composition, fiber area, satellite cell content, myonuclear number and domain) in skeletal muscle of elderly men.   Methods: Thirteen healthy elderly men (age range, 66-77 years) were randomly assigned into training (T) (n=7) and control (C) (n=6) groups. 52 weeks of progressive strength training was performed. Before and after the training, muscles biopsies were collected from the middle part of the vastus lateralis by percutaneous needle biopsy technique. Muscle biopsies were examined for muscle fiber type composition, fiber type-specific hypertrophy and alterations in satellite cell content, myonuclear content and domain using immuno-histochemistry.   Results: At baseline, myonuclear content and mean fiber area was larger in type I fibers compared to type II fibers (p<0.05). No statistically significant differences were found in fiber type composition, mean fiber area, satellite cell content and myonuclear domain between T and C groups at baseline. By the end of the training period, fiber area was increased by 59% (p<0.05) in type I and 71% (p<0.05) in type II. Satellite cell content, myonuclear content and myonuclear domain were increased after training in type I by 58% (p<0.05), 33% (p<0.05), and 20% (p<0.05), respectively. Similar increases in satellite cell content (+65%; p <0.05), myonuclear content (+36%; p <0.05) and myonuclear domain (+25%; p<0.05) were seen in type II fibers. Conclusion: The current study reported that long-term strength training is an excellent tool to prevent sarcopenia. It is demonstrated that skeletal muscle in elderly is capable to enhance satellite cell and myonuclear content, which contributed to muscle hypertrophy.

presentation was made in august 2012 and thesis is approved and got result as well in november 2012

For an enhanced reading experience go to a later version: http://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-31017.

This study was a part of a larger research project studying adaptations to strength, endurance and combined training

Context: The metabolic syndrome, characterized by central obesity with dyslipidemia, hypertension, and hyperglycemia, identifies people at high risk for type 2 diabetes. Objective: Our objective was to determine how the insulin resistance of the metabolic syndrome is related to muscle fiber composition. Design:Thirty-nine sedentary men and women (including 22 with the metabolic syndrome) had insulin responsiveness quantified using euglycemic clamps and underwent biopsies of the vastus lateralis muscle. Expression of insulin receptors, insulin receptor substrate-1, glucose transporter 4, and ATP synthase were quantified with immunoblots and immunohistochemistry. Participants and Setting: Participants were nondiabetic,metabolic syndrome volunteers and sedentary control subjects studied at an outpatient clinic. Main Outcome Measures: Insulin responsiveness during an insulin clamp and the fiber composition of a muscle biopsy specimen were evaluated. Results: There were fewer type I fibers and more mixed (type IIa) fibers in metabolic syndrome subjects.Insulin responsiveness and maximal oxygen uptake correlated with the proportion of type I fibers.Insulin receptor,insulin receptor substrate-1, and glucose transporter 4 expression were not different in whole muscle but all were significantly less in the type I fibers of metabolic syndrome subjects when adjusted for fiber proportion and fiber size.Fat oxidation and muscle mitochondrial expression were not different in the metabolic syndrome subjects. Conclusion:Lower proportion of type I fibers in metabolic syndrome muscle correlated with the severity of insulin resistance. Even though whole muscle content was normal, key elements of insulin action were consistently less in type I muscle fibers, suggesting their distribution was important in mediating insulin effects

Ageing is accompanied by a progressive decline in skeletal muscle mass and strength which may lead to impaired ability to perform activities of daily living in older adults. Although the exact cause of the gradual decline in muscle mass is unknown, identifying efficient strategies aiming to prevent age-related loss of muscle mass and strength is important in order to promote healthy ageing. The overall aim of this thesis was to explore the effects of resistance training alone or combined with a healthy diet on skeletal muscle mass and function of healthy recreationally active older women and to determine mechanisms by which elevated systemic inflammation may contribute to the age-related decline of muscle mass in older adults. The combination of resistance training and a healthy diet induced gains in leg lean mass as well as greater gains in dynamic explosive force than resistance training alone in healthy recreationally active older women. The observed gains in leg lean mass were accompanied by increases in the size of type IIA muscle fibres together with down-regulation in gene expression of a pro-inflammatory factor (IL-1β) and upregulation in gene expression of a regulator of cellular growth (mTOR) in skeletal muscle of older women. Additionally, reduced muscle protein synthesis and size of muscle cells may mediate the detrimental effects of elevated circulating markers of inflammation on muscle mass in older adults. In conclusion, the present thesis depicts mechanistic links between elevated systemic marker of inflammation and muscle mass and provides new information on the effects of combined resistance training and healthy diet on muscle mass and strength in a group of healthy recreationally active older women. This knowledge is instrumental for development of strategies aiming to prevent age-related loss of muscle mass and function.

Chronic kidney disease (CKD) is a catabolic condition associated with skeletal muscle wasting and dysfunction, both of which have important clinical implications. Exercise interventions are capable of improving physical function and exercise capacity in CKD patients; with those incorporating strength training significantly improve muscle size and strength. This thesis investigated the effects of aerobic only (AE) and combined aerobic and resistance exercise (CE) on skeletal muscle hypertrophy and function, and the molecular responses following acute unaccustomed and accustomed bouts of exercise. The primary hypothesis tested was that CE would result in greater muscle hypertrophy and increases in muscle function in comparison to aerobic AE (Chapter 5), and that this would occur with altered expression of genes and proteins associated with the regulation of muscle mass in CKD (Chapters 6, and 7). Both AE and CE resulted in increased quadriceps muscle volume and strength, however these were substantially greater in those performing CE. Muscle biopsies from participants completing both exercise interventions demonstrated a failure to upregulate p-Akt and mRNA expression of the myogenic regulators following the initial bout of exercise indicating that CKD patients may exhibit an impaired response to the exercise stimulus in the untrained state. This response appears to be restored following 12-weeks of CE but following AE. Moreover, both groups demonstrated a substantial increase in the gene expression of inflammatory cytokines following unaccustomed exercise, however this was not observed following accustomed exercise. This thesis demonstrates that CE produces superior increases in muscle size and strength compared to AE alone. This appears to occur through the modulation of intramuscular pathways following regular exercise and therefore highlights the importance of incorporating regular resistance exercise into exercise interventions aiming to improve muscle dysfunction in CKD.

Mass spectrometry coupled with liquid chromatography and gel electrophoresis enables separation and detection of components in a complex mixture. During the last two decades, its applications were dramatically extended and remarkable progress has been made in many fields, in particular, environmental and biological analyses. This dissertation focuses on identification and characterization of biologically active compounds and comparative analysis of protein expression changes. The first two projects (Chapters 2 and 3) focus on the application of LC/MS approach to profile the bioactivated intermediates of 4, 4'-methylenedianiline (DAPM) from rat vascular smooth muscle cells (VSMCs) and bile. In our study, several DAPM metabolites were detected and characterized in detail by liquid chromatography-electrospray tandem mass spectrometry. The structural assignments of these metabolites from VSMCs and rat bile significantly improve our understanding of DAPM biotransformations and toxicity. The third project described in Chapter 4 focuses on using electrospray tandem mass spectrometry (ES-MS/MS) and theoretical calculation (GAUSSIAN 03 program) to investigate the unusual methyl radical loss and consecutive fragment ions that dominate the low-energy collision induced dissociation (CID) mass spectra of prodiginine compounds. Structures of the fragment ions are proposed and explanations are given to rationalize the observed competition between the formation of even-electron ions and radical ions. Our study shows that the lower apparent threshold associated with methyl radical loss points to a lower kinetic barrier. In Chapter 5, hypoxia-induced changes of zebrafish skeletal muscle were studied using two-dimensional difference in-gel electrophoresis (2D-DIGE) in vivo after 48 h in hypoxia vs. normoxia. The results showed that proteins involved in mitochondrial oxidative metabolism are down-regulated, whereas glycolytic enzymes are up-regulated to compensate for the loss of ATP synthesis in aerobic metabolism. The up-regulation of two spots identified as hemoglobin variants was also observed. These protein expression changes are consistent with a hypoxic response that enhances anaerobic metabolism or O2 transport to tissues.

The purpose of this experiment was to investigate skeletal muscle blood flow and glucose uptake in m. biceps (BF) and m. quadriceps femoris (QF) 1) during recovery from high intensity cycle exercise, and 2) while wearing a compression short applying ~37 mmHg to the thigh muscles. Blood flow and glucose uptake were measured in the compressed and non-compressed leg of 6 healthy men by using positron emission tomography. At baseline blood flow in QF (P = 0.79) and BF (P = 0.90) did not differ between the compressed and the non-compressed leg. During recovery muscle blood flow was higher compared to baseline in both compressed (P<0.01) and non-compressed QF (P<0.001) but not in compressed (P = 0.41) and non-compressed BF (P = 0.05; effect size = 2.74). During recovery blood flow was lower in compressed QF (P<0.01) but not in BF (P = 0.26) compared to the non-compressed muscles. During baseline and recovery no differences in blood flow were detected between the superficial and deep parts of QF in both, compressed (baseline P = 0.79; recovery P = 0.68) and non-compressed leg (baseline P = 0.64; recovery P = 0.06). During recovery glucose uptake was higher in QF compared to BF in both conditions (P<0.01) with no difference between the compressed and non-compressed thigh. Glucose uptake was higher in the deep compared to the superficial parts of QF (compression leg P = 0.02). These results demonstrate that wearing compression shorts with ~37 mmHg of external pressure reduces blood flow both in the deep and superficial regions of muscle tissue during recovery from high intensity exercise but does not affect glucose uptake in BF and QF. © 2013 Sperlich et al.

:doi 10.1371/journal.pone.0060923

Mestrado em Biomedicina Molecular
Physical inactivity is a major risk for obesity. This chronic disease results from a caloric imbalance causing an enlargement of adipocytes by excessive fat storage. With an increasing prevalence, childhood obesity is correlated with endothelial dysfunction, inflammation and oxidative stress conducting to the development of other diseases not only in children but also during adulthood. In other hand, numerous children practice exercise of high duration or intensity in high competition sports, which can have harmful effects at physical, physiological and psychological level. In high competition young athletes, oxidative stress and immunosuppression can happen leading to an elevated risk of infection. However, an improved lipid profile is found in childhood athletes. Thus, the objective of the present study was to analyze the impact of childhood obesity as well as intense swimming training in body composition, inflammation and lipid profile, through blood analysis, bioimpedance and immunodetection of the pro-inflammatory cytokines (IL-6 and TWEAK), a myokine (Myostatin) and an acute-phase protein (CRP). For that, 24 young people were recruited into three groups: obese, athlete and lean. The obese group had high levels of body fat, an atypical lipid profile (low HDL and high LDL), high levels of lactate dehydrogenase in the blood indicating tissue damage, chronic inflammation (high IL-6, CRP and TWEAK) and low muscle mass (high Myostatin) without muscle damage (low CK). However, low serum levels of hepatic enzyme (AST and ALT) in these obese children do not associate obesity with liver disease. In other hand, intense physical exercise is not a harmfull activity for young athletes, since the lipid profile is improved and the increased levels of inflammatory markers is not significant. The main benefit of intensive training is the decreased levels of glucose being a protective role for diabetes.
A inatividade física é um dos principais riscos para a obesidade. Esta doença crónica resulta de um desiquilíbrio calórico causando um alargamento dos adipócitos através do excesso de armazenamento de gordura. Com um aumento da prevalência, a obesidade infantil correlaciona-se com a disfunção endotelial, inflamação e stress oxidativo, conduzindo ao desenvolvimento de outras doenças não só em criança, mas também durante a idade adulta. Por outro lado, muitas crianças praticam exercício de elevada duração ou intensidade em desportos de alta competição, o que pode ter efeitos prejudiciais a nível físico, fisiológico e psicológico. Em jovens atletas de alta competição, stress oxidativo e imunossupressão podem ocorrer levando ao elavado risco de infeção. No entanto, perfis lipídicos melhorados são encontrados em crianças atletas. Desta forma, o objetivo do presente estudo foi analizar o impacto da obesidade infantil bem como de treinos intensivos de natação na composição corporal, inflamação e perfil lipídico através de análises ao sangue, bioimpedância e imunodeteção de citocinas pró-inflamatórias (IL-6 e TWEAK), uma miocina (Miostatina) e uma proteina de fase aguda (CRP). Para tal, foram recrutados 24 jovens divididos em três grupos: obesos, atletas e normoponderais. O grupo de obesos apresentou elevados níveis de gordura corporal, um perfil lipídico atípico (baixo HDL e elevado LDL), níveis elevados de lactato desidrogenase no sangue indicando dano tecidual, inflamação crónica (elevado IL-6, CRP e TWEAK) e massa muscular diminuida (elevada Miostatina) sem dano muscular (baixo CK). No entanto os baixos níveis de enzimas hepáticas (AST e ALT) no soro não associam a obesidade com doença hepática. Por outro lado, o exercício físico intenso não é uma atividade prejudicial para os jovens atletas, uma vez que o perfil lipídico é melhorado e o aumento dos níveis de marcadores inflamatórios não é significativo. O principal benefício do treino intensivo é a diminuição dos níveis de glucose tendo um papel protetor para a diabetes.

Orientador: Denise Vaz de Macedo
Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Biologia
Made available in DSpace on 2018-08-16T10:10:49Z (GMT). No. of bitstreams: 1 Gandra_PauloGuimaraes_D.pdf: 3901290 bytes, checksum: ee5d5ae8b4367d8ada3a77f8e845aec2 (MD5) Previous issue date: 2010
Resumo: A presente tese apresenta os resultados de dois estudos utilizando análise proteômica, sobre os efeitos agudos e crônicos do exercício de endurance no músculo de ratos. No primeiro estudo foram coletadas amostras de gastrocnemio de animais controle não exercitados, e exercitados em teste incremental de media duração em esteira ate a exaustão. Os ratos foram sacrificados 3h e 24h após o exercício. Utilizamos a abordagem clássica da análise proteômica quantitativa, que utiliza a eletroforese bidimensional (2DE) para separação das proteínas, e a espectrometria de massas para identificação destas proteínas. Seis spots apresentaram alterações significativas no volume relativo. Os spots identificados como gliceraldeido-3-fosfato desidrogenase, triose fosfato isomerase 1, subunidade beta da piruvato desidrogenase E1, carnitina palmitoil transferase 2 e HSC70 mostraram-se mais abundantes apos o exercício. Já o spot identificado como ?-actina mostrou-se menos abundante apos o exercício. Estes resultados sugerem que um único estímulo de endurance em animais destreinados não estimula a síntese de proteínas miofibrilares, mas sim de proteínas sarcoplasmáticas e mitocondriais. Essas alterações no músculo destreinado serviriam para precondicionar o músculo para realização de um exercício subsequente. No segundo estudo apresentamos a análise proteômica da porção vermelha (GV) e branca (GB) do gastrocnemio de ratos controle não treinados (C), de ratos bem adaptados ao exercício de endurance (T1), e de ratos treinados e submetidos a um período de overtraining (T2). Os ratos do grupo T2 foram subdivididos ainda em grupo overreaching funcional (FOR), que exibiram aumento ou manutenção do desempenho após o overtraining, e grupo overreaching não funcional (NFOR), cujo nível de desempenho estava diminuído apos o overtraining. Na comparação entre C, T1 e T2, 32 spots demonstraram alterações no GV e 22 no GB. No GV as maiores alterações ocorreram no grupo T2. As proteínas com aumento na abundancia indicam aumento da biogênese mitocondrial, da capacidade de captar lipídeos, maior capacidade antioxidante, maiores abundancia de chaperonas e transformação das fibras no sentido de rápidas para lentas, sugerindo que um período de overtraining e eficiente em adaptar o músculo esquelético. Já no GB as adaptações esperadas com o treinamento de endurance não foram aparentes. A diminuição da abundância de spots da aconitase sugere um maior ataque oxidativo no GB do que no GV. Após o estímulo crônico proteínas do miofilamento e de interação com o miofilamento e citoesqueleto demonstraram abundância alterada. No seu conjunto, nossos resultados sugerem que a resposta inicial do músculo a um único estimulo de endurance envolve um aumento inespecífico da capacidade de produção de ATP, enquanto a estimulação crônica aumenta somente a capacidade oxidativa, com uma concomitante diminuição da abundancia de proteínas glicoliticas. Além disso, chamam a atenção para um papel chave das mitocôndrias e proteínas dos miofilamentos e citoesqueleto no processo adaptativo e maldaptativo ao exercício.
Abstract: In the present work the acute and chronic changes in rat skeletal muscle in response to endurance exercise were investigated by proteomic analysis. The results are presented in two separated studies. In the first study gastrocnemius muscle were sampled from control non exercised animals and from animals exercised to exhaustion in an incremental manner in a treadmill. Exercised rats were sacrificed 3 and 24h after exercise cessation. We used the classic proteomic approach which utilizes two dimensional electrophoresis (2DE) to separate the proteins and mass spectrometry to identify these proteins. Six spots presented significant alterations in their relative volume. Spots identified as GAPDH, triose phosphate isomerase 1, beta subunit of pyruvate dehydrogenase E1, carnitine palmitoil transferase 2 and HSC70 were up-regulated after exercise. The spot identified as ?-actin was down-regulated after exercise. This results suggests that one bout of endurance exercise in untrained muscle may stimulate sarcoplasmic and mitochondrial proteins synthesis but not myofibril proteins. Proteins presenting increased abundance after one single bout of endurance exercise may be important for the preconditioning of skeletal muscle for a subsequent exercise bout. In the second study we present the proteomic analysis of the red (RG) and white portion (WG) of gastrocnemius muscle sampled from rats well adapted to endurance exercise (T1), well trained and submitted to an overtraining period (T2) and from control non exercised rats (C). Rats from group T2 were also subdivided in a functional overreaching group (FOR) which is composed by rats demonstrating an enhanced or unchanged performance after the overtraining period or a non functional overreaching group (NFOR) which is composed by rats demonstrating decreased performance levels after the overtraining period. When comparing C, T1 and T2, 32 spots demonstrated altered abundance in RG and 22 in the WG. The main alterations in RG were observed in the T2 group and indicated increased mitochondrial biogenesis, increased capacity of lipid uptake, antioxidant capacity, chaperone function, and a shift of fiber type from a fast-glycolytic to a slow-oxidative pattern. All these changes demonstrated the efficiency of an intensified training period to adapt skeletal muscle. The expected adaptations to endurance training were not evident in WG and the results such as decreased aconitase spots volume suggest higher oxidative stress levels in WG than in RG during overtraining. Myofilament and myofilament interacting proteins abundance were altered after chronic endurance stimuli. The results presented here suggests that the initial response of skeletal muscle to one single bout of endurance exercise encompasses an nonspecific increase of ATP production capacity while chronic stimulation increases only the oxidative capacity with a concomitant decrease in glycolytic proteins abundance. Also the results draw attention to the roles of mitochondria and myofilament proteins in adaptation and maladaptation to endurance exercise.
Doutorado
Bioquimica
Doutor em Biologia Funcional e Molecular

L’utilisation de glucocorticoïdes (GC) pour le traitement de maladies inflammatoires ou d’antagonistes des androgènes pour le cancer de la prostate est limitée par l’induction d’effets secondaires, tels que l’atrophie musculaire. Comme les mécanismes sous-jacents étaient mal connus, nous avons caractérisé le rôle de ces hormones dans la régulation des fonctions musculaires. Nos résultats montrent que le récepteur aux GC des myofibres contrôle négativement la masse musculaire par des actions distinctes en présence de concentrations physiologiques et pharmacologiques de GC. De plus, notre étude a permis d’identifier de nouveaux réseaux de gènes contrôlés par les GC dans le muscle. Nous avons également démontré que les androgènes favorisent le gain de performance musculaire via l’amélioration de la force. Ainsi, cette étude a clarifié les mécanismes régulant l’homéostasie musculaire et ouvre des perspectives prometteuses pour identifier de nouvelles cibles thérapeutiques
The use of glucocorticoids (GC) to treat inflammatory diseases or androgen antagonists for prostate cancer is limited by the occurrence of side effects such as muscle atrophy. As the underlying mechanisms were unclear, we characterized the effects of GC and androgens on muscle mass and function. Our results demonstrate that myofiber GC receptor negatively controls muscle mass by distinct actions under physiological and pharmacological levels of GC. Moreover, our data identified many genes and networks controlled by GC in myofibers. We also showed that androgens promote the gain in muscle performance during postnatal development via the improvement of specific maximal force and power. Thus, this study allowed to clarify the molecular and cellular mechanisms regulating muscle homeostasis, and paves the way to identify new therapeutic targets

A dexametasona (DEXA) é um potente agente imunossupressor e antiinflamatório, mas apresenta importantes efeitos colaterais, tais como a atrofia muscular e a resistência à ação da insulina nos músculos esqueléticos. Neste contexto, a suplementação com leucina poderia representar uma estratégia nutricional terapêutica capaz de limitar os efeitos colaterais do tratamento com DEXA. Neste estudo, foram investigados os efeitos da suplementação com leucina em baixas e altas doses sobre a massa muscular, força muscular, assim como vários marcadores metabólicos que estão sob controle da insulina em ratos com restrição calórica e em ratos tratados com DEXA. Como a resposta da suplementação com leucina pode também estar ligada à forma de administração desse aminoácido, realizamos experimentos com leucina administradas via gavagem (bolus) versus leucina diluída no bebedouro dos animais. A suplementação com leucina demonstrou preservar a massa muscular, a força muscular voluntária média e a homeostasia da glicose em animais sob restrição calórica, mas este efeito foi observado apenas com a leucina suplementada em baixas concentrações/doses. Este efeito da leucina sobre a massa muscular esteve associado com a expressão de genes envolvidos no remodelamento da musculatura esquelética. Quanto ao efeito da leucina sobre a homeostasia da glicose, um efeito benéfico do aminoácido foi observado com a suplementação em baixas doses, o qual foi evidenciado pelos dados metabólicos avaliados. No entanto, sob tratamento com DEXA, a suplementação com leucina agravou o estado \"diabetogênico\" dos animais. Por último, a via de administração da leucina influenciou significativamente a resposta a este aminoácido, onde a suplementação via gavagem mostrou-se menos prejudicial do que a suplementação com leucina diluída nos bebedouros, ao menos em relação ao aspecto diabetogênico causado pelo tratamento concomitante com DEXA
Dexamethasone (DEXA) is a potent immunosupressor and anti-inflammatory agent but presents side effects such as muscle atrophy and insulin resistance in skeletal muscles. In this context, leucine supplementation may represent a way to limit the DEXA side effects. In this study, we investigated the effects of a low and a high dose of leucine on muscle mass, on muscle strength as well as on several metabolic markers that are under insulin control in energy-restricted and DEXA-treated rats. Since leucine response may also be linked to the way of administration of this amino acid, we performed experiments with leucine given in a gavage versus leucine given in drinking water way. Leucine supplementation was found to spare muscle mass, voluntary medium strength and glucose homeostasis in energy restricted animals but the effect was observed only with the low dose/concentration of leucine. The leucine effect on muscle mass was associated with expression of genes involved in muscle remodeling. However, under DEXA treatment, leucine supplementation was found to aggravate the diabetogenic state. Lastly, the route of leucine administration was found to significantly influence this variable to this amino acid, where leucine supplemented via gavage demonstrated to be less deleterious than supplemented diluted in the water drink, concomitantly with DEXA treatment

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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES
The study is part of a randomized, parallel clinical trial entitled "Effect of nutritional intervention and olive oil in severely obesity (DieTBra Trial)." The original articles seek to investigate sarcopenia in severe obese adults in terms of prevalence, factors associated with its diagnosis and the effectiveness of extra virgin olive oil and the traditional Brazilian diet as a dietary intervention. A total of 111 severe obese individuals (body mass index [BMI] ≥ 35.0 kg/m²) participated in the clinical trial, with a follow-up of 12 weeks and three intervention groups: Olive oil = extra virgin olive oil (52 mL/day); DieTBra = traditional Brazilian diet; DieTBra + Olive Oil = DieTBra + extra virgin olive oil (52 mL/day). Appendicular skeletal muscle mass (MMEA), measured in the total form (kg), adjusted by squared height (appendicular skeletal muscle mass index [IMMEA]) and by BMI (MMEA/BMI), strength of manual (FPM) and BMI adjusted (FPM/BMI), and walking speed. The prevalence calculation considered the cutoff points proposed in the literature and the calculation of -2 standard deviation (SD) of the mean value of the parameters of muscle mass evaluated in the study population. The ANOVA test was applied to evaluate the difference between the means of the parameters of second to the age group. The prevalence according to cutoff points proposed in the literature varied from 2.88% for IMMEA, 6.73% for total MMEA and 62.50% according to MMEA/BMI. When adopting - 2 SD below the mean of the study population, the prevalence was 2.88% for total MMEA and 3.85% for IMMEA and MMEA/BMI. Although no statistically significant difference (p > 0.05) was found between the means of the parameters according to the age group, prevalence values higher than those previously demonstrated in the age group ≥ 40 years were observed. In the second article, the explanatory variables considered were age, lifestyle, health conditions, food consumption and biochemical tests. Those with p value < 0.20 in simple linear regression were included in multiple linear regression. Among the factors inversely associated with IMMEA are serum levels of tetraiodothyronine (T4) and smoking. MMEA/BMI was inversely associated with age, serum T4 levels and presence of diabetes. MMEA also remained inversely associated with serum T4 levels and diabetes. The reduction of FPM and FPM/BMI were associated with advancing age and presence of hypercholesterolemia. Already the low speed of march was associated with the presence of diabetes and hypothyroidism. The primary endpoint considered in the third article was the IMMEA and the secondary ones were: FPM, gait speed, MMEA/IMC, total MMEA, total body fat and percentage. In the endpoints and covariates analyzed, the delta was also calculated, which is the difference between the value of the end of follow-up and the baseline. Covariance analysis (ANCOVA) was performed to analyze the effect of covariates delta weight, delta physical activity, delta time of sedentary lifestyle, sex and age, on the outcomes. A significance level of 5% was adopted. After performing the ANCOVA, the covariates of the delta weight adjusted the following outcomes in the DieTBra intervention group: reduction of delta total body fat (p = 0.016), increase in delta walking speed (p = 0.042) and delta FPM (p = 0.044 ). And also for reduction of delta body fat in the DieTBra + Olive oil group (p = 0.004). When adjusted for the delta time of sedentary lifestyle, total body fat presented a significant reduction in the DieTBra + Olive oil group (p = 0.001). The prevalence of sarcopenia differed as different assessments were used for muscle mass, evidencing the need to standardize the criteria and cutoff points used in its classification. The factors associated with the evaluation parameters, evidenced the importance of the creation of clinical measures and public health aimed at the prevention of sarcopenia. The positive effects of DieTBra and DieTBra + Olive oil on the parameters of sarcopenia and adiposity, reveal the importance of the adequate evaluation, diagnosis and treatment of sarcopenia in adults with severe obesity.
O estudo está inserido no ensaio clínico, randomizado e paralelo, intitulado “Effect of nutritional intervention and olive oil in severely obesity (DieTBra Trial)”. Os artigos originais buscam investigar a sarcopenia em adultos obesos graves em termos de prevalência, fatores associados ao seu diagnóstico e a efetividade do azeite de oliva extravirgem e da dieta tradicional brasileira como intervenção dietética. Participaram do ensaio clínico 111 obesos graves (índice de massa corporal [IMC] ≥ 35,0 Kg/m²), com seguimento de 12 semanas e três grupos de intervenção: Azeite = azeite de oliva extravirgem (52 mL/dia); DieTBra = dieta tradicional brasileira; DieTBra + Azeite = DieTBra + azeite de oliva extravirgem (52 mL/dia). Foram considerados como parâmetros de avaliação da sarcopenia: massa muscular esquelética apendicular (MMEA), avaliada na forma total (kg), ajustada pela altura ao quadrado (índice de massa muscular esquelética apendicular [IMMEA]) e pelo IMC (MMEA/IMC), força de preensão manual (FPM) máxima e ajustada pelo IMC (FPM/IMC), e velocidade de marcha. O cálculo da prevalência considerou os pontos de corte propostos na literatura e o cálculo de -2 desvio padrão (DP) do valor médio dos parâmetros de massa muscular avaliados na população do estudo. O teste ANOVA foi aplicado para avaliar a diferença entre as médias dos parâmetros de segundo a faixa etária. A prevalência segundo pontos de corte propostos pela literatura variou de 2,88% por IMMEA, 6,73% pela MMEA total e 62,50% segundo MMEA/IMC. Ao adotar - 2 DP abaixo da média da população de estudo, a prevalência foi de 2,88% pela MMEA total e de 3,85% por IMMEA e MMEA/IMC. Embora não tenha sido estabelecida diferença estatística significante (p > 0,05) entre as médias dos parâmetros segundo a faixa etária, foi observado valores de prevalência superiores aos anteriormente demonstrados na faixa etária ≥ 40 anos. No segundo artigo, as variáveis explanatórias consideradas foram idade, estilo de vida, condições de saúde, consumo alimentar e exames bioquímicos. Aquelas com valor p < 0,20 na regressão linear simples foram incluídas na regressão linear múltipla. Dentre os fatores inversamente associados ao IMMEA está níveis séricos de tetraiodotironina (T4) e ser fumante. MMEA/IMC foi inversamente associado a idade, níveis séricos de T4 e presença de diabetes. A MMEA também se manteve inversamente associada a níveis sérico de T4 e diabetes. A redução da FPM e FPM/IMC foram associadas ao avançar da idade e presença de hipercolesterolemia. Já a baixa velocidade de marcha esteve associada com a presença de diabetes e hipotireoidismo. O desfecho primário considerado no terceiro artigo foi o IMMEA e os secundários foram: FPM, velocidade de marcha, MMEA/IMC, MMEA total, gordura corporal total e percentual. Nos desfechos e nas covariáveis analisadas calculou-se também o delta, que é a diferença entre o valor do final do seguimento e a linha de base. Foi realizada análise de covariância (ANCOVA) para analisar o efeito das covariáveis delta peso, delta atividade física, delta tempo de sedentarismo, sexo e idade, sobre os desfechos. Adotou-se nível de significância de 5%. Após realização da ANCOVA, a covariável delta peso ajustou os seguintes desfechos no grupo de intervenção DieTBra: redução do delta gordura corporal total (p = 0,016), aumento do delta velocidade de marcha (p = 0,042) e do delta FPM (p = 0,044). E ainda para redução do delta gordura corporal no grupo DieTBra + Azeite (p = 0,004). Quando ajustada pelo delta tempo de sedentarismo, a gordura corporal total apresentou redução significativa no grupo DieTBra + Azeite (p = 0,001). A prevalência de sarcopenia diferiu à medida que se empregou diferentes avaliações para massa muscular, evidenciando a necessidade de padronização dos critérios e pontos de corte empregados na sua classificação. Os fatores associados aos parâmetros de avaliação, evidenciaram a importância da criação de medidas clínicas e saúde pública direcionadas a prevenção da sarcopenia. Os efeitos positivos da DieTBra e DieTBra + Azeite sobre os parâmetros da sarcopenia e adiposidade, revelam a importância da adequada avaliação, diagnóstico e tratamento da sarcopenia em adultos com obesidade grave.

Poor health and injury represent major obstacles to the future economic security of Australia. The national economic cost of work-related injury is estimated at $57.5 billion p/a. Since exposure to high physical demands is a major risk factor for musculoskeletal injury, monitoring and managing such physical activity levels in workers is a potentially important injury prevention strategy. Current injury monitoring practices are inadequate for the provision of clinically valuable information about the tissue specific responses to physical exertion. Injury of various soft tissue structures can manifest over time through accumulation of micro-trauma. Such micro-trauma has a propensity to increase the risk of acute injuries to soft-tissue structures such as muscle or tendon. As such, the capacity to monitor biomarkers that result from the disruption of these tissues offers a means of assisting the pre-emptive management of subclinical injury prior to acute failure or for evaluation of recovery processes. Here we have adopted an in-vivo exercise induced muscle damage model allowing the application of laboratory controlled conditions to assist in uncovering biochemical indicators associated with soft-tissue trauma and recovery. Importantly, urine was utilised as the diagnostic medium since it is non-invasive to collect, more acceptable to workers and less costly to employers. Moreover, it is our hypothesis that exercise induced tissue degradation products enter the circulation and are subsequently filtered by the kidney and pass through to the urine. To test this hypothesis a range of metabolomic and proteomic discovery-phase techniques were used, along with targeted approaches. Several small molecules relating to tissue damage were identified along with a series of skeletal muscle-specific protein fragments resulting from exercise induced soft-tissue damage. Each of the potential biomolecular markers appeared to be temporally present within urine. Moreover, the regulation of abundance seemed to be associated with functional recovery following the injury. This discovery may have important clinical applications for monitoring of a variety of inflammatory myopathies as well as novel applications in monitoring of the musculoskeletal health status of workers, professional athletes and/or military personnel to reduce the onset of potentially debilitating musculoskeletal injuries within these professions.

Les androgens(ADs) et les glucocorticoïdes (GCs) sont des hormones stéroïdiennes qui exercent des effets pléiotropes chez les mammifères. Leurs effets sont relayés par deux récepteurs nucléaires, le récepteur des androgènes (AR) et le récepteur des glucocorticoïdes (GR), respectivement. Même si les GCs sont fréquemment utilisés pour traiter les maladies inflammatoires et les antiandrogènes pour le cancer de la prostate, les traitements à long terme induisent des effets secondaires majeurs, notamment l'atrophie musculaire.Afin de préciser les mécanismes d’action de ces hormones, nous avons réalisé des analyses phénotypiques, transcriptomiques et cistromiques. La première partie de ce travail démontre que GR des myofibres contrôle négativement la masse et la force musculaire aux niveaux physiologiques de GCs. La perte de GR dans les muscles squelettiques n'affecte pas les voies cataboliques, mais augmente l’expression de facteurs anaboliques et réduit celle de facteurs anti-anaboliques. Nous avons également montré que GR se lie à des éléments de réponse du GR (GREs) situés aux enhancers, en association avec Myod1 et Foxf2, et interagit avec des facteurs liés aux promoteurs, tels que Nrf1, pour favoriser la transcription des gènes.Dans la deuxième partie de ce travail, nous avons comparé le cistrome et le transcriptome du GR dans la prostate et le muscle squelettique, et identifié des sites de liaison pour d'autres facteurs de transcription proche des GREs, indiquant que ces facteurs contribuent à la spécificité tissulaire. De plus, en comparant les cistromes et transcriptomes d’AR et de GR dans la prostate, nous montrons que les éléments de réponse liés par les deux récepteurs sont distincts de ceux liés uniquement par AR ou GR, et que la sélectivité du récepteur dépend de la liaison d’autres facteurs de transcription.Enfin, nous avons comparé les données transcriptomiques et épigénétiques du tissu musculaire squelettique et de myoblastes et myotubes C2C12, et nous fournissons une description détaillée de gènes, voies de signalisation et facteurs de transcription exprimés de façon différentielle pendant la différenciation myogénique.En conclusion, nos travaux ont permis de clarifier les mécanismes moléculaires régulant l'homéostasie musculaire et ont établi la base d'une compréhension moléculaire des effets spécifiques des ADs et des GCs dans divers types cellulaires
Androgens (ADs) and glucocorticoids (GCs) are steroid hormones exerting pleiotropic effects in mammals. Their effects are mediated by two nuclear receptors, the androgen (AR) and the glucocorticoid (GR) receptor, respectively. Although GCs are extensively used to treat inflammatory diseases and antiandrogens for prostate cancer, long-term treatments induce major side effects such as muscle atrophy.To determine the mechanisms underlying their effects in muscle, we performed phenotypic, transcriptomic and cistromic analyses. The first part of this work demonstrates that myofiber GR negatively controls muscle mass and strength under physiological GCs levels. GR loss in skeletal muscle did not affect catabolic pathways, but enhanced the expression of anabolic factors and reduced that of anti-anabolic ones. We also showed that myofiber GR binds DNA to GR response elements (GREs) located at enhancers, in association with Myod1 and Foxf2, and interact with promoter-bound factors such as Nrf1 to promote gene transcription.In the second part of this work, we compared GR cistromes and transcriptomes in prostate and skeletal muscle, and identified binding sites for additional transcription factors in the vicinity of GREs, indicating that they contribute to the tissue specificity. In addition, by comparing the AR and GR cistromes and transcriptomes in prostate, we show that the response elements bound by both receptors are distinct from those bound by either AR or GR, and that the receptor-selectivity depends mostly on the surrounding factors.Finally, we compared transcriptomic and epigenetic data of skeletal muscle tissue and C2C12 myoblasts and myotubes and provide a detailed description of genes, signaling pathways and transcription factors that are differentially expressed during myogenic differentiation.In conclusion, our work allowed to clarify the molecular mechanisms regulating muscle homeostasis and provides the basis of a molecular understanding of tissue- and/or promoter-specific activity of ADs and GCs

Under-nutrition and weight loss in older people remain poorly recognized and so are undermanaged. Those at nutritional risk, and especially those losing weight, experience a loss of muscle mass referred to as sarcopenia, which is related to many different adverse health outcomes, including falls and increased risk of fracture. Although research into the condition has gained momentum over the last two decades, especially for those aged eighty years and older, research has predominately been conducted overseas. In Australia, very few studies have investigated the prevalence of sarcopenia in our older population. Local evidence is required in order to inform Australian policy makers and the health and aged care sector. Furthermore, in spite of the increasing call for appreciation, screening and early diagnosis of the condition, there is no consensus as to a preferred screening method. Without acceptable clinical screening tools, identification of sarcopenia continues to be problematic. It is therefore important to develop a simple clinical test to facilitate early detection in primary or aged care settings as part of continuing and increasing Australian research into sarcopenia. Additionally, whilst appetite loss is known to be a contributing factor, the relationship between inflammation and appetite loss in healthy individuals with no recent history of weight loss is unclear. The aims of this thesis were therefore: (1) to identify the prevalence of sarcopenia in primary care; (2) to develop and validate simple anthropometric prediction equations (PE) for lean body mass (LBM) and appendicular skeletal muscle mass (ASM); (3) to determine the performance of the ASM PE compared to dual absorptiometry x-ray assessment (DXA) of ASM in combination with grip strength; and (4) to explore the association between cytokines and appetite in a healthy population. Research from this doctoral thesis has confirmed that sarcopenia is common in community dwelling older Australians and increases with age. Anthropometric prediction equations for LBM and ASM were developed and validated: LBM= 22.932326 + 0.684668 (weight) - 1.137156 (BMI) -0.009213 (age) + 9.940015 (if male) and ASM= 10.047427 + 0.353307 (weight) - 0.621112 (BMI) - 0.022741 (age) + 5.096201 (if male). Cut-offs for low muscle mass for use in Australia was also developed. The use of ASM PE for the identification of low muscle mass, in combination with a measure of low muscle function, such as grip strength, performs well as a ‘rule out’ screening test for sarcopenia when compared to the diagnostic test of ASM assessed using DXA in combination with low grip strength. At the same time, appetite was found to be negatively associated with serum levels of pro-inflammatory IL-1ß and positively associated with serum levels of anti-inflammatory cytokine IL-10 in apparently healthy people with no recent weight loss. Research from this doctoral thesis has contributed to increased awareness that sarcopenia is common and this will aid early intervention. At the same time, a clinical screening tool to support the early diagnosis of sarcopenia was developed.
Thesis (Ph.D.) (Research by Publication) -- University of Adelaide, School of Medicine, 2014.

Thesis (Ph. D.)--University of Illinois at Chicago, 2004.
Includes bibliographical references (leaves 172-194). Also available online (PDF file) by a subscription to the set or by purchasing the individual file.

碩士
長庚科技大學
護理系碩士在職專班
107
Hemodialysis is the most common type of dialysis replacement therapy—up to 90% of all dialysis patients in Taiwan. There are 40% to 75% hemodialysis patients have protein energy malnutrition (PEM), which is a common nutritional problem, and presentations of PEM include muscle mass. After long-term hemodialysis for 1year, patients lost 1.6kg of muscle mass, if they combined with malnutrition, inflammation, diabetes will accelerate the loss of muscle mass. muscle mass resulted in muscle weakness, impaired physical performance, high risk for falling and depression, poorer quality of life, and reduced survival. There are few studies in Taiwan explore correlation with diet quality, muscle mass and nutritional status in hemodialysis patients. This study aimed to explore physical activity, muscle mass and nutritional status correlate with demographics, clinical disease characteristics, and diet quality in hemodialysis patients. In the research based on the cross-sectional design and convenience sampling for 104 routine outpatient hemodialysis patients as the subjects form a hospital in the south Taiwan, during their weekly routine hemodialysis treatment, we will interview using a semi-structured questionnaires, included 4 items: demographics, clinical characteristics, diet quality, nutritional status and physical activity and estimating muscle mass by Body Composition Monitor (BCM; Fresenius Medical Care, Bad Homburg, Germany), for collected data. The results showed gender, age, vintage, FTI (fat tissue Index, FTI) and physical activity were predictive factor of muscle mass loss (p<.001), and gender, vintage and nutritional status was significantly correlated with normal muscle mass (p=.001). 59.6% of the patients with muscle mass were normal, 40.4% were lower, 64.4% of the patients were insufficient physical activity, 88.2% of the patients were well-nourished. 80.8% of the patients had poor diet quality, because 65.38% of the patients exceed saturated fat foods and had the lower components of vegetables and fruits. In summary, it can be known that more than half of the hemodialysis patients had insufficient physical activity. Our study recommended that hemodialysis patients should be encouraged to develop regular exercise habits for increasing physical activity to prevent the loss of muscle mass. In terms of diet quality, the nursing staff should teach patients to avoid eating foods rich in saturated fa. Hemodialysis patients need to limit intake of potassium, which affects intake of fruit, but there is no research to explore correlation between the intake of fresh fruits and vegetables and high blood potassium. Expecting to have relevant research and investigation in the future, as a reference for clinical nursing staff to correctly guide to improve the quality of diet.

We assessed potential mechanisms that may jeopardize skeletal muscle perfusion during surgery leading to adverse outcomes including muscle injury and flap hypoxia. In craniotomy patients, we observed an increase in serum lactate and creatine kinase and urine myoglobin; indicative of muscle damage. The early rise in lactate correlated with elevated BMI, suggesting that obesity caused tissue compression and muscle ischemia. In our rodent model, we investigated the effects of flap preparation and phenylephrine on muscle perfusion by assessing microvascular blood flow and tissue PO2. Phenylephrine reduced muscle blood flow by ~20%, yet increased PO2 by ~10% suggestive of decreased O2 metabolism. At baseline, muscle flap blood flow was reduced by ~50% while PO2 was severely reduced ~80% (~5 torr) suggesting that flap perfusion was attenuated and O2 metabolism was increased. Phenylephrine infusion further reduced muscle flap perfusion. These data demonstrate multiple mechanisms by which muscle perfusion is jeopardized during surgery.

Access to abstract permanently restricted to Ball State community only.
Access to dissertation permanently restricted to Ball State community only.
School of Physical Education, Sport, and Exercise Science

Master of Science
Department of Kinesiology
Brad J. Behnke
Prostate cancer is the most common type of non-skin cancer found in men and preliminary evidence suggests prostate cancer has atrophic effects on cardiac and left ventricle (LV) mass which are associated with reduced endurance exercise capacity in rats. Using a pre-clinical orthotopic model of prostate cancer, echocardiography was utilized to test the hypothesis that exercise training will mitigate prostate cancer induced-cardiac and skeletal muscle atrophy and improve LV function versus sedentary tumor-bearing counterparts. Methods: Dunning R-3327 AT-1 prostate cancer cells were injected orthotopically in male Copenhagen rats aged (n=39; ~5 mo. old). Animals were randomized into four groups, exercise-trained tumor-bearing (EXTB) or control (EXCON) and sedentary tumor-bearing (SEDTB), or control (SEDCON). Exercise training was performed via a rodent treadmill set at 15m/min with a 15° incline for 60 min/day for ~30 days. Animals underwent echocardiographic evaluation using the parasternal short axis view to examine ventricle dimensions pre-cancer or exercise (PRE) and 15 (Post 1) and 30 (Post 2) days post cancer cell injection and/or exercise training with tissues collected immediately after Post 2. Results: Cardiac and LV mass of SEDTB animals were significantly lower than all groups (p<0.05). Tumor mass was significantly negatively correlated with LV mass in EXTB (-0.75, p<0.02) and SEDTB animals (-0.72, p<0.02). EXCON group had significantly higher stroke volume Post 2 assessment compared to both sedentary groups (p<0.05), but not EXTB animals. Conclusion: The current investigation demonstrates prostate cancer independent of anti-cancer treatment significantly reduces cardiac mass, and LV mass as well as locomotor muscle masses. However, moderate intensity exercise training can mitigate cardiac and skeletal muscle atrophy with prostate cancer.

Skeletal muscle regeneration is hindered in severe injuries and degenerative diseases, including volumetric muscle loss (VML), due to the failure of current treatments to induce functional tissue growth. Various biological functions in skeletal muscle are supported by the extracellular matrix (ECM), a collection of proteins and glycosaminoglycans. In vivo studies on murine plantaris muscle hypertrophy indicate that ECM remodeling facilitates muscle growth, but a global analysis of ECM protein dynamics during skeletal muscle hypertrophy and repair are unknown. Understanding this influence of the ECM can establish instructive cues for regenerative therapies. Here, we define global proteomic changes throughout stages of plantaris muscle hypertrophy, with an emphasis on characterizing ECM proteins. Synergistic ablation of the gastrocnemius and soleus muscles induced a compensatory hypertrophic effect causing a 40% mass increase in the plantaris muscle 28 days post injury. Liquid chromatography-tandem mass spectrometry revealed the differential abundance of 1233 proteins, including 99 ECM proteins, across five time points. After two days of injury, a significant increase of ECM glycoproteins was observed although the overall collagen abundance decreased. Throughout the duration of injury, the relative abundance of type I collagen decreased while there was an increase of proteins associated with type I collagen fibrillogenesis (types III and V) and basement membrane (types IV and VI). Collectively, these results provide a better understanding of ECM dynamics throughout skeletal muscle hypertrophy. Future studies will evaluate protein synthesis by using non-canonical amino acids to identify newly synthesized proteins. Temporal analysis of protein dynamics symbolic to injury and tissue growth will provide tissue engineers with precise information to develop successful regenerative therapies to restore functional muscle in VML.

碩士
國防醫學院
公共衛生學研究所
106
The elderly population and its prevalence of obesity have increased year by year. Various aspects of obesity may be assessed by anthropometry. With age body composition changes, body fat increases, and lean body mass, especially skeletal muscle mass decreases. Elderly with sarcopenic obesity, are more likely to be frail. A longitudinal study based on the 1999-2000 National Nutrition and Health Survey in Taiwan for adults 65 years of age or older has been linked to the National Health Insurance database until 2006 and the National Death Registration database until 2008. Obesity and skeletal muscle mass indices have been considered in relation to medical service utilization and mortality in this population. Generalized linear models with appropriate adjustments were used to assess differences in utilization and costs of medical service for elderly according to body composition. BMI or waist circumference and skeletal muscle mass index (SMMI) were combined (Q1= low SMMI group; Q2-Q4= high SMMI group), to explore the effect of obesity and low SMMI on medical service utilization and expenditure. The Cox proportional-hazards model was used to estimate the relative risk of mortality after adjusting for covariates. Regardless of index, obese elderly used more outpatient services (including chronic diseases) and incurred greater expenditure, and those who were underweight had longer hospitalization(days), used emergency services more often, and had greater total medical expenditure. Compared with the normal BMI-high SMMI group, the obese-low SMMI group had 29% (exp(β) = 1.29, 95% CI: 1.15-1.44) more expenditure on chronic disease. Compared with the non-abdominally obese and high SMMI group, the abdominally obese-low SMMI had 11% more outpatient services (exp(β) = 1.11, 95% CI: 1.06-1.16), 10% more chronic disease services (exp(β) = 1.10, 95% CI: 1.03-1.17) and a 67% increase in risk of death (HR = 1.67, 95% CI: 1.13-2.44). The underweight-low SMMI group had 84% more emergency attendances (exp(β) = 1.84, 95% CI: 1.41-2.39) and 96% more emergency expenditures (exp(β) = 1.96, 95%CI: 1.12-3.46) as well as double the hospitalization (exp(β) = 2.25, 95% CI: 2.10-2.42) and the total medical expenditure (exp(β) = 2.13, 95% CI: 1.58-2.87) along with triple the hospitalization expenditure (exp(β) = 3.18, 95% CI: 1.63-6.21) and the risk of death (HR: 2.73, 95% CI: 1.84-4.04). Taking BMI and waist circumference into account, the normal BMI-abdominally obese-low SMMI group had an increased the risk of death of 1.3 times (HR = 2.32, 95% CI: 1.48-3.81). In conclusion, either obesity or underweight, in combination with low SMMI increase the risk of medical utilization and mortality in the elderly. Keywords: Medical utilization, Mortality, Older adults, Obesity indices, Sarcopenic obesity

碩士
國立臺南大學
體育學系碩士班
99
Purpose：This study investigated the effect of endurance training and calorie restriction on skeletal muscle mass and energy metabolism in female rats for 8 weeks. Method：48 female Wistar rats（7 weeks）were randomly divided into four groups（n＝12 in each group）：low intensity (70% VO2max) endurance training（LIT）, high intensity (85% VO2max) endurance training（HIT）, control group（CON） and diet control group（DCON）. Exercise groups received treadmill training for 8 weeks：60 minutes a day and 5 days a week. For calorie restriction, DCON group were daily fed 80%-90% of exercise groups. Weights were recorded twice a week. Measured muscle weight and assayed activity of citrate Synthase (CS), 3-hydroxyacyl-CoA dehydrogenase (β-HAD), lactate dehydrogenase (LDH) and phosphofructokinase (PFK) after experiment for each group. Recorded data was analyzed by One-way analysis of variance (ANOVA) to compare weight, muscle weight and enzyme activity. Results：DCON group was significantly lower than HIT group, LIT group and CON group（p&lt;.05）after 2th weeks. For muscle weight, Soleus (SOL) weight of DCON group was significantly lower than other 3 groups（p&lt;.05）；Extensor digitorum longus (EDL) weight of DCON group was significantly lower than LIT and HIT groups. On the part of skeletal muscle energy metabolism enzyme, there was no significant effect in CS, β-HAD, LDH and PFK activity of SOL, and no significant effect in CS, β-HAD and PFK activity of EDL, either. DCON group is higher than HIT group（p&lt;.05）in LDH activity. Conclusion：Calorie restriction lower weight in female rats. In addition, there wasn’t significant effect in endurance training to increase energy metabolism enzyme activity in skeletal muscle. However, calorie restriction increased LDH activity in EDL.

碩士
國防醫學院
公共衛生學研究所
106
Background: As time went on, the social age structure change. Low skeletal muscle has already become one of important topic for ages healthy, but this syndrome may happen to the young people who body fat ratio too high. This study expects examining low skeletal muscle mass index (SMMI) through Anthropometric and biochemical values, which are more accessible and economical. Aim to find out which body position indexes or biochemical indexes are able to evaluate skeletal muscle mass. Method: Use 2001-2002 National Health and Nutrition Examination Survey (NHANES) open database, find out which body position indexes or biochemical indexes about low SMMI. The low SMMI test result is by dual-energy X-ray absorptiometry (DEXA), explore the association between low skeletal muscle mass index, body indexes and biochemical indexes. Results: The result shows in five body indexes, four body indexes have high Pearson correlation with SMMI, p-value<0.001, however, biochemical indexes are not ideal, only insulin’s Pearson correlation have 0.4, p-value<0.001. Linear multiple regression shows the SMMI increase with arm circumference, maximal calf circumference, thigh circumference and waist circumference increase every 1 cm, the triceps skinfold have negative effect to SMMI in man. In woman, the arm circumference, maximal calf circumference and thigh circumference have a positive effect to SMMI, the waist circumference and triceps skinfold have negative effect to SMMI. Logistic regression shows arm circumference, maximal calf circumference and thigh circumference are protected factor to a man, arm circumference and triceps skinfold are protected factor to a woman. Conclusion: The body indexes could be SMMI’s good evaluation index, biochemical indexes only insulin more suitable to evaluate SMMI, consider the accessible, economically and safely, totally as the body indexes a focus to evaluate SMMI. Non-Hispanic black’s muscle mass possible higher than other races, muscle strength training could be very significant influences effect to muscle mass.

Background/Objectives: Individuals with a spinal cord injury (SCI) experience reductions in lower-extremity muscle mass and increased fatty-infiltration of skeletal muscle, predisposing them to an increased risk of specific secondary health conditions. To date, few investigations have prospectively examined changes in muscle in the chronic stage of SCI. Peripheral quantitative computed tomography (pQCT) is an imaging technique capable of measuring lower-extremity skeletal muscle cross-sectional area (CSA) and muscle density, the latter is a surrogate measure of muscle fatty infiltration. The purpose of this project was to a) determine the magnitude of muscle CSA and muscle density reduction in a chronic-SCI population with diverse impairments; b) identify demographic and injury characteristics associated with muscle CSA and density status; and c) determine if muscle CSA and muscle density change over a two-year period following chronic-paralysis and if so, what factors are associated with the changes. Materials and Methods: Seventy individuals [50/20 m/f, mean (± SD) age 48.9 ± 11.5 years; duration of injury 15.5 ± 10.0 years] with chronic (>2 years post-injury) SCI (C1-T12, AIS A-D) were enrolled in a two-year cohort study. Muscle CSA and muscle density values were calculated from pQCT scans of the 66%-site of the calf obtained at baseline and two follow-up visits separated by one year. Possible correlates of muscle CSA and density selected a priori included: gender, age, height, weight, waist circumference, age at injury, level of injury, injury duration, leg spasm frequency and severity scale score (SFSS), ISNCSCI calf-muscle lower-extremity motor score (cLEMS), wheelchair use, serum vitamin D level, and physical activity level. Dependent t-tests were used to compare muscle CSA and muscle density values of participants with complete and incomplete-SCI to age, gender, and height matched able-bodied controls. Multiple linear regression models were used to determine correlates of muscle CSA and muscle density. Repeated measures analysis of variance (rANOVA) were used to examine change in muscle CSA and density over the two-year study duration and multiple linear regression models were created to determine correlates of muscle CSA and density change from baseline. Results: Individuals with motor-complete SCI had a 45% reduction in muscle CSA and a 32% reduction in muscle density relative to controls. Participants with motor-incomplete SCI had a 17% reduction in muscle CSA and a 14% reduction in muscle density relative to controls. A reduced height, waist circumference, cLEMS, and wheelchair use were associated with a smaller muscle CSA in the best-fitting regression model (R2 = 0.66; p<0.0001). In the best-fitting regression model for muscle density, increased age, a lower cLEMS, reduced SFSS, fewer minutes of daily vigorous physical activity, and wheelchair use were associated with a lower muscle density (R2= 0.37; p<0.001). A high degree of individual variability in muscle CSA change (mean ± SD: -1.9 ± 6.2cm2; range: -22.6 to 8.5 cm2) and muscle density change (mean ± SD: -1.2 ± 3.28mg/cc; range: -8.6 to 6.4 mg/cc) was observed in those with both complete and incomplete SCI over the two-year study duration. rANOVA indicated a significant reduction in both muscle CSA and density after controlling for individual variability. A greater waist circumference at baseline was weakly associated with a reduction in muscle CSA (R2 = 0.14, p<0.05), and a lower weight and waist circumference at baseline were associated with a reduction in muscle density (R2 = 0.26, p < 0.001 and R2 = 0.20, p < 0.01, respectively). Conclusion: Age, completeness of injury, spasticity, physical activity participation, and ambulation ability were identified as potential clinical predictors of muscle status in individuals with chronic-SCI. Muscle CSA and density does not reach a “steady-state” after chronic-SCI. Further investigation is needed to determine the mechanisms responsible muscle CSA and density change in order to prevent continued reductions after chronic-SCI.

Although life expectancy is increasing, this often comes at the cost of declining health through an increased incidence of cancer, cardiovascular disease and arthritis in older age. In addition, a decline in muscular performance is commonly observed with increasing age, combining a loss of skeletal muscle (‘sarcopenia’), a decrease in muscle oxidative capacity and a reduction in muscle strength. Research has shown that it is possible to arrest, or even reverse, the changes in muscle mass and oxidative capacity that occur with age. Two of the most successful strategies identified to date in this regard are exercise, in particular resistance-based training, and protein supplementation. We devised a series of four related studies to investigate and refine strategies for the prevention or mitigation of sarcopenia among the elderly.

碩士
國防醫學院
公共衛生學研究所
106
Background: Sarcopenia is the degenerative loss of skeletal muscle mass and strength associated with aging; neurodegenerative diseases and sleep may affect the development of sarcopenia. Abnormal metabolism of homocysteine (Hcy) leads to poor sleep and increases the risk of neurodegenerative diseases. In this regard, the relationship between Hcy and its metabolic-related nutrients (vitamins B-2, B-6, B-12 and folate) with sarcopenia may be relevant. Aim: To assess whether the Hcy metabolic pathway or its related nutrients are associated with skeletal muscle mass in elderly Taiwanese. Study design: Cross-sectional population-based study. Methods: Participants were those in the Elderly Nutrition and Health Survey in Taiwan (1999-2000) (n=1204). Skeletal muscle mass (SMM) index [SMMI= SMM (kg) /height (m2)] was used to identify sarcopenia. Those with the lowest 25% SMMI value (Q1), who were known to have a higher risk of death, were classified as the low SMMI group and the rest of the population as the high SMMI group. SUDAAN was used to weight and adjust for the design effects of cluster sampling. Logistic regression was used to ascertain any association between plasma Hcy concentration and related nutrients with low SMMI. Results: The risk of low SMMI in men who were clinically vitamin B-6 deficient was 1.07 times more than their non-deficient counterparts (95% CI=1.18- 3.62, p=0.013). Hcy concentration and vitamin B-6 and B-12 nutritional status in men showed a J-shaped risk for low SMMI when Hcy and related nutrients were grouped by quintiles. This finding may be caused by illness or treatment of the disease. However, after consideration of each disease (sensitivity analyses), the risk of low SMMI in vitamin B-2 deficiency men was 1.87 times more than when non-deficient (p=0.041); the risk of the low SMMI with vitamin B-6 deficiency was 2 times more than when non-deficient (p=0.046). Findings for women were not concordant with those for men. Conclusion: Vitamin B-2 and B-6 status in older men are independently associated with SMMI. Although associations were not evident between vitamin B-12 or folate and SMMI, they may still operate indirectly through the Hcy metabolic pathway. However, there is no evidence that plasma Hcy concentration or vitamin B group status are independently associated with SMMI in older women, perhaps because of unmeasured confounding factors.

The modern obesogenic lifestyle encompasses an environment that promotes weight gain in the form of body fat accumulation. Genetic variations can predispose some individuals to be more susceptible to developing obesity in a similar environment (Hainer et al. 2000; Maes et al. 1997; Mustelin et al. 2009). As the prevalence of obesity increases worldwide, and becomes a substantial socioeconomic issue, the need for research that deepens our understanding of the underlying genetic influences on complex regulatory mechanisms governing energy homeostasis becomes increasingly necessary. The fat mass and obesity-associated (FTO) gene has been strongly linked to an increased obesity risk through numerous genome wide association (GWA) studies over the past decade. However, information regarding FTO’s peripheral influences, specifically on skeletal muscle metabolism, is limited. The broad aim of this dissertation was to identify metabolic differences between risk allele and non-risk variants of FTO, and to determine the impact of physical stress (in the form of exercise) on FTO expression and function. Thus, the experiments presented in this dissertation were designed to investigate whether differences across genotype alleles of the FTO rs9939609 (T>A) polymorphism existed for metabolic flexibility in response to a nutritional challenge, and for metabolic profiles, FTO expression and FTO function in skeletal muscle following acute exercise stimuli.

Potassium (K+) regulation during exercise is vital in preserving muscle membrane excitability, a failure of which has been linked to muscle fatigue. This thesis investigated the regulation of arterial and venous plasma K+ concentration ([K+]) during and following intense exercise and its importance for exercise performance, muscular force and excitability via three interventional studies, comparing two- versus one-legged cycling (Study 1), acute oral digoxin versus placebo intake (Study 2), and high-intensity intermittent training versus non-training control (Study 3). Study 1. The effects of different contracting muscle mass were investigated on arterial and venous plasma [K+], fatigability and muscle torque following exhaustive two- versus one- legged high-intensity intermittent cycling exercise. Eleven recreationally active adults performed two- (2L) and one-legged (1L) trials, which comprised cycling for six, 2 min repetitions at 80% V̇ O2peak, then at 90% V̇ O2peak continued to fatigue. Radial arterial (a) and antecubital venous (v) plasma [K+] ([K+]a, [K+]v, respectively) were measured prior to and during exercise bouts, and for 30 min recovery. The quadriceps maximal isometric voluntary contraction (MVC), as well as potentiated quadriceps twitch force (Qtw,pot), doublet and tetani (20 Hz) and vastus medialis (VM) and vastus lateralis (VL) M-wave (amplitude, duration and area) evoked via magnetic stimulation, were measured prior to exercise, 1 min after exercise bouts 1, 3 and 6, and up to 30 min in recovery. Plasma [K+]a increased throughout exercise (P < 0.05, time main effect), being greater in 2L than 1L (P < 0.05, treatment main effect) and with [K+]a being greater in 2L than 1L during 90% V̇ O2peak after 2 min and at fatigue, reaching 6.03 ± 0.58 vs 5.21 ± 0.52 mmol.1-1 at fatigue for 2L and 1L, respectively (P < 0.05). Plasma [K+]v increased at fatigue for 2L and 1L, reaching 5.98 ± 0.64 and 5.34 ± 0.43 mmol.1-1 respectively, but did not differ significantly between trials. The [K+]a-v difference across the inactive forearm was higher throughout exercise to fatigue (P < 0.05, time main effect) and was greater in 2L than 1L (treatment main effect, P < 0.05). Plasma [Lac-]a increased throughout exercise, reaching 7.40 ± 1.74 and 5.28 ± 1.12 mmol.1-1 at fatigue for 2L and 1L, respectively (P < 0.05), with 2L greater than 1L during recovery at 2-30 min (P < 0.05). The MVC was decreased after exercise and in recovery (P < 0.05, time main effect), falling at fatigue (P < 0.05) by 17% for 2L (rest 135 ± 59 vs. fatigue 112 ± 57 Nm) and by 26% for 1L (rest 144 ± 57 vs. fatigue 107 ± 63 Nm). Each of the evoked Qtw,pot, doublet and 20 Hz torque declined after fatigue and remained depressed at 30 min recovery (P < 0.05, time main effect), with Qtw,pot less in 1L than 2L at 30 min recovery (P < 0.05). The twitch M-wave amplitude declined throughout exercise and recovery, whilst duration was extended after fatiguing exercise, in both VM and VL (P < 0.05, time main effect), with area also reduced after fatigue only in VM (P < 0.05); there were no significant differences between 1L and 2L. In conclusion, exercise with a large contracting muscle mass augmented [K+]a, suggesting a greater K+ release from contracting muscles. The greater [K+]a-v across the forearm in 2L cycling suggests also greater K+ uptake by inactive muscle, probably via activation of muscle Na+,K+-ATPase. Nonetheless, plasma [K+] was tightly regulated during intense exercise, with only relatively small differences evident between trials, despite substantially differing contracting muscle mass. Despite elevated [K+]a, 2L was accompanied by lesser percentage declines in MVC compared to 1L exercise; whilst the M-wave characteristics give some evidence of excitability changes with fatigue, but with minimal differences between trials. Thus, the slightly greater [K+]a disturbances during cycling to fatigue with 2L than 1L exercise, were not accompanied by greater post-exercise reductions in muscle torque and changes in M-wave characteristics. Study 2. The effects of acute digoxin intake on K+ regulation, muscle performance, muscle excitability, and fatigability were investigated in ten recreationally active adults, in a randomised, crossover, double-blind, counterbalanced study design. Ten healthy adults received orally 0.50 mg digoxin or placebo 60 min prior to cycling exercise, which was 1 min at 60% V̇ O2peak and at 95% V̇ O2peak, then continued at 95% V̇ O2peak until fatigue. Radial arterial (a) [K+] ([K+]a) was measured pre-exercise, during exercise and for up to 60 min recovery. Quadriceps MVC, as well as muscle torque (Qtw,pot, doublet and 20 Hz tetani) and M-wave characteristics (amplitude, duration and area) evoked via magnetic stimulation were measured pre-exercise, 1 min following exercise and for 60 min recovery. Serum digoxin concentration at 60 min post-ingestion was 3.36 ± 0.8 nM (mean ± SD) in digoxin and less than the detectable level of 0.2 nM in placebo. Time to fatigue was 7.8% shorter during digoxin than placebo (P < 0.05). Plasma [K+]a increased during exercise and decreased early in recovery, being lower than baseline at 3-20 min recovery (P < 0.05, time main effect). During digoxin, plasma [K+]a was slightly greater than placebo (4.93 ± 0.2 vs. 4.88 ± 0.2, respectively) and the post-exercise [K+]a decline was less ( b o t h P < 0.05, treatment main effect). After exercise, the MVC torque, Qtw,pot, doublet and 20 Hz tetani (percentage pre- exercise) each decreased 1 min after fatigue and remained less than baseline at 60 min post- exercise (P < 0.05, time main effect) but did not differ between trials. Following exercise to fatigue the M-wave characteristics demonstrated variability between muscles and with time; amplitude was increased post-exercise in VL, duration increased at 60 min recovery in both VL and VM, whilst area increased at 60 min recovery in VM and 10 min post-exercise in VL (P < 0.05, treatment main effect). In VL, duration was greater with digoxin than placebo at fatigue (P < 0.05). Thus digoxin impaired cycling exercise performance to fatigue, with a slight increase in [K+]a but did not affect the fatigue-induced reductions in MVC, evoked torque or M-wave characteristics, other than a prolonged M-wave duration in VL. Hence, although plasma [K+] was increased and fatigability during cycling lessened with digoxin, it was not possible to conclude that acute digoxin treatment is linked to worsened muscle excitability. Study 3. The effects of High Intensity Interval Training (HIIT) were investigated on plasma [K+]a and [K+]v, muscle performance and muscle excitability Sixteen healthy adult participants were randomly allocated to training (HIIT, n = 8) or control (CON, n = 8). Exercise testing comprised a 2 min cycling bout at each of 60% V̇ O2peak and 80% V̇ O2peak, then followed by two 30s maximal sprints, separated by 120 s; these tests were repeated Pre and Post HIIT and CON. Radial arterial (a) and antecubital venous (v) blood samples were measured prior to and during exercise bouts, and in recovery for 60 min. Quadriceps MVC, and the potentiated quadriceps twitch force (Qtw,pot), doublet and tetani (20 Hz) and the vastus medialis (VM) and vastus lateralis (VL) M-wave (amplitude, duration area) evoked via magnetic stimulation, were measured prior to exercise, 1 min after 80% V̇ O2peak, after sprint exercise bouts, and for 60 min recovery. HIIT comprised repeated 30 s sprints during 3 sessions per week for 7 weeks. Plasma [K+]a was increased above rest during 60% and 80% V̇ O2peak exercise and returned to resting values at 2 min recovery, for both HIIT and CON (P < 0.05, time main effect). There was no trial main effect for [K+]a. For HIIT, there was a significant trial x time interaction, with lower [K+]a evident at Post compared to Pre during 80% V̇ O2peak and at 1 min recovery after the sprint bouts (P < 0.05). Plasma [K+]v increased during 60% V̇ O2peak, 80% V̇ O2peak exercise and the two sprint bouts (P < 0.05, time main effect) and was slightly above rest late in recovery (P < 0.05, time main effect); there was no trial main effect for [K+]v. There were significant trial x time interactions with higher [K+]v Post than Pre at fatigue for HIIT (P < 0.05) and 1 min recovery for CON (P < 0.05). The [K+]a-v difference across the forearm was increased with submaximal and sprint exercise for both HIIT and for CON (P < 0.05,time main effect ). Plasma [K+]a-v did not differ between trials. The peak power, total work and fatigue index were unchanged after HIIT. Sprint performance during the four 30 s sprints of the last training session after HIIT was unchanged compared to the first training session. There were decreases for all torque values with fatigue and also changes in M-wave characteristics (amplitude, duration and area). For MVC, there was no trial main effect, although MVC during HIIT was greater than CON after the first sprint bout (88 ± 9 vs. 65 ± 14% pre-exercise MVC, respectively, P < 0.05, trial x time interaction). For each of the quadriceps twitch, doublet and 20 Hz tetani torque or M-wave characteristics, there were no differences between trials. Thus, whilst HIIT improved K+ regulation with submaximal exercise and after two sprint bouts, this did not result in corresponding improvements in muscle voluntary and evoked contractile performance and muscle excitability. In conclusion, this thesis investigated the effects of differences in the active muscle mass, acute digoxin treatment and HIIT, on each of K+ regulation, muscle performance, muscle excitability and fatigue in humans. Plasma [K+]a increased during exercise then decreased early in recovery, with elevations in plasma [K+]a during 2L compared to 1L cycling, and in digoxin compared to placebo, lower [K+]a after HIIT during sub-maximal exercise and 1 min after sprint exercise. Interestingly, the MVC torque decline was less for 2L than 1L and for HIIT Post compared to Pre, whilst no difference was found between digoxin and placebo trials. The time to fatigue showed no significant difference between trials during the active muscle mass study but was 7.8% shorter for digoxin than placebo. Whilst considerable variability was evident in M- wave measures, there is evidence to suggest impaired muscle excitability after exercise. Thus, greater active muscle mass, acute digoxin and HIIT interventions that differentially affected K+ regulation during and after exercise did not show corresponding changes in muscle voluntary or evoked torque or excitability after exercise.

As the age increases, the physical fitness of seniors decreases. This shows the fragility of their body. Managing everyday activities becomes increasingly more difficult for them. Result of this is reduced self-sufficiency of the seniors, which leads to reduced mobility and to the greater loss of muscle mass and higher dependence on professional care. Aging is accompanied by loss of muscle mass and muscle strength - sarcopenia. This is one of the main causes of geriatric fragility. Sarcopenia presents a serious health problem with both social and economic consequences. The term sarcopenia (from Greek words sarx - meaning flesh referring to muscle and penia - loss) was first used in 1989 by Irwin Rosenberg to describe the loss of muscle mass accompanying aging. Exactly defining the term sarcopenia has helped explain this gradual loss of muscle mass. Three objectives were set in the thesis. The first objective was to find out whether sarcopenia reduces the quality of life in the elderly. The second goal was to determine, which quality of life tests are suitable for testing sarcopenia and the last one was whether the SARC - F questionnaire predicts sarcopenia.Quantitative research was used for the empirical part of this work. Data collection was performed using a method of a questionnaire. These were standardized questionnaires aimed at assessing sarcopenia and quality of life. The research was carried out with a total of 77 respondents with sarcopenia and respondents without sarcopenia. The quantitative part of the research was statistically processed using the MS Excel computer program.

Chemotherapy is an effective first-line cancer-treatment to slow or even cure cancer. Despite it being widely used to treat a variety of cancers, the majority of agents used induce a myriad of serious sequalae. Recently, chemotherapy emerged as a key contributing factor to the induction of devastating wasting condition, cachexia. Cachexia involves the progressive loss of body mass, underscored by severe skeletal muscle wasting and dysfunction (skeletal myopathy). Unravelling the molecular mechanisms involved in the onset and persistence of chemotherapy-induced cachexia represents a complex scientific challenge and is of great clinical interest to identify novel drug targets and efficacious adjuvants. This thesis characterised the impact of individual chemotherapeutic agents on the skeletal muscular system of mice [doxorubicin (DOX) and irinotecan (IRI), 5-fluorouracil (5FU)] and evaluated the therapeutic efficacy of mitoprotective adjuvant candidates, sodium nitrate (with DOX) and BGP-15 (for 5FU and IRI) to protect body mass and skeletal muscle during chemotherapy. Additionally, since chemotherapeutic agents are usually administered to cancer patients in combination regimens which might escalate cachexia, we also characterised the impact of the ‘7+3’ (cytarabine and daunorubicin) chemotherapy induction regimen (CIR) utilised as standard treatment against acute myeloid leukemia. In this regard, we developed and characterised a novel murine model of AML CIR-induced cachexia. We also used this model to trace the course of cachexia during and after treatment and to evaluate whether voluntary exercise could be protective. The major findings of thesis were that the onset and severity of chemotherapy-induced cachexia is agent/regimen specific. While DOX, an anthracycline and topoisomerase-II inhibitor, and IRI, a topoisomerase- I inhibitor, induced a cachectic phenotype characterised by diminished body composition indices, and skeletal myopathy, 5FU, an anti-metabolite, did not cause cachexia. Interestingly, the multi-agent CIR induced severe cachexia. The recovery post-CIR was mixed with skeletal muscle mass returning to normal levels, while body and lean mass not completely recuperating in the 2-week recovery period. At the molecular level, the expression of key structural cytoskeletal proteins, i.e. dystrophin, were impacted by IRI and 5FU whether skeletal myopathy was observed or not. These data suggest that loss of dystrophin might be an early event in the myopathy associated with cachexia. With regard to the adjuvant candidates evaluated, sodium nitrate was not protective against DOX-induced cachexia, despite protecting against early signs of cardiomyopathy. BGP-15 displayed modest protection against IRI-induced cachexia but was not afforded the opportunity when evaluated in combination with 5FU. Alongside the CIR voluntary activity was not protective against cachexia, rather it potentiated CIR-induced cachexia, likely driven through enhanced loss of fat mass. Overall, these findings highlight that further investigation is required regarding the efficacy of mitoprotective adjuvant therapies against chemotherapy-induced cachexia.

Este estudo teve como objetivo comparar a aptidão muscular e óssea entre jovens com e sem fratura óssea recorrente. Metodologia A amostra incluiu 534 participantes, de ambos os géneros (247 raparigas e 277 rapazes). A composição corporal, nomeadamente a massa gorda, a massa magra e a massa óssea foram avaliadas através da DXA. A aptidão muscular foi avaliada nos membros superiores através da força de preensão e nos membros inferiores através da força e potência muscular com uma plataforma de saltos, e através da distância de salto vertical e horizontal. As fraturas ósseas foram avaliadas através de questionário. Resultados: Constatou-se que as raparigas com fraturas ósseas recorrentes apresentam menor índice de massa magra apendicular e de potência muscular dos membros inferiores do que as raparigas sem qualquer fratura óssea. Nos rapazes, verificou-se uma tendência para fragilidade óssea ao nível do colo do fémur naqueles com fraturas ósseas recorrentes, mas não se observou diferenças na aptidão muscular ou na massa magra entre estes e os rapazes sem fratura óssea prévia. Conclusão: Tendo em vista a prevenção de fraturas ósseas de forma recorrente, a aptidão muscular incluindo a massa magra apendicular deve ser desenvolvida nos jovens dos 10 aos 17 anos, especialmente nas raparigas.
This study aimed to compare muscle and bone capacity among young people with and without recurrent bone fracture. Methodology: The sample included 534 participants of both genders (247 girls and 277 boys). Body composition, namely fat mass, lean mass and bone mass were evaluated by DXA. Muscle fitness was assessed in the upper limbs by grip strength and in the lower limbs by muscular strength and power with a jumping platform, and by the vertical and horizontal jumping distance. Bone fractures were assessed by questionnaire. Results: Girls with recurrent bone fractures were found to have lower appendicular lean mass index and lower limb muscle power than girls with no bone fracture. In boys, there was a tendency for bone fragility at femoral neck level in those with recurrent bone fractures, but no differences in muscle fitness or lean mass were found between boys and boys without previous bone fracture. Conclusion: In order to prevent recurrent bone fracture, muscle fitness including appendicular lean mass should be developed in young people aged 10 to 17, especially girls.

Doutoramento em Motricidade Humana na especialidade de Saúde e Condição Física
The chemical maturity does not occur until postpubescence is reached, and in young athletes, due to the biological phenomena occurring with exercise, there are dynamic fluctuations of body components beyond the natural growing process. The use of multi-component models is recommended instead of two-component approaches, dividing body weight into body fat and FFM. The limitations of body composition methods that do not account for the variability of the FFM may be also partially overcome by using age- and gender-specific constants of FFM components, although among young athletes, there is lack of these specific constants. The current dissertation assembled data of young Portuguese athletes, aged 8-18 years. Overall, it was demonstrated that: 1)the specific constants of FFM hydration developed by Lohman provide valid total body water estimates; 2)muscle mass can be accurately predicted using newly developed anthropometric equations; 3)there is a dose-dependent relationship between weekly training hours and molecular and cellular components, above 9 hrs/wk, independently of sports; 4)bone and lean mass molecular components are associated with participation in anaerobic and high impact sports, while body cell mass is related with an aerobic and non-gravitational sport; 5)young male competitive swimmers do not differ from non-athletic age-matched controls in bone mineral status.
A maturidade química não ocorre até que a pós-adolescência é alcançada, e em jovens atletas, devido aos fenómenos biológicos consequentes do exercício, existem flutuações dinâmicas das componentes corporais para além do processo de crescimento. O uso de modelos multi-compartimentais é recomendado no lugar de abordagens a dois-compartimentos. As limitações dos métodos de avaliação da composição corporal que não controlam para a variabilidade da massa magra (MM) podem também ser parcialmente ultrapassadas usando constantes das componentes da MM específicas para a idade e género, embora para jovens atletas, haja falta destas constantes. A presente dissertação reúne dados de atletas portugueses, com 8-18 anos. Globalmente, foi demonstrando que: 1)as constantes de hidratação desenvolvidas por Lohman fornecem estimativas precisas da água corporal; 2)a massa muscular pode ser estimada de forma precisa usando novas equações antropométricas; 3)existe uma relação dose-resposta entre as horas de treino e as componentes celular e molecular, acima das 9 horas por semana, independentemente da modalidade; 4)a massa óssea e magra estão associadas à participação em desportos anaeróbios e de impacto, enquanto que a massa celular a desportos aeróbios e sem impacto; 5)jovens nadadores de competição não diferem nos níveis de massa óssea de um grupo controlo composto por não-atletas.

Hematooncological diseases are often accompanied by dietary restriction, especially in cytotoxic therapy. The main purpose of the work was to assess the effect of high-dose chemotherapy on the change of nutritional status in two groups of hematooncological patients. A total of 16 patients were enrolled. Changes of the body composition were evaluated using bioelectrical impedance analysis supplemented by monitoring of biochemical nutritional indicators. Observations showed that in both groups the majority lost weight. In the first group of eight patients with acute myeloid leukemia observed during three consecutive hospitalizations, the median of change of body weight was -3.7 kg (-4.3%). Loss of lean body mass with a median value of -4.8 kg (-7.2%) was detected at all patients. Body fat was reduced at half of the patients. In some cases, with length of observation, there was an increase in fat mass along with visceral fat. In the second group, which included eight patients (after autologous hematopoietic stem cell transplantation) at whom one hospitalization was evaluated, body weight was reduced at six patients. The medianof change of body weight was -2.1 kg (-2.3%). At five patients, the treatment representeda loss of active metabolic mass. The change of the weight of the lean body mass was shown...