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.

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.

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.

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第20620号 / 医博第4269号 / 新制||医||1023(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 坂井 義治, 教授 小西 靖彦, 教授 川口 義弥 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

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

Submitted by Marlene Santos (marlene.bc.ufg@gmail.com) on 2018-07-20T21:04:52Z No. of bitstreams: 2 Tese - Jacqueline Danesio de Souza - 2017.pdf: 1896817 bytes, checksum: 8b8d4091000aa37121f775268ad356c0 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Approved for entry into archive by Luciana Ferreira (lucgeral@gmail.com) on 2018-07-23T12:09:45Z (GMT) No. of bitstreams: 2 Tese - Jacqueline Danesio de Souza - 2017.pdf: 1896817 bytes, checksum: 8b8d4091000aa37121f775268ad356c0 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Made available in DSpace on 2018-07-23T12:09:45Z (GMT). No. of bitstreams: 2 Tese - Jacqueline Danesio de Souza - 2017.pdf: 1896817 bytes, checksum: 8b8d4091000aa37121f775268ad356c0 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Previous issue date: 2017-06-09 / 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.

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

Investigou-se os efeitos da L-glutamina (1g/kg de massa corpórea) em camundongos jejuados por 24 horas. A L-glutamina atenuou a perda de massa muscular e a diminuição da área das fibras musculares esqueléticas causadas pelo jejum via Akt-mTOR. No sóleo, a L-glutamina estimulou a Akt (início da via), e no EDL ativou a S6 (final da via). Investigou-se também os efeitos da L-glutamina em miotubos (C2C12) cultivados por 48 horas. A diminuição de L-glutamina no meio (de 2 para zero mM) causou balanço proteico negativo e aumento do conteúdo dos aminoácidos livres, exceto dos produtos da glutaminólise, indicando estimulação de proteólise. O aumento de L-glutamina no meio (de 2 para 8 e 16 mM) não alterou o conteúdo intracelular de proteínas e dos aminoácidos livres. Na presença de 2 mM de glutamina no meio, a insulina teve efeito positivo no balanço proteico via Akt/mTOR/S6K, estimulando a S6K. Na ausência de glutamina, houve maior fosforilação de eIF2&alpha; estimulada por dexametasona e portanto menor síntese proteica. / We investigated the effects of L-glutamine (1g/kg of body mass) on 24 h fasted mice. L-Glutamine attenuated the loss of muscle mass and the reduction of the skeletal muscle fibers area caused by fasting. This attenuation occurred via Akt-mTOR, however, glutamine stimulated Akt (upstream) in the soleus, whereas it activated S6 (dowstream) in EDL. The effects of L-glutamine on myotubes (C2C12) cultured for 48 hours were also examined. The reduction of L-glutamine in the medium (from 2 to zero mM) decreased protein content and increased contents of all amino acids, except products of glutaminolysis, indicating stimulation of proteolysis. The increased L-glutamine levels in the medium (from 2 to 8 and 16 mM) did not change the intracellular contents of protein and free amino acids. In the presence of 2 mM glutamine, insulin had a positive effect on total protein content through Akt/mTOR/S6K pathway, stimulating S6K. In turn, in the absence of L-glutamine, there was increased eIF2&alpha; phosphorylation stimulated by dexamethasone and thus less protein synthesis.

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...