Nitric oxide (NO) is an important chemical factor that controls vascular tone in the cardiovascular system. NO is a vasodilatory molecule that plays a role in blood pressure and blood flow regulation as well as vessel formation and tissue cell proliferation. NO influences the flow by which nutrients and other metabolites required for growth are transported to the tissues. The aim of this study was to investigate if NO, through mediation by the NO donors Sodium Nitroprusside (SNP) and S-Nitrosoglutathione (GSNO) affect growth and oxygen consumption of prenatal broiler chicken. The results indicate that, although the treatments did not have clear significant effects on the embryos or the organs examined, a slight delay in development can be observed in the GSNO treatment embryos. The study could not conclude, however, if this was due to effects of NO donors

Although artificially selected goldfish exhibit swimming performance decrements, with the most derived morphotypes more affected, they can be utilized to explore functional design and movement pattern principles in aquatic vertebrates. Drag, steady swimming kinematics (tailbeat frequency, amplitude, stride length), energetics (standard and active metabolic rate), fast-start performance (average and maximum velocity and acceleration), stability in yaw and roll and propulsive muscle ultrastructural characteristics (mitochondrial volume density and spacing, myofibril diameter and capillary to fibre ratio in red and white muscle) were measured for four morphotypes: common, comet, fantail and eggfish, of comparable length (≈ 5 cm). A performance “pairing” (common and comet; fantail and eggfish) was a recurrent theme for most performance parameters. Vertebral numbers (30), segment lengths (≈ 0.85 mm) and standard metabolic rates (≈ 140 mg O2 kg-1 hr-1) are exceptions where values are the same. Fantail and eggfish drag and drag coefficients (referenced to frontally projected area ≈ 0.6 - 0.9) were higher (requiring more thrust at any given velocity) than those for the more streamlined common and comet (≈ 0.3 - 0.6; P < 0.05). This is reflected in kinematics; tailbeat frequency and stride length at any given velocity for the common and comet are lower and higher respectively than that of the fantail and eggfish (P < 0.05). Common and comet fatigue times are not significantly different from that of their ancestor, Crucian carp (P > 0.05), and are lower than those of the fantail and eggfish (P < 0.05). The cost of transport of the common and comet (≈ 0.6 mg O2 kg-1 m-1) is accurately predicted from the mass scaling relationship for fish (P > 0.05), but values for the fantail and eggfish (≈ 1.3 mg O2 kg-1 m-1) are not (P < 0.05). Eggfish steady swimming (dorsal fin absent) was characterized by rolling and yawing motions associated with significant energy losses. Common and comet fast-start performance (average velocity ≈ 0.45 m s-1, maximum velocity ≈ 1.2 m s-1, average acceleration ≈ 7.5 m s-2, maximum acceleration ≈ 35 m s-2) was similar to that of other locomotor generalists (e.g. trout). Eggfish maximum acceleration (≈ 5 m s-2) is poor due to the absence of inertial and lifting contributions to thrust from the dorsal fin and energy wasting rolling motions. Artificially selected fish can bear upon fitness related adaptations associated with form and movement, providing insights into the “performance envelope” of natural systems subject to ecological speciation. / Science, Faculty of / Zoology, Department of / Graduate

Le but cette thèse était d’explorer l’influence du niveau d’activité physique et du niveau de performance physique sur la densité minérale osseuse, la géométrie osseuse de la hanche et le score de l’os trabéculaire chez de jeunes hommes en surpoids et obèses. Trois principales études ont été menées. Une première étude a montré que la pratique d’activités physiques a un effet positif sur le CMO, la DMO et la section transversale du col fémoral chez les hommes en surcharge pondérale. Une deuxième étude a suggéré que le niveau d’activité physique influence positivement les paramètres osseux chez les hommes en surpoids et obèses et que l’optimisation de la masse maigre, de la VO2 max (L/min) et de la force maximale des membres inférieurs peut aider à prévenir l’ostéoporose chez les hommes en surpoids et obèses. Enfin, une dernière étude, a été la première à démontrer une relation positive entre la VO2 max (ml/mn/kg) et les indices de résistance osseuse du col fémoral (le CSI, le BSI et l’ISI) chez les jeunes hommes en surpoids et obèses et a donc suggéré que l’augmentation de la VO2 max chez les hommes en surpoids et obèses pourrait aider à réduire les fractures stéoporotiques. Ces différents résultats suggèrent une adaptation ostéogénique significative des jeunes hommes en surpoids et obèses en réponse à l’entrainement physique. / The aim of this thesis was to explore the influence of physical activity level and physical performance on bone mineral density, hip geometry and trabecular bone score in young overweight and obese men. Three main studies have been conducted. The first study has shown that physical activity practice has a positive effect on BMC, BMD and femoral neck crosssectional area in overweight men. The second study has shown that physical activity level positively affects bone variables in overweight/obese men and that increasing lean mass, VO2 max (L/min) and muscular strength of the lower limbs can help to prevent osteoporosis in overweight and obese men. Finally, the last study, was the first to show positive associations between maximal oxygen consumption (milliliter per minute per kilogram) and composite indices of FN strength (CSI, BSI and ISI) in young overweight and obese men and therefore suggested that enhancing VO2 max in overweight and obese men may help to reduce osteoporotic fractures. These different results suggest a significant osteogenic adaptation in young overweight and obese men in response to physical training.

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第22694号 / 医博第4638号 / 新制||医||1045(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 生田 宏一, 教授 竹内 理, 教授 濵﨑 洋子 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

An increasing amount of hikers have added hiking poles to their outings to aid in reducing fatigue of the lower body and enhance stability. However, very little research has been conducted on the use of poles during continuous uphill hiking. The purpose of this study was to investigate the effect of pole use under field conditions on the rate of perceived exertion, physiological variables [oxygen consumption (VO2), heart rate (HR), non-protein respiratory exchange ratio (RER), & total energy expenditure (TEE)], and time to completion during a 1.68 km continuous uphill (12.6% grade) hike. Ten male and ten female (Mean age = 22.7 ± 2.0 years) hikers participated in this experimental study using a within subject cross over design with randomized, counter-balanced order. Participants hiked with and without poles, at self-selected speeds. Rate of perceived exertion was collected at five minute intervals. Physiological measures (V02, HR, RER, and METs) were measured continuously (every two seconds) during all hiking conditions using a portable metabolic system (VmaxST, SensorMedics, Yorba Linda, CA). Heart rate data was recorded by a Polar transmitter belt worn by the participant with a receiver integrated into the VmaxST base system. Hiking pole use resulted in increased oxygen consumption (M= 29.8 ± 2.6 ml∙kg⁻¹∙min⁻¹ vs. M= 28.6 ± 2.8 ml∙kg⁻¹∙min), and total energy expenditure (M= 223.3 ± 57.9 kcals vs. 209.6 ± 47.7 kcals) compared to hiking without poles. Duration, RER, HR, and RPE were not significantly different between conditions. These results indicate that the use of hiking poles during uphill hiking increases the energy cost of hiking without increasing the perceived exertion in novice pole users. To fully evaluate the effects of hiking pole use and confirm the results from this study, future field research should be conducted with and without poles, including novice and expert groups, at grades above and below 15 %.

The growing public health burden associated with insufficient physical activity has resulted in the development of numerous health initiatives and products aimed at stabilizing and reversing the negative trends reported in epidemiological literature. A relatively novel product that has only recently made its way to the market are wearable weights called Body Togs®. These products are designed to be worn on the lower legs and arms along with regular clothing as a means to increase caloric expenditure. However, no research to date has tested the efficacy of this product. PURPOSE: Compare the physiological responses within bouts of aerobic exercise that vary on intensity and the presence of wearable weights. METHODS: Seventeen (11 female, 6 male, mean age = 24 years ± 5.92) healthy volunteers were tested for aerobic fitness on a treadmill to determine VO2 max (mean = 42.68 ml x kg-1 x min-1). Participants then completed eight 30-minute walking trials on a treadmill while oxygen consumption (VO2) and heart rate (HR) were monitored while walking at different speeds and with varying combination of upper and lower body wearable weights. The design included two intensities (slow walking and brisk walking) and four conditions (no weights, arm weights, leg weights, and arm and leg weights) for a total of eight experimental trials. RESULTS: Data were analyzed using ANOVA and pair-wise comparisons. Analyses revealed that VO2 was significantly lower without the wearable weights in comparison to wearing both upper and lower weights in the slow walk trial (P < 0.001; ES = 0.69) and also during the brisk walk trial (P < 0.001; ES = 0.62). HR was significantly higher during the brisk walk trials with togs on both the arms and legs (P=0.029, ES=0.31). CONCLUSIONS: Findings suggest that exercising while using wearable weights increases energy expenditure and has minimal impact on HR. PRACTICAL APPLICATIONS: This finding suggests that physical activity associated with daily living could be enhanced through the wearing of the Body Tog® weights that can be worn under clothing. Additionally, wearing the togs during exercise increases energy cost of walking, therefore allowing for possible weight loss applications.

The purpose of this dissertation series was to examine oxygen uptake kinetics in skeletal muscle by evaluating responses of local muscle deoxygenation during incremental exercise in healthy individuals using near-infrared spectroscopy (NIRS). Metabolic activity in skeletal muscle, as part of the integrative responses of the cardiovascular, respiratory and neuromuscular systems, are major determinants of an individual’s physical capacity and function. The workings of these systems, called whole-body metabolism, affect the capability of an individual to engage in activities of daily living, to exercise, and participate in athletic performance. Thus, they have a strong impact on health as engagement in physical activity is well known to be effective in improving cardiorespiratory fitness and reducing the risks of chronic disease. At this time, the in vivo relationships between whole-body metabolism and local muscle metabolic activity are not well understood, but with the availability of NIRS technology this is possible. NIRS is a noninvasive optical technique used to continuously measure changes in muscle tissue oxygen saturation locally, allowing interrogation of the functional integration between muscle metabolism and the cardiovascular system in intact human beings, which is what the series of studies in this dissertation evaluate. Healthy adults and adolescents were enrolled as healthy control participants into an observational study evaluating changes in local muscle oxygen uptake in neuromuscular disease during exercise. Participants performed a maximal cardiopulmonary exercise test (CPET) on a recumbent cycle ergometer. Changes in muscle deoxygenation (HHb), reflecting local oxygen uptake, were measured using NIRS and whole-body metabolism was assessed synchronously via expired gas analysis. After an initial increase in HHb at exercise onset, a consistent pattern of plateau in HHb was observed in the healthy participants near the end of peak exercise. Despite increasing workload and oxygen uptake (VO2) in the final minutes of the test, it was unclear what mechanisms were contributing to this HHb response. It was hypothesized that the HHb-Workload relationship evaluated at the time of VO2peak would be non-linear, such that a greater maximum workload achieved at VO2peak would not be linearly matched by greater ΔHHb (i.e., greater total change from rest to VO2peak). First, a critical evaluation of the literature was conducted to explore this hypothesis. Chapter 2 provides the results of a scoping review that was performed in order to better understand the scientific evidence using NIRS that describes the relationships between indices of muscle oxygen saturation and workload during incremental exercise. This formed the basis to pursue the hypothesis-driven research presented in the subsequent chapters, interrogating the overarching question of this dissertation related to the HHb-Workload relationship. The review revealed there are three methodological approaches to examining changes in muscle oxygen saturation and workload, the least common of which was examination of HHb and workload at the VO2peak time point. Changes in muscle oxygen saturation and work have also been studied as the change in muscle oxygenation over the duration of exercise and at a certain time point or intensity during incremental exercise. Based on the literature, it was clear that there was a dearth of research examining the HHb plateau response in relation to work at VO2peak. Accordingly, chapter 3 provides the results of a pilot study that evaluated the relationship between change in HHb (ΔHHb) and the maximum workload (MW) achieved at VO2peak, where it was hypothesized that the relationship at this time point would be non-linear. A polynomial regression model was used to describe the relationship. The results of this study showed that at lower maximum workloads there were initial increases in ΔHHb with increasing maximum workload but at the highest maximum workloads, ΔHHb attenuated. A polynomial model including ΔHHb and MW, with VO2peak (an indicator of cardiorespiratory fitness) as a covariate, best characterized the relationship. Age was not significantly related to ΔHHb or MW, and VO2peak appeared to play a partial role as its inclusion as a covariate helped explain approximately a quarter of the variance, suggesting other factors may be contributing to the attenuated HHb response. From this pilot work it was hypothesized that the attenuation in ΔHHb at higher maximum workloads, and the HHb plateau observed during CPET, could be explained by muscle efficiency. If so, a longer duration and lesser slope of the HHb plateau in the minutes leading up to VO2peak occurs in muscles with higher metabolic efficiency. As muscle efficiency is defined as a ratio of external work accomplished to internal energy expended, the hypothesis, if true, would support a better matching of the internal work (VO2) to the external work (workload on the ergometer). Chapter 4 provides the results of a secondary analysis that sought to determine whether the observed plateau in HHb reflected muscular efficiency by comparing the slope of the HHb plateau (HHb[s]) to a commonly used method of assessing muscle efficiency, delta efficiency (DE). It was hypothesized that HHb[s] and DE would be inversely and significantly correlated, providing a potential mechanism for the attenuated HHb response and a noninvasive method for assessing muscle efficiency. In contrast to the hypothesis, HHb[s] and DE were not associated, suggesting that a mechanism other than muscle efficiency is contributing to the HHb plateau. Collectively, this series of studies demonstrate that there is a need to better understand the relationship between HHb and workload in healthy individuals, because of a paucity of evidence exploring the HHb-MW relationship at VO2peak, the finding that ΔHHb attenuates at higher maximum workloads, and that results suggest the HHb plateau phenomenon cannot be explained by muscle efficiency. Future work should seek to elucidate the mechanism that allows healthy individuals to achieve higher workloads (i.e., continue exercising at high intensity) without further increasing muscle oxygen uptake, in a larger more heterogeneous sample.

Mitochondria are important cytosolic organelles present in nearly all eukaryotic cells. The main function of mitochondria are to generate the vast majority of ATP through the process of oxidative phosphorylation. Mitochondria have key roles regarding other systems in the body as well, such as regulation of apoptosis, calcium homeostasis, reactive oxygen production etc. Mitochondrial diseases are caused by impaired mitochondrial function, originating from mutations in either the mitochondrial DNA or the nuclear DNA. Epilepsy is a common symptom of mitochondrial disease, especially in children. The pathophysiology behind mitochondrial epilepsy is primarily based on ATP deficit, leading to a negative effect on a range of different nervous system related functions that in the end leads to seizures. The study aimed to investigate the effect on mitochondrial respiration of two commonly used antiepileptic drugs, namely valproic acid and Topiramate, and the anesthesic drug propofol, commonly used in case of refractory status epilepticus. The three drugs were titrated in different concentrations in a high-resolution respirometer from Oroboros Instruments (n=6). Propofol seemed especially inhibiting of mitochondrial function, and both propofol and topiramate had a significant decrease in mitochondrial respiration within the clinical concentrations. The result of the study supported research stating that propofol should be used with caution in patients with a mitochondrial disease, but further research should be done regarding all three drugs in order to draw definite conclusions.

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