by Chan Suk Ping. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1998. / Includes bibliographical references (leaves 105-119). / Abstract also in Chinese. / Acknowledgments --- p.i / Abstract --- p.ii / List of Tables --- p.ix / List of Figures --- p.xii / Abbreviation --- p.xiv / Chapter CHAPTER ONE --- INTRODUCTION / Chapter 1.1 --- Background --- p.1 / Chapter 1.2 --- The Research Problem --- p.7 / Chapter 1.2.1 --- Purpose of The Study --- p.7 / Chapter 1.2.2 --- Variables and Definition of Terms --- p.8 / Chapter 1.2.3 --- Hypotheses --- p.10 / Chapter 1.2.4 --- Significance of The Study --- p.11 / Chapter CHAPTER TWO --- REVIEW OF LITERATURE / Chapter 2.1 --- Benefits and Potential Disadvantages of Stretching --- p.12 / Chapter 2.1.1 --- Benefits of Stretching --- p.12 / Chapter (a) --- Muscle Relaxation --- p.12 / Chapter (b) --- Performance Enhancement --- p.14 / Chapter (c) --- Prevention of Injury --- p.17 / Chapter (d) --- Increase of Range of Motion --- p.19 / Chapter (e) --- Prevention of Muscle Soreness --- p.20 / Chapter 2.1.2 --- The Potential Disadvantages of Stretching --- p.20 / Chapter 2.2 --- Limiting Factors of Flexibility --- p.22 / Chapter 2.2.1 --- Muscle --- p.22 / Chapter (a) --- Histologic Components of Muscle --- p.22 / Chapter (b) --- Muscular Elongation --- p.23 / Chapter (c) --- The Effects of Immobilization --- p.23 / Chapter 2.2.2 --- Connective Tissue --- p.24 / Chapter (a) --- Collagen --- p.25 / Chapter (b) --- Elastic Tissue --- p.27 / Chapter (c) --- Tissue Composed of Connective Tissue --- p.27 / Chapter 2.2.3 --- The Mechanical Properties of Soft Tissue --- p.30 / Chapter 2.2.4 --- "Age, Gender, Physical Activity and Temperature" --- p.33 / Chapter 2.3 --- Neurophysiology of Stretching --- p.34 / Chapter 2.3.1 --- Muscle Spindles and Golgi Tendon Organs --- p.34 / Chapter (a) --- Structure and Role of Muscle Spindle --- p.35 / Chapter (b) --- Structure and Role of Golgi Tendon Organs --- p.38 / Chapter (c) --- Parallel and Series End Organs --- p.38 / Chapter 2.3.2 --- Electromyography --- p.39 / Chapter 2.4 --- Hamstrings --- p.43 / Chapter 2.4.1 --- Functions of Hamstrings --- p.43 / Chapter 2.4.2 --- Limited Range of Motion in Hamstrings --- p.45 / Chapter 2.4.3 --- Measurement of Hamstrings Flexibility --- p.46 / Chapter 2.5 --- Stretching Protocol --- p.50 / Chapter 2.5.1 --- Modes of Stretching --- p.50 / Chapter 2.5.2 --- Intensity of Stretching --- p.53 / Chapter CHAPTER THREE --- METHOD / Chapter 3.1 --- Subjects --- p.55 / Chapter 3.2 --- Instrumentation --- p.57 / Chapter 3.3 --- Procedure --- p.60 / Chapter 3.4 --- Reliability Study --- p.69 / Chapter 3.5 --- Data Analysis --- p.70 / Chapter CHAPTER FOUR --- RESULTS / Chapter 4.1 --- Reliability Study --- p.72 / Chapter 4.2 --- Experimental Study --- p.73 / Chapter 4.2.1 --- Range of Motion of Pre-Test and Post-Test --- p.74 / Chapter 4.2.2 --- Passive Resistance of Pre-Test and Post-Test --- p.75 / Chapter 4.2.3 --- Subjective Rating of Pre-Test and Post-Test --- p.76 / Chapter 4.2.4 --- Myoelectric Activities of Hamstrings of Pre-Test and Post-Test --- p.76 / Chapter 4.2.5 --- Hamstrings Performance of Pre-Test and Post-Test --- p.79 / Chapter 4.2.6 --- Range of Motion Difference among Trained and Untrained Groups --- p.81 / Chapter 4.2.7 --- Passive Resistance of Hamstrings Difference among Trained and Untrained Groups --- p.82 / Chapter 4.2.8 --- Subjective Rating of Perceived Stretch Difference among Trained and Untrained Groups --- p.82 / Chapter 4.2.9 --- Myoelectric Activities of Hamstrings Difference among Trained and Untrained Groups --- p.83 / Chapter 4.3.0 --- Performance of Hamstrings Difference among Trained and Untrained Groups --- p.83 / Chapter CHAPTER FIVE --- DISCUSSION / Chapter 5.1 --- Hamstrings Flexibility Analysis --- p.92 / Chapter 5.2 --- Hamstrings Passive Resistance Analysis --- p.94 / Chapter 5.3 --- Rating of Perceived Stretch Analysis --- p.97 / Chapter 5.4 --- Hamstrings Myoelectric Activities Analysis --- p.98 / Chapter 5.5 --- Hamstrings Performance Analysis --- p.100 / Chapter 5.6 --- Limitations and Suggestions --- p.102 / Chapter 5.7 --- Conclusions --- p.103 / REFERENCES --- p.105 / APPENDIX / Appendix A. Informed Consent / Appendix B. Personal Particulars and Past Medical History Screening Sheet / Appendix C. Perceived Stretch Rating Scale / Appendix D. Record Sheet

Dab2是一個細胞內接頭蛋白和腫瘤抑制因子。在小鼠胚胎中，應用免疫熒光染色技術，從E8.5-E11.0 Dab2發現表達於肌節的生皮肌節中。從E8.5 E9.5，Dab2表達於生皮肌節的中部。在E10.5，Dab2表達於生皮肌節的腹外側唇部，與肌肉發育的早期標誌基因Pax3和 Myf5共定位。從E11.5-E14.5，Dab2表達於四肢與軀體的肌肉中,Dab2在出生後小鼠肌肉中的表達逐漸減弱。此外，因為肌肉正常發育需要很多細胞信號的調節並且Dab2已經發現調節MAPK, TGF-β和 Wnt信號轉導通路。這些發現預示了Dab2在肌肉發育和分化中可能具有重要作用。 / 為了進一步研究它在肌肉發育中的作用，非洲爪蟾的胚胎和C2C12 肌原細胞在此研究中分別被用作體內和體外的研究模型。原位雜交結果揭示非洲爪蟾的Dab2基因表達於其胚胎的肌節中，並與肌肉發育的標誌基因XPax3, XMyoD, XMef2c和 XMyos共定位於此。用morpholino敲低XDab2 在非洲爪蟾胚胎中的表達，下調了許多肌肉發育標誌基因的表達，例如：XPax3, XMyf5, XMef2c, XMyoS 和XAC100。與此同時，免疫熒光技術也檢測到MHC(MF20)和12/101在肌節中的表達下調。 / 來源於小鼠肌肉衛星細胞的C2C12肌原細胞系被用作體外模型來檢測Dab2基因在骨骼肌發育和分化中的作用。在C2C12肌原細胞被誘導分化形成肌管的過程中，Dab2基因在RNA和蛋白水平的表達被誘導性的升高。Dab2基因超表達能夠加速肌原細胞的融合，從而增加肌小管的形成。利用miRNA敲低Dab2基因的表達能夠減緩肌原細胞的融合，從而減少肌小管的形成。利用慢病毒shRNA技術我們得到了2個Dab2穩定敲低細胞系，命名為克隆5-2和克隆5-7。這兩個克隆具有減少或抑制減少或抑制肌小管形成的特點。蛋白免疫印跡實驗表明，磷酸化p38 MAPK的表達在這兩個克隆中被抑制。在克隆5-2中超表達Dab2基因能夠恢復肌小管的形成。這個研究表明Dab2基因在肌小管的形成過程中具有至關重要的作用。 / 利用Affymetrix微陣列技術，我們檢測並分析了在克隆5-2和對照細胞中差異表達的基因。235個探針（155個基因）的顯示出超過2倍的差異表達。在這155個基因中，127個基因下調表達，28個基因上調表達。熒光定量PCR結果顯示出與微陣列結果相一致的結果。這些差異表達基因的功能發現與肌肉系統的發育和功能具有顯著地聯系。它影響了與肌肉收縮，橫紋肌的收縮，肌前體細胞的分化和肌肉發育相關功能的基因。基因網絡分析結果揭示，在克隆5-2中Mef2c基因的下調表達可能是一個導致肌細胞分化抑制的原因。 Mef2c基因在克隆5-2中超表達能夠拯救肌細胞的分化。 / 總括來說，體內和體外實驗共同表明Dab2基因是一個肌肉發育和分化的正調控基因。 / Dab2 is an intracellular adaptor protein and a tumor suppressor. In mouse embryos, Dab2 was found to be expressed in the dermomyotome of somites from E8.5 to E11.0 using immunofluorescence staining, with expression first detected in the medial aspect of the dermomyotome at E8.5 and then co-localized with the early muscle markers Pax3 and Myf5 at the ventrolateral lip of the dermomyotome at E10.5. From E11.5 to E14.5, Dab2 was expressed in muscle masses of limb buds and the trunk. Dab2 expression in skeletal muscles was gradually decreased after birth. These observations suggested potential roles of Dab2 in the skeletal muscle myogenesis. In addition, since the normal development of skeletal muscles requires proper signal transduction, and Dab2 has been known to be involved in the MAPK, TGF-β and Wnt signaling pathways, Dab2 may therefore be important for the muscle development. / To determine the role of Dab2 in the skeletal muscle development, Xenopus laevis embryos and C2C12 myoblasts were employed as in vivo and in vitro models, respectively. In situ hybridization results showed that XDab2 was expressed in somites of Xenopus embryos and co-localized with the muscle markers XPax3, XMyoD, XMef2c and XMyos. Knockdown of XDab2 expression with antisense morpholinos down regulated the expression of several muscle markers in somites including XPax3, XMyf5, XMef2c, XMyoS and XAC100. Down-regulation of MHC and 12/101 were also observed in whole mount preparations and transverse sections of XDab2 morpholino-injected embryos after immunohistochemical staining. / The C2C12 cell line derived from mouse muscle satellite cells was then employed as an in vitro model to determine the role of Dab2 during early muscle development. When C2C12 myoblasts were induced to differentiate into myotubes, Dab2 expression was simultaneously increased at RNA and protein levels. Dab2 over-expression after transfection with Dab2 plasmids resulted in enhanced myoblast fusion and increased numbers of myotubes. Conversely, suppression of Dab2 expression with miRNAs resulted in reduced myoblast fusion and decreased numbers of myotubes. Lentiviral shRNA-mediated Dab2 stable knockdown reduced myotube formation in 2 representative stable clones, clone 5-2 and clone 5-7. Western blot analysis showed that expression of phospho-p38 MAPK was down-regulated in clone 5-2 and 5-7. Dab2 re-expression through plasmid-mediated transient transfection in clone 5-2 could partially restore the myotube formation. These observations therefore suggested that Dab2 plays essential roles in the formation of myotubes. / Comprehensive profiling of differentially expressed genes was performed with the Affymetrix microarray analysis between the Dab2-knockdown clone 5-2 and the C2C12 parental cell line. As compared to the parental cells, the clone 5-2 showed significant changes in the expression of 235 probe sets representing 155 genes (p<0.05) with 2 folds or greater changes. Among the 155 genes, 127 were down-regulated, while 28 up-regulated. qRT-PCR results were found to be consistent with the microarray results. Functions of the differentially expressed genes were found to be significantly associated with the development and functions of the muscular system. Knockdown of Dab2 affected the genes involved in muscle contraction, the contraction of striated muscle, differentiation of muscle precursor cells, and the development of skeletal muscle fibers. A network analysis and a gene expression study revealed that Mef2c down-regulation was related to the inhibition of myogenic differentiation in the clone 5-2. Furthermore, forced expression of Mef2c in the clone 5-2 could rescue the myogenic differentiation. / In conclusion, these results indicated that Dab2 is positive regulator of the skeletal muscle development and differentiation both in vivo and in vitro. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Shang, Na. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2012. / Includes bibliographical references (leaves 211-227). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese. / Abstract --- p.i / 摘要 --- p.iv / Acknowledgements --- p.vi / Table of contents --- p.vii / Abbreviation --- p.xiii / Chapter Chapter 1 --- General Introduction --- p.1 / Chapter 1.1 --- Characterizations of the Dab2 gene --- p.1 / Chapter 1.2 --- The role of Dab2 in Wnt/ beta-catenin signaling --- p.2 / Chapter 1.3 --- The role of Dab2 in TGF beta signaling --- p.3 / Chapter 1.4 --- The role of Dab2 in Ras-MAPK signaling --- p.4 / Chapter 1.5 --- The role of Dab2 in protein trafficking and endocytosis --- p.5 / Chapter 1.6 --- Dab2 expression and its functions. --- p.7 / Chapter 1.7 --- Somite and skeletal muscle development --- p.8 / Chapter 1.8 --- The formation of the somite and its structure --- p.9 / Chapter 1.9 --- The formation of dermomyotome and its function --- p.10 / Chapter 1.10 --- The formation of myotome and its function --- p.11 / Chapter 1.11 --- The formation of muscle fibers and musculatures --- p.12 / Chapter 1.12 --- The formation of satellite cells and its function in skeletal muscle differentiation --- p.12 / Chapter 1.13 --- The gene expression during skeletal muscle development and differentiation --- p.13 / Chapter 1.14 --- Dab2 genetically modified mice --- p.16 / Chapter 1.15 --- Objectives of this research --- p.17 / Chapter Figures and legends --- p.21 / Chapter Chapter 2 --- Expression of Dab2 in the mouse somites and skeletal muscles --- p.32 / Chapter 2.1 --- Introduction --- p.32 / Chapter 2.2 --- Materials and Methods --- p.34 / Chapter 2.2.1 --- Mouse embryos and tissue isolation --- p.34 / Chapter 2.2.2 --- Histological preparation of embryos and tissues --- p.34 / Chapter 2.2.3 --- Immunostaining using Tyramide signal amplification kits --- p.35 / Chapter 2.3 --- Results --- p.36 / Chapter 2.3.1 --- Dab2 expression in somites of the mouse embryos --- p.36 / Chapter 2.3.2 --- Dab2 expression in skeletal muscles of embryonic and postnatal mice --- p.36 / Chapter 2.3.3 --- Co-localization of Dab2 and Pax3 immunoreactivities with double immunofluorescence staining --- p.37 / Chapter 2.3.4 --- Co-localization of Dab2 and Myf5 immunoreactivities with double immunofluorescence staining --- p.38 / Chapter 2.3.5 --- Co-localization of Dab2 and Myogenin immunoreactivities with double immunofluorescence staining --- p.38 / Chapter 2.4 --- Discussion --- p.40 / Chapter 2.5 --- Summary --- p.42 / Chapter Table 2.1 --- p.44 / Chapter Figures and Legends --- p.45 / Chapter Chapter 3 --- Dab2 is a positive regulator of skeletal muscle development in Xenopus embryos --- p.58 / Chapter 3.1 --- Introduction --- p.58 / Chapter 3.2 --- Materials and Methods --- p.61 / Chapter 3.2.1 --- RNA extraction --- p.61 / Chapter 3.2.2 --- Reverse-transcription polymerase chain reaction (RT-PCR) --- p.61 / Chapter 3.2.3 --- Gene cloning and sequencing analysis --- p.61 / Chapter 3.2.4 --- Transformation --- p.62 / Chapter 3.2.5 --- Plasmid mini and midi-preparation --- p.62 / Chapter 3.2.6 --- Frogs and embryos handling --- p.63 / Chapter 3.2.7 --- Synthesis of mRNA for microinjection --- p.64 / Chapter 3.2.8 --- Microinjection --- p.64 / Chapter 3.2.9 --- Synthesis of DIG-labeled anti-sense RNA probe --- p.65 / Chapter 3.2.10 --- Whole mount in situ hybridization (WMISH) and whole mount immunohistochemical localization --- p.65 / Chapter 3.3 --- Results --- p.67 / Chapter 3.3.1 --- Cloning of Xenopus Dab2 long isoform and the sequence analysis --- p.67 / Chapter 3.3.2 --- Phylogenetic analysis --- p.67 / Chapter 3.3.3 --- RT-PCR analysis of Xenopus Dab2 (XDab2) expression --- p.68 / Chapter 3.3.4 --- Xenopus Dab2 spatial and temporal expression examined by WMISH analysis --- p.68 / Chapter 3.3.5 --- Dab2 expression in somites and its colocalization with myogenic transcription factors --- p.69 / Chapter 3.3.6 --- XDab2 knockdown led to down-regulation of myogenic transcription factors and muscle markers at the RNA level --- p.70 / Chapter 3.3.7 --- XDab2 knockdown led to down-regulation of muscle markers at the protein level --- p.70 / Chapter 3.3.8 --- XDab2 overexpression led to up-regulation of XPax3, XMyf5 and XMyoS --- p.71 / Chapter 3.4 --- Discussion --- p.72 / Chapter 3.5 --- Summary --- p.77 / Chapter Table 3.1 --- p.78 / Chapter Figures and Legends --- p.79 / Chapter Chapter 4 --- Potential roles of Dab2 in C2C12 myoblast differentiation --- p.99 / Chapter 4.1 --- Introduction --- p.99 / Chapter 4.2 --- Materials and Methods --- p.101 / Chapter 4.2.1 --- Cell culture and differentiation in vitro --- p.101 / Chapter 4.2.2 --- Cell sample preparation --- p.102 / Chapter 4.2.3 --- Real-time PCR --- p.102 / Chapter 4.2.4 --- SDS-PAGE --- p.103 / Chapter 4.2.5 --- Western blotting and immunodetection --- p.104 / Chapter 4.2.6 --- Plasmids used for transient over-expression --- p.105 / Chapter 4.2.7 --- Generation of miRNAs targeting at Dab2 --- p.105 / Chapter 4.2.8 --- C2C12 differentiation after transfection --- p.106 / Chapter 4.2.9 --- Immunohistochemical staining for myotubes --- p.106 / Chapter 4.2.10 --- Lentiviral shRNA mediated Dab2 stable knockdown --- p.107 / Chapter 4.2.10.1 --- shRNA Lentiviral Transduction Particles and sequence information --- p.107 / Chapter 4.2.10.2 --- Optimization of puromycin treatment on C2C12 myoblasts --- p.107 / Chapter 4.2.10.3 --- Determination of the optimal MOI for C2C12 --- p.108 / Chapter 4.2.10.4 --- Lentivirus transduction method --- p.109 / Chapter 4.2.10.5 --- Stable cell line generation --- p.109 / Chapter 4.2.11 --- Rescue experiments --- p.109 / Chapter 4.2.12 --- Serum starvation and FGF treatment --- p.110 / Chapter 4.2.13 --- Microarray and data analysis --- p.110 / Chapter 4.3 --- Results --- p.113 / Chapter 4.3.1 --- Expression of Dab2 during myogenesis --- p.113 / Chapter 4.3.2 --- Generation of miRNAs targeting at Dab2 --- p.113 / Chapter 4.3.3 --- Improvement of the transfection efficiency --- p.114 / Chapter 4.3.4 --- Knockdown efficiencies of the 4 miRNAs --- p.114 / Chapter 4.3.5 --- Down-regulation of Dab2 expression by transient transfection inhibited C2C12 differentiation --- p.115 / Chapter 4.3.6 --- Up-regulation of Dab2 expression by transient transfection enhanced myogenic differentiation --- p.116 / Chapter 4.3.7 --- Lentivirus-mediated Dab2 stable knockdown inhibited myotube formation --- p.117 / Chapter 4.3.8 --- Re-expression of Dab2 partially restored myogenic differentiation in the clone 5-2 --- p.120 / Chapter 4.3.9 --- Dab2 knockdown affected the MAPK signaling pathway --- p.122 / Chapter 4.3.10 --- Transcriptome and network analysis revealed changes of gene expression patterns in the C2C12 cell line after Dab2 knockdown --- p.123 / Chapter 4.3.11 --- Mef2c down-regulation was related to the inhibition of the myotube formation in the clone 5-2 --- p.126 / Chapter 4.4 --- Discussion --- p.128 / Chapter 4.4.1 --- Dab2 expression was found to be induced upon differentiation and down-regulated after myotube formation --- p.128 / Chapter 4.4.2 --- Dab2 was found to be a positive regulator of C2C12 differentiation --- p.129 / Chapter 4.4.3 --- Dab2 knockdown affected the MAPK signaling pathway --- p.131 / Chapter 4.4.4 --- Potential roles of Dab2 in myogenic differentiation revealed by transcriptome and network analysis --- p.133 / Chapter 4.4.5 --- Mef2c down-regulation may be involved in the inhibition of myogenic differentiation after Dab2 knockdown --- p.135 / Chapter 4.5 --- Summary --- p.138 / Chapter Table 4.1 --- p.141 / Chapter Table 4.2 --- p.142 / Chapter Table 4.3 --- p.143 / Chapter Table 4.4 --- p.144 / Chapter Table 4.5 --- p.147 / Chapter Table 4.6 --- p.148 / Chapter Table 4.7 --- p.149 / Chapter Figures and Legends --- p.150 / Chapter Chapter 5 --- Conclusions and discussion --- p.192 / Chapter 5.1 --- Dab2 expression in somites and skeletal muscles of mouse embryos --- p.192 / Chapter 5.1 --- Dab2 as a positive regulator for skeletal muscle development in Xenopus embryos in vivo --- p.194 / Chapter 5.3 --- Dab2 as a positive regulator of skeletal muscle development in vitro --- p.196 / Chapter 5.3.1 --- Dab2 was found to be a positive regulator of C2C12 differentiation --- p.196 / Chapter 5.3.2 --- Dab2 knockdown affected the MAPK signaling pathway --- p.198 / Chapter 5.3.3 --- Potential functions of Dab2 revealed by transcriptomeand network analysis --- p.200 / Chapter 5.3.4 --- Mef2c down-regulation was closely related to the inhibition of myogenic differentiation upon Dab2 knockdown --- p.202 / Appendix I --- p.204 / Appendix II --- p.205 / References --- p.211

Abstract not available

Two experiments were undertaken. The objective of Experiment One was to identify the lower limb muscles that were most frequently active during the early period of a step turning task for further testing in Experiment Two. In Experiment Two participants undertook multiple trials of a step-turning task, 30 and 60° to the left and right of midline, at a self-selected pace in response to a visual cue. There were five objectives to Experiment Two. Firstly, to identify the predominant order in the onset of foot movement so that anticipatory muscle activity could be defined for this task. Secondly, to identify whether there is a consistent temporal order in movement onset between the head and the feet. Thirdly, to identify whether and how consistently anticipatory lower limb muscle activity is present bilaterally. Fourthly, to assess whether there is a consistent sequence in the onset of anticipatory muscle activity among muscles active in at least 80% of trials. The final objective was to identity whether there was a consistent temporal relationship in the onset of the anticipatory muscle activity present in at least 80% of trials, with the onset of head and foot movement. Study Design: A repeated measures design was used. Background: Anticipatory lower limb muscle activity in gait initiation and forward stepping studies has been reported to be consistently present, and associated with initial and important balance responses. Falls during turning are associated with a high incidence of hip fractures in the elderly population. The presence of anticipatory lower limb muscle activity turning has not been previously reported. Participants: There were five participants in Experiment One, and ten in Experiment Two. All were between 18 and 40 years of age and did not have neurological or musculoskeletal disorders, or severe visual loss. Results: In Experiment One, four muscles were consistently active bilaterally, during the early period of step-turning and were: tibialis anterior, gastrocnemius, biceps femoris and gluteus medius. In Experiment Two the ipsilateral foot moved before the contralateral foot in 68% of trials towards the left, and 79% of trials towards the right. The onset of head movement consistently occurred before the onset of foot movement during turns towards both directions. The percentage of trials in which the four muscles were active in an anticipatory manner was low bilaterally, ranging from 12 to 38% of trials. Objectives that involved the further analysis of muscles active in at least 80% of trials were unable to be completed. Conclusions: During a step-turning task young healthy adults predominantly move their ipsilateral foot before their contralateral foot. The consistent onset of head movement prior to that of the feet, indirectly suggests that the visual system might influence the temporal onset of the feet. The low levels of anticipatory muscle activity during step-turning suggest that the lower limbs are not involved with the initial balance responses for this task thus making it inherently different to gait initiation and forward stepping.

Tibial stress fractures are common in runners. However, it is unclear what factors are associated with tibial stress fractures. This study aimed to investigate 1) magnitudes of bone contact forces occurring while running 2) whether or not repeated application of running loads is sufficient to explain tibial stress fractures and 3) whether or not muscle fatigue alters the potential of tibial stress fractures. Tibial stress fractures were predicted through an estimation of the minimum number of cycles to failure (Nfail) using an integrated experimental and mathematical modeling approach. Short running trials within a speed range of 3.5-4 m/s of ten male runners were evaluated with a coupled force plate and 3 dimensional motion analysis system. The collected data were used to estimate joint reaction forces (JRF) and joint moments. Using these JRF and muscle forces predicted from optimization, 2-D bone contact forces at the distal end of the tibia were determined. Next, tibial stresses were estimated by applying these bone contact forces to a tibial model, which were then used to predict the Nfail. All procedures were repeated after plantarflexors fatigued from prolonged running. This study found that peaks of compressive and posterior shear forces occurred during mid stance, and these peaks equaled 8.91 ± 1.14 BW and -0.53 ± 0.16 BW, respectively. These bone contact forces led to a backward bending of the tibia during most of the stance phase and resulted in the maximum stresses of - 43.4 ± 10.3 MPa on the posterior face of the tibia. These maximum stresses predicted the group mean of Nfail as being 5.28*10⁶ cycles. However, 2.5% to 56% of population of runners have a chance of getting tibial stress fractures within 1 million cycles of a repeated foot impact. Within the context of muscle force and stress estimation procedures used in this study, Nfail appeared to increase after fatigue, not decrease as we hypothesized. / Graduation date: 2005

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

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

Introduction The physiological effects of single and multiday road running races have been studied extensively and include the occurrence of rhabdomyolysis, reflected by significantly increased urinary myoglobin (uMb), as well as increased concentrations of serum creatine phosphokinase (CPK), high sensitivity C-reactive protein (hsCRP), cortisol and cardiac troponin-T (cTnT), dehydration and compromised renal function. Furthermore, in hyperthermic athletes, a positive relationship has been noted between hyperthermia, muscle damage, dehydration and pacing. The physiological effects of a multiday trail run of similar duration to single day road races, however, are unknown. The side-effects of the use of statin medication for hypercholesterolaemia include muscle fatigue, cramping and increased muscle damage. These have been found to be aggravated in endurance athletes and it has been reported that females, especially when being medicated from a young age, are more susceptible to these side-effects. Objectives 1. To investigate the effect of a three-day trail run on systemic and urinary markers of muscle damage and inflammation in recreational runners and to establish the association of dehydration and hyperthermia with these markers. 2. To observe the effect of the three day trail run on systemic and urinary markers of muscle damage and inflammation on an additional hypercholesterolaemic female athlete using statin medication in combination with a lipid uptake inhibitor. Method Firstly, an observational cohort study was conducted on 19 recreational male (n=6) and female (n=13) athletes during a 95km trail run over three days. Pre-and post-stage and 24 and 72 h post-race concentrations of serum CPK, hsCRP, cortisol, cTnT, and osmolality (sOsm) as well as uMb, changes in body mass, delayed onset muscle soreness (DOMS) and thigh circumference (TC) were measured. Continuous recordings of heart rate (HR) and intestinal temperature (Tintest ) were made throughout each stage. In addition, a case report is included on one trained female endurance athlete currently being treated for familial hypercholesterolaemia with 20 mg Aspavor and 10 mg Ezetrol daily and not included in the above cohort, to investigate the degree of muscle damage and inflammation she experienced as a result of participation in the three-day event. Results: Heart rate ranged between 77 and 83% age-predicted-maximum (APmax) and Tintest between 36.1 and 40.2 ºC during the three stages. Significant rises in mean serum CPK, hsCRP, sOsm and blood neutrophil count reached peak concentrations of 1 488U/L, 8.91mg/l, 298mosm/L and 10.21 10^9/L (p≤0.001), respectively. No evidence of elevations in uMb and cTnT were detected. The stage-induced increments in DOMS correlated positively with CPK, r=0.71; 95% CI [0.62, 0.78]. TC decreased significantly post S1post and S2post (p≤0.05) and a maximum mean body mass loss of 3.09% (±1.04%) occurred during S2. There was no significant difference between nonsteroidal anti-inflammatory drug (NSAID) users and non-users in terms of serum CPK, hsCRP, cortisol, post race DOMS scores, running times, TC or sOsm (p>0.05). The post-pre change in sOsm during each stage correlated inversely with the changes in % body mass, r = -0.36, 95% CI [-0.57,-0.094] and the pooled data examining the relationship between the change of sOsm and change in serum CPK for the three stages (n=57), revealed an insignificant positive correlation (r= 0.034, 95% CI [-0.228, 0.291]. The maximum Tintest ranged between 38.3 º C and 40.2 º C and only exceeded 40º C in two of the 12 athletes monitored. The relationship between the change in Tintest and serum CPK was insignificant (p>0.05) for the 11 individuals from whom complete sets of data were available (r= 0.24, 95% CI [-0.42, 0.734]. In the hypercholesterolaemic athlete, the maximum serum CPK (665U/L), hsCRP (1.9mg/Ll) and cortisol (845nmol/L) concentrations corresponded with undetected uMb despite a maximum body mass loss of 4.5% Conclusion: Three consecutive days of 95km trail running resulted in low markers of muscle damage and inflammation, when compared to results obtained in previous single day road races of similar duration despite the maintenance of a heart rate above 77% APmax, Tintest rising above 39o C and mean body mass decrement of >2.0%. The unchanged concentrations of serum cTnT and uMb confirmed the low values of the markers of muscle damage and inflammation. An insignificant positive correlation between muscle damage and dehydration was noted. Furthermore the daily use of 0.4 mg/kg Atorvastatin in combination with 10mg Ezetrol did not result in the subject experiencing subjective myalgia, cramps, fatigue or increased markers of muscle damage following her participation in the trail run. / Thesis (M.Med.Sc.)-University of KwaZulu-Natal, 2012.

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

This study examined the effects of 14 days of L-carnitine supplementation on blood and muscle lactate concentrations, and carnitine fractions, during high intensity sprint cycling exercise. Eight subjects performed three experimental trials - control I (CON I, 0 days), control II (CON II, 14 days), and L-carnitine (LCN, 28 days). Each trial consisted of a 4 min ride at 90% VO2max, followed by a rest period of 20 min, and then 5 x 1 min rides at 115% VO2max (2 min restbetween each). Following CON II, all subjects began dietary supplementation of L-carnitine for a period of 14 days (4 g/day). L-carnitine supplementation had no significant effect on either muscle carnitine or lactate concentrations following the 4 min 90% ride. Plasma total acid soluable and free carnitine concentrations were significantly higher at all time points following supplementation. Differences observed in blood hydrogen ion and lactate concentrations between CON I and CON II appear to be the result of an order effect. The data from the present investigation indicate that L-carnitine supplementation has no significant effect on blood or muscle lactate accumulation following high intensity sprint cycling exercise. / School of Physical Education