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PISPERO, ALBERTO. "THE USE OF THE OPERATING MICROSCOPE IN DENTAL PRACTISE: POSTURAL ANALYSIS AND CLINICAL EVALUATION." Doctoral thesis, Università degli Studi di Milano, 2019. http://hdl.handle.net/2434/695210.
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THE USE OF OPERATING MICROSCOPE IN DENTAL PRACTISE: POSTURAL ANALYSIS AND CLINICAL EVALUATION Abstract Author: Alberto Pispero Dipartimento di Scienze Biomediche, Chirurgiche ed Odontoiatriche, Università degli Studi di Milano The study is in collaboration with Politecnico di Milano, Dipartimento di Ingegneria Elettronica, prof. Marco Marcon Study design: randomized controlled clinical trial. Setting of the clinical trial: Dental Clinic G. Vogel, via Beldiletto ASST Santi Carlo e Paolo Ospedale. Dr. Alberto Pispero, the surgeon for all the interventions; Prof. Giovanni Lodi is the head of research. PURPOSE The study investigates the effectiveness of microscope in dental practice in terms of posture improvement for the operator and clinical advantages for the patients. We carried out 4 studies: 1. Postural assessment in dentistry based on multiple markers tracking 2. The use of magnifying instrument for the extraction of lower third molar: Postural assessment 3. The use of magnifying instrument for the extraction of lower third molar: Clinical assessment 4. The influence of dental loupes on the quality of adhesive removal in orthodontic debonding: in vitro study. Background Attention and awareness towards MSDs in the dental profession has increased considerably in last years. From recent literature reviews, it is learned that prevalence of MSDs in dentists is 64-93%. Use of magnification systems improves the operator's visual capabilities, improves posture, and helps to prevent the onset of back and neck disorders. Moreover, the goal of dental treatment is to preserve tissues with minimally invasive prosthetics, conservatives and endodontics therapies, and to reconstruct periodontal soft and hard tissues performing microsurgery treatments in order to get the best aesthetic results and the least pain and complications. Over time, the degree of precision required immediately calls for magnification. METHODS Study 1: First, we conducted a study (study 1) on posture assessment to find an innovative method of postural analysis. In order to do that we worked with Politecnico of Milano. We presented a novel approach for upper limb posture assessment based on the tracking of a set of planar markers placed on the clothes of the worker. Thanks to this non-invasive approach, we were able to follow the 3D position and orientation of all the limbs involved in a specific activity during the job execution. Data will be evaluated through the index RULA (rapid upper limb assesment) to define whether there is a change in exposure to the risk of MSDs (Muskolo - skeletal - disease). Study 2: We used the method mentioned above in a randomized controlled three arms clinical trial where the surgeons performed 90 intervention. It was evaluated dentist posture during extraction of third lower molars depending on whether the operator performs the intervention by the use of surgical loupes or surgical microscope systems or performs a naked eyes surgery. Static and dynamic operator’s posture has been monitored by markers positioned on a slim fit t-shirt and high definition cameras acquired data in real time (study 2). Study 3: To evaluate whether the use magnifying system, could influence the postoperative course of a patient after extraction of a lower third molar. Each patient will be recalled for follow-up visits at 7 days. During this session will be carried out the removal of stitches and data will be recorded as follows: VAS pain and trismus, number of painkillers taken, control photographs, Posse Scale. These data were analyzed considering type of magnification and difficulty of extraction (study 3). Study 4: In order to investigate the effect of using different magnifying systems for removal of composite residues and in the prevention of iatrogenic enamel damage we conducted an in vitro study. 27 permanent extracted teeth were used, The teeth were randomized into 3 groups named. Each tooth was photographed and scanned with the intraoral scanner CS3600-Carestream before bracket placement (T0), post bracket positioning (T1), after removal of bracket (T2) and after debonding (T3). RESULTS Study 1: The analysis that we performed can be easily integrated into classical ergonomics assessment tools like RULA providing an objective methodology that does not involve an operator in a subjective interpretation of the monitored job. Study 2: From step 1 to step 8 in RULA worksheet, we put the same score in all cases, in the same way in steps 11, 13 and 14. By the use of magnification system, the operator’s posture didn’t change in terms of leg positioning or arm raising and wrist twist. We verified that despite the big range between neck bending, from 40 to 3 degrees, the final RULA score is the same for all interventions. Study 3: From the results obtained it is clear that the methods taken into consideration, the operating microscope, the surgical loupes with coaxial illumination and the naked eye, do not have a statistically significant influence on pain intensity (VAS), quality of life (PoSSe) or the number of painkillers taken by patients. The complexity of the magnifying system does not increase the duration of the operating time Study 4: There is a statistically significant difference between the procedures performed with the naked eye and those performed with surgical loupes. This result can be explained by greater attention and accuracy in removing the residual composite from the operator when using magnification systems. Microscope and surgical loupes were slower but got the best results in removal of composite remnants. Intraoral scanner that we used to evaluate the teeth surfaces does not appear useful to discriminate damage to the enamel. CONCLUSION We developed a new approach for posture assessment, precise and accurate, and we have had 3d data of the whole body, which can discriminate differences of one degree. We need long term studies conducted on many dentists (male and female) and a new method of posture data analysis to define the correlation between upper limbs posture and WMSDs accurately. We wanted to test magnification systems in fields of dentistry different from endodontics in which microscope is generally used. Even if data had no statistical significance, on the other hand microscope didn't affect the operating time. Despite common perceptions, the use of the microscope in oral surgery didn't slow down the intervention. We decided to test the microscope potential in debonding. In our research, the procedures performed without a magnification system are on average faster than those performed with the aid of a magnification. This result can be explained by greater attention and accuracy in removing the residual composite from the operator when using magnification systems. Microscope and surgical loupes were slower but got the best results in removal of composite remnants.
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Foxton, Ruth. "Dysferlin in skeletal muscle and skeletal muscle disease." Thesis, University of Newcastle Upon Tyne, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.268429.
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Terry, Rebecca Louise. "Modification of skeletal muscle phenotype to treat Duchenne muscular dystrophy." Thesis, Royal Veterinary College (University of London), 2013. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.618307.
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Hopkinson, Nicholas Shaun. "Skeletal muscle dysfunction in chronic obstructive pulmonary disease." Thesis, Imperial College London, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.417140.
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Swallow, Elisabeth. "Skeletal muscle dysfunction in chronic obstructive pulmonary disease." Thesis, Imperial College London, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.508993.
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Torres-Palsa, Maria Jose. "ICAM-1 in Skeletal Muscle Disease and Regeneration." University of Toledo / OhioLINK, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=toledo1461860958.
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Behnke, Bradley Jon. "Skeletal muscle oxygen exchange in health and disease /." Search for this dissertation online, 2003. http://wwwlib.umi.com/cr/ksu/main.
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Vlahovich, Nicole. "The role of cytoskeletal tropomyosins in skeletal muscle and muscle disease." Thesis, View thesis, 2007. http://handle.uws.edu.au:8081/1959.7/32176.
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Cells contain an elaborate cytoskeleton which plays a major role in a variety of cellular functions including: maintenance of cell shape and dimension, providing mechanical strength, cell motility, cytokinesis during mitosis and meiosis and intracellular transport. The cell cytoskeleton is made up of three types of protein filaments: the microtubules, the intermediate filaments and the actin cytoskeleton. These components interact with each other to allow the cell to function correctly. When functioning incorrectly, disruptions to many cellular pathway have been observed with mutations in various cytoskeletal proteins causing an assortment of human disease phenotypes. Characterization of these filament systems in different cell types is essential to the understanding of basic cellular processes and disease causation. The studies in this thesis are concerned with examining specific cytoskeletal tropomyosin-defined actin filament systems in skeletal muscle. The diversity of the actin filament system relies, in part, on the family of actin binding proteins, the tropomyosins (Tms). There are in excess of forty Tm isoforms found in mammals which are derived from four genes: α, β, γ and δTm. The role of the musclespecific Tms in striated muscle is well understood, with sarcomeric Tm isoforms functioning as part of the thin filament where it regulates actin-myosin interactions and hence muscle contraction. However, relatively little known about the roles of the many
cytoskeletal Tm isoforms. Cytoskeletal Tms have been shown to compartmentalise to form functionally distinct filaments in a range of cell types including neurons (Bryce et al., 2003), fibroblasts (Percival et al., 2000) and epithelial cells (Dalby-Payne et al., 2003). Recently it has been shown that cytoskeletal Tm, Tm5NM1 defines a cytoskeletal structure in skeletal muscle called the Z-line associated cytoskeleton (Z-LAC) (Kee et al., 2004).The disruption of this structure by over-expression of an exogenous Tm in transgenic mice results in a muscular dystrophy phenotype, indicating that the Z-LAC plays an important role in maintenance of muscle structure (Kee et al., 2004). In this study, specific cytoskeletal Tms are further investigated in the context of skeletal muscle. Here, we examine the expression, localisation and potential function of cytoskeletal Tm isoforms, focussing on Tm4 (derived from the δ- gene) and Tm5NM1 (derived from the γ-gene). By western blotting and immuno-staining mouse skeletal muscle, we show that cytoskeletal Tms are expressed in a range of muscles and define separate populations of filaments. These filaments are found in association with a number of muscle structures including the myotendinous junction, neuromuscular junction, the sarcolemma, the t-tubules and the sarcoplasmic reticulum. Of particular interest, Tm4 and Tm5NM1 define cytoskeletal elements in association with the
saroplasmic reticulum and T-tubules, respectively, with a separation of less than 90 nm between distinct filamentous populations. The segregation of Tm isoforms indicates a role for Tms in the specification of actin filament function at these cellular regions. Examination of muscle during development, regeneration and disease revealed that Tm4 defines a novel cytoskeletal filament system that is orientated perpendicular to the sarcomeric apparatus. Tm4 is up-regulated in both muscular dystrophy and nemaline myopathy and also during induced regeneration and focal repair in mouse muscle. Transition of the Tm4-defined filaments from a predominsnatly longitudinal to a predominantly Z-LAC orientation is observed during the course of muscle regeneration. This study shows that Tm4 is a marker of regeneration and repair, in response to disease, injury and stress in skeletal muscle.
Analysis of Tm5NM1 over-expressing (Tm5/52) and null (9d89) mice revealed that compensation between Tm genes does not occur in skeletal muscle. We found that the levels of cytoskeletal Tms derived from the δ-gene are not altered to compensate for the loss or gain of Tm5NM1 and that the localisation of Tm4 is unchanged in skeletal muscle of these mice. Also, excess Tm5NM1 is sorted correctly, localising to the ZLAC. This data correlates with evidence from previous investigations which indicates that Tm isoforms are not redundant and are functionally distinct (Gunning et al., 2005). Transgenic and null mice have also allowed the further elucidation of cytoskeletal Tm function in skeletal muscle. Analyses of these mice suggest a role for Tm5NM1 in glucose regulation in both skeletal muscle and adipose tissue. Tm5NM1 is found to colocalise with members of the glucose transport p fibres and analysis of both transgenic and null mice has shown an alteration to glucose uptake in adipose tissue. Taken together these data indicate that Tm5NM1 may play a role in the translocation of the glucose transport molecule GLUT4. In addition to this Tm5NM1 may play a role in adipose tissue regulation, since over-expressing mice found to have increased white adipose tissue and an up-regulation of a transcriptional regulator of fat-cell formation,
PPAR-γ.
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Vlahovich, Nicole. "The role of cytoskeletal tropomyosins in skeletal muscle and muscle disease." View thesis, 2007. http://handle.uws.edu.au:8081/1959.7/32176.
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Thesis (Ph.D.)--University of Western Sydney, 2007.A thesis presented to the University of Western Sydney, College of Health and Science, School of Natural Sciences, in fulfilment of the requirements for the degree of Doctor of Philosophy. Includes bibliographies.
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Petrany, Michael J. "Consequences of Cell Fusion and Multinucleation for Skeletal Muscle Development and Disease." University of Cincinnati / OhioLINK, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1595847866440328.
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Chrisam, Martina. "Novel insights into the role of skeletal muscle autophagy in health and disease." Doctoral thesis, Università degli studi di Padova, 2016. http://hdl.handle.net/11577/3424327.
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Structurally or functionally altered and unnecessary cellular components are physiologically removed from the cell through a self-degradative process named autophagy. An impairment of the autophagic machinery was shown to have a central role in the pathogenesis of several neurodegenerative, cardiac and age-related diseases. In the laboratory of Prof. Paolo Bonaldo, it was previously shown that an impairment of the autophagy pathway plays a key role in the pathogenesis of Bethlem Myopathy (BM) and Ullrich Congenital Muscular Dystrophy (UD), inherited human pathologies associated to collagen VI (COL6) deficiency and primarily affecting skeletal muscle. Moreover, autophagy reactivation by genetic, pharmacological and nutritional approaches was shown to rescue the dystrophic phenotype of Col6a1−/− mice, a model for human COL6-related myopathies.
Although a large number of stimuli and molecules induce autophagy, their efficiency in counteracting muscle disease progression need to be carefully evaluated at the preclinical and clinical level. During my PhD I took part to the evaluation of the outcomes of a normocaloric low protein diet (LPD)-based clinical trial for BM and UD patients, whose results are very promising. Due to the low level of daily protein intake, LPD is however not safe for pediatric BM and UD patients and alternative autophagy-inducing strategies need to be identified. Toward this aim, I devoted a large part of my PhD work to investigate the effects of spermidine, a naturally occurring non-toxic autophagy-inducing molecule, on Col6a1−/− mice. I demostrated that spermidine administration reactivates autophagy in this pathological context, and this is paralleled by structural and functional ameliorations in COL6-deficient myopathic muscles. This work paves the way for the formulation of novel diet-based therapies for the treatment of BM and UD.
Another major aim of my PhD project was investigating the mechanisms underlying autophagy regulation in skeletal muscle, focusing on AMBRA1 (activating molecule in BECN1-regulated autophagy). Studies in mice with a randomly mutated Ambra1 locus (Ambra1gt/gt) showed that this gene is essential for the development of the central nervous system, and may also play a key role for muscle development in zebrafish and mouse. To better clarify the role of AMBRA1 in skeletal muscles, we generated mice with a floxed Ambra1 allele (Ambra1f/f). I verified in vivo that the conditional allele for Ambra1 works properly, by breeding Ambra1f/f mice with a CAG-Cre transgenic line, which express Cre recombinase in the oocytes, to obtain the null allele for Ambra1. Mice bearing this allele either in homozygosity (Ambra1−/−) or in heterozygosity (Ambra1+/−) were preliminarily characterized. Moreover, I produced skeletal muscle-specific AMBRA1 null (Ambra1f/f::Mlc1f-Cre) mice and investigated muscle defects caused by AMBRA1 deficiency. Interestingly, data in adult Ambra1f/f::Mlc1f-Cre mice indicate that a high proportion of mature AMBRA1-deficient myofibers contain inclusion bodies. Ongoing experiments are aimed at identifying the composition of these inclusions and evaluating the activation status of autophagy and ubiquitin-proteasome system. The data I obtained until now exclude the presence of amyloid material in the inclusions, and highlight an impairment of both these degradation processes.
As side projects, during my PhD I also participated in the study of autophagy status in other hereditary muscle pathologies. First, I contributed to the identification of an autophagy impairment in the tibialis anterior of mdx mice, a model for Duchenne Muscular Dystrophy. Then I was involved in the characterization of an aggresome-autophagy process occurring in muscle biopsies from a patient carrying a p.C150R mutation in the FHL1 gene, and affected by severe sarcopenia and rigid spine syndrome (RSS). It emerges from these studies that autophagy is a commonly dysregulated process in different muscle pathologies, and that autophagy modulation may be a promising therapeutic strategy in different pathological contexts.
In summary, the data obtained with this PhD work underline the important pathogenetic role of autophagy dysregulation in congenital muscle pathologies, provide some basis for the development of novel therapeutic strategies based on autophagy modulation, and pave the way for unraveling the role of AMBRA1 in skeletal muscle.Componenti cellulari alterati o non più necessari vengono fisiologicamente rimossi dalla cellula attraverso un processo di auto-degradazione chiamato autofagia. E’ stato dimostrato che un difetto di autofagia può svolgere un ruolo centrale nella patogenesi di diverse malattie neurodegenerative, cardiache e legate all'invecchiamento. Nel nostro laboratorio è stato precedentemente dimostrato che una compromissione del flusso autofagico svolge un ruolo chiave nella patogenesi della miopatia di Bethlem (BM) e della distrofia muscolare congenita di Ullrich (UD), patologie umane congenite associate a carenza di collagene VI (COL6) che colpiscono principalmente il muscolo scheletrico. Inoltre è stato dimostrato che la riattivazione dell’autofagia attraverso strategie genetiche, farmacologiche o nutrizionali è in grado di migliorare il fenotipo miopatico dei topi Col6a1−/−, modello animale per le malattie dovute a deficit di COL6. Nonostante siano noti molti stimoli e molecole che inducono autofagia, la loro efficienza nel contrastare la progressione delle patologie muscolari deve essere valutata attentamente caso per caso, sia a livello preclinico che in ambito clinico. Durante il mio dottorato ho partecipato alla valutazione degli effetti di un trial clinico effettuato somministrando una dieta normocalorica a basso contenuto proteico (Low Protein Diet, LPD) ad un gruppo di pazienti BM e UD. Nonostante i risultati siano molto promettenti, questa terapia non è adatta a pazienti pediatrici a causa del bassissimo apporto proteico giornaliero. Strategie alternative per contrastare la progressione di BM e UD devono essere identificate e testate, perciò ho dedicato buona parte del mio dottorato di ricerca allo studio degli effetti della spermidina. Questa molecola è naturalmente presente in molti alimenti, non è tossica ed è stato dimostrato che induce autofagia in molti organismi modello. La somministrazione di spermidina riattiva l'autofagia nel muscolo di topi Col6a1−/−, e questo è accompagnato da un miglioramento della struttura e della funzione dei muscoli miopatici privi di COL6. Questo lavoro apre la strada alla formulazione di nuove terapie basate sulla dieta per BM e UD. Un altro obiettivo importante del mio progetto di dottorato è stato lo studio dei meccanismi alla base della regolazione dell’autofagia nel muscolo scheletrico. Mi sono concentrata in particolare sul chiarimento del ruolo di AMBRA1 (activating molecule in BECN1-regulated autophagy). Studi condotti su topi in cui il locus Ambra1 è stato mutato in modo casuale (Ambra1gt/gt) hanno dimostrato che questo gene è essenziale per lo sviluppo del sistema nervoso centrale, ed anche del muscolo scheletrico. Per chiarire meglio il ruolo di AMBRA1 nel muscolo scheletrico, abbiamo generato topi con un allele condizionale per Ambra1 (Ambra1f/f). Ho verificato in vivo il corretto funzionamento di questo allele, tramite incrocio con topi transgenici CAG-Cre, che esprimono la Cre ricombinasi negli ovociti, ottenendo l'allele null per Ambra1. Ho caratterizzato in modo preliminare topi omozigoti (Ambra1−/−) o eterozigoti (Ambra1+/−) per questo allele. Ho poi ottenuto topi knockout muscolo specifici per il gene Ambra1 (Ambra1f/f ::Mlc1f-Cre). I dati preliminari che ho sinora ottenuto sono molto interessanti: un'elevata percentuale di fibre muscolari prive di AMBRA1 contengono corpi di inclusione. Attualmente mi sto occupando di identificare la composizione di queste inclusioni e valutare lo stato di attivazione dell'autofagia e del sistema ubiquitina-proteasoma. I miei primi dati escludono la presenza di materiale amiloide nelle inclusioni, ed evidenziano un deficit in entrambi questi processi degradativi. Durante il dottorato ho inoltre contribuito a due progetti nei quali la condizione dell’autofagia è stata studiata in altre patologie muscolari ereditarie, identificando un deficit autofagico nel tibiale anteriore di un modello murino della distrofia muscolare di Duchenne, il topo mdx. Ho inoltre contribuito allo studio di biopsie muscolari prelevate da una paziente con una mutazione p.C150R nel gene FHL1, affetta da grave sarcopenia e da sindrome della colonna vertebrale rigida (Rigid Spine Syndrome, RSS), nelle quali abbiamo evidenziato un’aumentata induzione di autofagia probabilmente volta alla degradazione degli aggregati presenti nelle miofibre. Questi studi dimostrano che una disregolazione dell’autofagia è un meccanismo patogenetico comune a svariate patologie muscolari su base genetica, e fornisce un’ulteriore conferma della validità della modulazione del flusso autofagico come strategia terapeutica. In sintesi il mio lavoro evidenzia come una disregolazione dell’autofagia possa rivestire un ruolo chiave nello sviluppo di patologie muscolari, inoltre fornisce una base per lo sviluppo di nuove strategie terapeutiche basate sulla modulazione dell’autofagia nel muscolo scheletrico ed apre la strada per chiarire il ruolo di AMBRA1 in questo tessuto.
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Gerdle, Björn. "Leisure and muscular performance in health and disease : a study of 40-64-year-old northern Swedes." Doctoral thesis, Umeå universitet, Institutionen för samhällsmedicin och rehabilitering, 1985. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-99339.
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Categories and frequencies of leisureactivities employed by 156 randomly selected males and females aged 40-44, 50-54, 60-64 were investigated by structured interviews and were related to leisuresatisfaction, to experienced health and socio-economic status. In equal numbers (15) of males and females from each group and in 24 males (60 +_6 years) with intermittent claudication (Cl) isokinetic plantar flexion performance was investigated with registrations of peak torque (PT), contractional work (CW), active range-of-motion (RoM) and integrated electromyograms from all threee triceps surae heads. Subjects performed a few maximum plantarflexions at different velocities of angular motion and also up to 200 consecutive plantar flexions at 60 °/s. The males aged 40-44 were re -investigated after two years additionally using electromyographic power frequency analyses. Leisure choice was mainly age and sex independent and extensively included outdoor activities. Leisure satisfaction was positively associated with relative frequency of activities. Symptoms of bodily discomfort, in particular backpain, were quite common and apparently caused relatively low level of mutual leisure activities. Thus, with in this age span, leisure activities appear rather rigid but often successfully, adhered to . Common ailments influence partnership mutuality negatively. Plantar flexion PT and CW are adequately p re dicta ble by sex, age and crural circumference. Uniformly a 3:2 male/female ratio characterizes mechanical output and iEMG. The latter is velocity independent. Output decreases with increasing age. Hence the output/excitation balance (CW/iEMG) is age, but not sex, dependent. CI-patients produce less PT and CW than do controls. Independently of this disease, of age and sex, PT and CW describe parallel negative exponential functions of velocity. During repeated manoeuvres plantar flexion output and iEMG initially drop, there after to maintain nearly steady-state levels. Throughout up to 200 contractions CW/iEMG was unaltered in the clinically healthy. Test/re-test with two years interval yielded nearly identical results. Leftshifts in mean power frequency in parallel with output-drop imply that the latter probably is due to FT-motor unit fatigue. For CW, but not for PT, the drop became slower and the (relative) steady-state level higher with increasing age, indicating significant increase in endurance with age. In the Cl-patients, output, but not excitation, decreased after a few repititions. Therefore, CW/iEMG fell dramatically, implying intramuscular fatigue. Taken together with findings of close associations between total cumulated work and measured/expected maximum walking tole rance it is suggested that measurements of CW and calculations of CW/iEMG are of clinical value.Härtill 5 uppsatser
digitaliserinlg@umu.se
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Struthers, Kyle Remington. "ISCHEMIA IMPAIRS VASODILATION IN SKELETAL MUSCLE RESISTANCE ARTERY." DigitalCommons@CalPoly, 2011. https://digitalcommons.calpoly.edu/theses/546.
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Functional vasodilation in arterioles is impaired with chronic ischemia. We sought to examine the impact of chronic ischemia and age on skeletal muscle resistance artery function. To examine the impact of chronic ischemia, the femoral artery was resected from young (2-3mo) and adult (6-7mo) mice and the profunda femoris artery diameter was measured at rest and following gracilis muscle contraction 14 days later using intravital microscopy. Functional vasodilation was significantly impaired in ischemic mice (14.4±4.6% vs. 137.8±14.3%, p<0.0001 n=8) and non-ischemic adult mice (103.0±9.4% vs. 137.8±14.3%, p=0.05 n=10). In order to analyze the cellular mechanisms of the impairment, a protocol was developed to apply pharmacological agents to the experimental preparation while maintaining tissue homeostasis. Endothelial and smooth muscle dependent vasodilation were impaired with ischemia, 39.6 ± 13.6% vs. 80.5 ± 11.4% and 43.0 ± 11.7% vs. 85.1 ± 10.5%, respectively. From this data, it can be supported that smooth muscle dysfunction is the reason for the observed impairment in arterial vasodilation.
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Natanek, Samantha Amanda. "Skeletal muscle in chronic obstructive pulmonary disease : Regulation of quadriceps muscle fibre characteristics." Thesis, Imperial College London, 2011. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.535008.
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BACI, DENISA. "Human induced pluripotent stem cells for skeletal muscle diseases." Doctoral thesis, Università degli Studi di Roma "Tor Vergata", 2014. http://hdl.handle.net/2108/201887.
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Regenerative medicine along with tissue engineering represent two closely related fields leading promising advances for the treatment of numerous musculoskeletal diseases and injuries. Nevertheless, new efforts are urgently needed to design a successful therapeutic approach for muscular disorders, aiming at identifying a functional stem cell population and biomaterial scaffolds in which cells and growth factors could be embedded. In this context, recent studies have suggested that reprogramming of somatic cells by defined transcription factors into induced pluripotent stem cells (iPS), as source for generating autologous muscle progenitor cells (MPs), overcomes several limitations related to adult myoblast therapy. The prospect of an unlimited cell source combined with properties such as a more proliferative capacity in vitro, suggesting a better regenerative capacity in vivo models, indicates that iPS could be a promising candidate for stem cell therapy to regenerate skeletal muscle. iPS have been shown to retain specific features that are remnants of epigenomes and transcriptomes of the donor tissue termed ‘epigenetic memory’. Given to these findings, during the first part of the present study, we generated iPS derived from skin fibroblasts and pericytes (known to have a remarkable myogenic capacity) from the same donor to determine whether the epigenetic memory could influence iPS properties, preferentially generating cells similar of the donor somatic cell type. Until now, different approaches have been reported to generate MPs from iPS. So far, these methods present limitations such as low efficiency/reproducibility and usually involve cell sorting for enrichment or forced expression of skeletal master genes risking undesired genetic recombination. Recently, substantial interest is mounting regarding extracellular vesicles (EVs) and their involvement in many cellular processes, including myogenesis. We explored the possibility to use EVs as "physiological liposomes" enriched with myogenic factors to trigger skeletal myogenesis. To this end, during the second part of the study we developed a new transgenic-free approach to obtain transplantable MPs by means of defined factors and extracellular vesicles (EVs) secreted from differentiated mouse skeletal myoblasts. We established a novel, robust stepwise protocol by treating iPS with a WNT agonist, CHIR 99021 and myotubes-derived EVs. Thus, this method has two main advantages: (i) studying molecular mechanisms of myogenesis which is overpassed in case of genetic manipulation; (ii) muscle progenitors are not terminally differentiated, and therefore have a better repair potential following transplantation. One of the major hurdles of stem cell therapy for skeletal muscle regeneration is the massive death following transplantation. Biomaterials exhibit immune protection properties and would ensure an artificial microenvironment which permits them to interact with host cells and exert their therapeutic benefits. With the purpose of a better engraftment, we employed Poly (ethylene glycol) (PEG) -fibrinogen hydrogel (PF) as cell carrier for skeletal muscle regeneration. When transplanted in a αsarcoglycan knockout/severe combined immunodeficiency beige (α-SGKO/SCIDbg) mice, PF-embedded myogenic progenitor cells exhibited stable long-term engraftment and participated in muscle regeneration by fusing with existing muscle fibers. Importantly, no teratoma and no abnormal structure were detected in the muscles transplanted with MPs Finally, our finding and differentiation system provide an effective method that facilitates further utilization of iPS .
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Manners, David Neil. "Magnetic resonance imaging and magnetic resonance spectroscopy of skeletal muscle." Thesis, University of Oxford, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.269250.
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Acharyya, Swarnali. "Elucidating molecular mechanisms of muscle wasting in chronic diseases." Columbus, Ohio : Ohio State University, 2007. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1180096565.
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Cramer, Megan L. "Novel signaling pathways in skeletal muscle: Modifiers of disease and the immune response to therapies." The Ohio State University, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=osu1531790292235549.
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Shrikrishnapalasuriyar, Dinesh. "ACE-inhibition and skeletal muscle dysfunction in chronic obstructive pulmonary disease." Thesis, Imperial College London, 2013. http://hdl.handle.net/10044/1/39299.
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This thesis addresses the impact of quadriceps wasting and physical inactivity across disease severity (GOLD stages I-IV) in Chronic Obstructive Pulmonary Disease (COPD) and assesses the influence of angiotensin-converting enzyme (ACE)-inhibition on quadriceps dysfunction in these patients. In a cross-sectional study of 161 COPD patients, ultrasound measurement of rectus femoris cross-sectional area was reduced in mild as well as advanced disease when compared to controls. Daily physical activity, measured using an armband accelerometer, was reduced in COPD subjects across all GOLD stages compared to controls. Physical activity was independently associated with quadriceps wasting in GOLD stage I, but not stage II-IV disease where residual volume to total lung capacity ratio was the only independent predictor of activity level. This data suggests that quadriceps wasting is not an end-stage phenomenon in COPD and highlights the need for early identification of these patients to guide lifestyle and therapeutic interventions. The effect of the ACE-inhibitor, fosinopril on quadriceps dysfunction in COPD was then investigated in a double-blind randomised controlled trial of 80 COPD patients with quadriceps weakness. Despite a significant reduction in systolic blood pressure and serum ACE activity in the treatment group compared to placebo, no significant differences were observed at 3 months in the primary outcome of non-volitional quadriceps endurance. Quadriceps strength improved in both groups, but there was a greater increase in the placebo arm. No significant changes were observed in mid-thigh cross-sectional area or incremental shuttle walk distance. The trial also assessed the effect of ACE-inhibition on vastus lateralis atrogene expression in COPD, with no significant differences observed between groups. In conclusion, although evidence from observational cohorts suggest a role for the renin-angiotensin system in the control of muscle phenotype, data from this thesis found that ACE-inhibition did not improve quadriceps function in a COPD population with quadriceps weakness.
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Reilly, Matthew Eliot. "Cellular and molecular mechanisms in the pathogenesis of alcoholic skeletal muscle myopathy." Thesis, King's College London (University of London), 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.313362.
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Janssen, Ian. "Linking age-related changes in skeletal muscle morphology with metabolism and disease." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2002. http://www.collectionscanada.ca/obj/s4/f2/dsk3/ftp05/NQ65676.pdf.
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Morris, Robert Tyler. "Maladaptation of cardiac and skeletal muscle in chronic disease effects of exercise /." Diss., Columbia, Mo. : University of Missouri-Columbia, 2007. http://edt.missouri.edu/Summer2007/Dissertation/MorrisR-080307-D8225/.
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Thesis (Ph. D.)--University of Missouri-Columbia, 2007.The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file. Vita. "August 2007" Includes bibliographical references.
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Steele-Stallard, Heather. "Induced pluripotent stem cell platforms for disease modelling of skeletal muscle laminopathies." Thesis, University College London (University of London), 2018. http://discovery.ucl.ac.uk/10058072/.
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Laminopathies are a clinically and genetically heterogeneous group of 16 disorders caused by mutations in LMNA. This gene codes for lamin A and lamin C, which together with lamin B1 and B2 form the nuclear lamina, a mesh-like structure located underneath the inner nuclear membrane. Laminopathy disorders show striking tissue specificity, with subtypes affecting striated muscle, peripheral nerve, and others causing multisystem disease with accelerated aging. The exact mechanisms underlying the pathology of laminopathies, and the cause of the tissue specific phenotypes are unknown, although several mechanisms have been proposed. Understanding the pathology of these disorders is limited by the rarity of cases, and lack of easily accessible cell types. Induced pluripotent stem cells (iPSCs) can be derived from easily accessible cell types, have unlimited proliferation potential, and can be differentiated into cell types that would otherwise be difficult and invasive to obtain. This PhD project aimed to use iPSCs from patients with skeletal muscle laminopathies to model disease phenotypes in vitro. In this thesis, fibroblasts from a patient with a skeletal muscle laminopathy were reprogrammed into iPSCs. This line, along with three already reprogrammed iPSC lines from skeletal muscle laminopathy patients were differentiated into mesodermal/mesenchymal progenitors, myogenic precursor cells and myotubes. Disease-associated phenotypes were observed in these cells, namely abnormal nuclear shape and mislocalisation of nuclear lamina proteins. Furthermore, work towards developing a therapy based on lamin A/C exon skipping was conducted. These results demonstrate that iPSCs from skeletal muscle laminopathy patients can be used to model disease-associated phenotypes in vitro. This lays the foundation for future therapy testing and disease modelling in skeletal muscle laminopathies using patient specific iPSCs.
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Scaramozza, Annarita <1982>. "The regulation of Satellite Cells during skeletal muscle regeneration and neuromuscular disease." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2012. http://amsdottorato.unibo.it/4258/1/Scaramozza_Annarita_tesi.pdf.
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Skeletal muscle possesses the remarkable capacity to complete a rapid and extensive regeneration, even following severe damage. The regenerative ability of skeletal muscle relies on Satellite Cells (SCs), a population of muscle specific adult stem cells. However, during aging or under several pathological conditions, the ability of skeletal muscle to fully regenerated is compromised. Here, a morphological and molecular study on SCs from patients affected by ALS is described. Moreover, the role of the cell cycle regulator P16Ink4a during skeletal muscle regeneration and aging has been investigated.
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Scaramozza, Annarita <1982>. "The regulation of Satellite Cells during skeletal muscle regeneration and neuromuscular disease." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2012. http://amsdottorato.unibo.it/4258/.
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Skeletal muscle possesses the remarkable capacity to complete a rapid and extensive regeneration, even following severe damage. The regenerative ability of skeletal muscle relies on Satellite Cells (SCs), a population of muscle specific adult stem cells. However, during aging or under several pathological conditions, the ability of skeletal muscle to fully regenerated is compromised. Here, a morphological and molecular study on SCs from patients affected by ALS is described. Moreover, the role of the cell cycle regulator P16Ink4a during skeletal muscle regeneration and aging has been investigated.
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Lindvall, Björn. "Immunohistological studies on muscle biopsies : clinical and pathogenetic aspects on inflammatory myopathies /." Linköping : Univ, 2002. http://www.bibl.liu.se/liupubl/disp/disp2002/med760s.pdf.
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Best, Heather Annette. "Gene discovery and mechanism of disease in the myopathies." Thesis, The University of Sydney, 2018. http://hdl.handle.net/2123/18940.
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Congenital myopathy and muscular dystrophy are two groups of inherited muscle diseases characterised by muscle weakness, and sub-classified by hallmark pathological features within a skeletal muscle biopsy. In order to understand the pathogenesis of inherited muscle disorders, and develop or apply therapies based on mechanistic insight, one must elucidate deep knowledge of the associated gene, genetic variant and the function of the encoded protein. This thesis focuses on three aspects of gene discovery in the inherited myopathies: (1) Identification of a novel variant and phenotype for a known disease gene; (2) understanding the functional role of a recently identified disease gene in skeletal muscle biology and disease; and (3) discovering a novel disease gene for congenital myopathy. We identified the first recessive variant within ACTA1 (encoding α-skeletal actin) as the genetic cause of congenital muscular dystrophy with rigid spine. This case uniquely describes recessive ACTA1 variants where α-skeletal actin protein is expressed. The unique clinical and histological presentation expands the spectrum of ACTA1 disease, and will help guide clinical care and future genetic diagnoses. Our team identified LMOD3 (leiomodin-3) as a novel disease gene for severe nemaline myopathy (NM). KLHL40 (encoding kelch-like family member 40) is another disease gene for severe NM. A recent study suggests mouse Klhl40 protects mouse Lmod3 protein from proteasome-mediated degradation, with the mechanistic basis of KLHL40-NM resulting from secondary loss of LMOD3. We investigated the regulation of human LMODs by human KLHL40, and unexpectedly found evidence that disputes the central paradigm that KLHL40 protects LMOD3 from proteasome-mediated degradation. We identified PYROXD1 as a new genetic cause of early-onset congenital myopathy. We provide the first characterisation of PYROXD1 as a nuclear-cytoplasmic oxidoreductase and our discovery highlights oxidative distress as a core mechanistic pathway in the myopathies. We derived a mouse model of Pyroxd1 deficiency, determining that global loss of mouse Pyroxd1 is embryonic lethal. We subsequently developed a mouse model with skeletal muscle knock-out of Pyroxd1 – as a means to elucidate the role of PYROXD1 in biology and disease.
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Yoshida, Takeshi. "A Skeletal Muscle Model of Infantile-onset Pompe Disease with Patient-specific iPS Cells." Kyoto University, 2019. http://hdl.handle.net/2433/236606.
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Shahriyari, Mina [Verfasser]. "Engineered skeletal muscle from human pluripotent stem cells to model muscle disease and regeneration / Mina Shahriyari." Göttingen : Niedersächsische Staats- und Universitätsbibliothek Göttingen, 2021. http://d-nb.info/123640176X/34.
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Mathur, Sunita. "Skeletal muscle strength and endurance in chronic obstructive pulmonary disease, a pilot study." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2000. http://www.collectionscanada.ca/obj/s4/f2/dsk2/ftp01/MQ57258.pdf.
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Picard, Martin. "Assessment of mitochondrial function in skeletal muscle during disease, disuse and normal aging." Thesis, McGill University, 2012. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=110394.
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Major cellular processes in skeletal muscle cells are regulated by mitochondria. To understand the role of this organelle in health and disease, it is essential to directly measure different aspects of mitochondrial function using the most appropriate methods. In this work, it is established that permeabilized myofibers are preferable to isolated mitochondria to directly measure mitochondrial function in skeletal muscle, as permeabilized preparations preserves natural mitochondrial morphology. The permeabilized myofibers method is then used to study skeletal muscle mitochondrial function in two different physiological contexts. First, I describe major differences in mitochondrial function from patients with chronic obstructive pulmonary disease (COPD), a clinical condition where mitochondrial dysfunction is hypothesized to exist, but where direct evidence is limited. This study and others in animals reinforce the notion of mitochondrial functional specialization. Second, to ascertain to what extent mitochondrial function is modified with aging and in relation to muscle atrophy, mitochondrial function was characterized in four distinct skeletal muscles from young adult and senescent rats. Findings indicated that aging induces relatively mild changes in mitochondrial function, which were unrelated to the degree of age-related atrophy. Finally, a subsequent study evaluated the effects of acute suppression of contractile activity in diaphragm of individuals receiving mechanical ventilation. This complete disuse paradigm led to maladaptive changes in several indices of mitochondrial function, gene expression and cellular energy metabolism. These studies: i) demonstrate that mitochondrial function is altered by the standard mitochondrial isolation process; ii) establish differences in mitochondrial function in COPD; iii) establish that changes in mitochondrial function across muscle fiber-types with aging is unrelated to age-related muscle atrophy; and iv) define metabolic and mitochondrial alterations of complete diaphragmatic disuse. Future work should consist in deciphering the mechanisms that establish mitochondrial functional specialization, and in evaluating the physiological consequences of changes in mitochondrial function on intracellular signaling pathways in health and disease.Les cellules musculaires s'adaptent à des variations aigues et chroniques de demande métabolique en modifiant leur contenu et la fonction des mitochondries. Pour comprendre le rôle de cette organelle dans différents états physiologiques et pathologiques, il est essentiel de mesurer différents aspects de la fonction mitochondriale, en usant les méthodes les plus appropriées. Dans le travail présenté ici, il est établi la méthode des fibres perméabilisées comme étant préférable aux mitochondries isolées pour mesurer la fonction intrinsèque des mitochondries de muscle squelettique. Nous employons ensuite la méthode des fibres perméabilisées pour décrire des différences de phénotype mitochondrial dans le muscle squelettique de patients atteints de maladies pulmonaires obstructives chroniques (MPOC). Cette étude, ainsi que d'autres sur muscles de rongeurs qui diffèrent de par leurs compositions de type de fibres, établissent un spectre de paramètres fonctionnels que les mitochondries de muscle squelettique adoptent en conditions physiologiques normales et durant le déconditionnement chronique. Ensuite, pour évaluer les changements de fonction mitochondriale au cours du vieillissement et en lien avec l'atrophie musculaire, nous avons caractérisé les phénotypes mitochondriaux de quatre muscles de rats jeunes et sénescents. Le vieillissement a mené à des changements modérés et distincts relativement à ceux induits par les conditions de déconditionnement chroniques et aigus. Finalement, un étude subséquente a visé à évalué les effets de suppression d'activité contractile du diaphragme chez des sujets recevant de la ventilation mécanique. Ce paradigme de déconditionnement complet fut associé à des changements délétères de plusieurs indices de fonction mitochondriale et de métabolisme énergétique cellulaire. Ces études : i) démontrent que la fonction mitochondriale est altérée par le processus standard d'isolation; ii) établissent des différences stables entre muscles contenant différents types de fibres musculaires; iii) établissent que les changements de fonction mitochondriale dans différents types de fibres musculaires n'est pas associé à l'atrophie musculaire; et iv) définissent des altérations mitochondriales et métaboliques de la ventilation mécanique chez l'homme. De futures études devraient se pencher sur les mécanismes qui établissent différents phénotypes mitochondriaux, et viseront à évaluer les conséquences physiologiques de phénotypes précis sur les voies de signalisation intracellulaires dans des conditions de santé et de maladies chroniques.
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Petchey, L. K. "Investigating the role of Prox1 in cardiac and skeletal muscle development and disease." Thesis, University College London (University of London), 2013. http://discovery.ucl.ac.uk/1401080/.
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Restricted expression of contractile protein gene isoforms contributes to the functional distinction between cardiac and skeletal striated muscle types, with these genes often misregulated in myopathic disease. The homeobox transcription factor Prox1 is expressed in both cardiac and skeletal muscle, and ablation of Prox1 specifically within cardiomyocytes resulted in the abnormal upregulation of the fast-twitch skeletal isoforms of the contractile protein genes troponin T (Tnnt3), troponin I (Tnni2), and MyLC 1 (Myl1) from early in heart development. Similar loss of function studies in skeletal muscle using a Myf5-driven Cre revealed overexpression of these same fast-twitch genes specifically in slow-twitch skeletal muscle, identifying Prox1 as the first transcription factor known to directly repress a program of fast-twitch skeletal genes across both cardiac and skeletal striated muscle types. Furthermore, loss of Prox1 expression in skeletal muscle was sufficient to cause a switch from a slow to a fast-twitch fibre-type, which has not previously been reported following knockout of a single transcription factor. Intriguingly, aberrant expression of Tnnt3, Tnni2, and Myl1 has been observed in other muscle-specific knockout models, including HDAC1/2 and miR-208a (cardiac), and Sox6 and miR-208b/miR-499 (skeletal), where the transcription factor directly responsible for their misexpression remains to be demonstrated. Recent work has revealed a lack of conservation in the regulation of these genes from the zebrafish, suggesting that in the mouse this role may be fulfilled by Prox1. This study has additionally uncovered novel putative regulatory relationships between Prox1 and miRNAs implicated in cardiac and/or skeletal muscle development, function, or disease, using a high-throughput in vitro screen. Herein is also the first description of the heart phenotype of survived cardiac-specific Prox1 knockouts, which develop severe dilated cardiomyopathy that is fatal within the first 14 weeks of life. Consequently, these mice model the functional impact of loss of Prox1 function on the adult heart, including the effect of ectopic fast-twitch contractile protein gene expression, and the molecular pathways that underlie the development of dilated cardiomyopathy. An improved understanding of the function of Prox1 in the developing and adult heart may provide new opportunities for therapeutic intervention.
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Johnson, Andrew William. "Metabolic control of energetics in human heart and skeletal muscle." Thesis, University of Oxford, 2012. http://ora.ox.ac.uk/objects/uuid:82c0dce6-a162-4c08-b061-3ea7f2e35134.
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Myocardial and skeletal muscle high energy phosphate metabolism is abnormal in heart failure, but the pathophysiology is not understood. Plasma non-esterified fatty acids (NEFA) increase in heart failure due to increased sympathetic drive, and regulate the transcription of mitochondrial uncoupling protein-3 (UCP3), through peroxisome proliferator-activated receptor-α. The aim of the work in this thesis was to determine whether cardiac PCr/ATP ratios and skeletal muscle PCr kinetics during exercise were related to cardiac and skeletal muscle UCP3 levels respectively, thus providing a mechanism for the apparent mitochondrial dysfunction observed in heart failure. Patients having cardiac surgery underwent pre-operative testing, including cardiac and gastrocnemius 31P magnetic resonance spectroscopy. Intra-operatively, ventricular, atrial and skeletal muscle biopsies were taken for measurement of mitochondrial protein levels by immunoblotting, along with mitochondrial function by tissue respiration rates. Fasting plasma NEFA concentrations increased in patients with ventricular dysfunction and with New York Heart Association (NYHA) class. Ventricular UCP3 levels increased and cardiac PCr/ATP decreased with NYHA class, however, demonstrated no relationship to each other. In skeletal muscle, maximal rates of oxidative ATP synthesis (Qmax) related to functional capacity. Skeletal muscle UCP3 levels increased with NYHA class but were unrelated to skeletal muscle Qmax. Tissue respiration experiments revealed no relationship between ventricular function and indices of mitochondrial coupling, furthermore, indices of mitochondrial coupling were unrelated to tissue UCP3 levels. No evidence was found to support mitochondrial uncoupling, mediated through UCP3, as a cause of the abnormalities in cardiac and skeletal muscle high energy phosphate metabolism.
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Wredenberg, Anna. "Mitochondrial dysfunction in ageing and degenerative disease /." Stockholm : Karolinska institutet, 2007. http://diss.kib.ki.se/2007/978-91-7357-311-5/.
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ZHOU, TINGYANG ZHOU. "Molecular Roles of ROS in Mouse Respiratory Skeletal Muscle." The Ohio State University, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=osu1531848449464785.
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Li, Mingxin. "Celluar and Molecular Mechanisms Underlying Regulation of Skeletal Muscle Contraction in Health and Disease." Doctoral thesis, Uppsala universitet, Klinisk neurofysiologi, 2010. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-123005.
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Morphological changes, genetic modifications, and cell functional alterations are not always parallel. Therefore, assessment of skeletal muscle function is an integral part of the etiological approach. The general objective of this thesis was to look into the cellular and molecular events occurring in skeletal muscle contraction in healthy and diseased condition, using a single fiber preparation and a single fiber in vitro motility assay, in an attempt to approach the underlying mechanisms from different physiological angles. In a body size related muscle contractility study, scaling of actin filament sliding speed and its temperature sensitivity has been investigated in mammals covering a 5,500-fold difference in body mass. A profound temperature dependence of actin filament sliding speed over myosin head was demonstrated irrespective of MyHC isoform expression and species. However, the expected body size related scaling within orthologus myosin isoforms between species failed to be maintained at any temperature over 5,500-fold range in body mass, with the larger species frequently having faster in vitro motility speeds than the smaller species. This suggest that apart from the MyHC iso-form expression, other factors such as thin filament proteins and myofilament lattice spacing, may contribute to the scaling related regulation of skeletal muscle contractility. A study of a novel R133W β-tropomyosin mutation on regulation of skeletal muscle contraction in the skinned single fiber prepration and single fiber in vitro motility assay suggested that the mutation induced alteration in myosin-actin kinetics causing a reduced number of myosin molecules in the strong actin binding state, resulting in overall muscle weakness in the absence of muscle wasting. A study on a type IIa MyHC isoform missense mutation at the motor protein level demonstrated a significant negative effect on the function of the IIa MyHC isoform while other myosin isoforms had normal function. This provides evidence that the pathogenesis of the MyHC IIa E706K myopathy involves defective function of the mutated myosin as well as alterations in the structural integrity of all muscle irrespective of MyHC isoform expression.
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Crawford, Parks Tara. "Novel Functions for the RNA-binding Protein Staufen1 in Skeletal Muscle Biology and Disease." Thesis, Université d'Ottawa / University of Ottawa, 2016. http://hdl.handle.net/10393/35627.
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Over the past decade several converging lines of evidence have highlighted the importance of post-transcriptional events in skeletal muscle. This level of regulation is controlled by multi-functional RNA-binding proteins and trans-acting factors. In fact, several RNA-binding proteins are implicated in neuromuscular disorders including myotonic dystrophy type I, spinal muscular atrophy and amyotrophic lateral sclerosis. Therefore, it is necessary to examine the impact of RNA-binding proteins during skeletal muscle development and plasticity in order to understand the consequences linked to their misregulation in disease. Here, we focused on the RNA-binding protein Staufen1, which assumes multiple roles in both skeletal muscle and neurons. We previously demonstrated that Staufen1 is regulated during myogenic differentiation and that its expression is increased in denervated and in myotonic dystrophy type I skeletal muscles. The increased expression of Staufen1 initially appeared beneficial for DM1 since further elevating Staufen1 levels rescued key hallmarks of the disease. However, based on the multi-functional nature of Staufen1, we hypothesized that Staufen1 acts as a disease modifier in DM1. To test this, we investigated the roles of Staufen1 in skeletal muscle biology and their implications for disease.
Our data demonstrated that Staufen1 is required during the early stages of muscle development, however its expression must remain low in postnatal skeletal muscle. Interestingly, the overexpression of Staufen1 impaired myogenesis through the regulation of c-myc translation. Since the function of c-myc in oncogenesis is well described, we investigated the role of Staufen1 in cancer biology. In particular, we determined novel functions of Staufen1 in rhabdomyosarcoma tumorigenesis, thus providing the first direct evidence for Staufen1’s involvement in cancer. Moreover, based on Staufen1’s role in myogenic differentiation and in myotonic dystrophy type I, we generated muscle-specific transgenic mice to examine the impact of sustained Staufen1 expression in postnatal skeletal muscle. Staufen1 transgenic mice developed a myopathy characterized by histological and functional abnormalities via atrogene induction and the regulation of PTEN mRNAs. In parallel, we further investigated Staufen1-regulated alternative splicing and our data demonstrated that Staufen1 regulates multiple alternative splicing events in normal and myotonic dystrophy type I skeletal muscles, both beneficial and detrimental for the pathology. Collectively, these findings uncover several novel functions of Staufen1 in skeletal muscle biology and highlight Staufen1’s role as a disease modifier in DM1.
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Gallagher, Ryan Robert. "THE IMPACT OF OUTWARD REMODELING ON VASODILATION IN SKELETAL MUSCLE RESISTANCE ARTERIES." DigitalCommons@CalPoly, 2012. https://digitalcommons.calpoly.edu/theses/914.
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Peripheral arterial occlusive disease (PAOD) is an ischemic disease characterized by narrowing of the peripheral arteries due to the accumulation of atherosclerotic plaque in the inner lining of the vessels, which disrupts blood flow to downstream tissues. Blood can be redirected into collateral vessels, natural bypasses around arterial occlusions, causing shear-induced outward remodeling of the vessels. The enlarged vessels facilitate transfer of increased blood flow to downstream tissues. The remodeling process, however, may impair vasodilation, which in turn may cause or contribute to intermittent claudication- transient pain brought on by locomotion. To stimulate the growth of collateral arteries, the femoral arteries of young, otherwise healthy mice were ligated distally to the profunda femoris, the stem to the gracilis collateral circuit. The diameter of the profunda femoris artery was measured at rest and following gracilis muscle contraction 7 and 28 days post-surgery using intravital microscopy. Enlarged resting diameter, consistent with collateral enlargement, and impaired vasodilation was observed at day 7, but not at day 28. To determine if impaired functional vasodilation is due to impaired endothelial- or smooth muscle-dependent responses during outward remodeling, cell-dependent vasodilators were applied to the hindlimb. Endothelial- and smooth muscle-dependent vasodilation was significantly impaired 7 days post-ligation, but not 28 days after. This data supports the hypothesis that smooth muscle dysfunction causes impaired functional vasodilation in the early stages of collateral enlargement.
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Kump, David S. "Physical inactivity induced dysregulation of skeletal muscle and adipose tissue metabolism." Diss., Columbia, Mo. : University of Missouri-Columbia, 2005. http://hdl.handle.net/10355/4154.
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Thesis (Ph. D.)--University of Missouri-Columbia, 2005.The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file. Vita. "May 2005" Includes bibliographical references.
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Raab, Staci R. "Characterization of Antibodies to Subcellular Fractions of Skeletal Muscles in Patients with Myasthenia Gravis and Autoimmune Rippling Muscle Disease." Youngstown State University / OhioLINK, 1999. http://rave.ohiolink.edu/etdc/view?acc_num=ysu999029324.
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Coleman, Kirsty Lee. "Exercise tolerance and skeletal muscle structure and function in patients with chronic obstructive pulminary disease." Master's thesis, University of Cape Town, 1998. http://hdl.handle.net/11427/17935.
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Bibliography: pages 143-154.Exercise intolerance is well documented in patients with chronic obstructive pulmonary disease (COPD). Historically, this exercise intolerance has been attributed to the central factors of lung damage and subsequent heart failure. However, recent evidence suggests that (i) patients with cardiac and renal failure suffer from skeletal muscle (SM) abnormalities that impair exercise tolerance and (ii) patients with chronic obstructive pulmonary disease (COPD) may have metabolic and functional abnormalities of SM. However, no studies have conducted a detailed investigation of SM structure and function and their relation to exercise tolerance in patients with COPD.
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MacMillan, Norah. "Comparison of skeletal muscle adaptations to eccentric versus concentric training in chronic obstructive pulmonary disease." Thesis, McGill University, 2013. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=119513.
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Currently, effective treatment strategies for patients with severe chronic obstructive pulmonary disease (COPD) are limited. A widely used treatment method is exercise rehabilitation, which has a multitude of benefits on quality of life, improving exercise tolerance and decreasing hospitalizations. However, patients with more severe cases of COPD are unable to train at exercise intensities high enough to significantly improve disease-related skeletal muscle abnormalities such as losses in muscle mass and strength. Our group has recently shown the feasibility and safety of an eccentric (ECC) cycle training intervention in COPD as an alternative modality that can load the muscle four times as much as typical concentric (CON) cycle training at the same metabolic cost (Rocha Vieira, Baril et al. 2011). However, the skeletal muscle adaptations to ECC cycling compared to CON cycling in COPD have not been examined in the literature. In our study, patients were randomized to either an ECC (n=8) or CON (n=7) cycle training group to train for 10 weeks, three times per week for 30 minutes and matched for metabolic cost at 60-80% CON V̇O2peak. Pre and post-training assessments were taken of the patient's body composition, peak muscle strength and muscle fiber type and size by immunolabeling cross-sections of vastus lateralis muscle needle biopsies. Compared to CON training, we found that ECC training resulted in significant increases in lean body mass with an accompanying decrease in body fat mass. Along with this we found that, ECC training resulted in significant increases in muscle strength, whereas CON training did not. At the single fiber level, we found that CON resulted in increases in average fiber size that was principally drive by an increase in type 1 fiber size, however no changes were seen in patients performing ECC training. In both groups no significant changes in fiber type proportions occurred with training. ECC cycling had a moderately greater augmenting effect on lean muscle mass and strength than CON cycling, making it a useful alternative for severe COPD patients due to its high force production at an equivalent metabolic cost, which may prove important in preventing disease related muscle atrophy.Actuellement, on constate un manque de stratégies de traitements efficaces pour les patientes atteints de maladie pulmonaire obstructive chronique (MPOC) sévère. Une méthode de traitement des plus répandues est l'exercice de réadaptation qui possède de nombreux bienfaits tels que l'amélioration de la qualité de vie, l'augmentation de la tolérance à l'effort et une diminution du nombre d'hospitalisations. Cependant, dans les cas les plus sévères plusieurs patients ne sont pas en mesure de faire de l'exercice à une intensité assez forte pour améliorer les anomalies des muscles squelettiques, une caractéristique importante de la MPOC, comme la perte de la masse musculaire, la force musculaire et un changement des proportions des fibres. Récemment, notre groupe de recherche a démontré la faisabilité et la sécurité d'une intervention en entraînement en cycle de musculation excentrique (EXC) dans les cas de MPOC. En effet, l'exercice excentrique permet d'ajouter 4 fois plus de résistance musculaire que l'entraînement en cycle concentrique (CONC) typique, et ce, au même cout métabolique. Par contre, les adaptations des muscles squelettiques au cycle EXC en comparaison à celles au cycle CONC dans les cas de MPOC n'ont pas été documentées dans les publications. Dans cette étude, les patients ont été randomisés en deux groupes, EXC (n=8) ou CONC (n=7) pour dix semaines d'entraînement, 3x par semaine pour 30 minutes pour un même coût métabolique CONC de 60-80% V̇O2max. Les mesures ont été prises avant et après l'entraînement : la composition corporelle, la force musculaire maximale, une biopsie à l'aiguille du vaste latéral pour l'analyse de l'expression protéinique MHC et pour la grandeur de la fibre musculaire. Les résultats ont démontré qu'en comparaison avec l'entraînement CONC, l'entraînement EXC permet une augmentation significative de la masse corporelle maigre accompagnée d'une diminution de la masse corporelle grasse. De plus, nous avons remarqué que l'entraînement EXC a résulté en une augmentation significative de la force musculaire, mais l'entraînement CONC n'a pas résulté en une augmentation significative de la force musculaire. Néanmoins, l'entraînement CONC a résulté en une augmentation plus grand de la grandeur des fibres en moyen et spécifique à fibres qui expresse le protéine MHC type 1. En les deux groupes, il n'y a pas un changement significatif des proportions des fibres après l'entraînement. L'entraînement EXC a résulté en une augmentation plus grande de la composition corporelle et la force musculaire que l'entraînement CONC. L'entraînement EXC est une alternative utile pour éviter la perte de la masse musculaire dans les patients plus sévère a cause de la diminution de la coûte métabolique et l'augmentation de la force musculaire pendant l'entraînement.
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Tai, Yunlin 1962. "Functional studies on the coxsackie and adenovirus receptor (CAR) in skeletal muscle cells." Thesis, McGill University, 2000. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=31548.
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CAR (for C&barbelow;oxsackievirus and A&barbelow;denovirus R&barbelow;eceptor) is a novel member of the Ig superfamily, which has recently been identified as a high affinity receptor for both Coxsackievirus and certain adenovirus (AV) serotypes. Virus bound by CAR is believed to be passed to integrins which bind an RGD (Arg-Gly-Asp) sequence in the viral penton base protein and act as secondary receptors responsible for virus internalization.Recent studies have shown that, in integrin-expressing cells, CAR-mediated AV uptake does not require the cytoplasmic (CP) domain of CAR, presumably because virus bound to the CAR extracellular (EC) domain can be passed to integrins for subsequent internalization. It has however also been reported that CAR can directly mediate AV uptake in the absence of penton base RGD-alphav integrin interactions. I therefore attempted to determine whether the CP domain of CAR is required for CAR-mediated AV uptake in cells which do not express integrins, or in which integrin function has been blocked by RGD-containing peptide.
As CAR is the primary AV receptor and integrins are secondary AV receptors I investigated the possibility that these proteins associate in a functional complex in the cell membrane. (Abstract shortened by UMI.)
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Tang, Teresa. "Effects of plasmas from seronegative myasthenia gravis patients on the function of skeletal muscle nicotinic acetylcholine receptor." Thesis, University of Oxford, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.365322.
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Farshidfar, Farnaz. "Effects of creatine supplementation on muscle metabolism in an Alzheimer mouse model." IOS Press, 2016. http://hdl.handle.net/1993/31212.
Full textAbstract:
Alzheimer’s disease (AD), the most common form of dementia in the elderly, is a global issue affecting about 24 million individuals. Because AD is a systemic pathology, dementia is not the only leading factor contributing to loss of independence in AD patients. AD may also impair skeletal muscle metabolism and function. Creatine (CR) supplementation may enhance skeletal muscle hypertrophy/mass and function in sarcopenia and muscular dystrophies, but has yet to be studied in AD. This study examined the effect of oral CR on muscle metabolism in a triple-transgenic (3xTg) AD mouse model. Twenty-four, 3×Tg AD mice (~8 month-old) were randomly assigned to control (CON) or CR (3% w/w) diet. Bodyweights and feed intakes were measured throughout the 8-week study. Lower limb (quadriceps muscle; QM and gastrocnemius; GM) and upper limb muscles (triceps; TM) were collected to analyze levels of CR, total protein, DNA, RNA, amino acids (AA), adenosine triphosphate (ATP), adenosine diphosphate (ADP), total and phosphorylated p70 ribosomal S6 kinase (p70S6K). Data (mean ± SEM) were assessed by analysis of variance (ANOVA) and Fisher’s least significant difference (LSD) post hoc test. In comparison to the CON group, CR supplementation increased CR content in both GM (p=0.002) and QM (p=0.037), with higher (p=0.032) ATP/ADP ratio in CR in comparison with CON in QM. A higher protein concentration (p<0.0001) was notable in GM of CR supplemented group vs. CON. Total branched-chain AA levels in QM increased 2-fold (p< 0.0001) in CR groups. Additionally, CR resulted in a higher (p<0.05) protein/DNA ratio; an index of muscle cell size, in both QM and GM for CR groups. The index of cell capacity for protein synthesis (RNA/DNA ratio) in GM was also higher (p=0.001) in CR groups. However, phosphorylation (activation) level of p70S6K, an integral component in protein synthesis signalling pathway, did not show any significant differences in female (p=0.161) and male (p=0.292) CR supplemented groups compared with CON. To conclude, CR supplementation is capable of inducing muscle hypertrophy/growth parameters in the 3×Tg AD mouse model, thereby enhancing protein synthesis capacity in skeletal muscles, thus possibly promoting muscle function in AD.May 2016
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Askew, Christopher D. "Exercise intolerance in peripheral arterial disease." Thesis, Queensland University of Technology, 2002. https://eprints.qut.edu.au/15869/1/Christopher_Askew_Thesis.pdf.
Full textAbstract:
Patients with Peripheral Arterial Disease have a reduced capacity for exercise, the exact causes of which are poorly understood. This thesis investigated alternative testing procedures that aim to provide a more complete and precise description of the exercise capacities of these patients. Furthermore, the potential roles of gastrocnemius muscle fibre morphometry, capillary supply and glycogen stores in the exercise tolerance of PAD patients were studied.
Study one aimed to determine the effect of test repetition on maximal exercise performance and test-to-test variability in PAD patients using an incremental treadmill walking test (T) (n=5), an incremental cycle test (C) (n=5), and incremental endurance (PF-endurance) and maximal strength (PF-strength) plantar flexion tests (n=5). Tests were conducted once per week for eight weeks. Performance was stable on the T (~530 s) and C (~500 s) tests across the eight weeks. Test-to-test variance on T decreased from 16%CV (CV: coefficient of variation) to 6%CV (p=.21,NS), and from ~8%CV to 2%CV on C (p<.05) over the eight week period. Variance of peak gas exchange variables tended to decrease with performance variance on both tests; however, other physiological variables, and the associated variance levels, were stable throughout the study. PF strength (635-712N) gradually increased over the initial 2-3 weeks (p<.05) which was accompanied by a reduction in variance from ~8%CV to ~3%CV (p<.05). Similarly, PF endurance increased over the first two weeks (~32,000 to 41500 N.s-1) while variance of this measure fell from ~21%CV to ~10%CV (p<.05) over the study duration. It is concluded that the implementation of familiarisation sessions leads to a reduction in whole body and local calf muscular performance variance in patients with PAD.
Using a randomised crossover design, study two aimed to compare performance and the physiological and symptomatic responses between a T test and a C test in 16 patients with PAD. Peak exercise time on C (690 s) was greater than that on T (495 s); however the two were significantly correlated (n=16, r=.69, p<.05). Peak HR (120 bpm), VO2 (~1.22 l.min-1) and rate pressure product (~20') did not differ between the two tests, nor did the post exercise ankle pressure (T: 56; C: 61 mmHg). In two subjects with lower back pain during C, the ankle pressure of their "worst" limbs failed to fall by >10mmHg. Performance on both the T and C tests was closely related to the onset of leg symptoms; however the site of pain during C was much more variable than during T. Incremental cycle testing would overcome some of the limitations of treadmill testing (e.g. measurement of mechanical work), and it appears to be an acceptable alternative for measuring the exercise capacity and physiological exercise responses in known claudicants. Use of cycle ergometry for the diagnosis of PAD requires testing in the general population.
Study three aimed to compare whole body (T test and C test) and local calf muscular (PF strength and endurance) exercise performance between 16 PAD patients (age: 63 ± 2; BMI: 25.9 ± 1.1) and 13 healthy, sedentary control (CON) subjects (age: 62 ± 1; BMI: 25.9 ± 0.4), and to describe relationships between the whole body and local calf muscular exercise capacities within the two groups. Furthermore, this study aimed to compare several histochemical characteristics of the medial gastrocnemius muscle fibres between PAD and CON, and to establish whether these factors were related to the exercise capacities of both groups. Maximal performance on T was 59% lower in the PAD group compared with the CON group, as was performance on C (50%), PF strength (25%), and PF endurance (58%). Compared with CON, PAD patients had a lower estimated calf muscle mass and a slight reduction (10%) in muscle fibre size (p=.14, NS). They also had a lower proportion of type I fibres (PAD: 49%; CON: 62%) that was offset by a greater proportion of type IIA fibres (PAD: 27%; CON: 16%), and a reduction in the capillary contacts per muscle fibre (PAD: 1.63; CON: 2.12) compared with CON. When expressed relative to fibre area there were no differences in capillarisation between PAD and CON; however this index was significantly related to resting and post exercise ABI in the PAD patients. There were no differences in the mixed muscle [glycogen], nor the optical density of glycogen in the individual fibres, between the two groups. PF endurance was poorly predictive of walking performance, and did not correlate with any of the morphological variables in both groups. Calf muscle mass correlated with PF strength (r=.59 - .62), and strength was correlated with T performance (r= .61 - .63) in both groups. In the PAD patients, T performance was correlated with the cross sectional area (n=12, r=.72, p<.05), capillary contacts (n=10, r=.81, p<.05) and glycogen density (n=9, r=.81, p<.05) of type I fibres. This study confirms that a reduction in calf strength, which appears to be mediated through muscle atrophy, plays some role in the reduced exercise capacity of claudicants. While both fibre area and capillary supply seem to be of relevance to the exercise capacity of PAD patients, these two factors are closely linked and further research is required to establish the determinants, and relative importance of both. An important, and possibly limiting role of carbohydrate oxidisation in PAD patients is supported by the strong relationship between type I glycogen stores and whole body exercise capacity.
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Askew, Christopher D. "Exercise intolerance in peripheral arterial disease." Queensland University of Technology, 2002. http://eprints.qut.edu.au/15869/.
Full textAbstract:
Patients with Peripheral Arterial Disease have a reduced capacity for exercise, the exact causes of which are poorly understood. This thesis investigated alternative testing procedures that aim to provide a more complete and precise description of the exercise capacities of these patients. Furthermore, the potential roles of gastrocnemius muscle fibre morphometry, capillary supply and glycogen stores in the exercise tolerance of PAD patients were studied.
Study one aimed to determine the effect of test repetition on maximal exercise performance and test-to-test variability in PAD patients using an incremental treadmill walking test (T) (n=5), an incremental cycle test (C) (n=5), and incremental endurance (PF-endurance) and maximal strength (PF-strength) plantar flexion tests (n=5). Tests were conducted once per week for eight weeks. Performance was stable on the T (~530 s) and C (~500 s) tests across the eight weeks. Test-to-test variance on T decreased from 16%CV (CV: coefficient of variation) to 6%CV (p=.21,NS), and from ~8%CV to 2%CV on C (p<.05) over the eight week period. Variance of peak gas exchange variables tended to decrease with performance variance on both tests; however, other physiological variables, and the associated variance levels, were stable throughout the study. PF strength (635-712N) gradually increased over the initial 2-3 weeks (p<.05) which was accompanied by a reduction in variance from ~8%CV to ~3%CV (p<.05). Similarly, PF endurance increased over the first two weeks (~32,000 to 41500 N.s-1) while variance of this measure fell from ~21%CV to ~10%CV (p<.05) over the study duration. It is concluded that the implementation of familiarisation sessions leads to a reduction in whole body and local calf muscular performance variance in patients with PAD.
Using a randomised crossover design, study two aimed to compare performance and the physiological and symptomatic responses between a T test and a C test in 16 patients with PAD. Peak exercise time on C (690 s) was greater than that on T (495 s); however the two were significantly correlated (n=16, r=.69, p<.05). Peak HR (120 bpm), VO2 (~1.22 l.min-1) and rate pressure product (~20') did not differ between the two tests, nor did the post exercise ankle pressure (T: 56; C: 61 mmHg). In two subjects with lower back pain during C, the ankle pressure of their "worst" limbs failed to fall by >10mmHg. Performance on both the T and C tests was closely related to the onset of leg symptoms; however the site of pain during C was much more variable than during T. Incremental cycle testing would overcome some of the limitations of treadmill testing (e.g. measurement of mechanical work), and it appears to be an acceptable alternative for measuring the exercise capacity and physiological exercise responses in known claudicants. Use of cycle ergometry for the diagnosis of PAD requires testing in the general population.
Study three aimed to compare whole body (T test and C test) and local calf muscular (PF strength and endurance) exercise performance between 16 PAD patients (age: 63 ± 2; BMI: 25.9 ± 1.1) and 13 healthy, sedentary control (CON) subjects (age: 62 ± 1; BMI: 25.9 ± 0.4), and to describe relationships between the whole body and local calf muscular exercise capacities within the two groups. Furthermore, this study aimed to compare several histochemical characteristics of the medial gastrocnemius muscle fibres between PAD and CON, and to establish whether these factors were related to the exercise capacities of both groups. Maximal performance on T was 59% lower in the PAD group compared with the CON group, as was performance on C (50%), PF strength (25%), and PF endurance (58%). Compared with CON, PAD patients had a lower estimated calf muscle mass and a slight reduction (10%) in muscle fibre size (p=.14, NS). They also had a lower proportion of type I fibres (PAD: 49%; CON: 62%) that was offset by a greater proportion of type IIA fibres (PAD: 27%; CON: 16%), and a reduction in the capillary contacts per muscle fibre (PAD: 1.63; CON: 2.12) compared with CON. When expressed relative to fibre area there were no differences in capillarisation between PAD and CON; however this index was significantly related to resting and post exercise ABI in the PAD patients. There were no differences in the mixed muscle [glycogen], nor the optical density of glycogen in the individual fibres, between the two groups. PF endurance was poorly predictive of walking performance, and did not correlate with any of the morphological variables in both groups. Calf muscle mass correlated with PF strength (r=.59 - .62), and strength was correlated with T performance (r= .61 - .63) in both groups. In the PAD patients, T performance was correlated with the cross sectional area (n=12, r=.72, p<.05), capillary contacts (n=10, r=.81, p<.05) and glycogen density (n=9, r=.81, p<.05) of type I fibres. This study confirms that a reduction in calf strength, which appears to be mediated through muscle atrophy, plays some role in the reduced exercise capacity of claudicants. While both fibre area and capillary supply seem to be of relevance to the exercise capacity of PAD patients, these two factors are closely linked and further research is required to establish the determinants, and relative importance of both. An important, and possibly limiting role of carbohydrate oxidisation in PAD patients is supported by the strong relationship between type I glycogen stores and whole body exercise capacity.
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Houchen-Wolloff, L. "The effects of resistance training and protein ingestion on skeletal muscle function in COPD." Thesis, Coventry University, 2012. http://curve.coventry.ac.uk/open/items/da5f48f3-46b3-4a1f-9ac7-f9c8e868a1ab/1.
Full textAbstract:
Chronic Obstructive Pulmonary Disease (COPD) is a complex disease, characterised by progressive airflow obstruction and is a major cause of morbidity, mortality and healthcare usage in the UK. Quadriceps muscle dysfunction is a key cause of exercise intolerance in patients with COPD, manifested by reduced muscle mass and strength. This problem also imposes a burden to the health system as quadriceps dysfunction is an independent predictor of hospitalisation and mortality. Importantly, the quadriceps may provide a target for therapy in an otherwise irreversible lung disease and changes in strength after resistance training (RT) are well documented. Protein supplementation has been successfully used as an adjunct to RT in healthy populations. However the role of this therapeutic combination has not before been studied in a COPD population. Methods: This thesis describes a randomised controlled trial (RCT) which aims to explore the role of protein supplementation given immediately after RT, upon functional outcomes, in patients with COPD. The hypothesis was that RT, in combination with protein ingestion (at the time of training) will have greater effects on functional outcomes than RT alone (chapter 4). Secondary aims were to precisely explore the training intensity progression, fatigue profile (chapter 5) and cardiorespiratory load imposed by the RT (chapter 6) and to examine the measurement properties of the ActiTrac® physical activity (PA) monitors (chapter 7). In all chapters the response to the intervention in patients with COPD, is compared to healthy, age-matched controls. 5 Results: The overriding message from this thesis is that protein supplementation can not be routinely recommended as an adjunct to RT for patients with COPD. All groups made significant improvements in quadriceps strength and thigh mass after RT but protein did not augment the outcome. Subjects with evidence of muscle wastage (based on fat-free mass criteria) responded less well to RT, although the study was underpowered to draw meaningful conclusions in this group. Subjects with COPD made comparable improvements to healthy age-matched controls, despite training at much lower intensities and experiencing greater decay in muscle force during a training session. Moreover, the RT programme was able to sufficiently activate the cardio-pulmonary system and led to significant improvements in wholebody exercise performance. PA did not change after the 8-week RT programme; suggesting that changes after RT are not routinely translated to increased habitual activity, particularly when the educational component of rehabilitation is missing. Conclusions: The RT programme utilised in this thesis was able to significantly improve both strength and endurance-related outcomes in patients with COPD. However, the provision of additional protein at the time of training did not enhance the benefits. The isokinetic RT programme provided a unique opportunity to precisely explore the training intensity progression, fatigue profile and cardiorespiratory load imposed by the training; comparing patients with COPD and healthy controls. The findings from this work provide some important considerations for clinical practice and require further investigation within a conventional rehabilitation setting.
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Calvert, Lorraine. "Exploration and modification of the skeletal muscle metabolic response to exercise in chronic obstructive pulmonary disease." Thesis, University of Leicester, 2009. http://hdl.handle.net/2381/7408.
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Clapp, Emma L. "The effect of therapeutic exercise and metabolic acidosis on skeletal muscle metabolism in chronic kidney disease." Thesis, Loughborough University, 2010. https://dspace.lboro.ac.uk/2134/6838.
Full textAbstract:
Muscle wasting and increased proteolysis is a major problem in chronic kidney disease (CKD). Exercise is potentially beneficial, but has been under-investigated in pre-dialysis CKD and could theoretically worsen acidosis through exercise-induced lactic acid generation. We therefore investigated effects of 6 months walking exercise with and without additional alkali therapy. 40 patients were recruited (23 male and 17 female, median age 58, range 20-83, mean eGFR±SEM 25.7±1.2ml/min/1.73m2). 20 undertook walking exercise at a Borg Rating of Perceived Exertion Rate (RPE) of 12-14 for at least 30 minutes, 5 times a week. The other 20 continued with normal physical activity (non-exercising controls). In addition to standard oral bicarbonate therapy (STD), 10 patients in each group were randomised to receive additional bicarbonate (XS). Blood and vastus lateralis muscle biopsies were drawn at baseline, one and six months. 18 exercisers (including 8 in XS group) and 14 controls (6 in XS group) completed the 6 month study. Exercise tolerance increased after 1 and 6 months in the exercisers, but not the controls, accompanied by a reduced acute lactate response in the XS, but not the STD exercising group. After 6 months of exercise, 9 intramuscular free amino acids showed striking depletion in the STD, but not XS bicarbonate group. This suggests an inhibition of active amino acid transporters, possibly the SNAT2 transporters that are inhibited by acidosis. Studies with cultured myotubes identified glucocorticoid as a possible mediator of acid s inhibitory effect on SNAT2. The preservation of amino acid concentrations in the XS exercising group was accompanied by strong suppression of ubiquitin E3-ligases MuRF-1 and MAFbx which activate proteolysis through the ubiquitin-proteasome pathway. However, other anabolic indicators (Protein Kinase B activation and suppression of the 14kDa actin fragment) were unaffected in the exercising XS group. Possibly because of this, overall suppression of myofibrillar proteolysis (3-methyl histidine excretion) and increased lean body mass (DEXA) were not observed in the exercising patients. As XS alkali had no effect in non-exercisers, it is concluded that alkali effects in the exercisers arose by countering exercise-induced acidosis. Sulphuric acid produced from the catabolism of sulphur-containing amino acids ingested in the diet is the main contributor to the daily titratable acid load and hence acidosis in CKD. In these patients the amount of sulphate excreted in urine over 24h varied widely between individuals. This directly correlated with 3-methyl histidine excretion suggesting that sulphate excretion may be a better clinical indicator of acidotic patients at long-term risk of cachexia than conventional measures such as venous bicarbonate. Studies with cultured myotubes confirmed that skeletal muscle is a source of sulphuric acid and showed that production of this acid is partly suppressed by L-Glutamine a potential novel way to control acidosis in CKD.