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1
Panta, Utsab, Adam chan und Debalina Das. „Osteonecrosis of Jaw: Common etiologies, uncommon treatments“. Digital Commons @ East Tennessee State University, 2019. https://dc.etsu.edu/asrf/2019/schedule/201.
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Introduction
First described in 2002, osteonecrosis of the jaw (ONJ, or avascular necrosis of the jaw) is an uncommon but potentially serious side effect of treatment with bisphosphonates. Although typically identified in patients with multiple myeloma and other malignancies, a few cases have been reported in patients taking bisphosphonates - a potent drug class used in the treatment of osteoclast-mediated bone resorption issues, including postmenopausal osteoporosis, Paget's disease, multiple myeloma, and malignant hypercalcemia. The clinical diagnosis of ONJ can be obscured by jaw pain, abscess, swelling, and fistulas, but exposed bone is a distinctive sign. This reports a case of ONJ secondary to bisphosphonate use in a 65-year-old woman and clinical management complications.
Case Presentation
A 65-year-old lady with history of age-related osteoporosis and compression fractures on alendronate for 4 years, squamous cell carcinoma of neck status post excision and radiotherapy 11-years prior, Sjogren's syndrome and discoid lupus on hydroxychloroquine, diabetes, hypertension, stroke and multiple dental abscesses presents with persistent neck pain. Initial CT neck with contrast showed diffuse fat stranding. Subsequently, alendronate was discontinued due to jaw necrosis suspicion. Eight months later, repeat CT scan showed new non-mass-like soft tissue thickening in the subcutaneous fat abutting the right anterior mandible with mandibular teeth cavities and periapical lucencies, likely to be periodontal cellulitis versus radiation osteonecrosis. Later, patient complained of a piece of bone penetrating the skin of her chin and presented with continuous drainage from sinus tract in her mandible, which was diagnosed as osteonecrosis attributed to bisphosphonates, previous radiation therapy, and dental abscesses. Patient was started on abaloparatide, an osteo-anabolic medication for osteoporosis and enrolled in hyperbaric oxygen therapy which immensely helped in controlling sinus drainage. Patient is currently awaiting mandibular reconstruction surgery.
Discussion
ONJ, often associated with pain, swelling, exposed bone, local infection, and pathologic fracture of the jaw, is a rare complication of bisphosphonate therapy. Currently, no prospective data exists to advise the benefits of therapy discontinuation however most clinical practices tend to discontinue at least temporarily. The incidence increases with longer treatment duration, particularly when therapy exceeds four years. Risk factors for developing ONJ while taking bisphosphonates include IV administration, anticancer therapy, dose and duration of exposure, dental extractions/implants, glucocorticoids, smoking, diabetes, and preexisting dental disease.
Case reports and series suggest benefit from hyperbaric oxygen therapy in wound healing, pain, and quality of life at three months, however no significant differences exist with outcomes beyond three months. Patients being considered for therapy with a bisphosphonate should be thoroughly evaluated for dental issues, prior to initiating therapy. Conservative management with limited debridement, antibiotic therapy as needed, and topical mouth rinses rather than aggressive surgical resection are recommended. Conservative therapy may result in healing in a significant proportion of patients. Surgical resection of necrotic bone should be reserved for refractory or advanced cases. Providers should remain cautious while prescribing high doses of bisphosphonates in patients with increased risk factors to prevent, timely diagnose and treat this condition.
References
Edwards BJ, Gounder M, McKoy JM, et al. Pharmacovigilance and reporting oversight in US FDA fast-track process: bisphosphonates and osteonecrosis of the jaw. Lancet Oncol 2008; 9:1166.
Khosla S, Burr D, Cauley J, et al. Bisphosphonate-associated osteonecrosis of the jaw: report of a task force of the American Society for Bone and Mineral Research. J Bone Miner Res 2007; 22:1479.
Hoff AO, Toth BB, Altundag K, et al. Frequency and risk factors associated with osteonecrosis of the jaw in cancer patients treated with intravenous bisphosphonates. J Bone Miner Res 2008; 23:826.
2
Roach, Denise Margaret. „Upregulation of matrix metalloproteinases -2 and -9 and type IV collagen degradation in skeletal muscle reperfusion injury“. Title page, contents and abstract only, 2002. http://web4.library.adelaide.edu.au/theses/09MD/09mdr6281.pdf.
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Includes bibliographical references (leaves 292-352) Determines the role of matrix metalloproteinases, MMP-2 and MMP-9 in reperfusion injury following skeletal muscle ischaemia; and, whether inhibition of MMPs by doxycycline protects against tissue damage.
3
Fouche, Celeste. „Differential effects of TNfα on satellite cell differentiation“. Thesis, Stellenbosch : Stellenbosch University, 2007. http://hdl.handle.net/10019.1/19596.
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Thesis (MSc)--University of Stellenbosch, 2007.ENGLISH ABSTRACT: Tumour necrosis factor alpha (TNFα) is a pleiotropic cytokine and has a wide variety of dose dependent cellular effects ranging from cell growth and differentiation, to inducing apoptosis. It has long been implicated in muscle and non-muscle inflammatory disorders, such as muscle wasting in chronic disease states, and rheumatoid arthritis. However, a physiological role for TNFα in muscle regeneration has been proposed as elevated levels of the cytokine are present when muscle regeneration processes are initiated: TNFα is secreted by infiltrating inflammatory cells, and by injured muscle fibres. Adult skeletal muscle contains a population of resident stem cell-like cells called satellite cells, which become activated, proliferate and differentiate following muscle injury to bring about repair of damaged muscle. Much research on the effects of TNFα on satellite cell differentiation has been conducted in recent years. It is however difficult to get a complete characterisation of the cytokine’s action as all models used slightly differ. We aimed therefore at providing comprehensive assessment of the effects of increasing doses of chronically supplemented TNFα on differentiating C2C12 cells. Cells were allowed to differentiate with or without TNFα supplementation for 7 days. Differentiation was induced at day 0. The effect on differentiation was assessed at days 1, 3, 5, and 7 by western blot analysis, and supplementary immunohistochemical analysis at days 1, 4, and 7 of markers of differentiation - muscle regulatory factors: MyoD and myogenin, markers of the cell cycle p21, PCNA, and the integral signalling molecule, p38MAPK. TNFα supplementation at day 1 tended to positively regulate early markers of differentiation. With continued supplementation however, markers of differentiation decreased dose dependently in treated cultures as the initial effect appeared to be reversed: A trend towards a dose dependent decrease in MyoD, myogenin and p21 protein existed in treated cultures at days 3, 5, and 7. These findings were significant at day 5 (p21, p<0.05), and day 7 (myogenin, p<0.05). A significant dose dependent decrease in p38 phosphorylation was evident at day 3 (p<0.05), while phospho-p38 was dose dependently increased at day 7 (p<0.05). Taken together, these data show that TNFα supplementation for 24 hours following the induction of differentiation in vitro, tends to increase levels of early markers of differentiation, and with continued TNFα supplementation decrease markers of differentiation in a dose dependent fashion. This study provides a comprehensive characterisation of the dose and time dependent effects of TNFα on satellite cell differentiaton in vitro. The model system used in the current study, allows us to make conclusions on more chronic disease states.
AFRIKAANSE OPSOMMING: Tumor nekrose faktor alfa (TNFα) is ‘n pleiotropiese sitokien wat ‘n wye verskeidenheid, dosis afhanklike, sellulêre effekte te weeg bring. Hierdie sellulêre effekte sluit sel groei en differensiasie tot sel dood in. TNFα is by beide spier en niespier inflammatoriese stoornisse soos spier tering in kroniese siektetoestande, en rumatiese artritis betrek. ‘n Fisiologiese rol vir TNFα is egter voorgestel aangesien verhoogde vlakke van die sitokien tydens inisiasie van spier herstel meganismes teenwoordig is: TNFα word deur infiltrerende inflammatoriese selle, asook deur beseerde spier vesels afgeskei. Volwasse skeletspier bevat ‘n populasie stamselagtige selle, sogenoemde satelliet selle. Laasgenoemde word geaktiveer, prolifereer en differensieër volgende spierbesering, om sodoende herstel van beskadigde spier te weeg te bring. Baie navorsing op die effekte van TNFα op satelliet sel differensiasie is onlangs uitgevoer. Dit is egter aansienlik moeilik om volgens hierdie navorsing‘n algehele beeld van TNFα se aksies te vorm aangesien alle modelle wat gebruik word verskil. Ons doel was daarom om ‘n omvangryke assessering van toenemende konsentrasies kronies gesupplementeerde TNFα op differensieërende C2C12 selle op ‘n enkele model uit te voer. Selle was vir 7 dae met of sonder TNFα supplementasie gedifferentieër. Differensiasie was by Dag 0 geïnduseer. TNFα se effek op differensiasie is op dae 1, 3, 5, en 7 deur middel van western blot analise geassesseer. Aanvullende immunohistochemiese bepalings op dae 1, 4, en 7 is verder deurgevoer. Merkers vir differensiasie het die spier regulatoriese faktore MyoD en miogenien, sel siklus merkers p21 en PCNA, asook die integrale sein transduksie molekule p38MAPK ingesluit. TNFα supplementasie by dag 1 het geneig om vroeë merkers van differensiasie positief te reguleer. Met voortdurende supplementasie is die vroeë positiewe effekte (op ‘n dosis afhanklike manier) egter omgekeer: ‘n neiging teenoor (‘n dosis afhanklike) vermindering in MyoD, miogenien en p21 proteïen het in behandelde kulture op dae 3, 5, en 7 bestaan. Hierdie bevindinge was beduidend by dag 5 (p21, p<0.05), en dag 7 (miogenien, p<0.05). A beduidende dosis afhanklike afname in p38 fosforilasie was duidelik by dag 3 (p<0.05), terwyl fosfo-p38 by dag 7 verhoog het met verhoogde konsentrasie TNFα (p<0.05). Bogenoemde saamgevat, dui aan dat TNFα supplementasie 24h volgende die induksie van differensiasie in vitro, verhoogde vlakke van vroeë differnsiasie merkers te weeg bring. Met voortdurende TNFα supplementasie, word differensiasie merkers egter met toenemende dosis verminder. Hierdie studie voorsien ‘n omvattende karakterisering van die dosis- en tyd afhanklike effekte van TNFα op satelliet sel differesiasie in vitro. Die model sisteem in hierdie studie gebruik, maak afleidings oor meer kroniese siektetoestande moontlik.
4
Johansson, Jan Å. „Psychosocial factors at work and their relation to musculoskeletal symptoms“. Lund : Dept. of Psychology, Göteborg University, 1994. http://catalog.hathitrust.org/api/volumes/oclc/39775906.html.
5
Stover, Bert D. „Validation and evaluation of a disability measure for upper extremity musculoskeletal disorder screening in the workplace and prognostic factors of long-term disability /“. Thesis, Connect to this title online; UW restricted, 2004. http://hdl.handle.net/1773/5407.
6
Wilkin, Linda Diane. „Rehabilitative influence of therapeutic ultrasound treatment on cellular markers of skeletal muscle regeneration following blunt contusion injury /“. The Ohio State University, 2002. http://rave.ohiolink.edu/etdc/view?acc_num=osu1486463321624146.
7
Leslie, Shirae. „An Injectable Stem Cell Delivery System for Treatment of Musculoskeletal Defects“. VCU Scholars Compass, 2016. http://scholarscompass.vcu.edu/etd/4472.
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The goal of this research was to develop a system of injectable hydrogels to deliver stem cells to musculoskeletal defects, thereby allowing cells to remain at the treatment site and secrete soluble factors that will facilitate tissue regeneration. First, production parameters for encapsulating cells in microbeads were determined. This involved investigating the effects of osmolytes on alginate microbead properties, and the effects of alginate microbead cell density, alginate microbead density, and effects of osteogenic media on microencapsulated cells. Although cells remained viable in the microbeads, alginate does not readily degrade in vivo for six months. Therefore, a method to incorporate alginate lyase in microbeads was developed and optimized to achieve controlled release of viable cells. Effectiveness of this strategy was determined through cell release studies and measuring proteins and expression of genes that are characteristic of the cell’s phenotype. Lastly, in vivo studies were done to assess the ability of alginate microbeads to localize microencapsulated cells and support chondrogenesis and osteogenesis. This project will provide insight to the tissue engineering field regarding cell-based therapies and healing musculoskeletal defects.
8
Spielholz, Peregrin. „A comparison of upper extremity physical risk factor measurement methods /“. Thesis, Connect to this title online; UW restricted, 1999. http://hdl.handle.net/1773/8468.
9
Byington, Randy L., Shane Keene, Ester L. Verhovsek und Jessica Depew. „Arthrogryposis Multiplex Congenita: A Review of Treatment Options for the Lower Extremities“. Digital Commons @ East Tennessee State University, 2012. http://ispub.com/IJWH/7/2/13981.
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Arthrogryposis, a congenital disorder characterized by multiple joint contractures, can limit one’s ability to perform even the simplest of tasks. The purpose of this paper is to outline the general limitations associated with arthrogryposis and examine the most common corrective procedures used to treat and manage deformities of the lower extremities. While the ultimate goal may be complete correction of the associated deformities, this may not be practical, as recurrence of contractures is common. Surgical and non-surgical methods discussed in this paper include casting with the Ponseti Method, use of bracing and night splinting, soft tissue release for the ankle and knee, talectomy and osteotomy procedures for the knee. The conclusions discussed in this paper determine that complete correction is not typically obtained, but quality of life can be improved through functional independence and ambulation when utilized in conjunction with thorough physical therapy rehabilitation.
10
Renz, Miriam Christina. „Laboratory investigation of a simulated industrial task pre- and post-ergonomics intervention“. Thesis, Rhodes University, 2004. http://hdl.handle.net/10962/d1015806.
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The focus of the present study was on the investigation of the effects of an intervention strategy on an industrial task in situ and a simulation of the same task within a laboratory setting. The task of offloading crates from a truck at a local business was simulated in a laboratory setting for rigorous analysis. The effect of an ergonomically sound intervention on selected physical, physiological and perceptual variables was evaluated in a test - retest experimental set-up using 28 young, healthy male students. Each of the two experimental conditions lasted for 16 minutes. In the pre-intervention task subjects were required to transfer the crates from one point to another by sliding them along the floor. During the execution of the post-intervention task responses to reductions in the stacking height and modifications of the working method were evaluated. Results obtained for spinal kinematics during the simulated industrial task indicated a high biomechanical risk, due to large ranges of motion, high velocities and accelerations in the sagittal and transverse planes. The heavy workload of the task was also evident in elevated physiological responses (HR, RF, VT, VE, VO2, RQ, EE) and perceptual ratings (RPE, Body Discomfort). Assessment of the intervention strategy revealed that the high risk industrial task was reduced to moderate acceptable, with measurements of spinal kinematics, physiological and perceptual variables being significantly reduced. An in situ re-assessment of the workers responses to the intervention also elicited reductions in heart rates and perceptual ratings compared to the original task.
11
Pagano, Stefanie L. „The Effect of Varying Bisphosphonate Treatment on Changes in Bone Microdamage in Osteoporotic Women“. UKnowledge, 2016. http://uknowledge.uky.edu/cbme_etds/40.
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Bisphosphonates (BPs) are used for the treatment of osteoporosis. This study evaluated changes in bone microdamage with BP treatment duration. Fifty-one iliac crest biopsies were obtained from Caucasian women, ages 41 to 87 years, who were previously diagnosed and treated for osteoporosis with oral BPs for 1-16 years duration. Patients diagnosed with any disease, drug, or substance abuse that may affect bone metabolism were excluded.
Bone samples were sectioned, stained, and histologically examined using light and fluorescence microscopy. Bone area, number and length of microcracks were quantified. Following adjustment for age, BMD, BV/TV, trabecular thickness, and turnover, regression analysis revealed a relationship between microcrack density and treatment duration (p=0.018). No significant relationship was observed between microcrack length and treatment duration.
This study provides novel data relating microdamage with varying BP treatment duration in human bone. Given information from other studies showing that microdamage amounts are related to changes in bone biomechanics, the BP treatment duration related changes in microdamage shown offer new information that may help optimize osteoporosis treatment.
12
Dillard, E. Margo (Edna Margo). „An Epidemiological Survey of Musculoskeletal Pain Among a Self-Selected Population of Organists“. Thesis, University of North Texas, 1998. https://digital.library.unt.edu/ark:/67531/metadc935779/.
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The purpose of this study was to investigate problem areas of organists' performance as indicated by common experiences of pain. The research problems were to determine the specific areas of the body that were affected by pain, to determine the perceived level of that pain on a scale indicative of its severity, and to explore the relationship between demographic and performance-related factors within the population and specific area of reported pain. An examination of the demographic, performance-related, and pain data, as well as subject comments, indicated possible relationships of the pain experience to other factors. Organists attributed their pain to instrument characteristics, such as keyboard action, music rack height, bench design, and pedalboard shape. Pain was also associated with the time spent playing the organ, playing literature which required large reaches and rapid passage work, such as french toccatas, or playing with incorrect posture. To explore these relationships to spinal and upper extremity pain, further research is indicated.
13
Jones, Daryl Rhys. „Treatment of prion diseases with camelid antibodies“. Thesis, Royal Veterinary College (University of London), 2013. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.618290.
14
Alkhatib, Thabat. „The potential of retinoids in the treatment of neurodegenerative diseases“. Thesis, University of Aberdeen, 2018. http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=236959.
15
Lam, Lap-fung, und 林立峰. „Flow cytometric analysis of intra-platelet VASP for evaluation of clopidogrel resistance in ischemic heart disease patients undergoingpercutaneous coronary intervention“. Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2012. http://hub.hku.hk/bib/B48421200.
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Ischemic heart disease (IHD) is the most common cause of death around the world. The underlying cause of IHD is myocardial ischemia as a result of progressive narrowing of coronary arteries due to atherosclerosis with potential thrombotic complications mediated by platelets. In addition to the role in hemostasis, platelets are increasingly recognized as an important mediator in this atherothrombotic disease. Basic management of IHD lies on medical therapy and coronary revascularization procedures. Percutaneous coronary intervention (PCI) is a commonly used revascularization procedure in the treatment of IHD especially for relief and reduction of symptoms. On the other hand, antiplatelet therapy is often administrated to patients undergoing PCI in an attempt to prevent major adverse cardiac events (MACE) following the procedures. However not all patients respond to the same degree of the antiplatelet therapy and some still develop MACE or stent thrombosis in the presence of the treatment with antiplatelet drugs.
Recently a flow cytometric-based assay has been developed to monitor the effect of the antiplatelet drug, particularly the P2Y12 receptor antagonist, in patients treated with this kind of drug. This assay measures the activity of platelets as platelet reactivity index (PRI) based on the phosphorylation state of an intracellular platelet protein called vasodilator stimulated phosphoprotein (VASP). The measured value of PRI is inversely related to the response of patient to the antiplatelet drug.
In this study, the response of patients to the P2Y12 receptor antagonist Clopidogrel was investigated following PCI. The PRI of patients was found to be significantly lower than normal subjects without taking this drug, indicating the therapeutic effect of this drug on the patients. However nearly one-third of patients (17 out of 59) studied were found to be non-responsive to clopidogrel treatment based on a cut-off established in this study for classifying patients into responders or non-responders. Furthermore, significant difference between the two types of stents used in PCI procedure, namely bare metal stent (BMS) and drug eluting stent (DES), was observed in the study. Patients receiving DES had nearly three times higher percentage of being non-responsive to clopidogrel than the BMS counterpart (45% vs. 16%, p<0.028). This study provides evidence that DES may be implicated in the non-responsiveness or drug resistance of clopidogrel in patient undergoing PCI.published_or_final_version
Pathology
Master
Master of Medical Sciences
16
Baloch, Baby Kanwal. „Development of a targeted drug delivery system for the treatment of hepatitis C virus infection“. Thesis, University of Nottingham, 2012. http://eprints.nottingham.ac.uk/14295/.
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Background: Hepatitis C virus infection affects more than 170 million people worldwide and is frequently associated with chronic liver disease and hepatocellular carcinoma. No protective vaccine is yet available and the current standard of care, consisting of pegylated interferon alpha and ribavirin, has limited efficacy. Ribavirin is a key component of any effective anti-HCV regimen. However, accumulation of ribavirin in the red cell compartment not only reduces drug efficacy as a result of diversion to extra-hepatic sites but also produces haemolytic anaemia which can lead to dose reduction or discontinuation of treatment. Lipid or polymer based nanoparticles can be used to deliver therapeutic agents, such as drugs or small interfering RNAs (siRNAs) directly to their site of action. We therefore elected to develop new antiviral strategies based on the targeted delivery of ribavirin to hepatocytes, coupled with the identification of new therapeutic targets. In order to inform the rational use of direct intracellular delivery of ribavirin, we enquired whether variation in expression of the ribavirin transporter may determine drug uptake and permit the identification of individuals who would benefit from these alternative approaches to treatment. Aims: The aims of this study were to: • identify host proteins involved in virus replication • demonstrate reduction of viral replication by modulation of host gene expression • develop and test a nanoparticle based system for the delivery of therapeutic molecules, including siRNAs either alone or in combination with ribavirin. • assess the relationship between ribavirin uptake by primary human hepatocytes and expression of ribavirin receptors Methods: A subgenomic HCV replicon system was established to study the virus-host relationship and identify host proteins supporting viral replication by using stealth siRNA. Viral RNAs were in vitro transcribed and transfected into Huh7 cells and expression assessed using engineered GFP as a reporter gene. siRNAs were co-transfected with viral RNAs using a nucleofector. Modulation of host gene expression was measured by both quantitative RT-PCR and protein blotting. Liposomal nanoparticles containing ApoB-100 duplexes were supplied by Lipoxen. Primary human hepatocytes were isolated by a modified two step collagenase perfusion method and cultured on collagen coated plates. HPLC and real time PCR conditions were used to measure and correlate drug uptake and receptor expression respectively. Equilibrative nucleoside transporter (ENT1) gene was analysed by direct sequencing. Results: A JFH1 (HCV genotype 2a) virus based subgenomic replicon system was successfully established. Using this model system, host proteins VAP-A and STAT3 were shown to positively regulate virus replication while ACTN1 had no effect. Liposomes failed to deliver either siRNA targeted at apoB-100 or ribavirin and this was found to be due to structural instability of the delivery vehicle. In contrast, fluorescently labelled liposomes were stable and could be taken up by human hepatocyte cell lines under optimised conditions. A protocol capable of efficient isolation and culture of hepatocytes from human donor was validated. Data from primary human hepatocytes show that ENT1 expression was highly variable in different sets of primary livers and correlated strongly with ribavirin uptake. Strikingly, Huh7 cells did not take up ribavirin despite expressing wild type ENT1. It was also found that interferon alpha does not modulate ENT1 expression and therefore ribavirin uptake, suggesting it to be a highly unlikely mode of synergism between the two drugs. Conclusion: Modulation of host proteins VAP-A and STAT3 inhibited viral replication, confirming that host genes can be used as a potential target to inhibit viral replication. Liposomes used in this study were, however, found to be ineffective vehicles for the delivery of ribavirin or siRNA, as the majority of drug leaked before cellular uptake. Polymer based nanoparticles are currently being assessed for antiviral drug delivery. Variation in ENT1 expression may account for differences in response rate in patients receiving anti-HCV therapy. Results in the Huh 7 cell line suggest that, while ENT1 is necessary, other factors are also required to mediate ribavirin uptake.
17
Ronga, Evangelia. „The ecology, pathology and treatment of Discocotyle sagittata (Leuckart, 1842) in an intensive aquaculture system“. Thesis, University of Liverpool, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.281991.
18
Chan, Rebeca, und 陳懿雯. „A systematic review on the effectiveness of the first-line treatment of gastroesophageal reflux disease in H. pylori infected patients“. Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2011. http://hub.hku.hk/bib/B47559895.
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Helicobacter pylori (H.pylori) had been confirmed by the World Health Organization (WHO) as Group 1 carcinogens, in which it has been identified to be related with the development of gastric carcinoma. Gastroesophageal reflux disease (GERD) is less commonly found in Asia, while the number of H.pylori infection is considerably to be higher than that of the Western population. The relationship between H.pylori and GERD still remains ambiguous nowadays. One of the contributing factors affecting the level of gastric secretion might be due to the genetic cause. The aim of this review is to assess whether the current first-line therapy on GERD would be effective or not in relieving the symptoms of the patients with H.pylori infection.published_or_final_version
Community Medicine
Master
Master of Public Health
19
Furlan, Roberto. „Development of herpesvirus-based vectors for the treatment of central nervous system autoimmune diseases“. Thesis, Open University, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.342890.
20
Ngcamu, Nokubonga Slindele (Sma). „Awkward working postures and precision performance as an example of the relationship between ergonomics and production quality“. Thesis, Rhodes University, 2009. http://eprints.ru.ac.za/1561/.
21
Larsman, Pernilla. „On the relation between psychosocial work environment and musculoskeletal symptoms : a structural equation modeling approach /“. Stockholm : Arbetslivsinstitutet, förlagstjänst, 2006. http://ebib.arbetslivsinstitutet.se/ah/2006/ah2006_02.pdf.
22
Cho, Jinsoo. „Velocity-based cardiac segmentation and motion-tracking“. Diss., Available online, Georgia Institute of Technology, 2004:, 2003. http://etd.gatech.edu/theses/available/etd-04082004-180106/unrestricted/cho%5Fjinsoo%5F200312%5Fphd.pdf.
23
Bell, Alison. „An ergonomic analysis of vacuum cleaning tasks using observational risk assessment tools“. School of Health Sciences - Faculty of Health & Behavioural Sciences, 2008. http://ro.uow.edu.au/theses/126.
Annotation:
This research thesis examined the risk of upper limb musculoskeletal disorders for cleaning workers while performing vacuum cleaning tasks in the normal course of their employment. The cleaning workers in this study were from three sectors of the workforce – government schools, hospitality and commercial office space. The vacuum cleaning tasks were divided into those performed with a back pack style vacuum cleaning machine and those using a canister/barrel machine. Three observational risk assessment tools were selected to measure the risk of these tasks to cleaning workers. The selected tools were the Manual Tasks Risk Assessment Tool (ManTRA) version 2.0; the Quick Exposure Check (QEC) (Li & Buckle, 1998); and the Rapid Upper Limb Assessment tool (RULA) (McAtamney & Corlett, 1993). Results of this thesis study demonstrated that vacuum cleaning is a risk to the musculoskeletal health of cleaning workers, with some variation between the tool ratings, reflecting the specificity and/or sensitivity of each tool. Differences were found between the three cleaning sectors in terms of overall risk posed by vacuum cleaning tasks. The sector with the greatest risk was found to be the government school cleaners, followed by the hospitality and then commercial office space cleaning sectors. The ‘risk experience’ difference between the sectors cannot be attributed only to vacuum cleaner characteristics, but also, the environment and length of shift worked by the cleaning staff. Further research is required to determine the difference in risk exposure between the two types of vacuum cleaner (back pack and canister).
24
陳潔兒 und Kit-yee Brenda Chan. „Making it a practice: a pre-admission pre-operation education programme for patients on elective CABG“. Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2008. http://hub.hku.hk/bib/B40720111.
25
Lai, Wing-hon Kevin, und 黎永漢. „Generation of vasculogenic progenitor cells from human induced pluripotent stem cells for the treatment of cardiovascular diseases“. Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2013. http://hdl.handle.net/10722/197112.
Annotation:
Pluripotent stem cells hold great promise in regenerative medicine. Theoretically, a variety of tissues can be generated from this progeny. The production of tailor-made stem cells for individualized patient treatment is the ultimate goal of stem cell based therapy. Human induced pluripotent stem cells (iPSCs) hold the precious key to success and promote the clinical application of stem cells. By reprogramming somatic cells, pluripotent stem cells can be generated in a patient-specific manner and subsequently differentiated into specific tissue for regeneration. Nonetheless exposure of hiPSCs to animal feeder cells and serum during generation and maintenance imposes a risk of transmitting animal pathogens to human subjects, thus hindering their potential therapeutic application. In addition, the efficacy of iPSC generation is < 1% of total somatic cells used. The first part of the study focused on the development of improved methods to produce a more efficient xenogen-free culture system to produce more clinically compatible iPSCs.
Specific tissue or cells derived from stem cells may offer a solution and cell therapy using endothelial cells and their progenitors may be possible in treatment of severe cardiovascular diseases. In theory, endothelial cells can be generated from different sources of progenitor cells although no direct comparison of these various derived endothelial cells (ECs) has been reported. Thus in the second part of the study, the functional and physiological properties of BM, ESC and iPSC-ECs will be evaluated to determine their therapeutic potential in ischemic disease. A mouse hind limb ischemia model was used to assess and monitor neovascularization by the derived ECs. The results can provide further insight to evaluate the possibility of using iPSCEC as the cell source for patient-specific treatment.
Use of pluripotent stem cells is a promising approach in therapeutic angiogenesis although numerous hurdles continue to hamper their widespread clinical use. Conditioned medium derived from progenitor cells may be another possible strategy in the treatment of ischemic diseases such that direct cell transplantation is avoided.
Conditioned media produced from ex vivo culture of endothelial cells contain a combination of angiogenic factors that can be applied to promote neovascularization in ischemic tissue. Nonetheless the efficacy of this angiogenic application is unknown. The third part of the study focused on the potential application of EC-derived conditioned media in the treatment of ischemic disease using a mouse hind limb ischemia model. Some cardiovascular risk factors such as diabetes might affect endothelial cell function such that autologous application of ECs and their conditioned media is not feasible. A human embryonic stem cell line may offer and alternative means to obtain stable quality ECs and conditioned medium for therapeutic use.
In summary, advances in stem cell technology hold great promise for the treatment of cardiovascular disease, further improved by the generation of patient-specific stem cells using iPSC technology. Vascular cells can be generated from different sources of stem cells with similar angiogenic properties and may be used in the treatment of ischemic diseases.published_or_final_version
Medicine
Doctoral
Doctor of Philosophy
26
Awotedu, Kofoworola Olajire. „Functional changes of the vasculature in HIV/AIDS patients on Haart and Haart Naïve HIV participants“. Thesis, Walter Sisulu University, 2013. http://hdl.handle.net/11260/185.
Annotation:
The present study sought to explore the functional changes that occur in the vasculature of HIV positive participants of African origin in Mthatha district of South africa which might lead to increased risk in their cardiovascular system. Available literature shows that arterial stiffness plays an important role in cardiovascular events such as stroke, vasculitis and myocardial infarction. Measurement of (aortic pulse wave velocity; PWV) provides some of the strongest evidence concerning the prognostic significance of large artery stiffening. This study was aimed at investigating the relationship between anthropometry, age, E-Selectin level, cytokine levels, haemodynamic variables, blood counts and blood lipid profile with pulse wave velocity. Some traditional cardiovascular risk factors such as alcohol, and smoking were also taken into account. This was a cross-sectional study comprising of 169 participants (62 males and 107 females). 63 were HIV negative (group A), 54 HIV positive on treatment (group B), and 52 were HIV positive not on treatment (group C). Pulse wave velocity (PWV) was assessed using the Sphygmocor Vx. Statistically, ANOVA was used for variables with normal distribution and non parametric tests were used for variables with skewed distribution. Notable significant differences were seen in the means of the following variables across all the 3 groups. Conclusion: This study showed that HIV infected patients with or without antiretroviral therapy have increase arterial stiffness which is associated with an increased cardiovascular risk. The sphygmocor is an accurate, non invassive and useful tool in the evaluation of arterial stiffness and its use in clinical practice should be encouraged. PWV and the augmentation index (AIx) are the two major non- iv invasive methods of assessing arterial stiffness. Life style modification should be incorporated into the management of HIV patients so as the continuous monitoring of their haematological and lipid profile.
27
Mitchell, Kierra. „Racial Disparities in the Diagnosis and Treatment of Type 1 Diabetes in Black American Youth“. Scholarship @ Claremont, 2019. https://scholarship.claremont.edu/scripps_theses/1239.
Annotation:
Introduction: Rates of childhood-onset type 1 diabetes (T1D) are steadily increasing among American youth, yet Black Americans are more likely to suffer from serious T1D-related complications caused by poor glycemic control. The aim of this thesis is to determine the external factors that are causing discrepancies in the development, diagnosis, treatment, and long-term management of T1D in Black youth.
Methods: Epidemiological studies were compiled from the American Diabetes Association, Center for Disease Control (CDC), International Diabetes Foundation (IDF), Kaiser Family Foundation (KFF), and the Claremont Colleges Library network to identify the sociocultural aspects that negatively affect long-term glycemic control in Black youth.
Results: Studies indicate that Black youth with T1D are more likely to face disadvantages in treatment regimen which are attributed to insurance coverage, socioeconomic status, education level, and implicit bias. Most studies demonstrate that these factors result in poor glycemic control, which subsequently leads to severe dysglycemia-related complications later in life.
Conclusion and Discussion: Many Black youth who suffer from T1D receive insufficient healthcare, which is often exacerbated by a lack of social and economic resources. As a result, they may not have the means to maintain consistent, healthy glycemic levels. System-level changes are necessary to change the morbidity and mortality of T1D in Black youth. Future research should include the analysis of other racial minority groups in order to uncover additional institutional disparities.
28
Genes, Nicholas G. „Chondrocyte Adhesion to RGD-bonded Alginate: Effect on Mechanotransduction and Matrix Metabolism: a Dissertation“. eScholarship@UMMS, 2003. https://escholarship.umassmed.edu/gsbs_diss/89.
Annotation:
The mechanism of mechanotransduction in chondrocyte matrix metabolism is not well understood, in part because of the density of cartilage and in part because of limitations in in vitroculture systems. Using alginate covalently modified to include the integrin adhesion ligand R-G-D (arginine-glycine-aspartate) represents a unique approach to studying mechanotransduction in that it allows for exploration of the role of integrin adhesion in mediating changes to chondrocyte behavior.
The hypothesis of this research was that chondrocytes will form a cytoskeletal adhesion to RGD-alginate mediated integrins, that this attachment will enable chondrocyte sensation of mechanical signals, and this signaling will alter chondrocyte matrix metabolism. The first aim of this research was to characterize chondrocyte attachment to RGD-alginate, and assess the role of substrate mechanics on chondrocyte attachment kinetics and morphology. Secondly, the effect of chondrocyte attachment to RGD-alginate in 3D culture on matrix biosynthesis was assessed, as were changes in substrate mechanics. Finally, this research aimed to determine the metabolic response of chondrocytes to changes in intrinsic and extrinsic mechanics.
It was found that the RGD ligand functionalized the alginate scaffold, enabling chondrocytes to sense the mechanical environment. Attachment kinetics, morphology, and proteoglycan metabolism were found to adapt to hydrogel matrix stiffness when an integrin adhesion was present. Externally applied compression was transmitted through this integrin attachment, causing changes in proteoglycan synthesis. Components of media serum were found to modulate the effects of integrin mechanotransduction.
These results were obtained by analyzing a novel approach with established techniques, such as the DMB dye assay for sulfated GAG content. The conclusions conform to diverse data from cartilage explant loading and monolayer culture studies, yet were accomplished using one versatile system in a straightforward manner. The potential of this system extends further, into identification of intracellular signaling pathways and extracellular modulation of matrix components. Seeded RGD-alginate is well suited for studying consequences of integrin attachment.
29
Matzelle, Melissa M. „Inflammation Inhibits Osteoblast-Mediated Bone Formation in Rheumatoid Arthritis and Regulates the Wnt and BMP Signaling Pathways: A Dissertation“. eScholarship@UMMS, 2012. https://escholarship.umassmed.edu/gsbs_diss/596.
Annotation:
Osteoclast-mediated focal articular bone erosion is a hallmark of rheumatoid arthritis, a disease of inflammation-induced bone loss. Inflammation in the bone microenvironment enhances osteoclast differentiation leading to bone erosion. Simultaneously, inflammation also inhibits osteoblast-mediated bone formation, further contributing to the net loss of bone. Previous studies have shown a paucity of mature osteoblasts at eroded bone surfaces correlating with suppression of bone formation and upregulation of antagonists of the Wnt pathway, a signaling cascade essential for osteoblast lineage commitment. Despite these observations, the exact pathogenesis of impaired bone formation in the setting of inflammation is not clearly understood.
This dissertation aims to delineate the mechanisms by which inflammation suppresses osteoblast differentiation and activity in inflammatory arthritis. Specifically, this research elucidates how inflammation-induced alterations in the Wnt and bone morphogenetic protein (BMP) osteogenic signaling pathways contribute to bone loss and formation at distinct inflammatory microenvironments within the bone. Secondly, the means by which cellular mediators, including lymphocytes and macrophages, facilitate bone erosion and formation was addressed.
Taken together, the research in this dissertation underscores the relationship between inflammation-induced bone loss and alterations in osteogenic signaling. Using an innovative murine inflammatory arthritis model, this study definitively demonstrates that resolving inflammation promotes osteoblast-mediated bone formation. Repair of erosions correlates with upregulation of synovial expression of Wnt10b, a Wnt agonist, and downregulation of sFRP1 and sFRP2, Wnt antagonists. This work also directly evaluates the contribution of sFRP1 to inflammation-induced bone destruction. Furthermore, this research demonstrates that expression of BMP3, a negative regulator of BMP signaling, is upregulated in osteoblasts by IL-17, a pro-inflammatory cytokine. BMP3-expressing osteoblasts are also observed at erosion sites in murine arthritis. Lastly, evaluation of the mediators of inflammation-induced periosteal bone formation implicates BMP2 as a means by which inflammation may positively regulate osteoblast function.
This dissertation further elucidates the role of T cells and macrophages in the erosion and formation processes, respectively. In the absence of lymphocytes, bone erosion occurred normally, demonstrating that RANKL-expressing lymphocytes are not absolutely required for the bone erosion. Preliminary studies also suggest that M2 macrophages are potential mediators of bone formation via the expression of BMP2.
In conclusion, this dissertation explores the ability of inflammation to act as a rheostat, which controls the fate of bone by modulating not only osteoclast differentiation, but also osteogenic signaling pathways and cellular mediators in the bone microenvironment. The soluble mediators and cell types identified in this research highlight novel mechanisms by which inflammation may regulate osteoblast activity within the bone microenvironment. Collectively, these data imply that strict control of inflammation may be necessary in order to create an anabolic environment that preserves bone architecture in diseases of inflammation-induced bone loss.
30
Briggs, Virginia G. „Injection Treatment for Lower Back Pain in Older Adults with Lumbar Spinal Stenosis: A Dissertation“. eScholarship@UMMS, 2009. https://escholarship.umassmed.edu/gsbs_diss/439.
Annotation:
Background:Lower back pain is one of the most common health-related complaints in the adult population. Thirty percent of Americans 65 years and older reported symptoms of lower back pain in 2004. With an aging population, the proportion of people over the age of 65 is expected to reach 20% by the year 2030. Because of this increase in older adults, lumbar spinal stenosis (LSS) associated with arthritic changes will also likely increase. In older adults, lower back pain is most often caused by degenerative lumbar spinal stenosis. Stenosis is the narrowing ofthe spinal canal, causing pressure on the nerve roots and is frequently treated surgically. Lumbar spinal stenosis is one of the most common reasons for back surgery in patients 65 years and older 2. However, risks associated with surgery increase with age 3-5 and older patients may choose non-surgical treatment for their lower back pain, including injection treatment.
Injection treatment, usually consisting of anti-inflammatory medications and analgesics, has improved since the mid-1990's when fluoroscopic guidance was developed. Information about injection treatment for lower back pain is limited, especially in the older population. An extensive review of published literature regarding injection treatment revealed a paucity of information about older adults diagnosed with lumbar spinal stenosis. In this study, three aims were designed to gain more information about the effectiveness of injection treatment in older patients with lumbar spinal stenosis. In the first (retrospective) study, information about receipt of second injections and time between injections was collected to examine injection usage. In the second and third (prospective) studies, information about pain relief and functional return following injection treatment was collected to examine the effectiveness of injection treatment in patients age 60 and older diagnosed with lumbar spinal stenosis. To our knowledge, such results have not been repolted for this population in the literature.
Objective:Injection treatment is a commonly used non-surgical procedure to alleviate lower back pain in older adults. However, older patients do not have enough information about how long pain relief will last after treatment or the amount of pain relief and functional return they will experience. These studies focused on three topics: 1) usage of injection treatment; 2) effectiveness of injection treatment on pain relief; 3) effectiveness of injection treatment on functional return. In addition, the variations of the effectiveness were examined by selected patient attributes.
Methods:In a retrospective study, medical records of patients aged 60 years or older from a high volume dedicated spine center at the University of Massachusetts Memorial Hospital were retrospectively reviewed. This study included those diagnosed with degenerative LSS, who had not received an injection for lower back pain within six months, and whom were treated between June I, 2006 and May 31, 2007.
In two prospective studies, patients scheduled for lumbar injection treatment between January 1 and June 30, 2008 were selected from the University of Massachusetts Memorial Hospital Spine Center. Selection criteria included patients age 60 and over, diagnosed with degenerative lumbar spinal stenosis and no previous lumbar injection within 6 months or lumbar surgery within 2 years. The Pain sub-score of the SF-36 questionnaire was used to measure pain at baseline and at one and three months post injection. The Physical Component Score (PCS) of the SF-36 questionnaire and the Oswestry Disability Index (ODI) were used to measure function at baseline and at one and three months post injection. Variations in longitudinal changes in scores by patient characteristics were analyzed in both unadjusted (univariate) analyses using one-way analysis of variance (ANOVA), and adjusted (multiple regression) analyses using linear mixed effects models.
Results: In the retrospective cohort, the mean age of the cohort was 68, 64% were female, 59% were married, with a mean Body Mass index of 32 kg/m2. Of 92 eligible patients, 57% returned for a second injection within six months of the first. The mean number of months between injections was 4.8 for all patients, ranging from 1 to 22 months. When patient characteristics were examined, the only variable that showed a statistically significant difference was age. Patients aged 70 years and older were found to be 67% less likely to return for a second injection when compared to patients age 60-69 (OR=0.33 (0.12 - 0.94)p In the prospective cohort, information was collected on 62 patients. Mean Pain scores improved significantly from baseline to one month (14.1 points), and from baseline to three months (8.3 points). Post injection changes in Pain scores varied by Body Mass Index (BMI) and baseline emotional health. Based on a linear mixed effects model analysis, higher baseline emotional health, as measured by the SF-36 Mental Component Score (MCS>50), was associated with greater reduction in pain over three months when compared to lower emotional health (MCS Conclusion: Patients over age 70 do not return for repeat injection as frequently as patients age 60-69. In addition, each year a patient ages over age 60, they are 10% less likely to return for a repeat injection. Lower back pain in older adults with LSS is clinically significantly alleviated after injection treatment. In addition, injection treatment for LSS is associated with return of lost function needed for daily living activities in older adults. Pain relief and functional return varies by patient personal and clinical characteristics. Higher emotional health was associated with more pain relief and more functional return experienced over three months following injection treatment. Additional information is needed about why older patients do not return for second injections at the same rate as younger patients and how emotional health affects response to injection treatment in older adults.
31
Wang, Kai, und 王凱. „Structure-function and physiological properties of HCN-encoded pacemaker channels“. Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2007. http://hub.hku.hk/bib/B39557273.
32
Skelton, Sarah Anne. „Combined and additive effects of assembly tasks and constrained body postures“. Thesis, Rhodes University, 2007. http://hdl.handle.net/10962/d1005185.
Annotation:
Despite extensive research into musculoskeletal disorders (MSDs) they continue to plague workers. Manual materials handling (MMH), in particular the concurrence of load manipulation and awkward body posture, has been identified as a key factor in the onset of MSDs. Only a few studies have looked at the interaction between manipulation tasks and working posture during assembly tasks and as a result their relationship has not been widely explored. Assessing the stresses resulting from individual task factors and body posture in isolation and adding them together may be too simplified to estimate an overall risk profile, since this does not take into account that there may be a non-linear interaction in strain responses when manipulation task and body posture interact. Therefore, the present study investigated biophysical, physiological and psychophysical responses to combined tasks, rather than individual tasks of body posture and manipulative tasks. The objective of the research was to establish the interactive effects of constrained body postures and manipulative tasks and to identify whether a cumulative or compensatory reaction occurs during this interaction. Nine conditions were assessed in a laboratory setting, which included combinations of three working postures (standing, sitting and stooping) and three assembly tasks (torque wrenching, precision and no task). Thirty-six subjects were required to complete all nine conditions, with each condition lasting ninety seconds. Muscle activity was recorded for seven muscles from the upper extremity, trunk and lower extremity regions and was complemented by physiological (heart rate, tidal volume, minute ventilation, oxygen consumption, energy expenditure and breathing frequency) and psychophysical (body discomfort) data. At the completion of all nine conditions subjects completed a retrospective psychophysical rating questionnaire pertaining to discomfort felt during the conditions. Responses obtained for the different task and posture combinations revealed compensatory reactions (additive > combined) for most of the conditions assessed for the biomechanical and physiological responses. In the majority of cases for muscle activity, no significant differences were found between the combined and the additive effects (p < 0.05), while for the physiological responses there were mostly significant differences observed. Psychophysical responses indicated that there was a significant difference overall between the additive and combined effects. The results of this study demonstrate that in order to identify risk areas, manipulation tasks and constrained working postures may be considered either in isolation and added together (additive) or as a combined task, since there were very few significant differences observed between these two effects. Further studies are required, however, to provide conclusive evidence.
33
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.
34
Wong, Shing Chau. „Treatment of neuropathic pain : by Chinese scorpion (Buthus martensii Karsch)“. HKBU Institutional Repository, 2011. https://repository.hkbu.edu.hk/etd_ra/1439.
35
Hott, Morgan E. „Cartilage tissue engineering: uses of injection molding and computer aided design for the fabrication of complex geometries with high dimensional tolerances: a dissertation“. eScholarship@UMMS, 2007. https://escholarship.umassmed.edu/gsbs_diss/325.
Annotation:
Cartilage Tissue Engineering. Joint pain and functional impairment due to cartilage damage from osteoarthritis and other means is a major source of disability for adults the world over. Cartilage is an avascular tissue with a very limited capacity for self repair. Current medical and surgical approaches to cartilage repair also have limited efficacy, and in all cases fail to completely restore a normal, healthy cartilage phenotype. Tissue engineering is a relatively new approach to cartilage repair that seeks to fabricate a replacement tissue, indistinguishable from healthy, native tissue.
The basic idea of the tissue engineering approach is to seed tissue synthesizing cells into a shapeable, biocompatible/bioabsorbable scaffold that serves as a temporary extracellular matrix with a localized source of bioactive molecules to direct the development of new tissue. The challenge of tissue engineering is to identify cells, scaffolds, and growth conditions that will be optimal for tissue regeneration. The goal of the current studies was to evaluate one aspect of all three of the major components of cartilage tissue engineering: cell source, scaffolding material and preparation, and controlled growth factor delivery.
We evaluated the chondrogenic potential of human nasal chondrocytes grown in calcium alginate in an in vivo culture system, the potential of computer-aided design and injection molding with calcium alginate to reliably reproduce complex geometries with high dimensional tolerances, and the potential for the controlled release of TGF-β1 from calcium alginate modified by the covalent addition of a recently discovered TGF-β binding peptide.
We found that adult human nasal chondrocytes show significant chondrogenic potential when grown within an alginate scaffold. We also found that alginate is readily amenable to an injection molding process that utilizes precision made molds from computer-aided design and solid free form fabrication, allowing for the fabrication of tissue engineered constructs with very precise shape fidelity. Additionally, we found that calcium alginate could be reliably modified by the covalent addition of peptides, and that the addition of a newly discovered TGF-β binding peptide delayed the release of pre-loaded TGF-β1. Together these results show some of the encouraging prospects for cartilage tissue engineering.
`Menière’s Syndrome.Menière’s syndrome is an inner ear disorder characterized by idiopathic endolymphatic hydrops with associated periodic tinnitus, vertigo, and progressive sensorineural hearing loss. It affects approximately 0.2% of the population, for whom it can be quite devastating. In addition to progressive hearing loss people with Menière’s syndrome are prone to sudden attacks of vertigo and tinnitus that are severe enough that they can lead to falls and potentially serious injury. People subject to frequent attacks are unable to drive, with obvious consequences on standard of living.
In the current studies we evaluated the standard animal model of Menière’s syndrome by comparing cochlear turn specific hearing thresholds and the degree of hydrops in that turn. A positive correlation between these had previously been established in the study of human temporal bones from people with Menière’s syndrome, but had not been reported in the animal model.
We also evaluated the potential of aminoguanidine, a relatively specific inhibitor of the inducible isoform of nitric oxide synthase, as a neuroprotective therapeutic agent for preservation of hearing in animals with surgically induced endolymphatic hydrops.
We found, for the first time, a partial correlation between cochlear turn specific hydrops and hearing thresholds in the most commonly used animal model of Menière’s syndrome, helping to validate the utility of this animal model for future studies. We also found that aminoguanidine did indeed partially preserve hearing in animals with surgically induced Menière’s syndrome. This encouraging result appears to be the first report of a medical intervention protective against hearing loss in an animal model of Menière’s syndrome, and may help us to understand the etiology pathology seen in Menière’s syndrome.
36
Reed, Suzanne Rene. „Epidemiology of joint injuries in thoroughbred racehorses in training“. Thesis, Royal Veterinary College (University of London), 2011. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.559071.
37
Kruger, Annie J. „Prediction, Prevention and Treatment of Virally Induced Type 1 Diabetes: A Dissertation“. eScholarship@UMMS, 2009. https://escholarship.umassmed.edu/gsbs_diss/424.
Annotation:
Several viral infections have been associated with human type 1 diabetes (T1D), although it has proven difficult to unequivocally establish them as causative agents. In rodent models, however, viruses have definitely been established to cause T1D. The treatment of weanling BBDR rats with the combination of a TLR3 ligand, pIC, and an ssDNA parvovirus, KRV, precipitates T1D in nearly 100% of rats within a short, predictable timeframe. In this dissertation, we utilized the BBDR rat model to (1) identify early serum biomarkers that could predict T1D precipitated by viral induction and (2) test the efficacy of leptin, a therapeutic agent, which may have the ability to prevent diabetes onset, reverse new onset diabetes and prevent autoimmune recurrence of diabetes in rats transplanted with syngeneic islet grafts.
Identification of biomarkers has long served as an invaluable tool for disease prediction. In BBDR rats, we identified an acute phase response protein, haptoglobin, as a potential biomarker for pIC + KRV induced T1D using the global proteomic profiling techniques, 2D gel analysis and iTRAQ. Upon validating this biomarker, we determined that haptoglobin was sensitive in predicting T1D in the pIC + KRV model, in which nearly 100% of the rats become diabetic, but not in models where diabetes expression was variable (KRV only or RCMV only models). However, analysis of the serum kinetics of haptoglobin and its functional capacity in the blood has given us insights into the potential role of early phase reactants in modulating virally mediated T1D.
An alternative means of regulating T1D pathogenesis is through leptin. Leptin is a hormone with pleotropic roles in the body, particularly affecting energy metabolism and immune regulation. These characteristics make leptin an intriguing candidate for therapeutic testing in T1D models. Our studies have determined that high doses of leptin delivered via an adenovirus (AdLeptin) or alzet pump delivery system can prevent diabetes in > 90% of rats treated with pIC + KRV. We further showed that serum hyperleptinemia was associated with decreased body weight, decreased non-fasting serum insulin levels and lack of islet insulitis in pIC + KRV treated rats pretreated with AdLeptin compared with those pretreated with PBS. We discovered that hyperleptinemia induced a profound decrease in splenic weight and splenic cellularity, including reductions in CD4+ and CD8+ T cells, DC/MACs and B cells. These findings indicate a potential mechanism whereby hyperleptinemia protects rats from virally induced T1D through the promotion of peripheral immunosuppression.
Among pIC + KRV treated rats, we have also found that leptin therapy can reverse hyperglycemia in a subset of new onset diabetics for up to 20 days. In the absence of exogenous insulin, leptin treatment of new onset diabetics prevented the rapid weight loss associated with osmotic diuresis, as well as the ketosis observed in vehicle treated diabetic rats. Overall, these findings point to the therapeutic value of leptin in maintaining glycemic control and preventing ketosis in an insulin deficient state, in the absence of exogenous insulin therapy.
Additionally, we have also determined that AdLeptin treatment can prolong the survival of syngeneic islets transplanted into diabetic BBDR rats for up to 50 days post transplant. Although hyperleptinemia generated by AdLeptin was unable to prevent insulitis into islet grafts, this insulitis did not appear to be destructive as islet grafts continued to stain positively for insulin when compared with control rats whose grafts succumbed to recurrent autoimmunity. In the various therapeutic settings in which we have tested leptin treatment, we have found this hormone to have significant beneficial effects. These findings merit further evaluation of leptin as a therapeutic agent in human T1D.
38
Miller, Ashton B. „EFFECTS OF PITUITARY PARS INTERMEDIA DYSFUNCTION AND PRASCEND® TREATMENT ON ENDOCRINE AND IMMUNE FUNCTION IN SENIOR HORSES“. UKnowledge, 2019. https://uknowledge.uky.edu/gluck_etds/41.
Annotation:
Pituitary pars intermedia dysfunction (PPID) is one of the most common endocrine diseases affecting senior horses. PPID causes abnormally high concentrations of adrenocorticotropic hormone (ACTH) in the plasma and a very distinct, long, shaggy haircoat (hypertrichosis). At present, the recommended treatment for PPID is daily oral administration of pergolide mesylate. Due to the increased ACTH levels associated with PPID, it is commonly thought that these horses are immunosuppressed and at increased risk of opportunistic infections, although current research in this area is sparse. Additionally, it is not well-understood how treatment with Prascend® (pergolide tablets) affects endocrine measures other than ACTH and if it also impacts the immune response.
To better understand how PPID influences endocrine and immune function in the horse, Non-PPID horses (n=10), untreated PPID horses (n=9), and PRASCEND-treated PPID horses (n=9) were followed over 15 months. Endocrine measures assessed included basal ACTH, ACTH responses to thyrotropin-releasing hormone (TRH) stimulation tests, basal insulin, insulin responses to oral sugar tests (OST), total cortisol, and free cortisol. Systemic immune function measures included basal and stimulated whole blood and peripheral blood mononuclear cell (PBMCs) cytokine and receptor expression, plasma myeloperoxidase levels, and complete blood counts. Localized immune function measures within the lung included cytokine and receptor expression after stimulation of cells obtained via bronchoalveolar lavage (BAL), myeloperoxidase levels in BAL fluid, and BAL fluid cytology. We hypothesized that PPID would affect immune function, but that any alterations would be corrected by treatment with PRASCEND.
Results for the endocrine analyses showed that basal ACTH was reduced in the PRASCEND-treated horses to the levels of the Non-PPID horses, but ACTH in response to TRH stimulation was only reduced in the PRASCEND-treated horses at non-fall timepoints. PPID did not affect basal insulin, insulin responses to OSTs, total cortisol, or free cortisol, and PRASCEND treatment did not appear to have an impact on these measures either. These results suggest that PPID and hyperinsulinemia/insulin dysregulation are distinct endocrine conditions, and that the excess ACTH in horses with PPID is inactive, as it is unable to stimulate a normal cortisol response.
In the immune function analyses, PPID horses had decreased expression of interferon gamma (IFNγ) from PBMCs stimulated with Rhodococcus equi and Escherichia coli and increased transforming growth factor beta (TGFβ) expression from the E. coli-stimulated PBMCs. TGFβ was also increased in PPID horses in the unstimulated whole blood samples. These results suggest that PPID horses are unable to mount an appropriate Th1 response, and that the regulatory subset of T-lymphocytes may be contributing to this decreased Th1 response. Results for the localized immune function analyses may indicate altered Th2 responses within the lung of PPID horses, although these results were severely limited by the sample size available for analyses. PRASCEND did not appear to affect immune function as measured in this study.
In summary, PRASCEND successfully reduces basal ACTH in PPID horses and remains the best choice for veterinarians in monitoring dosage and response to PRASCEND treatment. Insulin, total cortisol, and free cortisol were not affected by PPID status or PRASCEND treatment in this study. Immune function was altered in horses with PPID, and it is likely that these horses are indeed at increased risk of opportunistic infection. PRASCEND treatment did not correct the differences in immune function in this study. Additional research is needed to further understand which mechanisms are driving the alterations in immune function for horses with PPID.
39
Anchala, Raghupathy. „Management of hypertension and prevention of cardiovascular diseases in India : the role of decision support systems“. Thesis, University of Cambridge, 2013. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.648283.
40
Kelly, Patricia J. „Morphological changes of collagenase induced tendinitis of achilles rat tendons utilizing augmented soft tissue mobilization“. Virtual Press, 1999. http://liblink.bsu.edu/uhtbin/catkey/1129629.
Annotation:
Augmented Soft Tissue Mobilization (ASTM) is a new noninvasive technique utilized to treat chronic musculoskeletal injuries. The purpose of this study was to trace the morphological events in collagenase injured rat Achilles tendons during ASTM treatment and to observe passive occurrence of post treatment remodeling in tendons. Twelve groups of rats were divided into the following categories, A) control, B) sham surgery, C) ASTM only, D) ASTM/sham , E) tendinitis, F) ASTM/tendinitis 1 week, G) ASTM/tendinits 2 weeks H) ASTM/tendinits 3 weeks I) ASTM/tendinits 4 weeks, J) Post ASTM 5 weeks, K) Post ASTM 10 weeks, L) Post ASTM 15 weeks. One week after the last designated treatment, the Achilles tendons were harvested and then prepared for light microscopy, electron microscopy, and bifringence polarizing microscopy. An increase in fibroblast activation and proliferation was noted with the tendinitis, ASTM/tendinitis, and post groups. Ossification occurred in the core of the Achilles tendon in all of the ASTM groups. The presence of inflammatory cells was observed in the tendons and longitudinal remodeling of the collagen fibers did not occur.Department of Biology
41
Bergh, Alison. „The effect of passive thoracic flexion-rotation movement on the total static compliance of the respiratory system and respiratory responses in ventilated patients“. Thesis, Link to the online version, 2007. http://hdl.handle.net/10019/408.
42
Smith, Brian A. „Computational Modeling to Assess Surgical Procedures for the Treatment of Adult Acquired Flatfoot Deformity“. VCU Scholars Compass, 2015. http://scholarscompass.vcu.edu/etd/4019.
Annotation:
Several surgically corrective procedures are considered to treat Adult Acquired Flatfoot Deformity (AAFD) patients, relieve pain, and restore function. Procedure selection is based on best practices and surgeon preference. Recent research created patient specific models of Adult Acquired Flatfoot Deformity (AAFD) to explore their predictive capabilities and examine effectiveness of the surgical procedure used to treat the deformity. The models’ behavior was governed solely by patient bodyweight, soft tissue constraints, and joint contact without the assumption of idealized joints. The current work expanded those models to determine if an alternate procedure would be more effective for the individual. These procedures included one hindfoot procedure, the Medializing Calcaneal Osteotomy (MCO), and one of three lateral column procedures: Evans osteotomy, Calcaneocuboid Distraction Arthrodesis (CCDA), Z osteotomy and the combination procedures MCO & Evans osteotomy, MCO & CCDA, and MCO & Z osteotomy all used in combination with a tendon transfer. The combination MCO & Evans and MCO & Z procedures were shown to provide the greatest amount of correction for both forefoot abduction and hindfoot valgus. However, these two procedures significantly increased the joint contact force, specifically at the calcaneocuboid joint, and ground reaction force along the lateral column. With exception to the lateral bands of the plantar fascia and middle spring ligament, the strain present in the plantar fascia, spring, and deltoid ligaments decreased after all procedures. The use of patient specific computational models provided the ability to investigate effects of alternate surgical corrections on restoring biomechanical function in flatfoot patients.
43
Chua, Ka Kit. „Randomized controlled clinical trials for the evaluation of efficacy and safety of Chinese medicine in treatment of neurodegenerative diseases“. HKBU Institutional Repository, 2015. https://repository.hkbu.edu.hk/etd_oa/231.
Annotation:
Background: Neurodegenerative diseases (NDD) are very common in the aging population, of which Parkinson’s disease (PD) and Alzheimer disease (AD) are the two most common. Since the etiology of the neuronal death in these diseases remains unclear, currently no curative therapy is available. Traditional Chinese medicine (TCM) has been used to treat certain diseases, which based on their symptoms we now know that they are included PD and AD, for thousands of years. However, our pervious systematic review reports that the quality of current TCM clinical trials related to this area had limited internal validity due to methodological flaws and insufficient data reporting. Methods: This study includes two add-on double-blinded randomized controlled trials (RCT), PD full-scale study and AD pilot study. It aims to provide evidence for the efficacy and safety of two specific TCM decoctions, Jia-Wei-Liu-Jun-Zi Tang (JWLJZT) and Di-tan decoction (DTD) in treating PD and AD, respectively. These clinical trials follow the Consolidated Standards of Reporting Trials (CONSORT) as well as the International Conference on Harmonization guidelines on Good Clinical Practice (GCP). Also, this two RCT obtained the approval from the Human and Animal Research Ethics Committee of Hong Kong Baptist University before the study and registered on the Chinese Clinical Trial Registry. Result: In the PD trial, 111 idiopathic PD patients were randomly assigned to receive either JWLJZT or placebo for 32 weeks. Although there was not significant difference in the primary outcome of Movement Disorder Society Sponsored Revision of Unified PD Rating Scale (MDS-UPDRS) Part I total score (p = 0.216), significant improvements was observed in the secondary outcome of Non-motor symptom assessment scale for Parkinson’s disease (NMSS) total score (p = 0.019), subtype of mood/cognition (p = 0.005) and hallucinations (p = 0.024). In addition, post-hoc analysis showed a significant reduction in constipation (p < 0.001). On the other hand, 40 AD patients were randomly assigned to receive either DTD or placebo for 24 weeks in the AD trial. There was an improvement trend in the primary outcome of the cognitive subscale of Alzheimer’s Disease Assessment Scale (ADAS-cog) total score in the DTD group though the difference relative to the placebo group was not statistically significant (p = 0.315). No significant difference was found in the secondary outcomes. Adverse events were mild and comparable between treatment and placebo groups in both trials. Discussion: JWLJZT did show some improvement in non-motor symptoms, including mood, cognition, and constipation, in PD patients, while, DTD did show a reducing trend in the cognitive impairment based on rigorous RCT. Further study focusing on the effective dosage, pharmacologic mechanism of JWLJZT and DTD are needed to give a fuller picture as well as better support for using them in human being as a routine treatment. In fact, JWLJZT and DTD are the only two examples of TCM for treating NDD. These two clinical trials are served as examples of how to evaluate efficacy and safety of TCM for the treatment of various diseases using rigorous RCT methods and standard. Keywords: Randomized Controlled Trials, Parkinson’s disease, Alzheimer disease, Traditional Chinese medicine, Jia-Wei-Liu-Jun-Zi Tang, Di-tan decoction, Efficacy, Safety
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Chiu, Sin-ming, und 趙善明. „Absence of Nucks1 enhances mesenchymal stem cells mediated cardiac protection“. Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2013. http://hdl.handle.net/10722/197087.
Annotation:
Despite major advances in diagnosis and prevention of coronary artery disease (CAD), the development of therapies to regenerate functional cardiomyocytes after myocardial infarction (MI) is very challenging. Studies have demonstrated that bone marrow derived mesenchymal stem cells (BM-MSCs) secrete a panel of growth factors and anti-inflammatory cytokines to activate resident cardiomyocytes and cardiac stem cells in myocardial repair after MI. However, the mechanisms of modulating BM-MSC secretions are not well understood. Recently, molecular candidates in regulating BM-MSCs paracrine secretion to improve cardiac protection have been explored. Amongst the molecular candidates, Nuclear casein kinase and cyclin-dependent kinase substrate 1 (Nucks1) is suggested as a regulatory protein in nuclear factor-kappa B (NF-κB) signaling pathway by interacting with TANK-binding kinase 1 (TBK1). TBK1 is a non-canonical I kappa B (IκB) kinase that can activate the NF-κB transcription factor and its transcriptional response. NF-κB signaling pathway controls many cellular responses such as cell survival, proliferation and cytokine productions. We hypothesizes Nucks1 may have potential roles in regulating mouse BM-MSCs secretion of growth factors and cytokine profiles in heart repairs after MI. To test our hypothesis, the cardiac protection efficacy of acute infarcted mouse myocardium was measured after the transplantation of WT versus Nucks1 KO BM-MSCs. To this end, we developed a mouse model of acute myocardial infarction (AMI) induced by ligation of left descendant coronary artery. Acute infarcted mouse myocardium receiving WT or Nuck1 KO BM-MSCs transplantation, demonstrated a significant improvement of left ventricular ejection fraction (LVEF), ESP, +dP/dt, ESPVR and vessel density, and reduced infarction size in comparison with PBS control group post-4 weeks of transplantation. Furthermore, acute infarcted mouse myocardium receiving Nucks1 KO BM-MSCs transplantation provided better cardioprotective effects than those receiving WT BM-MSCs transplantation. Immunostaining disclosed CD31 and smooth muscle actin (SMA) expression in acute infarcted mouse myocardium receiving Nucks1 KO BM-MSCs were relatively higher than those receiving WT BM-MSCs transplantation. Additionally, a distinct secretion profile of growth factors and cytokines between Nucks1 KO BM-MSCs versus WT BM-MSCs under in vitro ischemia was studied. Expression of vascular endothelial growth factor alpha (VEGFα) in Nucks1 KO BM-MSCs under hypoxia/ serum deprivation was significantly higher than that of WT BMMSCs.
Taken together, our data suggested BM-MSCs provide cardiac protection in acute infarcted myocardium. Transplantation of Nucks1 KO BMMSCs may further enhance the cardiac repair of the acute infracted myocardium through an induction of VEGFα.published_or_final_version
Medicine
Master
Master of Philosophy
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Chan, Hoi Huen. „The vascular modulation effect of Panax ginseng“. HKBU Institutional Repository, 2013. http://repository.hkbu.edu.hk/etd_ra/1518.
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Stewart, Simon. „Optimising therapeutic efficacy in acute and chronic cardiac disease states /“. Title page, contents and abstract only, 1999. http://web4.library.adelaide.edu.au/theses/09PH/09phs851.pdf.
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Davidson, Anne. „Investigation of treatment related neurotoxicity following childhood cancer by proton magnetic resonance spectroscopy“. Thesis, University of Newcastle Upon Tyne, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.287842.
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Galdun, John P. „A MECHANISTIC STUDY OF AN iPSC MODEL FOR LEIGH’S DISEASE CAUSED BY MtDNA MUTATAION (8993 T>G)“. VCU Scholars Compass, 2016. http://scholarscompass.vcu.edu/etd/4411.
Annotation:
Mitochondrial diseases encompass a broad range of devastating disorders that typically affect tissues with high-energy requirements. These disorders have been difficult to diagnose and research because of the complexity of mitochondrial genetics, and the large variability seen among patient populations. We have devised and carried out a mechanistic study to generate a cell based model for Leigh’s disease caused by mitochondrial DNA mutation 8993 T>G. Leigh’s disease is a multi-organ system disorder that depends heavily on the mutation burden seen within various tissues. Using new reprogramming and sequencing technologies, we were able to show that Leigh’s disease patient fibroblasts reprogrammed to induced pluripotent stem cells maintain the same level of mutation burden seen in the original patient cell line. Mutation burden was maintained through several passages and spontaneous differentiation. This cell based model could be useful for future pathogenesis studies, or therapeutic drug screenings in a patient and tissue specific manner.
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Cielinski, Matthew Joseph. „Osteoclast Ontogeny-Experimental Studies in Two Osteopetrotic Mutations in the Rat: A Dissertation“. eScholarship@UMMS, 1994. https://escholarship.umassmed.edu/gsbs_diss/141.
Annotation:
Osteopetrosis is a metabolic bone disease in mammals characterized by a generalized skeletal sclerosis caused by reduced bone resorption. This reduced bone resorption is manifested in afflicted animals by abnormal bone shape, reduced or absent marrow cavities, extramedullary hemopoiesis, abnormal mineral homeostasis and absent or delayed tooth eruption. The available osteopetrotic animal mutations have been a constant source of fruitful investigations concerning the systemic regulation of osteoclastogenesis and bone metabolism. Tooth eruption, on the other hand, is a localized manifestation of the timely activation of bone resorption and bone formation on opposite sides of an erupting tooth. Its rate-limiting step is the speed of bone resorption to form the eruption pathway. In this dissertation, we used two osteopetrotic rat mutations, toothless (tl) and microphthalmia blanc (mib), to investigate the abnormal development of osteoclasts and tooth eruption in mutant rats with an emphasis on the role of systemic and local factors. The significant contributions to this work are listed below.
1. In the toothless rat, a mutation lacking erupted dentition due to severely reduced bone resorption, colony-stimulating factor-1 (CSF-1) promoted tooth eruption but this was delayed compared to normal rats. Eruption was accompanied by changes in the populations of tartrate-resistant acid phosphatase-positive (TRAP+) mononuclear cells in the dental follicle and TRAP+ osteoclasts on adjacent alveolar bone surfaces. These cell populations were dramatically increased in treated mutants compared to untreated tl rats, but the timing of their appearance was delayed compared to normal littermates. This lag in the appearance of osteoclasts and their precursors corresponded to the delay in eruption of first molars in treated tl rats.
2. CSF-1 also accelerated the eruption of molars in normal rats. CSF-1 increased the number of TRAP+ mononuclear cells in the dental follicle and TRAP+ osteoclasts on adjacent alveolar bone surfaces, but had no effect on the timing of their appearance in normal rats.
3. Our data revealed a differential effect on tooth eruption of the growth factors CSF-1 and epidermal growth factor (EGF). CSF-1 accelerated eruption of molars in normal rats, but had no effect on incisor eruption. On the other hand, EGF accelerated incisor eruption; but did not affect molar eruption in normal rats.
4. We have described the mechanism for the transient, mild form of osteopetrosis inherited by mib rats. Mutant animals possess a typical sclerosis at birth, which diminished--but was not resolved--during the first postnatal month. These characteristics are caused by early reductions in osteoclast number and function which improve to normal levels by 4 weeks. Osteoclast numbers were severely reduced in mib rats between birth and 2 weeks, but improved to near normal levels by 4 weeks. Neonatal abnormalities in osteoclast function included reduced staining for the functional enzymes TRAP and TrATPase, decreased levels of mRNA for both TrATPase and CAll, and inability to form a well-developed ruffled border. None of these defects were apparent after the first postnatal month.
5. Finally, we have shown that the dental abnormalities caused by the mild, transient form of osteopetrosis in mib rats are limited to incisor defects and delayed eruption of all teeth. Histologic and radiographic examination of mutant incisors revealed that, contrary to the situation in normal rats, the apex of the incisors of mib rats failed to extend past the first molar region to the third molar. The incisor apex of newborn mib rats was misshaped due to ankylosis of incisor matrices with alveolar bone. This ankylosis was temporary, being resolved by the third postnatal day. The delayed eruption of incisors in mib rats and abnormal shape and occlusion of these teeth in older animals is a consequence of the temporary ankylosis in newborn rats.
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Sishi, Balindiwe J. N. „An investigation into the P13-K/AKT signalling pathway in TNF-a-induced muscle proeolysis in L6 myotubes“. Thesis, Stellenbosch : Stellenbosch University, 2008. http://hdl.handle.net/10019.1/3039.
Annotation:
Thesis (MSc (Physiological Sciences))--Stellenbosch University, 2008.Introduction: Skeletal muscle atrophy is a mitigating complication that is characterized by a reduction in muscle fibre cross-sectional area as well as protein content, reduced force, elevated fatigability and insulin resistance. It seems to be a highly ordered and regulated process and signs of this condition are often seen in inflammatory conditions such as cancer, AIDS, diabetes and chronic heart failure (CHF). It has long been understood that an imbalance between protein degradation (increase) and protein synthesis (decrease) both contribute to the overall loss of muscle protein. Although the triggers that cause atrophy are different, the loss of muscle mass in each case involves a common phenomenon that induces muscle proteolysis. It is becoming evident that interactions among known proteolytic systems (ubiquitin-proteosome) are actively involved in muscle proteolysis during atrophy. Factors such as TNF-α and ROS are elevated in a wide variety of chronic inflammatory diseases in which skeletal muscle proteolysis presents a lethal threat. There is an increasing body of evidence that implies TNF-α may play a critical role in skeletal muscle atrophy in a number of clinical settings but the mechanisms mediating its effects are not completely understood. It is also now apparent that the transcription factor NF-κB is a key intracellular signal transducer in muscle catabolic conditions. This study investigated the various proposed signalling pathways that are modulated by increasing levels of TNF-α in a skeletal muscle cell line, in order to synthesize our current understanding of the molecular regulation of muscle atrophy. Materials and Methods: L6 (rat skeletal muscle) cells were cultured under standard conditions where after reaching ± 60-65% confluency levels, differentiation was induced for a maximum of 8 days. During the last 2 days, myotubes were incubated with increasing concentrations of recombinant TNF-α (1, 3, 6 and 10 ng/ml) for a period of 40 minutes, 24 and 48 hours. The effects of TNF-α on proliferation and cell viability were measured by MTT assay and Trypan Blue exclusion technique. Morphological assessment of cell death was conducted using the Hoechst 33342 and Propidium Iodide staining method. Detection of apoptosis was assessed by DNA isolation and fragmentation assay. The HE stain was used for the measurement of cell size. In order to determine the source and amount of ROS production, MitoTracker Red CM-H2 X ROS was utilised. Ubiquitin expression was assessed by immunohistochemistry. PI3-K activity was calculated by using an ELISA assay and the expression of signalling proteins was analysed by Western Blotting using phospho-specific and total antibodies. Additionally, the antioxidant Oxiprovin was used to investigate the quantity of ROS production in TNF-α-induced muscle atrophy. Results and Discussion: Incubation of L6 myotubes with increasing concentrations of recombinant TNF-α revealed that the lower concentrations of TNF-α used were not toxic to the cells but data analysis of cell death showed that 10 ng/ml TNF-α induced apoptosis and necrosis. Long-term treatment with TNF-α resulted in an increase in the upregulation of TNF- α receptors, specifically TNF-R1. The transcription factors NF-κB and FKHR were rapidly activated thus resulting in the induction of the ubiquitin-proteosome pathway. Activation of this pathway produced significant increases in the expression of E3 ubiquitin ligases MuRF-1 and MAFbx. Muscle fibre diameter appeared to have decreased with increasing TNF-α concentrations in part due to the suppressed activity of the PI3-K/Akt pathway as well as significant reductions in differentiation markers. Western blot analysis also showed that certain MAPKs are activated in response to TNF-α. No profound changes were observed with ROS production. Finally, the use Oxiprovin significantly lowered cell viability and ROS production. These findings suggest that TNF-α may elicit strong catabolic effects on L6 myotubes in a dose and time dependent manner. Conclusion: These observations suggest that TNF-α might have beneficial effects in skeletal muscle in certain circumstances. This beneficial effect however is limited by several aspects which include the concentration of TNF-α, cell type, time of exposure, culture conditions, state of the cell (disturbed or normal) and the cells stage of differentiation. The effect of TNF-α can be positive or negative depending on the concentration and time points analysed. This action is mediated by various signal transduction pathways that are thought to cooperate with each other. More understanding of these pathways as well as their subsequent upstream and downstream constituents is obligatory to clarify the central mechanism/s that control physiological and pathophysiological effects of TNF-α in skeletal muscle.