Medicine (Western Health) - Research Publications

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    A comparative study of the effect of submicron porous and smooth ultrafine-grained Ti-20Mo surfaces on osteoblast responses
    Gui, N ; Xu, W ; Abraham, AN ; Myers, DE ; Mayes, ELH ; Xia, K ; Shukla, R ; Qian, M (WILEY, 2018-07)
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    Osteochondral repair using an acellular dermal matrixpilot in vivo study in a rabbit osteochondral defect model
    Ye, K ; Traianedes, K ; Robins, SA ; Choong, PFM ; Myers, DE (WILEY, 2018-07)
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    Picolinic Acid, a Catabolite of Tryptophan, Has an Anabolic Effect on Bone In Vivo
    Duque, G ; Vidal, C ; Li, W ; Al Saedi, A ; Khalil, M ; Lim, CK ; Myers, DE ; Guillemin, GJ (WILEY, 2020-11)
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    A case of triple pathology: seronegative anti-glomerular basement membrane antibody-mediated glomerulonephritis and membranous nephropathy in a patient with underlying diabetic kidney disease
    Tan, S-J ; Ducharlet, K ; Dwyer, KM ; Myers, D ; Langham, RG ; Hill, PA (OXFORD UNIV PRESS, 2013-06)
    In diabetic patients with acute kidney injury (AKI), kidney biopsy often reveals non-diabetic kidney pathology. This case describes a patient with known Type 1 diabetes who presented with AKI, nephrotic syndrome and haematuria. Combination pathology of seronegative anti-glomerular basement membrane antibody-mediated glomerulonephritis (anti-GBM GN), membranous nephropathy (MN) and diabetic nephropathy (DN) was demonstrated. Strong linear GBM IgG-staining on biopsy with crescentic GN and clinical AKI led to a diagnosis of anti-GBM GN, although serum antibodies were not detectable. Features of DN, Kimmelstiel-Wilson nodules and albumin staining were also present, along with features of MN, such as subepithelial deposits on electron microscopy. Despite treatment with immunosuppression and plasmapheresis, there was no recovery of kidney function. Coexisting anti-GBM GN and MN is well recognized, but the concurrent diagnosis with DN has not been described.
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    The molecular pathogenesis of osteosarcoma: a review.
    Broadhead, ML ; Clark, JCM ; Myers, DE ; Dass, CR ; Choong, PFM (Hindawi Limited, 2011)
    Osteosarcoma is the most common primary malignancy of bone. It arises in bone during periods of rapid growth and primarily affects adolescents and young adults. The 5-year survival rate for osteosarcoma is 60%-70%, with no significant improvements in prognosis since the advent of multiagent chemotherapy. Diagnosis, staging, and surgical management of osteosarcoma remain focused on our anatomical understanding of the disease. As our knowledge of the molecular pathogenesis of osteosarcoma expands, potential therapeutic targets are being identified. A comprehensive understanding of these mechanisms is essential if we are to improve the prognosis of patients with osteosarcoma through tumour-targeted therapies. This paper will outline the pathogenic mechanisms of osteosarcoma oncogenesis and progression and will discuss some of the more frontline translational studies performed to date in search of novel, safer, and more targeted drugs for disease management.
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    Chondrogenesis of Infrapatellar Fat Pad Derived Adipose Stem Cells in 3D Printed Chitosan Scaffold
    Ye, K ; Felimban, R ; Traianedes, K ; Moulton, SE ; Wallace, GG ; Chung, J ; Quigley, A ; Choong, PFM ; Myers, DE ; Reilly, G (PUBLIC LIBRARY SCIENCE, 2014-06-11)
    Infrapatellar fat pad adipose stem cells (IPFP-ASCs) have been shown to harbor chondrogenic potential. When combined with 3D polymeric structures, the stem cells provide a source of stem cells to engineer 3D tissues for cartilage repair. In this study, we have shown human IPFP-ASCs seeded onto 3D printed chitosan scaffolds can undergo chondrogenesis using TGFβ3 and BMP6. By week 4, a pearlescent, cartilage-like matrix had formed that penetrated the top layers of the chitosan scaffold forming a 'cap' on the scaffold. Chondrocytic morphology showed typical cells encased in extracellular matrix which stained positively with toluidine blue. Immunohistochemistry demonstrated positive staining for collagen type II and cartilage proteoglycans, as well as collagen type I. Real time PCR analysis showed up-regulation of collagen type II, aggrecan and SOX9 genes when IPFP-ASCs were stimulated by TGFβ3 and BMP6. Thus, IPFP-ASCs can successfully undergo chondrogenesis using TGFβ3 and BMP6 and the cartilage-like tissue that forms on the surface of 3D-printed chitosan scaffold may prove useful as an osteochondral graft.
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    Bioactive Coatings for Orthopaedic Implants-Recent Trends in Development of Implant Coatings
    Zhang, BGX ; Myers, DE ; Wallace, GG ; Brandt, M ; Choong, PFM (MDPI AG, 2014-07)
    Joint replacement is a major orthopaedic procedure used to treat joint osteoarthritis. Aseptic loosening and infection are the two most significant causes of prosthetic implant failure. The ideal implant should be able to promote osteointegration, deter bacterial adhesion and minimize prosthetic infection. Recent developments in material science and cell biology have seen the development of new orthopaedic implant coatings to address these issues. Coatings consisting of bioceramics, extracellular matrix proteins, biological peptides or growth factors impart bioactivity and biocompatibility to the metallic surface of conventional orthopaedic prosthesis that promote bone ingrowth and differentiation of stem cells into osteoblasts leading to enhanced osteointegration of the implant. Furthermore, coatings such as silver, nitric oxide, antibiotics, antiseptics and antimicrobial peptides with anti-microbial properties have also been developed, which show promise in reducing bacterial adhesion and prosthetic infections. This review summarizes some of the recent developments in coatings for orthopaedic implants.
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    In Vivo Measurement of Hippocampal GABAA/cBZR Density with [18F]-Flumazenil PET for the Study of Disease Progression in an Animal Model of Temporal Lobe Epilepsy
    Vivash, L ; Gregoire, M-C ; Bouilleret, V ; Berard, A ; Wimberley, C ; Binns, D ; Roselt, P ; Katsifis, A ; Myers, DE ; Hicks, RJ ; O'Brien, TJ ; Dedeurwaerdere, S ; Najbauer, J (PUBLIC LIBRARY SCIENCE, 2014-01-21)
    PURPOSE: Imbalance of inhibitory GABAergic neurotransmission has been proposed to play a role in the pathogenesis of temporal lobe epilepsy (TLE). This study aimed to investigate whether [(18)F]-flumazenil ([(18)F]-FMZ) PET could be used to non-invasively characterise GABAA/central benzodiazepine receptor (GABAA/cBZR) density and affinity in vivo in the post-kainic acid status epilepticus (SE) model of TLE. METHODS: Dynamic [(18)F]-FMZ -PET scans using a multi-injection protocol were acquired in four male wistar rats for validation of the partial saturation model (PSM). SE was induced in eight male Wistar rats (10 weeks of age) by i.p. injection of kainic acid (7.5-25 mg/kg), while control rats (n = 7) received saline injections. Five weeks post-SE, an anatomic MRI scan was acquired and the following week an [(18)F]-FMZ PET scan (3.6-4.6 nmol). The PET data was co-registered to the MRI and regions of interest drawn on the MRI for selected structures. A PSM was used to derive receptor density and apparent affinity from the [(18)F]-FMZ PET data. KEY FINDINGS: The PSM was found to adequately model [(18)F]-FMZ binding in vivo. There was a significant decrease in hippocampal receptor density in the SE group (p<0.01), accompanied by an increase in apparent affinity (p<0.05) compared to controls. No change in cortical receptor binding was observed. Hippocampal volume reduction and cell loss was only seen in a subset of animals. Histological assessment of hippocampal cell loss was significantly correlated with hippocampal volume measured by MRI (p<0.05), but did not correlate with [(18)F]-FMZ binding. SIGNIFICANCE: Alterations to hippocampal GABAA/cBZR density and affinity in the post-kainic acid SE model of TLE are detectable in vivo with [(18)F]-FMZ PET and a PSM. These changes are independent from hippocampal cell and volume loss. [(18)F]-FMZ PET is useful for investigating the role that changes GABAA/cBZR density and binding affinity play in the pathogenesis of TLE.
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    Applying advanced imaging techniques to a murine model of orthotopic osteosarcoma
    Broadhead, ML ; Lokmic, Z ; Tan, ML ; Stevenson, A ; Binns, DS ; Cullinane, C ; Hicks, RJ ; Choong, PFM ; Myers, DE (FRONTIERS MEDIA SA, 2015)
    INTRODUCTION: Reliable animal models are required to evaluate novel treatments for osteosarcoma. In this study, the aim was to implement advanced imaging techniques in a murine model of orthotopic osteosarcoma to improve disease modeling and the assessment of primary and metastatic disease. MATERIALS AND METHODS: Intra-tibial injection of luciferase-tagged OPGR80 murine osteosarcoma cells was performed in Balb/c nude mice. Treatment agent [pigment epithelium-derived factor (PEDF)] was delivered to the peritoneal cavity. Primary tumors and metastases were evaluated by in vivo bioluminescent assays, micro-computed tomography, [(18)F]-Fluoride-PET and [(18)F]-FDG-PET. RESULTS: [(18)F]-Fluoride-PET was more sensitive than [(18)F]-FDG-PET for detecting early disease. Both [(18)F]-Fluoride-PET and [(18)F]-FDG-PET showed progressive disease in the model, with fourfold and twofold increases in standardized uptake value (p < 0.05) by the study endpoint, respectively. In vivo bioluminescent assay showed that systemically delivered PEDF inhibited growth of primary osteosarcoma. DISCUSSION: Application of [(18)F]-Fluoride-PET and [(18)F]-FDG-PET to an established murine model of orthotopic osteosarcoma has improved the assessment of disease. The use of targeted imaging should prove beneficial for the evaluation of new approaches to osteosarcoma therapy.
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    Chondrogenesis of Human Infrapatellar Fat Pad Stem Cells on Acellular Dermal Matrix
    Ye, K ; Traianedes, K ; Choong, PFM ; Myers, DE (FRONTIERS MEDIA SA, 2016-01-26)
    Acellular dermal matrix (ADM) has been in clinical use for decades in numerous surgical applications. The ability for ADM to promote cellular repopulation, revascularisation and tissue regeneration is well documented. Adipose stem cells have the ability to differentiate into mesenchymal tissue types, including bone and cartilage. The aim of this study was to investigate the potential interaction between ADM and adipose stem cells in vitro using TGFβ3 and BMP6. Human infrapatellar fat pad-derived adipose stem cells (IPFP-ASC) were cultured with ADM derived from rat dermis in chondrogenic (TGFβ3 and BMP6) medium in vitro for 2 and 4 weeks. Histology, qPCR, and immunohistochemistry were performed to assess for markers of chondrogenesis (collagen Type II, SOX9 and proteoglycans). At 4 weeks, cell-scaffold constructs displayed cellular changes consistent with chondrogenesis, with evidence of stratification of cell layers and development of a hyaline-like cartilage layer superficially, which stained positively for collagen Type II and proteoglycans. Significant cell-matrix interaction was seen between the cartilage layer and the ADM itself with seamless integration between each layer. Real time qPCR showed significantly increased COL2A1, SOX9, and ACAN gene expression over 4 weeks when compared to control. COL1A2 gene expression remained unchanged over 4 weeks. We believe that the principles that make ADM versatile and successful for tissue regeneration are applicable to cartilage regeneration. This study demonstrates in vitro the ability for IPFP-ASCs to undergo chondrogenesis, infiltrate, and interact with ADM. These outcomes serve as a platform for in vivo modelling of ADM for cartilage repair.