Thesis (Ph.D.)--University of Western Australia, 2007.

Thesis (M. Sc.)--University of Canterbury, 2008. / Typescript (photocopy). "Supervised by Associate Professor Neville Blampied, Dr Lois Surgenor, and Dr Mike Davis." Includes bibliographical references (leaves 125-138). Also available via the World Wide Web.

No description available.

No description available.

No description available.

Bone remodelling, the process by which the skeleton adapts to environmental changes, is dependent on the actions of osteoclasts that resorb bone and osteoblasts which make new bone matrix. Aberrant remodelling underpins bone loss in several debilitating skeletal diseases such as osteoporosis, metastatic breast cancer and multiple myeloma. Changes in remodelling activity can also arise as a consequence of therapeutic intervention for instance intravenous bisphosphonate treatment is associated with osteochemonecrosis of the jaw and localised osteoradionecrosis is a common side effect of radiotherapy. Hyperbaric oxygen is often used as an adjunctive therapy in the treatment of these disorders. HBO involves the administration of 100% oxygen at atmospheric pressures greater than one in sealed chambers. The following studies aimed to evaluate the effect of HBO, hyperoxia, and pressure on RANKL-induced osteoclast differentiation and bone resorption from RAW264.7 and human peripheral blood mononuclear cells (PBMC), and osteoblast differentiation in vitro. The study also aimed to further examine the effect of HBO on ex vivo osteoclast formation from peripheral blood monocytes obtained from patients undergoing HBO. Daily exposure to HBO for ninety minutes significantly suppressed osteoclast differentiation and bone resorption in mouse and human monocytes in normoxic and hypoxic conditions in vitro. The suppressive action of HBO on osteoclast formation was associated with a significant reduction in HIF-1α and RANK mRNA expression and HBO also caused a significant reduction in NFATc1 and DC-STAMP expression. This study has for the first time shown that HBO is able to reduce the ability of precursors to form bone resorbing osteoclast. HBO also suppressed the ability of peripheral blood monocytes to develop into RANKL-induced resorptive osteoclasts. In an ex vivo culture system the suppressive effect of HBO was meditated by an action prior to activation of osteoclast differentiation by RANKL and must therefore be an inhibitory effect on the ability of precursors to differentiate along the osteoclastic lineage. HBO also accelerates the rate of osteoblast differentiation and augments early stages of mineralization and has a more pronounced effect than hyperoxia or pressure alone. HBO enhanced bone nodule formation and ALP activity in human osteoblasts. Furthermore HBO promoted the expression of type I collagen and Runx-2 in both normoxic and hypoxic conditions. HBO had a greater effect on these key markers of osteoblast differentiation than hyperoxia or pressure alone. This study suggests that HBO suppresses osteoclast activity and promotes osteoblastic bone formation, which may at least in part mediate its beneficial effects on necrotic bone. This provides evidence supporting the use of HBO as an adjunctive therapy to prevent osteoclast formation in a range of skeletal disorders associated with low oxygen partial pressure. The study also provides further support for the use of HBO in the treatment of skeletal disorders associated with excessive resorption such as osteomyelitis, and also provides a potential mechanism through which short term HBO may help fracture healing.

The aim of this study was to test the application of an in situ–formed synthetic polyethylene glycol (PEG) as a biodegradable membrane with a variety of graft materials and hyperbaric oxygen (HBO) for enhanced bone regeneration. Critical-sized rabbit calvarial defects were created in bilateral parietal bones. Group 1 served as a control with unfilled defects, Group 2 had defects filled with morcelized autogenous bone, and Group 3 had defects filled with biphasic calcium phosphate. One defect was protected PEG membrane and half the animals were subjected to HBOT treatment. The unsupported membrane didn’t produce the desired bone regeneration in the unfilled and bone grafted groups. HBO didn't ameliorate the bone grafted or ceramic filled defects over the 6-week time period. Caution is recommended with the membrane over unsupported defects. Future assessments with HBO should be completed at the 12-week time point.

The aim of this study was to test the application of an in situ–formed synthetic polyethylene glycol (PEG) as a biodegradable membrane with a variety of graft materials and hyperbaric oxygen (HBO) for enhanced bone regeneration. Critical-sized rabbit calvarial defects were created in bilateral parietal bones. Group 1 served as a control with unfilled defects, Group 2 had defects filled with morcelized autogenous bone, and Group 3 had defects filled with biphasic calcium phosphate. One defect was protected PEG membrane and half the animals were subjected to HBOT treatment. The unsupported membrane didn’t produce the desired bone regeneration in the unfilled and bone grafted groups. HBO didn't ameliorate the bone grafted or ceramic filled defects over the 6-week time period. Caution is recommended with the membrane over unsupported defects. Future assessments with HBO should be completed at the 12-week time point.

Akademisk avhandling--Gothenburg. / Bibliography: p. 69-74.

Spinal cord injury (SCI) is a physically and mentally devastating condition for which there is no curative treatment. It involves primary trauma from the impact and secondary damage in the form of biochemical cascades that threaten the integrity of functional tissue. Therapeutic interventions can only prevent secondary damages, given the irreversibility of the primary laceration. Experimental therapies for SCI can aim to promote neuronal growth and/or regeneration, promote neuroplasticity in surviving neurons and networks, and enhance neuroprotection, or the survival of spared neurons. Surgical decompression and hypothermia are neuroprotective strategies that usually precede rehabilitational strategies in SCI. Hyperbaric oxygen (HBO) treatment constitutes another promising therapy that can increase the amount of oxygen dissolved in the blood, and therefore, the amount delivered to tissues. Both pre-clinical and clinical studies have illustrated that HBO therapy can enhance motor recovery and exert neurological improvements after SCI. A plethora of pre-clinical studies have elucidated several aspects of its function in SCI; HBO seems to suppress apoptosis, edema, and inflammation, as well as mitigate oxidizing conditions. It can also promote angiogenesis, enhance nerve conduction, and inhibit neural degeneration. The limited number of clinical studies and the heterogeneity of protocols allow for fewer conclusions on the roles of HBO in human SCI: motor benefits are hinted in several clinical trials, while neuroprotective effects include increases in blood oxygen, and suppression of inflammatory responses. However, the number and variety of pre-clinical studies suggest that HBO can exert additional neuroprotective benefits in human SCI, which remain to be explored in the future.