Browsing by Author "Brown, T"

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    Bismuth-NSAIDs as colorectal cancer chemopreventives
    (Australian Institute of Nuclear Science and Engineering (AINSE), 2018-11-18) Brown, T; Dillon, CT; Holt, SA; Andrews, P; Piantavigna, S
    To date, epidemiological studies, animal studies and clinical trials have indicated the potential of non-steroidal anti-inflammatory drugs (NSAIDs) for the chemoprevention of colorectal cancer (CRC) [1]. Unfortunately, the use of NSAIDs for CRC chemoprevention is significantly limited due to the severe gastrointestinal (GI) side effects that have been associated with their long term use [1]. It is hypothesised that the coordination of NSAIDs to bismuth, a heavy metal with proven gastrointestinal sparing properties [2], may allow the use of NSAIDs as chemopreventives for CRC while also combating their associated GI side effects. The present study investigates the interactions of bismuth-coordinated NSAIDs (BiNSAIDs) with eukaryotic membrane mimics with the aim of establishing the possible uptake mechanisms of these compounds. This knowledge will be extended by investigating the behaviour of BiNSAIDs in more complex systems, including CRC cells and a CRC animal model. QCM-D studies involving biological membrane mimics composed of POPC or POPC/cholesterol demonstrated that BiNSAIDs and their parent NSAIDs interact with biological membranes [3]. Neutron reflectometry was also used to study the membrane interactions of BiNSAIDs and provided further evidence of the membrane interactions of BiNSAIDs, suggesting that passive diffusion is a likely method of uptake of these compounds [3]. These strength of these membrane interactions was an indicator of BiNSAID cytotoxicity against CRC cells.3 A CRC animal study has recently been completed with aspirin, which has promising preliminary results. In conclusion, the aforementioned studies continue to highlight the potential of BiNSAIDs as candidates for further investigations into their potential for the chemoprevention of CRC. © The Authors
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    Late Pleistocene deglaciation history of the SW British Isles: new evidence from Lundy and the outer Bristol Channel
    (International Union for Quaternary Research (INQUA), 2019-07-27) Rolfe, C; Hughes, PD; Brown, T; Bateman, M; Gibbard, P; Fink, D
    The SW British Isles was glaciated by the British-Irish Ice Sheet during the Late Pleistocene. Glacial deposits are widely preserved in the Bristol Channel and are revealed in boreholes and geophysical data. Lundy, an island in the Outer Bristol Channel, displays unique terrestrial evidence of glaciation in the Outer Bristol Channel. The evidence is dominated by erosional evidence of ice-scouring, although there are wide spreads of erratic cobbles and pebbles several of which contain evidence of striae and faceting. In addition, subsurface thick silt-clay deposits are common on the island with clay mineralogy indicating limited weathering, in contrast to occasional pockets of strongly weathered granite (growan). These deposits are interpreted as subglacial in origin. Offshore of Lundy, especially to the E and NE, geophysical data reveals the presence of thick glacial deposits and dense fields of boulders. This suggests that an ice limit occurred between Lundy and the mainland. This allowed the drainage of the proto-Severn to drain between this ice limit and the mainland in Devon, and the course of this palaeochannel can be traced in bathmetry and geophysical survey data. Periglacial activity after deglaciation is recorded by the presence of coversands, loess, ventifacts, scree slopes and associated colluvial deposits. Luminescence ages from colluvial sands on Lundy date to 24-26 ka indicating that this island was deglaciated by marine isotope stage (MIS) 2. This is consistent with deglaciation and exposure of the island in MIS 3 following glaciation in MIS 4 or possibly earlier. Previously obtained exposure ages from ice-scoured bedrock surfaces have been recalculated using the most recent production rate models and support this interpretation. In addition, a new programme of cosmogenic exposure dating of glacially-transported boulders and displaced tors will further test the previously obtained exposure age data from glaciated bedrock surfaces. In contrast to other weathered granite surfaces in the British Isles, Lundy has not experienced a prolonged weathering history through multiple glacial cycles. Whilst the precise timing of deglaciation is undergoing further testing, the current evidence overwhelmingly indicates that Lundy was eroded by an ice sheet during the Late Pleistocene. Morphometric analysis of weathering pits in the ice-moulded granite bedrock on Lundy supports this exposure history as do the OSL ages from sands overlying the bedrock surfaces. Evidence from elsewhere around the Celtic Sea indicates that the glaciation of Lundy most likely occurred in MIS 4 with ice retreating in MIS 3. However, during MIS 2 ice reached to the continental shelf in the Celtic Sea. This apparent paradox may be explained by a highly mobile Irish Sea Ice Stream which changed its configuration in response to fluctuating marine incursions in MIS 3 before exploiting the exposed continental shelf to the southwest during MIS 2. ©The Authors.