Oral cancer: role of the basement membrane in invasion

The document attached has been archived with permission from the Australian Dental Association. An external link to the publisher’s copy is included.Invasive growth of cancer cells is a complex process involving specific interactions between tumour cells and the orderly, integrated complexes of the extracellular matrix. Basement membranes have been proposed as one constituent of extra-cellular matrix which carries responsibility for regulating invasion and metastasis.David F. Wilson, Jiang De-Jun, Angela M. Pierce and Ole W. Wiebki

The Influence of Prednisolone (PRED) and Methotrexate (MTX) on the Cell and Connective Tissue Content of Subcutaneously Implanted Polyurethane Sponges in Rats

Findings indicate that prednislone and methotrexate have profound effects on the cellular events of acute and chronic inflammation, and influence the synthesis or degradation of connective tissue macromolecules at certain stages of the inflammatory process

Convergence of marine megafauna movement patterns in coastal and open oceans

Author Posting. © The Author(s), 2017. This is the author's version of the work. It is posted here for personal use, not for redistribution. The definitive version was published in Proceedings of the National Academy of Sciences of the United States of America 115 (2018): 3072-3077, doi:10.1073/pnas.1716137115.The extent of increasing anthropogenic impacts on large marine vertebrates partly depends on the animals’ movement patterns. Effective conservation requires identification of the key drivers of movement including intrinsic properties and extrinsic constraints associated with the dynamic nature of the environments the animals inhabit. However, the relative importance of intrinsic versus extrinsic factors remains elusive. We analyse a global dataset of 2.8 million locations from > 2,600 tracked individuals across 50 marine vertebrates evolutionarily separated by millions of years and using different locomotion modes (fly, swim, walk/paddle). Strikingly, movement patterns show a remarkable convergence, being strongly conserved across species and independent of body length and mass, despite these traits ranging over 10 orders of magnitude among the species studied. This represents a fundamental difference between marine and terrestrial vertebrates not previously identified, likely linked to the reduced costs of locomotion in water. Movement patterns were primarily explained by the interaction between species-specific traits and the habitat(s) they move through, resulting in complex movement patterns when moving close to coasts compared to more predictable patterns when moving in open oceans. This distinct difference may be associated with greater complexity within coastal micro-habitats, highlighting a critical role of preferred habitat in shaping marine vertebrate global movements. Efforts to develop understanding of the characteristics of vertebrate movement should consider the habitat(s) through which they move to identify how movement patterns will alter with forecasted severe ocean changes, such as reduced Arctic sea ice cover, sea level rise and declining oxygen content.Workshops funding granted by the UWA Oceans Institute, AIMS, and KAUST. AMMS was supported by an ARC Grant DE170100841 and an IOMRC (UWA, AIMS, CSIRO) fellowship; JPR by MEDC (FPU program, Spain); DWS by UK NERC and Save Our Seas Foundation; NQ by FCT (Portugal); MMCM by a CAPES fellowship (Ministry of Education)

The use of hepatocytes for drug metabolism and toxicity studies.

Biphenyl metabolism has been extensively studied in isolated viable adult rat hepatocytes in suspension with regard to both phase I and phase II reactions. A wide range of primary and secondary metabolites are produced by these cells, which closely reflects the situation appertaining vivo. Using biphenyl, and the three primary metabolites, 2-, 3- and 4-hydxoxybiphenyl, assessment of toxicity due to the substrate, primary or secondary metabolites, examination of the relationship between phase I and phase II metabolism, and the effect of inducers and inhibitors on the total metabolic profile has been made. Possible rate limiting phenomena operating in the intact cell that affect the rate of xenobiotic metabolism have also been studied. With this insight into the isolated hepatocytes metabolic capabilities, particularly with respect to xenobiotic metabolism, isolated adult rat hepatocytes in suspension and primary maintenance Culture were then used as to vitro model systems for the assessment of xenobiotic-induced toxicity. Using a mixed liver cell approach, the fibroblast cytotoxicity (as measured by inhibition of cell growth) of a number of xenobiotics is shown to be fully expressed only when metabolised to their 'active' species by the hepatocytes to vitro, closely reflecting the situation known to occur to vivo. The versatility and general applicability of such a mixed-cell approach, to in vitro toxicity and carcinogenicity assessment of xenobiotics is discussed. In order to decide whether hepatocytes model systems could be used to assess a xenobiotics hepatotoxic potential, the changes in viability and functional capabilities of cultured hepatocytes were monitored after exposure to known in vivo hepatotoxic agents. Results presented here indicate that xenobiotics that are hepatotoxic in vivo are also hepatotoxic vitro, though whether by a similar mechanism is as yet unclear. The advantages and limitations to the use of such in vitro hepatocyte model systems for the assessment of xenobiotic-induced toxicity in the light of the wide range and variety of other in vitro models that are currently being used are discussed

The use of hepatocytes for drug metabolism and toxicity studies.

Biphenyl metabolism has been extensively studied in isolated viable adult rat hepatocytes in suspension with regard to both phase I and phase II reactions. A wide range of primary and secondary metabolites are produced by these cells, which closely reflects the situation appertaining vivo. Using biphenyl, and the three primary metabolites, 2-, 3- and 4-hydxoxybiphenyl, assessment of toxicity due to the substrate, primary or secondary metabolites, examination of the relationship between phase I and phase II metabolism, and the effect of inducers and inhibitors on the total metabolic profile has been made. Possible rate limiting phenomena operating in the intact cell that affect the rate of xenobiotic metabolism have also been studied. With this insight into the isolated hepatocytes metabolic capabilities, particularly with respect to xenobiotic metabolism, isolated adult rat hepatocytes in suspension and primary maintenance Culture were then used as to vitro model systems for the assessment of xenobiotic-induced toxicity. Using a mixed liver cell approach, the fibroblast cytotoxicity (as measured by inhibition of cell growth) of a number of xenobiotics is shown to be fully expressed only when metabolised to their 'active' species by the hepatocytes to vitro, closely reflecting the situation known to occur to vivo. The versatility and general applicability of such a mixed-cell approach, to in vitro toxicity and carcinogenicity assessment of xenobiotics is discussed. In order to decide whether hepatocytes model systems could be used to assess a xenobiotics hepatotoxic potential, the changes in viability and functional capabilities of cultured hepatocytes were monitored after exposure to known in vivo hepatotoxic agents. Results presented here indicate that xenobiotics that are hepatotoxic in vivo are also hepatotoxic vitro, though whether by a similar mechanism is as yet unclear. The advantages and limitations to the use of such in vitro hepatocyte model systems for the assessment of xenobiotic-induced toxicity in the light of the wide range and variety of other in vitro models that are currently being used are discussed

Distribution of the epithelial rests of Malassez and their relationship to blood vessels of the peridontal ligament during rat tooth development

Copyright © 2003 Australian Orthodontic JournalBackgroundThere is some evidence that the epithelial cell rests of Malassez partition the root surface from the periodontal ligament blood vessels, and may protect the root from resorption.ObjectiveThe aim of the present study was to determine the distributions of the epithelial rests of Malassez (ERM) and blood vessels in the periodontal ligament (PDL) of the developing rat first molar before, during and after emergence.MethodsFour Sprague-Dawley rats were sacrificed at two days, one week, two weeks, three weeks, four weeks and six weeks of age. After processing, the maxillae were embedded in paraffin, and sectioned longitudinally and transversely. The sections were stained with a double immuno-histochemical technique which utilised a keratin antibody AE1-AE3 (1:2,000) and an endothelial antibody Factor VIII (1:10,000) to enable simultaneous labelling of ERM and blood vessels. ERM and blood vessel counts were obtained from the mesio-buccal roots of three week, four week and six week-old rats, whilst qualitative observations were made for the earlier developmental stages.ResultsERM cells and cell clusters were found in the tooth third of the PDL width at the three, four and six week stages. Cells and cell clusters increased in number with age, especially in the upper third of the mesio-buccal root. The largest numbers of cells and clusters were found on the distal surfaces of the roots in all age groups. Cells and clusters in all root surfaces increased from three to four weeks, but decreased from four to six weeks. The greatest number of blood vessels was found in the bone-side third of the PDL. The distal surface had the highest proportion of blood vessels, and the palatal surface the least proportion. The number of blood vessels in all surface quadrants did not vary much from three to four weeks of age, but increased from four to six weeks of age, possibly as a reaction to tooth emergence and occlusal function. Physiological root resorption was only observed after tooth emergence, and appeared to be related to loss of continuity of the ERM network and the incursion of blood vessels.ConclusionsOrthodontic root resorption can be regarded as an exaggerated response to loss of PDL homeostatic control, possibly mediated by the epithelial rests of Malassez.Petrina Kat, Wayne Sampson, David Wilson, Ole Wiebki