A study has been made of the factors that contribute to the decreased rates of lipid peroxidation under different pro-oxidant conditions in intact Novikoff tumour cells, and in microsomal suspensions prepared from Novikoff tumour cells, compared with isolated normal rat hepatocytes and microsomal suspensions prepared from normal rat liver. The pro-oxidant conditions were the addition of either NADPH, NADPH + ADP + iron, NADPH + CCl4 or ascorbate+iron to the experimental systems used, or exposure to gamma-radiation. Contributory factors to the lower rates of lipid peroxidation observed include: a significant decrease in the polyunsaturated fatty acid content of Novikoff cells or Novikoff microsomes; the decreases are especially marked for the C20:4 and C22:6 fatty acids; a very marked reduction in NADPH-cytochrome c reductase; and no detectable content of cytochrome P-450. Another, and in our opinion critical, contribution to the diminished rate of lipid peroxidation in the tumour material is the substantial increase in alpha-tocopherol relative both to total lipid and to methylene-interrupted double bonds in fatty acids. Moreover, the alpha-tocopherol is the major contributor to lipid-soluble chain-breaking antioxidant in lipid extracts of normal liver and of Novikoff tumour material.
Using the experimental model of partial hepatectomy in the rat, we have examined the relationship between cell division and lipid peroxidation activity. In rats entrained to a regime of 12 h light/12 h dark and with a fixed 8 h feeding period in the dark phase, partial hepatectomy is followed by a rapid regeneration of liver mass with cycles of synchronized cell division at 24 h intervals. The latter phenomenon is indicated in this study by pulses of thymidine kinase activity having maxima at 24 h, 48 h and 72 h after partial hepatectomy. Microsomes prepared from regenerating livers show changes in lipid peroxidation activity (induced by NADPH/ADP/iron or by ascorbate/iron), which is significantly decreased relative to that in microsomes from sham-operated controls, again at 24 h, 48 h and 72 h after the operation. This phenomenon has been investigated with regard to possible underlying changes in the content of microsomal fatty acids, the microsomal enzymes NADPH:cytochrome c reductase and cytochrome P-450, and the physiological microsomal antioxidant alpha-tocopherol. The cycles of decreased lipid peroxidation activity are apparently due, at least in part, to changes in microsomal alpha-tocopherol content that are closely associated in time with thymidine kinase activity.
Three models of different stent designs implanted in a cerebral aneurysm, originating from the Virtual Intracranial Stenting Challenge 2007 (visc'07), are meshed and the flow characteristics simulated using commercial Computational Fluid Dynamics (cfd) software in order to investigate the effects of non-Newtonian viscosity and pulsatile flow. Conventional mass inflow and Wall Shear Stress (wss) output are used as a means of comparing the cfd simulations. In addition, a wss distribution is presented, which clearly discriminates in favour of the stent design identified by other groups. We conclude that non-Newtonian and pulsatile effects are important to include in order to avoid underestimating wss, understand dynamic flow effects and to discriminate more effectively between stent designs.
Local haemodynamic factors in large arteries are associated with the pathophysiology of cardiovascular diseases such as atherosclerosis and strokes. In search of these factors and their correlation with atheroma formation, quantitative haemodynamic data in realistic arterial geometry become crucial. At present no in vivo non-invasive technique is available that can provide accurate measurement of three-dimensional blood velocities and shear stresses in curved and branching sites of vessels where atherosclerotic plaques are found frequently. This paper presents a computer modelling technique which combines state-of-the-art computational fluid dynamics (CFD) with new noninvasive magnetic resonance imaging techniques to provide the complete haemodynamic data in 'real' arterial geometries. Using magnetic resonance angiographic and velocity images acquired from the aortic bifurcation of a healthy human subject, CFD simulations have been carried out and the predicted flow patterns demonstrate the non-planar-type flow characteristics found in experimental studies.
Rats entrained to a strictly regulated lighting and feeding schedule have been subjected to partial hepatectomy or a sham operation. In the partially hepatectomised animals the period of liver regeneration is characterised by regular bursts of thymidine kinase activity. Liver microsomes from rats, at times corresponding to maximum thymidine kinase activity, have much reduced rates of lipid peroxidation compared to control preparations: this is due in part to increased levels of lipid-soluble antioxidant at times of maximal DNA synthesis. This temporal relationship between thymidine kinase and lipid peroxidation is consistent with the view that lipid peroxidation is decreased prior to cell division. Lipidperoxidation Liver regeneration CeN division u-Tocopherol Thymidine kinase
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