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Monoterpenes such as limonene and perillyl alcohol (PA) are currently under investigation for their chemotherapeutic properties which have been tied to their ability to affect protein isoprenylation. Because PA affects the synthesis of isoprenoids’ such as ubiquinone’ and cholesterol is the end product of the synthetic pathway from which this isoprenoid pathway branches’ we investigated the effects of this compound upon cholesterol metabolism in the colonic adenocarcinoma cell line SW480. PA (1 mM) inhibited incorporation of 14C-mevalonate into 21–26 kDa proteins by 25% in SW480 cells. Cholesterol (CH) biosynthesis was assessed by measuring the incorporation of 14C-acetate and 14C-mevalonate into 27-carbon-sterols. Cells treated with PA (1 mM) exhibited a fourfold increase in the incorporation of 14C-acetate but not 14C-mevalonate into cholesterol. Mevinolin (lovastatin)’ an inhibitor of 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase’ at 2 μM concentration’ inhibited CH synthesis from 14C-acetate by 80%. Surprisingly’ concurrent addition of mevinolin and PA did not significantly alter the stimulatory effects of PA. As observed differences in 14C-acetate and 14C-mevalonate precursor labeling could indicate PA affects early pathway events’ the effects of this monoterpene on HMG-CoA reductase activity were evaluated. Unexpectedly’ 1 mM PA did not stimulate activity of this enzyme. Consistent with its action as a reversibly bound inhibitor’ in washed microsomes’ 2 μM mevinolin pretreatment increased reductase protein expression causing a 12.7 (±2.4)-fold compensatory HMG-CoA reductase activity increase; concurrent treatment with 1 mM PA attenuated this to a 5.3 (±0.03)-fold increase. Gas chromatographic analysis confirmed CH was the major lipid present in the measured thin-layer chromatography spot. Since 14C-acetate incorporation into free fatty acid and phospholipid pools was not significantly affected by PA treatment’ nonspecific changes in whole acetate pool sizes were not indicated. Because increases in endogenous CH synthesis should result in compensatory changes in exogenous sterol utilization’ the effects of PA upon low density lipoprotein (LDL) receptor activity were evaluated. Consistent with the observed increases in CH synthesis’ 1 mM PA decreased 125I-LDL internalization to 50% of the fetal bovine serum control; concurrent addition of 2 μM mevinolin attenuated this effect to a reduction of 80% of the control value. Data suggest that in certain colonic tumor cells PA strongly affects cholesterol metabolism via a mechanism of action that is insensitive to the HMG-CoA reductase inhibitor mevinolin. 相似文献
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Small W. IV Metzger M.F. Wilson T.S. Maitland D.J. 《IEEE journal of selected topics in quantum electronics》2005,11(4):892-901
Due to the narrow (3-h) treatment window for effective use of the thrombolytic drug recombinant tissue-type plasminogen activator (rt-PA), there is a need to develop alternative treatments for ischemic stroke. We are developing an intravascular device for mechanical thrombus removal using shape memory polymer (SMP). We propose to deliver the SMP microactuator in its secondary straight rod form (length=4 cm, diameter=350 /spl mu/m) through a catheter distal to the vascular occlusion. The microactuator, which is mounted on the end of an optical fiber, is then transformed into its primary corkscrew shape by laser heating (diode laser, /spl lambda/=800 nm) above its soft-phase glass transition temperature (T/sub gs/=55/spl deg/C). Once deployed, the microactuator is retracted, and the captured thrombus is removed to restore blood flow. The SMP is doped with indocyanine green (ICG) dye to increase absorption of the laser light. Successful deployment of the microactuator depends on the optical properties of the ICG-doped SMP, as well as the optical coupling efficiency of the interface between the optical fiber and the SMP. Spectrophotometry, thermal imaging, and computer simulation aided the initial design effort and continue to be useful tools for optimization of the dye concentration and laser power. Thermomechanical testing was performed to characterize the elastic modulus of the SMP. We have demonstrated laser activation of the SMP microactuator in air at room temperature, suggesting this concept is a promising therapeutic alternative to rt-PA. 相似文献
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IV Bychkovskaia RP Stepanov PV Antonov DN Cherniakova 《Canadian Metallurgical Quarterly》1996,36(6):926-931
Electron microscopic investigation of capillary endothelium cells in myocardium of irradiated rats revealed an unusual effect of persistent increase of probability of cell damage, similar in many relations to that described earlier for various unicellular species. New effect, unlike those traditionally studied, is characterised by non-stochastic nature, large number of the involved cells, reveals itself even after faint influences, and can be induced as well by agents other than radiation. The question is put on the probable commonness between these changes and the pseudomutagenesis which has the similar phenomenology. 相似文献
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A comparative analysis is given of the gastric cancer incidence in the Tjumen Province for a period of 1959--1973. There was noted a direct dependence between the rate and number of risk factors (the complexes of unfavourable factors) in males and females. A conclusion is made that a higher incidence rate (1.7 times more) of gastric cancer among males may be attributed to the complexes of infavourable factors to which they are subject to a greater extent, 1.7 times as often as females, (mainly to bad habits) but not to biological features of the organism. Elimination of these harmful effects on the body would lessen the risk of this affection. 相似文献
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