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Showing 2001–2020 of 2058 publications.
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Grant, Adrienne J.; Jessup, Wendy K.; Dean, Roger T.We have previously shown that the intracellular half-life of endocytosed oxidized albumin is much longer than that of native albumin. We now report that the regions of oxidized albumin which contain oxidation products (carbonyls and fluorophores), are less readily released as small degradation products by cell-free proteolysis than is the molecule overall. We deduce that oxidized moieties in the polypeptide chain can confer localized resistance to enzymatic proteolysis. Such resistance to proteolysis may account for the intracellular accumulation of some endocytosed oxidized protein which we have previously observed. 1993 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted.
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Ingold, Keith U.; Bowry, Vincent W.; Stocker, Roland; Walling, ChevesRecent studies on the initial stages in oxidation of low density lipoprotein (LDL) have revealed certain previously unrecognized similarities to emulsion polymerization and some quite unexpected features including the following: (i) ascorbate is an extremely effective antioxidant for LDL containing a?-tocopherol (?-TOH); (ii) in the presence of ?-TOH and in the absence of both ascorbate and ubiquinol 10 (Q<inf>10</inf>H<inf>2</inf>), oxidation of LDL occurs via a free radical chain; (iii) Q<inf>10</inf>H<inf>2</inf> is a much better antioxidant for LDL than ?-TOH, although the reverse is true in homogeneous systems. We show here that these problems can be solved on the basis of three simple hypotheses, each of which is based on known chemistry: (i) ?-TOH in LDL can be regenerated from its radical, ?-TO, by ascorbate; (ii) in the absence of ascorbate and Q<inf>10</inf>H<inf>2</inf>, the ?-TOH in LDL acts as a chain-transfer agent rather than as a radical trap; (iii) Q<inf>10</inf>H<inf>2</inf> is a much more effective chain-breaking antioxidant than ?-TOH in LDL because the semiquinone radical Q<inf>10</inf>H exports its radical character from the LDL into the aqueous phase. Our conclusions imply that the search for better antiatherosclerotic drugs might profitably focus on antioxidants capable of exporting radicals from LDL particles or otherwise increasing the traffic of radicals between particles.
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Sullivan, David R.; Lam, Christopher Wai Kei; Jessup, Wendy K.; Dean, Roger T.; Hensley, William J.We investigated the reciprocal changes in apolipoprotein(a) concentration in the lipoprotein of d > 1.006 and the triglyceride-rich lipoprotein (TRL) fractions of plasma which occur in vivo following fat ingestion. Twenty fasting subjects were studied before and 4 h after a fat-rich meal. In 75% of cases, in vitro incubation of the postprandial (4-h) TRL with autologous fasting (0-h) lipoproteins of d > 1.006 resulted in further substantial (>5% total) reciprocal changes in apo(a) concentration of the 2 fractions. The increase in re-isolated postprandial TRL apo(a) was 25.1% 5.1% of the total apo(a), compared to the insignificant increase (0.1% 0.1%) in re-isolated fasting TRL. Most of the further increase in 4-h TRL apo(a) (94% 4%) could be achieved by incubation with the corresponding 4-h chylomicron fraction (CM) alone. The re-isolated 4-h TRL apo(a) concentration correlated positively with 4-h plasma TG concentration (r = 0.65, P < 0.01) and other indices of postprandial lipaemia. In vitro incubation of pooled serum lipoproteins of d > 1.006 with serial dilutions of nascent CM obtained from chylous ascitic fluid revealed that the reciprocal changes in apo(a) concentration exhibit a curvilinear relationship with the concentration of CM triglyceride which plateaued round 7 mmol/1 in this instance. We conclude that the reciprocal changes in apo(a) concentration between TRL and lipoproteins of d > 1.006 which occur in the postprandial phase are quantitatively significant and largely represent a redistribution process rather than de novo synthesis because they can be reproduced by in vitro incubation. 1993.
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Tomlinson, Stephen A.; Stanley, Keith K.; Esser, Alfred F.The 3' region of trout C9 has been resequenced and found to differ from the previously published sequence (Stanley and Herz, EMBO J. 6:1951; 1987). In contrast to other sequenced C9 molecules, but in common with the other terminal complement components, trout C9 was found to contain an additional carboxy terminal thrombospondin domain. This domain does not restrict polymerization, as has been previously suggested (Stanley and Luzio, Nature 334:475; 1988), since alternative pathway activation of trout complement by rabbit erythrocytes lead to the formation of circular membrane attack complement lesions on the erythrocyte membrane. Although the trout C9 molecule is larger than human C9, the diameters of circular trout membrane attack complexes were approximately 30% smaller than their human counterparts. No lysis of erythrocytes bearing human C5b-7 or C5b-8 complexes was detected following incubation with trout serum containing EDTA, which suggests that trout C8 and C9 are unable to bind to human C7 and C8, respectively. Finally, trout and human serum were equally effective at killing the human serum-sensitive strain Salmonella minnesota Re595. 1993.
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Dawes, JoanHeparins are exposed in vivo to a complex environment containing heparin-binding proteins in solution, on the surface of cells and in the extracellular matrix. However, most studies of heparin binding have been carried out in simplified systems which fail to address the competition for binding resulting both from the different concentrations of constitutent proteins and their relative affinities for heparin. In the blood heparin binds to platelets in a saturable, specific and reversible interaction which occurs in the presence of competing plasma proteins and which may be prothrom- botic. Similar binding to monocytes and endothelial cells occurs but has not yet been confirmed in whole blood. Such interactions could inhibit coagulation resulting from generation of tissue factor activity and modulate endothelial responses which affect coagulation, fibrinolysis and cell growth as well as representing a physiologically significant anti-inflammatory function of heparin. Low-molecular-weight (LMW) heparins have lower affinities than unfraclionated heparin for all cell receptors studied and are less likely to exert their effects through cellular interactions. In whole plasma in the absence of platelet release, antithrombin III was the most abundant protein bound to therapeutic doses of unfractionated heparin, and histidine-rich glycoprotein its only effective competitor, while both histidine-rich glycoprotein and vitronectin were potentially important modulators of LMW heparin activity. Sequestration of vitronectin and complement factor H by immobilised heparins could promote an effective defence against complement-mediated prothrombotic activity and cell damage under physiological conditions. In addition, the ability of immobilised heparin to bind fibronectin, vitronectin and fibrinogen in a plasma milieu may increase the exposure of these adhesive ligands and stimulate interaction with activated platelets through the ?<inf>IIb</inf>/?<inf>3</inf>-integrin. 1993 S. Karger AG, Basel.
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Dudman, Nicholas Peter B.; Wilcken, David E.L.; Stocker, RolandElevated circulating homocyst(e)ine is a risk factor for occlusive vascular disease. We explored whether elevated plasma homocyst(e)ine is associated with increased plasma lipid hydroperoxides that might trigger vascular disease. We obtained plasma containing high levels of homocyst(e)ine from four patients with a homozygous deficiency of cystathionine ?-synthase activity and also from four heterozygotes with a deficiency of this enzyme after an oral methionine load. The mean plasma non-protein-bound homocyst(e)ine level in all subjects was more than 11-fold higher than the mean normal fasting value. Levels of high density lipoprotein (HDL) cholesteryl ester hydroperoxides (CEOOH), normalized against the concentration of free cholesterol in HDL, were not elevated in our subjects (meanSD, 0.00910.0061) compared with values for 14 fasting healthy donors (0.01640.0086). An inverse dependency was observed between plasma total homocyst(e)ine and HDL CEOOH (r=-0.78, p=0.023). Also, the ubiquinol-10/ubiquinone-10 ratio in HDL, which is expected to fall during oxidative stress, increased with plasma homocyst(e)ine. Since HDL contains the majority of detectable plasma lipid hydroperoxides, of which CEOOHs are the most abundant, our data suggest that an elevated plasma homocyst(e)ine level does not enhance oxidative stress, increase the levels of lipid hvdroperoxides in plasma, or generate vascular damage by this mechanism.
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Dean, Roger T.; Gieseg, Steven Paul; Davies, Michael J.Hydroperoxides and catechols are described as novel reactive products of radical attack on proteins. These species, like other components of oxidized and otherwise damaged proteins, may accumulate in some biological systems. We propose that the reactive species may then attack other biomolecules, and constitute both a marker and a mechanism of age-related pathologies. 1993.
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Hazell, Linda J.; Stocker, RolandOxidation of low-density lipoprotein (LDL) lipid is thought to represent the initial step in a series of oxidative modification reactions that ultimately transform this lipoprotein into an atherogenic high-uptake form that can cause lipid accumulation in cells. We have studied the effects of hypochlorite, a powerful oxidant released by activated monocytes and neutrophils, on isolated LDL. Exposure of LDL to reagent hypochlorite (NaOCl) at 4C resulted in immediate and preferential oxidation of amino acid residues of apoprotein B-100, the single protein associated with LDL. Neither lipoprotein lipid nor LDL-ssociated antioxidants, except ubiquinol-10, represented major targets for this oxidant. Even when high concentrations of NaOCl were used, only low levels of lipid hydroperoxides could be detected with the highly sensitive h.p.l.c. post-column chemiluminescence detection method. Lysine residues of apoprotein B-100 quantitatively represented the major target, scavenging some 68% of the NaOCl added, with tryptophan and cysteine together accounting for an additional 10% of the oxidant. Concomitant with the loss of LDL's amino groups, chloramines were formed and the anionic surface charge of the lipoprotein particle increased, indicated by a 3-4-fold increase in electrophoretic mobility above that of native LDL on agarose gels. While both these changes could be initially reversed by physiological reductants such as ascorbic acid and methionine, incubation of the NaOCl-modified LDL at 37C resulted in increasing resistance of the modified lysine residues against reductive reversal. Exposure of mouse peritoneal macrophages to NaOCl-oxidized LDL resulted in increased intracellular concentrations of cholesterol and cholesteryl esters. These findings suggest that lipid-soluble antioxidants associated with LDL do not efficiently protect the lipoprotein against oxidative damage mediated by hypochlorite, and that extensive lipid oxidation is not a necessary requirement for oxidative LDL modification that leads to a high-uptake form of the lipoprotein.
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Jessup, Wendy K.; Dean, Roger T.[No abstract available]
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Christen, Stephan; Stocker, RolandA convenient and rapid method for the simultaneous determination by HPLC of 3-hydroxyanthranilic acid and the dimer derived by its oxidation, cinnabarinic acid, is described. Buffers or biological samples containing these two Trp metabolites were acidified to pH 2.0 and extracted with ethyl acetate with recoveries of 96.5 0.5 and 93.4 3.7% for 3-hydroxyanthranilic and cinnabarinic acid, respectively. The two compounds were separated on a reversed-phase (C<inf>18</inf>) column combined with ion-pair chromatography and detected photometrically or electrochemically. The method was applied successfully to biological systems in which formation of either 3-hydroxyanthranilic or cinnabarinic acid had been described previously. Thus, interferon-?-treated human peripheral blood mononuclear cells formed and released significant amounts of 3-hydroxyanthranilic acid into the culture medium and mouse liver nuclear fraction possessed high "cinnabarinic acid synthase" activity. In contrast, addition of 3-hydroxyanthranilic acid to human erythrocytes resulted in only marginal formation of cinnabarinic acid. We conclude that the method described is specific, sensitive, and suitable for the detection of the two Trp metabolites in biological systems. 1992.
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Christen, Stephan; Stacker, Roland; Southwell-Keely, Peter T.Since 3-hydroxyanthranilic acid (3HAA), an oxidation product of tryptophan metabolism, is a powerful radical scavenger [Christen, S., Peterhans, E., & Stocker, R. (1990) Proc. Natl. Acad. Sci. U.S.A. 87, 2506], its reaction with peroxyl radicals was investigated further. Exposure to aqueous peroxyl radicals generated at constant rate under air from the thermolabile radical initiator 2, 2'-azobis[2-amidinopropane] hydrochloride (AAPH) resulted in rapid consumption of 3HAA with initial accumulation of its cyclic dimer, cinnabarinic acid (CA). The initial rate of formation of the phenoxazinone CA accounted for ?75% of the initial rate of oxidation of 3HAA, taking into account that 2 mol of 3HAA are required to form 1 mol of CA. Consumption of 3HAA under anaerobic conditions (where alkyl radicals are produced from AAPH) was considerably slower and did not result in detectable formation of CA. Addition of superoxide dismutase enhanced autoxidation of 3HAA as well as the initial rates of peroxyl radical-induced oxidation of 3HAA and formation of CA by ?40-50%, whereas inclusion of xanthine/xanthine oxidase decreased the rate of oxidation of 3HAA by ?50% and inhibited formation of CA almost completely, suggesting that superoxide anion radical (O<inf>2</inf> .- was formed and reacted with reaction intermediate(s) to curtail formation of CA. Formation of CA was also observed when 3HAA was added to preformed compound I of horseradish peroxidase (HRPO) or catalytic amounts of either HRPO, myeloperoxidase, or bovine liver catalase together with glucose/glucose oxidase. In the case of preformed HRPO compound I, oxidation of 3HAA into CA proceeded to the same extent under both aerobic and anaerobic conditions, indicating that it did not require molecular oxygen per se. The results suggest that oxidative dimerization of 3HAA into CA can be obtained by initial and successive one-electron oxidation reactions mediated by either free radicals or compound I of peroxidases or catalase. 1992, American Chemical Society. All rights reserved.
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Grant, Adrienne J.; Jessup, Wendy K.; Dean, Roger T.Native bovine serum albumin (BSA) was endocytosed and degraded at a steady rate by resident peritoneal murine macrophages with barely detectable amounts remaining within the cells. Radical-damaged BSA was endocytosed and degraded up to 25-fold more rapidly than native BSA, but some radical-damaged BSA accumulated within the cells in a time-dependent manner. The extent of accumulation increased in parallel with that of radical damage. Thus, some radical-damaged BSA was processed less efficiently than native BSA. Such inefficient catabolism of radical-damaged proteins may contribute to certain diseases such as atherosclerosis. 1992.
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Lackmann, Martin; Cornish, Coralie J.; Simpson, Richard J.; Moritz, Robert L.; Geczy, Carolyn L.In delayed-type hypersensitivity reactions, cytokine-mediated cell migration leads to localized accumulation of neutrophils and mononuclear cells over 4-48 h. In contrast to transient (2-6 h) responses elicited by other chemotactic factors, earlier studies indicated that a chemotactic activity previously described in our laboratory elicited skin test responses over 24 h, identical to those induced by injection of antigen into a sensitized test subject. We have isolated this factor, a 10.3-kDa chemotactic protein designated CP-10, from supernatants of activated murine spleen cells. Purification to homogeneity was achieved using affinity chromatography on iminodiacetic acid-immobilized copper and cation-exchange, mixed mode (cation exchange/metal affinity), reversed-phase, and size-exclusion high performance liquid chromatography. CP-10 had maximal chemotactic activity for neutrophils at 10-13 M. The 76-amino acid sequence, obtained by automated N-terminal microsequence analysis of native CP-10, and fragments derived from trypsin digestion and cyanogen bromide cleavage indicated no sequence identity with any known cytokine or chemotactic factor but revealed up to 55% sequence homology with S100, Ca2+-binding proteins. CP-10 appears to be the first protein of this family with a well defined function affecting cell migration, and its biological potency suggests an important role for this cytokine in cellular immune reactions.
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Jessup, Wendy K.; Mander, Erin L.; Dean, Roger T.We have studied the effect of several chemical modifications to low-density lipoprotein (LDL) on its intracellular fate in macrophages. Native, acetylated and oxidized 125I-LDL were supplied to cultured peritoneal macrophages and the accumulation and distribution of labelled protein was measured both during uptake and a subsequent chase period. The intracellular accumulation of macromolecular oxidized LDL protein greatly exceeded that of acetylated LDL, despite similar rates of uptake and common endocytic receptors. The accumulation of intracellular apoprotein was proportional to the extent to which the LDL was first oxidized. ApoB of oxidized LDL was more resistant to proteolysis by lysosomal enzymes than native apoB. Interestingly, acetylated apoB is more rapidly hydrolysed than the native protein. 125I-LDL modified with 4-hydroxynonenal (HNE) and myricetin, but not with malondialdehyde (MDA), was also accumulated within macrophages in a high-molecular weight fraction, and was resistant to cell-free lysosomal proteolysis. These forms of LDL also contained crosslinked apoB molecules. It is suggested that the accumulation of oxidized LDL within macrophages may he due, at least in part, to the formation of interior intra-molecular crosslinks in apoB which render it less accessible to proteolysis. 1992.
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Jessup, Wendy K.; Mohr, Detlef; Gieseg, Steven Paul; Dean, Roger T.; Stocker, RolandThe potential role of nitric oxide radical (NO ) in macrophage-mediated oxidation and conversion of human low density lipoprotein (LDL) to a high-uptake form was examined by exposing LDL to aerobic solutions to either NO or 3-morpholinosydnonimine-hydrochloride (SIN-1, a compound that spontaneously forms NO and superoxide anion radical) or to mouse peritoneal macrophages in the presence and absence of modulators of cellular NO synthesis. Incubation with NO alone caused oxidation of LDL's ubiquinol-10 and accumulation of small amounts of lipid hydroperoxidases, but failed to form any high-uptake ligand for endocytosis by macrophages and did not alter the LDL particle charge or the integrity of apoB. Exposure of LDL to SIN-1 resulted in complete consumption of all antioxidants and substantial formation of lipid hydroperoxidases, but again had little effect on the lipoprotein particle charge or generation of high-uptake form. Preincubation of macrophages with interferon-? increased the cells ability to generate reactive nitrogen metabolites. The extent of cell-mediated oxidation of LDL and the generation of high-uptake LDL was substantial in resident cells in which NO synthesis was barely detectable, depressed in cells active in NO synthesis and restored when NO synthesis was suppressed by the arginine analogue, NMMA. These results suggest that, while longer with superoxide anion radical, NO can oxidize LDL, its synthesis is not required for macrophage-mediated oxidation of LDL in vitro; rather it exerts a protective role in preventing oxidative LDL modification by macrophages. 1992.
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Dawes, Joan; Pepper, Duncan S.Heparin and other anticoagulant glycosaminoglycans were radiolabelled with 125I and their catabolism by human vascular endothelial cells in culture was studied. Heparin, heparan sulphate and pentosan polysulphate were associated with the cellular fraction and incorporated into the subendothelial matrix, but dermatan sulphate was not found in either fraction. High molecular weight, fully desulphated carbohydrate chains were major catabolic products of all those glycosaminoglycans which were taken up by the cells. Pentosan polysulphate was not degraded further, but the catabolism of heparan sulphate, and to a lesser extent that of heparin, also yielded small oligosaccharides. Thus the first step in catabolism of exogenous glycosaminoglycans by human vascular endothelial cells appears to be complete desulphation, which destroys their biological activity, followed by depolymerisation of the carbohydrate chain. This alternative to the sequential action of lysosomal exoenzymes is dependent upon binding to the cell; thus dermatan sulphate, which is not associated with the cellular fraction, is not catabolised.
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Buffinton, Gary D.; Christen, Stephan; Peterhans, Ernst; Stocker, RolandAs oxidative stress has been implicated in the pathogenesis of certain viral diseases we determined antioxidant and prooxidant parameters in lungs and bronchoalveolar lavage fluid (BALF) of mice infected with a lethal dose of influenza A/PR8/34 virus. Viral infection was characterized by massive infiltration of leukocytes, mainly polymorphonuclear leukocytes, into the alveolar space. The total number of BALF cells increased up to 8-fold (day 3 post-infection) and these cells appeared activated as judged by their increased rates of superoxide anion radical (O<inf>2</inf>-) generation upon stimulation. Maximal rates of radical generation by BALF cells during the early stages of infection were 15- or 70-fold higher than those of cells from control animals when expressed per cell or total BALF cells, respectively. At the terminal stages of infection the total capacity of BALF cells to release of declined to ? 35-fold the control values. Infection also resulted in increased in vivo formation of hydrogen peroxide (H2O2) within the lungs at a time that coincided with the maximal capacity of BALF cells to release O<inf>2-</inf>. Whereas pulmonary activities of glutathione peroxidase and reductase remained unaltered, levels of ascorbate in the cell-free BALF decreased significantly during the early stages of the infection and then returned to normal levels and above, late in infection. The oxidation state of the dehydroascorbic acid/ ascorbate couple increased concomitantly with the decrease in ascorbate concentrations early in infection and remained elevated throughout the infection. As assessed by the prevention of peroxyl radical-induced loss of phycoerythrin fluorescence, the total antioxidant capacity present in lung tissue homogenate from terminally ill animals was not diminished when compared to that prepared from lungs of control mice. We conclude that although early stages of influenza infection are associated with the presence of oxidative stress in the lung tissue and alveolar fluid lining the epithelial cells, this stress does not appear to overwhelm local antioxidant defenses. The results therefore do not support a direct causative role of oxidative tissue damage in the pathogenesis of influenza virus infection. 1992 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted.
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Bowry, Vincent W.; Ingold, Keith U.; Stocker, RolandUptake of oxidatively modified low-density lipoprotein (LDL) by cells in the arterial wall is believed to be an important early event in the development of atheroscelerosis. Because vitamin E is the major antioxidant present in human lipoproteins, it has received much attention as a suppressor of LDL lipid oxidation and as an epidemiological marker for ischaemic heart disease. However, a careful examination of lipid peroxidation in LDL induced by a steady flux of aqueous peroxyl radicals has demonstrated that, following consumption of endogenous ubiquinol-10, the rate of peroxidation (i) declines as vitamin E is consumed, (ii) is faster in the presence of vitamin E than following its complete consumption, (iii) is substantially accelerated by enrichment of the vitamin in LDL, either in vitro or by diet, and (iv) is virtually independent of the applied radical flux. We propose that peroxidation is propagated within lipoprotein particles by reaction of the vitamin E radical (i.e. ?-tocopheroxyl radical) with polyunsaturated fatty acid moieties in the lipid. This lipid peroxidation mechanism, which can readily be rationalized by the known chemistry of the ?-tocopheroxyl radical and by the radicalisolating properties of fine emulsions such as LDL, explains how reagents which reduce the ?-tocopheroxyl radical (i.e. vitamin C and ubiquinol-10) strongly inhibit lipid peroxidation in vitamin E-containing LDL.
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Supanaranond, Wichai; Davis, Timothy M.E.; Dawes, Joan; Silamut, Kamolrat; Vilaiwanna, Nitatt; White, Nicholas J.To investigate in vivo platelet function in acute falciparum malaria plasma concentrations of ?thromboglobulin (?TG), platelet factor 4 (PF4) and thrombospondin (TSP) were determined in 10 severely-ill Thai patients and 11 healthy volunteers. 8 patients recovered. At presentation, the platelet counts of the 10 patients were significantly lower (p < 0.025) than those of the controls, and a slight but significant increase (p < 0.05) in ?TG/PF4 ratios in the patients suggested low-grade platelet activation. Presentation plasma ?TG and PF4 concentrations did not differ from control values, probably due to the opposing effects of decreased circulating platelet mass and increased activation. By contrast, admission concentrations of TSP in the surviving patients were markedly lower (p < 0.001) than those of the controls; ?TG/PF4 ratios, but not TSP levels, returned to normal during treatment. Hepatic dysfunction and oliguric renal failure probably contributed to a sustained increase in plasma ? - TG and TSP in the 2 fatally ill patients, but associated elevated PF4 levels indicated concomitant platelet activation. Our results support the suggestion that in vivo platelet activation, which appears to be rapidly controlled by treatment, occurs in patients with severe, non-fatal falciparum malaria. TSP production, apparently from non-platelet sources, was decreased and/or its consumption was increased in these patients, perhaps by factors such as cytoadherence of infected erythrocytes and consequent endothelial damage. 1992 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted.
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Mohr, Detlef; Bowry, Vincent W.; Stocker, RolandUbiquinol-10 (CoQH<inf>2</inf>, the reduced form of coenzyme Q<inf>10</inf>) is a potent antioxidant present in human low-density lipoprotein (LDL). Supplementation of humans with ubiquinone-10 (CoQ, the oxidized coenzyme) increased the totaentrations of CoQH<inf>2</inf> in plasma acid and in all of its lipoproteins. Intake of a single oral dose of 100 or 200 mg CoQ increased the total plasma coenzyme content by 80 or 150%, respectively, within 6 h. Long-term supplementation (three times 100 mg CoQ/day) resulted in 4-fold enrichment of CoQH<inf>2</inf> in plasma and LDL with the latter containing 2.8 CoQH<inf>2</inf> molecules per LDL particle (on day 11). Approx. 80% of the coenzyme was present as CoQH<inf>2</inf> and the CoQH<inf>2</inf>/CoQ ratio was unaffected by supplementation, indicating that the redox state of coenzyme Q<inf>10</inf> is tightly controlled in the blood. Oxidation of LDL containing various [CoQH<inf>2</inf>] by a mild, steady flux of aqueous peroxyl radicals resulted immediately in very slow formation of lipid hydroperoxides. However, in each case the rate of lipid oxidation increased markedly with the disappearance of 80-90% CoQH<inf>2</inf>. Moreover, the cumulative radical dose required to reach this 'break point' in lipid oxidation was proportional to the amount of CoQH<inf>2</inf> incorporated in vivo into the LDL. Thus, oral supplementation with CoQ increases CoQH<inf>2</inf> in the plasma and all lipoproteins thereby increasing the resistance of LDL to radical oxidation. 1992.
