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C E Thomas

Publications and source records attributed to C E Thomas.

At least 55 records · Page 3Linked to original sources
PubMed1996

Isolation and analysis of a fur mutant of Neisseria gonorrhoeae.

The pathogenic Neisseria spp. produce a number of iron-regulated gene products that are thought to be important in virulence. Iron-responsive regulation of these gene products has been attributed to the presence in Neisseria spp. of the Fur (ferric uptake regulation) protein. Evidence for the role of Fur in neisserial iron regulation has been indirect because of the inability to make fur null mutations. To circumvent this problem, we used manganese selection to isolate missense mutations of Neisseria gonorrhoeae fur. We show that a mutation in gonococcal fur resulted in reduced modulation of expression of four well-studied iron-repressed genes and affected the iron regulation of a broad range of other genes as judged by two-dimensional polyacrylamide gel electrophoresis (PAGE). All 15 of the iron-repressed spots observed by two-dimensional PAGE were at least partially derepressed in the fur mutant, and 17 of the 45 iron-induced spots were affected by the fur mutation. Thus, Fur plays a central role in regulation of iron-repressed gonococcal genes and appears to be involved in regulation of many iron-induced genes. The size and complexity of the iron regulons in N. gonorrhoeae are much greater than previously recognized.

Bacterial Proteins↗
PubMed1996

Asymmetry of intracranial hemodynamics as an indicator of mass effect in acute intracerebral hemorrhage. A transcranial Doppler study.

BACKGROUND AND PURPOSE: Hematoma volume is an important determinant of outcome and predictor of clinical deterioration in patients with intracerebral hemorrhage. In many cases, worsening results from herniation due to compartmentalized pressure gradients. We used transcranial Doppler sonography (TCD) to assess the impact of hematoma volume on symmetry of intracranial hemodynamics in patients with acute intracerebral hemorrhage. The goal was to evaluate TCD as a noninvasive method for monitoring compartmentalized mass effect. METHODS: TCD was performed an average of 1.1 days (range, 0 to 3 days) after onset in 30 patients with supratentorial intracerebral hemorrhage. Hematoma, hematoma + edema, and intraventricular hemorrhage volumes were calculated from admission CT scans using computerized planimetry and were compared with combined TCD values from the middle cerebral and internal carotid arteries. RESULTS: Ipsilateral pulsatility indexes were consistently elevated and mean velocities consistently depressed when intracerebral hemorrhage volumes exceeded 25 mL. Compared with patients with small hemorrhages, those with large hemorrhages (> or = 25 mL, n = 10) had significantly higher ipsilateral pulsatility indexes (1.72 versus 1.13, P < .0001) and higher ratios of ipsilateral-to-contralateral pulsatility (1.29 versus 1.06, P = .001). The ratio of ipsilateral-to-contralateral mean velocity was similarly reduced in patients with large versus small hemorrhages (0.87 versus 1.06, P = .01), but this effect was less pronounced. In a multiple regression analysis, ipsilateral and contralateral pulsatility indexes correlated primarily with intraventricular hemorrhage volume (P < .001), whereas the ratio of ipsilateral-to-contralateral pulsatility correlated with total hemispheric lesion (hematoma + edema) volume (P = .003). CONCLUSIONS: Asymmetry of intracranial hemodynamics as assessed by TCD occurs when intracerebral hemorrhage volumes exceed 25 mL. Alterations of pulsatility index reflect intracranial lesion volume more reliably than mean velocity. Although pulsatility is strongly influenced by the presence of intraventricular blood, elevated ratios of ipsilateral-to-contralateral pulsatility correlate primarily with hemispheric lesion volume and may reflect compartmentalized intracranial pressure gradients.

Acute Disease↗
PubMed1995

Characterization of the hgbA locus encoding a hemoglobin receptor from Haemophilus ducreyi.

Haemophilus ducreyi can bind hemoglobin and use it as a source of heme, for which it has an obligate requirement. We previously identified and purified HgbA, a hemoglobin-binding outer membrane protein from H. ducreyi. In this report, we describe the molecular cloning, expression, DNA sequence, and mutagenesis of the structural gene for HgbA, hgbA. H. ducreyi and recombinant Escherichia coli expressing hgbA bound [125I]hemoglobin, establishing HgbA as a receptor. Insertions or deletions in the cloned hgbA gene abolished expression of HgbA and hemoglobin binding in E. coli. Mutagenesis of H. ducreyi by allelic exchange of insertions into hgbA abolished its ability to bind [125I]hemoglobin or utilize hemoglobin as a source of heme. The deduced protein sequence was similar to those of the TonB-dependent family of outer membrane receptors. The most similar member was HutA (heme receptor) from Vibrio cholerae. Tbp1 and Lbp1 (transferrin and lactoferrin receptors, respectively, from pathogenic Neisseria spp.) also showed very significant homology. Thus, by characterizing the hgbA locus, this work elucidates a potentially important role of HgbA in obtaining heme and/or iron from the host.

Amino Acid Sequence↗
PubMed1994

In vitro and in vivo activity of a novel series of radical trapping agents in model systems of CNS oxidative damage.

Many laboratory and clinical studies suggest that oxygen radical formation and resultant cell damage contribute to CNS injury following stroke and neurotrauma. Accordingly, antioxidants represent a viable therapeutic approach for management of CNS oxidative damage. Recently, several investigators have reported that the spin trap PBN protects against stroked-induced damage and reduces aging-associated neurological deficits. We have prepared and tested a cyclic analog of PBN, MDL 101,002, in a number of in vitro and in vivo assays designed to assess its neuroprotective properties. MDL 101,002 was found to be an effective .OH trap, to inhibit lipid peroxidation, and to decrease infarct size in a gerbil model of stroke. These results further indicate that oxidative damage arising from stroke contributes to infarct formation, and that spin traps are effective in ameliorating ischemia and reperfusion-induced CNS injury.

Animals↗
PubMed1994

Multiple mechanisms for inhibition of low density lipoprotein oxidation by novel cyclic nitrone spin traps.

Oxidation of low density lipoproteins (LDL) may be a critical atherogenic event owing to the diverse array of biologic effects attributed to modified LDL. Recently, we and others have demonstrated that the lipophilic nitrone spin trap alpha-phenyl-N-tert-butyl nitrone (PBN) can inhibit Cu(2+)-dependent LDL oxidation while the related, more hydrophilic analog alpha-(4-pyridyl-1-oxide)-N-tert-butyl nitrone is ineffective. Because the inhibitory activity of PBN is relatively weak as compared to hydrophobic phenolic antioxidants, we have synthesized a number of cyclic analogues of PBN that encompass a wide range of hydrophobicity and examined their ability to inhibit LDL oxidation in vitro. Formation of a six-membered ring by a bond formed from one methyl of the tert-butyl group to the aromatic ring yielded MDL 101,002, which was 3- and 24-fold more active than PBN against Cu2+ and 2,2'-azobis-2-amidinopropane hydrochloride-dependent oxidation, respectively. The effect of aromatic substituents was examined and, in general, activity positively correlated with hydrophobicity, particularly with Cu2+. Electron spin resonance (ESR) spectroscopy demonstrated that the PBN adduct in oxidized LDL is composed of a mobile component (exposed to the LDL aqueous phase) and an immobilized component, localized in the lipid-protein interface or in the bulk lipid. The most active cyclic nitrones exhibited only highly immobilized adducts, suggesting they are buried within the particle. Studies with MDL 105,185 (which is a chloro-substituted nitrone containing a seven-membered ring rather than six-membered as for MDL 101,002) demonstrated radical trapping in both the lipid and apoprotein fractions. Compounds in which a spirocyclohexyl ring was substituted for the gem-dimethyl methylene (MDL 102,832 and 101,694) formed hydrophobic Cu2+ complexes that were observed in the lipid fraction by ESR. This result was confirmed by fractionation of LDL oxidation reaction mixtures and spectrophotometric quantitation of associated Cu2+. The ability to bind Cu2+ was dependent upon the presence of the spirocyclohexyl ring. These data demonstrate that cyclic nitrones can inhibit LDL oxidation at exceedingly low concentrations by multiple mechanisms: 1) trapping of lipid-derived radicals, 2) trapping of apoprotein B-derived radicals, and 3) binding of Cu2+ ions. It is suggested that this new class of highly potent spin traps may be used as effective radical traps in free radical biology and medicine.

Copper↗
PubMed1994

Human hepatic triglyceride lipase expression reduces high density lipoprotein and aortic cholesterol in cholesterol-fed transgenic mice.

We have produced a line of transgenic mice expressing human hepatic triglyceride lipase (hH-TGL) to examine the in vivo effects of hepatic lipase expression on high density lipoprotein catabolism. Activation of metallothionine I promoter-hH-TGL cDNA transgene produced high levels of lipase mRNA in liver, heart, and kidney and elevated enzyme activity as assayed in post-heparin plasma. In a series of hyperlipidemic diet studies in which zinc was included in the diet to induce the transgene, hH-TGL expression was associated with a 34% lowering of plasma HDL-cholesterol levels (p < 0.01) when compared with animals on the same hyperlipidemic diet without zinc. This lowering of HDL cholesterol was paralleled by a decrease in total cholesterol and a decrease in HDL particle size. SDS-polyacrylamide gel electrophoresis analysis of the smaller HDL particles revealed that apolipoprotein AI was still the major apoprotein associated with the HDL. Quantitative analysis of abdominal aortic cholesterol content from the same animals suggests that the observed changes in plasma HDL by hH-TGL over-expression correlated with a decrease in the accumulation of aortic cholesterol (42%, p < 0.01). These data support the hypothesis that hH-TGL mediates a non-receptor pathway for the clearance of cholesterol from the plasma compartment.

Animals↗
PubMed1994

Cloning and constitutive expression of structural genes encoding gonococcal porin protein in Escherichia coli and attenuated Salmonella typhimurium vaccine strains.

Previous reports [Gotschlich et al., Proc. Natl. Acad. Sci. USA 84 (1987) 8135-8139; Carbonetti and Sparling, Proc. Natl. Acad. Sci. USA 84 (1987) 9084-9088; Carbonetti et al., Proc. Natl. Acad. Sci. USA 85 (1988) 6841-6845] concluded that synthesis of the porin protein (Por) from Neisseria gonorrhoeae in Escherichia coli was toxic to that organism, which limited studies of the biology of Por in foreign hosts. We assembled intact por genes from the gonococcal strains, FA19 (serogroup PIA) and FA6434 (a hybrid Por containing epitopes from serogroups PIA and PIB), and observed stable expression in E. coli without evident toxicity. Expression of por from strain MS11 (serogroup PIB) in E. coli was difficult, but por from MS11 was expressed without toxicity when the -35 region of the por promoter was removed. Encouraged by this, we moved por from E. coli into attenuated Salmonella typhimurium strains and expressed por either in single copy from the chromosome or in multiple copy from plasmids. Expression levels of por in S. typhimurium were higher from plasmids than from the chromosome, probably due to a gene dosage effect. This work will enable study of the immune response to Por in mice vaccinated orally with live S. typhimurium.

Bacterial Vaccines↗
PubMed1994

The representation of location in visual images.

By definition, visual image representations are organized around spatial properties. However, we know very little about how these representations use information about location, one of the most important spatial properties. Three experiments explored how location information is incorporated into image representations. All of these experiments used a mental rotation task in which the location of the stimulus varied from trial to trial. If images are location-specific, these changes should affect the way images are used. The effects from image representations were separated from those of general spatial attention mechanisms by comparing performance with and without advance knowledge of the stimulus shape. With shape information, subjects could use an image as a template, and they recognized the stimulus more quickly when it was at the same location as the image. Experiment 1 demonstrated that subjects were able to use visual image representations effectively without knowing where the stimulus would appear, but left open the possibility that image location must be adjusted before use. In Experiment 2, distance between the stimulus location and the image location was varied systematically, and response time increased with distance. Therefore image representations appear to be location-specific, though the represented location can be adjusted easily. In Experiment 3, a saccade was introduced between the image cue and the test stimulus, in order to test whether subjects responded more quickly when the test stimulus appeared at the same retinotopic location or same spatiotopic location as the cue. The results suggest that location is coded retinotopically in image representations. This finding has implications not only for visual imagery but also for visual processing in general, because it suggests that there is no spatiotopic transform in the early stages of visual processing.

Adolescent↗
PubMed1994

Identification and cloning of a fur homologue from Neisseria meningitidis.

The iron response in a number of bacterial systems is mediated by fur (ferric uptake regulation)-like regulatory systems. We have cloned and characterized a gene from Neisseria meningitidis that was homologous to Escherichia coli fur. This clone was capable of modulating expression from both E. coli and neisserial iron-regulated promoters in response to iron, and it produced a protein that reacted with anti-E. coli fur serum. Although the DNA and predicted amino acid sequences were very similar to those of four other published fur homologues, meningococcal fur was the most divergent of the group. Inability to construct a meningococcal fur mutant suggested that fur may be essential in this species.

Amino Acid Sequence↗
PubMed1994

Protective effects of a cyclic nitrone antioxidant in animal models of endotoxic shock and chronic bacteremia.

Evidence of a role for oxygen-derived free radicals in the pathophysiology of endotoxic shock has been found in animal models. However, the importance of free radicals in chronic models of bacterial infection has not been examined. In this study a novel nitrone radical spin trap is described and its activity in animal models of endotoxic shock and chronic bacteremia were explored. MDL 101,002 is a cyclized variant of alpha-phenyl N-tert-butyl nitrone (PBN), an established spin trap. MDL 101,002 can react with free radicals to form persistent adducts as demonstrated by electron paramagnetic resonance (EPR) spectroscopy. This agent is about 10 times more potent than PBN as an in vitro antioxidant and scavenger of hydroxyl radicals. In a rat endotoxic shock model MDL 101,002 (3-30 mg/kg, i.p.) administered 30 min prior to endotoxin (30 mg/kg, i.p.) treatment reduced mortality in a dose-dependent manner. Peroxide-enhanced chemiluminescence in hepatic homogenates from endotoxin treated rats was elevated indicating that oxidative stress and antioxidant depletion was increased. Importantly, treatment with MDL 101,002 (30 mg/kg, i.p.) 30 min prior to, and 120 min following endotoxin, minimized the increase in chemiluminescence. MDL 101,002 also reduced mortality in a model of chronic bacteremia employing implantation of infected fibrin clots into the peritoneal cavity of gentamicin-treated leukopenic rats. MDL 101,002 (2.5 mg/kg/hr) increased survival from 24% to 52% in these rats. These data are consistent with a role for free radicals in the pathophysiology of endotoxic shock and suggest free radicals are also important mediators in chronic models of sepsis.

Animals↗
PubMed1994

Nitrone spin trap lipophilicity as a determinant for inhibition of low density lipoprotein oxidation and activation of interleukin-1 beta release from human monocytes.

One means by which oxidation of low density lipoproteins (LDL) may contribute to atherogenesis is by their ability to induce the release of interleukin-1 beta from monocytes. In the present study, the effect of the lipophilic nitrone spin trap alpha-phenyl-tert-butylnitrone (PBN) on lipoprotein oxidation and subsequent release of interleukin-1 beta was examined. The hydrophilic nitrone spin trap alpha-(4-pyridyl 1-oxide)-N-tert butylnitrone (POBN) was also studied to evaluate the importance of spin trap localization within the lipoprotein. PBN inhibited copper-induced modification of low density lipoproteins in a dose-dependent fashion as judged by measurement of thiobarbituric acid reactive substances, electrophoretic mobility, and fluorescence changes, while POBN was relatively ineffective. As demonstrated by electron spin resonance spectrometry, spectra of PBN adducts were highly immobilized, which reflects their presence within the LDL matrix. Experiments using chromium oxalate, a paramagnetic relaxing agent, revealed that the PBN adduct is composed of a mobile component (exposed to the LDL aqueous phase) and an immobilized component, localized in the lipid-protein interface or in the bulk lipid. Cholesteryl ester phospholipid dispersions in which only the core cholesteryl esters are subject to oxidation were also used to compare PBN and POBN. Again, PBN prevented the oxidation of the core lipids while POBN had little effect, further suggesting that PBN is capable of localization within the core of LDL. In agreement, attenuation of low density lipoprotein oxidation by PBN also decreased their ability to induce interleukin-1 beta release from human monocytes. Conversely, POBN had little effect on the release of interleukin-1 beta from cells incubated with copper-oxidized lipoproteins. These results suggest that the ability of a nitrone spin trap to prevent low density lipoprotein oxidation and its biologic effect(s) requires its incorporation into the particle.

Cyclic N-Oxides↗
PubMed1994

Multiple lipid oxidation products in low density lipoproteins induce interleukin-1 beta release from human blood mononuclear cells.

Oxidized low density lipoproteins (LDL) induce the release of interleukin-1 beta (IL-1 beta) from human peripheral blood mononuclear cells, a process that may contribute to atherogenesis. While 9-hydroxyoctadecadienoic acid (9-HODE) is a constituent of oxidized LDL and can by itself induce IL-1 beta release, its potency relative to oxidized LDL suggested that other components of modified LDL may also contribute to this phenomenon. In this study, LDL of varying oxidation states were prepared by altering the Cu2+ to LDL ratio and/or the length of oxidation. The oxidation status of LDL was measured as thiobarbituric acid reactive substances (TBARS), electrophoretic mobility in agarose gels, and the content of 9- and 13-HODE. High Cu2+ to LDL ratios promoted extensive TBARS formation and these LDL were the most potent activators of IL-1 beta release, although LDL with TBARS greater than 50 nmol/mg protein were cytotoxic and IL-1 beta release was diminished. An inverse correlation between HODE content and TBARS was found indicating lipid-derived aldehydes also contribute to IL-1 beta release by oxidized LDL. Accordingly, dialysis of oxidized LDL removed nearly all aldehydes and rendered the LDL unable to induce IL-1 beta release. The alkenals 2,4-decadienal and 2-octenal were tested and shown to induce IL-1 beta release while their saturated homologues had no effect. The predominant aldehyde in Cu(2+)-oxidized LDL was hexanal, with the unsaturated aldehydes 2,4-heptadienal, 2-octenal, and 2,4-decadienal also being present. These data indicate that multiple, lipid-derived species exist in oxidized LDL that can contribute to the release of IL-1 beta.

Aldehydes↗
PubMed1992

The influence of medium components on Cu(2+)-dependent oxidation of low-density lipoproteins and its sensitivity to superoxide dismutase.

The extent of in vitro Cu(2+)-dependent oxidation of low-density lipoproteins (LDL) has been reported to vary widely depending upon reaction conditions. In this study, the effect of proteins and amino acids on Cu(2+)-induced LDL oxidation was examined. Treatment of LDL with 5 microM CuSO4 for 18 h in either phosphate-buffered saline (PBS) or Ham's F-10 medium resulted in extensive oxidation as determined by the content of thiobarbituric acid reactive substances (TBARS) and by increased lipoprotein electronegativity. In PBS, oxidation was entirely blocked by histidine and the tripeptide, gly-his-lys (GHK). Oxidation was also prevented by bovine serum albumin, but superoxide dismutase (SOD) provided only 20% protection. Both proteins bound similar amounts of Cu2+, but albumin appeared to be a more effective peroxyl radical trap as evidenced by its ability to prevent LDL oxidation induced by 2,2'-azo-bis(2-amidinopropane hydrochloride). In F-10 medium, SOD had marked inhibitory effects, in contrast to PBS. The addition of disulfides to PBS markedly enhanced the ability of SOD to inhibit oxidation. These results indicate that medium components which affect Cu2+ availability influence LDL oxidation and suggest that albumin is ideally suited as a plasma antioxidant to prevent oxidative modification of LDL. Furthermore, in certain instances, the inhibitory effects of SOD may be attributable to effects such as Cu2+ binding rather than dismutation of superoxide.

Copper↗
PubMed1992

Induction of interleukin 1 beta expression from human peripheral blood monocyte-derived macrophages by 9-hydroxyoctadecadienoic acid.

Oxidatively modified low density lipoproteins (LDL) have recently been proposed to play a role in atherogenesis by promoting foam cell formation and endothelial cell toxicity. The purpose of the present study was to determine whether modified LDL could also induce macrophage release of interleukin 1 beta (IL-1 beta), a cytokine which enhances vascular smooth muscle cell proliferation, another feature of the atherosclerotic process. LDL were oxidatively modified by incubation with either Cu2+ (Cu(2+)-LDL) or human peripheral blood monocyte-derived macrophages (M-LDL). Incubation of these modified LDL with macrophages (6 x 10(6) cells/culture) resulted in a dose-dependent induction of IL-1 beta release. At 300 micrograms protein/ml, Cu(2+)-LDL and M-LDL induced 422 and 333 pg of IL-1 beta/culture, respectively. Saponified Cu(2+)-LDL and M-LDL were shown to contain 9- and 13-hydroxyoctadecadienoic acid (HODE), lipid oxidation products of linoleate. When tested for activity in macrophage culture (3 x 10(6) cells/culture), it was found that 9-HODE and 13-HODE (final concentration 33 microM) induced the release of 122 and 43 pg of IL-1 beta/culture, respectively, whereas untreated cells released only 4 pg of IL-1 beta/culture. Incubation of macrophages with cholesteryl-9-HODE also induced IL-1 beta release; however, the degree of induction of IL-1 beta release by 9-HODE or its cholesteryl ester relative to modified LDL suggests that other components in oxidized LDL may also contribute to IL-1 beta induction. 9-HODE was rapidly taken up by macrophages, and the kinetics were similar to IL-1 beta release. A 1.5- to 6-fold increase in the level of IL-1 beta mRNA was detected as little as 3-h post-9-HODE treatment. The induction of IL-1 beta release from human monocyte-derived macrophages by 9-HODE and cholesteryl-9-HODE suggests a role for modified LDL, and its associated linoleate oxidation products, in vascular smooth muscle cell proliferation.

Actins↗
PubMed1992

Modulation of the physical state of cellular cholesteryl esters by 4,4'-(isopropylidenedithio)bis(2,6-di-t-butylphenol) (probucol).

The effect of 4,4'-(isopropylidenedithio)bis(2,6-di-t-butylphenol) (probucol) on cholesteryl ester physical state was examined in dry mixtures, phospholipid-containing dispersions, and cells. Probucol has little effect on the solid to isotropic transition of cholesteryl oleate, but broadens and decreases the enthalpy of the liquid-crystalline transitions at concentrations as low as 1-2 mol %. A probucol transition is only observed at concentrations greater than 20 mol %. The mesomorphic phases of the cholesteryl oleate/probucol mixtures were identified by visual inspection and polarized light microscopy. Mixtures are liquid at probucol concentrations in excess of 5 mol % at 37 degrees C. Probucol also dramatically reduces the enthalpy of the liquid-crystalline transitions of the cholesteryl oleate core of dispersions of the ester with phospholipids at a concentration of 10 mol %, reducing the enthalpy by greater than 80% and the transition temperatures by approximately 2 degrees C. The phase state of cholesteryl esters in Fu5AH rat hepatoma cells was examined after incubation with cholesterol/phospholipid dispersions that caused the accumulation of anisotropic cholesteryl ester droplets. Differential scanning calorimetry scans of cells incubated with cholesterol-rich phospholipid dispersions indicated a phase transition near 48 degrees C, which was abolished when the cells were co-incubated with 50-100 micrograms/ml of probucol in the loading medium. Subsequent to the formation of isotropic cholesteryl ester droplets in the presence of probucol, the rate of efflux of cholesterol from the cells to phosphatidylcholine-containing acceptors in the medium was increased. These data show that probucol is relatively soluble in cholesteryl esters and that probucol changes the phase state of cholesteryl ester droplets in cells to a more fluid phase in which the cholesteryl esters are more readily mobilized.

Animals↗
PubMed1992

Ascorbate and phenolic antioxidant interactions in prevention of liposomal oxidation.

Efficient prevention of membrane lipid peroxidation by vitamin E (alpha-tocopherol) may involve its regeneration by vitamin C (ascorbate). Conceivably, the efficacy of antioxidants designed as therapeutic agents could be enhanced if a similar regeneration were favorable; thus, a model membrane system was developed which allowed assessment of interaction of phenolic antioxidants with ascorbate and ascorbyl-6-palmitate. Ascorbate alone (50-200 microM) potentiated oxidation of soybean phosphatidylcholine liposomes by Fe2+/histidine-Fe3+, an effect which was temporally related to reduction of Fe3+ generated during oxidation. Addition of 200 microM ascorbate to alpha-tocopherol-containing liposomes (0.1 mol%) resulted in marked, synergistic protection. Accordingly, in the presence but not absence of ascorbate, alpha-tocopherol levels were maintained relatively constant during Fe2+/histidine-Fe3+ exposure. Probucol (4,4'-[(1-methylethylidine)bis(thio)]bis[2,6-bis(1,1- dimethylethyl)]phenol), an antioxidant which prevents oxidation of low density lipoproteins, and its analogues MDL 27,968 (4,4'-[(1-methylethylidene)bis(thio)]bis[2,6- dimethyl]phenol) and MDL 28,881 (2,6-bis(1,1-dimethylethyl)-4-[(3,7,11- trimethyldodecyl)thio]phenol) prevented oxidation but exhibited no synergy with ascorbate. Ascorbyl-6-palmitate itself was an effective antioxidant but did not interact synergistically with any of the phenolic antioxidants. Differential scanning calorimetry revealed significant differences among the antioxidants in their effect on the liquid-crystalline phase transition of dipalmitoyl phosphatidylcholine (DPPC) liposomes. Both alpha-tocopherol and MDL 27,968 significantly reduced the phase transition temperature and the enthalpy of the transition. MDL 28,881 had no effect while probucol was intermediate. The potential for ascorbate or its analogues to interact with phenolic antioxidants to provide a more effective antioxidant system appears to be dictated by structural features and by the location of the antioxidants in the membrane.

Antioxidants↗
PubMed1991

Inhibition of IL-1 beta expression in THP-1 cells by probucol and tocopherol.

The cytokine interleukin-1, IL-1, likely plays an important role in the early stages of atherogenesis. The possible action of probucol and tocopherol on the expression and secretion of IL-1 beta was investigated using the human monocytic leukemia cell line, THP-1. Both probucol and D-alpha-tocopherol inhibit the phorbol ester-induced release of IL-1 beta without altering differentiation. Analysis of IL-1 beta mRNA levels revealed that probucol and tocopherol had an inhibitory effect on the activation of expression of the IL-1 beta gene. The data suggest that the beneficial effects of probucol may be related to inhibition of IL-1 at an early phase of atherosclerotic plaque formation.

Cell Differentiation↗