Gangliosides and atherosclerosis

The ganglioside levels in atherosclerotic lesions of human aorta are considerably higher than those in unaffected areas of aorta, and atherosclerotic patients frequently have increased concentrations of serum gangliosides. The present review summarizes recent findings that suggest the possible involvement of aortic gangliosides in platelet activation and adhesion of platelets to the vessel wall. The effect of gangliosides on the structure of low density lipoproteins (LDL), on the interaction of LDL with macrophages and hepatic cells and on the LDL-regulated biosynthesis of cholesterol is also discussed.In vitro experiments have demonstrated that a major ganglioside of the intima of atherosclerotic aorta induces rapid adhesion, aggregation and spreading of platelets. Moreover, gangliosides present in elevated amounts in the intercellular space of atherosclerotic aortic tissue modify the surface structure and stimulate aggregation of LDL. Ganglioside-modified LDL are readily recognized and taken up by macrophages, while preincubation of LDL with low concentrations of gangliosides inhibits LDL binding to hepatic cells. Thus, ganglioside enrichment of LDL is likely to interfere with LDL clearancevia the hepatic cells. Thus, ganglioside enrichment of LDL is likely to interfere with LDL clearancevia the hepatic LDL receptor, and to stimulate binding of LDL to the scavenger receptor of macrophages. It is postulated that high ganglioside levels in the aorta and serum may be an additional risk factor in atherosclerosis. The abbreviations used for gangliosides are standard abbreviations as recommended by Svennerholm [Svennerholm, L. (1964)J. Lipid Res. 5, 145–155].     

Studies on biochemical effects of nitrogen dioxide: I. Lipid peroxidation as measured by ethane exhalation of rats exposed to nitrogen dioxide

This research was in order to follow the periodic fluctuation of lipid peroxidation by a new method in rats exposed to nitrogen dioxide. Wistar male rats were examined for lipid peroxidation as demonstrated by ethane exhalation. In rats continuously exposed to 10 ppm nitrogen dioxide for 2 weeks, the amount of ethane exhaled fluctuated in a complex manner during the exposure. Ethane exhalation decreased slightly after the first day of exposure and then increased rapidly. The maximal values were observed after the fourth day of exposure and then decreased gradually to the initial level. Furthermore, the activity of glutathione peroxidase in lungs of rats exposed to 10 ppm nitrogen dioxide varied symmetrically against the change of ethane formation. Similar changes in ethane exhalation were observed in rats exposed to the lower levels of nitrogen dioxide (0.4, 1.2 and 4.0 ppm) for 4 months. Compared to 10 ppm nitrogen dioxide exposure for 14 days, the characteristics in rats exposed to the low levels (0.4–4.0 ppm) of nitrogen dioxide were: the decline of ethane formation, the delay in alterations, and the tendency toward gradual increased during the longer period exposure.     

Low density lipoprotein of synovial fluid in inflammatory joint disease is mildly oxidized

Oxidatively modified low density lipoprotein (LDL) has many biological activities which could contribute to the pathology of the atherosclerotic lesion. Because atherosclerosis has an inflammatory component, there has been much interest in the extent to which LDL could be oxidatively modified in vivo by inflammation. The present study examined LDL present in an accessible inflammatory site, the inflamed synovial joint, for evidence of compositional change and oxidative modification. LDL was isolated from knee joint synovial fluid (SF) from subjects with inflammatory arthropathies and also from matched plasma samples. SF and plasma LDL had similar free cholesterol and α-tocopherol content, but SF LDL had a lower content of esterified cholesterol. On electrophoresis, SF LDL was slightly more electronegative than LDL from matched plasma samples, but the changes were much less than those resulting from Cu²⁺-treatment of LDL. Oxidized cholesterol was not detected in any samples, but cholesterol ester hydroperoxide levels were greater in SF than in plasma LDL. When samples from three subjects were incubated with macrophages, the SF LDL did not cause significant loading of the cells with cholesterol or cholesterol esters, in contrast to the situation with acetylated LDL. Overall, the SF LDL displayed evidence of slightly increased oxidation by comparison with matched plasma samples. Despite their isolation from an environment with active inflammation, changes were modest compared with those resulting from Cu²⁺ treatment. Thus, extensive LDL oxidation is not a necessary correlate of location in a chronic inflammatory site, even though it is characteristic of atherosclerotic lesions.     

Protective effect of olive oil and its phenolic compounds against low density lipoprotein oxidation

The protective effect of phenolic compounds from an olive oil extract, and of olive oils with (extra-virgin) and without (refined) phenolic components, on low density lipoprotein (LDL) oxidation was investigated. When added to isolated LDL, phenolics [0.025–0.3 mg/L caffeic acid equivalents (CAE)] increased the lag time of conjugated diene formation after copper-mediated LDL oxidation in a concentration-dependent manner. Concentrations of phenolics greater than 20 mg/L inhibited formation of thiobarbituric-acid reactive substances after AAPH-initiated LDL oxidation. LDL isolated from plasma after preincubation with phenolics (25–160 mg/L CAE) showed a concentration-dependent increase in the lag time of conjugated diene formation after copper-mediated LDL oxidation. Refined olive oil (0 mg/L CAE) and extra-virgin olive oil (0.1 and 0.3 mg/L CAE) added to isolated LDL caused an increase in the lag time of conjugated diene formation after copper-mediated LDL oxidation that was related to olive oil phenolic content. Multiple regression analysis showed that phenolics were significantly associated with the increase in lag time after adjustment for effects of other antioxidants; α-tocopherol also achieved a statistically significant effect. These results indicate that olive oil phenolic compounds protect LDL against peroxyl radical-dependent and metal-induced oxidation in vitro and could associate with LDL after their incubation with plasma. Both types of olive oil protect LDL from oxidation. Olive oil containing phenolics, however, shows more antioxidant effect on LDL oxidation than refined olive oil.     

The effect of γ-interferon to inhibit macrophage-high density lipoprotein interactions is reversed by Δ12,14-prostaglandin J2J2

Macrophage activation has been recognized as playing a central role in chronic inflammatory diseases in general and more specifically, in the vascular wall during the progression of atherosclerotic lesions. Macrophage-activating factors present within the atherosclerotic lesion include the colony-stimulating factors and gamma interferon (IFN_γ). In the present study, the effects of IFN_γ on macrophage binding and uptake of fluorochrome-labeled high density lipoprotein (HDL) were investigated by flow cytometry and by measuring the amount of the type B scavenger receptors CD36 and scavenger receptor type B (SR-BI) by Northern blot analysis. IFN_γ-, but not granulocyte macrophage colony-stimulating factor (GM-CSF)-treated murine peritoneal macrophages displayed a two- to threefold decrease in Dil-labeled HDI uptake. This effect was observed in the absence of a comparable decrease in SR-BI meassage and protein or CD36 message. This decrease in both HDL binding and uptake was reversed by the peroxisome proliferator-activated receptor gamma (PPAR_γ) agonist, Δ^12,14-prostaglandin J₂ (15d-PGJ₂), which also inhibited the IFN_γ inductin of the β2 integrin CD1 1a. Furthermore, 15d-PGJ₂ increased the expression of SR-BI and CD36 message and SR-BI protein which was reflected in an increase in HDL binding and uptake. These results suggest a role for PPAR_γ agonists in modulating the IFN_γ-mediated macrophage effector functions relevant to atherosclerotic disease progression.     

Quantitative determination of low density lipoprotein oxidation by FTIR and chemometric analysis

This study was conducted to develop a quantitative FTIR spectroscopy method to measure LDL lipid oxidation products and determine the effect of oxidation on LDL lipid and protein. In vitro LDL oxidation at 37°C for 1 h produced a range of conjugated diene (CD) (0.14–0.26 mM/mg protein) and carbonyl contents (0.9–3.8 μg/g protein) that were used to produce calibration sets. Spectra were collected from the calibration set and partial least squares regression was used to develop calibration models from spectral regions 4000-650, 3750-3000, 1720-1500, and 1180-935 cm⁻¹ to predict CD and carbonyl contents. The optimal models were selected based on their standard error of prediction (SEP), and the selected models were performance-tested with an additional set of LDL spectra. The best models for CD prediction were derived from spectral regions 4000-650 and 1180-935 cm⁻¹ with the lowest SEP of 0.013 and 0.013 mM/mg protein, respectively. The peaks at 1745 (cholesterol and TAG ester C=O stretch), 1710 (carbonyl C-O stretch), and 1621 cm⁻¹ (peptide C=O stretch) positively correlated with LDL oxidation. FTIR and chemometrics revealed protein conformation changes during LDL oxidation and provided a simple technique that has potential for rapidly observing structural changes in human LDL during oxidation and for measuring primary and secondary oxidation products.     

Fourier transform infrared spectroscopy evaluation of low density lipoprotein oxidation in the presence of quercetin,catechin, and α-tocopherol

We investigated the changes in human LDL primary and secondary lipid oxidation products and modification of the apolipoprotein B-100 (apoB-100) secondary structures during Cu²⁺-mediated oxidation by FTIR spectroscopy in the presence of catechin, quercetin, and α-tocopherol at physiological concentrations. Catechin- and quercetin-containing samples had slower rates and longer lag phases for conjugated diene hydroperoxide (CD) formation than α-tocopherol-containing samples; however, all antioxidant-treated LDL samples generated similar CD levels (P<0.05). A lower maximum (98.4 nmol/mg LDL protein) of carbonyl compounds was produced in the quercetin- and catechin-treated samples than in α-tocopherol samples. Modification of the apoB-100 secondary structures corresponded closely to the formation of carbonyls and was hampered by the presence of antioxidants. Physiological concentrations of catechin and quercetin offered similar levels of protection against modification by carbonyls of the apoB-100 at advanced stages (carbonyls ∼96.0 nmol/mg LDL protein) but not at the intermediate stages (carbonyls ∼58.0 nmol/mg LDL protein) of LDL oxidation probably owing to differences in the protein-binding mechanisms of catechin and quercetin. Relationships between peroxide formation, carbonyl products, and LDL protein denaturation were shown by the FTIR approach. The FTIR technique provided a simple new tool for a comprehensive evaluation of antioxidant performance in protecting LDL during in vitro oxidation.     

Phospholipids and oxophospholipids in atherosclerotic plaques at different stages of plaque development

We identified and quantified the hydroperoxides, hydroxides, epoxides, isoprostanes, and core aldehydes of the major phospholipids as the main components of the oxophospholipids (a total of 5–25 pmol/μmol phosphatidylcholine) in a comparative study of human atheroma from selected stages of lesion development. The developmental stages examined included fatty streak, fibrous plaque, necrotic core, and calcified tissue. The lipid analyses were performed by normal-phase HPLC with on-line electrospray MS using conventional total lipid extracts. There was great variability in the proportions of the various oxidation products and a lack of a general trend. Specifically, the early oxidation products (hydroperoxides and epoxides) of the glycerophosphocholines were found at the advanced stages of the plaques in nearly the same relative abundance as the more advanced oxidation products (core aldehydes and acids). The anticipated linear accumulation of the more stable oxidation products with progressive development of the atherosclerotic plaque was not apparent. It is therefore suggested that lipid infiltration and/or local peroxidation is a continuous process characterized by the formation and destruction of both early and advanced products of lipid oxidation at all times. The process of lipid deposition appears to have been subject to both enzymatic and chemical modification of the normal tissue lipids. Clearly, the appearance of new and disproportionate old lipid species excludes randomness in any accumulation of oxidized LDL lipids in atheroma.     

The Initial Human Atherosclerotic Lesion and Lipoprotein Modification—A Deep Connection

Atherosclerosis research typically focuses on the evolution of intermediate or advanced atherosclerotic lesions rather than on prelesional stages of atherogenesis. Yet these early events may provide decisive leads on the triggers of the pathologic process, before lesions become clinically overt. Thereby, it is mandatory to consider extracellular lipoprotein deposition at this stage as the prerequisite of foam cell formation leading to a remarkable accumulation of LDL (Low Density Lipoproteins). As progression of atherosclerosis displays the characteristic features of a chronic inflammatory process on the one hand and native LDL lacks inflammatory properties on the other hand, the lipoprotein must undergo biochemical modification to become atherogenic. During the last 25 years, evidence was accumulated in support of a different concept on atherogenesis proposing that modification of native LDL occurs through the action of ubiquitous hydrolytic enzymes (enzymatically modified LDL or eLDL) rather than oxidation and contending that the physiological events leading to macrophage uptake and reverse transport of eLDL first occur without inflammation (initiation with reversion). Preventing or reversing initial atherosclerotic lesions would avoid the later stages and therefore prevent clinical manifestations. This concept is in accordance with the response to retention hypothesis directly supporting the strategy of lowering plasma levels of atherogenic lipoproteins as the most successful therapy for atherosclerosis and its sequelae. Apart from but unquestionable closely related to this concept, there are several other hypotheses on atherosclerotic lesion initiation favoring an initiating role of the immune system (‘vascular-associated lymphoid tissue’ (VALT)), defining foam cell formation as a variant of lysosomal storage disease, relating to the concept of the inflammasome with crystalline cholesterol and/or mitochondrial DAMPs (damage-associated molecular patterns) being mandatory in driving arterial inflammation and, last but not least, pointing to miRNAs (micro RNAs) as pivotal players. However, direct anti-inflammatory therapies may prove successful as adjuvant components but will likely never be used in the absence of strategies to lower plasma levels of atherogenic lipoproteins, the key point of the perception that atherosclerosis is not simply an inevitable result of senescence. In particular, given the importance of chemical modifications for lipoprotein atherogenicity, regulation of the enzymes involved might be a tempting target for pharmacological research.     

Dietary polyunsaturated fat decreases interaction between low density lipoproteins and arterial proteoglycans

Polyunsaturated dietary fat (n−3 and n−6) results in less atherosclerosis in monkeys compared to lard (Parks, J.S., Kaduck-Sawyer, J., Bullock, B.C., and Rudel, L.L.,Arteriosclerosis 10, 1102–1112; Rudel, L.L., Parks, J.S., Johnson, F.L., and Babiak, J.,J. Lipid Res. 27, 465–474, 1986). We hypothesized that this was due, in part, to a decreased reactivity of low density lipoproteins (LDL) with arterial proteoglycans (PG). To test this hypothesis, cynomolgus monkeys were fed diets containing lard, safflower oil (n−6 polyunsaturated; Poly), menhanden fish oil (FO), or oleic acid-rich safflower oil (oleinate; Mono) for 14 mon, and plasma LDL were isolated and characterized. Several properties of LDL thought to be important in the interaction of LDL with arterial PG were measured including LDL particle size, chemical composition, sialic acid content, density distribution, apolipoprotein E (apoE) content and cholesteryl ester transition temperature. Plasma LDL cholesterol concentrations (mg/dL) after 14 mon of diet consumption averaged (mean±SEM): FO (366±45), Lard (352±27), Poly (279±24), and Mono (230±43). The composition of LDL was similar among diet groups except that FO LDL were relatively depleted of cholesteryl ester and enriched in protein and were smaller in size. LDL sialic acid content was similar among diet groups (4.5–5.0 μg/mg LDL protein). The LDL apoE/B molar ratio, a measure of the apoE content per LDL particle averaged: Mono (3.0±1.0), Poly (2.0±0.1), Lard (1.8±0.5), and FO (1.0±0.2). The FO group had a lower proportion (13%) of the apoE enriched d=1.015–1.025 g/mL subfraction of LDL than did the other diet groups (31–45%). The transition temperature of the LDL cholesteryl esters was below body temperature for the FO and Poly groups (36°C) and above for the Lard and Mono groups (40–44°C). The percentage of LDL cholesterol that formed insoluble complexes with arterial chondroitin sulfate PG averaged: Mono (29±4%), Lard (18±3%), Poly (14±3%), and FO (7±2%). Among all diet groups, there was a significant positive correlation (r=0.54) between LDL-PG complex formation and LDL apoE/B molar ratio. We conclude that dietary FO and Poly result in LDL that are less reactive with arterial PG compared to Lard or Mono fats. While FO appears to decrease PG binding by decreasing the apoE content and amount of the largest LDL subfraction, Poly fat appears to affect LDL-PG interactions by other mechanisms. Decreased LDL-PG interactions may lead to decreased atherosclerosis in animals fed polyunsaturated dietary fat.     

Peroxisome proliferator-activated receptor alpha,gamma coagonist LY465608 inhibits macrophage activation and atherosclerosis in apolipoprotein E knockout mice

The apolipoprotein F (apoF) knockout mouse has provided an approach to the investigation of the effect of both cellular and humoral processes on atherosclerotic lesion progression. In the present study, pharmacologic modulation of both interferon gamma (IFNγ)-inducible macrophage effector functions, and atherosclerotic lesions in the apoE knockout mouse were investigated using the peroxisome proliferator-activated receptor (PPAR) α,γ coagonist LY465608. LY465608 inhibited, in a concentration-dependent manner, IFNγ induction of both nitric oxide synthesis and the β2 integrin CD11a in elicited peritoneal macrophages from apoE knockout mice. Similar effects were observed ex vivo following 10 d of treating mice with 10 mg/kg of LY465608. Treatment of apoE knockout mice for 18 wk with LY465608 resulted in a statistically significant 2.5-fold reduction in atherosclerotic lesion area in en face aorta preparations. These effects were apparent in the absence of any reduction in total serum cholesterol or in lipoprotein distribution. Finally, treatment of apoE knockout mice with established atherosclerotic disease resulted in a modest but not statistically significant decrease in aortic lesional surface area. These results demonstrate the utility of PPAR coagonists in reducing the progression of the atherosclerotic lesion.     

Sorption kinetics of carbon dioxide onto rubidium carbonate

Rubidium carbonate was used as an adsorbent to capture carbon dioxide from gaseous stream of carbon dioxide, nitrogen, and moisture in a fixed-bed to obtain the breakthrough data of CO₂. Experiments were carried out at flow rates of carbon dioxide and nitrogen (5×10⁻⁶–35×10⁻⁶ m³/min), moisture (0.5×10⁻⁶–3.0×10⁻⁶ m³/h), amount of adsorbent (0.5×10⁻³–1.8×10⁻³ kg), mole fraction of carbon dioxide (0.03–0.22), and different sorption temperatures (323–353 K) at atmospheric pressure. The deactivation model in the non-catalytic heterogeneous reaction systems was used to analyze the sorption kinetics among carbon dioxide, carbonate, and moisture, employing the experimental breakthrough data that fit the deactivation model better than the adsorption isotherm models in the literature.     

Effect of n−3 fatty acid-rich fish oil supplementation on the oxidation of low density lipoproteins

This study was aimed at determining the effect of fish oil supplementation on copper-catalyzed oxidation of low density lipoproteins (LDL) from nine hypertriglyceridemic human subjects. A rapid headspace gas chromatographic method was used to measure the volatile oxidation products from LDL. Propanal and hexanal were the major volatile products formed in the oxidation of n−3 and n−6 polyunsaturated fatty acids (PUFA), respectively. Fish oil supplementation resulted in a significant increase in propanal formation from 3.7 to 13.4 nmol/mL LDL (P<0.01); it also resulted in small decreases in pentanal formation from 14.7 to 11.4 nmol/mL LDL and in hexanal formation from 138 to 108 nmol/mL LDL (P<0.05). The changes in peroxidation products paralleled the changes in LDL composition, which showed a significant increase in n−3 PUFA from 3.2 to 14.6% (P<0.01) and a decrease in n−6 PUFA from 43.7 to 35.0% (P<0.05). Propanal formation was highly and significantly correlated with n−3 PUFA content (r=0.950,P<0.001). Since total volatiles remained unchanged, this indicated that the two groups of LDL samples did not differ in overall oxidative susceptibility. Although fish oil intake did not alter the oxidative susceptibility of LDL, the chemically modified LDL particles generated a distinct pattern of volatile oxidation products that reflected changes in their fatty acid composition.     

AGE-RAGE Axis Stimulates Oxidized LDL Uptake into Macrophages through Cyclin-Dependent Kinase 5-CD36 Pathway via Oxidative Stress Generation

Advanced glycation end products (AGEs) are localized in macrophage-derived foam cells within atherosclerotic lesions, which could be associated with the increased risk of atherosclerotic cardiovascular disease under diabetic conditions. Although foam cell formation of macrophages has been shown to be enhanced by AGEs, the underlying molecular mechanism remains unclear. Since cyclin-dependent kinase 5 (Cdk5) is reported to modulate inflammatory responses in macrophages, we investigated whether Cdk5 could be involved in AGE-induced CD36 gene expression and foam cell formation of macrophages. AGEs significantly increased Dil-oxidized low-density lipoprotein (ox-LDL) uptake, and Cdk5 and CD36 gene expression in U937 human macrophages, all of which were inhibited by DNA aptamer raised against RAGE (RAGE-aptamer). Cdk5 and CD36 gene expression levels were correlated with each other. An antioxidant, N-acetyl-l-cysteine, mimicked the effects of RAGE-aptamer on AGE-exposed U937 cells. A selective inhibitor of Cdk5, (R)-DRF053, attenuated the AGE-induced Dil-ox-LDL uptake and CD36 gene expression, whereas anti-CD36 antibody inhibited the Dil-ox-LDL uptake but not Cdk5 gene expression. The present study suggests that AGEs may stimulate ox-LDL uptake into macrophages through the Cdk5–CD36 pathway via RAGE-mediated oxidative stress.     

Uptake and oxidation of malonaldehyde by cultured mammalian cells

Primary cultures of rat skin fibroblasts were used as a model system to investigate the cellular uptake and oxidation of malonaldehyde (MA). The cells were grown in a medium containing 10⁻⁵ M, 10⁻⁴ M or 10⁻³ M concentrations of [1,3-¹⁴C]MA. There was a limited, concentration-dependent uptake of MA by 24 hr (∼4% at all concentrations). The uptake of [1,2-¹⁴C]acetate by 24 hr was ∼24%; 83–89% of the¹⁴C in the MA taken up was oxidized to¹⁴CO₂ by 24 hr and ∼5% was recovered in the major lipids. Despite its low uptake and rapid oxidation to CO₂, pretreatment of the cells with 10⁻³ M MA for 24 hr produced a latent inhibition of [¹⁴C]glucose oxidation. Limited cellular uptake of MA may explain the tolerance of cells grown in culture to relatively high MA concentrations.     

Functional and nutritional properties of acylated rapeseed proteins

Rapeseed flour was acylated to various degrees with acetic and succinic anhydrides to produce acetylated rapeseed protein concentrates (SRPC) and succinylated rapeseed protein concentrates (SRPC), respectively. With both acylating agents, approximately 5–82% (ARPC-5 to ARPC-82) and 5–56% (SRPC-5 to SRPC-56) of ε-amino groups of lysine were acylated. Changes in functional properties were monitored; nitrogen solubility, emulsifying properties and specific viscosity were improved by acylation. The effects on functional properties were more pronounced with succinylation than acetylation. The nutritive value of succinylated rapeseed protein concentrates was determined and compared with those of unmodified rapessed protein concentrate and rapessed flour. Succinylation reduced the availability of lysine and decreased (p<0.05) the net protein ratio (NPR) and apparent digestibility coefficient (ADC) of nitrogen in rapessed protein concentrates. Supplementation of SRPC with lysine improved the NPR compared to that of SRPC-56.     

Fenofibrate protects lipoproteins from lipid peroxidation: Synergistic interaction with α-tocopherol

One of the earliest steps of atherosclerotic plaque formation is an increase of circulating apolipoprotein B-containing lipoproteins which, after infiltrating the subendothelial space, undergo oxidative modification. Fenofibrate is an effective cholesterol- and triglyceride-lowering agent which has been shown to be beneficial in the treatment of atherosclerosis. Vitamin E, or α-tocopherol, is a powerful antioxidant which has been shown in a variety of studies to prevent lipoprotein peroxidation. The purpose of the present study was to investigate the effect of fenofibrate treatment, either alone or in combination with α-tocopherol, in reducing the susceptibility of lipoproteins to oxidative modification. Rats fed a normal diet were treated for up to 27 d with fenofibrate, either alone or in combination with equimolar doses of α-tocopherol. Combined VLDL (very low density lipoproteins) and LDL (low density lipoproteins) isolated after fenofibrate treatment were more resistant to coppermediated oxidation, as assessed by conjugated diene formation. Lag time was prolonged up to 3.2-fold, while the maximal rate of diene production was significantly decreased by up to 2.2-fold. Treatment of rats with α-tocopherol alone at the selected dose had no significant effect on lag time, while the propagation rate was slightly decreased. Coadministration of fenofibrate with α-tocopherol prolonged the lag phase to a greater extent than fenofibrate alone, showing a synergistic interaction between the two compounds. Finally, the combination of fenofibrate and α-tocopherol was significantly more effective in modifying lipoprotein oxidation parameters than what was observed with α-tocopherol and bezafibrate or gemfibrozil. Thus, in addition to its well-established effects on lipoprotein concentrations and atherogenic parameters, fenofibrate reduces the susceptibility of VLDL and LDL to oxidative modification and exerts its action synergistically with α-tocopherol.     

Oxidative reforming of methane on structured Ni-Al<Subscript>2</Subscript>O<Subscript>3</Subscript>/cordierite catalysts

The catalytic properties of Ni/Al₂O₃ composites supported on ceramic cordierite honeycomb monoliths in oxidative methane reforming are reported. The prereduced catalyst has been tested in a flow reactor using reaction mixtures of the following compositions: in methane oxidation, 2–6% CH₄, 2–9% O₂, Ar; in carbon dioxide and oxidative carbon dioxide reforming of methane, 2–6% CH₄, 6–12% CO₂, and 0–4% O₂, and Ar. Physicochemical studies include the monitoring of the formation and oxidation of carbon, the strength of the Ni-O bond, and the phase composition of the catalyst. The structured Ni-Al₂O₃ catalysts are much more productive in the carbon dioxide reforming of methane than conventional granular catalysts. The catalysts performance is made more stable by regulating the acid-base properties of their surface via the introduction of alkali metal (Na, K) oxides to retard the coking of the surface. Rare-earth metal oxides with a low redox potential (La₂O₃, CeO₂) enhance the activity and stability of Ni-Al₂O₃/cordierite catalysts in the deep and partial oxidation and carbon dioxide reforming of methane. The carbon dioxide reforming of methane on the (NiO + La₂O₃ + Al₂O₃)/cordierite catalyst can be intensified by adding oxygen to the gas feed. This reduces the temperature necessary to reach a high methane conversion and does not exert any significant effect on the selectivity with respect to H₂.     

Free fatty acid metabolism during stress: Exercise,acute cold exposure,and anaphylactic shock

Rates of turnover and oxidation of plasma free fatty acid (FFA) were determined in unanesthetized dogs during exercise, acute cold exposure and anaphylactic shock, with the aid of a technique involving the continuous infusion of albumin-bound palmitate-1-¹⁴C and the simultaneous measurement of O₂ uptake, CO₂ output and the specific activities of CO₂ and FFA. During exercise in normal untrained dogs, plasma FFA supplied 20–30% of the energy, whereas in trained dogs 70–90% of the energy was derived from the FFA oxidation. In resting dogs at room temperature the plasma FFA level was 0.58 μEq/ml with a turnover rate of 18.6 μEq/kg/min of which 22% was immeditely oxidized and contributed 29% to the exhaled CO₂. These results were compared with data obtained in pancreatectomized and thyroidectomized dogs. Acute cold exposure (temperature 4–5C) increased the FFA level and turnover rate to 1.02 μEq/ml and 28.0 μEq/kg/min, respectively, of which 33% was immedaitely oxidized, contributing 46% to the exhaled CO₂. During anaphylactic shock, blood lactate increased, FFA level and turnover rate were reduced, and the fraction which was immediately oxidized was depressed markedly, i.e., 3–9% of FFA turnover. Sodium lactate infusion, which induces a blood lactate level comparable to that seen in anaphylaxis or nicotinic acid infusion, markedly decreased the level and turnover rate of FFA. However the fraction of turnover oxidized remained the same as during the preinfusion period (range of 21–40%. Exercise or the administration of norepinephrine during anaphylactic shock provided results suggesting that endogenous lactic acid interferes with FFA oxidation, whereas exogenous, lactate had no effect on this oxidation.     

Modeling of alpha-tocopherol loss and oxidation products formed during thermoxidation in triolein and tripalmitin mixtures

The degradation of α-tocopherol and the formation of α-tocopherol and triacylglycerol oxidation products at high temperatures (150–250°C) over a heating period (0–4h) for a model system ranging between triolein and tripalmitin were modeled by use of an experimental design. The oxidation products of α-tocopherol formed under these conditions were α-tocopherolquinone (1.4–7.7%) and epoxy-α-tocopherolquinones (4.3–34.8%). The results indicate a very high susceptibility of α-tocopherol to capture peroxyl radicals upon oxidation, leading to the formation of polar tocopherol oxidation products. Both α-tocopherolquinone and epoxy-α-tocopherolquinones were not stable upon prolonged heating and were further degraded to other unknown oxidation products. The kinetics of α-tocopherol oxidation were significantly influenced by the triolein/tripalmitin ratio. By increasing the level of triacylglycerol unsaturation the rate of α-tocopherol recovery after heating increased significantly from 2.2 to 44.2% whereas in the meantime triacylglycerol polymerization increased from 0 to 3.7%.