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Biomedical subjects

R A Gibson

Publications and source records attributed to R A Gibson.

At least 91 records · Page 5Linked to original sources

Erythrocyte docosahexaenoic acid correlates with the visual response of healthy, term infants.

Recent studies have reported that formula-fed preterm infants score lower on visual and developmental tests relative to breast-fed preterm infants. This phenomenon has been associated with the presence of docosahexaenoic acid (DHA), an omega-3 fatty acid, in breast milk and its absence from infant formula. To investigate the possibility that DHA status of healthy, term infants is also related to neuronal function of the visual pathway, we studied the erythrocyte fatty acid profiles of 16 infants at 22.3 +/- 3.9 wk of age and related these to maturity of the visual pathway as assessed by visual-evoked potentials. Healthy, term infants fed breast milk had better visual-evoked potential acuity (p < 0.05) and higher DHA levels (p < 0.001) than infants who received infant formula as their major energy source. There was a positive correlation between erythrocyte DHA and visual-evoked potential acuity (p < 0.01). The data are preliminary and the long-term effects as yet unknown. However, our results suggest that there is an urgent need to evaluate the dietary fatty acid supply of formula-fed term infants.

Breast Feeding↗

Incorporation of dietary oleate, linoleate, alpha-linolenate and eicosapentaenoate into the plasma lipid fractions of four strains of rat.

Four strains of rat (Dark Agouti, DA; Ginger Hooded, GH; Portion, P; Hooded Wistar, HW) were fed elemental diets containing different sources of fat at the 10% (w/w) level. The dietary fats used included the following oils; olive (rich in oleate), sunflower (rich in linoleate), linseed (rich in alpha-linolenate) and fish (rich in eicosapentaenoate and docosahexaenoate). Differences between strains in response to individual diets were modest compared with the much greater differences achieved by the dietary treatments. In general, the changes in polyunsaturated fatty acid (PUFA) levels in the plasma lipids of all rat strains followed the major PUFA in the diet. There were, however, strong interactions between dietary n-6 and n-3 PUFA which affected not only the level of particular PUFA in lipid fractions but also the lipid fraction in which a particular PUFA appeared. Our findings indicate that a response to dietary fats in the plasma lipids of one strain of rat can be expected to occur with relatively minor variations in other commonly used rat strains.

Animals↗

Inhibition of human neutrophil leukotriene B4 synthesis by combination auranofin and eicosapentaenoic acid.

It has been demonstrated that both auranofin and eicosapentaenoic acid (EPA) have anti-inflammatory properties and both inhibit neutrophil leukotriene B4 (LTB4) synthesis. In the present study, we examined interactions between auranofin and EPA with regard to inhibition of human neutrophil LTB4 synthesis. Auranofin inhibited A23187-stimulated LTB4 synthesis, but the dose required for inhibition of LTB4 was greater than that required for inhibition of other 5-lipoxygenase metabolites; namely, the all-trans isomers of LTB4 and 5-hydroxyeicosatetraenoic acid. These results were explained after a comparison of the rates of synthesis of these 5-lipoxygenase metabolites in the presence and absence of added arachidonic acid which led to the conclusion that leukotriene A hydrolase, the enzyme catalysing the formation of LTB4, was saturated with substrate and rate-limiting for LTB4 synthesis during A23187 stimulation. In combination, auranofin and EPA had a simple additive effect on inhibition of the 5-lipoxygenase pathway. Favorable drug/EPA combinations have the potential to provide a beneficial anti-inflammatory effect with lower levels of each component than are required when used individually.

Arachidonic Acid↗

The effect of dietary supplementation with eicosapentaenoic acid on the phospholipid and fatty acid composition of erythrocytes of marmoset.

Adult male marmoset monkeys were fed eicosapentaenoic acid (20:5n-3) as the ethyl ester in diets containing either 32% (reference diet, no added cholesterol) or 7% (atherogenic diet with 0.2% added cholesterol) linoleic acid (18:2n-6) for 30 wk. No changes were seen in the level of phosphatidylcholine (PC) or phosphatidylethanolamine (PE) but minor changes were observed in both the sphingomyelin (SPM) and phosphatidylinositol plus phosphatidylserine (PI+PS) fractions of erythrocyte lipids. The extent of total n-3 fatty acid incorporation into membrane lipids was higher in atherogenic diets (polyunsaturated/monounsaturated/saturated (P/M/S) ratio 0.2:0.6:1.0) than reference diets (P/M/S ratio 1:1:1) and this was true for both PE (33.4 +/- 1.0% vs 24.3 +/- 1.1%) and PC (9.3 +/- 0.5% vs 4.9 +/- 0.3%). Although suitable controls for cholesterol effects were not included in the study, earlier results obtained with marmosets lead us to believe such effects were probably small. Regardless of basic diet (atherogenic, reference), 20:5n-3 was preferentially incorporated into PE (10.8 +/- 0.2%, 6.0 +/- 0.02%) while smaller amounts were incorporated into PC (6.9 +/- 0.4%, 3.2 +/- 0.2%). The major n-3 polyunsaturated fatty acid found in PE in response to dietary 20:5n-3 was the elongation metabolite 22:5n-3 in both the atherogenic (17.7 +/- 0.7%) and reference (14.3 +/- 1.0%) dietary groups; 22:6n-3 levels were less affected by diet (4.7 +/- 0.3% and 3.9 +/- 0.2%, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Gamma linolenic acid (GLA) content of encapsulated evening primrose oil products.

The fatty acid composition of 16 brands of evening primrose oil (EPO) capsules was determined by capillary gas chromatography. Fourteen of these EPO brands contained gamma-linolenic acid (GLA) levels between 7% and 10% (mean, 8.7; range, 1.9-10.5%) and there was generally good agreement between the level of GLA claimed by the manufacturer and the level determined by analysis. Low levels of the monoenes 22:1 and 24:1 found in some brands may indicate contamination of EPO with borage oil.

Capsules↗

Effect of n-3 and n-6 dietary fats on the lipoxygenase products from stimulated rat neutrophils.

Fish oil was fed to rats in combination with an equal amount of olive, sunflower or linseed (flax) oil in semisynthetic diets for 3 weeks. Following stimulation of isolated neutrophils with calcium ionophore the levels of leukotrienes (LT) were determined by HPLC. Graphical presentation of the resultant data show a direct linear relationship between LTB production and substrate concentration with no preferential conversion of n-3 or n-6 substrates. In addition the results highlighted the greater conversion of eicosapentaenoic acid (EPA) and arachidonic acid (AA) to 5-hydroxy metabolites in stimulated neutrophils. There is no suggestion in our results of inhibition of any of the enzymatic conversion steps between EPA or AA and LTB production by any of the dietary fatty acids except by altering the EPA/AA ratio in neutrophil membranes.

Animals↗

Determination of the optimal ratio of linoleic acid to alpha-linolenic acid in infant formulas.

The fatty acid composition of erythrocyte total lipids taken from a group of term infants 10 weeks after being fed a commercial infant formula with a high ratio of linoleic acid (18:2n-6) (LA) to alpha-linolenic acid (18:3n-3) (ALA) (19:1; LA, 14%; ALA, 0.7%; group A, n = 10) was compared with the fatty acid composition of erythrocytes from infants fed formulas that contained LA/ALA ratios reduced by either increasing ALA (4:1; LA, 13%; ALA, 3.3%; group B, n = 11) or decreasing LA (3:1; LA, 3.5%; ALA, 1.1%; group C, n = 8). Results were compared with those in an age-controlled group (n = 9) of breast-fed infants. Decreasing the LA/ALA ratio increased n-3 C20 and C22 fatty acid incorporation (formula B = 8.98% +/- 0.65%; formula C = 9.30% +/- 0.95%) relative to formula A (5.97% +/- 0.76%; p less than 0.05). Although docosahexaenoic acid (22:6n-3) (DHA) incorporation was highest in infants fed formulas B and C (4.78% +/- 0.45% and 4.48% +/- 0.49%, respectively) relative to formula A (3.47% +/- 0.46%; p less than 0.05), it did not reach levels found in breast-fed infants (6.55% +/- 1.23%; p less than 0.05). In addition, levels of arachidonic acid (20:4n-6) (AA) were lower in all formula-fed groups (p less than 0.05) relative to those in breast-fed infants. Based on some equations, it is predicted that AA levels in tissues of infants fed lower LA/ALA ratios would be reduced even further. Because both AA and DHA are probably essential for normal neural development of the infant, formulas with LA/ALA ratios below 4:1 are likely to result in fatty acid profiles notably different from those of breast-fed infants.

Arachidonic Acid↗

Linoleate inhibits EPA incorporation from dietary fish-oil supplements in human subjects.

Thirty healthy male subjects were randomly allocated into one of two treatment groups: group H subjects were maintained on a high-linoleic acid (LA) diet with the saturated fatty acids kept low and those in group L were kept on a low-LA, low saturate diet. After a 3-wk run-in period, subjects consumed a fish-oil supplement containing 1.6 g eicosapentaenoic acid (EPA)/d and 0.32 g docosahexaenoic acid as triglycerides for a further 4 wk. The diets alone resulted in a significant change in neutrophil phospholipid LA (H = 12.7 +/- 2.9%, L = 9.0 +/- 0.9%; P less than 0.05). Dietary supplementation with fish oil resulted in a significant increase in EPA in neutrophil phospholipids that was greater in group L (mean 2.0 +/- 0.4%) than group H (mean 1.5 +/- 0.3%; P less than 0.005). Reductions in arachidonic acid concentrations in neutrophil membranes were not different, nor could differences in leukotriene B4 production be detected. Our study indicates that the ingestion of n-6 fatty acids within the diet is an important determinant of EPA incorporation into neutrophil membranes.

Diet↗

The effect of adjuvant-induced arthritis on rat leukocyte membrane phospholipid fatty acid levels following fish oil feeding.

Inflamed rats with adjuvant-induced polyarthritis showed similar incorporation of dietary eicosapentaenoic acid (EPA) into peritoneal exudate cell (PEC) membrane phospholipids compared to pair fed non-inflamed control rats. Arachidonic acid (AA) content was similar in PEC phospholipids of inflamed and control rats whereas the linoleic acid content was consistently higher in inflamed rats.

Animals↗

Strategies for increasing the antiinflammatory effect of fish oil.

While both animal and human studies have shown that fish oil can exert antiinflammatory actions, the effects are modest and require large doses. The effects may be amplified by modifying the intake of other dietary fats and by making use of favourable interactions between fish oil and drugs.

Animals↗

Interaction between fish and vegetable oils in relation to rat leucocyte leukotriene production.

We examined the influence of mixtures of dietary fish oil and three vegetable oils (linseed, olive and sunflower) on the incorporation of dietary eicosapentaenoic acid (EPA) into rat leucocyte phospholipids and the subsequent metabolism of EPA and arachidonic acid by 5-lipoxygenase. Eicosapentaenoic acid in leucocyte phospholipids of fish oil-fed rats was decreased by the addition of each vegetable oil to the dietary fish oil, with sunflower oil, the oil highest in linoleate (LA), having the largest EPA-lowering effect (66% decrease). The rate of synthesis of leukotriene B4 (LTB4) was increased by the addition of each vegetable oil to the basic fish oil diet, with sunflower oil having a significant effect on LTB4 synthesis (145% increase). The effects of olive oil (enriched in oleate) were similar to those of linseed oil (enriched in alpha-linolenic acid) with regard to EPA incorporation (mean decrease = 30%) and LTB4 synthesis (mean increase = 72%). The level of arachidonic acid in leucocyte membranes and the rate of synthesis of LTB4 were proportional to the level of dietary LA added to the basic fish oil diet. The results indicate that olive or linseed oil ingested in combination with fish oil have less effect than does sunflower oil on leucocyte EPA content and LTB4 production. They further suggest that, when ingested with fish oil, dietary linoleic acid is more important than oleate or alpha-linolenic acid as a determinant of these variables.

Animals↗

Incorporation and effects of dietary eicosapentaenoate (20:5(n-3)) on plasma and erythrocyte lipids of the marmoset following dietary supplementation with differing levels of linoleic acid.

The effect of dietary eicosapentaenoic acid (EPA, 20:5(n-3), as the ethyl ester) on plasma lipid levels and the incorporation of EPA into erythrocyte and plasma lipids were investigated in the marmoset monkey. Marmosets were fed high mixed-fat diets (14.5% total fat) supplemented with or without 0.8% EPA for 30 weeks. Markedly elevated plasma cholesterol (16.4 mmol/l) was induced by an atherogenic-type diet but with EPA supplementation, plasma cholesterol increased to only 6.6 mmol/l. Plasma triacylglycerol levels were not elevated with an atherogenic type diet. Substantial EPA incorporation was evident for plasma phospholipid, triacylglycerol and cholesterol ester fractions. The proportion of docosapentaenoic acid (22:5(n-3)) but not docosahexaenoic acid (22:6(n-3)) was also elevated in these plasma lipid fractions. Greatest incorporation of EPA occurred when it was administered with an atherogenic type diet having a P:M:S (polyunsaturated:monounsaturated:saturated) fatty acid ratio of about 0.2:0.6:1.0 in comparison to the control diet of 1.0:1.0:1.0. Incorporation of EPA and 22:5(n-3)) into erythrocyte phospholipids was also apparent and this was at the expense of linoleic acid (18:2(n-6)). These results in the marmoset highlight both the cholesterol-lowering properties of EPA and the extent of its incorporation into plasma lipids and erythrocyte membrane phospholipids with far greater incorporation occurring when the level of dietary linoleic acid was reduced.

Animals↗

Effect of dietary oils on the production of n-3 and n-6 metabolites of leukocyte 5-lipoxygenase in five rat strains.

We examined the influence of various dietary oils, including linseed and fish oil on the relative rates of leukotriene B4 (LTB4) and LTB5 production by rat peritoneal exudate cells in five rat strains. While there was an association between the membrane phospholipid levels of the fatty acid precursors (arachidonic acid (AA) and eicosapentaenoic acid (EPA)) and the rate of synthesis of their respective 5-lipoxygenase products (LTB4 and LTB5), the rate of LTB4 synthesis was a combined function of both AA and EPA levels. We observed a strong linear relationship (correlation coefficient = 0.99) between the ratio of EPA/AA in the cell membrane phospholipids and the ratio of LTB5/LTB4 produced by these cells in vitro; this association was independent of genetic (strain) variability and was independent of the source of EPA (dietary EPA or EPA endogenously synthesized from dietary alpha-linolenic acid).

Animals↗

A comparison of lung lamellar body phospholipids from premature and term infants: is sphingomyelin a contaminant of surfactant?

Lamellar bodies were isolated from homogenates of lungs obtained at autopsy from premature infants (n = 9), and compared to lamellar bodies from three full term reference groups including 55 infants with sudden infant death syndrome (SIDS), 14 control infants, and 3 who succumbed to intra-uterine death (IUD) at term. Analysis of the phospholipids was expected to reveal a high proportion of sphingomyelin (Spm) in the lamellar bodies isolated from the lungs of premature infants (24 to 33 weeks gestational age) since at this stage of their development the percentage of Spm in the amniotic fluid is high. However, Spm was either absent or a small proportion of the total phospholipid in lamellar body surfactant from these premature infants. Spm was also a small percentage of phospholipid in the lamellar body surfactant of infants with SIDS and from control and IUD specimens. It is suggested that Spm may not be a normal constituent of lamellar body surfactant but rather a contaminant from membranes.

Amniotic Fluid↗

Comparison of cell membrane phospholipid fatty acids in five rat strains fed four test diets.

The fatty acid composition of phospholipids in peritoneal exudate cells and spleen cells was assessed in five rat strains fed four test diets of differing fatty acid composition. Distinctive patterns of fatty acids were seen in the total phospholipid preparations in both cell types in response to the diets which contained either olive, sunflower, linseed or fish oil. In general, similar fatty acid profiles were seen in each of the rat strains fed the same diet with the only evidence of possible genetic (strain) variation being a relative deficiency of delta 4 desaturase in Dark Agouti rats.

Animals↗

The effect of dietary fish oil supplement upon the content of dihomo-gammalinolenic acid in human plasma phospholipids.

Patients (n = 23) with definite or classical rheumatoid arthritis were given 18 g/day fish oil in gelatin capsules which provided 3.2 g/day EPA and 2.0 g/day DHA. The treatment period was 12 weeks followed by a 4 week washout period. Fish oil supplementation to the diet resulted in a substantial increase in the content of EPA and DHA in each of the plasma fractions examined (PL, TG, and CE). Little change was seen in the AA level of the TG and CE fractions but a modest decrease in AA was seen in PL. However the intake of fish oil caused a significant depression in the content of DGLA in the PL (p less than 0.005) and CE (p less than 0.01) fractions relative to baseline values. All changes had reverted to near baseline levels 4 weeks after dietary intervention. Since DGLA is the precursor of PGE1, which has been shown to be anti-inflammatory, our findings suggest that the anti-inflammatory effects of fish oil consumption could be mitigated by an associated reduction in DGLA.

8,11,14-Eicosatrienoic Acid↗