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Biomedical subjects

M A Neumann

Publications and source records attributed to M A Neumann.

At least 37 records · Page 2Linked to original sources

Differences in fatty acid composition of immature and mature articular cartilage in humans and sheep.

Chondrocytes are imbedded in an avascular, highly charged extracellular matrix which could form a barrier to the transfer of dietary essential fatty acids (EFA) to chondrocytes. A study was designed to assess the composition of immature and mature joint cartilage with respect to essential and nonessential fatty acids relevant to EFA deficiency. Cartilage and muscle samples were obtained from human fetus, infant and adult cadavers, and from fetal and mature sheep. Lipid extracts were prepared and the fatty acid composition determined. In human and sheep joint cartilage, linoleic acid (LA; 18:2n-6) content was lower, and n-9 eicosatrienoic acid (ETrA; 20:3n-9) and arachidonic acid (AA; 20:4n-6) were higher in fetuses compared to mature subjects. An intermediate pattern was seen in infant cartilage. n-3 Fatty acids tended to be higher in fetal than in mature cartilage in humans and in sheep. In human muscle (and in other noncartilaginous comparison tissues), similar differences between fetuses and adults were seen in LA and AA, but not in ETrA. In fetal sheep muscle, very low LA, reduced AA and raised ETrA levels compared to mature sheep muscle were seen. However, although the pattern is characteristic of EFA deficiency, the abundance of n-6 EFA in liver and spleen of human fetuses and of n-3 EFA in liver and spleen of fetal sheep suggests that placental transfer of EFA is not likely to be limiting. During fetal development, the metabolism of fatty acids is distinctive and differs between the species. ETrA appears to be a readily measurable component of some tissues at certain stages of development when its presence in tissues does not indicate EFA deficiency.

8,11,14-Eicosatrienoic Acid↗

Sudden infant death syndrome: effect of breast and formula feeding on frontal cortex and brainstem lipid composition.

METHODOLOGY: Docosahexaenoic acid levels were measured by gas chromatography in samples of frontal lobe and brainstem taken from 28 and 26 infants, respectively, who had died of sudden infant death syndrome (SIDS). RESULTS: Significantly higher levels of docosahexaenoic acid were present in the frontal lobe tissues derived from the 13 breast fed infants (age range = 3.3-36.3 weeks; mean 15.9 +/- 11.3 weeks) compared to the 15 formula fed infants (age range = 6.9-47.7 weeks; mean 19.3 +/- 10.6 weeks); mean (+/- s.d.) levels were 8.5 +/- 1.1% and 7.6 +/- 0.8% of total fatty acids (P = 0.019). There was, however, no significant difference in brainstem docosahexaenoic acid levels between breast and formula fed infants. CONCLUSIONS: Given these variable findings, further investigation of the relationship between dietary fatty acid intake and cerebral lipid levels may help to clarify whether different modes of feeding have a role in the pathogenesis of SIDS.

Autopsy↗

Inhibition of human neutrophil leukotriene B4 synthesis in essential fatty acid deficiency: role of leukotriene A hydrolase.

A female subject dependent on long-term total parenteral nutrition developed an aversion and noncompliance to a prescribed weekly lipid infusion designed to meet essential fatty acid (EFA) requirements. Fatty acids (FA) in the subject's plasma and isolated peripheral blood neutrophils were analyzed in search of biochemical evidence of EFA deficiency. Neutrophil 5-lipoxygenase metabolism was examined to assess the possible effects of EFA deficiency on neutrophil eicosanoid metabolism. EFA deficiency was confirmed by marked depletion of linoleic acid (18:2n-6) and accumulation of eicosatrienoic acid (ETrA; 20:3n-9) in plasma and neutrophil phospholipids. In the neutrophils, ETrA comprised 5.2% of phospholipid FA (normal reference values < 0.1%), and arachidonic acid (AA; 20:4n-6) comprised 8.6% of phospholipid FA (normal reference range 10-16%). When stimulated by A23187 in vitro on three separate occasions, the subject's neutrophils displayed impaired synthesis of leukotriene B4 (LTB4), but produced normal amounts of 5-hydroxy-eicosatetraenoic acid and all-trans isomers of LTB4 formed nonenzymatically from leukotriene A4 (LTA4). This pattern of synthesis suggested inhibition of LTA hydrolase and was also seen in neutrophils from healthy subjects by addition of exogenous ETrA in vitro. Comparative studies of the effects of ETrA and eicosapentaenoic acid (20:5n-3) on neutrophils in vitro suggested that ETrA is the more potent inhibitor. Accumulation of ETrA, rather than depletion of AA, appears principally responsible for the observed impairment of neutrophil LTB4 synthesis seen in this EFA-deficient subject.

Adult↗

Ratios of linoleic acid to alpha-linolenic acid in formulas for term infants.

Commercial infant formulas with a ratio of linoleic acid (LA) to alpha-linolenic acid (ALA) of 10:1 or higher are nutritionally inadequate; the tissue levels of docosahexaenoic acid (DHA) are lower and the visual function indices are reduced in infants who are fed these formulas. All the evidence points to using LA:ALA ratios of less than 8:1, but there has been only one study in infants that used formulas with reduced LA:ALA ratios, and only biochemical indices were monitored. There is a need for both short-term studies to establish the ratios of LA to ALA that will make possible the accumulation of DHA to levels close to those in breast-fed infants and long-term trials to determine the effects of such fat blends on growth and development.

Breast Feeding↗

Fatty acid composition of brain, retina, and erythrocytes in breast- and formula-fed infants.

Breast-fed infants score better on visual and developmental tests than do formula-fed infants and this has been related to higher concentrations of erythrocyte docosahexaenoic acid (DHA, 22:6 omega 3). This prompted an investigation into the relationship between brain, retina, and erythrocyte fatty acids and diet in infancy. Total lipids of erythrocytes, retina, and brain cortex from 35 term infants were analyzed by capillary gas chromatography. Breast-fed infants had a greater proportion of DHA in their erythrocytes and brain cortex relative to those fed formula (P < 0.005) but differences were not observed in retina. Cortex DHA increased in breast-fed (but not formula-fed) infants with age (r2 = 0.72, P < 0.01, n = 15), largely an effect of length of feeding (r2 = 0.62, P < 0.01, n = 35). There was an association between age at death and erythrocyte DHA with cortex DHA (r2 = 0.50, P < 0.01). In contrast, accretion of cortex arachidonic acid was dependent on age but not diet. The higher concentration of DHA in brains of breast-fed infants may explain the improved neurodevelopment reported in breast-fed compared with formula-fed infants.

Arachidonic Acid↗

Effect of dietary supplementation with n-9 eicosatrienoic acid on leukotriene B4 synthesis in rats: a novel approach to inhibition of eicosanoid synthesis.

Studies were undertaken to assess the biochemical effects of dietary supplementation with n-9 eicosatrienoic acid (ETrA), an arachidonic acid analogue that is normally present in cell membranes at very low levels but is raised in the presence of essential fatty acid deficiency (EFAD). The incorporation of dietary ETrA into rat neutrophils and its effect on A23187-stimulated 5-lipoxygenase metabolism in these cells was examined; in addition, the effect of ETrA was compared with that of another arachidonic acid analogue, eicosapentaenoic acid (EPA), which is known to accumulate in cell membranes and inhibit synthesis of leukotriene B4 (LTB4) a product of the 5-lipoxygenase metabolic pathway. Rats were fed a defined diet that was sufficient in essential fatty acids and that contained EPA or ETrA (0.014% of energy) or no added fatty acid, for 3 wk. In the cells from ETrA-fed rats, LTB4 synthesis was inhibited relative to control values, but synthesis of the other products of 5-lipoxygenase metabolism, 5-hydroxyeicosatetraenoic acid (5-HETE) and the all-trans isomers of LTB4, were not inhibited. This pattern indicates inhibition of LTA hydrolase in ETrA-fed rats. In EPA-fed rats, there was inhibition of LTB4 and the all-trans isomers of LTB4, but there was no inhibition of 5-HETE. This pattern indicates inhibition of LTA synthase in EPA-fed rats. The results establish that dietary ETrA effectively inhibits synthesis of the inflammatory mediator, LTB4, and suggest that ETrA may confer antiinflammatory benefits similar to those observed with EFAD or dietary fish oil (which contains EPA). Because ETrA is substantially less unsaturated than EPA, it can be expected to have greater chemical stability, which could be an important practical advantage when used as a dietary constituent or supplement.

8,11,14-Eicosatrienoic Acid↗

Simple relationships exist between dietary linoleate and the n-6 fatty acids of human neutrophils and plasma.

Eicosanoids, the enzymatically oxygenated products of arachidonic acid (AA), appear to be overproduced in some disorders of inflammation. Dietary strategies for decreasing tissue AA require information on the relationships between dietary linoleic acid (LA) and tissue concentrations of AA. The use of either high- or low-LA spreads and cooking oils by healthy male volunteers resulted in a range of LA intakes of 2.5-17.5% of energy, as estimated by diet-diary analysis. Analysis of LA and AA concentrations in neutrophils and plasma lipid fractions from these subjects indicated that there were positive linear relationships between dietary LA and the LA concentrations in neutrophil phospholipids, plasma triglycerides, and plasma cholesteryl esters. By contrast, differences in dietary LA within a broad range were not associated with differences in concentrations of AA in these same neutrophil and plasma fractions. AA concentrations were decreased by supplementation of the diet with 4 g fish oil (1.6 g eicosapentaenoic acid, 0.3 g docosahexaenoic acid). The results suggest that the LA content of tissue lipids may be used to estimate LA intake, and the reduction of dietary LA by using standard dietary strategies is not likely to lead to reduction in tissue AA whereas this can be accomplished by fish-oil supplementation.

Adult↗

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↗

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↗

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↗

Long duration Jakob-Creutzfeldt disease.

The first patient was a woman hospitalized at the age of 43 years; she received the diagnosis of presenile dementia because of a progressive deterioration of her intellectual functions over an interval of 3 years. On admission there were no localizing neurological findings. During the ensuing years she became unable to speak and was no longer able to respond to commands. Death occurred at the age of 46 years from bronchopneumonia. The brain showed marked atrophy of the frontal lobes, moderate in the temporal lobes. The anterior horns of the lateral ventricles were greatly dilated. Microscopically cortical atrophy was severe, with marked depletion of neurons in involved regions. Lamination and polarity were not preserved. There was considerable increase of astrocytes and microglia, and focal sponginess was prominent. The hippocampus showed atrophy of Sommer's sector and subiculum. There were no neurofibrillary tangles and no argyrophilic plaques. The occipital sections showed little neuronal loss and no increased astrocytes or sponginess. The insulae showed neuronal loss and gliosis. There was bilateral atrophy of the caudate nuclei and globus pallidus adjacent to the dystrophic anterior limbs of the internal capsule. In the brain stem the frontopontine tracts were partially demyelinated and showed reactive gliosis. Ventral horns were atrophic with moderate glial reaction. In the second patient the microscopic changes were quite similar to those in Case 1, but there was more severe degeneration of the corticospinal tracts and the ventral horns of the spinal cord which showed considerable loss of neurons and degenerative changes in the remaining nerve cells and nerve fibers. There were many instances of axonal degeneration.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗