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Biomedical subjects

R A Gibson

Publications and source records attributed to R A Gibson.

At least 109 records · Page 6Linked to original sources

Weaning foods cannot replace breast milk as sources of long-chain polyunsaturated fatty acids.

Breast-milk lipids contain long-chain polyunsaturated fatty acids (PUFA) not found in infant formulas. Because the erythrocyte membranes of formula-fed infants are depleted in long-chain PUFA, we sought food sources of these 20- and 22-carbon polyunsaturates suitable for use as dietary supplements. A variety of commercially available infant foods containing meats and egg products in addition to some whole foods (meat, eggs) were analyzed by gas chromatography. Commercially available infant foods contained only low levels of long-chain PUFA. The richest source of omega-3 and omega-6 PUFA was found to be lamb brains but lamb and chicken livers as well as egg yolks also contained high levels. However, the lipid content of most whole foods including brains, eggs, and liver is so low that prohibitively large amounts of food would be required to be fed to infants. It is concluded that it is virtually impossible to supplement the diet of formula-fed infants to match the long-chain PUFA intake of breast-fed infants with currently available whole foods.

Breast Feeding↗

The effect of diets containing fish and fish oils on disease risk factors in humans.

Fish and fish oils are rich in omega 3 polyunsaturated fatty acids which are capable of acting as both a source of active eicosanoids and as inhibitors of synthesis of eicosanoids from arachidonic acid by a variety of human cells. There is an extensive literature on the role of omega 3 polyunsaturates in ameliorating the risk factors associated with coronary heart disease, including both atherosclerotic and thrombotic factors. In addition, there is a limited number of studies which report the results of trials testing the effects of fish oils on other clinical conditions including diabetes, arthritis, migraine and psoriasis. There appears to be sufficient evidence to suggest that patients at risk from heart disease could benefit from low dose (1-6 g/day) of fish oil in conjunction with a prudent diet.

Animals↗

Halothane induced hepatic necrosis in rats: the role of in vivo lipid peroxidation.

Hepatic damage was induced in phenobarbitone pretreated male Fischer 344 rats by the administration of 1% halothane in 14% oxygen for either 1 or 2 hours. Ethane production during the exposure period was not significantly different between the halothane and non-halothane exposed groups. Animals were sacrificed 1, 2, 6 and 24 hrs from commencement of anaesthesia and the hepatic microsomal fraction analyzed for diene conjugates, lipid hydroperoxides, total lipid content and fatty acid composition. Animals exposed to halothane and sacrificed at 2 and 24 hrs had significantly elevated levels of diene conjugates (P less than 0.05), while lipid hydroperoxide concentration and serum alanine aminotransferase increased in only those animals sacrificed at 24 hrs. Alterations in total lipid content and hepatic microsomal fatty acid composition were not observed in animals sacrificed after 1 and 2 hrs. A significant reduction in total lipid and arachidonic acid content occurred only in those animals sacrificed 24 hrs after exposure, however a concomitant increase in the saturated fatty acid fraction was not observed. It is proposed that alterations in fatty acid composition in vivo and evidence of lipid peroxidation occur as a result of cell death rather than an initiating event in halothane induced hepatic necrosis in rats.

Alanine Transaminase↗

Mitochondrial membrane fatty acid composition in the marmoset monkey following dietary lipid supplementation.

Diets supplemented with high levels of saturated fatty acids derived from sheep kidney (perirenal) fat or unsaturated fatty acids derived from sunflowerseed oil were fed to marmoset monkeys for 22 wk. The effect of such diets on plasma, red blood cell phospholipids, and liver, heart, kidney and brain mitochondrial phospholipid fatty acids was determined. Despite large differences in the level and type of lipid present in the experimental diets, there was little effect on the proportion of saturated to unsaturated fatty acids in the phospholipids of the membranes examined. The diets did, however, alter the proportion of the various classes of polyunsaturated fatty acids in the membrane phospholipids, with the sunflowerseed oil diet elevating and the sheep kidney fat diet reducing the n-6/n-3 unsaturated fatty acid ratio, relative to a low (mixed fat) reference diet. This change occurred in all membranes except brain, in which only a small response to altered dietary lipid intake was observed. Elevation of dietary linoleic acid led to an increase in membrane linoleic acid and a marked decrease in membrane arachidonic acid, such that the membranes from animals fed the sunflowerseed oil diet exhibited the lowest proportion of arachidonic acid. In this latter respect, the response of the marmoset monkey to dietary lipid supplementation differs markedly from the rat. Our inability to alter significantly membrane lipid saturation/unsaturation supports the notion that a homeostatic mechanism is in some way responsible for buffering membranes from the effects of significant changes in the nature of the dietary lipid intake.

Animals↗

Changes in lung surfactant lipids associated with the sudden infant death syndrome.

The lipid composition of lung surfactant obtained by lung lavage at autopsy in 40 infants dying from Sudden Infant Death Syndrome (SIDS) was compared with that obtained from 12 infants dying from other causes (control group). Analysis of the total lipids extracted from the surfactant of the SIDS and the control groups showed no major differences in the proportion of the various phospholipids including the major phospholipid, phosphatidylcholine (PC). However, a significantly reduced proportion of the PC was in the form of the biologically active species, disaturated phosphatidylcholine (DSPC) (P less than 0.005). In surfactant from SIDS infants, mean DSPC amounted to 65.8% (s.e.m. = 1.6) compared with normal surfactant 77.4% (s.e.m. = 3.5). A functional consequence of such a reduction in DSPC content of lung surfactant of SIDS infants could be a greater degree of fluidity of surfactant, particularly at exhalation. Such a biophysical change in surfactant properties could have a profound influence on lung function and, perhaps in response to external or internal stimuli, could be a causative factor in sudden infant death.

Female↗

Secretion of cholesteryl ester-enriched very low density lipoproteins by the liver of cholesterol-fed rabbits.

The output of lipids and lipoproteins by isolated perfused livers of normal-fed and cholesterol-fed rabbits has been examined. There was a comparable output of triglyceride by the livers of both groups, resulting in an accumulation of 40-50 mg triglyceride/liver/2 h in the perfusate in each case. The output of cholesteryl esters, however, was very much greater from the livers of cholesterol-fed (45 mg/liver/2 h) than from normal-fed (3.3 mg/liver/2 h) rabbits. The major lipoproteins in liver perfusates from both groups of animals were very low density lipoproteins (VLDL). In the perfusate of normal livers the VLDL were enriched with triglyceride and depleted of cholesteryl esters when compared with plasma VLDL from normal animals. VLDL in the perfusate of livers from cholesterol-fed rabbits, on the other hand, were markedly enriched with cholesteryl esters; cholesteryl esters accounted for 33% by mass of VLDL from cholesterol-fed livers and only 3.1% of VLDL from normal livers. The cholesteryl esters in the plasma lipoproteins of cholesterol-fed rabbits were relatively enriched with cholesteryl oleate when compared to those in normal plasma. Similarly, cholesteryl oleate predominated in the VLDL in the liver perfusate of the cholesterol-fed animals, consistent with an hepatic acyl CoA/cholesterol acyltransferase origin. Thus, cholesterol-feeding in the rabbit results in a marked increase in the hepatic secretion of cholesteryl esters as a component of VLDL.

Animals↗

Fatty acid composition of breast milk from three racial groups from Penang, Malaysia.

The fatty acid composition of samples of breast milk obtained from 51 mothers (26 Malay, 15 Chinese, 10 Indian) residing in Penang, Malaysia was determined by gas chromatography. Despite living in close physical proximity the mothers from the three racial groups showed distinct cultural differences in dietary intake. These differences were reflected in differences in the fatty acid composition of breast milk samples. The milk of Chinese mothers was generally less saturated (41%) than that of Malay and Indian mothers (52 and 50% respectively). The milk of Chinese mothers was also richer in linoleic acid (17%) than that of Malay and Indian mothers (9% and 11% respectively). Overall the level of individual fatty acids fell within the range of values reported for Western mothers on well nourished diets and pointed to breast milk of high standard despite large variations in the diet of Malaysian mothers.

Adult↗

Abnormal bowel permeability in ankylosing spondylitis and rheumatoid arthritis.

Intestinal permeability was measured using a low molecular weight polyethylene glycol as a permeability marker in patients with osteoarthritis, ankylosing spondylitis (AS) and rheumatoid arthritis (RA). Patients with AS showed a significant increase in bowel permeability when compared to controls. Intestinal permeability was also increased in patients with active RA but was less than the control group in RA patients who did not have active joint disease.

Absorption↗

Homeostatic control of membrane fatty acid composition in the rat after dietary lipid treatment.

Diets in which both the lipid content and composition (polyunsaturated to saturated fatty acid ratio) were varied were fed to rats for 20 weeks, and the effects on the tissue lipid profiles were determined. The fatty acid profile of the plasma lipids, and the phospholipid fatty acids of the mitochondrial and microsomal fractions of liver, heart, kidney and brain, as well as erythrocyte membranes were determined. Despite large differences in the level and type of lipid present in the experimental diets and in the proportion of saturated fatty acids in the plasma lipids in response to the various diets, there was little effect on the proportion of saturated to unsaturated fatty acids in the phospholipids of the various membranes examined. The major effect of altering the dietary level of polyunsaturated to saturated fatty acids was on the ratio of the omega 6/omega 3 series of unsaturated fatty acids in the membrane lipids. This change occurred in all tissues except the brain, in which only a small response to altered dietary lipid intake was observed. The omega 6/omega 3 ratio was elevated upon feeding a diet rich in omega 6 polyunsaturated fatty acids, but decreased when a diet rich in saturated fatty acids was fed. The failure to significantly alter membrane lipid saturation/unsaturation in the tissues examined would suggest that a homeostatic mechanism is operative in biological membranes and may act to buffer membranes from the effects of changes in the nature of the dietary lipid intake.

Animals↗

A lack of correlation between linoleate and arachidonate in human breast milk.

The levels of arachidonic acid and linoleic acid found in the lipid fraction of human milk samples were compared. No correlation was found between the level of precursor linoleate and product arachidonate in 80 samples of colostrum (day 3-5) or 60 samples of mature breast milk. We attempted to test the hypothesis that the absence of a precursor-product relationship was caused by a constant level of arachidonate being secreted in the phospholipids (PL) of breast milk cells. Examination of the fatty acid (FA) composition of the PL and triglyceride fractions revealed arachidonate in high concentration in PL but that most of the total arachidonate existed in triglycerides.

Arachidonic Acid↗

A comparison of mitochondrial respiration and membrane lipid composition in the rat and marmoset following dietary lipid supplementation.

Rats and marmosets were fed different lipid supplemented diets and the phospholipid fatty acid composition and the respiration rate of liver and heart mitochondria were determined. For both species, diets of differing lipid saturation had little effect on the ratio of saturated to unsaturated fatty acids in the mitochondrial membranes, however the omega 6/omega 3 unsaturated fatty acid ratio was significantly altered by diets of different lipid saturation. In comparison to animals fed low fat diets, mitochondrial respiration in the marmoset was reduced by high fat diets irrespective of the dietary level of lipid saturation. This effect of high fat diets on mitochondrial respiration was not observed for the rat.

Animals↗

Comparative levels of arachidonic acid and eicosapentaenoic acid in Malaysian fish.

Total lipids were extracted from 22 species of Malaysian fish and the constituent fatty acids were analysed by gas chromatography. Malaysian fish generally contained high levels of saturated fatty acids (range 36-55% total fatty acids) and contained variable amounts of monounsaturates, chiefly palmitic and stearic acids, but only trace levels of 20:1 and 22:1. Unlike fish caught in colder northern hemisphere waters, Malaysian fish were found to contain arachidonic acid (20:4 omega 6, range 2-12%) in addition to the expected eicosapentaenoic acid (20:5 omega 3, range 1-13%) and docosahexaenoic acid (22:6 omega 3, range 6.6-40.4%).

Animals↗

Optimized liquid-chromatographic determination of metronidazole and its metabolites in plasma.

Metronidazole and its known metabolites in plasma can be rapidly separated by a "high-pressure" liquid-chromatographic method that can also be adapted for rapid determination of tinidazole. Samples deproteinized with trichloroacetic acid (50 g/L final concentration) undergo isocratic separation on a reversed-phase C18 column eluted with an 8/92 (by vol) mixture of acetonitrile/KH2PO4 (5 mmol/L, pH 3.0). The method is sensitive, reliably detecting as little as 25 micrograms of metronidazole and (or) its metabolites per milliliter of plasma. The detector response varied linearly with concentration for all compounds tested over a wide range (25-500 micrograms/L). Within-day and between-day variation was generally less than 2.5% for all concentrations of all compounds tested. Various other antibiotics tested did not interfere.

Chromatography, High Pressure Liquid↗

Differential modulation of rat heart mitochondrial membrane-associated enzymes by dietary lipid.

Diets supplemented with high levels of saturated fatty acids derived from sheep kidney (perirenal) fat or unsaturated fatty acids derived from sunflower seed oil were fed to rats and the effect on heart mitochondrial lipid composition and membrane-associated enzyme behaviour was determined. The dietary lipid treatments did not change the overall level of membrane lipid unsaturation but did alter the proportion of various unsaturated fatty acids. This led to a change in the omega 6/omega 3 unsaturated fatty acid ratio, which was highest in the sunflower seed oil fed rats. Arrhenius plots of the mitochondrial membrane associated enzymes succinate-cytochrome c reductase and oligomycin-sensitive adenosinetriphosphatase (ATPase) after dietary lipid treatment revealed different responses in their critical temperature. For succinate-cytochrome c reductase, the critical temperature was 29 degrees C for rats fed the sheep kidney fat diet and 20 degrees C for rats fed the sunflower seed oil diet. In contrast, no shift in the critical temperature for the mitochondrial ATPase was apparent as a result of the differing dietary lipid treatments. The results suggest that the discontinuity in the Arrhenius plot of succinate-cytochrome c reductase is induced by some change in the physical properties of the membrane lipids. In contrast, mitochondrial ATPase appears insensitive, in terms of its thermal behaviour, to changes occurring in the composition of the membrane lipids. However, the specific activity of the mitochondrial ATPase was affected by the dietary lipid treatment being highest for the rats fed the sheep kidney fat diet. No dietary lipid effect was observed for the specific activity of succinate-cytochrome c reductase. This differential response of the two mitochondrial membrane enzymes to dietary-induced changes in membrane lipid composition may affect mitochondrial oxidative phosphorylation.

Adenosine Triphosphatases↗

The effect of dietary lipids on the thermotropic behaviour of rat liver and heart mitochondrial membrane lipids.

Diets supplemented with relatively high levels of either saturated fatty acids derived from sheep kidney fat (sheep kidney fat diet) or unsaturated fatty acids derived from sunflower seed oil (sunflower seed oil diet) were fed to rats for a period of 16 weeks and changes in the thermotropic behaviour of liver and heart mitochondrial lipids were determined by differential scanning calorimetry (DSC). The diets induced similar changes in the fatty acid composition in both liver and heart mitochondrial lipids, the major change being the omega 6 to omega 3 unsaturated fatty acid ratio, which was elevated in mitochondria from animals on the sunflower seed oil diet and lowered with the mitochondria from the sheep kidney fat dietary animals. When examined by DSC, aqueous buffer dispersions of liver and heart mitochondrial lipids exhibited two independent, reversible phase transitions and in some instances a third highly unstable transition. The dietary lipid treatments had their major effect of the temperature at which the lower phase transition occurred, there being an inverse relationship between the transition temperature and the omega 6 to omega 3 unsaturated fatty acid ratio. No significant effect was observed for the temperature of the higher phase transition. These results indicate that certain domains of mitochondrial lipids, probably containing some relatively higher melting-point lipids, independently undergo formation of the solidus or gel phase and this phenomenon is not greatly influenced by the lipid composition of the mitochondrial membranes. Conversely, other domains, representing the bulk of the membrane lipids and which probably contain the relatively lower melting point lipids, undergo solidus phase formation at temperatures which reflect changes in the membrane lipid composition which are in turn, a reflection of the nature of the dietary lipid intake. These lipid phase transitions do not appear to correlate directly with those events considered responsible for the altered Arrhenius kinetics of various mitochondrial membrane-associated enzymes.

Animals↗

The influence of water on the phase transition of sheep lung surfactant. A possible mechanism for surfactant phase transitions in vivo.

The effect of water on the thermal properties of sheep lung surfactant lipids was determined by differential scanning calorimetry. Dry surfactant exhibited a phase transition with an upper limit of about 54 degrees C, whereas that of the fully hydrated surfactant was about 30 degrees C. The effect of water was confined to a range of hydration values from 0 to 25%. The results indicate that pulmonary surfactant lipids are capable of undergoing both thermotropic and lyotropic mesomorphism in vitro. The degree of hydration of the surfactant could influence its in vivo biophysical role in alveolar dynamics. Indeed, small changes in the surfactant to water ratio induced by regional differences in the surfactant concentration at the alveolar surface during alveolar expansion and contraction could be sufficient to trigger isothermal phase transitions in the surfactant lipids. This would allow changes to occur in the equilibrium between solidus and fluidus surfactant during the respiratory cycle.

Animals↗