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Biomedical subjects

R T Holman

Publications and source records attributed to R T Holman.

At least 73 records · Page 4Linked to original sources
PubMed1985

Abnormal polyunsaturated fatty acid patterns of serum lipids in alcoholism and cirrhosis: arachidonic acid deficiency in cirrhosis.

Patterns of polyunsaturated fatty acids of serum phospholipids were measured for groups of alcoholics without cirrhosis, alcoholics with cirrhosis, cirrhotics without alcoholism, and a control population. Alcoholics without cirrhosis showed increased polyunsaturated fatty acids derived from linoleic and linolenic acids, but in cirrhotics these products were decreased. Alcoholism accentuated the abnormal polyunsaturated fatty acid pattern of cirrhosis. In alcohol abuse without cirrhosis, the level of 20:3 omega 9 (20 acyl carbon atoms:3 double bonds, omega, 9 carbon atoms beyond last double bond) was significantly increased, despite adequate levels of linoleic and arachidonic acids. Liver involvement appears necessary for development of deficiencies of polyunsaturated fatty acids in serum phospholipids, of which arachidonic acid deficiency is of the largest magnitude.

Adolescent↗
PubMed1984

Serum arachidonic acid levels in normal and preeclamptic pregnancies.

Fifteen serum samples from 11 women with preeclampsia and 19 samples from 10 normal third-trimester pregnancies were analyzed for total nonesterified fatty acids and total nonesterified arachidonic acid. The percentages of arachidonic acid in nonesterified fatty acids, in phospholipids, in triglycerides, and in cholesterol esters were also measured in each sample. The same analyses were done on serum from six samples of cord blood from each group. Cord blood sera from preeclamptic and normal pregnancies had much less total nonesterified fatty acids than the corresponding maternal sera but had much higher percentages of arachidonic acid in each of the major lipid categories. The maternal phospholipids and cholesterol esters had higher proportions of arachidonic acid in preeclampsia than in normal pregnancy. Samples from placentas of preeclamptic pregnancies had significantly lower proportions of arachidonic acid in the nonesterified fatty acids and triglycerides than normal placentas. These findings suggest a decreased availability of arachidonic acid in the fetal circulation which may result in decreased production of prostacyclin in preeclampsia.

Adolescent↗
PubMed1984

The hydrogenation of the series of methylene-interrupted cis,cis-octadecadienoic acids by pure cultures of six rumen bacteria.

The hydrogenation of all the methylene-interrupted cis,cis-octadecadienoic acids was examined using pure cultures of six rumen bacteria able to hydrogenate linoleic acid to stearic acid or its immediate precursor, trans-11-octadecenoic acid, after first conjugating the linoleic acid to cis,trans-9,11-octadecadienoic acid. Only the delta 14-cis,17-cis-isomer was not hydrogenated by at least one of the bacteria and no evidence was found that conjugation was necessary before hydrogenation except for the delta 2-cis,5-cis- and delta 9-cis,12-cis-isomers. Several isomers were hydrogenated to an extent close to that achieved with linoleic acid (delta 9-cis,12-cis). Those bacteria only able to hydrogenate linoleic to trans-11-octadecenoic acid gave only octadecenoic acid products and those bacteria able to hydrogenate linoleic acid to stearic gave variable yields of octadecenoic acids and stearic acid except with the isomers delta 12-cis,15-cis and delta 13-cis,16-cis when only octadecenoic acids were detected. At the substrate levels used (20 micrograms/ml), both inhibition and stimulation of growth were found but no common pattern emerged, nor was the growth consistently related to the extent of hydrogenation.

Animals↗
PubMed1984

Effects of biotin deficiency on polyunsaturated fatty acid metabolism in rats.

The effects of biotin and protein-calorie deficiency on metabolism of liver phospholipids in rats were determined. Weanling male Long-Evans rats were fed ad libitum a biotin-deficient (0.4 micrograms biotin/g diet) or a biotin-adequate (2.4 micrograms biotin/g diet) diet for 49 days. A pair-fed group was fed biotin-adequate diet but restricted to the amount consumed by biotin-deficient rats. The effects of these diets on food intake, weight gain, biotin content of serum and fatty acid composition of liver phospholipid were determined. Growth and food intake were significantly depressed in biotin-deficient and pair-fed rats. Biotin concentration in serum was significantly reduced in biotin-deficient and in pair-fed rats. Biotin deficiency caused significantly increased concentrations of 15:0, 17:0 and total odd-chain fatty acids in liver phospholipids. Combined biotin and protein-calorie deficiency and protein-calorie deficiency alone caused significantly increased concentrations of 18:2 omega 6 in liver phospholipids. Biotin deficiency caused significant reduction in liver phospholipid 20:3 omega 6. Reduced arachidonic acid (20:4 omega 6) level was due to combined biotin protein-calorie deficiency. Protein-calorie deficiency alone was primarily responsible for reduced levels of 22:5 omega 6. Biotin deficiency alone caused significant increases in liver phospholipids 18:3 omega 3 and 22:6 omega 3.

Animals↗
PubMed1984

Influence of reduced food intake on polyunsaturated fatty acid metabolism in zinc-deficient rats.

The influence of reduced food intake on metabolism of liver phospholipids (PL) in zinc-deficient (ZD) rats was measured. Wealing male Long-Evans rats were fed ad libitum zinc-deficient (2 micrograms Zn/g diet) and zinc-adequate (20 micrograms Zn/g diet) diets for 21 days. A pair-fed (PF) group was included. ZD and PF rats displayed significantly increased levels of linoleic (18:2 omega 6) and dihomo-gamma-linolenic acid (20:3 omega 6). Both ZD and PF rats displayed increased levels of gamma-linolenic acid (18:3 omega 6), but the increase was significant only in PF rats. ZD and PF rats displayed decreased levels of arachidonic acid (20:4 omega 6), but the decrease was significant only in PF rats. Both ZD and PF rats displayed significantly reduced levels of 22:5 omega 6. Both ZD and PF rats displayed increased products of delta 6 desaturation and decreased products of delta 5 and delta 4 desaturation. Significantly increased products of delta 9 desaturation were noted in both ZD and PF rats. ZD and PF rats displayed significant increases in C20 elongation products. ZD and PF rats displayed significantly decreased levels of omega 6 metabolites but not total omega 6 acids. ZD rats showed significantly increased levels of total omega 3 acids and omega 3 metabolites. ZD and PF rats showed significant increases in omega 9 acids but not significant changes in omega 9 metabolites. This study does not indicate that zinc affects the delta 6 desaturase in the metabolism of essential fatty acids. The aberrations previously attributed to zinc deficiency are probably due to the accompanying decreased food intake.

Animals↗
PubMed1983

Effects of polyunsaturated fatty acid diets on plasma lipids of patients with adrenomultineuronal degeneration, hepatosplenomegaly and fatty acid derangement.

The effect on plasma fatty acid composition of 3-6 weeks feeding of standard diets supplemented with various omega 6 polyenoic fatty acids (18:2, 18:3, 20:3 or 20:4) was studied in two young brothers with multineuronal degeneration plus. These boys had mental retardation or maldevelopment, neurosensory hearing loss, retinitis pigmentosa, progressive muscular atrophy, hepatosplenomegaly and adrenal failure. The study objectives were to localize the site of metabolic block and to assess the safety and short-term clinical effect of dietary treatment. Our studies have shown that the low plasma levels of 20:4 omega 6 can be corrected by feeding ethyl arachidonate and that no adverse effects were experienced. A diet enriched in ethyl linoleate produced no obvious increases of 18:2 omega 6 metabolites, indicating that these patients do not have a linoleate deficiency in their omega 6 polyenoic fatty acid pathway. Lack of incorporation of 20:4 omega 6 and a retroconversion of 20:3 omega 6 to 18:2 omega 6 after a dihomo-gamma-linolenate-enriched diet suggest that a defect of delta 5 desaturase may be involved.

Abnormalities, Multiple↗
PubMed1983

Arachidonic acid deficiency in streptozotocin-induced diabetes.

Fatty acid compositions of phospholipids of heart, liver, kidney, aorta, and serum from rats having streptozotocin-induced diabetes were determined and compared with those of nondiabetic controls. Linoleic and dihomo-gamma-linolenic acids were increased whereas arachidonic acid was decreased in most tissues, suggesting an impairment of delta 5-desaturase activity. Acids derived from linolenic acid were increased in some diabetic tissues from diabetic animals although the linolenic content was normal, indicating less impairment in the desaturation of the omega 3 series of fatty acids. Diabetes suppressed all polyunsaturated acids in the whole animal, but the competition between omega 3 and omega 6 acids favored the excessive suppression of long-chain omega 6 acids and an increase in the proportion of omega 3 acids in lipids of vital tissues. These changes in fatty acid composition of the phospholipids may have significant effects on cellular functions and vasoregulatory control mechanisms in diabetes.

Animals↗
PubMed1983

Suppression of arachidonic acid in lipids of rat tissues by dietary mixed isomeric cis and trans octadecenoates.

The influence of dietary isomeric cis and trans octadecenoic fatty acids (ICTO) on the metabolism of polyunsaturated fatty acids in rat tissues was studied by feeding a defined diet rich in partially hydrogenated soybean oil. Experimental and control animals received equal and more than adequate amounts of linoleic and linolenic acids. The total phospholipid (PL) fatty acids of liver, heart, testis, brain and sciatic nerve, and the fatty acids of liver triacylglyceride, cholesteryl ester and individual PL classes were analyzed by capillary gas chromatography. The content of arachidonic acid in the total fatty acids of liver lipids of ICTO-fed rats was found to be lower than those from control rats by the following amounts (in percent): total PL, 35; phosphatidylcholine, 50; phosphatidylinositol, 35; phosphatidylserine 26; phosphatidylethanolamine, 12; cholesteryl ester, 55; and tryglyceride 75. PL 18:2 omega 6 and 20:3 omega 6 levels were elevated, suggesting inhibition of the desaturase-elongase enzymes involved in synthesis of arachidonic acid. Synthesis of 20:5 omega 3 and 20:3 omega 9 was accentuated by the ICTO diet, suggesting an omega 6 series-specific inhibition. A nearly perfect negative correlation between cis 12-18:1 and arachidonic acid was found in liver PL.

Animals↗
PubMed1983

Decrease in liver norepinephrine in response to exercise and hypoglycemia.

The existence of the sympathetic innervation of the liver has been known for many years, but the role of this system in regulation of liver metabolism is unclear. The purpose of these experiments was to identify physiological conditions for activation of liver sympathetics. Liver norepinephrine (NE) was measured in normal resting rats and in rats exposed to swimming, treadmill running, fasting, and insulin-induced hypoglycemia. Liver NE decreased significantly in response to swimming (-71% of control), treadmill running (-53% of control), and hypoglycemia (-24% of control). Rats that are endurance trained by daily bouts of treadmill running for 3 mo show no decrease in liver NE in response to a 60-min run on the treadmill, whereas nontrained rats show a 50% decrease in liver NE with the same amount of exercise. We conclude that the liver sympathetics are activated in response to swimming, treadmill exercise and hypoglycemia, and that endurance training causes a reduction in the degree of exercise-induced activation of these neurons.

Animals↗
PubMed1982

Accumulation and depletion of trans octadecenoic acid in rat peripheral nerve phospholipid.

The accumulation and depletion of trans 18:1 acids in the sciatic nerve phospholipids was studied in rats fed a diet containing 18% partially hydrogenated soybean oil of which 45% was trans 18:1. The nerve phospholipid of rats fed partially hydrogenated soybean oil beginning at weaning age reached a maximum incorporation of trans 18:1 or 0.8% in 4 weeks; whereas the nerve phospholipid of 18-day-old pre-weanling pups of mothers fed the partially hydrogenated soybean oil diet since their weaning contained 3.3% trans 18:1. The trans content decreased rapidly after the weaning of these second-generation rats to a steady-state level 50% higher than the maximum level reached in the first generation. Upon removal of partially hydrogenated soybean oil from the diet, the trans 18:1 of nerve phospholipid decreased much more slowly than from liver or heart phospholipid. Essential fatty acid deficiency had no influence on incorporation or removal of trans 18:1 in nerve phospholipid. The accumulation and depletion of trans 18:1 in nerve phospholipid of second-generation partially hydrogenated soybean oil-fed rats paralleled the changes of polyunsaturated fatty acids and was quite different from the changes observed in 18:0 and cis 18:1. Polyunsaturated fatty acids increased in nerve phospholipid from second but not first-generation rats fed partially hydrogenated soybean oil and declined rapidly when partially hydrogenated soybean oil was removed from the diet.

Aging↗
PubMed1982

Abnormal polyunsaturated fatty acid patterns of serum lipids in Reye's syndrome.

Fatty acid patterns of the serum lipids were measured in 17 children with Reye's syndrome (RS). Serial measurements of total serum free fatty acids (FFA) showed that levels were increased during RS and, after recovery, were significantly lower in the patients who survived. Fatty acid patterns of serum FFA, triglycerides, and phospholipids in patients with RS were significantly different from those in controls. In RS the polyunsaturated fatty acid content of phospholipids was less than control values; in the FFA, it was higher. This was consistent with the possible involvement of increased phospholipase activity. The increase in polyunsaturated fatty acids in FFA, the precursors of prostaglandins, suggests that a grossly disturbed prostaglandin pattern may occur in RS. These changes in lipid metabolism may be related to the abnormal hepatic and neurological functions observed in RS.

Fatty Acids, Nonesterified↗
PubMed1982

Perturbation of the metabolism of essential fatty acids by dietary partially hydrogenated vegetable oil.

Rats were fed purified diets containing (i) partially hydrogenated soybean oil as source of isomeric octadecenoic acids, (ii) hydrogenated coconut oil as source of saturated fatty acids, and (iii) a low level of corn oil as low-fat control. All diets contained 18% of the linoleate requirement. Rat liver and heart phospholipids were analyzed by gas/liquid chromatography for fatty acids, and liver, microsomes were assayed for desaturase (acyl-CoA, hydrogen-donor: oxidoreductase, EC 1.14.99.5) activities. Products of desaturation reactions measured analytically provided more information with greater statistical significance than did the enzymatic assays. Rats fed isomeric octadecenoic acids showed more severe essential fatty acid deficiency than did saturated-fat and control groups. The suppression of linoleate metabolites was largely due to decreased delta 5 and delta 6 desaturase activities. At several levels of linoleate, the deficiency was more severe at the higher level of isomeric octadecenoic acids. Increasing the intake of linoleate to 7.5% of calories did not suppress deposition of isomeric unsaturated acids in tissue lipids.

Animals↗
PubMed1982

A case of human linolenic acid deficiency involving neurological abnormalities.

A 6-yr-old girl who lost 300 cm of intestine was maintained by total parenteral nutrition. After 5 months on a preparation rich in linoleic acid but low in linolenic acid she experienced episodes of numbness, paresthesia, weakness, inability to walk, pain in the legs, and blurring of vision. Diagnostic analysis of fatty acids of serum lipids revealed marginal linoleate deficiency and significant deficiency of linolenate. When the regimen was changed to emulsion containing linolenic acid neurological symptoms disappeared. Analysis indicated that linoleate deficiency had worsened but linolenate deficiency had been corrected. The requirement for linolenic acid is estimated to be about 0.54% of calories.

Child↗
PubMed1982

Endurance training attenuates stress hormone responses to exercise in fasted rats.

Endurance exercise training produces major adaptations in hormonal and metabolic responses to exercise. This study was designed to determine whether the differences in hormone response persist in the fasted condition when liver glycogen is depleted. Rats were run on a motor-driven rodent treadmill 5 days/wk for periods up to 2 h/day for 10 wk. Trained and nontrained rats were then fasted 24 h and were run for periods ranging from 0- to 60 min. At the end of 60 min of exercise muscle glycogen was higher in trained rats (2.9 +/- 0.3 vs. 1.1 +/- 0.1 mg/g). Blood glucose was maintained at higher levels in trained rats throughout the course of the exercise (3.2 +/- 0.1 vs. 2.3 +/- 0.1 mM after 60 min). Plasma concentrations of glucagon and epinephrine increased in both groups during the exercise but were significantly lower in trained animals. Differences between trained and nontrained animals in stress hormone responses to exercise persist in the fasted state and appear to be a consequence of the capacity of trained animals to maintain higher blood glucose levels.

3-Hydroxybutyric Acid↗
PubMed1982

Suspected faulty essential fatty acid metabolism in Sjögren-Larsson syndrome.

The aim of the present study was to examine the fatty acid patterns of plasma phospholipids, cholesteryl esters, triglycerides and free fatty acids in patients with Sjögren-Larsson syndrome in order to detect whether absorption or metabolism is essential fatty acids may be abnormal. The fatty acid patterns were analyzed by gas liquid chromatography. The proportions of 23 fatty acids were calculated. The parameters used for assessment of the essential fatty acid metabolic status were calculated and compared with those from a group of institutionalized mentally retarded patients and from a group of healthy controls. There was no significant difference in either the fatty acid components or parameters used to evaluate the essential fatty acid metabolic study when the mentally retarded and control groups were compared. The relative concentration of linoleic acid (18:2 omega 6) in plasma phospholipids in patients with Sjögren-Larsson syndrome did not differ significantly from that of the healthy or mentally retarded controls, indicating that the Sjögren Larsson syndrome does not involve a dietary essential fatty acid deficiency or a defect in absorption of linoleate. In the phospholipids of Sjörgren-Larsson syndrome patients, the metabolites derived from linoleic acid were found to be significantly lower than in health controls, suggesting the metabolic defect. The total products of delta 6 desaturation were reduced to 3% of that in controls, whereas the products of delta 5 and delta 9 desaturation were not noticeably affected in the patients with Sjögren-Larsson syndrome. All individuals with Sjörgren-Larsson syndrome exhibited decreased products of delta 6 desaturation which also affected subsequent metabolites in the metabolite sequence.

Adolescent↗
PubMed1981

Beta-oxidation of the geometric and positional isomers of octadecenoic acid by rat heart and liver mitochondria.

The cis and trans isomers of delta 4 through delta 16 octadecenoic acid, all present in partially hydrogenated soybean oil, were compared as substrates for beta-oxidation by isolated rat heart and liver mitochondria. The fatty acids were converted to their coenzyme A esters and oxygen uptake rates measured polarographically in the presence of L-malate, L-carnitine, ADP, and optimum albumin. The cis isomers were catabolized in a similar pattern by heart and liver. The even-positioned cis isomers were oxidized significantly more slowly than adjacent odd-positioned isomers. Most odd-positioned cis isomers were oxidized as rapidly as oleoyl-CoA. The pattern of catabolism of the trans isomers, however, was different from the cis isomers. Liver mitochondria oxidized most even-positioned trans isomers significantly more rapidly than adjacent odd-positioned isomers. The same pattern was observed with heart mitochondria only for the trans isomers in which the double bond was located near the middle of the acyl chain. Heart mitochondria oxidized nearly all the trans isomers significantly more slowly than stearoyl-CoA; however, liver mitochondria oxidized the even-positioned trans isomers nearly as rapidly as stearoyl-CoA. Both heart and liver mitochondria oxidized the cis isomers, especially delta 9 and delta 11, significantly more rapidly than their respective trans isomers, with three notable exceptions: delta 8, delta 10, and delta 14. 3-Hydroxyacyl-CoA epimerase and delta 3-cis-delta-2-trans-enoyl-CoA isomerase account for most of the observed beta-oxidation patterns. An additional and more efficient pathway for the beta-oxidation of n-6 fatty acids is suggested.

Animals↗