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Biomedical subjects

M G Traber

Publications and source records attributed to M G Traber.

At least 73 records · Page 4Linked to original sources
PubMed1994

beta-Carotene transport in human lipoproteins. Comparisons with a-tocopherol.

The purpose of this study was to investigate the temporal relationships of the transport of beta-carotene in human lipoproteins. We administered 60 mg beta-carotene with breakfast to nine fasting subjects, then blood samples were collected at intervals of up to 75 h, lipoproteins were isolated, and beta-carotene was quantitated. beta-Carotene concentrations in chylomicrons and very low density lipoproteins (VLDL) peaked at 6 and 9 h, respectively. Nonetheless, at all time points the majority of plasma beta-carotene was contained in low density lipoproteins (LDL), while high density lipoproteins (HDL) carried a smaller portion (at 24 h, 73 +/- 8% in LDL as compared with 23 +/- 5% in HDL). In three subjects, transport of beta-carotene was compared with the results of earlier studies on the transport of stereoisomers of alpha-tocopherol. Unlike plasma RRR-alpha-tocopherol concentrations, which are maintained by the preferential incorporation of RRR-alpha-tocopherol into VLDL by the liver, beta-carotene increased and decreased in VLDL similarly to SRR-alpha-tocopherol, a stereoisomer whose concentrations are not maintained in plasma. In conclusion, beta-carotene is primarily transported in the plasma in LDL, but its incorporation by the liver into lipoproteins does not appear to be enhanced.

Biological Transport↗
PubMed1994

Discrimination between RRR- and all-racemic-alpha-tocopherols labeled with deuterium by patients with abetalipoproteinemia.

The ability to discriminate between stereoisomers of alpha-tocopherol was studied in five patients with abetalipoproteinemia (ABL) because an impairment in secretion of apolipoprotein B-containing lipoproteins might impede the normally enhanced plasma transport of RRR-alpha-tocopherol. An oral dose containing 3.7 g of each 2R, 4'R,8'R-alpha-[5-C2H3]tocopheryl acetate (d3RRR-alpha-tocopheryl acetate) and 2RS,4'RS,8'RS-alpha-[5,7-(C2H3)2]tocopheryl acetate (d6 all rac-alpha-tocopheryl acetate) was administered, then the labeled and unlabeled alpha-tocopherol contents of plasma and red blood cells from multiple blood samples obtained at selected times up to 72 h following the dose were quantitated. ABL plasma contained about 1%-10% of the d3-RRR-alpha-tocopherol concentrations of normal subjects given only 150 mg of each isotope. Three of the patients discriminated between forms of alpha-tocopherol with ratios of RRR-/allrac-alpha-tocopherol > or = 1.8, similar to normals. These data suggest that the hepatic tocopherol binding protein is present and functional in ABL patients. Although two of the patients did not discriminate between stereoisomers of alpha-tocopherol, it is likely that this resulted from nearly a complete block in very low density lipoprotein (VLDL) secretion. Thus, the ability of ABL patients to absorb and transport orally administered vitamin E is markedly impaired and variable among patients.

Abetalipoproteinemia↗
PubMed1994

Concomitant brainstem axonal dystrophy and necrotizing myopathy in vitamin E-deficient rats.

The purpose of this study was to simultaneously evaluate in rats the effects of vitamin E depletion on tissue alpha-tocopherol (alpha-T) concentrations, electrophysiologic measurements and histopathology. Rats (21-day-old male Wistar) were fed either vitamin E-deficient or supplemented (control) diets (n = 6/group) for 10, 16, and 61 weeks. At these times, electrophysiologic tests (electromyography, spinal and somatosensory evoked potentials, and motor nerve conduction velocity) were performed, the rats were killed and alpha-T concentrations of adipose tissue, sciatic nerve, and cervical and lumbar spinal cord were measured along with histopathologic evaluation of skeletal muscles and the nervous system. By 61 weeks, depletion of alpha-T from adipose tissue and peripheral nerve was more severe (< 1% of controls) than from cervical and lumbar spinal cord (15 and 8% of controls, respectively). Electrophysiologic tests were normal at all times. Histopathologic evaluation at 61 weeks revealed normal peripheral nerve structure, but necrosis of type 1 muscle fibers and increased numbers of spheroids in the gracile and cuneate nuclei. Our results confirm that low alpha-T concentrations in tissues precede histologic changes in peripheral nerves and skeletal muscle. Furthermore, pathologic changes associated with vitamin E deficiency occur independently in muscle and nervous tissue of rats.

Adipose Tissue↗
PubMed1994

Determinants of plasma vitamin E concentrations.

Vitamin E, a lipid soluble antioxidant, is transported in plasma lipoproteins. This review will summarize the mechanisms for the preferential incorporation of RRR-alpha-tocopherol into lipoproteins. Special attention is devoted to the hepatic tocopherol binding protein, and to patients who are vitamin E deficient because they apparently have a genetic defect in this protein. The regulation of plasma vitamin E by the tocopherol binding protein as a determinant of the biologic activity of various forms of vitamin E is also discussed.

Animals↗
PubMed1994

Efficacy of water-soluble vitamin E in the treatment of vitamin E malabsorption in short-bowel syndrome.

A water-soluble form of vitamin E, tocopheryl succinate polyethylene glycol 1000 (TPGS), was used as an oral vitamin E supplement in a 71-y-old patient with severe fat malabsorption and vitamin E deficiency secondary to short-bowel syndrome. An absorption test with deuterium-labeled TPGS demonstrated that TPGS was absorbed and the released alpha-tocopherol was transported normally in lipoproteins. The disappearance portion of the deuterated alpha-tocopherol curves were parallel to those in control subjects, suggesting normal metabolic turnover of alpha-tocopherol. Long-term (3 y) supplementation with orally administered TPGS (10,360 mg or 4000 IU/d) maintained normal plasma alpha-tocopherol concentrations, raised adipose tissue alpha-tocopherol concentrations, and prevented further progression of the neurological abnormalities resulting from vitamin E deficiency. Thus, TPGS can be an effective vitamin E supplement in short-bowel syndrome despite severe fat malabsorption.

Aged↗
PubMed1994

Intestinal expression of human apolipoprotein A-IV in transgenic mice fails to influence dietary lipid absorption or feeding behavior.

Two transgenic mouse lines, expressing low or high amounts of human apo A-IV were created. In low and high expressor HuAIVTg mice on a chow diet, serum human apo A-IV levels were 6 and 25 times the normal human level and on a high fat diet, they were 12 and 77 times higher. Human apo A-IV was equally distributed between lipoprotein (mainly HDL) and lipid-free fractions. Intestinal absorption of radiolabeled cholesterol and triglycerides was unaffected in HuAIVTg mice. Vitamin A, carried exclusively in chylomicrons and their remnants, was catabolized normally. When an intragastric vitamin E bolus is given to the HuAIVTg mice, the initial absorption and appearance in triglyceride-rich lipoproteins was similar to that observed in normal mice. However, elevated amounts of vitamin E were subsequently observed in the VLDL of the HuAIVTg mice. Furthermore, in the fed state, serum VLDL triglycerides were markedly elevated in HuAIVTg mice. This effect was greater in high expressor mice. Serum total cholesterol was not elevated, but the distribution was altered in the HuAIVTg mice; VLDL-C was increased at the expense of VLDL-C. Kinetic studies suggested a delayed clearance of VLDL in HuAIVTg mice. Apo A-IV has been suggested to be a satiety factor, but no effect on feeding behavior or weight gain was observed in these HuAIVTg mice. In summary, our studies with HuAIVTg mice show that additional apo A-IV does not effect intestinal absorption of fat and fat-soluble vitamins, and at least chronic elevation of plasma apo A-IV does not effect feeding behavior in this model system.

Animals↗
PubMed1993

Depletion of adipose tissue and peripheral nerve alpha-tocopherol in adult dogs.

To assess the relationship between tissue alpha-tocopherol depletion and histopathologic or functional changes in nervous tissue, a longitudinal study of male 1-year-old beagle dogs, two fed a vitamin E-deficient diet (0.05 +/- 0.02 mg alpha-tocopherol/kg;--E dogs) and two fed a vitamin E-supplemented diet (114 +/- 14 mg alpha-tocopherol/kg; +E dogs), was carried out. Plasma and adipose tissue alpha-tocopherol concentrations, neurological examinations, and sensory and motor nerve conduction velocities were determined at approximately 8-wk intervals over 109 wk. Tibial nerve alpha-tocopherol concentrations were measured at 65 and 109 wk; adjacent sections were examined for histologic changes. In the two -E dogs, plasma alpha-tocopherols declined linearly on a semilog plot to < 0.1 microgram/mL by 109 wk. Plasma alpha-tocopherol concentrations were depleted to half of the initial concentrations in approximately 87 d. Adipose tissue alpha-tocopherol concentrations (based on wet weight, cholesterol or triglyceride) also declined linearly on semilog plots, and were depleted to half of the initial concentrations in approximately 120 d. Tibial nerve alpha-tocopherols (ng/microgram cholesterol) in -E dogs decreased to 16% of average +E at 65 wk, and to 2% at 109 wk. Neurologic examinations, histologies and nerve conduction velocities were normal in all dogs throughout the study. Our results demonstrate in dogs that depletion of plasma, adipose tissue and nerve alpha-tocopherol precedes histologic and functional changes in peripheral nerves during vitamin E deficiency.

Adipose Tissue↗
PubMed1993

Alpha-tocopherol concentrations of the nervous system and selected tissues of adult dogs fed three levels of vitamin E.

The effects of dietary vitamin E levels on tissue alpha-tocopherol (alpha-T) concentrations in different parts of the nervous system are largely unknown. Therefore, we measured the alpha-T contents of nervous and other tissues obtained from beagle dogs fed for two years a vitamin E-deficient diet (-E, 0.05 +/- 0.02 mg vitamin E/kg diet, n = 2), a vitamin E-supplemented diet (+E, 114 +/- 14 mg/kg, n = 2), or a standard chow diet (En, 74 +/- 6 mg/kg, n = 3). Brain regions and spinal cords of +E dogs contained about double the alpha-T concentrations of En dogs, and about 10-fold those of -E dogs. The various brain regions of -E dogs, compared with En dogs, retained 12-18% of the alpha-T concentrations, with the exception of the caudal colliculus, which retained 48%. Peripheral nerve alpha-T concentrations in +E dogs (67 ng/mg wet weight) were nearly 5-fold higher than in En dogs (13.4 +/- 5.9 ng/mg) and 80-fold higher than in -E dogs (0.8 ng/mg). Within each dietary group, the lowest alpha-T concentrations in the central nervous system (CNS) were in the spinal cord. Peripheral nerves were the most susceptible to vitamin E repletion or depletion: in +E dogs, nerves contained higher concentrations of alpha-T than most brain regions; in En dogs, they contained similar concentrations; but in -E dogs, they contained less alpha-T than most brain regions. Muscles and other tissues of -E dogs retained from 1 to 10% of En values.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Vitamin E deficiency in dogs does not alter preferential incorporation of RRR-alpha-tocopherol compared with all rac-alpha-tocopherol into plasma.

The plasma and lipoprotein transport of RRR and all rac-alpha-tocopherols, labeled with different amounts of deuterium [2R,4'R,8'R-alpha-[5-C2H3]tocopheryl acetate (d3RRR-alpha-tocopheryl acetate] and 2RS, 4'RS, 8'RS-alpha-[5,7-(C2H3)2]tocopheryl acetate (d6all rac-alpha-tocopheryl acetate), was studied in adult beagle dogs that had been fed a vitamin E-deficient (-E; two dogs) or supplemented (+E; two dogs) diet for two years. We set out to test the hypothesis that the activity of the hepatic tocopherol binding protein (which is thought to preferentially incorporate RRR-alpha-tocopherol into the plasma) is up-regulated by vitamin E deficiency. Labeled alpha-tocopherols increased and decreased similarly in plasma of both -E and +E dogs. Irrespective of diet, d3RRR-alpha-tocopherol was preferentially secreted in plasma. Thus, vitamin E deficiency in dogs does not markedly increase the apparent function of the hepatic tocopherol binding protein. We also studied vitamin E transport in a German Shepherd dog with degenerative myelopathy (DM). Based on the coincident appearance of d3RRR-alpha-tocopherol in plasma and chylomicrons, we suggest that the abnormality in DM may be associated with abnormal vitamin E transport resulting from an impaired function of the hepatic tocopherol binding protein.

Animals↗
PubMed1993

Alterations in plasma alpha- and gamma-tocopherol concentrations in response to intravenous infusion of lipid emulsions in humans.

To study the fate of intravenously infused vitamin E, we infused lipid emulsions rich in gamma-tocopherol (Intralipid, Kabi, Stockholm, Sweden), or in both alpha- and gamma-tocopherols (Lipidem, Hausmann Laboratories, St Gallen, Switzerland); in normal human volunteers. Plasma gamma-tocopherol levels increased in four subjects infused with Intralipid 10% (0.3 g triglyceride [TG]/kg/h for 6 hours) from 3 +/- 1 to 25 +/- 2 nmol/mL, but by 24 hours they decreased to 5 +/- 1 nmol/mL. Although eight times more gamma-tocopherol was infused, plasma alpha-tocopherol levels also increased from 26 +/- 7 to 39 +/- 9 nmol/mL at 8 hours and decreased to 24 +/- 5 nmol/mL at 24 hours. Increases of alpha-tocopherol in the very-low-density lipoprotein (VLDL) density range occurred at 6 and 8 hours, while decreases occurred in low-density lipoprotein (LDL) and high-density lipoprotein (HDL) density ranges at 3, 6, 8, and 24 hours. Infusion of both emulsions in random order to six subjects at therapeutic rates (0.1 g/kg/h for 6 hours) resulted in (1) a threefold increase in plasma gamma-tocopherol concentrations at 6 hours, (2) increases in plasma alpha-tocopherol concentrations only with Lipidem (from 14.3 +/- 1.0 nmol/mL at 0 hours to 18.4 +/- 2.7 at 6 hours and 18.9 +/- 1.1 at 24 hours), and (3) no decreases in lipoprotein alpha-tocopherol levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1993

Interrelationships of alpha-tocopherol with plasma lipoproteins in African green monkeys: effects of dietary fats.

The distributions of plasma lipoprotein alpha-tocopherol and lipids were studied in African green monkeys consuming diets enriched in saturated, monounsaturated, or polyunsaturated fatty acids. Plasma total alpha-tocopherol concentrations were not different among the animals fed the three diets, whereas plasma total cholesterol concentrations were significantly different among the diet groups. The alpha-tocopherol: total lipid molar ratio in plasma high density lipoproteins (HDL) was significantly higher compared to low density lipoproteins (LDL) and very low plus intermediate-sized low density lipoprotein (VLDL + ILDL) of each diet group, suggesting that HDL may exhibit a greater affinity for alpha-tocopherol. The presence of a positive correlation between HDL alpha-tocopherol and plasma apoA-I concentration and the absence of a correlation between HDL alpha-tocopherol and total lipid in HDL suggested that alpha-tocopherol associates with the protein moiety of HDL on the surface of the particle. A direct relationship between the plasma apoA-I: apoB molar ratio and the percentage of alpha-tocopherol found in the HDL fraction indicated that a greater proportion of alpha-tocopherol associates with HDL as the number of HDL particles in plasma increases relative to LDL particles. LDL from monkeys fed diets high in saturated fat contained 40% and 33% fewer alpha-tocopherol molecules per particle than LDL from monkeys fed polyunsaturated and monounsaturated fats, respectively. The phase transition temperature of LDL cholesteryl esters, indicative of the physical state of the lipids in the particle core, was well above body temperature in LDL from saturated fat-fed monkeys and was significantly higher compared to the other diet groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Impaired discrimination between stereoisomers of alpha-tocopherol in patients with familial isolated vitamin E deficiency.

We assessed whether patients with familial isolated vitamin E deficiency could discriminate between natural (RRR-) and synthetic (SRR-) stereoisomers of alpha-tocopherol labeled with six (d6) or three (d3) deuterium atoms, respectively. After oral administration of 20 mg of each of the stereoisomers, patients (seven) and controls (seven) had similar concentrations of both in chylomicrons, similar initial increases of both, and similar rates of decrease of d3-SRR-alpha-tocopherol in plasma. Patients and controls differed in their abilities to maintain plasma d6-RRR-alpha-tocopherol concentrations. Controls maintained plasma d6-RRR-alpha-tocopherol concentrations by preferentially secreting it in very low density lipoprotein (VLDL). Three of seven patients did not discriminate between the two stereoisomers and their plasma and lipoprotein d6-RRR-alpha-tocopherol concentrations declined rapidly. The remaining patients were intermediate between non-discriminators and controls in their ability to discriminate and maintain plasma d6-RRR-alpha-tocopherol concentrations. The degree of discrimination between the two stereoisomers in the patients was correlated with the age of onset of the neurologic disability (r2 = 0.64, P < 0.03). Estimates based on the rate of decrease of plasma d6-RRR-alpha-tocopherol in non-discriminators suggest that the entire plasma alpha-tocopherol pool of normal subjects is replaced daily. We suggest 1) that a hepatic alpha-tocopherol binding protein, which preferentially incorporates RRR-alpha-tocopherol into VLDL, is required to maintain plasma RRR-alpha-tocopherol concentrations; 2) that non-discriminators are lacking this protein, or have a marked defect in the RRR-alpha-tocopherol binding region of the protein; and 3) that patients who discriminate, but have difficulty maintaining plasma RRR-alpha-tocopherol concentrations, have a less severe defect, or perhaps a defect in the transfer function of the protein.

Carrier Proteins↗
PubMed1992

Studies on the transfer of tocopherol between lipoproteins.

The net transfer of labeled alpha-tocopherol from donor to acceptor lipoproteins at physiological concentrations was investigated. Labeled lipoproteins were isolated i) following in vitro addition of [3,4-3H] all rac-alpha-tocopherol to plasma, or ii) from plasma obtained 12-16 h after ingestion by normal subjects of an oral dose (100 mg each) of 2R,4'R,8'R-alpha-[5,7-(C2H3)2]tocopheryl acetate and 2S,4'R,'R-alpha-[5-C2H3]tocopheryl acetate. A constant amount (on a protein basis) of labeled lipoprotein was incubated with an increasing amount of unlabeled acceptor lipoprotein for 2 h at 37 degrees C. No discrimination between stereoisomers of alpha-tocopherol was detected. Labeled VLDL and labeled LDL (very low and low density lipoproteins, respectively) tended to retain their labeled tocopherol. Labeled high density lipoproteins (HDL) readily transferred the labeled tocopherol to VLDL (> 60% transferred), while the transfer to LDL was dependent upon the ratio of labeled HDL/LDL with a lower net transfer at higher ratios. This dependency of the distribution of tocopherol upon the ratio of HDL/LDL was also observed in vivo. The tocopherol/mg HDL protein was measured in 11 subjects with varying HDL levels. As the % HDL in the plasma increased from 14 to 50%, the tocopherol/HDL protein also increased (r2 = 0.37, P < 0.05).

Cholesterol↗
PubMed1992

Comparison of four erythrocyte fragility tests as indicators of vitamin E status in adult dogs.

Plasma alpha-tocopherol (alpha-T) concentrations, erythrocyte osmotic fragility and detergent sensitivity were measured at 8 week intervals in two 1-year-old male beagle dogs fed a vitamin E-deficient diet (< 0.08 mg per kg alpha-T) and in two control beagles fed the same diet supplemented with vitamin E (> 90 mg per kg alpha-T). Beginning at 24 weeks, dialuric acid haemolysis and spontaneous haemolysis were evaluated also. In the vitamin E-deficient dogs, plasma alpha-T concentrations declined progressively from baseline values of 20.5 and 31.3 micrograms per ml to 0.11 and 0.07 micrograms per ml, respectively, by 90 weeks. The supplemented dogs maintained alpha-T concentrations between 18.3 and 38.4 micrograms per ml. Both dialuric acid haemolysis (R = -0.89) and spontaneous haemolysis (R = -0.91) increased with declining plasma alpha-T concentration. In the dialuric acid haemolysis assay, 50 per cent haemolysis occurred when plasma alpha-T declined to 1.7 micrograms per ml, compared with spontaneous haemolysis in which 50 per cent haemolysis occurred when plasma alpha-T declined to 0.5 micrograms per ml. Osmotic fragility and detergent sensitivity remained unchanged in the vitamin E-deficient dogs throughout the study. Of the four tests, dialuric acid haemolysis was the most sensitive in-vitro assay for vitamin E deficiency in adult dogs.

Animals↗
PubMed1992

Discrimination between forms of vitamin E by humans with and without genetic abnormalities of lipoprotein metabolism.

To study the mechanisms of discrimination between various forms of vitamin E, four normal subjects, one patient with lipoprotein lipase deficiency, and three patients with abnormal apolipoprotein B-100 production were given an oral dose containing three tocopherols labeled with differing amounts of deuterium (2R,4'R,8'R-alpha-(5,7-(C2H3)2)tocopheryl acetate (d6-RRR-alpha-tocopheryl acetate), 2S,4'R,8'R-alpha-5-(C2H3)tocopheryl acetate (d3-SRR-alpha-tocopheryl acetate), and 2R,4'R,8'R-gamma-(3,4-2H)tocopherol (d2-RRR-gamma-tocopherol). The tocopherol contents of plasma, red cells, and lipoproteins were measured up to 76 h after the dose. In normal subjects all three tocopherols were absorbed and secreted in chylomicrons with equal efficiencies. Both d2-gamma- and d3-SRR-alpha-tocopherols peaked at similar concentrations in the other lipoprotein fractions, then decreased similarly, but 2-4 times more rapidly than did d6-RRR-alpha-tocopherol. A lipoprotein lipase-deficient patient and a patient with prolonged production of chylomicrons with absent apolipoprotein B-100 also demonstrated the lack of discrimination between tocopherols during absorption. Despite abnormal apolipoprotein B-100 production in two patients, the "VLDL" was preferentially enriched in d6-RRR-alpha-tocopherol. Our results show that there is no discrimination between the three tocopherols during absorption and secretion in chylomicrons, but subsequently there is a preferential enrichment of very low density lipoprotein (VLDL) with RRR-alpha-tocopherol. Catabolism of this VLDL results in the maintenance of plasma RRR-alpha-tocopherol concentrations.

Administration, Oral↗
PubMed1990

Vitamin E uptake by human intestinal cells during lipolysis in vitro.

Vitamin E uptake by Caco-2 cells, a human intestinal cell line, was studied by incubating the cells with alpha-tocopherol/triglyceride emulsions with or without bile activated lipase or lipoprotein lipase. During a 1-h incubation, vitamin E was transferred to Caco-2 cells only in the presence of triglyceride hydrolysis by bile activated lipase and not by lipoprotein lipase. Incubation with either lipase resulted in hydrolysis of approximately 20% of the medium [3H]-triolein to free fatty acids and a 3-5-fold increase in cellular radioactivity. In the absence of lipases but the presence of taurocholate, addition of oleic acid in an amount equal to the molar concentration of triglyceride (5.7 mM) to triglyceride emulsions containing either alpha-tocopherol or cholesteryl ester resulted in an increase in cellular [3H]-triglyceride and alpha-tocopherol or cholesteryl ester. We suggest that the absorption of hydrophobic molecules such as vitamin E may occur in the presence of bile and amphipathic lipids via the uptake of micellar neutral lipids by the intestine.

Cell Line↗