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R V Acuff

Publications and source records attributed to R V Acuff.

11 recordsLinked to original sources
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

Relative bioavailability of RRR- and all-rac-alpha-tocopheryl acetate in humans: studies using deuterated compounds.

Vitamin E in nutritional supplements in its most common form is alpha-tocopheryl acetate. Available stereoisomeric forms are RRR- (1 stereoisomer) and all-rac- (8 stereoisomers). We evaluated the relative bioavailability of RRR- and all-rac-alpha-tocopheryl acetate using the deuterium-labeled isotopes [5-CD3] 2R, 4'R and 8'R-alpha-tocopheryl acetate (d3), and [5,7-(CD3)2]-all-rac-alpha-tocopheryl acetate (d6). Six adults (three males, three females), aged 25-59 y, received 150 mg each of d3 and d6 for 11 consecutive days. Blood samples were collected on days -1, 0, 1-11, 13, 14, 20, 25, 30, 60, 74, 88, 102, 122, and 137. Plasma and red blood cell tocopherol were evaluated by using HPLC and gas chromatography/mass spectrometry to distinguish between d3 and d6 tocopherols. Cholesterol, triglycerides, and LDL and HDL cholesterol were measured. Relative bioavailability of d3 when compared with d6 was 2.0 +/- 0.06 when area under the plasma time concentration curve (AUC d3/d6) by trapezoidal rule (P < 0.05) was used. Correcting for lipid yielded the same finding. Unlabeled tocopherol (d0) decreased (P < 0.05) with vitamin E administration. It was concluded that the ratio of bioavailability of RRR-/all-rac-alpha-tocopheryl acetate is significantly greater than the currently accepted ratio of 1.36.

Administration, Oral↗
PubMed1993

Pharmacokinetics and bioavailability of the RRR and all racemic stereoisomers of alpha-tocopherol in humans after single oral administration.

The plasma and red blood cell pharmacokinetics and bioavailability of the natural source (RRR, d) and all racemic (all rac, dl) stereoisomers of alpha-tocopherol were studied in 12 men in a double-blind randomized crossover study. Subjects were administered two 400-mg soft-gelatin capsules of either RRR or all rac alpha-tocopherol. Plasma alpha-tocopherol concentrations were determined by high-performance liquid chromatography at various time intervals for up to 96 hours postadministration. Pharmacokinetic modeling of the data showed that alpha-tocopherol was absorbed after a 2 to 4 hour lagtime and maximum plasma concentration occurred from 12 to 14 hours postadministration. There were no significant differences in the Ka, t1/2 a, beta, or t1/2 beta between RRR and all rac. Mean plasma alpha-tocopherol concentrations were greater for RRR than all rac from 10 to 96 hours postadministration and significantly greater at 24 hours (P < .05). The red blood cell alpha-tocopherol concentration from the RRR preparation was significantly greater than from the all rac preparation from 24 to 96 hours postadministration with Cmax for RRR (4.8 micrograms/mL) significantly greater than for all rac (4.0 micrograms/mL, P < .05). The RRR AUC0-96 for both plasma and red blood cells were significantly greater than the all rac AUC0-96 (P < .05) indicating a greater bioavailability of RRR versus all rac alpha-tocopherol. This difference in overall bioavailability was apparently not due to a single pharmacokinetic component.

Administration, Oral↗
PubMed1991

Vitamin E supplements fail to protect mice from acute MPTP neurotoxicity.

The effect of chronic treatment with vitamin E (VE) on acute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity, as assessed by striatal dopamine (DA) depletion, was studied. Male C57B1/6J mice were fed VE (48 mg kg-1 per day, intragastric) for 4, 8, or 12 weeks prior to administration of MPTP (20 mg kg-1, i.p. x 3, 2 h intervals) or its diluent. Brain VE concentration was increased by exogenous supplements for 12 weeks. Striatal DA content was reduced by 85% to 90% after MPTP in control and VE-treated mice. Mice with elevated cerebral VE were not protected from MPTP toxicity, with DA content as an indicator. In conclusion, these findings indicate that moderate elevation of brain VE is not adequate for protecting DA-containing neurons against the toxic actions of a high dose of MPTP.

Animals↗
PubMed1988

Prolonged, intravenous paraquat infusion in the rat. I. Failure of coinfused putrescine to attenuate pulmonary paraquat uptake, paraquat-induced biochemical changes, or lung injury.

Paraquat (PQ) was administered to rats for 7 days by iv infusion from osmotic minipump at dosage rates of 250 and 500 nmol PQ/hr. The efficacy of putrescine in attenuating pulmonary PQ accumulation in vivo and the resulting PQ-induced biochemical changes and lung injury were assessed in these animals by coinfusion of putrescine at rates of 2500 or 5000 nmol/hr. Dose-dependent, steady-state blood levels of both PQ and putrescine were achieved by 18 hr and maintained throughout the infusion period. Lung PQ content at 7 days was dose-dependent and up to 18-fold greater than corresponding blood levels. No evidence of toxicity was observed in low-dose PQ animals while weight loss and overt toxicity was observed in high-dose PQ rats between Days 4 and 5. Histopathological examination of high-dose PQ rat lungs revealed qualitative changes typical of PQ toxicity. Significant (p less than 0.05) increases in lung glutathione and activities of glucose-6-phosphate dehydrogenase and GSSG reductase resulted from both PQ doses, reflecting PQ-induced oxidant stress and increased demand on lung NADPH. A net decrease in lung NADPH (p less than 0.05) was directly measured in high-dose PQ rats and may have contributed to the PQ-induced lung injury. Although putrescine is an effective inhibitor of pulmonary PQ uptake in vitro, the blood putrescine levels achieved in this study did not appear to inhibit this process in vivo. This was evidenced by putrescine's failure to decrease 7-day lung PQ content, PQ-induced biochemical changes, or lung injury.

Animals↗
PubMed1988

Prolonged, intravenous paraquat infusion in the rat. II. Paraquat-induced alterations in lung polyamine metabolism.

The effects of paraquat (PQ) on lung putrescine, spermidine, and spermine levels, and ornithine decarboxylase (ODC) activity were assessed in rats after 7 days of iv infusion of the herbicide via osmotic minipump. Paraquat administration at a rate of 250 nmol/hr [673 +/- 40 nmol/kg/hr (n = 15)] had no effect on these parameters. In contrast, significant (p less than 0.05) elevations in lung putrescine (407% of control), spermidine (202% of control), and ODC activity (174% of control were measured in lungs of rats given 500 nmol PQ/hr [1.31 +/- 0.53 mumol/kg/hr (n = 14)]. Since evidence of lung damage was, likewise, observed only in the high-dose PQ rats, these changes in polyamine metabolism could have been a nonspecific response to PQ-induced lung injury rather than a direct biochemical effect of PQ. The results suggest that stimulation of polyamine biosynthesis may play an important role in PQ-induced lung injury. This role may involve regulation of repair mechanisms or, conversely, the polyamines may actually mediate PQ-induced fibrotic changes in the lung.

Animals↗
PubMed1987

Effects of postoperative carbohydrate overfeeding.

Forty-three indirect calorimetric studies were performed on 24 patients who received postoperative supplemental nutrition for a total of 1088 days. Patients were retrospectively grouped into Group 1 (G1) (respiratory quotient greater than 0.95) and Group 2 (G2) (respiratory quotient less than 0.95). The two groups had similar preoperative biochemical values, prognostic nutritional index, nitrogen intake and excretion, predicted resting energy expenditure and caloric intake. Minimal postoperative biochemical changes were noted between the two groups. Postoperative length of stay was longer for GI than GII patients (P = NS). However, septic episodes and mortality were higher (100% vs 40% and 28% vs 10%, P greater than 0.05), respectively, in G1 than in G2 patients. It is concluded that carbohydrate overfeeding may be associated with a high morbidity and mortality.

Adult↗
PubMed1983

The influence of cysteine and methionine supplements on polyamine biosynthesis in the rat.

Previous reports from this laboratory have shown that supplementation of diets containing the optimal level (0.02%) of dietary inorganic sulfate (SO4(2-] with cysteine instead of methionine can affect several metabolic pathways. It is possible that these results reflect alterations in the biosynthesis of potent physiological compounds, the polyamines. Adult male albino rats were fed diets containing 15% casein and a constant level of inorganic sulfate (0.02%) supplemented with cysteine (0.505%) or methionine (0.62%). The polyamines (putrescine, spermidine and spermine) and the controlling enzymes for their biosynthesis ornithine decarboxylase (ODC) and S-adenosylmethionine decarboxylase (SAMD) were evaluated in liver, kidney and brain tissue homogenates following a 17-day dietary period. Rats fed the diet supplemented with cysteine had increased ODC activity and decreased SAMD activity when compared to rats fed diets supplemented with methionine. Polyamine concentrations varied in tissues with a trend toward increasing amounts in animals fed the cysteine-supplemented diet. Based on these data, it appears that dietary cysteine stimulates the biosynthesis and increased tissue concentration of polyamines.

Adenosylmethionine Decarboxylase↗
PubMed1983

A metabolic comparison of cysteine and methionine supplements in the diet of a rat.

Adult male Long-Evans rats (250-300 g) were fed diets containing 15% of casein not supplemented with amino acids, supplemented with 0.505% cysteine or supplemented with 0.620% methionine for a period of 17 days. Rats fed the diets supplemented with cysteine had an increased incorporation of the 14C-radioactivity from [U-14C]alanine into liver glycogen and a decreased incorporation from [U-14C]acetate into fatty acids. Pyruvate carboxylase activity was slightly increased and citrate cleavage enzyme activity decreased in the livers of those rats fed the diets supplemented with cysteine. Rats fed diets supplemented with methionine had a decreased liver phosphoenolpyruvate carboxykinase activity. Based on these data it appears that rats fed diets supplemented with cysteine adapt metabolically to store energy as glycogen, while those fed diets supplemented with methionine tend to store energy as lipid.

Animals↗
PubMed1983

An effect of dietary sulfur on liver inorganic sulfate in the rat.

The effect of dietary sulfur on liver inorganic sulfate concentration was determined by feeding rats diets containing 0.0002, 0.02, 0.1 and 0.42% of inorganic sulfate for a period of 17 days. Each diet contained 15% of casein supplemented with decreasing levels of methionine as the dietary inorganic sulfate was increased, to keep the sulfur as sulfate concentration constant at 0.67%. The molarity of the liver sulfate calculated on the basis of moles of sulfate per 1,000 g of wet tissue was 0.98, 1.3, 2.2 and 1.5 mM for rats fed the diets containing 0.0002, 0.02, 0.1 and 0.42% of inorganic sulfate, respectively. Thus it appears that the liver sulfate pool is limited by a combination of the rate of oxidation of the sulfur-containing amino acids and the extraction of sulfate from the portal system.

Animals↗