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Biomedical subjects

R M Russell

Publications and source records attributed to R M Russell.

At least 145 records · Page 8Linked to original sources

Characterization of beta-apo-13-carotenone and beta-apo-14'-carotenal as enzymatic products of the excentric cleavage of beta-carotene.

Two new products from the incubation of beta-carotene with intestinal mucosa homogenates of human, monkey, ferret, and rat were isolated using high-performance liquid chromatography (HPLC). Identification by comparing retention times in HPLC, by monitoring ultraviolet/visible spectra, by reduction to corresponding alcohol, by oxime formation, and by mass spectrometry demonstrated that they are beta-apo-13-carotenone and beta-apo-14'-carotenal. These compounds were not found in incubations done without intestinal homogenates or with disulfiram as an inhibitor. Under standard incubation conditions, these products increased linearly for 60 min and up to a protein concentration of 1.5 mg/mL and increased along with increasing concentrations of beta-carotene. Therefore, they are enzymatic cleavage products from beta-carotene. The formation of the beta-apo-13-carotenone and beta-apo-14'-carotenal provides direct evidence for an enzymatic excentric cleavage mechanism.

Animals↗

Enzymatic conversion of beta-carotene into beta-apo-carotenals and retinoids by human, monkey, ferret, and rat tissues.

Whether the conversion of beta-carotene into retinoids involves an enzymatic excentric cleavage mechanism was examined in vitro with homogenates prepared from human, monkey, ferret, and rat tissue. Using high-performance liquid chromatography, significant amounts of beta-apo-12'-, -10'-, and -8'-carotenals, retinal, and retinoic acid were found after incubation of intestinal homogenates of the four different species with beta-carotene in the presence of NAD+ and dithiothreitol. No beta-apo-carotenals or retinoids were detected in control incubations done without tissue homogenates. The production of beta-apo-carotenals was linear for 30 min and up to tissue protein concentrations of 1.5 mg/ml. The rate of formation of beta-apo-carotenals from 2 microM beta-carotene was about 7- to 14-fold higher than the rate of retinoid formation in intestinal homogenates, and the rate of beta-apo-carotenal production was fivefold greater in primate intestine vs rat or ferret intestine (P less than 0.05). The amounts of beta-apo-carotenals and retinoids formed were markedly reduced when NAD+ was replaced by NADH, or when dithiothreitol and cofactors were deleted from the incubation mixture. Both beta-apo-carotenal and retinoid production from beta-carotene were inhibited completely by adding disulfiram, an inhibitor of sulfhydryl-containing enzymes. Incubation of beta-carotene with liver, kidney, lung, and fat homogenates from each species also resulted in the appearance of beta-apo-carotenals and retinoids. The identification of three unknown compounds which might be excentric cleavage products is ongoing. These data support the existence of an excentric cleavage mechanism for beta-carotene conversion.

Animals↗

Reversal of protein-bound vitamin B12 malabsorption with antibiotics in atrophic gastritis.

The role of bacteria in the bioavailability of protein-bound vitamin B12 was examined in eight elderly subjects who had atrophic gastritis and in eight normal controls. On separate days and in random order, vitamin B12 absorption tests were performed using either radiolabeled crystalline or protein-bound vitamin B12. At the same time, bacterial samples were collected from the upper gastrointestinal tract. The tests and gastrointestinal aspirates were performed before and during tetracycline therapy. Crystalline vitamin B12 was absorbed to the same extent in the two study groups. Atrophic gastritis subjects absorbed significantly less protein-bound vitamin B12 than normal controls (mean +/- SEM, 0.7% +/- 0.2% vs. 1.9% +/- 0.5%, respectively). However, protein-bound vitamin B12 absorption in these subjects normalized after antibiotic therapy. These results suggest that the small amounts of vitamin B12 released from the protein binders is readily absorbed (as shown in vitro) and/or metabolized by bacteria.

Achlorhydria↗

Serum concentrations of retinol and retinyl esters in adults in response to mixed vitamin A and carotenoid containing meals.

Previous studies using spectrophotometric methods for vitamin A analysis concluded that fasting prior to blood collection is not necessary for determining vitamin A status of children or young adult subjects. We measured the effect of mixed vitamin A and carotenoid containing meals with less than 3, 50, and 100% of the recommended dietary allowance (RDA) for vitamin A on serum concentrations of retinyl esters, retinol, and carotenoids in elderly and young adults after an overnight fast. Retinyl ester concentrations rose significantly in both age groups with a numerically higher rise over baseline in the elderly subjects: 6.0 +/- 0.9 micrograms/dl for elderly (p less than 0.001), 5.0 +/- 0.5 micrograms/dl for young (p less than 0.001) at 50% RDA; 9.0 +/- 1.3 micrograms/dl for elderly (p less than 0.001) and 6.8 +/- 1.6 micrograms/dl for young (p less than 0.05) at 100% RDA. We conclude that in both young and elderly adults, but especially in the elderly, fasting conditions are necessary for the accurate assessment of vitamin A status if spectrophotometric methods are used for measuring vitamin A.

Adult↗

Vitamin B-6 deficiency impairs interleukin 2 production and lymphocyte proliferation in elderly adults.

The effect of vitamin B-6 deficiency on immune response was studied in eight healthy elderly adults. The protocol consisted of a 5-d baseline (BL) period; a vitamin B-6-depletion period of less than or equal to 20 d; three stages of vitamin B-6-repletion, each lasting 21 d; and a 4-d final phase. The amounts of vitamin B-6 ingested during the different phases of the study were 3.00, 15.00, 22.50, and 33.75 micrograms.kg body wt-1.d-1, respectively. During the final phase the subjects ingested 50 mg vitamin B-6/d. Fasting blood was collected at the end of each period. Vitamin B-6 depletion significantly decreased percentage and total number of lymphocytes, mitogenic responses of peripheral blood lymphocytes to T- and B-cell mitogens, and interleukin 2 production. These indices returned to BL values after the third vitamin B-6-repletion period, when the total vitamin B-6 intakes were 1.90 +/- 0.18 mg/d for women and 2.88 +/- 0.17 mg/d for men. Vitamin B-6 deficiency impairs in vitro indices of cell-mediated immunity in healthy elderly adults. This impairment is reversible by vitamin B-6 repletion.

Aged↗

Calcium absorption in elderly subjects on high- and low-fiber diets: effect of gastric acidity.

In vitro studies suggest that the effect of fiber in inhibiting calcium absorption is pH dependent. In nine normal, elderly control subjects and eight elderly subjects with achlorhydria, 47Ca was ingested with three test meals: a low-fiber meal (0.5 g dietary fiber), a high-fiber meal (10.5 g), and a high-fiber meal with 120 mL of 0.1 mol HC/L. In control subjects calcium retention, measured in a whole-body counter, was 25.7 +/- 4.0% (mean +/- SD) with the low-fiber meal, 19.1 +/- 1.9% with the high-fiber meal (P less than 0.002 vs low fiber), and 18.9 +/- 3.3% with the high-fiber-plus-acid meal (P less than 0.002 vs low fiber, NS vs high fiber). Calcium absorption in achlorhydric subjects was not different from control subjects: 26.2 +/- 8.0% with low fiber, 19.6 +/- 4.1% with high fiber (P less than 0.04 vs low fiber), and 21.0 +/- 5.8% with high fiber plus acid (P less than 0.04 vs low fiber, NS vs high fiber). We conclude that, in humans, the reduction in calcium absorption with high fiber intake is unaffected by gastric pH.

Absorption↗

Age-related effects of chronic ethanol intake on vitamin A status in Fisher 344 rats.

The present study was designed to investigate the interaction of age and ethanol on vitamin A status in rats. Rats aged 2 and 19 mo were fed a liquid diet containing 36% of total energy as ethanol or pair-fed a diet containing isoenergetic carbohydrate in place of ethanol. After 3 wk older rats had lower serum retinol (P = 0.04) and higher vitamin A concentrations in liver (P = 0.0001), esophagus (P = 0.0001) and the proximal (P = 0.03) and distal (P = 0.0001) colon than younger animals. Hepatic microsomal cytochrome P-450, retinyl ester hydrolase (REH) and cellular retinol-binding protein (cRBP) were significantly reduced; acyl coenzyme A: retinol acyltransferase (ARAT) was increased; and alcohol (retinol) dehydrogenase (ADH) activity was unchanged with age. Ethanol ingestion increased serum retinol as well as esophageal and colonic vitamin A levels in both age groups. Hepatic cRBP decreased further in the older rats with ethanol feeding, but no change was noted in the percentage of hepatic vitamin A as retinol or retinyl esters. Ethanol ingestion decreased REH (P = 0.0001) and ARAT activities (P = 0.02) and increased cytochrome P-450 (P = 0.04) but had no effect on the activity of ADH in either age group. These data indicate that, regardless of age, chronic ethanol ingestion significantly alters the tissue distribution of vitamin A; however, ethanol reduced cRBP levels only in older rats.

Acyltransferases↗

Vitamin B-6 requirements of elderly men and women.

The vitamin B-6 requirements of 12 men and women over 60 y old were studied. The protocol consisted of a 5-d baseline period and four experimental periods during which the subjects successively received 0.003, 0.015, 0.0225 and 0.03375 mg of vitamin B-6/(kg body wt.d). Dietary protein was 1.2 or 0.8 g/(kg body wt.d). At 5- or 6-d intervals, xanthurenic acid (XA) after a 5-g L-tryptophan load and 4-pyridoxic acid (4-PA) in 24-h urine, erythrocyte aspartate aminotransferase activity coefficient (EAST-AC) and plasma pyridoxal-5'-phosphate (PLP) were measured. These measurements were abnormal during vitamin B-6 depletion but returned to normal during repletion. Men who ingested approximately 120 g protein/d required 1.96 +/- 0.11 mg of vitamin B-6 to normalize XA; women who ingested 78 g protein/d required 1.90 +/- 0.18 mg of vitamin B-6 to normalize XA. To attain normal levels of EAST-AC and 4-PA in men, 2.88 +/- 0.17 mg of vitamin B-6 were needed; to normalize PLP, 1.96 +/- 0.11 mg of vitamin B-6 were required. Women required 1.90 +/- 0.18 mg or more of vitamin B-6 to normalize these measurements. Vitamin B-6 requirements were not decreased in two of three subjects who ingested 54 g of protein daily. Thus, vitamin B-6 requirements of elderly men and women are about 1.96 and 1.90 mg/d, respectively.

Aged↗

Effect of chronic ethanol feeding on hepatic and extrahepatic distribution of vitamin E in rats.

The effect of chronic ethanol feeding on the status of alpha- and gamma-tocopherol in plasma, liver, lung, and testes of Sprague-Dawley rats was characterized. Rats were pair-fed liquid diets containing 36% of total calories either as ethanol or isocaloric carbohydrates. After 3 weeks, ethanol ingestion resulted in a significant (p less than or equal to 0.05) increase in liver weight and induced fatty liver without affecting total body weight. Ethanol feeding did not affect the plasma concentration of alpha-tocopherol but doubled that of gamma-tocopherol. When expressed per milligram of tissue, liver alpha-tocopherol did not vary with ethanol ingestion, whereas gamma-tocopherol concentration increased 2.5 times that of control animals. However, the concentration of alpha-tocopherol expressed per milligram of total lipids was significantly (p less than or equal to 0.01) decreased in the liver with ethanol feeding. In contrast to the liver, ethanol feeding significantly increased alpha- and gamma-tocopherol levels per milligram of total lipids in the testes. The concentration of gamma-tocopherol (but not alpha-tocopherol) per milligram of lung tissue and per total lung was significantly (p less than or equal to 0.05) increased with ethanol feeding. These data indicate that chronic ethanol ingestion significantly alters the distribution of alpha-tocopherol and gamma-tocopherol in hepatic and extrahepatic tissues of the rat.

Alcoholism↗

Postprandial plasma vitamin A metabolism in humans: a reassessment of the use of plasma retinyl esters as markers for intestinally derived chylomicrons and their remnants.

We investigated postprandial vitamin A metabolism by measuring retinyl ester, triglyceride, and apolipoprotein (apo)B-48 in the plasma lipoproteins of human subjects before and after fat-feeding. Following a 14-hour fast, eight healthy subjects (two men, six women, 28 to 79 years) were given a fat-rich meal (1 g fat/kg body weight) containing vitamin A (40 retinol equivalents per kilogram body weight). Blood was collected every 3 hours for 12 hours and lipoproteins were isolated by sequential ultracentrifugation. Mean plasma retinyl ester concentration peaked 6 hours after the fat-rich meal, whereas mean plasma triglyceride peaked at 3 hours. Data obtained from hourly samples in 3 subjects showed that changes in the postprandial plasma concentration of retinyl ester occurred 1 to 2 hours after changes in the plasma triglyceride concentration. In triglyceride-rich lipoproteins (TRL) of d less than 1.006 g/mL, retinyl ester similarly peaked at 6 hours, whereas triglyceride as well as apoB-48 peaked at 3 hours. Although retinyl esters were found mainly in TRL in the initial postprandial period (84%, 3 hours; 83%, 6 hours), in fasting and postprandial plasma, particularly 9 or more hours after fat-feeding, a large percentage of plasma retinyl esters were in low-density lipoproteins (LDL) (44%, fasting; 9%, 3 hours; 9%, 6 hours; 19%, 9 hours; 32%, 12 hours). A small percentage of retinyl esters were also found in postprandial high-density lipoproteins (HDL) (2% to 7%). ApoB-48 was not detected in LDL of fasting or postprandial plasma.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Descriptors of alcohol consumption among noninstitutionalized nonalcoholic elderly.

This paper describes relationships between reported alcohol consumption and selected sociodemographic and health variables. Two hundred and four men and 367 women aged 60-95 years were examined as part of a nutritional status survey of elderly. Fifty-three percent of men and 44% of women reported drinking at least 2 g of alcohol per week. Men were more likely to drink than women, and the level of alcohol consumption decreased with age. Drinking was positively associated with education (p less than 0.01) and negatively associated with recent medical care (p less than 0.01), history of MI (p less than 0.05), and denture use (p less than 0.05). Among drinkers, reported alcohol intake was higher for subjects less than age 70 (p less than 0.01), males (p less than 0.01), the college educated (p less than 0.01), and smokers (p less than 0.05). Level of alcohol intake was lower for those who had received medical care in the year preceding study participation (p less than 0.05). Identical results were observed for alcohol intake expressed as percent of total calories. Intake ranged from 3.8% of total calories among subjects 80+ years old to 6.2% of total calories among 60-69-year-olds.

Age Factors↗

Test-retest reproducibility of the relative dose response for vitamin A status in Guatemalan adults: issues of diagnostic sensitivity.

The relative dose response (RDR) test has been used as a functional measure of whole-body stores of vitamin A in humans. We have examined the reproducibility of the RDR procedure in a population of Guatemalan adult subjects who would be expected to show a moderate prevalence of hypovitaminosis A. Fifty-one subjects were administered a standard RDR test, and the plasma samples were analyzed for retinol, tocopherol, retinol binding protein (RBP) and prealbumin (PAL). Thirty-four of the subjects underwent repeat RDR tests 7 d later. Plasma levels in fasted subjects were as follows: retinol, 1.35 +/- 0.30 mumol/L; RBP, 37.8 +/- 7.7 mg/L; PAL, 187.0 +/- 39.0 mg/L; and tocopherol, 16.6 +/- 6.2 mumol/L. RDRs ranged from -35.2% to +63.1%, with a mean of 2.6 +/- 10.4%. Overall, we observed poor within-subject reproducibility of the RDR procedure whether expressed numerically or by diagnostic classification. Moreover, in contrast to previous studies in children, we observed fewer positive RDR tests than would be expected for the population studied. Nevertheless, the mean RDR was inversely proportional to fasting retinol levels, thus confirming the validity of the biological basis of the RDR procedure in humans. Because of high intra-individual variability with this test, investigators should be cautious when using the RDR procedure in serial studies to monitor the efficacy of therapeutic interventions or subject compliance to dietary regimens.

Administration, Oral↗

Test-retest reproducibility of the relative dose response for vitamin A status in Guatemalan adults: issues of diagnostic specificity.

The relative dose response (RDR) test was examined with regard to specificity and reproducibility in subjects with adequate dietary intake and normal liver reserves of vitamin A. Twelve subjects were administered an RDR test four times over 22 d, including one placebo test in which the oral dose of vitamin A was omitted. Additionally, static measures of retinol, tocopherol, retinol binding protein (RBP) and prealbumin (PAL) were taken to determine the intra- and inter-individual coefficient of variation for these blood constituents. Intra-individual coefficients of variation were as follows: retinol, 8.8%; RBP, 11.5%; PAL, 7.6%; and alpha-tocopherol, 8.8%. The mean RDR in vitamin A-replete subjects was 1.2% and ranged from approximately -25% to 11%. No differences were observed between placebo and true RDR (i.e., with vitamin A) test responses, and there was no difference among the three true RDRs over a period of 22 d. Consistent with the hypothesis upon which the RDR test is based, nascently absorbed vitamin A evidently entered a storage pool in the liver of vitamin A-replete subjects without immediate release to peripheral sites of utilization. Because the RDR test results were normal in all subjects, the procedure appears to offer high test specificity and does not falsely diagnose hypovitaminosis A. Nevertheless, the magnitude and direction of the RDR within an individual over 22 d were highly variable, and this variability may preclude the use of a single measure of the RDR to grade the relative vitamin A nutriture of an individual subject.

Administration, Oral↗

Postprandial plasma retinyl ester response is greater in older subjects compared with younger subjects. Evidence for delayed plasma clearance of intestinal lipoproteins.

Postprandial vitamin A and intestinal lipoprotein metabolism was studied in 86 healthy men and women, aged 19-76 yr. Three independent experiments were carried out. In the first experiment, a supplement dose of vitamin A (3,000 retinol equivalents [RE]) was given without a meal to 59 subjects, aged 22-76 yr. In the second experiment, 20 RE/kg body wt was given with a fat-rich meal (1 g fat/kg body wt) to seven younger subjects (aged less than 50 yr) and seven older subjects (aged greater than or equal to 50 yr). In both experiments, postprandial plasma retinyl ester response increased significantly with advancing age (P less than 0.05). In the third experiment, retinyl ester-rich plasma was infused intravenously into nine young adult subjects (aged 18-30 yr) and nine elderly subjects (aged greater than or equal to 60 yr), and the rate of retinyl ester disappearance from plasma during the subsequent 3 h was determined. Mean (+/- SE) plasma retinyl ester residence time was 31 +/- 4 min in the young adult subjects vs. 57 +/- 8 min in the elderly subjects (P less than 0.05). These data are consistent with the concept that increased postprandial plasma retinyl ester concentrations in older subjects are due to delayed plasma clearance of retinyl esters in triglyceride-rich lipoproteins of intestinal origin.

Adult↗

The prevalence of cardiovascular risk factors among elderly Chinese Americans.

In 1981 to 1983, the nutrition and health status of 346 Chinese immigrants in Boston, Mass, aged 60 to 96 years was surveyed and analyzed for cardiovascular risk factors. These elderly Chinese were physically active and seldom obese and consumed a high-carbohydrate (57% of total energy intake), low-fat (24% of total energy intake), low-ascorbic acid (0.62 mmol/d) diet. Current cigarette smoking was common (39%) only in men, while alcoholism was rare in both sexes. Compared with elderly whites, they had lower mean blood pressure and blood levels of total, low-density lipoprotein, and high-density lipoprotein cholesterol, apolipoproteins A-I and B, and ascorbic acid. These characteristics resemble those of the urban population in mainland China, where hemorrhagic stroke is the major cause of cardiovascular mortality.

Aged↗

13-cis-retinoic acid is an endogenous compound in human serum.

The occurrence of 13-cis-retinoic acid as an endogenous component in human serum has been confirmed by cochromatography with standards in both normal-phase and reverse-phase high-performance liquid chromatographic (HPLC) system, by the lambda max of its UV spectrum recorded simultaneously with the HPLC run, and by chromatography of its methyl derivative. The method using solid-phase extraction followed by a gradient reverse-phase HPLC procedure with an internal standard and sensitive UV detector, provides an efficient and sensitive technique for the separation and quantification of serum 13-cis- and all-trans-retinoic acid. Serum levels of 13-cis- and all-trans-retinoic acid in 26 fasting volunteers ranged from 1.0 to 2.2 ng/ml (mean +/- SEM = 1.4 +/- 0.3 ng/ml) and from 1.1 to 1.9 ng/ml (mean +/- SEM = 1.4 +/- 0.2 ng/ml), respectively. The levels determined by a liquid-liquid double-phase extraction method were 90% higher in both 13-cis- and all- trans-retinoic acid than those from a solid-phase extraction. Human small intestine can isomerize all-trans-retinoic acid. 13-cis-Retinoic acid is the predominant cis isomer after incubation of intestinal mucosa homogenates with all-trans-retinoic acid. Moreover, the concentration of retinoic acid in serum is related to diet in that the level of total retinoic acid was 36% higher (n = 10) 2 h after a nonstandard breakfast than in fasting subjects.

Adult↗