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Biomedical subjects

R M Russell

Publications and source records attributed to R M Russell.

At least 127 records · Page 7Linked to original sources

Riboflavin requirement of healthy elderly humans and its relationship to macronutrient composition of the diet.

The riboflavin requirements of two groups of riboflavin-deficient, but otherwise healthy, Guatemalan elderly persons over the age of 60 y were studied by varying the fat:carbohydrate ratio in two diets. The first group consumed a diet similar in macronutrient content to a Western-type diet with low carbohydrate and high fat; the second group consumed a typical Guatemalan diet with high carbohydrate and low fat. Energy and protein intakes of both groups were similar. Riboflavin status was monitored by weekly measurements of erythrocyte glutathione reductase activity coefficient (EGRAC) and urinary riboflavin excretion. Increasing increments of riboflavin were added to the subjects' diets until their status was normalized, as indicated by EGRAC of < 1.34 and a sharp increase in urinary riboflavin excretion. Using the EGRAC method, the mean value of riboflavin intake at which the subjects' EGRAC reached the limit of normality was 1.37 +/- 0.03 mg/d in the first phase and 1.29 +/- 0.03 mg/d in the second phase. The sharp increase in urinary excretion occurred at riboflavin intakes of 1.13 and 1.03 mg/d for Groups 1 and 2, respectively. Thus, the differences between the two groups suggest that diets with a lower fat:carbohydrate ratio can decrease the dietary need for riboflavin. The dietary requirement of riboflavin, as estimated by the more reliable urinary excretion method, was 1.1-1.3 mg/d for those consuming the Western-type diet, which is similar to values found over 40 y ago in young adults. We conclude that the dietary requirements of riboflavin in the elderly do not differ from those of young adults.

Adult↗

Retinoic acid regulates retinol metabolism via feedback inhibition of retinol oxidation and stimulation of retinol esterification in ferret liver.

When the plasma concentration of retinoic acid is increased, there is an accompanying reduction of circulating levels of retinol, suggesting that retinoic acid may have a regulatory effect on retinol metabolism in vivo. To determine which specific step(s) of retinol metabolism might be regulated by retinoic acid, retinol was incubated with ferret liver microsomes or cytosol with retinoic acid in vitro. Incubating the microsomal fraction with retinoic acid resulted in a dose-dependent (up to 0.5 mumol/L) decrease in the formation of retinal. On the contrary, no retinoic acid inhibitory effect was observed on retinal synthesis in the cytosol incubation, or in the cytosol plus microsome incubation. However, when retinoic acid was added to the cytosolic incubation mixture in the presence of the retinal oxidative inhibitor, citral, a dose-dependent inhibition of retinal synthesis was observed. Furthermore, the effect of retinoic acid on retinyl ester metabolism in ferret liver was studied by using endogenous retinyl esters of ferret liver as the substrate. When retinoic acid was added to the incubation mixture of microsomes plus cytosol, small, nonsignificant increases in retinol and retinyl esters were observed. When retinoic acid was added in the presence of citral, both the inhibition of retinol oxidation and the stimulation of retinol esterification were dose dependent up to approximately 0.3 mumol/L and then remained the same up to 1.0 mumol/L. These data strongly suggest that retinoic acid has a regulatory effect on retinol metabolism in ferret liver, which may occur via feedback inhibition of retinol oxidation and stimulation of retinol esterification.

Animals↗

Contribution of apoB-48 and apoB-100 triglyceride-rich lipoproteins (TRL) to postprandial increases in the plasma concentration of TRL triglycerides and retinyl esters.

After the ingestion of a fat-rich meal, there is a postprandial increase in the plasma concentration of both apolipoprotein B-48- and apoB-100-containing triglyceride-rich lipoproteins (apoB-48 and apoB-100 TRL). In order to determine the contribution of these lipoproteins to postprandial lipemia, the concentration of triglycerides (TG) and retinyl esters (RE) was measured in apoB-48 and apoB-100 TRL after an oral fat load. Six normolipidemic male subjects were fed heavy cream (1 g fat per kg body weight) containing vitamin A (3000 retinol equivalents). TRL were isolated by ultracentrifugation from plasma samples obtained at regular intervals after the meal, and apoB-100 TRL were separated from apoB-48 TRL by affinity chromatography using monoclonal antibodies. Postprandial increase in plasma TG concentration was due to an increase in TG in the TRL fraction, which in turn was predominantly (82 +/- 4%) due to an increase in TG in apoB-48 TRL. Contribution of apoB-100 TRL to postprandial increase in TRL TG was 3-27% in individual subjects. ApoB-100 TRL remained a significant carrier of total plasma triglyceride in the fed state, as reflected by similar apoB-100 and apoB-48 TRL TG concentrations at 2, 4, and 6 h after the fat meal. Retinyl esters were regularly detected in apoB-100 TRL. Seventy-five (+/- 9) percent of the increase in TRL-RE was due to RE in apoB-48 TRL and 25 +/- 9% was due to RE in apoB-100. These data suggest that RE in plasma are not always associated with apoB-48-containing lipoproteins.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Retinoic acid can be produced from excentric cleavage of beta-carotene in human intestinal mucosa.

The hypothesis that retinoic acid (RA) is produced from the excentric cleavage of beta-carotene was tested in human intestinal homogenates in vitro. Significant amounts of RA were identified by HPLC and derivatization after incubation of intestinal mucosal homogenates with retinal, beta-carotene, or beta-apocarotenals at 37 degrees C for 60 min. RA formation was inhibited, in a dose-dependent fashion, when retinal was incubated in the presence of 0.1-3.0 mM citral (3,7-dimethyl-2,6-octadienal) under identical experimental conditions. The formation of RA from both beta-carotene and beta-apocarotenals was dose and time dependent and RA was the major metabolite of both beta-apo-8'-carotenal and beta-apo-12'-carotenal after the incubation. However, citral (0.1 to 4 mM) did not inhibit the formation of beta-apocarotenals and RA from 2 microM beta-carotene (P greater than 0.05), which proves the existence of an excentric cleavage mechanism for beta-carotene conversion into retinoids. Furthermore, RA formation from both beta-apo-8'-carotenal and beta-apo-12'-carotenal in human intestinal homogenate occurred in the presence of citral, which demonstrates that RA can be produced from excentric cleavage of beta-carotene via a series of beta-apocarotenals as intermediates.

Acyclic Monoterpenes↗

Evidence for diminished B12 absorption after gastric bypass: oral supplementation does not prevent low plasma B12 levels in bypass patients.

Vitamin and mineral assays were performed on blood in 20 gastric bypass patients preoperatively and 6 and 12 months postoperatively. Values were compared with serial food records in nine patients. Postoperatively, all patients were prescribed a supplement containing the recommended dietary allowances (RDA) for vitamins and minerals. Weight, calorie and protein intake, and total serum protein decreased over the study interval (p less than 0.01). Dietary intakes of vitamins B1, B2, B6, folate, iron and zinc fell (p less than 0.01), but total intake (i.e., diet + supplement) did not decrease with the exception of iron. Blood indicators of these nutrients were normal preoperatively and did not decline. However, plasma vitamin B12 levels decreased from 385 pg/ml preoperatively to 234 pg/ml at 1 year (p = 0.0064), despite an increase in total vitamin B12 intake from 2.6 to 11.7 micrograms/day (p = 0.1173). Five patients (27.8%) had abnormally low plasma vitamin B12 levels at 1 year postoperatively; four were taking at least the RDA for vitamin B12 as supplements. Although oral supplementation containing the RDA for micronutrients can prevent abnormal blood indicators of most vitamins and minerals, it is insufficient to maintain normal plasma B12 levels in about 30% of gastric bypass patients.

Absorption↗

Lack of an effect of multivitamins containing vitamin A on serum retinyl esters and liver function tests in healthy women.

Two hundred eighty-four female adults (aged 40-70 years) were longitudinally studied to investigate the relationship between dietary supplemental vitamin A and serum biochemical markers of vitamin A toxicity. Serum retinol, retinyl esters, and retinol-binding protein (RBP), alkaline phosphatase and aspartate aminotransferase activities and bile acids were measured at baseline, 1 and 2 years. Fasting serum retinol and retinyl ester concentrations were determined by high-performance liquid chromatography, and dietary and supplemental intake of vitamin A were assessed by 3-day food records. There was no difference in dietary vitamin A intake between supplement users and nonusers. In supplemental users, the mean +/- SEM supplemental vitamin A intake was 952 +/- 81 IU/day (range 250-5000 retinol equivalents/day). Serum retinol, retinyl esters, and RBP concentrations were not different between the two groups during the 2-year period. For each group, serum retinyl esters significantly increased over time (p < 0.03), but the magnitude of the increase was not different between the groups. Serum levels of retinol, retinyl esters, and RBP were not correlated with vitamin A intake or age in either group. Biochemical measures of liver damage (serum alkaline phosphatase and aspartate aminotransferase activities and serum bile acids) were not related to serum retinol, retinyl esters or RBP concentrations, nor were they different between nonusers and users of supplemental vitamin A. This study provides evidence that long-term supplemental vitamin A in doses commonly found in multivitamin supplements does not present a risk for hypervitaminosis A.

Adult↗

Evaluation of vitamin A absorption by using oil-soluble and water-miscible vitamin A preparations in normal adults and in patients with gastrointestinal disease.

We evaluated vitamin A absorption in 50 healthy adults and 26 gastrointestinal-disease patients by measuring the postabsorptive response in plasma retinyl esters after oral doses of the vitamin. On 3 consecutive days, two physiologic-dose tests of 2000-2400 retinol equivalents (RE) and one pharmacologic-dose test (84,000 RE) were administered. The physiologic doses were given as an oil-soluble or a water-miscible preparation. In gastrointestinal-disease patients the physiologic-dose test was highly correlated with the pharmacologic-dose test for the oil-soluble preparation as determined by peak rise (r = 0.50, P less than 0.05) and area under the curve (r = 0.56, P less than 0.01), suggesting that the physiologic dose is valid for investigating vitamin A absorption. Intestinal-disease or resection patients absorbed preparations poorly. Pancreatic-disease patients absorbed the oil-soluble preparation poorly. Physiologic rather than pharmacologic doses of vitamin A can be used to study vitamin A absorption.

Absorption↗

Effect of vitamin B-6 deficiency on fasting plasma homocysteine concentrations.

The catabolism of homocysteine through cystathionine synthesis requires pyridoxal-5'-phosphate, thus the effect of vitamin B-6 deficiency on plasma homocysteine concentrations was evaluated. Total fasting plasma homocysteine concentrations were measured in 11 elderly subjects aged 64.4 +/- 1.7 y (mean +/- SE) who consumed a vitamin B-6-deficient diet for less than or equal to 20 d. Only 1 of the 11 subjects was found to have elevated homocysteine concentrations even though all subjects exhibited high urinary xanthurenic acid concentrations after a tryptophan load, a measure indicative of vitamin B-6 deficiency. In a supporting study, fasting plasma homocysteine concentrations were measured in 3- and 23-mo-old rats fed vitamin B-6-deficient diets and were compared with those of vitamin B-6-replete, pair-fed controls. There was no difference in homocysteine concentrations between deficient and pair-fed animals after 6 wk of the dietary regimen for either age group; after 9 wk a modest elevation was observed in the 3-mo-old deficient rats whereas no difference was observed for the 23-mo-old rats. It is concluded that fasting plasma homocysteine concentrations are not initially elevated in vitamin B-6 deficiency and therefore fasting plasma homocysteine concentrations are not a good indicator of vitamin B-6 status.

Aged↗

Changes in gastrointestinal function attributed to aging.

There are numerous reports in the literature of impaired gastrointestinal function with aging. However, most gastrointestinal functions remain relatively intact because of the large reserve capacity of the intestine, pancreas, and liver. Clinically important changes in gastrointestinal function with aging in human include decreased taste thresholds, hypochlorhydria due to atrophic gastritis, and decreased liver blood flow and size. Increased absorbability of lipids and large size molecules has been demonstrated in aging animals, but this has not been studied in humans. Nutrients with impaired gastrointestinal bioavailability in aging include dietary B-12, calcium carbonate, and ferric iron in atrophic gastritis; calcium, zinc, and possibly carbohydrate in a mixed meal. The implications of these changes for health maintenance and chronic disease in elderly people are in need of study.

Aging↗

Distribution of orally administered beta-carotene among lipoproteins in healthy men.

Plasma and lipoprotein concentrations of beta-carotene (BC) were measured in men for 10 d after an oral dose of BC (120 mg) (experimental subjects, n = 11) or no BC (control subjects, n = 5). Lipoproteins were separated by sequential ultracentrifugation and BC was measured by HPLC. Plasma and lipoprotein BC concentrations in control subjects were steady. In experimental subjects, plasma BC content increased by 6 h postdosing (P less than 0.015), peaked at 24 h (P less than 0.05), and returned to baseline by 7 d. Maintenance of plasma BC concentrations suggests homeostatic control. Of the 11 experimental subjects, only 4 had a plasma response. Early increases in the BC content of chylomicrons, very-low-density lipoproteins, and intermediate-density lipoproteins. Intestinal input accounts for early rises in circulating BC concentrations whereas hepatic secretion is the source of later increases. Among all of the lipoproteins, transfer of BC may occur.

Administration, Oral↗

Studies on the application of the relative-dose-response test for assessing vitamin A status in older adults.

We investigated the time course and the reproducibility of the relative-dose-response (RDR) test for assessing vitamin A status in older adults. The maximum plasma retinol response to 480 retinol equivalents (RE) of retinyl palmitate in abnormal responses was at 6 or 7 h after dosing compared with the 5-h sampling interval recommended by others for younger adults and children. With respect to reproducibility, the diagnostic concordance of two RDR tests at 7-d intervals in 14 elders was 71%. In 29% of tests, one test was abnormal and the other normal. Linear regression of the two RDR values in these 14 subjects gave a correlation coefficient of -0.08. We conclude that the procedure for the RDR should be modified when applied to persons greater than 60 y of age, and that multiple repetitions of the test are needed to provide a stable indication of vitamin A stores in an elderly individual.

Aged↗

Sex differences in postabsorptive plasma vitamin A transport.

This study examined postabsorptive plasma vitamin A after doses of retinyl palmitate in healthy men (n = 28) and women (n = 31). On consecutive days one physiologic [3000 retinol equivalents (RE)] and one pharmacologic dose (105,000 RE) were administered and blood samples collected. Plasma retinol and retinyl esters were measured by HPLC. Tolerance curves were constructed by plotting plasma retinyl ester concentration vs time. Postprandial retinyl ester response was measured as peak rise in retinyl ester concentration and area under the curve (AUC). Peak plasma retinyl ester concentration occurred earlier for females but the earlier peak was significant only for younger subjects (< or = 50 y, P < 0.02) given the low dose and older subjects (> 50 y, P < 0.02) given the high dose. Peak rise and AUC were lower in females than in males, but this difference was significant for the high dose only (P < 0.05). In the high-dose experiment, when each age group was evaluated for sex differences the peak rise was significantly greater in males than in females in the older subjects (P < 0.05). Postabsorptive plasma retinol did not change from fasting concentrations. A lower plasma response in retinyl esters in women could be due to a more efficient chylomicron-remnant clearance.

Adult↗

Beta-carotene, retinol and retinyl ester concentrations in serum and selected tissues of ferrets fed beta-carotene.

The concentrations of beta-carotene, retinol and retinyl esters in serum and selected tissues of ferrets fed diets supplemented with beta-carotene (80 micrograms/g wet diet) for 3 wk were determined. The initial concentration of serum beta-carotene was 0.011 +/- 0.006 mumol/L (mean +/- SEM); at the end of the experimental period it was 5.75 +/- 1.60 mumol/L. No significant differences in serum retinol and total retinyl esters were observed between beta-carotene-fed and control ferrets that had been fed an unsupplemented diet. The predominant retinyl esters in serum were retinyl stearate (53%) and retinyl palmitate (35%). Of the tissues analyzed after beta-carotene feeding, the liver contained the highest concentration of beta-carotene (78.8 +/- 18.8 nmol/g). Other tissues that contained beta-carotene in amounts ranging from 17 to 20 nmol/g were adrenals, small intestine, stomach and colon; lesser amounts (6.9 nmol/g) were found in kidneys. Amounts ranging from 1.2 to 2.3 nmol/g were found in muscle, bladder, adipose tissue, lungs and skin; only 0.37 and 0.34 nmol/g were present in brain and eyes, respectively. Thus, like humans, ferrets have the capacity to absorb intact beta-carotene and to store this compound in tissues, especially the liver. However, compared with humans, ferrets have elevated concentrations of retinyl esters in serum, liver and other tissues.

Absorption↗

Nutrition mission to Iraq for UNICEF.

At the request of UNICEF, the authors conducted a rapid nutritional assessment of children from birth to five years of age in southern Iraq during the second half of June 1991. With support from local UNICEF staff, the nutrition team examined 680 children, measuring weight, height, and mid-upper arm circumference and observing clinical signs of anemia, vitamin A deficiency, and dehydration. These measurements and observations were performed in 14 rural, urban, and periurban settings in Basrah and Amarah governorates. Evidence of both acute and chronic malnutrition was found in large numbers of the children examined. However, the acute nutritional signs of impending famine were not evident at the time of the survey. This is true notwithstanding epidemic levels of infectious disease, market prices for basic food items three to 20 times prewar levels, and a reported crisis in mothers' ability to breastfeed. Other signs of impending famine (distress sales of family assets, disintegration of social structures, etc.) may have existed, but were not evident to the team.

Child Nutritional Physiological Phenomena↗

Inhibition of dapsone-induced methaemoglobinaemia by cimetidine in the presence of trimethoprim in the rat.

Administration of dapsone in combination with trimethoprim and cimetidine to male rats resulted in a marked decrease (P less than 0.05) in measured methaemoglobin levels (46.2 +/- 24% Met Hb h) compared with administration of dapsone alone (124.5 +/- 24.4% Met Hb h). The elimination half-life of dapsone (814 +/- 351 min) was more than doubled in the presence of trimethoprim and cimetidine compared with control (355 +/- 160 min, P less than 0.05). However, there were no significant differences in AUC and clearance when dapsone was administered in combination with trimethoprim and cimetidine compared with dapsone alone. Co-administration of trimethoprim with dapsone in the absence of cimetidine did not affect either methaemoglobin formation, AUCs, half-lives, or clearance values of dapsone compared with control. There was a threefold increase in the AUC of trimethoprim (6296 +/- 2249 micrograms min mL-1) in the presence of dapsone compared with trimethoprim alone (2122 +/- 552 micrograms min mL-1). There was also a corresponding decrease in the clearance of trimethoprim in the presence of dapsone compared with control (19.1 +/- 6.9 vs 60.8 +/- 21.0 mL min-1). However, there was no change in the elimination half-life of trimethoprim between the two experimental groups (273 +/- 120 vs 292 +/- 54 min). The AUC of trimethoprim increased more than threefold in the presence of cimetidine (7100 +/- 1501 micrograms min mL-1) compared with trimethoprim alone (2122 +/- 552 micrograms min mL-1).(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylation↗

Intestinal uptake and lymphatic absorption of beta-carotene in ferrets: a model for human beta-carotene metabolism.

To determine the appropriateness of the ferret as a model for human beta-carotene (beta-C) metabolism, we have perfused both 15,15'-beta-[14C]C and unlabeled beta-C through the upper 30-cm portion of the small intestine of ferrets in vivo. The effluents of a mesenteric lymph duct cannulation and a common bile duct cannulation, as well as portal vein blood periodically sampled via an indwelling catheter, were collected. Ten percent (9.5 +/- 0.06%) of the total administered beta-C was taken up by the intestine after a 4-h perfusion. Of the radioactivity taken up, 68.6 +/- 6.5% remained in the intestinal mucosa, 3.2 +/- 0.2% was recovered in the lymph, and 28.2 +/- 6.5% (calculated) was absorbed via the portal system. The total uptake/absorption of beta-C was 12.9 +/- 6.8 nmol.h-1.30 cm intestine-1. Large amounts of unchanged beta-C and relatively small amounts of both beta-apo-12'-carotenal and beta-apo-10'-carotenal were isolated in the intestinal mucosa after a 4-h perfusion with beta-C. Considerable amounts of metabolites more polar than retinol were formed and comprised 35% of the total radioactivity recovered in the intestinal mucosa. Polar metabolites were absorbed mostly into the portal venous system, whereas retinol and retinyl esters were absorbed mainly into the mesenteric lymph. Of the total absorbed radioactivity in lymph, 10 +/- 1.0% appeared as unchanged beta-C, with peak absorption occurring at 3 h after beginning the perfusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗