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Biomedical subjects

R M Russell

Publications and source records attributed to R M Russell.

At least 109 records · Page 6Linked to original sources

Biosynthesis of 9-cis-retinoic acid from 9-cis-beta-carotene in human intestinal mucosa in vitro.

The role of 9-cis-beta-carotene (9-cis-beta-C) as a potential precursor of 9-cis-retinoic acid (9-cis-RA) has been examined in human intestinal mucosa in vitro. By using HPLC, uv spectra, and chemical derivatization analysis, both 9-cis-RA and all-trans-retinoic acid (all-trans-RA) have been identified in the postnuclear fraction of human intestinal mucosa after incubation with 9-cis-beta-C at 37 degrees C. The biosynthesis of both 9-cis-RA and all-trans-RA from 9-cis-beta-C was linear with increasing concentrations of 9-cis-beta-C (2-30 microM) and was linear with respect to tissue protein concentration up to 0.75 mg/ml. Retinoic acid was not detected when a boiled incubation mixture was incubated in the presence of 9-cis-beta-C. The rate of synthesis of 9-cis- and all-trans-RA from 4 microM 9-cis-beta-C were 16 +/- 1 and 18 +/- 2 pmol/hr/mg of protein, respectively. However, when 2 microM all-trans-beta-C was added to the 4 microM 9-cis-beta-C, the rate of all-trans-RA synthesis was increased to 38 +/- 6 pmol/hr/mg of protein, whereas the rate of 9-cis-RA synthesis remained the same. These results suggest that 9-cis-RA is produced directly from 9-cis-beta-C. Furthermore, incubations of either 0.1 microM 9-cis- or all-trans-retinal under the same incubation conditions showed that 9-cis-RA could also arise through oxidative conversion of 9-cis-retinal. Although only 9-cis-RA was detected when 9-cis-RA was used as the substrate, the isomerization of the all-trans-RA to 9-cis-RA cannot be ruled out, since both all-trans-RA and trace amounts of 9-cis-RA were detected when all-trans-retinal was incubated as the substrate. These data indicate that 9-cis-beta-C can be a source of 9-cis-RA in the human. This conversion may have a significance in the anticarcinogenic action of beta-C.

Carotenoids↗

Nutrition.

It has been proposed that the government fortify certain foods with folate in order to benefit the greatest number of women of childbearing age. Physicians should be concerned about an inadequate B-vitamin status in the adult population.

Health Promotion↗

Bacterial overgrowth without clinical malabsorption in elderly hypochlorhydric subjects.

BACKGROUND/AIMS: Bacterial overgrowth of the small intestine commonly occurs in association with hypochlorhydria caused by atrophic gastritis or during treatment with omeprazole. The purpose of this study was to determine the clinical significance of bacterial overgrowth on small intestinal absorption and permeability and to evaluate the reliability of noninvasive breath tests to detect bacterial overgrowth in subjects with hypochlorhydria. METHODS: Seventeen healthy, elderly subjects with atrophic gastritis or omeprazole treatment (40 mg/day) and documented bacterial overgrowth were studied. RESULTS: There was no evidence of fat malabsorption (72-hour fecal fat) or clinically significant carbohydrate malabsorption (25 g D-xylose and fecal pH) in any subject. The ratio of lactulose to mannitol excreted was normal in both atrophic gastritis and omeprazole-treated groups. Three subjects in each group had abnormally high alpha 1-antitrypsin clearances. Lactulose (10 g) and glucose (80 g) hydrogen breath tests were only abnormal in 1 out of 17 subjects, whereas the 1 g [14C]D-xylose test was abnormal in 6 out of 17 subjects. CONCLUSIONS: Bacterial overgrowth caused by atrophic gastritis or omeprazole treatment is typically not associated with clinically significant fat or carbohydrate malabsorption. Noninvasive breath tests for bacterial overgrowth are not reliable in subjects with hypochlorhydria.

Achlorhydria↗

High concentrations of vitamin A esters circulate primarily as retinyl stearate and are stored primarily as retinyl palmitate in ferret tissues.

OBJECTIVE AND METHODOLOGY: We determined the kinds and amounts of vitamin A compounds (retinol and various retinyl esters) circulating in serum and stored in liver and other selected tissues of ferrets, using high-performance liquid chromatography. RESULTS: The concentration of total retinyl esters in serum (43 +/- 1 mumol/L, mean +/- SEM) was 25 times greater than that of retinol (1.7 +/- 0.2 mumol/L). In serum, 56% of retinyl esters was retinyl stearate, 33% was retinyl palmitate, and 5% was retinyl oleate. In contrast, in liver, vitamin A was stored primarily as retinyl palmitate (51%); smaller amounts of retinyl oleate (19%) and retinyl stearate (16%) were found. In kidneys, adrenals, small intestine, adipose tissue, skin, stomach, and eyes, retinyl palmitate was also the predominant retinyl ester, followed by retinyl stearate. In colon, lungs, and bladder, equal amounts of retinyl palmitate and retinyl stearate were observed. Other retinyl esters present in smaller amounts in most of these tissues were retinyl oleate, retinyl linoleate and/or -myristate, retinyl heptadecanoate, retinyl arachidonate, and retinyl laurate. CONCLUSIONS: Thus, the primary form of vitamin A that circulates in the blood of ferrets is retinyl stearate, whereas the primary storage form of the vitamin in tissues is retinyl palmitate. Concentrations of total vitamin A in ferret serum and other tissues were 3-73 times greater than those reported for their corresponding human tissues.

Animals↗

Effect of hypochlorhydria due to omeprazole treatment or atrophic gastritis on protein-bound vitamin B12 absorption.

OBJECTIVE: To investigate the effects of hypochlorhydria and acidic drink ingestion on protein-bound vitamin B12 absorption in elderly subjects. METHODS: Absorption of protein-bound vitamin B12 was examined in elderly normal subjects (n = 8), and in hypochlorhydric subjects due to omeprazole treatment (n = 8) or with atrophic gastritis (n = 3). Subjects underwent absorption tests of protein-bound vitamin B12 ingested with water, cranberry juice and 0.1 N hydrochloric acid. RESULTS: Protein-bound vitamin B12 absorption was lower in the omeprazole-treated group (0.50%) compared to the normal group (1.21%; p < 0.001). With cranberry juice ingestion, the omeprazole-treated group showed an increase in absorbed protein-bound vitamin B12 (p = 0.025). With dilute hydrochloric acid ingestion, there was a further increase in vitamin B12 absorption (p < 0.001). CONCLUSION: Omeprazole causes protein-bound vitamin B12 malabsorption, and ingestion of an acidic drink improves protein-bound vitamin B12 absorption.

Absorption↗

Beta-carotene supplementation increases antioxidant capacity of plasma in older women.

The antioxidant effect of dietary beta-carotene supplementation on the peroxidation potential of plasma was investigated in a randomized double-blind, placebo-controlled study. Twelve healthy women (62-80 y) supplemented their usual daily diet with 90 mg of beta-carotene (n = 6) or placebo (n = 6) capsules for 3 wk. Plasma concentrations of beta-carotene, alpha- and gamma-tocopherol, ascorbate, urate, bilirubin and in vitro production of phosphatidylcholine hydroperoxides (PC-OOH) and utilization of plasma antioxidants in the presence of 50 mmol/L 2,2'-azobis (2-aminopropane) hydrochloride (AAPH), a free radical generator, at 37 degrees C were measured before and after dietary treatment. Plasma beta-carotene increased from 0.76 +/- 0.16 to 6.45 +/- 1.16 micromol/L (P < 0.05) in supplemented but not placebo-treated subjects. The plasma concentrations of other antioxidants did not change significantly in either group. beta-Carotene supplementation did not affect basal levels of plasma PC-OOH as measured by HPLC post-column chemiluminescence but did affect AAPH-induced production of PC-OOH. Before supplementation, the induction period of plasma PC-OOH production was 2.4 +/- 0.4 h, with levels reaching 5.39 +/- 1.50 micromol/L after 6 h of incubation. After supplementation, the induction period increased significantly to 4.2 +/- 0.4 h (P < 0.01), with a lower PC-OOH production of 2.16 +/- 0.90 micromol/L after 6 h (P < 0.05). In this system, plasma ascorbate concentrations were depleted first, followed by loss of bilirubin and alpha-tocopherol and then by the sequential loss of gamma-tocopherol, urate and beta-carotene. These results indicate that beta-carotene supplementation increases the plasma antioxidant capacity of older women.

Aged↗

Diet, Helicobacter pylori infection, food preservation and gastric cancer risk: are there new roles for preventative factors?

Risks for gastric cancer in relation to diet and other environmental factors are receiving renewed attention. New developments include the emerging relationship between Helicobacter pylori infection and an increased risk for gastric cancer, and positive results of chemoprevention trials in decreasing gastric cancer risk with the use of beta-carotene and vitamin E supplements. Factors that may enhance risk include consumption of nitrites, nitrates, alcohol, and highly salted, pickled, fermented, or smoked foods. Other environmental factors which may promote cancer are H. pylori infection, inappropriate food storage, metal and cement dust exposure, and cigarette smoking. High intakes of fruits and vegetables or of antioxidants, such as beta-carotene, vitamin E, and vitamin C may decrease risk.

Animals↗

Enhancement of ethanol induced rectal mucosal hyper regeneration with age in F344 rats.

Experimental studies in rats have shown an independent stimulation of rectal cell turnover by either chronic ethanol consumption or age. In this study the combined effect of these two factors on colorectal cell regeneration has been investigated. Ninety male F344 rats aged 2, 12, and 22 months were pair fed nutritionally adequate liquid diets containing 36% of total energy either as ethanol or isoenergetic carbohydrates. After four weeks of feeding, colorectal crypt cell production rates were measured using a stathmokinetic technique with vincristine. While age by itself did not affect colorectal cell renewal, chronic ethanol consumption stimulated rectal, but not colonic crypt cell production rate in an age dependent manner. While no significant effect of ethanol was noted in young animals, cell proliferation was significantly enhanced in middle aged animals by 81% (4.1 (2.7-5.5) v 7.4 (6.0-8.7) cells/crypt/hour, p < 0.001) and in old animals by 138% (4.5 (3.3-5.6) v 10.7 (8.9-12.4) cells/crypt/hour, p < 0.001) after ethanol ingestion. Because acetaldehyde, the first and most toxic metabolite of ethanol, has been detected in the colorectal mucosa and may lead to tissue injury influencing cell regeneration, acetaldehyde concentrations have been measured in the colons of 15 male F344 rats of various ages after an acute intraperitoneal dose of ethanol (2.5 g/kg bodyweight). There was a significant positive correlation between crypt cell production rate and acetaldehyde concentrations measured in the distal and proximal colon after an acute dose of ethanol (r = 0.5955, p < 0.005). These data clearly show that the ethanol mediated stimulation of cell regeneration in the rectum is age dependent. As reported earlier, there was found indirect evidence that acetaldehyde participates in the pathogenesis of rectal hyperregeneration after chronic alcohol consumption. This hyperregeneration of the rectal mucosa after alcohol drinking could by itself favour carcinogenesis, which is especially relevant in old age.

Acetaldehyde↗

Nutritional consequences of intestinal bacterial overgrowth.

The bacterial overgrowth syndrome occurs when there are alterations in intestinal anatomy, gastrointestinal motility, or a lack of gastric acid secretion. Clinically, patients present with nonspecific gastrointestinal symptoms that include abdominal pain, bloating, excessive gas production, diarrhea, weight loss, and malabsorption. The nutritional consequences of intestinal bacterial overgrowth include vitamin deficiencies, fat malabsorption, and malnutrition. The diagnosis requires a high index of clinical suspicion and can be established by specialized testing, such as the 1-gram 14C-xylose breath test. The goal of treatment is eradication of the bacterial overgrowth (usually with antibiotics) and the correction of nutritional deficiencies.

Bacterial Infections↗

Establishment of creatinine clearance reference values for older women.

Age-adjusted reference ranges for creatinine clearance were determined in 279 women, ages 40-95 years, who were housed in a metabolic research unit and consumed a meat-free diet. Creatinine clearance, but not serum creatinine, declined with age by 0.63 mL/min per 1.73 m2 per year. Serum and urine creatinine concentrations, used to calculate clearances, were analyzed by a kinetic Jaffé procedure. In a subset of 100 subjects, fasting serum creatinine values averaged 8.3 +/- 5.2 (SD) mumol/L higher when measured by the kinetic Jaffé procedure than by an enzymatic method (creatinine PAP). The Cockcroft-Gault formula for estimating creatinine clearance from serum creatinine in women was validated, and the modification factor for the male equation was determined to be 0.84 (95% confidence interval 0.83-0.86) confirming the suggested 15% correction. A prediction formula derived from this population was similar in accuracy to the Cockcroft-Gault formula.

Adult↗

Epidermis and serum protect retinol but not retinyl esters from sunlight-induced photodegradation.

Sunlight-induced photodegradation of retinyl esters and retinol in human skin, blood and cultured keratinocytes was investigated. Using high-performance liquid chromatography with an extraction method that avoided saponification, the analysis of human foreskin (Caucasian) showed that levels of retinyl esters and retinol were approximately 3.5 and 5.0 times higher, respectively, in the epidermis than in the dermis. Upon irradiation by sunlight, a significant reduction in epidermal retinyl esters was observed in both summer and winter. However, epidermal retinol, dermal retinol and dermal retinyl esters did not show statistically significant reductions. When serum from volunteers who had taken a large dose of retinyl palmitate to elevate serum retinyl esters was exposed to sunlight, the retinyl esters in the serum rapidly disappeared after 10 min of exposure--similar to the photodegradation seen for retinyl palmitate in an organic solvent. While retinol in an organic solvent rapidly photodegraded similar to serum retinyl palmitate, serum retinol slowly declined upon sunlight irradiation. When cultured keratinocytes that took-up 3H-retinol and thereafter contained 3H-retinyl esters and 3H-retinol were exposed to sunlight, 80% of the 3H-retinyl esters disappeared upon sunlight irradiation whereas only about 20% of the 3H-retinol did so. These results suggest that the epidermis, serum and keratinocytes selectively protect retinol from sunlight-induced photodegradation. It is most likely that serum retinol-binding protein and cellular retinol-binding protein protect retinol, a vital epithelial growth factor, from photodegradation.

Blood↗

Nutrition.

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Health Promotion↗

Intestinal perfusion of beta-carotene in the ferret raises retinoic acid level in portal blood.

To determine whether beta-carotene (beta-C) can serve as a source of intestinally-derived retinoic acid (RA), either 15,15'-[14C]beta-C or unlabeled beta-C was perfused through 30 cm jejunal segments of ferrets in vivo. Portal vein blood was sampled periodically via an indwelling catheter. RA was identified in portal blood by comparing retention times in HPLC, by UV absorption, and by derivatization (methylation) and subsequent GC-MS analysis. The RA concentration in the portal blood increased 3-fold with perfusion of beta-C (P < 0.05), and remained at 18 nmol/L during the perfusion of beta-C. The single peak of RA in HPLC was shown to consist of four separate peaks by GC-MS, which may be cis-trans isomers of RA. The concentration of RA in portal blood returned to the initial level (5 nmol/L) after a 2 h period of intestinal perfusion with 5% dextrose. Retinyl ester concentration in portal blood did not change before or after the perfusion, whereas retinol decreased significantly during the perfusion of beta-C. This study clearly indicates that a considerable quantity and number of polar metabolites, including RA, are formed from beta-C in the ferret intestine which are transported via the portal vein to the liver.

Animals↗

Vitamin requirements of elderly people: an update.

This article is an update of our 1987 literature review of vitamin requirements of elderly people (Am J Clin Nutr 1987;45:501-12). Poor dietary intake is the cause of much vitamin malnutrition in elderly people. Nevertheless, there is strong evidence that aging affects the requirement for certain vitamins. The 1989 recommended dietary allowances (RDAs) appear to be too low for elderly people for vitamin D, riboflavin, vitamin B-6, and vitamin B-12, and too high for vitamin A. For several vitamins there is enough information to establish an RDA for the category > or = 70 y.

Aged↗

Prevalence of riboflavin deficiency among Guatemalan elderly people and its relationship to milk intake.

Six groups of elderly subjects from central Guatemala were assessed for riboflavin status by using the erythrocyte glutathione reductase activity coefficient (EGRAC). The prevalence of riboflavin deficiency ranged from 50% to 76% among the free-living rural elderly subjects. Milk intake data that were collected from some of the subjects showed a significant correlation (P < 0.0001) between frequency of milk intake and riboflavin status. In a short-term riboflavin supplementation experiment in which nine riboflavin-deficient subjects were given 10 mg riboflavin/d for 3 d, all the subjects' EGRACs were normalized by the supplementation. However, they returned to a state of deficiency within 2 wk while consuming their usual diets without supplementation. It appears that the high prevalence of riboflavin deficiency in elderly Guatemalan people is caused by inadequate intake of riboflavin-rich foods such as dairy products, and that sufficient amounts of riboflavin need to be ingested regularly to maintain satisfactory riboflavin status.

Aged↗