PubMed HealthSearch

Biomedical subjects

R M Russell

Publications and source records attributed to R M Russell.

At least 19 recordsLinked to original sources

Similar metabolites formed from beta-carotene by human gastric mucosal homogenates, lipoxygenase, or linoleic acid hydroperoxide.

To determine the basis for the formation of excentric cleavage products of beta-carotene (beta-C) after incubation with human gastric mucosal homogenates, we have studied the effect of lipoxygenase in beta-C metabolism. beta-C was incubated with human gastric mucosal homogenates, soybean lipoxygenase with linoleic acid, or the lipoxygenase primary product, 13(S)-hydroperoxycis,trans-9,11-octadecadienoic acid (13-LOOH). The beta-C metabolites, beta-apo-14', -12', -10', and -8'-carotenals, beta-apo-13-carotenone, retinoic acid, and retinal were detected and quantified by HPLC after a 30-min incubation with 1.8 microM beta-C. The products from the lipoxygenase plus linoleic acid incubation and from the lipoxygenase primary product, 13-LOOH, with beta-C were exactly the same as the products from a human gastric mucosal homogenate incubation. Significantly larger amounts of the same beta-C metabolites were formed when beta-C was incubated with gastric mucosal homogenates and lipoxygenase together. Furthermore, nordihydroguaiaretic acid (NDGA), a specific lipoxygenase inhibitor, was found to significantly inhibit the formation of beta-apo-carotenoids and retinoids produced by gastric mucosal homogenates incubated with beta-C. The similarity of the beta-C metabolites when beta-C was incubated with human gastric mucosal homogenate, lipoxygenase plus linoleic acid, or 13-LOOH and the inhibition of beta-C metabolite production by NDGA in gastric tissue incubation with beta-C suggest that lipoxygenase is involved in beta-C metabolism in gastric mucosa. The activity of 13-LOOH in our hands would indicate that an enzyme-linked process is occurring in gastric tissue producing fatty acid hydroperoxides, and that the hydroperoxide, or a radical species derived from it, is able to carry out the oxidation of beta-C independently of the enzyme.

Biotransformation

Nutrition.

The treatments of obesity with anorexigenic medications is now being considered. The role of antioxidants in protecting against chronic diseases is in the process of being defined. A National Institutes of Health Consensus Conference recommended that adult calcium intake be between 1000 and 1500 mg/d.

Humans

Use of pedicled fat pad graft as an adjunct in the reconstruction of palatal cleft defects.

The purpose of this article is to provide the rationale for the use of pedicled buccal fat pad grafts as an adjunct to the reconstruction of palatal or dentoalveolar clefts in cases when healing by secondary intention may need to be considered and integrated into the initial treatment plan because of the size of the defect or qualitative or quantitative tissue constraints. Four representative cases are presented in which a pedicled buccal fat graft was adjunctively used in conjunction with pedicled mucosal flaps to gain closure of large oroantral or oronasal cleft deformity.

Adipose Tissue

Serum retinoic acid levels in patients with resected benign and malignant colonic neoplasias on beta-carotene supplementation.

To determine whether patients with colon cancer metabolize beta-carotene differently from benign colon polyp patients, a normal control group (n = 13) and groups of resected colon polyp patients (n = 29) or resected colon cancer patients (Dukes A and B1, n = 21) were supplemented with placebo or beta-carotene (30 mg/day) taken with their morning meals for three months. Serum samples at zero and three months of the study were analyzed blindly for retinoic acid and beta-carotene. The results showed that beta-carotene levels in the serum of colon polyp and colon cancer groups were 8- to 12-fold higher than in the untreated control or the placebo-treated groups. The benign polyp subjects (n = 17) receiving beta-carotene showed a significant rise in serum trans-retinoic acid at three months compared with Time 0. The trans-retinoic acid values from the colon cancer group receiving beta-carotene (n = 11) or placebo (n = 10) were significantly lower than the values from the beta-carotene-supplemented colon polyp group. It appears that trans-retinoic acid levels in response to beta-carotene supplementation are different between treated cancer and benign patients because of different body demands for retinoic acid.

Adult

Survival of yogurt-containing organisms and Lactobacillus gasseri (ADH) and their effect on bacterial enzyme activity in the gastrointestinal tract of healthy and hypochlorhydric elderly subjects.

The effect of the live bacterial yogurt cultures, namely Streptococcus thermophilus and Lactobacillus bulgaricus, and a mucosal adhering strain of Lactobacillus gasseri (ADH) on small intestinal and fecal bacterial characteristics was examined in 10 elderly subjects with atrophic gastritis and 23 elderly normal volunteers (11 received yogurt and 12 received ADH). Neither S thermophilus nor L bulgaricus was recovered from the stomach or small intestine of subjects fed yogurt or pasteurized yogurt. ADH was recovered from gastric or small intestinal aspirates in three of four subjects and in the stools of four of five subjects diagnosed with atrophic gastritis. In 11 of 12 normal subjects, ADH was isolated from stools. There was a significant reduction in fecal bacterial enzyme activity in both normal volunteers and subjects with atrophic gastritis after being fed with viable ADH. Adherent strains of bacteria such as ADH are likely to survive passage through the gastrointestinal tract and thus have greater metabolic effects.

Aged

Discrimination in absorption or transport of beta-carotene isomers after oral supplementation with either all-trans- or 9-cis-beta-carotene.

Human subjects (n = 24) were supplemented with 100 mg beta-carotene/d for 6 d, either as synthetic all-trans-beta-carotene or a natural beta-carotene preparation derived from the alga Dunaliella salina, which consists of a 50:50 mixture of all-trans- and 6-cis-beta-carotene. This loading dose was followed by a 23-d maintenance dose consisting of alternate-day supplementation with 50 mg all-trans-beta-carotene or either 66 or 100 mg of the natural 50:50 isomeric mixture. The loading dose resulted in significant increases in plasma concentrations of both isomers, with the all-trans-beta-carotene-supplemented group showing a 7.2- and 5.0-fold increase in the all-trans and 9-cis concentrations in plasma, respectively. The group receiving the 50:50 mixture showed a 4.0- and 3.7-fold increase in the all-trans and 9-cis concentrations in plasma, respectively, without any apparent dose-dependency. However, even with the 50:50 mixture, the 9-cis concentrations were only a small fraction of the total plasma beta-carotene. Results after an additional 23-d period of alternate-day supplementation were not significantly different from those described above for the 6-d supplementation. Increases in low-density-lipoprotein concentrations of total beta-carotene correlated strongly with the increases seen in plasma concentrations. Lipid-soluble antioxidants vitamin E and ubiquinol were unaffected by beta-carotene supplementation. However, the amount of lycopene in the low-density lipoprotein decreased during this supplementation period. A strong discrimination between these two geometric isomers of beta-carotene was demonstrated, although the tissue site of discrimination was not determined.

Administration, Oral

Mineral requirements of elderly people.

Poor mineral nutrition reported in elderly people is attributed in large part to low dietary intake. Evaluation of the adequacy of mineral nutriture is limited for several minerals because of inadequate methods for assessing mineral status. In addition, there is a general lack of information about mineral nutriture and metabolism in very old people (> 85 y). Given these reservations, the 1989 recommended dietary allowance (RDA) for iron, zinc, and selenium appears adequate for elderly people, as does the estimated safe and adequate daily dietary intake (ESADDI) recommendation for copper. In contrast, the current RDAs for calcium and magnesium and the ESADDI for chromium need careful reevaluation. Current recommendations for calcium may be too low, whereas those for magnesium and chromium may be higher than necessary. For phosphorus, iodine, manganese, fluoride, and molybdenum the available data are insufficient to make a critical judgment about the appropriateness of the dietary recommendations for elderly people.

Aged

Relation between beta-carotene intake and plasma and adipose tissue concentrations of carotenoids and retinoids.

We evaluated the relation between beta-carotene intake and plasma and adipose tissue concentrations of carotenoids and retinoids. In Study 1, beta-carotene intakes were significantly greater in vegetarians than in nonvegetarians. Plasma concentrations of beta-carotene were also significantly higher in vegetarians than in nonvegetarians but only after two nonvegetarians with excessive intake of carrots were omitted. Plasma retinoid (retinol, retinyl esters, and retinoic acid) concentrations were not different between the two groups. In Study 2, female subjects ingested a daily placebo or 90 mg beta-carotene for 3 wk. In the group fed beta-carotene, plasma beta-carotene concentrations were significantly increased from baseline at 1, 2, and 3 wk. No beta-carotene changes were observed in the placebo-fed group. Plasma retinoid concentrations did not change in either group. In Study 3, adipose tissue beta-carotene and retinoid concentrations were measured in men after an oral beta-carotene dose (120 mg, experimental subjects) or no beta-carotene (control subjects). In the experimental subjects, adipose beta-carotene concentrations increased from baseline at 5 and 10 d postdosing. The control group's adipose tissue beta-carotene concentration did not change over a 10-d period. Changes in retinoids in adipose tissue were not significant in either group. In conclusion, dietary and supplemental beta-carotene increased plasma beta-carotene concentrations but had no effect on plasma retinoid concentrations. There may be little tissue metabolism of beta-carotene to retinoids. Therefore, the anticarcinogenic effect of beta-carotene, if any, may be due to properties of the molecule itself.

Adipose Tissue

Effect of Helicobacter mustelae infection on ferret gastric epithelial cell proliferation.

The effect of Helicobacter mustelae infection on gastric epithelial proliferation was studied in ferrets colonized with H.mustelae and specific pathogen-free (SPF) ferrets not infected with H.mustelae. Thirteen H. mustelae-infected ferrets between the ages of 13 and 32 months and 16 SPF ferrets between 6 and 18 months were analyzed. Bacterial cultures, urease tests and Warthin-Starry stains were used to identify H.mustelae. Tissues obtained from the antrum and the body regions of the stomach were assayed by proliferating cell nuclear antigen (PCNA) immunohistochemistry and measured using a computerized color image analysis system. PCNA-expressing gastric epithelia in the antrum and the body regions were significantly increased in the H.mustelae-infected ferrets versus the SPF ferrets (P < 0.001). PCNA positivity in the antrum regions of both the H.mustelae-infected ferrets and SPF ferrets was significantly higher than that of the body regions (P < 0.001). Comparison of the histopathology of infected ferrets indicated that PCNA positivity correlated with the histological severity of gastritis. This study suggests that cell proliferation in ferret gastric mucosa increases with H.mustelae infection and provides evidence that PCNA is a useful biomarker for studying the changes in cell kinetics in the ferret stomach. The data also further support the use of the H.mustelae-infected ferret as an animal model for studying the pathogenesis of Helicobacter pylori-induced gastric diseases of humans.

Animals

Long-term supplementation of canthaxanthin does not inhibit gastric epithelial cell proliferation in Helicobacter mustelae-infected ferrets.

The effect of canthaxanthin (CX), a nonprovitamin A carotenoid, on gastric epithelial proliferation was studied in ferrets colonized with Helicobacter mustelae, which causes a chronic gastritis and an increased gastric epithelial cell proliferation. Seven spayed female ferrets were dosed by gavage with CX beadlets (50 mg/kg body wt, 5 d/wk) over 2 y, whereas seven control animals were given placebo beadlets. At the end of the 2-y-period, ferrets were killed, and gastric tissues were obtained from the antrum and body regions. A cell-proliferating biomarker, proliferating cell nuclear antigen (PCNA), was assayed by immunohistochemistry. The PCNA positivity was measured by a computer-based image analysis system. Serum concentrations of carotenoids, retinoids and tocopherols were analyzed by HPLC. Serum antioxidant status was measured by the oxygen radical absorbance capacity (ORAC) assay. The PCNA positivity in both antrum and body regions was not significantly different between CX-fed ferrets and controls. Serum CX concentrations were significantly higher in CX-fed ferrets vs. controls (P < 0.001), whereas levels of other carotenoids, retinoids and tocopherols were not significantly different. The ORAC values were not significant different between groups. This study does not suggest inhibitory effects of CX on gastric epithelial cell proliferation in H. mustelae infected ferrets.

Animals

Skin lycopene is destroyed preferentially over beta-carotene during ultraviolet irradiation in humans.

This placebo-controlled study examined in healthy women the effects of ingestion of a single large dose of beta-carotene (120 mg) on the concentrations of beta-carotene and lycopene in plasma and skin, and the effects of UV light exposure on the concentrations of beta-carotene and lycopene in the skin. Ingestion of beta-carotene increased plasma beta-carotene concentration by 127%, from 0.26 +/- 0.06 (mean +/- SEM) to 0.59 +/- 0.07 mumol/L after 1 d, and the level remained elevated at 0.54 +/- 0.11 mumol/L after 5 d. beta-Carotene in skin, analyzed after 6 d, increased by 23%, from 1.41 +/- 0.74 to 1.74 +/- 0.72 nmol/g. beta-Carotene ingestion had no effect on the lycopene concentrations of plasma (0.37 +/- 0.11 mumol/L) or skin (1.60 +/- 0.62 nmol/g). A single exposure of a small area of one volar forearm to a dose of solar-simulated light (three times the individually determined minimal erythema dose) resulted in 31 to 46% reductions in skin lycopene concentration compared with an adjacent non-exposed area. The same UV dose did not result in significant changes in skin beta-carotene concentration. We conclude that a single 120-mg dose of beta-carotene increases plasma and skin beta-carotene concentrations and has no effect on plasma and skin lycopene concentrations. The amounts of lycopene in plasma and skin are comparable to or even greater than those of beta-carotene. When skin is subjected to UV light stress, more skin lycopene is destroyed compared with beta-carotene, suggesting a role of lycopene in mitigating oxidative damage in tissues.

Administration, Oral

Supplementing ferrets with canthaxanthin affects the tissue distributions of canthaxanthin, other carotenoids, vitamin A and vitamin E.

To study the effects of canthaxanthin supplementation on the tissue distribution of canthaxanthin, other carotenoids, vitamin A and vitamin E, 26 spayed female ferrets (2 mo of age) were used. Ferrets were assigned to receive a commercial ferret diet and a gavage of canthaxanthin [50 mg/(kg body wt.d)] or a gavage of placebo beadlets (0 mg canthaxanthin) 5 d/wk. Serum canthaxanthin concentrations in the canthaxanthin-fed group increased from 0 at baseline to 37.76 +/- 5.34 nmol/L trans and 77.10 +/- 12.60 nmol/L cis canthaxanthin at 12 mo. Further accumulation of canthaxanthin did not occur with continuous dosing. After 2 y of receiving canthaxanthin beadlets by gavage, the ferrets did not show a detectable concentration of canthaxanthin in the eyes, nor did they have clinical signs of toxicity. Canthaxanthin concentrations were highest in liver, with high concentrations also seen in fat, lung and small intestine. The sum of alpha and beta-carotene concentrations detected in livers was significantly higher in the canthaxanthin-fed group than in the placebo-fed group, but not significantly higher when individual carotenes were compared. However, alpha-tocopherol concentrations in the livers and lungs and lutein/zeaxanthin in the fats of the ferrets fed canthaxanthin were significantly lower than in those fed the placebo. Retinoid concentrations in tissues of the ferrets fed canthaxanthin were not different from those of the placebo-fed group. The effects of canthaxanthin supplementation on other antioxidants and vitamin A nutrients demonstrate either a synergistic or antagonistic relationship, depending on the specific tissue assayed.

Adipose Tissue

Changes in small-intestine permeability with aging.

OBJECTIVE: To evaluate small-intestine mucosal integrity and permeability with advancing age as measured by the lactulose/mannitol absorption test in healthy subjects. DESIGN: Prospective cohort study. SETTING: Clinical research unit of the USDA Human Nutrition Research Center on Aging. STUDY PARTICIPANTS: Fifty-six subjects were recruited in three age groups: 20 to 39 years (n = 20), 40 to 59 years (n = 19), and > or = 60 years (n = 17). Subjects were healthy, community-dwelling volunteers. INTERVENTION: After an 8-hour fast, all subjects ingested 10 g of lactulose and 5 g of mannitol. Urine was collected for 6 hours and analyzed for lactulose and mannitol by high performance liquid chromatography. Twenty-four-hour urinary creatinine clearances were determined. MAIN OUTCOME MEASURES: Percentages of lactulose and mannitol excreted, the lactulose/mannitol ratio (x100), and the 24-hour creatinine clearance. RESULTS: With increasing age, both the percentage of lactulose excreted (P = 0.09) and the percentage of mannitol excreted (P = 0.05) tended to decrease progressively. The lactulose/mannitol ratio (x100) did not change with increasing age (P = 0.65) because both the percentages of lactulose and mannitol excreted declined. The creatinine clearance decreased markedly with advancing age (P < .001) and accounted for the decline in percentages of lactulose and mannitol excreted (P < .02). CONCLUSIONS: There is a progressive decline in the ability to excrete lactulose and mannitol with increasing age. This is probably attributable to a decline in renal function with advancing age. However, because of parallel decreases in lactulose and mannitol excretion, the lactulose/mannitol ratio does not change. Thus small-intestine "leakiness" does not increase with aging as measured by the lactulose/mannitol absorption test.

Adult

Measurement of carotenoids, retinoids, and tocopherols in human lenses.

PURPOSE: To determine the levels of carotenoids, retinoids, and tocopherols in normal and cataractous human lenses. METHODS: Concentrations of carotenoids, retinoids, and tocopherols were measured by high-performance liquid chromatography (HPLC) in 12 American normal lenses, 9 American cataractous lenses, and 10 Indian cataractous lenses. RESULTS: On a per gram wet weight of tissue basis, human lenses contained 11 to 25 ng xanthophylls (lutein and zeaxanthin), 31 to 50 ng retinol, 21 to 25 ng retinyl palmitate, 1573 to 2550 ng alpha-tocopherol, and 257 to 501 ng gamma-tocopherol. Concentrations of lutein, zeaxanthin, and retinol were significantly higher in Indian cataractous lenses than in American normal or cataractous lenses. There were no differences in the lutein-zeaxanthin, retinoid, or alpha-tocopherol contents between American normal lenses and American cataractous lenses. The range of ratios of lutein to zeaxanthin in human lenses was 1.6 to 2.2. The mean age of the Indian lens donors was 20 years younger than the American lens donors. Comparisons using contralateral lenses indicated that there was significant interindividual variance in human lens concentrations of xanthophylls, retinoids, and tocopherols. beta-carotene and lycopene, major carotenoids in human serum and other tissues, were not detected in human lenses. CONCLUSIONS: Xanthophylls (lutein and zeaxanthin) are the only carotenoids detected in human lens. Retinol, retinyl palmitate, and alpha- and gamma-tocopherols also are present in human lens. Determinants of lens concentration of nutrients are not defined, but dietary factors are likely to be important.

Carotenoids

Intestinal absorption and metabolism of 9-cis-beta-carotene in vivo: biosynthesis of 9-cis-retinoic acid.

This study was done to examine the intestinal absorption and cleavage of 9-cis-beta-carotene in vivo. A micellar solution, containing either no addition or 10 mumol of 9-cis- or all-trans-beta-carotene, was perfused for 2 h through the upper portion of the small intestine of ferrets. The effluent of a mesenteric lymph duct cannulation was collected, as well as intestinal mucosa scrapings, a portal blood sample, and a liver biopsy, both before and after perfusion. Carotenoids and retinoids were measured by reverse-phase, high performance liquid chromatography. 9-Cis- and all-trans-beta-carotene were transported equally well into mesenteric lymph, although the intestinal concentration of the corresponding isomer was tenfold higher after perfusion of the 9-cis- isomer than after perfusion of all-trans-beta-carotene. Regardless of which isomer was used, perfusion of beta-carotene resulted in the biosynthesis of similar amounts of retinoic acid in portal blood, liver, and intestine. However, after the perfusion of all-trans-beta-carotene, all the retinoic acid formed was in the all-trans- form, whereas the perfusion of 9-cis-beta-carotene resulted in the biosynthesis of about 50% of the total retinoic acid as the 9-cis-isomer. We conclude that in the in vivo ferret model, 9-cis-beta-carotene has a good bioavailability and is a precursor of 9-cis-retinoic acid.

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

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

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