Search PubMed⌕ Search

Biomedical subjects

R M Russell

Publications and source records attributed to R M Russell.

At least 37 records · Page 2Linked to original sources

The aging process as a modifier of metabolism.

Because elderly adults have distinct metabolic characteristics that alter various nutrient requirements, simple extrapolations of nutrient requirements for younger adults are not warranted. Gastrointestinal function is well preserved with aging regarding the digestion and absorption of macronutrients, but the aging gastrointestinal tract becomes less efficient in absorbing vitamin B-12, vitamin D, and calcium. The new dietary reference intakes considered recent studies in aging adults and concluded that the recommended dietary allowances (RDAs) should be 1200 mg and 15 microg for calcium and vitamin D, respectively, for persons over the age of 70 y. The new RDAs for riboflavin, niacin, thiamine, folate, vitamin B-6, and vitamin B-12 are not different for persons in the oldest age category (>70 y) than for those aged 51-70 y. Because this is a quickly advancing field, it will be important to closely follow new research on nutrient requirements and aging over the next several years.

Absorption↗

Effects of physiological versus pharmacological beta-carotene supplementation on cell proliferation and histopathological changes in the lungs of cigarette smoke-exposed ferrets.

There remains a remarkable discordance between the results of observational epidemiological studies and intervention trials using beta-carotene as a potential chemopreventive agent. One question that needs to be examined is whether the adverse outcomes of human beta-carotene trials are related to the large doses of beta-carotene that were administered. In the present study, ferrets were given a physiological (low) dose or a pharmacological (high) dose of beta-carotene supplementation (0.43 mg versus 2.4 mg/kg body wt/day, which is equivalent to 6 mg versus 30 mg/day in humans) and exposed to cigarette smoke for 6 months. We investigated the effects of these doses of beta-carotene on retinoid concentrations, expression of retinoic acid receptors (RARs), activator protein 1 (AP-1; c-Jun and c-Fos), cyclin D1, proliferating cellular nuclear antigen (PCNA), and histopathological changes in the lungs of both normal and cigarette smoke-exposed ferrets. Thirty-six male ferrets were treated in six groups-control, smoke-exposed (SM), low-dose beta-carotene (LBC), high-dose beta-carotene (HBC), low-dose beta-carotene plus smoke exposure (LBC+SM) or high-dose beta-carotene plus smoke exposure (HBC+SM)-for 6 months. Retinoic acid concentration and RAR beta gene expression, but not expression of RAR alpha and RAR gamma, was reduced in the lung tissue of HBC+SM, HBC, SM and LBC+SM ferrets, but not in that of LBC ferrets, as compared with the control group. Expression of AP-1 and PCNA was greater in HBC+SM, HBC, SM and LBC+SM ferrets, but not in the LBC ferrets, as compared with the control group. Increased amounts of cyclin D1 and keratinized squamous metaplasia were observed in the lung tissue of HBC+SM, HBC and SM groups but not in that of the LBC+SM, LBC or control groups. These data suggest that, in contrast with a pharmacological dose of beta-carotene, a physiological dose of beta-carotene in smoke-exposed ferrets has no potentially detrimental effects and may afford weak protection against lung damage induced by cigarette smoke.

Animals↗

Tissue distribution of lycopene in ferrets and rats after lycopene supplementation.

To determine lycopene uptake and tissue distribution in ferrets (Mustela putorius furo) and F344 rats, we supplemented orally 4.6 mg/(kg body wt.d) lycopene in a tomato oleoresin-corn oil mixture (experimental groups). After 9 wk of supplementation, the animals were killed and blood and organs were collected. Plasma and tissue carotenoids were extracted and measured using HPLC. Mean concentrations of lycopene (nmol/kg wet tissue) in saponified tissues of ferrets were as follows: liver 933, intestine 73, prostate 12.7 and stomach 9.3. Levels of lycopene (nmol/kg wet tissue) in saponified tissue of rats were as follows: liver 14213, intestine 3125, stomach 78.6, prostate 24 and testis 3.9. When these organs were extracted without saponification, the lycopene levels were lower, except for rat testis. All-trans-lycopene was the predominant isomer found in tomato oleoresin and in the majority of rat tissues, whereas cis-lycopenes were predominant in rat prostate and plasma. This pattern was reversed in ferrets. The results show the following: 1) lycopene from tomato oleoresin is absorbed and stored primarily in the liver of both animals; 2) saponification generally improves the extraction of lycopene from most tissues of both animals; 3) cis-lycopene and all-trans-lycopene are the predominant isomers in ferret and rat tissues, respectively; and 4) rats absorb lycopene more effectively than ferrets.

Administration, Oral↗

Retinoids, carotenoids, and human breast cancer cell cultures: a review of differential effects.

Cancer of the breast is the most common incident cancer and cause of death from cancer in women. Several epidemiologic studies have reported a significant inverse relationship between the intake of vitamin A and/or provitamin A-rich foods and the incidence of certain cancers, including breast cancer. A large number of studies have been conducted to determine the effect of retinoids (all-trans-retinoic acid, in particular), and to a lesser extent of carotenoids, on breast cancer using cell culture models. In general, the results of these studies demonstrate beneficial effects of all-trans-retinoic acid on different breast cancer cells. This review compares studies conducted in different laboratories using retinoids and carotenoids as treatments for breast cancer cells and suggests what may be the underlying reasons for the differential effects of these compounds on the same cell lines.

Breast Neoplasms↗

Effect of chronic alcohol consumption on total plasma homocysteine level in rats.

BACKGROUND: Chronic alcoholism in humans is associated with the development of hyperhomocysteinemia, the mechanism of which remains unclear. Among the causes of hyperhomocysteinemia is depletion of folate, vitamin B12, or vitamin B6. Population-based studies indicate that folate is the strongest vitamin determinant of hyperhomocysteinemia and, in most settings, folate supplementation effectively lowers elevated homocysteine levels. However, it is not clear whether folate deficiency is the cause of alcohol-related hyperhomocysteinemia. METHODS: In the present study, 10 male Sprague Dawley rats were fed ethanol-containing Lieber-DeCarli diets with 13 mg of folic acid per kilogram of diet. This represents a folate intake more than 20 times the basal requirement. Ethanol represented 36% of total energy, which yielded a concentration of 6.2% (vol/vol). The same number of rats were pair-fed with isocaloric control diets that contained an identical level of folate in which ethanol was entirely replaced by maltodextrin. RESULTS: At the end of 4 weeks, alcohol-fed rats did not show any significant reduction in plasma or hepatic folate concentrations, plasma pyridoxal-5'-phosphate concentration, or plasma vitamin B12 concentration. On the other hand, alcohol-fed rats were significantly hyperhomocysteinemic (17.24 +/- 4.63 micromol/liter,p < 0.01) compared to the nonalcohol group (10.73 +/- 2.76 micromol/liter). Alcohol-fed rats also had a significantly lower hepatic S-adenosylmethionine and higher hepatic S-adenosylhomocysteine levels. CONCLUSIONS: Chronic alcohol consumption produces hyperhomocysteinemia by a mechanism that is related to interference with one-carbon metabolism, and not through vitamin depletion.

Alcohol Drinking↗

The transport rate of cholera toxin B subunit in the retinofugal pathways of the chick.

This study investigated the transport rate of the tracer, cholera toxin B subunit, within the retinofugal pathway of the chick hatchlings. Following intraocular injections, the chicks were allowed to survive for various time-periods. The immunoreactivity of cholera toxin B subunit was then examined in the retinofugal pathways. Two hours post-injection, retinal ganglion cells began to take up the tracer and transport it to the most rostroventral portion of the optic tectum. After a 4 h survival period, the labeled retinal axons progressively innervated all retinofugal targets. Within the tectum, the labeling density varied from layer to layer with heavily labeled terminals in layer 5b, less label in layer 7 and the most diffuse label in layers 2-4. Scattered labeling was seen in the nucleus dorsolateralis anterior thalami, pars lateralis, the nucleus geniculatus lateralis, pars ventralis, the nucleus basal optic root, the nucleus lateralis anterior thalami, and the pretecal lentiformis nucleus of mesencephalon. After 6- and 8 h survival periods, increased labeling was seen in all retinofugal nuclei. There were increased numbers of retinal terminals in all retinorecipient layers of the tectum. It was noted that some of the retinal axons "overshot" into layers deeper than layer 7. In addition, retinal projections were found scattered throughout the ipsilateral nucleus basal optic root. Maximal labeling in all retinofugal targets was observed at a 10 h survival period. The present study suggests that cholera toxin B subunit can be used to trace retinal axons along their retinofugal paths up to the small terminal zones at a rate of 4.25 mm/h or 102 mm/day. Also, evidence of synchronous retinal terminations in layers 5b and 7 indicates that the transport of cholera toxin B subunit is independent of axon diameters of retinal ganglion cells. Finally, given the changing status of the embryo, the rapid transport of cholera toxin B subunit can be applied for tracing developing pathways.

Animals↗

Fat-soluble nutrient concentrations in different layers of human cataractous lens.

PURPOSE: Recent epidemiologic studies suggest that differential risk for cataract in different areas of the lens may be related to intake of carotenoids, retinol, and tocopherol. Nevertheless, there is little information about differential localization of these nutrients in the lens. To determine the spatial distribution of fat-soluble nutrients within the lens, we determined levels of these nutrients in the epithelium/ outer cortex vs. inner cortex/nucleus. METHODS: Concentrations of carotenoids, retinol, and tocopherol were determined in the epithelial/cortical (younger, more metabolically active tissue) and nuclear (older, less metabolically active) layers of human cataractous lenses (n = 7, 64-75 yr) by reverse-phase high-performance liquid chromatography (HPLC). RESULTS: Lutein/zeaxanthin was the only carotenoid, which was detected, in human lens. Consistent with prior reports, no beta-carotene or lycopene were detected. Concentrations of lutein/zeaxanthin, tocopherol, and retinol in epithelium/cortex tissue were approximately 3-, 1.8-, and 1.3-fold higher than in the older lens tissue. Specifically, the epithelial/cortical lens layer, comprising about half of the tissue, contains 74% of lutein/zeaxanthin (44 ng/g wet wt), 65% of alpha-tocopherol (2227 ng/g wet wt), and 60% of retinol (30 ng/g wet wt). CONCLUSIONS: The data suggest that upon development and aging, there is differential localization of these nutrients. The data are also consistent with a protective role of these nutrients against oxidative damage in the epithelium and cortex of the human lens.

Aged↗

Beta-carotene and other carotenoids as antioxidants.

Carotenoids are natural pigments which are synthesized by plants and are responsible for the bright colors of various fruits and vegetables. There are several dozen carotenoids in the foods that we eat, and most of these carotenoids have antioxidant activity. Beta-carotene has been best studied since, in most countries it is the most common carotenoid in fruits and vegetables. However, in the U.S., lycopene from tomatoes now is consumed in approximately the same amount as beta-carotene. Antioxidants (including carotenoids) have been studied for their ability to prevent chronic disease. Beta-carotene and others carotenoids have antioxidant properties in vitro and in animal models. Mixtures of carotenoids or associations with others antioxidants (e.g. vitamin E) can increase their activity against free radicals. The use of animals models for studying carotenoids is limited since most of the animals do not absorb or metabolize carotenoids similarly to humans. Epidemiologic studies have shown an inverse relationship between presence of various cancers and dietary carotenoids or blood carotenoid levels. However, three out of four intervention trials using high dose beta-carotene supplements did not show protective effects against cancer or cardiovascular disease. Rather, the high risk population (smokers and asbestos workers) in these intervention trials showed an increase in cancer and angina cases. It appears that carotenoids (including beta-carotene) can promote health when taken at dietary levels, but may have adverse effects when taken in high dose by subjects who smoke or who have been exposed to asbestos. It will be the task of ongoing and future studies to define the populations that can benefit from carotenoids and to define the proper doses, lengths of treatment, and whether mixtures, rather than single carotenoids (e.g. beta-carotene) are more advantageous.

Animals↗

A randomized trial of Lactobacillus acidophilus BG2FO4 to treat lactose intolerance.

BACKGROUND: Lactose intolerance is the most common disorder of intestinal carbohydrate digestion. Lactobacillus acidophilus BG2FO4 is a strain of lactobacilli with properties of marked intestinal adherence and high beta-galactosidase activity. OBJECTIVE: This study was designed to determine whether oral feeding of Lactobacillus acidophilus BG2FO4 leads to a lactose-tolerant state. DESIGN: We studied 42 subjects with self-reported lactose intolerance and performed breath-hydrogen tests to determine whether they were lactose maldigesters. Subjects with established lactose maldigestion (n = 24) were invited to be randomly assigned to an omeprazole-treated (hypochlorhydric) group or a non-omeprazole-treated group, but 6 subjects chose not to participate. All randomly assigned subjects (n = 18) ingested Lactobacillus acidophilus BG2FO4 twice per day for 7 d and stool samples were collected. Breath-hydrogen tests were performed and symptom scores were recorded at baseline and after lactobacilli ingestion. RESULTS: Lactose maldigestion was established in 24 of 42 subjects (57%) with self-reported lactose intolerance. In 18 lactose-maldigesting subjects, overall hydrogen production and symptom scores after ingestion of Lactobacillus acidophilus BG2FO4 were not significantly different from baseline values. Live Lactobacillus acidophilus BG2FO4 was recovered in stool samples from 7 subjects. CONCLUSIONS: Lactose intolerance is overreported in subjects with gastrointestinal symptoms after lactose ingestion. Treatment of lactose-maldigesting subjects with and without hypochlorhydria with Lactobacillus acidophilus BG2FO4 for 7 d failed to change breath-hydrogen excretion significantly after lactose ingestion.

Adult↗

Assessment of total body stores of vitamin A in Guatemalan elderly by the deuterated-retinol-dilution method.

BACKGROUND: Deuterated retinol dilution (DRD) gives quantitative estimates of total body stores of vitamin A. OBJECTIVES: In elderly people, we studied 1) the time when an oral dose of deuterated vitamin A equilibrates with body stores, 2) whether serum ratios of deuterated to nondeuterated retinol (D:H) at 3 or 6 d postdosing predicted body stores, and 3) the ability of DRD to detect changes in the size of the body vitamin A pool. DESIGN: A 10-mg oral dose of [2H4]retinyl acetate was administered to 60-81-y-old Guatemalans (n = 47); percentage enrichment of serum retinol with deuterated retinol was determined at 1-3 time points per subject at 3, 6, 7, 14, 20, 21, and 54 d. In subjects from whom blood was obtained at 3 and 21 d (n = 15) and at 6 and 20 d (n = 9), total body stores were calculated by using the formula of Furr et al (Am J Clin Nutr 1989;49:713-6) with 21- or 20-d data and correlated with serum D:H at 3 or 6 d postdosing. Nine subjects received diets containing 982+/-20 microg RE (x+/-SEM) plus 800 microg RE as retinyl acetate supplements for 32 d. DRD, serum retinol, and relative dose response were used to assess vitamin A status before and after the intervention. RESULTS: Deuterated retinol equilibrated with the body pool by 20 d postdosing. Vitamin A supplementation for 32 d increased body stores, although unexplained exaggerated increases were seen in some subjects. An inverse linear relation was found between estimates of body stores and serum D:H at 3 d postdosing (r = -0.75, P = 0.002); at 6 d postdosing, the correlation was weaker. CONCLUSIONS: DRD can detect changes in total body stores of vitamin A, although factors affecting serum D:H need to be elucidated. Serum D:H 3 d postdosing might be used as an early indicator of total body stores of vitamin A, although a predictive equation will need to be developed.

Administration, Oral↗

Green and yellow vegetables can maintain body stores of vitamin A in Chinese children.

BACKGROUND: Vitamin A activity of plant provitamin A carotenoids is uncertain. OBJECTIVE: The objective was to determine whether plant carotenoids can sustain or improve vitamin A nutrition during the fall season in kindergarten children in the Shandong province of China. DESIGN: The serum vitamin A concentration of 39% of the children was <1.05 micromol/L and of 61% of the children was > or = 1.05 micromol/L. For 5 d/wk for 10 wk, 22 children were provided approximately 238 g green-yellow vegetables/d and 34 g light-colored vegetables/d. Nineteen children maintained their customary dietary intake, which included 56 g green-yellow vegetables/d and 224 g light-colored vegetables/d. Octadeuterated and tetradeuterated vitamin A were given before and after the interventions, respectively, and their enrichments in the plasma were determined by gas chromatography-mass spectrometry. Serum retinol and carotenoid concentrations were measured by HPLC. RESULTS: Carotenoid nutrition improved after consumption of green-yellow vegetables. Serum concentrations of retinol were sustained in the group fed green-yellow vegetables but decreased in the group fed light-colored vegetables (P < 0.01). The isotope-dilution tests confirmed that total-body vitamin A stores were sustained in the group fed green-yellow vegetables, but decreased 27 micromol (7700 microg retinol) per child, on average, in the group fed light-colored vegetables (P < 0.06). CONCLUSION: Green-yellow vegetables can provide adequate vitamin A nutrition in the diet of kindergarten children and protect them from becoming vitamin A deficient during seasons when the provitamin A food source is limited.

Analysis of Variance↗

Methods for assessing the biological effects of specific plant components.

Until very recently, phytonutrient research was the province of natural product chemists and consisted of primarily anecdotal clinical references. In recent years, an extensive set of qualitative and semi-quantitative dietary epidemiologic data has been developed. This developing base of epidemiologic data is now being supplemented by biochemical, mechanistic, and genetic epidemiology of a more quantitative nature. As we seek to understand the mechanisms that explain a large body of epidemiologic evidence, newer laboratory methods continue to be developed. Though there is a continuing need for even more discriminating nutrition epidemiology to drive the basic research in this area forward, the focus of in vitro, animal and clinical (human) studies must continue to be refined, and appropriate biomarkers for chronic and acute (death) disease end-points must be developed.

Animals↗

Procarcinogenic and anticarcinogenic effects of beta-carotene.

A large body of observational epidemiologic studies has consistently demonstrated that individuals who eat more fruits and vegetables, which are rich in carotenoids, and people who have higher serum beta-carotene levels have a lower risk of cancer, particularly lung cancer. In contrast to these observations, two human intervention studies that used high-dose beta-carotene supplements reported an increased risk for lung cancer among smokers. Recently, in vitro and in vivo studies have shed light on the present conundrum regarding the potential chemopreventive activity of beta-carotene; that is, beta-carotene itself may act as an anticarcinogen, but its oxidized products may facilitate carcinogenesis. These studies support the hypothesis that the carcinogenic response to high-dose beta-carotene supplementation reported in the human intervention trials is related to the instability of the beta-carotene molecule in the free radical-rich environment in the lungs of cigarette smokers. This is especially possible because smoke also causes decreased tissue levels of other antioxidants, such as ascorbate and alpha-tocopherol, which normally have a stabilizing effect on the unoxidized form of beta-carotene. Nutritional intervention using a combination of antioxidants (beta-carotene, alpha-tocopherol, and vitamin C) as anticarcinogenic agents could be an appropriate way to rationally and realistically reduce cancer risk.

Antioxidants↗

Vitamin B12 deficiency in the elderly.

Vitamin B12 deficiency is estimated to affect 10%-15% of people over the age of 60, and the laboratory diagnosis is usually based on low serum vitamin B12 levels or elevated serum methylmalonic acid and homocysteine levels. Although elderly people with low vitamin B12 status frequently lack the classical signs and symptoms of vitamin B12 deficiency, e.g. megaloblastic anemia, precise evaluation and treatment in this population is important. Absorption of crystalline vitamin B12 does not decline with advancing age. However, compared with the younger population, absorption of protein-bound vitamin B12 is decreased in the elderly, owing to a high prevalence of atrophic gastritis in this age group. Atrophic gastritis results in a low acid-pepsin secretion by the gastric mucosa, which in turn results in a reduced release of free vitamin B12 from food proteins. Furthermore, hypochlorhydria in atrophic gastritis results in bacterial overgrowth of the stomach and small intestine, and these bacteria may bind vitamin B12 for their own use. The ability to absorb crystalline vitamin B12 remains intact in older people with atrophic gastritis. The 1998 recommended daily allowance for vitamin B12 is 2.4 micrograms, but elderly people should try to obtain their vitamin B12 from either supplements or fortified foods (e.g. fortified ready-to-eat breakfast cereals) to ensure adequate absorption from the gastrointestinal tract. Because the American food supply is now being fortified with folic acid, concern is increasing about neurologic exacerbation in individuals with marginal vitamin B12 status and high-dose folate intake.

Aging↗

[Vegetables rich in carotenoids on the vitamin A status of children].

Vitamin A (VA) deficiency is still an important nutritional problem in our country. In order to determine whether plant carotenoids ingestion can improve VA nutrition, a study by using yellow and dark green vegetables was conducted in two classes of a kindergarten for ten weeks in September through December in 1996. The VA nutritional status was marginal to adequate among 41 children (5.3-6.6 year-old), and serum retinols in 39% of these children were below 0.30 mg/L. Each child in class A was provided with about 238 g/d of green and yellow vegetables (spinach, Chinese chive, carrots, and red yams) and 34 g/d of light colored vegetables (cabbage, Chinese cabbage, potato, cucumber, turnip and winter melon). Each child in class B consumed the usual diet with only 56 g/d of green and yellow vegetables and 193 g/d of light colored vegetables. Serum retinol concentration collected before and after the intervention were used to assess VA nutritional status. The results showed that vitamin A nutrition was improved by increasing the intake of green and yellow vegetables. Serum retinol was sustained in the group fed green and yellow vegetables and decreased in the group fed light colored vegetables. Thus, dietary green and yellow vegetables could provide adequate VA nutrition in these children.

Carotenoids↗

Chronic alcohol intake reduces retinoic acid concentration and enhances AP-1 (c-Jun and c-Fos) expression in rat liver.

Chronic ethanol intake may interfere with retinoid signal transduction by inhibiting retinoic acid synthesis and by enhancing activator protein-1 (AP-1) (c-Jun and c-Fos) expression, thereby contributing to malignant transformation. To determine the effect of ethanol on hepatic retinoid levels, retinoic acid receptors (RARs) and AP-1 (c-Jun and c-Fos) gene expression, chronic ethanol (36% of total calorie intake) pair-feeding was conducted on rats for a 1-month period. Retinoic acid, retinol, and retinyl ester concentrations in both liver and plasma were examined by using high-performance liquid chromatography (HPLC). Both retinoic acid receptor (alpha, beta, gamma) and AP-1 (c-Jun and c-Fos) expression in the rat liver were examined by using Western blot analysis. Treatment with high-dose ethanol led to a significant reduction of retinoic acid concentration in both the liver and the plasma (11- and 8.5-fold reduction, respectively), as compared with animals pair-fed an isocaloric control diet containing the same amount of vitamin A. Similar to the retinoic acid reductions, both retinol and retinyl palmitate levels in the livers of the alcohol-fed group decreased significantly, but in smaller fold reduction (6.5- and 2.6-fold reduction, respectively). Ethanol did not modulate the expression of RARalpha, -beta, and -gamma genes in the liver. However, chronic alcohol feeding enhanced AP-1 (c-Jun and c-Fos) expression by 7- to 8-fold, as compared with the control group. These data suggest that functional downregulation of RARs by inhibiting biosynthesis of retinoic acid and up-regulation of AP-1 gene expression may be important mechanisms for causing malignant transformation by ethanol.

Animals↗