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Biomedical subjects

John W Finley

Publications and source records attributed to John W Finley.

At least 19 recordsLinked to original sources

Determination of selenium bioavailability from wheat mill fractions in rats by using the slope-ratio assay and a modified torula yeast-based diet.

Selenium is an essential mineral micronutrient for animals, and significant evidence supports an association between supranutritional Se intake and a reduction in the incidence of some forms of cancer. Thus, supplemental Se intake may provide an avenue for reducing cancer incidence. However, an important issue to consider is the form of Se that should be provided in such a supplement, because the bioavailability and bioactivity of Se can vary dramatically depending on the chemical form in which it is delivered. Because wheat products are the largest source of Se in U.S. diets, the absorption of Se was evaluated in different fractions of milled wheat that exhibits very high Se levels, owing to its production on naturally Se-rich soils. An experiment was conducted to determine the bioavailability of Se from three milled fractions of high-Se wheat. The method used was the slope-ratio assay, which measures the ability of Se from the wheat fractions to regenerate Se-dependent enzyme activities and tissue Se concentrations in Se-deficient rats. The responses generated from wheat Se were compared to a standard response curve generated by feeding graded amounts of Se as sodium selenite (Na2SeO3; NaSelenite) or selenomethionine (SeMet) in an AIN-93G-Torula yeast-based diet. Results showed that Se from wheat flour ( approximately 75% extraction) was nearly 100% available by a number of measures including plasma, liver, kidney, and muscle Se concentrations and liver and erythrocyte Se-dependent enzyme activities when compared with similar measures in rats fed NaSelenite or SeMet. However, on the basis of similar criteria, Se from wheat shorts was only about 85% available and that from wheat bran was about 60% available for absorption. These results indicate that high-Se wheat products, mainly those made from refined flour alone, might be particularly well suited for use as dietary Se supplements.

Animals↗

Allyl sulfur compounds from garlic modulate aberrant crypt formation.

The health benefits of garlic, including inhibition of carcinogenesis, are supported by several epidemiologic and laboratory findings. Garlic's sulfur components have been reported to suppress experimentally induced tumor incidence in several organs, including the colon. Studies in humans also suggest that dietary garlic constituents reduce the risk of colorectal adenomatous polyps, which are considered precursors to colon cancer. Aberrant crypt foci (ACF) are proposed to be early preneoplastic lesions of adenoma-carcinoma in humans and chemically induced colon cancer in rodents. In preclinical studies, both water- and lipid-soluble allyl sulfur compounds arising from processed garlic inhibited ACF. The response to these allyl sulfur compounds appears to depend on several factors, including the speciation, quantity, and duration provided.

Adenoma↗

Bioavailability of selenium from foods.

Selenium (Se), an essential nutrient, is needed for activity of several important proteins. Additionally, the consumption of Se in amounts that exceed the Recommended Dietary Allowance (RDA) may protect against prostate and colorectal cancer. Supplemental Se may be acquired through the diet, but Se bioavailability depends on the source. Therefore, dietary advice concerning improvement of Se intake depends on characterization of Se bioavailability from Se-containing food sources.

Antioxidants↗

Aqueous extracts of selenium-fertilized broccoli increase selenoprotein activity and inhibit DNA single-strand breaks, but decrease the activity of quinone reductase in Hepa 1c1c7 cells.

Depending on growth conditions, broccoli may be enriched in the isothiocyanate sulforaphane and/or the mineral selenium (Se); both compounds may play an important role in the reduction of intracellular oxidative stress and chronic disease prevention. Sulforaphane up-regulates transcription of Phase II detoxification proteins (e.g. quinone reductase [QR]), whereas Se is needed for the production of thioredoxin reductase (TR) and glutathione peroxidase-1 (GPx1), both of which exhibit antioxidant activity. The objective of the present study was to determine whether the fertilization of broccoli with Se increases the antioxidant ability of broccoli. Hydrogen peroxide-induced DNA single-strand breaks (measured by single cell electrophoresis, Comet assay) and activity of antioxidant enzymes (GPx, TR and QR) were measured in mouse hepatoma cells (Hepa 1c1c7 cells) treated with purified sulforaphane, sodium selenite or extracts of selenized broccoli. When supplied separately as chemically pure substances, sodium selenite was more effective than sulforaphane for reduction of single-strand breaks. Se-fertilized broccoli extracts were the most effective for reduction of DNA single-strand breaks, and extracts that contained 0.71 microM Se and 0.08 microM sulforaphane inhibited 94% of DNA single-strand breaks. A significant positive association (r = 0.81, p = 0.009) between GPx1 activity and inhibition of DNA single-strand breaks as well as a 24h lag time between addition of Se, sulforaphane or broccoli extract and inhibition of single-strand breaks suggests that some of the antioxidant protection is mediated through selenoproteins. Conversely, fertilization of broccoli with Se decreased the ability of broccoli extract to induce QR activity. These results demonstrate that Se and sulforaphane, alone or as a component of broccoli, may help decrease oxidative stress. They further suggest that Se is the most important for decreasing oxidative stress, but maximizing the Se content of broccoli also may compromise its ability to induce Phase II detoxification proteins.

Antioxidants↗

Effect of selenium fertilizer on free amino acid composition of broccoli (Brassica oleracea Cv. Majestic) determined by gas chromatography with flame ionization and mass selective detection.

Selenium-enriched broccoli florets, harvested from plants grown on soil fertilized with four levels of sodium selenate, were evaluated for their free amino acid composition using alkylchlorformate derivatization, solid-phase extraction, and GC-FID or GC-MS. The selenium-enriched florets contained 0.4 (control), 5.7 (treatment A), 98.6 (treatment B), and 879.2 (treatment C) microg/g Se (dry weight). Twenty-one free amino acids were identified in the control and all three treatments. The total free amino acid content of the broccoli florets ranged from 178 mmol/kg (dry weight), for the control, to 479 mmol/kg (dry weight), for treatment C. Broccoli from treatment C contained the highest level of Se, had the most total free amino acids, and had an extremely high level of glutamine (Gln) when compared to the control and the other two treatments. In general, the smallest addition of Se to the soil (treatment A) induced increased levels of all detectable amino acids when compared to the control, whereas increased additions of Se (treatments B and C) produced mixed responses. Florets from treatment A contained the highest essential amino acid content.

Amino Acids↗

Phytochemicals in broccoli transcriptionally induce thioredoxin reductase.

Previous studies have demonstrated transcriptional induction of thioredoxin reductase (TR) by sulforaphane (SF) purified from broccoli; the mechanism of induction is via an antioxidant response element (ARE) in the promoter region of the gene. The purpose of the present study was to further characterize the induction of TR by compounds in broccoli and to determine if SF is the primary compound responsible for this induction. Aqueous extracts were made from broccoli with low or high concentrations of selenium (Se) and/or SF and tested in a TR/luciferase reporter gene system in cultured cells. Phenolic acids commonly found in broccoli (sinapic, caffeic, ferulic, and protocatechuic) and ascorbic acid were also tested. At SF concentrations of < or =2 microM, broccoli extracts and purified SF activated transcription equally well, but 4 microM SF in broccoli extracts resulted in almost twice as much induction as 4 microM purified SF (P < 0.05). All broccoli extracts significantly increased TR and quinone reductase activity relative to controls (P < 0.05), but only extracts highest in Se increased glutathione peroxidase activity (P < 0.05). No phenolic acids tested induced transcription, but ascorbic acid resulted in modest dose-dependent induction between 0 and 120 microM (P < 0.001). These data suggest that SF accounts for most of the ARE-activated transcriptional induction of antioxidant genes by broccoli.

Ascorbic Acid↗

Proposed criteria for assessing the efficacy of cancer reduction by plant foods enriched in carotenoids, glucosinolates, polyphenols and selenocompounds.

BACKGROUND AND AIMS: The cancer-protective properties of vegetable consumption are most likely mediated through 'bioactive compounds' that induce a variety of physiologic functions including acting as direct or indirect antioxidants, regulating enzymes and controlling apoptosis and the cell cycle. The 'functional food' industry has produced and marketed foods enriched with bioactive compounds, but there are no universally accepted criteria for judging efficacy of the compounds or enriched foods. SCOPE: Carotenoids, glucosinolates, polyphenols and selenocompounds are families of bioactive compounds common to vegetables. Although numerous studies have investigated the agricultural and human health implications of enriching foods with one or more of these compounds, inadequate chemical identification of compounds, lack of relevant endpoints and inconsistencies in mechanistic hypotheses and experimental methodologies leave many critical gaps in our understanding of the benefits of such compounds. This review proposes a decision-making process for determining whether there is reasonable evidence of efficacy for the both the compound and the enriched food. These criteria have been used to judge the evidence of efficacy for cancer prevention by carotenoids, polyphenols, glucosinolates and selenocompounds. CONCLUSIONS: The evidence of efficacy is weak for carotenoids and polyphenols; the evidence is stronger for glucosinolates and lycopene, but production of enriched foods still is premature. Additionally there is unacceptable variability in the amount and chemical form of these compounds in plants. The evidence of efficacy for selenocompounds is strong, but the clinical study that is potentially the most convincing is still in progress; also the variability in amount and chemical form of Se in plants is a problem. These gaps in understanding bioactive compounds and their health benefits should not serve to reduce research interest but should, instead, encourage plant and nutritional scientists to work together to develop strategies for improvement of health through food.

Animals↗

The case for strategic international alliances to harness nutritional genomics for public and personal health.

Nutrigenomics is the study of how constituents of the diet interact with genes, and their products, to alter phenotype and, conversely, how genes and their products metabolise these constituents into nutrients, antinutrients, and bioactive compounds. Results from molecular and genetic epidemiological studies indicate that dietary unbalance can alter gene-nutrient interactions in ways that increase the risk of developing chronic disease. The interplay of human genetic variation and environmental factors will make identifying causative genes and nutrients a formidable, but not intractable, challenge. We provide specific recommendations for how to best meet this challenge and discuss the need for new methodologies and the use of comprehensive analyses of nutrient-genotype interactions involving large and diverse populations. The objective of the present paper is to stimulate discourse and collaboration among nutrigenomic researchers and stakeholders, a process that will lead to an increase in global health and wellness by reducing health disparities in developed and developing countries.

Animals↗

Cultivation conditions and selenium fertilization alter the phenolic profile, glucosinolate, and sulforaphane content of broccoli.

Broccoli is a food often consumed for its potential health-promoting properties. The health benefits of broccoli are partly associated with secondary plant compounds that have bioactivity; glucosinolates and phenolic acids are two of the most abundant and important in broccoli. In an effort to determine how variety, stress, and production conditions affect the production of these bioactive components broccoli was grown in the greenhouse with and without selenium (Se) fertilization, and in the field under conventional or organic farming procedures and with or without water stress. High-performance liquid chromatography/mass spectrometry was used to separate and identify 12 primary phenolic compounds. Variety had a major effect: There was a preponderance of flavonoids in the Majestic variety, but hydroxycinnamic esters were relatively more abundant in the Legacy variety. Organic farming and water stress decreased the overall production of phenolics. Se fertilization increased glucosinolates in general, and sulforaphane in particular, up to a point; above that Se fertilization decreased glucosinolate production. Organic farming and water stress also decreased glucosinolate production. These data show environmental and genetic variation in phenolics and glucosinolates in broccoli, and warn that not all broccoli may contain all health-promoting bioactive components. They further show that selection for one bioactive component (Se) may decrease the content of other bioactive components such as phenolics and glucosinolates.

Agriculture↗

Selenium bioavailability from buckwheat bran in rats fed a modified AIN-93G torula yeast-based diet.

Selenium (Se) is an essential nutrient for humans and animals. The Se RDA for adult humans is 55 mug/d; however, dietary amounts as high as 200 mug/d in the highly available form of selenomethionine in yeast were shown to reduce the incidence of certain cancers. A number of natural foods contain relatively high amounts of Se; for the most part, however, the availability of food Se for absorption and utilization is unknown. This experiment was conducted to determine the bioavailability of Se from a high-protein, high-fiber bran-isolate of buckwheat groats that contains Se. The method used was based on the ability of Se from buckwheat bran to restore Se-dependent enzyme activities and tissue Se concentrations in Se-deficient rats. The responses produced from buckwheat bran Se were compared with a standard response curve generated by feeding graded amounts of Se as sodium selenite (Na(2)SeO(3); Na selenite) or selenomethionine (SeMet) in a newly reformulated AIN-93G-Torula yeast diet with a more balanced nutrient composition than older diets of this nature. Relative bioavailability was determined by using the slope-ratio assay method for enzyme data, or the parallel lines assay method for tissue Se concentration data. Results showed that Se availability from buckwheat bran based on the restoration of plasma Se was 70-80% as high as Na selenite or SeMet. However, when based on the restoration of muscle Se, buckwheat bran was 90% as high as Na selenite, but only 60% as high as SeMet. When using the ability of dietary Se to restore whole blood and liver glutathione peroxidase activity, buckwheat bran Se was 75-80% as high as Na selenite or SeMet. However, for the restoration of liver thioredoxin reductase, buckwheat bran Se was only 40% as high as Na selenite and 70% as high as SeMet. The relative bioavailability of Se from buckwheat bran with all variables considered was approximately 73% whether measured against Na selenite or SeMet. Although some variables indicated low bioavailability of Se from buckwheat bran, other factors such as Se speciation in the bran, digestibility of the bran, the cooking process, and combinations with other foods in the diet should be considered and analyzed before firm conclusions can be reached.

Animals↗

Selenium enrichment of broccoli: interactions between selenium and secondary plant compounds.

Multiple components of broccoli, such as sulforaphane (Sf) and phenolic acids, may inhibit cancer. Additionally, broccoli can accumulate selenium (Se), and Se has been demonstrated to reduce the risk of cancer. Studies were conducted to determine whether enhancement of broccoli with Se would produce a plant with superior health benefits. Although increasing the concentration of Se in broccoli from <1.0 to >800 microg/g resulted in inhibition of colon cancer in rats, it also decreased the Sf content by >80% and inhibited production of most phenolic acids. The inclusion of Se-enriched broccoli in the diet of rats induced the activity of the selenoprotein thioredoxin reductase beyond the maximum activity induced by Se alone. These results emphasize the complex interactions of bioactive chemicals in a food; attempts to maximize one component may affect accumulation of another, and consumption of high amounts of multiple bioactive compounds may result in unexpected metabolic interactions within the body.

Anticarcinogenic Agents↗

Selenium accumulation in plant foods.

Selenium (Se) is an essential nutrient, and Se deficiency is associated with disease conditions and general impairment of the immune system. Supplementation of Se to humans already consuming the RDA may help to prevent certain cancers. A convincing argument can be made for augmenting the food supply with Se, and Se-enhanced plants may be the best means of accomplishing this. Plants accumulate varying amounts of Se in different chemical forms; some plants accumulate Se in direct relationship to the amount available from the soil, whereas others (Se-accumulators) may accumulate Se in concentrations many orders of magnitude above that in the soil. There are many different chemical forms of Se in plants, and the form partially dictates the metabolism of Se by the animal that consumes the plant. The Se content and the chemical form of Se within plants may be altered by manipulation of plant genetics or by agricultural production conditions. However, attempts to maximize Se in plants may have unintended consequences and must be carefully monitored.

Adolescent↗

Evaluation of the pulsed discharge helium ionization detector for the analysis of hydrogen and methane in breath.

Under the appropriate separation conditions the pulsed discharge helium ionization detector (PDHID) was used to detect hydrogen and methane separated from the matrix components of human breath samples. The sensitivity of this method is over an order of magnitude better than published methods using a flame ionization detector (FID) and a thermal conductivity detector (TCD), and has the further advantage of detecting both analytes with only one detector. Limits of detection were 0.3 ppmv for both hydrogen and methane and the method had a linear dynamic range (LDR) of three orders of magnitude (0.3-400 ppm, v/v). The PDHID was also compared to the FID and the TCD in regard to selectivity, sensitivity and reproducibility for high-speed gas chromatography (HSGC). It was shown that the PDHID is as sensitive as the FID for fast separations but is limited by the difficulty of resolving analyte peaks from O2 and N2. The PDHID was at least three orders of magnitude more sensitive than the TCD for all of the analytes examined.

Breath Tests↗

Manganese alters mitochodrial integrity in the hearts of swine marginally deficient in magnesium.

It was previously reported that pigs marginally deficient in magnesium (Mg) and fed diets high in manganese (Mn) died suddenly with signs of sudden cardiac death. Manganese, which has properties similar to Mg, may exacerbate Mg-deficiency and be accumulated by mitochondria resulting in ultrastructural damage. The objective of this study was to determine whether deaths of the type previously observed were mediated by adverse interactions of Mn and Mg resulting in ultrastructural damage to the myocardium, alterations in electrocardiographic recordings and tissue retention of Mn, Mg and calcium (Ca). Forty-eight pigs were fed one of six diets in a 2 X 3 factorial arrangement of Mg (100 or 1000 mg Mg/kg) and Mn (5, 50 or 500 mg Mn/kg) for 8 weeks. Left ventricle muscle samples were collected for examination by transmission electron microscopy. No differences in heart muscle ultrastructure were observed between pigs fed low and adequate dietary Mg. However, marked myocardial necrosis and mitochondrial swelling were observed in pigs fed high dietary Mn when combined with low Mg. Feeding low dietary Mg elevated minimum (P < 0.01), maximum (P < 0.05) and average (P < 0.001) heart rates. Low dietary Mg resulted in a 55% probability of a ventricular beat being recorded (P = 0.05) and lower Mg (P < 0.02) and Ca (P < 0.04) contents in heart atria and ventricles. These results suggest that high Mn, when fed in combination with low Mg, disrupts mitochondrial ultrastructure and is associated with the sudden deaths previously reported.

Animals↗

Does environmental exposure to manganese pose a health risk to healthy adults?

Manganese is an essential nutrient that also may be toxic at high concentrations. Subjects chronically exposed to manganese-laden dust in industrial settings develop neuropsychological changes that resemble Parkinson's disease. Manganese has been proposed as an additive to gasoline (as a replacement for the catalytic properties of lead), which has generated increased research interest in the possible deleterious effects of environmental exposure to manganese. Low-level exposure to manganese has been implicated in neurologic changes, decreased learning ability in school-aged children, and increased propensity for violence in adults. However, a thorough review of the literature shows very weak cause-and-effect relationships that do not justify concern about environmental exposure to manganese for most of the North American population.

Behavior↗

Cruciferous vegetables: cancer protective mechanisms of glucosinolate hydrolysis products and selenium.

Dietetic professionals urge Americans to increase fruit and vegetable intakes. The American Institute of Cancer Research estimates that if the only dietary change made was to increase the daily intake of fruits and vegetables to 5 servings per day, cancer rates could decline by as much as 20%. Among the reasons cited for this health benefit are that fruits and vegetables are excellent sources of fiber, vitamins, and minerals. They also contain nonnutritive components that may provide substantial health benefits beyond basic nutrition. Examples of the latter are the glucosinolate hydrolysis products, sulforaphane, and indole-3-carbinol. Epidemiological studies provide evidence that the consumption of cruciferous vegetables protects against cancer more effectively than the total intake of fruits and vegetables. This review describes the anticarcinogenic bioactivities of glucosinolate hydrolysis products, the mineral selenium derived from crucifers, and the mechanisms by which they protect against cancer. These mechanisms include altered estrogen metabolism, protection against reactive oxygen species, altered detoxification by induction of phase II enzymes, decreased carcinogen activation by inhibition of phase I enzymes, and slowed tumor growth and induction of apoptosis.

Anticarcinogenic Agents↗

Bioavailability of selenium from meat and broccoli as determined by retention and distribution of 75Se.

The concentration of selenium (Se), an essential nutrient, is variable in foods, depending, in part, on how and where foods are produced; some foods accumulate substantial amounts of Se when produced on high-Se soils. The chemical form of Se also differs among foods. Broccoli is a Se-accumulating plant that contains many methylated forms of Se, and Se bioavailability from broccoli has been reported to be low. Red meats such as pork or beef could accumulate Se when the animal is fed high-Se diets, and Se from such meats has been reported to be highly bioavailable for selenoprotein synthesis. In a further attempt to characterize the utilization of Se from broccoli and meats such as pork or beef, we have fed rats diets adequate (0.1 microg Se/g diet) in Se or high in Se (1.5 microg S/g diet), with the Se source being either high-Se broccoli or beef. Rats were then given test meals of broccoli or pork intrinsically labeled with 75Se. When dietary Se was nutritionally adequate (0.1 microg/g diet), more 75Se from pork than broccoli was retained in tissues; however, there were no significant differences in whole-body retention when dietary Se was high (1.5 microg/g diet). A significantly greater percentage of 75Se from broccoli than pork was excreted in the urine and dietary Se did not affect urinary excretion of broccoli 75Se, but the amount excreted from pork varied directly with dietary Se intake. Radiolabeled 75Se derived from pork effectively labeled selenoproteins in all tissues examined, but 75Se from broccoli was undetectable in selenoproteins. These differences in retention and distribution of Se from broccoli or pork are consistent with reported differences in bioavailability of Se from beef and broccoli. They also suggest that there are fewer differences in bioavailability when Se is consumed in supranutritional amounts.

Animal Feed↗

Speciation of selenium compounds from high selenium broccoli is affected by the extracting solution.

The speciation of selenium compounds from high selenium broccoli (876 microg/g) depends on the extraction conditions. Twenty-seven extraction conditions were explored involving nine different buffering systems between pH 1 and pH 9. In nonbuffered extractions of broccoli, more than 40% of the spiked Se-methylselenocysteine was not recovered in the filtered solution. However, in buffered extractions, losses for Se-methylselenocysteine ranged from 10 to 20%. Mass balance indicated that approximately 30% of naturally occurring selenium in broccoli samples was volatilized and lost to the atmosphere when buffered extractions were made. Solid phase extractions indicated that the polarity of selenium compounds in solution was also dependent on the extracting solution. High-pressure liquid chromatography coupled to an inductively coupled plasma mass spectrometer was used to show that selenium compounds extracted from broccoli reacted with the extracting solution. Compound identities were assigned by matching retention times to standards of selenite, selenate, methylseleninic acid, Se-methylselenocysteine, selenomethionine, and the selenonic acids of Se-methylselenocysteine and selenomethionine. Changes in speciation were analyte-, pH-, and buffer-dependent, but generally, a higher pH resulted in more highly oxidized selenium compounds. For valid conclusions to be drawn from the analytical data, the extraction conditions should match the conditions present in the matrix or be specified for a particular application such as a simulated gastrointestinal digestion.

Brassica↗