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Biomedical subjects

O A Levander

Publications and source records attributed to O A Levander.

At least 19 recordsLinked to original sources
PubMed1992

Selenium and sulfur in antioxidant protective systems: relationships with vitamin E and malaria.

The metabolic relationships among the antioxidant nutrients selenium, sulfur, and vitamin E are particularly close. Selenium and vitamin E have long been known to spare one another in certain nutritional diseases of animals, and selenium has been considered to have a key antioxidant defense function as a component of glutathione peroxidase. However, the antioxidant role of glutathione peroxidase has been questioned and new proteins containing selenium have been identified: phospholipid hydroperoxide glutathione peroxidase, selenoprotein P, and iodothyronine deiodinase. Glutathione peroxidase activity independent of selenium resides in the glutathione S-transferases. Glutathione participates in both enzymatic and nonenzymatic antioxidant defense systems. Some low-molecular weight selenium compounds (e.g., ebselen) exhibit glutathione peroxidase-like action. Certain low molecular weight thiols decompose peroxides nonenzymatically (e.g., the ovothiols). Murine malaria appears to be a useful experimental model for investigating interrelationships of selenium and vitamin E. Vitamin E deficiency protects against the parasite, especially when the mice are concurrently fed peroxidizable fat such as fish or linseed oils. Selenium deficiency, on the other hand, has little or no protective effect against the parasite. Any practical utility of pro-oxidant diets in combating human malaria remains to be determined.

Antioxidants↗
PubMed1991

Effect of aging and diet on proton NMR spectra of rat urine.

500 MHz 1H NMR studies of rat urine are used to assess metabolic changes resulting from aging (0.5-20 months) and changes in diet (casein versus chow). Aging rats fed chow diets decrease their excretion of citrate and 2-oxoglutarate, while the output of taurine and creatinine increases. Only young rats (1 month or less postweaning) excrete significant amounts of betaine and trimethylamine-N-oxide. Rats fed casein diets for 1 month postweaning do not excrete 2-oxoglutarate and excrete lower levels of hippurate, succinate, and citrate compared to rats fed chow diets. They also excrete N-methylnicotinamide. These high resolution proton NMR studies provide metabolic profiles which are not readily available by other techniques.

Aging↗
PubMed1991

Selenium in diet, blood, and toenails in relation to human health in a seleniferous area.

To determine whether high dietary selenium intake was associated with adverse effects, selenium in diet, blood, and toenails was studied in relation to human health in adults residing in western South Dakota and eastern Wyoming. Over a 2-y period 142 subjects were recruited from households selected at random and from ranches where unusually high selenium intakes were suspected. Subjects completed health questionnaires, underwent physical examinations, provided blood samples for clinical assessment, and provided blood, urine, toenails, and duplicate-plate food collections for selenium analysis. About half of the 142 free-living subjects had selenium intakes greater than 2.54 mumol/d (200 micrograms/d) (range 0.86-9.20 mumol/d, or 68-724 micrograms/d). Physical findings characteristic of selenium toxicity were not present nor were clinically significant changes in laboratory tests or frequency of symptoms related to selenium in the blood, toenails, or diet. We found no evidence of toxicity from selenium in subjects whose intake was as high as 9.20 mumol/d (724 micrograms/d).

Adult↗
PubMed1991

Human [74Se]selenomethionine metabolism: a kinetic model.

A study was undertaken to investigate the pharmacokinetics of an organically bound form of selenium. Six adults received a single oral 200-micrograms dose of 74Se as L-selenomethionine. A kinetic model was developed to simultaneously account for the appearance and disappearance of the tracer in plasma, urine, and feces. The model included absorption distributed along the gastrointestinal tract, uptake by the liver-pancreas subsystem, enterohepatic recirculation, distribution to two large tissue pools, and transport through four components of the plasma pool. Average turnover time of the plasma components varied from 0.01 to 1.1 d. The turnover time in the liver-pancreas subsystem ranged from 1.6 to 3.1 d. Turnover time ranged from 61 to 86 d in the peripheral tissues with the slowest turnover. The whole-body residence time was approximately five-fold greater than the turnover time of the tissue pool with the slowest turnover, reflecting substantial reutilization of labeled material.

Absorption↗
PubMed1991

Scientific rationale for the 1989 recommended dietary allowance for selenium.

During the past 15 years, our knowledge of human selenium requirements has improved greatly, primarily because of research conducted in the People's Republic of China. Dietary surveys demonstrated that Keshan disease, a juvenile cardiomyopathy, was absent in parts of China where the food supply provided at least 19 and 13 micrograms selenium per day for men and women, respectively. Such intakes can be regarded as minimum daily requirements for selenium. Chinese scientists also carried out a study in an area where Keshan disease was prevalent to determine the amount of dietary selenium needed to maximize the activity of the selenium-containing enzyme, glutathione peroxidase, in plasma. For a man weighing 60 kg, enzymatic activity reached a plateau at selenium intakes of about 40 micrograms per day. These data were used by the US National Research Council as the basis for its 1989 Recommended Dietary Allowance (RDA) for selenium. The RDA was calculated as 70 and 55 micrograms per day for adult men and women, respectively, after correcting for differences in body size and taking into consideration possible individual variations in requirements. This RDA is readily satisfied by typical diets in countries with relatively selenium-rich soils, such as the United States. In selenium-poor areas of the world (eg, China, New Zealand, Scandinavia), diets would not readily furnish such intakes.

Animals↗
PubMed1990

Plasmodium yoelii: comparative antimalarial activities of dietary fish oils and fish oil concentrates in vitamin E-deficient mice.

Feeding vitamin E-deficient diets containing either fish oils such as menhaden, salmon, or anchovy oil or fish oil concentrates based on n-3 ethyl esters or free fatty acids protected mice against Plasmodium yoelii as indicated by decreased parasitemia and improved survival. The fish oil concentrates depressed plasma tocopherol levels more strongly in vitamin E-supplemented mice than the menhaden oil. The free fatty acid concentrate appeared to suppress parasitemia in vitamin E-deficient mice better than the menhaden oil, although ultimate survival was similar in both groups. Dietary manipulation of host antioxidant status offers promise as a possible means of malaria control.

Animals↗
PubMed1990

Nutritional status and growth in juvenile rheumatoid arthritis.

The specific cause of short stature in juvenile rheumatoid arthritis (JRA) is unknown. One hypothesis links altered growth to inadequate dietary intake. In this study, nutritional status was assessed in 34 children with JRA (8 with systemic JRA, 14 with polyarticular JRA, and 12 with pauciarticular JRA) and 9 healthy controls using 3-day diet records, anthropometrics, and biochemical analyses. Differences in growth were found among the three types of JRA. One third of all subjects were at or below the 10th percentile in height for age (these being predominantly among the systemic and polyarticular groups). With few exceptions, the mean dietary intake for calories and essential nutrients was found to be adequate for each of the three groups. However, more than half of those with systemic JRA reportedly consumed less than the recommended caloric intake for their age and weight. No significant correlations were found linking dietary intake to growth percentiles in any of the groups studied. Biochemical abnormalities were found among the systemic and polyarticular groups. These abnormalities included low plasma levels of vitamins A and C, proteins (albumin, prealbumin, and retinol binding protein) and zinc; and increased levels of copper and glutathione peroxidase activity. Plasma selenium and vitamin E levels were unchanged. The discrepancy between intake and certain circulating nutrient levels may reflect alterations in the requirements, absorption, or use of these nutrients in the presence of chronic inflammation.

Adolescent↗
PubMed1990

The effect of early caloric restriction on colonic cellular growth in rats.

Although the inhibitory effect of caloric restriction on tumorigenesis is substantial and well known, the pertinent mechanisms remain to be determined. We recently suggested that the risk of cancer may be directly related to the total number of dividing cells within an affected organ. This study evaluates the effects of early caloric restriction on the cellular growth of the colon. The experiment began one day postpartum and ended six weeks later with the killing of all animals. It consisted of two consecutive periods: a) three weeks of suckling and b) three weeks postweaning. Animals whose food was restricted only during the suckling period showed normal colons when killed at six weeks. Caloric restriction (40%) for three weeks postweaning resulted in colons of lower weight with fewer cells (less total DNA) and reduced total DNA synthesis [( 3H]thymidine uptake, dpm/colon) when compared with animals fed ad libitum postweaning. Conversely, only rats fed ad libitum from birth through the first three weeks after weaning demonstrated an increase (21%) in the rate of DNA synthesis (dpm/mg DNA) compared with other animals. In addition, the colonic crypts showed no differences in the number of cells or the number of dividing cells, as determined by autoradiography. By contrast, the total number of crypts (and/or the number of mucosal cells between crypts) are reduced, and hence the total number of colonic mucosal cells dividing at any given time are similarly decreased. The reduced number of dividing cells in the colons of these animals (i.e., those restricted postweaning) could explain previous data suggesting that they are resistant to the induction of colon cancer.

Animals↗
PubMed1990

The effect of elevated selenium intake on colonic cellular growth in rats.

Both selenium and calorie restriction are anticarcinogenic in many tumor models, but the mechanisms of action are unknown. This study compared the effects of elevated selenium (Se) intake and calorie restriction on colonic cellular growth. Female weanling rats were divided into four groups: control, 40% calorie restricted, and 4 or 6 mg Se/l H2O as selenate. Control rats and rats given Se consumed the control diet ad libitum. Rats in the 40% calorie-restricted group were pair fed 40% less than the total intake of control rats with a diet designed to provide equal nutrients except calories from carbohydrate. After three weeks, rats were injected with [3H]thymidine (1 muCi/g body wt) and killed one hour later. Se at 4 and 6 mg/l H2O and 40% calorie restriction significantly decreased food intake, weight gain, colon weight, and total colon DNA compared with controls. Total number of cells per crypt was not affected by any treatment, whereas total DNA synthesis was significantly decreased, suggesting that the total number of colonic crypts are reduced by calorie restriction and Se treatment. The rate of cell division was decreased only in rats given 6 mg Se/l H2O. These results indicate that elevated Se intake and caloric restriction decrease colonic mucosal growth by decreasing growth in general, but only very high intakes of Se affect colonic cell turnover.

Animals↗
PubMed1990

Selenium intake, age, gender, and smoking in relation to indices of selenium status of adults residing in a seleniferous area.

Duplicate meals, serum, whole blood, and toenails were collected every 3 mo for 1 y from a group of 44 free-living adults residing in high-selenium areas of South Dakota and Wyoming to assess the relation of selenium intake to indices of selenium status. The average selenium values for the group were as follows: dietary intake, 174 +/- 91 micrograms/d (mean +/- SD), 2.33 +/- 1.08 micrograms/kg body wt; serum, 2.10 +/- 0.38 mumol/L; whole blood, 3.22 +/- 0.79 mumol/L; and toenails, 15.2 +/- 3.0 nmol/g. Selenium intake (micrograms/kg body wt) was strongly correlated (all values, P less than 0.01) with selenium concentration of serum (r = 0.63), whole blood (r = 0.62), and toenails (r = 0.59). Men and women had similar mean values of serum, whole blood, and toenail selenium despite higher selenium intakes in men. Smokers had lower tissue selenium concentrations than did nonsmokers due, at least in part, to lower selenium intake. Age was not associated with tissue selenium content. Of the variables examined selenium intake was clearly the strongest predictor of tissue selenium concentration.

Adult↗
PubMed1990

Effect of various dietary factors on the deposition of selenium in the hair and nails of rats.

Noninvasive techniques to monitor selenium (Se) status at higher intake levels should be developed if Se supplements are to be given to human subjects as possible anti-cancer agents. Hair and nails have been suggested as indices of Se status because they are easily obtained, transported and stored. However, there has been little research on the potential influence of such factors as dietary Se intake or nutritional status on the levels of Se in hair and nails. Here we report the effects of chemical form of dietary Se and of methionine (Met) status on the Se content of rat hair and nails. Rats were fed diets containing 0.5, 1.5 or 2.5 micrograms/g of Se as sodium selenate (Na2SeO4) or L-selenomethionine (SeMet) for 8 wk. Hair and nail Se retention was two- to threefold greater when dietary SeMet was fed. Hair and nail Se levels increased as liver and muscle Se retention increased in rats fed SeMet, whereas in rats fed Na2SeO4, hair, nails and liver accumulated Se but muscle Se levels remained relatively unchanged. In a second experiment, rats were fed diets containing 0.1, 0.5 or 2.5 micrograms/g of Se as Na2SeO4 or SeMet, +/- added Met (0.3%) for 6 (+Met) or 7 (-Met) wk. Hair and nail Se retention was greater when Met was deficient than when this amino acid was not limiting. These results suggest that factors other than dietary Se intake affect hair and nail Se content and that these tissues should be used with caution for Se status assessment purposes.

Animals↗
PubMed1990

Comparative toxicity and tissue retention of selenium in methionine-deficient rats fed sodium selenate or L-selenomethionine.

Selenium (Se) toxicity is known to be affected by level of intake of the mineral, but there are conflicting reports on the relative toxicities of the various chemical forms of Se. We monitored Se toxicity in rats fed Torula yeast-based diets containing 0.1, 0.5 or 2.5 micrograms Se/g of diet as either sodium selenate (Na2SeO4) or L-selenomethionine (SeMet). Half the diets were supplemented to contain adequate dietary methionine (Met). Weights were monitored weekly for 6 (Met-adequate) or 7 (Met-deficient) wk, at which time the rats were killed. There were no significant differences in final weight among Met-adequate rats, regardless of level or form of dietary Se. Methionine-deficient rats all gained significantly less weight than their Met-adequate counterparts. Selenosis was most severe in the Met-deficient rats fed 2.5 micrograms Se/g of diet as Na2SeO4, as indicated by significantly impaired weight gains. Nonetheless, Se retention in serum, heart, brain, bone, testes, colon, skin, lungs and pancreas was greater in rats fed SeMet than in those fed Na2SeO4, and Met deficiency further intensified this trend. The kidney was the only organ in which Se levels were markedly higher in the severely poisoned Met-deficient rats fed Na2SeO4. Further research is needed to determine whether elevated kidney Se levels are related to the greater toxicity observed in the Met-deficient rats fed Na2SeO4.

Animals↗
PubMed1989

Qinghaosu, dietary vitamin E, selenium, and cod-liver oil: effect on the susceptibility of mice to the malarial parasite Plasmodium yoelii.

Young female mice were fed torula-yeast-based diets deficient in vitamin E or selenium or supplemented with cod-liver oil to determine the effect of host antioxidant status on the therapeutic efficacy of the Chinese traditional antimalarial drug qinghaosu (QHS), a sesquiterpene endoperoxide. Vitamin E deficiency enhanced the antimalarial action of QHS against Plasmodium yoelii, both in terms of decreased parasitemia and improved survival but Se deficiency did not. A vitamin E-deficient diet containing 5% cod-liver oil had such strong antimalarial activity in itself that no additional therapeutic benefit of QHS could be demonstrated. Hematocrit values in parasitized mice treated with QHS or fed the cod-liver-oil-supplemented, vitamin E-deficient diet were normal. Nutritional manipulation of host antioxidant status may provide a promising prophylactic and/or therapeutic tool for the control of malaria.

Animals↗
PubMed1989

Upper limit of selenium in infant formulas.

At present, the amount of selenium in infant formulas is not controlled and varies depending upon the selenium content of the raw materials used in its manufacture. Since selenium deficiency has been associated with two diseases of childhood, prudence dictates that the concentration of selenium in infant formula be standardized. Extrapolation from studies with human adults indicates that a daily intake of 10 microg of selenium is sufficient to meet the nutritional requirement of the infant while providing a reasonable margin of safety. Extrapolation from adult studies also suggests that intakes of 75-160 microg/d might have harmful effects in infants. On the other hand, no cases of selenosis in infants have been reported in high selenium areas of the United States, where human breast milk supplies as much as 47 microg/d. Therefore, it is proposed that infant formulas contain enough selenium to provide 10-45 microg/d.

Female↗
PubMed1989

Human selenite metabolism: a kinetic model.

A model is developed to describe the kinetics of sodium selenite metabolism in humans, based on plasma, urine, and fecal samples obtained from six subjects over a 4-wk period after a single oral 200-micrograms dose of the enriched stable isotope tracer 74Se. The model describes absorption, distributed along the gastrointestinal tract, and enterohepatic recirculation. The model includes four kinetically distinct plasma components, a subsystem consisting of the liver and pancreas, and a slowly turning-over tissue pool. For the six subjects, the ranges of mean residence times for the four plasma components are, respectively, 0.2-1.1 h, 3-8 h, 9-42 h, and 200-285 h; for the hepatopancreatic subsystem 4-41 days; and for the tissue pool 115-285 days. Approximately 84% of the administered dose was absorbed, and after 12 days approximately 65% remained in the body. The model predicts that after 90 days approximately 35% of this Se would be retained, primarily in the tissues. Separating Se metabolism into several distinct kinetic components is a first step in identifying the efficacious, nutritious, and toxic forms of the element.

Feces↗
PubMed1987

Relative nutritional availability to rats of selenium in Finnish spring wheat (Triticum aestivum L.) fertilized or sprayed with sodium selenate and in an American winter bread wheat naturally high in Se.

A Finnish national programme to fertilize crops with sodium selenate led us to compare the nutritional availability to rats of selenium in two Finnish spring wheats (Triticum aestivum L.), either fertilized or sprayed with sodium selenate, with that in an American winter bread wheat naturally high in Se. Weanling male rats were given a Se-deficient Torula yeast diet for 4 weeks followed by either continued depletion or repletion for 4 weeks with graded levels of Se as sodium selenite (standard) or wheat (test food). Plasma and liver Se levels and plasma and liver glutathione peroxidase (EC 1.11.1.9; GSH-Px) activities were used as criteria of body Se status. The availability of Se under these conditions was calculated with the point-slope technique at two dietary levels of Se (Expt 1) and with the slope-ratio method (Expt 2). In the point-slope assay, the level of dietary Se fed had a considerable effect on the apparent availability values obtained which made interpretation of the results difficult. In the slope-ratio assay, no difference in the availability of Se from the various wheats was observed when plasma or liver Se levels were used as the response criteria. The Se in the fertilized wheat was somewhat more available than that in the sprayed wheat when plasma or liver GSH-Px activities were the response criteria. Overall, availability values (%) derived by averaging all four response criteria were 86, 77 and 73 for the fertilized and sprayed Finnish wheats and the American wheat respectively (sodium selenite 100). These results show that wheat is a relatively available source of Se to rats regardless of whether its Se content is naturally high or is increased by fertilization or spraying.

Animals↗
PubMed1987

Dietary selenium intake and selenium concentrations of plasma, erythrocytes, and breast milk in pregnant and postpartum lactating and nonlactating women.

The selenium status of a group of 23 lactating and 13 nonlactating women was assessed from 37-wk gestation through 6-mo postpartum. The mean overall dietary Se intake of both groups of women was 80 +/- 37 micrograms/d. Plasma and erythrocyte Se levels were lower in the lactating than in the nonlactating mothers both before and after parturition. Breast-milk Se concentrations fell from 20 micrograms/L (0.25 mumol/L) at 1-mo postpartum to 15 micrograms/L (0.19 mumol/L) at 3- and 6-mo postpartum. A weak (r = 0.38) but statistically significant (p less than 0.025) relationship was observed between maternal plasma Se level and breast-milk Se concentration. The dietary Se intake of these lactating North American women appears sufficient to maintain satisfactory Se nutriture in their breast-fed infants during the first 6 mo of lactation.

Adult↗