Search PubMed⌕ Search

Biomedical subjects

O A Levander

Publications and source records attributed to O A Levander.

At least 37 records · Page 2Linked to original sources
PubMed1998

Dietary oxidative stress and the potentiation of viral infection.

Oxidative stress is implicated in the pathogenesis of several viral infections, including hepatitis, influenza, and AIDS. Dietary oxidative stress due to either selenium or vitamin E deficiency increases cardiac damage in mice infected with a myocarditic strain of coxsackievirus B3. Such dietary oxidative stress also allows a normally benign (i.e., amyocarditic) coxsackievirus B3 to convert to virulence and cause heart damage. This conversion to virulence is due to a nucleotide sequence change in the genome of the benign virus, which then resembles more closely the nucleotide sequence of virulent strains. Although it has been known for many years that poor nutrition can affect host response to infection, this is the first report of host nutrition affecting the genetic sequence of a pathogen. Further research is needed to determine whether poor host nutrition plays any role in the emergence of new viral diseases via alterations in he genotype of an infectious agent.

Animals↗
PubMed1997

Influence of dietary selenium on the disposition of arsenate in the female B6C3F1 mouse.

Interactions between arsenic (As) and selenium (Se) at the metabolic level are multifaceted and complex. These interactions are of practical significance because populations in various parts of the world are simultaneously exposed to inorganic As in drinking water and Se mainly in the diet at varying levels. The primary goal of this study was to investigate whether differing dietary Se status would alter the profile of urinary metabolites or their time course for elimination after exposure to arsenate [As(V)]. Weanling female B6C3F1 mice were maintained for 28 d on either a control diet of powdered rodent meal sufficient in Se (A, 0.2 ppm) or Torula yeast-based (TYB) diets deficient (B, 0.02 ppm Se), sufficient (C, 0.2 ppm Se), or excessive (D, 2.0 ppm Se) in Se; mice then received by oral gavage 5 mg (As)/kg as sodium [73As] arsenate. The time course for elimination of total arsenic and metabolites in urine was measured over a 48-h period, and total arsenic was determined in feces and tissues at 48 h. Mice on the Se excess diet excreted a significantly higher percentage of urinary As as inorganic As, with a significantly decreased ratio of organic to inorganic As compared to Se-sufficient mice, suggesting that As methylation was decreased. Mice on the Se-deficient diet appeared to eliminate As(V), arsenite, and dimethylarsinic acid (DMA) in urine more slowly than Se-sufficient mice; however, further studies are required to confirm this finding. Mice on the Se-sufficient meal diet (A) excreted significantly less (by percent) arsenate-derived radioactivity in urine and more in feces compared to mice on the Se-sufficient TYB diet (C), with total elimination being similar for both groups. This indicates that mice on the meal diet absorbed significantly less As(V) than mice on the TYB diet, and this may be due to more fiber or "bulk" in the meal diet. This finding emphasizes the importance of considering dietary composition when interpreting and comparing As disposition studies. Overall this study provides suggestive evidence that dietary Se status alters As metabolism and disposition. This indicates that dietary Se status may be an issue that should be considered in the design and interpretation of epidemiologic studies.

Analysis of Variance↗
PubMed1997

Interacting nutritional and infectious etiologies of Keshan disease. Insights from coxsackie virus B-induced myocarditis in mice deficient in selenium or vitamin E.

In 1979, Chinese scientists reported that selenium had been linked to Keshan disease, an endemic juvenile cardiomyopathy found in China. However, certain epidemiological features of the disease could not be explained solely on the basis of inadequate selenium nutrition. Fluctuations in the seasonal incidence of the disease suggested involvement of an infectious agent. Indeed, a coxsackievirus B4 isolated from a Keshan disease victim caused more heart muscle damage when inoculated into selenium-deficient mice than when given to selenium-adequate mice. Those results led us to study the relationship of nutritional status to viral virulence. Coxsackievirus B3/0 (CVB3/0), did not cause disease when inoculated into mice fed adequate levels of Se and vitamin E. However, mice fed diets deficient in either Se or vitamin E developed heart lesions when infected with CVB3/0. To determine if the change in viral phenotype was maintained, we passaged virus isolated from Se-deficient hosts, designated as CVB3/0 Se-, back into Se-adequate hosts. The CVB3/0 Se- virus caused disease in Se-adequate mice. To determine if the phenotype change was due to changes in the viral genome, we sequenced viruses isolated from Se-deficient mice and compared them with the input CVB3/0 virus. Six point mutations differed between the parent strain and the recovered CVB3/0 Se- isolates. When the experiment was repeated using vitamin E-deficient mice, the same 6 point mutations were found. This is the first report of a specific host nutritional deficiency altering viral genotype. Keshan disease may be the result of several interacting causes including a dominant nutritional deficiency (selenium), other nutritional factors (vitamin E, polyunsaturated fatty acids), and an infectious agent (virus).

Animals↗
PubMed1997

The effect of high n-3 fatty acids diets on the ultrastructural development of Eimeria tenella.

A study of development of Eimeria tenella in chickens fed high n-3 fatty acids (n-3FA) diets showed ultrastructural degeneration of both asexual and sexual parasite stages. Abnormal shedding of asexual and sexual parasite developmental stages into the cecal lumen was also observed. Ultrastructural degeneration was characterized by cytoplasmic vacuolization, chromatin condensation within the nucleus, a lack of parasitophorous vacuole delineation, and, in some cases, a complete loss of parasite ultrastructural organization. The results of this study indicate that diets high in n-3FA may be useful in the control of avian coccidia.

Animal Feed↗
PubMed1997

Nutrition and newly emerging viral diseases: an overview.

Infectious diseases are on the increase worldwide. When discussing interactions of nutrition and infection, nutritionists have traditionally considered only the effects of diet on the host. Recent data, however, indicate that, at least for an RNA virus, host nutriture can influence the genetic make-up of the pathogen and thereby alter its virulence. This symposium was organized to alert the nutrition community to this discovery and its possible implications for the investigation of nutrition-infection interrelationships. Topics covered in the symposium include the following: the public health threat of emerging viral diseases; the rapid evolution of viral RNA genomes; oxidants and antioxidants in viral diseases-disease mechanisms and metabolic regulation; and increased virulence of coxsackievirus B3 due to vitamin E or selenium deficiency. If the findings with coxsackievirus are more broadly applicable to other RNA viruses, the results could be of great public health significance because RNA viruses constitute the majority of all plant, animal and human viruses.

Antioxidants↗
PubMed1997

Interaction of dietary flaxseed with coccidia infections in chickens.

Two experiments were conducted to determine effects of diets containing n-3 fatty acids (n-3FA) from whole as well as ground flaxseed on the performance of broilers during coccidia infections. Diets were fed from 1 d of age through 3 wk of age. Chickens were infected with coccidia at 2 wk of age and the effects of infection assessed at 6 d postinfection. The first experiment contrasted effects of several high n-3FA-containing diets, including one supplemented with whole flaxseed, on infections with Eimeria tenella or Eimeria maxima. Infected chickens that consumed the flaxseed-supplemented diet had the lowest weight gains, but they were not significantly different from gains of infected chickens on the control diet. Diets supplemented with 5% menhaden oil or 15% flaxseed significantly reduced lesions caused by E. tenella, but had no effect on lesions caused by E. maxima. In a second experiment, diets supplemented with 5 or 10% ground flaxseed were assessed for effects on the performance of broilers infected with three dose levels (500, 5,000, or 50,000 oocysts) of E. maxima. Neither flaxseed diet protected weight gain during infection with 50,000 oocysts. However, a 5% flax diet protected weight gains in chickens infected with 500 or 5,000 oocysts. Diets supplemented with 5 or 10% ground flaxseed exacerbated lesions in chickens infected with 5,000 or 50,000 E. maxima oocysts compared to the control diet. Thus, diets containing high amounts of n-3 fatty acids do not affect the development of all Eimeria sp. in the same manner. The oxidative stress produced by these diets may more adversely affect development of E. tenella, which infects the relatively oxygen-poor ceca, whereas it does not affect development of E. maxima which parasitizes the middle portion of the small intestine.

Animals↗
PubMed1997

Vitamin E-deficient diets enriched with fish oil suppress lethal Plasmodium yoelii infections in athymic and scid/bg mice.

Mice fed vitamin E-deficient diets containing omega-3 fatty acids survive infection with lethal Plasmodium yoelii. The current study sought to determine if antimalarial T- and B-cell responses were required for such dietary-mediated protection. In the first set of experiments, nu/nu mice (which lack alphabeta T-cell-receptor-positive T cells and do not produce antimalarial antibody) and nu/+ mice were fed casein-based diets containing 4% menhaden oil, with or without vitamin E supplementation, for 4 weeks prior to infection with lethal P. yoelii. All mice fed diets containing vitamin E developed fulminating parasitemias and quickly died, whereas both nu/nu and nu/+ mice fed diets deficient in vitamin E controlled their parasitemias for the first 18 days of infection. Thereafter, the nu/nu mice became anemic and died, whereas the nu/+ mice produced antimalarial antibodies and survived. In the second set of experiments, scid/scid.bg/bg mice (which lack B cells and alphabeta and gammadelta T cells and have reduced NK-cell activity) were fed the experimental diet for 6 weeks and then infected with the less virulent 17XNL strain of P. yoelii. Mice fed vitamin E-containing diets quickly died, whereas those fed the vitamin E-deficient diet survived without developing detectable parasitemias. Results from these experiments show that under prooxidant dietary conditions, mice were able to control and even survive malaria in the absence of malaria-primed T cells and antimalarial antibody. These results emphasize the importance of cellular oxidative processes in parasite elimination.

Animals↗
PubMed1997

The effect of antioxidant vitamin supplementation on traditional cardiovascular risk factors.

BACKGROUND: Evidence from observational epidemiologic studies has indicated that antioxidants consumed through the diet or as dietary supplements lower the risk of developing atherosclerotic cardiovascular disease. Evidence suggesting that the major mechanism for the protective effect of antioxidants is mediated through decreased oxidation of lipids, particularly low-density lipoprotein (LDL) cholesterol is accumulating. Other evidence, however, suggests that antioxidants may influence traditional modifiable cardiovascular risk factors such as the blood pressure and serum lipids favorably. The purpose of this study was to determine the effect of antioxidant vitamin supplementation on modifiable risk factors for atherosclerotic cardiovascular disease. DESIGN: A randomized, placebo-controlled, clinical trial of antioxidant vitamin supplementation, conducted at a single community-based clinical research center. METHODS: We assigned 297 retired teachers who were members of the Maryland Retired Teachers Association randomly to 2-4 months of dietary supplementation with placebo or combined antioxidant vitamin capsules providing 400 IU/day vitamin E, 500 mg/day vitamin C, and 6 mg/day beta-carotene. The outcome measures were the blood pressure, fasting serum total cholesterol, high-density lipoprotein cholesterol, LDL cholesterol, and fasting glucose. RESULTS: After 2-4 months of supplementation the combined antioxidant supplement had had no significant effect on the systolic and diastolic blood pressures, fasting serum lipids (total cholesterol, high-density lipoprotein cholesterol, and LDL cholesterol) and fasting glucose, with unadjusted and adjusted analyses. CONCLUSION: Data from this trial suggest that the protective effect from antioxidant vitamin supplementation, if there is one, likely results from mechanisms other than modification of traditionally modifiable cardiovascular risk factors.

Antioxidants↗
PubMed1997

Naturally occurring selenium compounds in cancer chemoprevention trials: a workshop summary.

Evidence from epidemiological studies and a human intervention trial indicates that selenium (Se) may have chemopreventive activity in humans. This report summarizes a workshop held by the National Cancer Institute to address the use of naturally occurring Se compounds in future cancer chemoprevention trials. Differences in the metabolism of inorganic and organic Se compounds can be seen both in the biochemical handling of these forms and in their kinetics in humans. Long-term supplementation could result in greater increases in muscle stores for organic rather than inorganic forms. Because of long half-lives, trials may have to be of long duration to assess efficacy and safety. The optimal size of dose for supplementation is controversial with respect to both efficacy and safety. In China, selenosis was observed in some individuals with a sustained intake of at least 750 micrograms/day but was not observed among others with intakes exceeding 1 mg. These levels exceed the reference dose, a measure of the maximal safe intake, which is 350 micrograms/day. A large-scale Se human intervention trial in the United States suggests no harm due to long-term Se intake of more than 200 micrograms/day. Se deficiency has been shown to have deleterious effects on the immune system, allowing, for example, a benign form of the Coxsackievirus to become virulent in mice. These recent results may provide an explanation of earlier findings showing a protective effect of elevated Se intakes against a mouse mammary tumor virus. Additional studies on the use of Se as a chemopreventive agent in man seem warranted.

Animals↗
PubMed1997

Selenium requirements as discussed in the 1996 joint FAO/IAEA/WHO expert consultation on trace elements in human nutrition.

In March 1996, WHO officially released an updated trace element nutrition report that presents much new information, especially regarding iodine, zinc, copper and selenium. For most minerals, both basal as well as normative requirements are given. The basal requirement refers to the intake needed to prevent clinically manifest signs of impaired function attributable to deficiency of the nutrient. The normative requirement refers to the intake needed to maintain a level of tissue storage (or index enzyme activity) judged to be desirable and appropriate. In the case of selenium, the population minimum mean intakes likely to meet basal requirements for adult males and females were 21 and 16 micrograms/day, respectively. These were derived from the amount needed to protect against Keshan disease plus a body weight correction factor. On the other hand, the population minimum mean intakes likely to meet normative requirements for adult males and females were 40 and 30 micrograms/day, respectively. These were calculated from the amount needed to achieve two-thirds of the maximal plasma glutathione peroxidase activity assuming an interindividual variability of normal dietary selenium intake of 16%. Further work is needed to determine the relationship between these nutritional standards and the actual dietary intakes of selenium around the world.

Adolescent↗
PubMed1996

Deliberations and evaluations of the approaches, endpoints and paradigms for selenium and iodine dietary recommendations.

Information is presented regarding the approaches that have been used to establish dietary recommendations for selenium and iodine. In the case of selenium, activity of the selenoenzyme glutathione peroxidase has served as a convenient biochemical endpoint for judging nutritional status. However, there are differences of opinion among various nutritionists as to whether full expression of this enzymatic activity is required for adequate nutriture, thereby resulting in differences in dietary recommendations. Endpoints for assessing selenium overexposure are much less satisfactory, but toxicological standards for selenium have nevertheless been established. Thus far, no nutritionists have attempted to shift the paradigm for determining dietary selenium recommendations away from prevention of deficiency disease to prevention of chronic degenerative disease (e.g., cancer). In the case of iodine, urinary excretion of the element is the most widely used endpoint for judging nutritional status. Numerous epidemiological surveys have been conducted to determine the level of urinary iodine excretion that is consistent with prevention of goiter, the most common endpoint of iodine deficiency. Because dietary iodine is essentially quantitatively excreted in the urine, determination of the latter in goitrous areas will allow an almost direct estimation of those intakes at risk of developing deficiency disease. Iodine toxicity is complicated by the fact that some persons are quite tolerant to the element whereas others are highly sensitive to it. There are relatively complete data sets concerning exposure vs. human health effects for both selenium and iodine so that sounder bases probably exist for their dietary recommendations than for many other trace elements.

Adolescent↗
PubMed1996

Use of selenium concentration in whole blood, serum, toenails, or urine as a surrogate measure of selenium intake.

We examined the validity of using the selenium level in a single biological specimen as a surrogate measure of usual intake. We used data from 77 free-living adults from South Dakota and Wyoming. Subjects provided multiple 1-day duplicate-plate food composites, repeated specimens of blood and toenails, and 24-hour urine collections. We developed a statistical calibration method that incorporated measurement error correction to analyze the data. The Pearson correlation coefficients between selenium intake and a single selenium status measure, after deattenuation to adjust for the effect of within-person variation in intake, were: 0.78 for whole blood, 0.74 for serum, 0.67 for toenails, and 0.86 for urine. We present formulas to estimate the intake of individuals, based on selenium levels in a single specimen of blood, toenails, or urine. In these data, the concentration of selenium in a single specimen of whole blood, serum, or toenails served reasonably well as a measure for ranking subjects according to long-term selenium intake but provided only a rough estimate of intake for each subject.

Adult↗
PubMed1996

Diets high in n-3 fatty acids reduce cecal lesion scores in chickens infected with Eimeria tenella.

Four experiments were run in which diets incorporating various levels of n-3 fatty acids (n-3FA) from fish (menhaden) oil or flax seed were tested for their abilities to reduce the severity of Eimeria tenella infections in young broiler chicks. The diets were fed from 1 d of age through 3 wk of age. Chickens were infected at 2 wk of age. Diets consisting of broiler starter ration supplemented with 2.5 to 10% fish oil, 10% flax seed oil, or 10% linseed oil significantly decreased cecal lesions and maintained weight gains as compared to unsupplemented diets. Light micrographs of ceca from chickens that consumed high n-3FA diets showed reduced parasite invasion and development. Short-term feeding of diets high in n-3FA to young chicks may be a practical method for reducing production losses from cecal coccidiosis.

Animals↗
PubMed1996

Association of lowered plasma carotenoids with protection against cecal coccidiosis by diets high in n-3 fatty acids.

A series of four experiments was run to assess the effectiveness of diets containing high amounts of n-3 fatty acids in reducing the pathological effects of cecal coccidiosis in chickens caused by Eimeria tenella. To determine whether the dietary effects were related to development of oxidative stress, plasma samples were analyzed for tocopherols and carotenoids. Plasma vitamin E (alpha-tocopherol) values were not consistent between experiments. Total plasma carotenoids, however, were significantly decreased by 2.5 to 20% diet supplementation with fish oil in several experiments. These decreases coincided with significant reductions in lesion scores. Under the experimental conditions, total plasma carotenoid concentrations may serve as a sensitive indicator for oxidative stress, which may be a factor in reducing cecal lesions in E. tenella infections.

Animals↗
PubMed1995

High concentrations of the carcinogen 2-amino-1-methyl-6-phenylimidazo- [4,5-b]pyridine (PhIP) occur in chicken but are dependent on the cooking method.

Heterocyclic aromatic amines (HAAs) are mutagenic and carcinogenic compounds found in meats cooked at high temperatures. Although chicken is consumed in large quantities in the United States, there is little information on its HAA content. The objective of this study was to measure the five predominant HAAs (IQ, MeIQ, MeIQx, DiMeIQx, and PhIP) in chicken cooked by various methods to different degrees of doneness. Chicken breasts were panfried, oven-broiled, or grilled/barbecued. Whole chickens were roasted or stewed. Skinless, boneless chicken breasts were cooked to three degrees of doneness: just until done, well done, or very well done. High levels of PhIP (ranging from 12 to 480 ng/g cooked meat) were found in chicken breasts when panfried, oven-broiled, and grilled/barbecued but not in while roasted or stewed chicken. PhIP concentration increased in skinless, boneless chicken breast with longer cooking time, higher internal temperature, and greater degree of surface browning. PhIP concentration was also high in chicken breasts cooked with skin and bones. MeIQx and DiMeIQx levels increased with the degree of doneness, whereas IQ and MeIQ were not detectable in any of these chicken samples. Certain cooking methods produce PhIP, a known colon and breast carcinogen in rodents and possibly a human carcinogen, at substantially higher levels in chicken than has been reported previously in red meat.

Animals↗
PubMed1995

Urinary malondialdehyde-equivalents during ingestion of meat cooked at high or low temperatures.

Excretion of malondialdehyde (MDA)-generating substances in the urine has been suggested as an indicator of in vivo lipid peroxidation. However, MDA in the urine also reflects the amount of lipid peroxidation products consumed in the diet. We determined MDA as the thiobarbituric acid (TBA)-MDA complex in urine of 19 healthy adults (10 male and 9 female) fed large quantities (3.6-4.1 g/kg body weight) of ground beef cooked at a low or a high temperature. Subjects ate a controlled diet with no alcohol or nutritional supplements. For 7 d they consumed ground beef cooked at 100 degrees C for 20 min (low-temperature meat) followed by 7 d with meat fried at 250 degrees C for 22 min (high-temperature meat). Prior to the study, subjects consumed their normal free choice diet with moderate amounts of meat. The concentration of MDA in urine at baseline was 2.1 +/- 0.3 mumol TBA-MDA equivalents/day (mean +/- SEM). After 7 d of low-temperature meat, urinary TBA-MDA equivalents increased to 23.1 +/- 1.4 mumol/d. Urinary TBA-MDA equivalents were consistently lower (6.9-8.0 mumol/d) 1, 2, 3, and 7 d after subjects changed to high-temperature meat. After 7 d of treatment, 97% of the MDA-equivalents in the meat was recovered in 24-h urine samples. The low temperature meat had 3-4 times more MDA than did the high-temperature meat. These data indicate that the amount of meat eaten and the cooking procedures used can dramatically alter urinary MDA. Dietary sources of MDA must be controlled if urinary MDA is to be used as an indicator of oxidative stress.

Adult↗
PubMed1995

Heterocyclic amine content in fast-food meat products.

Heterocyclic aromatic amines are sometimes formed during the cooking of muscle meats, and their mutagenic and carcinogenic effects are of potential concern in the aetiology of human cancer. In a large survey of the heterocyclic amine content of foods, fried or charbroiled hamburgers, fried chicken, chicken breast sandwiches, fish sandwiches and breakfast sausages were purchased from fast-food restaurants. At least three different chains were visited per product and samples from five stores from each chain were pooled. The solid-phase extraction and HPLC method was used to analyse pooled samples for heterocyclic amine content and mutagenic activity with the Ames/Salmonella assay. Samples were analysed in a blind study which also contained quality control samples of two types, one high and one low in heterocyclic amine content and mutagenic activity. Results from the fast-food products showed undetectable levels of heterocyclic amines in 10 of 17 samples and only low levels [< or = 1 ng/g total of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx)] in the remaining samples. Compared with literature values based primarily on laboratory and home cooking conditions, fast-food meat products appear to contribute only a small percentage of the estimated daily dietary intake of heterocyclic amines.

Amines↗