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J L Beard

Publications and source records attributed to J L Beard.

At least 19 recordsLinked to original sources

Regional distribution of iron, transferrin, ferritin, and oxidatively-modified proteins in young and aged Fischer 344 rat brains.

Iron dysregulation in the brain is thought to contribute to the oxidative damage seen in neurodegenerative diseases including Alzheimer's disease and Parkinson's disease. A role for iron in the oxidative stress thought to contribute to normal ageing is less certain. To better characterize the role of iron in normal ageing, the concentrations of iron, transferrin, ferritin, and protein carbonyl groups are measured in nine separate regions of Fischer 344 rats. The largest (approximately 30%) age-related increases in brain iron concentration are seen in the temporal cortex, medial septum, and cerebellum. Ferritin concentration in these same brain regions increases 50 to 250% with age, while protein carbonyl concentration is only -27 to +4%, of young rats. These results indicate that an increase in the major iron-binding protein ferritin compensates for any age-related increase in iron concentration, and suggest that the increased ferritin is cytoprotective, serving to prevent the accumulation of protein carbonyl groups (a principal product of metal-catalysed oxidation of proteins).

Aging

Chromium picolinate supplementation and resistive training by older men: effects on iron-status and hematologic indexes.

Chromium competes with iron for binding to transferrin, and high-dose chromium supplementation has been hypothesized to adversely affect iron status. This study examined the effects of chromium picolinate supplementation on hematologic indexes and selected indexes of iron status in 18 men aged 56-69 y who participated in an introductory resistive training program. The men were randomly assigned (double-blind design) to groups (n = 9) that consumed either 17.8 mumol Cr/d (924 micrograms Cr/d) as chromium picolinate or a low-chromium placebo for 12 wk while engaging in resistive training twice weekly (3 sets of 8-12 repetitions at 80% of one repetition maximum for 5 exercises). Hematocrit, hemoglobin, red blood cell (erythrocyte) count, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, red blood cell distribution width, platelet count, and mean platelet volume were within normal clinical ranges and were unchanged by either chromium picolinate supplementation or resistive training. Resistive training decreased total-iron-binding capacity from 38.4 +/- 9.3 to 27.3 +/- 5.6 mumol/L (P < 0.0001) and increased transferrin saturation from 35.7 +/- 16.3% to 45.4 +/- 16.9% (P = 0.050). Chromium picolinate supplementation did not influence these responses. Serum iron concentrations and serum ferritin concentrations were unchanged by either resistive training or chromium picolinate supplementation. These data suggest that high-dose chromium picolinate supplementation for 12 wk did not influence hematologic indexes or indexes of iron metabolism or status in older men. The decrease in total-iron-binding capacity and increase in transferrin saturation (%) with resistive training are largely opposite to changes associated with iron depletion and suggest a novel effect of resistive training on iron transport.

Aged

Regional brain iron, ferritin and transferrin concentrations during iron deficiency and iron repletion in developing rats.

Iron deficiency in young rats leads to a decrease in brain iron and ferritin concentrations, an increase in transferrin (Tf) concentration, and an increased rate of uptake of iron from the plasma pool. We conducted two experiments to determine whether brain iron, Tf and ferritin respond quickly to iron repletion and to determine whether brain regions respond heterogeneously. Weanling male Sprague-Dawley rats were fed an iron-deficient diet (<5 mg/kg Fe) for 2 wk followed by an iron-adequate diet (REPL group, 35 mg/kg Fe in Experiment 1 and 15 mg/kg Fe in Experiment 2) for 2 or 4 wks, respectively. Age-matched iron-deficient (ID) and control rats composed the other two groups. Fourteen days of repletion with 35 mg/kg Fe dietary treatment were adequate to normalize hematology, brain microsomal and cytosolic Fe and brain ferritin (Experiment 1). Brain transferrin concentrations in REPL rats, however, were significantly above the levels of controls. Regional brain iron decreased heterogeneously due to dietary iron deficiency (Experiment 2), with some regions having a propensity to keep iron (e.g., substantia nigra, pons, and thalamus) and others losing significant amounts of iron (cortex and hippocampus). Ferritin and Tf concentrations also varied significantly across brain regions in ID and control rats. The hippocampus had the most dramatic Tf response to iron deficiency with elevations of approximately 100%, whereas other regions, except striatum, were unaffected. The brain of developing rats thus distributes iron and iron regulatory proteins differently from the brain of adult rats and is quite avid in its reacquisition of iron during iron therapy.

Anemia, Iron-Deficiency

Age, fitness, and regional blood flow during exercise in the heat.

During dynamic exercise in warm environments, the requisite increase in skin blood flow (SkBF) is supported by an increase in cardiac output (Qc) and decreases in splanchnic (SBF) and renal blood flows (RBF). To examine interactions between age and fitness in determining this integrated response, 24 men, i.e., 6 younger fit (YF), 6 younger sedentary (YS), 6 older fit (OF), and 6 older sedentary (OS) rested for 50 min, then exercised at 35 and 60% maximal O2 consumption (VO2max) at 36 degrees C ambient temperature. YF had a significantly higher Qc and SkBF than any other group during exercise, but fitness level had no significant effect on any measured variable in the older men. At 60% VO2max, younger subjects had significantly greater decreases in SBF and RBF than the older men, regardless of fitness level. Total flow redirected from these two vascular beds (deltaSBF + deltaRBF) followed YF >> YS > OF > OS. A rigorous 4-wk endurance training program increased exercise SkBF in OS, but deltaSBF and deltaRBF were unchanged. Under these conditions, older men distribute Qc differently to regional circulations, i.e., smaller increases in SkBF and smaller decreases in SBF and RBF. In younger subjects, the higher SkBF associated with a higher fitness level is a function of both a higher Qc and a greater redistribution of flow from splanchnic and renal circulations, but the attenuated splanchnic and renal vasoconstriction in older men does not appear to change with enhanced aerobic fitness.

Adult

The role of nutrition in the development of normal cognition.

The goal of this section of the meeting was to review the relation between nutrition and cognition. The topics selected for discussion included generalized malnutrition, iodine deficiency, iron metabolism, and the relation of fatty acids to the development of the nervous system. Each subject is immense and demands a detailed exposition, but can be treated here only in brief form. However, these short essays should give some insight into the status of our current knowledge.

Brain

Purified ferritin and soybean meal can be sources of iron for treating iron deficiency in rats.

Ferritin and soybean meal were reevaluated as dietary treatments of iron deficiency in rats. Isotopes that had been used in the past were avoided because of contemporary knowledge of the physiological and structural complexity of ferritin protein and the solid iron mineral. Rats made anemic by iron-deficient diets were given equivalent amounts of iron as FeSO4, horse spleen ferritin, baked soybean meal, or soybean meal plus ferritin. Full recovery (89-109%) from anemia and increased tissue iron occurred after 28 d of treatment with any of the iron sources, which contrasts to past bioavailability studies using 59Fe-labeled ferritin and generally shorter periods of observation. Cultivar-specific variability was observed in soybean seed soluble iron and ferritin content (1.9-2.0 times the control cultivar, Arksoy), which was apparently heritable. The combined data suggest that manipulating ferritin expression and other soluble components of seed iron in soybeans and possibly other seeds, using Mendelian and biotechnological approaches, could contribute to a sustainable solution to global problems of iron deficiency.

Anemia, Iron-Deficiency

Iron metabolism: a comprehensive review.

Despite its abundance in the earth's crust, iron deficiency is a serious health issue in many parts of the world. Although fundamental observations about iron metabolism and the significance of iron nutriture were first noted some time ago, the molecular mechanisms involved in iron metabolism are just now being defined.

Animals

Iron nutrition in rural home bound elderly persons.

The objective of this study was to describe the iron status of a sample of rural elderly home-delivered meals recipients as determined by a relatively non-invasive capillary blood sampling system. Fifty-six persons were assessed in their homes. The incidence of iron deficiency was considerable and was similar to incidences reported in other elderly populations. Females were at higher risk for iron deficiency than males despite a similar low dietary iron intake of 10-11 mg/day in both genders. Data were collected on drug use, general health conditions and other variables that may alter iron status in the elderly but they had no significant statistical effects in this study. We interpret this data on a high prevalence of iron deficiency in females as suggestive that they are at considerable risk of iron deficiency due to a lifelong poorer iron status than men.

Activities of Daily Living

Iron deficiency and anemia of chronic disease in elderly women: a discriminant-analysis approach for differentiation.

To differentiate iron-deficiency anemia and anemia associated with chronic inflammatory diseases in elderly women, subsets of laboratory, dietary, and functional assessment variables were obtained by using discriminant analysis. Fifty-one subjects (70-79 y of age) were classified into one of four groups on the basis of the presence of iron deficiency and chronic inflammatory disease. Iron deficiency was defined on the basis of a significant response in hemoglobin concentration after iron supplementation. The discriminating subset of laboratory tests consisted of measures for serum ferritin, plasma transferrin receptors, and erythrocyte sedimentation rate. The discriminant function classified subjects into iron-deficient, anemia of chronic disease, or a category in which the two coexist, with an error rate of 18.6%. The addition of other variables (dietary iron and functional assessment information) did not appreciably improve the classification. The results of these three key laboratory tests may help to identify functional iron deficiency in the presence of chronic inflammation.

Aged

Classical selenium-dependent glutathione peroxidase expression is decreased secondary to iron deficiency in rats.

While there are reports that classical selenium-dependent glutathione peroxidase (Se-GPX1) activity is decreased during iron deficiency, the relationship between tissue iron status and Se-GPX1 activity remains speculative. This study was undertaken to investigate the mechanism for the decrease in Se-GPX1 activity during iron deficiency. Male weanling Sprague-Dawley rats were given free access to either an iron-deficient or an iron-adequate diet for eight weeks, after which blood, livers, kidneys, hearts, brains and testes were surgically excised. During iron deficiency, Se-GPX1 mRNA levels in liver tissue were decreased by approximately 55%. Similarly, the concentration of immunoreactive Se-GPX1 protein and total selenium-dependent glutathione peroxidase (Se-GPX) activity were decreased by 55% and 60%, respectively. In kidney, heart and brain total Se-GPX activities were depressed as much as 33%. Selenium concentration in liver was reduced by 42%, whereas the decrease in Se concentrations in kidney, heart, and brain ranged from 17 to 25%. Concentrations of plasma Se also were reduced by 18%, but testes showed little change in either Se-GPX activity or Se concentration during iron deficiency. Results suggest that the synthesis of Se-GPX1 protein is decreased during iron deficiency possibly due to pretranslational regulation.

Anemia, Iron-Deficiency

Brain iron, transferrin and ferritin concentrations are altered in developing iron-deficient rats.

To study the iron, transferrin, and ferritin distribution at subcellular levels in response to acute dietary iron deficiency, we tested the hypothesis that early post-weaning iron deficiency can change iron and iron regulatory protein concentrations in rat brain. Male Sprague-Dawley rats were fed diets containing either 2 or 35 micrograms iron/g for 2, 3 or 4 wk starting at 21 d of age. Brain iron, transferrin and ferritin concentrations in cytosolic and microsomal fractions of either whole brain or pons and cerebellum were then determined. After 14 d of dietary iron restriction, brain iron concentrations were 50% lower in the microsomal fraction and 30% lower in cytosol compared with controls. Brain cytosolic transferrin concentration almost doubled in the same animals. Brain ferritin concentration in fractions from rats fed the iron-deficient diet for 14 d was lower than in controls, but then remained fairly constant. Absolute brain weight and total brain protein contents were unaffected by iron restriction. This study extends previous research by demonstrating that the brain responds to changes in body iron status with a change in transferrin concentration. If the dietary restriction is quite severe, this adaptation is insufficient. This study also notes that brain ferritin decreases with decreasing body iron status, though it was less responsive than nonheme iron in liver. The concept that iron enters the brain through a highly regulated endocytotic process at the blood brain barrier, that undoubtedly involves the regulation of transferrin receptors in capillary endothelial cell, is supported by our observation of elevated transferrin concentrations in brain of iron-deficient rats.

Anemia, Iron-Deficiency

Sensory acceptability of meat and dairy products and dietary fat in male collegiate swimmers.

This study was undertaken to determine whether high-level training alters food choice behavior with regard to meat and dairy products because of their high fat content. Twenty male collegiate swimmers were compared to 20 male sedentary students for dietary fat intake, nutrition knowledge, and liking of meat and dairy products. There was no significant difference between the two groups for restraint, energy intake, dietary fat intake, and energy derived from fat. Nutrition knowledge, energy derived from saturated fat, and cholesterol intake, however, were significantly higher in the athletes. The two groups did not differ in their hedonic ratings of flavor or in their overall degree of liking of the meat and dairy products, and the athletes actually liked the appearance and texture of the products significantly more than did the sedentary students. This study shows that the sensory appeal of fat-containing animal products is not affected in male swimmers by a high level of exercise.

Adult

Effect of thyroid hormone replacement in iron-deficient rats.

To determine if the previously observed alterations in norepinephrine (NE) metabolism and resting metabolic rate in iron-deficient (ID) rats result from hypothyroidism, exogenous thyroxine (T4) and 3,5,3'-triiodothyronine (T3) were administered to ID rats in doses sufficient to normalize the plasma concentrations of these hormones, whereas other ID and control (CN) rats received placebo treatment. Resting oxygen consumption was approximately 25% higher in ID than CN rats; T4 but not T3 treatment alleviated this elevated oxygen uptake. The NE content of interscapular brown adipose tissue (IBAT), liver, and heart was 70-80% lower in ID than CN rats, and NE turnover in the same tissues was likewise 40-60% lower in ID than CN rats, with no systematic effect of either T3 or T4 treatment. Liver T(4)5'-deiodinase activity was 70% lower in ID than CN rats and increased with T4 but not T3 treatment. These experiments show that iron deficiency alters NE and energy metabolism in a way that is mostly independent of its effects on thyroid hormone metabolism.

Adipose Tissue, Brown

Growth in iron-deficient rats.

Poor growth in iron deficiency is commonly observed in animal studies. Previous studies from our laboratory showed that iron-deficient rats are metabolically inefficient and have less body fat than controls and proposed that iron deficiency was related to increased metabolic rates and heat loss. To examine these points more completely, we examined growth and metabolic rate of iron-deficient rats at two environmental temperatures, 25 degrees C and 32 degrees C, and feed efficiency in separate groups of rats during a period of rapid growth. Iron deficiency (hemoglobin [Hb] approximately 60 g/liter) was associated with a systematic elevation of metabolic rate over the 24-hr day with animals at 25 degrees C. This did not occur in animals living in thermoneutrality. Iron deficiency affected growth of animals at 25 degrees C but not at 32 degrees C. Feed efficiency (kcal retained/kcal absorbed) was 25 +/- 4.2 and 31 +/- 4.9 kcal (P < 0.0001), respectively, in iron deficient rats and animals were not anorexic. Use of food-restricted animals allowed the direct calculation that iron deficiency was associated with a 10%-15% increase requirement for growth. We conclude that iron deficiency anemia is associated with a poor feed efficiency and that it is attenuated when nonshivering thermogenesis is minimized by a thermoneutral environment.

Anemia, Iron-Deficiency

Effects of long-term moderate exercise on iron status in young women.

The impact of long-term (6-month) moderate exercise on the iron status of previously sedentary women was determined by randomly assigning 62 college-age women into one of the following four groups: 1) 50 mg.d-1 iron supplement, low iron diet (N = 16); 2) Placebo, free choice diet (N = 13); 3) Meat supplement to achieve 15 mg.d-1 iron intake (N = 13); and 4) Control, free choice diet (N = 20). All groups except the Control group exercised 3 d.wk-1 at 60%-75% of their heart rate reserve. VO2max was measured at baseline and week 24. Blood was sampled at baseline and every 4 wk thereafter for 24 wk to measure iron status and to elucidate the causes for alterations in iron status. Subjects had depleted iron stores throughout the study as indicated by their serum ferritin levels (< 15 ng.ml-1). Serum iron, total iron binding capacity and transferrin saturation were not compromised with exercise. Mean hemoglobin level in the Placebo/Ex group was significantly (P < 0.05) lower than the 50 Fe/Ex and the Meat/Ex groups by week 24. However, changes in serum albumin, haptoglobin, and erythropoietin data from the study cannot explain these changes.

Adult

Altered monamine metabolism in caudate-putamen of iron-deficient rats.

The effect of iron deficiency on brain monoamine metabolism using in vivo microdialysis techniques has not been previously reported. We, therefore, examined the monoamines, dopamine and norepinephrine, and their metabolites at steady state by in vivo microdialysis in rat brain caudate-putamen in 11-week-old iron-deficient anemic (hemoglobin < 7 g/dl) and control rats (Hb > 14 g/dl). Caudate-putamen dopamine (DA), dihydroxyphenyl acetic acid (DOPAC), and homovanillic acid (HVA) concentrations were increased by 53%, 57%, and 30% (p < 0.001), respectively, in iron-deficient rats in samples collected over a 4-h period. While diminished numbers of D2 receptors have been previously reported, the present findings suggest an additional defect in monoamine uptake and catabolism.

3,4-Dihydroxyphenylacetic Acid

Iron deficiency: assessment during pregnancy and its importance in pregnant adolescents.

The assessment of iron deficiency in pregnancy requires the accurate determination of indicators that have significant within-subject variability. For instance, serum ferritin concentrations may vary by as much as 25% from one day to the next. Added to this uncertainty about biological variability is the influence of plasma volume expansion on concentration-dependent indexes such as ferritin, plasma iron, and hemoglobin. Multiple measurements of iron status are suggested, and, if this is not possible, within-subject variability needs to be included in the confidence of assigning individuals to iron-status groups. An example of this former approach is shown for a group of pregnant adolescents with a very high prevalence of iron deficiency. Although the assessment of iron status in human populations is advanced compared with that of other nutrients, there is still a large uncertainty about absolute diagnosis during pregnancy.

Adolescent

Day-to-day variation in iron-status indexes in elderly women.

Day-to-day variability in biochemical indicators of iron status in well-hydrated and healthy women 70-79 y old (n = 10) was determined. Venous blood was collected on 4 nonconsecutive days during a 2-wk period. Analytical (sigma 2 rep) and biological (sigma 2 fd) variance components were computed based on a previously established scheme in younger adults. These two variance components were summed to obtain the total day-to-day variability (sigma 2 fd). Our results indicate that biological variation contributed most to the intraindividual variation. We calculated that sampling once for most iron indexes and twice for plasma transferrin receptors in elderly individuals is adequate to accurately determine these indexes whereas serum iron and transferrin saturation, indexes with high CVfd, require seven and eight measurements, respectively. These data, compared with previously published data in younger adults, demonstrate that aging is associated with a decreased variation in some indexes of iron status such as serum ferritin.

Aged