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Biomedical subjects

J L Beard

Publications and source records attributed to J L Beard.

At least 73 records · Page 4Linked to original sources

The impact of varying degrees of iron nutriture on several functional consequences of iron deficiency in rats.

The impact of varying severities of iron-deficiency anemia on fasting blood glucose, plasma triiodothyronine, heart norepinephrine concentrations and resting oxygen consumption were evaluated. Male weanling Sprague-Dawley rats were assigned to one of six dietary groups (4, 6, 11, 16, 23 or 40 mg Fe/kg diet) for 6 wk. Hemoglobin, liver iron and transferrin saturation were significantly lower in the 4 and 6 mg Fe/kg diet groups relative to the other groups and were indicative of anemia, low tissue iron stores and impaired erythropoiesis. Fasting blood glucose and heart norepinephrine concentrations were significantly higher and lower, respectively, in the 4 and 6 mg Fe/kg diet groups than the three highest dietary Fe groups. Although fasting blood glucose was significantly inversely correlated (r = -0.89, P = 0.0001) with hemoglobin concentration; a significant quadratic relationship (R 2 = 0.70, P = 0.0001) existed between hemoglobin and heart norepinephrine concentration. Differences in plasma triiodothyronine concentrations and resting oxygen consumption were not significant among the groups. Thus, base on hemoglobin concentration as an index of the severity of iron deficiency, these findings demonstrate that certain physiological manifestations of iron deficiency occur at even moderate-to-mild degrees of anemia.

Anemia, Hypochromic↗

Impaired thermoregulation and thyroid function in iron-deficiency anemia.

Ten women with iron-deficiency anemia, 8 with depleted iron stores (nonanemic), and 12 control women, all of similar body fatness, were exposed to a 28 degrees C water bath to test the hypothesis that iron-deficiency anemia impairs thermoregulatory performance. The anemic women had lower rectal temperatures than did control women (36.0 +/- 0.2 vs 36.2 +/- 0.1 degree C, respectively, P = 0.001) and a lower rate of oxygen consumption (5.28 +/- 0.26 vs 5.99 +/- 0.29 mL.min-1.kg body wt-1, respectively, P = 0.04) at 100 min of cold exposure. Plasma thyroxine and triiodothyronine concentrations were significantly (P less than 0.002) lower in anemic than in control women at baseline and during cold exposure. Responses of iron-depleted subjects were similar to those of control subjects. Iron supplementation corrected the anemia, significantly (P = 0.03) improved rectal temperature at 100 min, and partially normalized plasma thyroid hormone concentrations. Plasma catecholamines were unaffected by iron status. This experiment demonstrates a functional consequence of iron-deficiency anemia in the balance of heat production and loss and suggests that thyroid-hormone metabolism may be responsible.

Adult↗

Interactions of iron deficiency and exercise training relative to tissue norepinephrine turnover, triiodothyronine production and metabolic rate in rats.

The interactions of iron deficiency and exercise training relative to resting metabolic rate (RMR), tissue norepinephrine (NE) turnover and triiodothyronine (T3) production were examined in male Sprague-Dawley rats. Animals were assigned to iron-deficient (ID) or control (CN) diets and to sedentary (SD) or treadmill-exercise (EX) groups for 6 or 12 wk. Iron-deficient animals (hemoglobin 7.2 +/- 0.2 g 100 mL-1) had a 17% higher RMR and had slower growth rates than CN animals. Exercise training affected growth but not RMR in iron deficiency. Oxygen consumption (Vo2) following pharmacologic injection of norepinephrine was similar in both iron-deficient and exercised groups despite a 35% lower maximal exercise Vo2 in trained iron-deficient rats. NE turnover was lower in heart (55%) and liver (80%) of iron-deficient animals relative to controls. Trained iron-deficient animals had lower NE turnover in interscapular brown adipose tissue (IBAT) than sedentary iron-deficient animals; however, training did not alter NE turnover in control animals. In vitro liver and IBAT T3 production was similar in all groups except for lower activities (40%) in 6-wk iron-deficient, exercised animals. The significant effect of exercise on the growth attenuation of iron-deficient, exercised animals is thus not explained by increased IBAT metabolic activity or a generalized sympathetic nervous system activation. Decreased T3 production during periods of rapid growth and lean body mass development, however, may be important in exercised, iron-deficient animals.

Adipose Tissue, Brown↗

Nutritional assessment of homebound rural elderly.

Approximately one quarter of Americans aged 65 and older live in rural areas. Homebound rural elderly are a hard to reach, often poor and frail population. Failure to include homebound rural elderly in nutritional studies may bias representativeness of samples of elderly persons. This paper discusses some challenges in recruiting homebound older persons to participate in nutritional studies and in establishing quality control procedures in a field setting.

Aged↗

Effects of iron repletion and correction of anemia on norepinephrine turnover and thyroid metabolism in iron deficiency.

The reversibility of the alterations in norepinephrine (NE) content and turnover in interscapular brown adipose tissue and heart of iron-deficient rats has not been demonstrated. We therefore examined NE metabolism in age-matched male Sprague-Dawley rats depleted of iron by dietary means and after repletion with iron dextran. Heart NE content was 58, 61, and 85% of controls at 0, 3, and 7 days after repletion, whereas interscapular brown adipose tissue-NE content was 87, 103, and 104% of controls. Fractional heart NE turnover was 225% greater in iron-deficient anemics than controls but normalized within 3 days. Interscapular brown adipose tissue NE turnover was 58%, 46%, and 20% above controls in iron-deficient rats after 0, 3, or 7 days of iron repletion. Hematocrit returned to 80% of normal in 7 days. Liver triiodothyronine production also increased to 80% of control in this period. A second experiment used isovolemic exchange transfusion to examine the influence of anemia per se on these alterations in organ NE turnover. Acute correction of anemia in iron deficiency did not alter brown fat NE turnover. Heart NE turnover was significantly lower in anemic animals regardless of iron status. Defects in heart and brown fat NE metabolism are reversible within 7 days of iron treatment as are alterations in triiodothyronine production. Anemia per se has little effect on brown fat NE metabolism but does dramatically decrease heart NE content.

Adipose Tissue, Brown↗

Norepinephrine turnover in iron deficiency: effect of two semi-purified diets.

The effects of two dietary treatments on norepinephrine turnover in iron deficiency were examined. These studies were designed to bridge the gap between previous studies of poor thermoregulation in iron deficiency which used a diet (HMW, Hubbel-Mendel-Wakeman formulation) relatively high in fat (46% of calories) and moderate in carbohydrate (46% of calories) and the more recent studies of thermogenesis in iron deficiency which use the AIN-76 recommended diet which is relatively low in fat (11% of calories) and high in carbohydrate (67% of calories). Iron deficient rats grew less well and had depressed thyroid hormone concentrations regardless of dietary treatment group. The HMW diet significantly increased norepinephrine turnover in heart in iron deficient animals relative to AIN diet but had no effect in controls. Brown adipose tissue norepinephrine turnover was threefold higher in HMW rats fed a low iron diet, and only 67 percent higher in control rats. This study demonstrates that certain modest macronutrient manipulations affect norepinephrine content and turnover more in iron deficient than controls. However, abnormalities in thyroid hormone concentrations persist in iron deficient animals regardless of these dietary treatments.

Adipose Tissue, Brown↗

Interactions of iron deficiency and exercise training in male Sprague-Dawley rats: ferrokinetics and hematology.

Ferrokinetic and hematologic studies were performed using adult male Sprague-Dawley rats to determine if 12 wk of exercise training alters the delivery of iron to the red blood cell (RBC) mass, the severity of the anemia or the maximal exercise performance of moderately iron-deficient animals. Forty rats were assigned to either iron-deficient (ID) or control (CN) diets, and further subdivided into sedentary (SD) and exercised (EX) groups. Exercised groups were trained on a treadmill, at a 15% grade, 65% VO2max, for 90 min/d, 4 d/wk. After 12 wk of exercise training and dietary iron deficiency, the final body weight of IDEX rats was 90.5% that of IDSD rats. Fractional plasma iron clearance in IDEX rats was 86% of that in IDSD rats (3.32 vs. 2.85%/min). Exercise training failed to increase absolute VO2max (ml/min) or change hemoglobin concentration in iron-deficient rats. Resting oxygen consumption in IDEX rats was 116% that in IDSD rats (42.8 vs. 32.5 ml.kg-1.min-1, P less than 0.05). We conclude that exercise training and iron deficiency interact to alter iron physiology in exercised, iron-deficient animals. This interaction affects the kinetic behavior of plasma iron, growth and basal oxygen consumption.

Animals↗

Increased insulin sensitivity in iron-deficient rats.

Iron deficient (ID) and control (C) rats were studied to determine if severe iron deficiency alters insulin-stimulated glucose disposal. Euglycemic hyperinsulinemic glucose clamps were conducted by infusing insulin (2 m mu.kg-1.min-1, constant rate) for 120 min while maintaining euglycemia. In a 12-h fasted state, ID rats were hyperglycemic (109.4 +/- 4.0 mg.dL-1 arterial plasma glucose, x +/- SEM) when compared with C rats (86.9 +/- 3.4 mg.dL-1) (P less than 0.05). Even though insulin was infused identically on a per kilogram body weight basis for both groups, the resulting hyperinsulinemia was higher in ID rats (3.1 +/- 0.27 ng.mL-1) compared with C rats (2.3 +/- 0.4 ng.mL-1) at the end of the clamp. Glucose infusion rates required to maintain euglycemia were twofold higher in ID rats (27.0 +/- 5.4 mg.kg-1.min-1) versus C rats (13.1 +/- 3.3 mg.kg-1.min-1) (P less than 0.05). Circulating lactic acid increased in both groups, and the concentrations in ID rats (3.2 +/- 0.4 mmol.L-1) were significantly higher than those in C rats (1.8 +/- 0.5 mmol.L-1) at the end of the clamp. When the efficiency of insulin to dispose glucose was evaluated by calculating the glucose disposal divided by the prevailing insulinemia, ID rats could dispose of almost twice the glucose per unit of insulin [9.0 +/- 0.6 (mg.kg-1.min-1)/(ng.mL-1)] when compared with C rats [5.6 +/- 0.9 (mg.kg-1.min-1)/(ng.mL-1)] (P less than 0.05). The data indicate that insulin sensitivity is increased in ID rats and that ID rats cannot metabolize exogenous insulin as well as C rats.

Anemia, Hypochromic↗

Iron deficiency anemia and steady-state work performance at high altitude.

Thirty-seven young adult male highland residents at 3,600-4,100 m in La Paz, Bolivia, performed short-duration cycle ergometry at 60, 80, and 100% of maximal voluntary O2 consumption (VO2max). Three groups of subjects representing the high-altitude population mean hemoglobin (Hb), the 10th percentile Hb, and below the 1st percentile were examined to test the hypothesis that the relationship of exercise performance to Hb concentration is similar to those relationships established at low altitude. Anemic individuals (n = 8) had 23% lower voluntary VO2max and 28% lower maximal work loads compared with controls (n = 17) or marginally anemic subjects (n = 12) although the relationship of VO2 to work load was similar. Anemic individuals maintained significantly higher arterial O2 partial pressures and Hb saturations during heavy exercise (90 +/- 0.5 vs. 85 +/- 0.6%) in conjunction with a greater heart rate up to maximal effort. A significantly decreased erythrocyte 2,3-diphosphoglycerate (2,3-DPG)-to-Hb molar ratio (0.70 +/- 0.04 vs. 1.12 +/- 0.06), suggestive of a left-shifted dissociation curve in anemics, is in contrast to the expected right-shifted curve. Moderate anemics were similar to controls. Anemic individuals did not differ in arterial lactate concentration from controls at absolute work loads; anemics had significantly lower arterial lactate concentrations at maximal effort than controls with no differences in the work load-to-lactate relationship. In conclusion, O2 transport during exercise at high altitude seems unaffected by the Hb concentrations as low as the 10th percentile of the population mean.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

A serum ferritin assay for prevalence studies of iron deficiency.

A specialized serum ferritin assay has been developed for the detection of iron deficiency in epidemiologic studies. An enzyme immunoassay (EIA) was employed to eliminate the need for radioisotopes. The problem of low sensitivity inherent with the EIA for serum ferritin was eliminated by the use of monoclonal immunologic reagents. The working range of the assay is 1-100 micrograms/L with a sensitivity of 0.5 micrograms/L. Excellent agreement in serum ferritin levels was observed between the present method and the two-site immunoradiometric assay (IRMA), while the variability at low ferritin concentrations was significantly less with the EIA. Because only 10 microliter of serum is required for each assay, duplicate measurements can be performed on a single capillary tube of blood. When an automatic microtiter plate reader for optical density measurements is used, 80-100 duplicate determinations can be completed by one technologist in a single working day.

Anemia, Hypochromic↗

Functional anemia of complicated protein-energy malnutrition at high altitude.

The effect of severe protein-energy malnutrition (PEM) on erythropoiesis in children living in the highlands of Bolivia, altitude 3700 m, was studied. Forty percent reduced hemoglobin concentrations, significantly lower arterial oxygen tensions, and a right-shifted, oxygen-dissociation curve were observed compared to high-altitude controls. Serum and erythrocyte folate concentrations were 44% and 82%, respectively, of control values. Low initial transferrin saturation decreased significantly during the 10-wk refeeding period. Thus, iron and folate deficiency contributed significantly to the poor red cell response. Results suggest that the anemia associated with severe PEM has a more significant impact on oxygen transport at high altitude than at sea level and requires an adaptive response in the oxygen-dissociation curve to satisfy tissue-oxygen demands. Furthermore, marginal iron and folate status and an inflammatory block of iron supply may limit the reestablishment of a normal tissue mass during refeeding.

Altitude↗

Soy protein products and heme iron absorption in humans.

Dual radioiron tags were used to measure both heme and nonheme iron absorption simultaneously from meat-containing meals in 76 healthy male volunteers. Partial substitution of beef with soy flour reduced the availability of nonheme iron but improved the percentage absorption of heme iron significantly (27 to 59% rise). In contradistinction three other powerful inhibitors of nonheme iron absorption, bran, tea, and desferrioxamine, had no appreciable effect on heme. Ascorbic acid (100 mg and 1000 mg in separate experiments) improved nonheme iron uptake markedly but also failed to alter the assimilation of heme. These studies demonstrate that the deleterious effects on iron nutrition of substituting soy protein for beef are partially offset by improved availability of the remaining heme iron as well as by an increase in the nonheme iron content of the meal.

Adolescent↗

Distribution of hemoglobin and functional consequences of anemia in adult males at high altitude.

In order to assess better the normal hemoglobin (Hb) range among adult males at high altitude, a hematological survey was completed in La Paz, Bolivia (3700 m). Two statistical methodologies were utilized to identify the anemic and polycythemic contributions to the Hb distribution of normal healthy men (n = 526). The Hb of normal men has a Gaussian distribution with mean and SD of 18.8 +/- 1.4 g/dl. Cutoff levels of 15.8 and 22.0 g/dl Hb were selected to identify the anemic and polycythemic subpopulations. Iron status in this high altitude population is similar to that of low altitude populations, and iron deficiency is the cause of most anemia found. An exercise test on a subsample of 56 men was utilized to validate the anemia cutoff level. Anemics as identified by the 15.8 g/dl Hb level showed a significant reduction in aerobic capacity as measured by PWC150 and estimated VO2max.

Adolescent↗

Iron absorption from legumes in humans.

Iron bioavailability in a variety of legumes was determined by radioisotopic measurements of iron absorption in human subjects. Soybeans, black beans, lentils, mung beans, and split peas were prepared as soups, labeled by the extrinsic tag method, and served to fasting subjects. Mean percentage absorption was uniformly low, ranging from 0.84 to 1.91%. Differences in absorption between the means were not statistically significant. The results indicate that these five commonly eaten legumes are all poor sources of dietary iron.

Absorption↗

Protein depletion and iron deficiency in rats.

Rats were fed on low iron diets containing 5, 10 and 30% protein. All animals demonstrated typical iron deficiency. Body size was reduced as protein intake decreased. The severity of anemia was related to the growth of the animal. Erythropoiesis appeared to be stimulated in proportion to the severity of the anemia. Iron absorption from the iron-deficient diet appeared unaffected by the associated protein deficiency. When doubly depleted animals were refed with iron, there was active red blood cell production despite the protein-depleted state, whereas with protein refeeding there was resumption of growth and increased anemia. These studies demonstrate the inverse relationship between protein and iron deficiency states when they coexist.

Anemia, Hypochromic↗

Iron deficiency decreases dopamine D1 and D2 receptors in rat brain.

Iron deficiency (ID) in early life is known to alter neurological development and functioning, but data regarding specific effects on dopamine biology are lacking. The objective of this study was to determine the extent of functional alterations in dopamine receptors in two dopaminergic tracts in young, growing, iron-deficient rats. Forty male and 40 female weanling Sprague-Dawley rats were fed either an iron-deficient (ID) diet or control (CN) diet for 6 weeks. ID decreased densities of D(1) and D(2) receptors in the caudate-putamen and decreased D(2) receptor densities in the nucleus accumbens. There were no apparent effects of ID on the affinities for the ligands in either receptor in several brain regions. In situ hybridization studies for both dopamine receptors revealed no significant effect of ID on mRNA expression for either receptor. Iron-deficient rats had a significantly higher ED(50) for raclopride-induced hypolocomotion in male and female rats compared to control rats of each sex. The loss of iron in the striatum due to dietary ID was significantly correlated with the decrease in D(2) receptor density; however, this relationship was not apparent in other brain regions. These experiments thus demonstrate abnormal dopamine receptor density and functioning in several brain regions that are related to brain regional iron loss. Importantly, the impact of ID on dopamine was more pronounced in males than females, demonstrating sex-related different sensitivities to nutrient deprivation.

Animals↗