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Biomedical subjects

J L Beard

Publications and source records attributed to J L Beard.

At least 19 recordsLinked to original sources

Abnormalities in CSF concentrations of ferritin and transferrin in restless legs syndrome.

CSF and serum were obtained from 16 patients with idiopathic restless legs syndrome (RLS) and 8 age-matched healthy control subjects. Patients with RLS had lower CSF ferritin levels (1. 11 +/- 0.25 ng/mL versus 3.50 +/- 0.55 ng/mL; p = 0.0002) and higher CSF transferrin levels (26.4 +/- 5.1 mg/L versus 6.71 +/- 1.6 mg/L; p = 0.018) compared with control subjects. There was no difference in serum ferritin and transferrin levels between groups. The presence of reduced ferritin and elevated transferrin levels in CSF is indicative of low brain iron in patients with idiopathic RLS.

Adult↗

Effectiveness and strategies of iron supplementation during pregnancy.

Iron deficiency continues to be one of the most prevalent single-nutrient deficiencies in the world. Interventions are often designed to prevent the decrease in hemoglobin concentration and the decline in iron stores associated with pregnancy. Although this is believed to be desirable for both the health of the mother and the well-being of the growing fetus, some scientists disagree. Enrichment and fortification of food items, and dietary changes resulting from education interventions, have met with some success in developed countries, but not often in the developing world. A therapeutic approach to iron supplementation, rather than a public health-based approach, is used throughout much of the world but suffers from real, or perceived, problems of compliance. Large doses of iron are most often prescribed and are associated with side effects and with increased oxidative damage. Alternatively, delayed-release preparations and intermittent oral iron supplementation lead to better overall compliance and alleviate side effects. Daily iron intervention provides more protection against a decline in the storage iron pool in pregnant women than does an intermittent schedule, but the latter is generally associated with fewer side effects, better compliance, and possibly a reduction in risk of oxidative damage. An improved cost-benefit ratio associated with a lower-dose oral iron supplement may prove to be quite positive in the future. Currently, no single approach may be universally acceptable, although a moderate iron dosage protocol will likely provide the most benefit to those who require supplemental iron.

Anemia, Iron-Deficiency↗

Variations in dietary iron alter brain iron metabolism in developing rats.

The rat has been widely used as a model for the study of iron deficiency (ID), but the differences in the timing of development of humans and rats must be taken into account to derive appropriate conclusions from the animal model. This study was designed to evaluate the effects of dietary ID and iron excess on rat brain iron and the iron metabolism proteins, transferrin (Tf), transferrin receptor (TfR) and ferritin. The experimental design is developmentally sensitive and permits control of the timing as well as the duration of the nutritional insult. Iron-deficient and iron-supplemented (SU) rats between postnatal day (PND) 10 and 21, PND 21 and 35 and PND 10 and 35 were used to study the effects of early, late, and long-term iron deficiency and supplementation. Some ID rats were iron repleted between PND 21 and 35. These experiments demonstrated several new findings: 1) Early ID/SU (PND 10-21) altered brain iron, TfR, Tf and ferritin concentration in many regions different from those observed in the later period (PND 21-35). 2) Two weeks of iron repletion were adequate for correcting the overall Fe concentration of the brain and of individual brain regions, although larger amounts of iron were necessary to fully normalize iron and its regulatory proteins. 3) Long-term ID/SU resulted accordingly in the continued decrease or increase in brain iron concentration in some brain regions and not others. In conclusion, brain regions regulate their iron concentration in response to local needs when faced with alterations in systemic iron delivery.

Animals↗

Iron requirements in adolescent females.

Adolescence is characterized by a large growth spurt and the acquisition of adult phenotypes and biologic rhythms. During this period, iron requirements increase dramatically in both boys and girls as a result of the expansion of the total blood volume, the increase in lean body mass and the onset of menses in young females. The overall iron requirements increase from a preadolescent level of approximately 0.7-0.9 mg Fe/d to as much as 2.2 mg Fe/d or perhaps more in heavily menstruating young women. These increased requirements are associated with the timing and size of the growth spurt as well as sexual maturation and the onset of menses. The available data on iron intakes in adolescents suggest that adolescent girls are unlikely to acquire substantial iron stores during this time period because intakes may average as little as 10-11 mg Fe/d. The bioavailability from diets in developing and industrialized countries indicates a negative iron balance is likely in many female populations. The low iron stores in these young women of reproductive age will make them susceptible to iron deficiency anemia during pregnancy because dietary intakes alone are insufficient, in most cases, to meet the requirements of pregnancy.

Adolescent↗

Kinetic analysis shows that iron deficiency decreases liver vitamin A mobilization in rats.

In view of evidence that nutritional status of iron and vitamin A may affect the other nutrient's metabolism, we used model-based compartmental analysis to examine effects of iron deficiency on whole-body vitamin A dynamics in rats. Weanling male Sprague-Dawley rats were fed the AIN93G diet with 2.5 nmol retinyl palmitate/g and either 45 [control (CN)] or 4 microg/g Fe [iron-deficient (ID)] for 8 wk. ID rats consumed food ad libitum; CN rats were food-restricted so that their body weights were the same as ID rats. Two rats/group were killed; liver vitamin A was determined and used for vitamin A balance calculations. [(3)H]Retinol-labeled plasma was administered intravenously to remaining rats, and 27 serial blood samples were collected for 7 wk. At killing, plasma vitamin A was 0.52+/-0.12 (ID, n = 5) vs. 1.34+/-0.12 micromol/L (CN, n = 6; P<0.001), and liver vitamin A was 809+/-94 (ID) vs. 112+/-24 nmol (CN, P<0.001). Plasma tracer data were fit to a three- or four-compartment model using the Simulation, Analysis and Modeling computer program and kinetic parameters were calculated. Vitamin A transfer rate between the retinyl ester storage pool [14+/-3 (ID) vs. 24+/-4 nmol/d (CN), P<0.05] and plasma was lower in ID rats. Vitamin A remained longer in the body [44+/-11 (ID) vs. 22+/-3 d (CN), P<0.05]. Adjusted mean disposal rate was lower in ID (10.0) than CN rats (19.9 nmol/d), as was estimated vitamin A absorption efficiency [58% (ID) vs. 76% (CN)]. Our results suggest that iron deficiency inhibits mobilization of vitamin A stores and may decrease the absorption and irreversible utilization of vitamin A.

Animals↗

Iron status and stores decline with age in Lewis rats.

In the context of a larger study examining the interaction of vitamin A (VA) status and age on immune function, we examined age-related changes in hematologic and iron status variables in male Lewis rats. Animals were fed a nutritionally adequate purified diet containing either 0.35 (marginal), 4.0 (control) or 50 (supplemented) mg retinol equivalents (as retinyl palmitate) per kg of diet from the time of weaning until killing at 8-10 (middle-aged) or 20-22 (old) mo of age. Neither VA nor VA and age interaction effects were significant for most iron variables examined. After controlling for body weight, old rats had significantly lower hemoglobin, hematocrit and plasma iron than middle-aged rats. This decrease in hematologic and transport iron variables was not accompanied by a shift of iron into other storage compartments. Old rats also had significantly lower total iron content and iron concentration in liver, spleen and bone marrow. Hemosiderin iron in marrow smears correlated significantly (r = 0.43-0.76, P: < 0.05) with chemical estimates of iron in storage, transport and functional pools. Old rats also tended to have less stained iron in femur marrow smears. Thus, body iron in functional, transport and storage compartments, namely the liver, spleen and bone marrow, were significantly lower in old than in middle-aged rats. Although iron stores and status are usually considered to increase with advancing age, our data show a consistent pattern of lower hematologic and storage iron variables in old than in middle-aged Lewis rats. Future research is indicated to understand the biology and functional consequences of the observed age-associated decline in body iron.

Aging↗

Bone structural and mechanical properties are affected by hypotransferrinemia but not by iron deficiency in mice.

Hypotransferrinemia is a genetic defect in mice resulting in <1% of normal plasma transferrin (Tf) concentrations; heterozygotes for this mutation (+/hpx) have low circulating Tf concentrations. We used this mutant mouse in conjunction with dietary iron deficiency to study the influence of Tf and iron on bone structural and mechanical properties. Twenty-one weanling wild-type BALB/cj +/+ mice and 21 weanling +/hpx mice were fed iron-deficient or iron-adequate diets for 8 weeks. Twelve hpx/hpx mice were fed the iron-adequate diet. Hypotransferrinemia resulted in increased tibia iron and calcium concentrations, lower femur failure load, and extrinsic stiffness. Because the femurs of the hpx/hpx mice were disproportionately small, these bones actually had increased tissue material properties (ultimate stress [US] and modulus of elasticity) than those of wild-type mice. This is the first report on the effect of dietary iron deficiency on bone structural and mechanical properties. Dietary iron deficiency in +/+ and +/hpx mice decreased tibia iron concentrations but had no effect on tibia calcium and phosphorus concentrations or femur structural or mechanical properties. Because the bones of the hpx/hpx mice were small, but had superior tissue mechanical properties, we conclude that Tf is important for normal bone mineralization.

Animals↗

Evidence of a role for neuropeptide Y and monoamines in mediating the appetite-suppressive effect of GH.

Among the many responses to GH administration is suppression of voluntary feed intake (FI) in some species, attributed to improvement in the efficiency of nutrient utilization and, therefore, reduced need for ingested substrates. Commercial broiler chickens have been genetically selected for generations for rapid growth, realized largely via the major correlated response of increased voluntary feed consumption. Neuropeptide Y (NPY) and monoamines play very important roles in the central regulation of feeding. Preliminary studies from our laboratory suggest that the appetite-suppressive effect of GH may be independent of its actions as a repartitioning agent, and may involve alterations in NPY expression at the pre-translational level. The purpose of this investigation was to explore the dose-response nature of the appetite-suppressive effect of GH in juvenile broilers, and the possible involvement of NPY and monoamines in this process. A GH dose-response study was conducted using 8-week-old female broilers infused i.v. with GH in a pulsatile pattern for 7 days at 0, 10, 50, 100 or 200 microgram/kg body weight per day. Hypothalamic NPY and epinephrine (EP) concentrations decreased in a dose-related manner with GH. At the highest dosage, voluntary FI decreased 19% (P<0.05) and hypothalamic NPY mRNA decreased approximately 50% in the infundibular nuclei and midline region (P<0.0001). In contrast, birds pairfed to the high-GH dosage group did not differ from controls, verifying that changes in NPY and monoamines were not secondary to reduced FI. We conclude that hypothalamic NPY and EP are likely candidates to explore further as mediators of the appetite-suppressive effect of GH.

Animals↗

Iron deficiency alters H- and L-ferritin expression in rat brain.

Ferritin (Ft) H and L subunits are independently regulated proteins with both transcriptional and translational regulation in response to cellular iron levels. While the heterogeneous distribution of ferritin and iron in the brain is now well established, the relative response of each subunit to iron deficiency and iron supplementation, is not well defined. Weanling male Sprague-Dawley rats (n=12 per group) were randomly assigned to an iron deficient (3.5 mg Fe/kg diet), control (35 mg Fe/kg diet) or supplemented (350 mg Fe/kg diet) diet for six weeks. The H-/L-ferritin subunit ratio and mRNA levels were determined. Overall, the protein ratio in control rats of H to L was approximately 45:1 compared to a ratio >60:1 in iron deficiency but the absolute amounts of each subunit varied greatly from one brain region to another. The ratio of H-:L-ferritin mRNA was 6:1 and was not affected by dietary iron deficiency in contrast to a potent effect on mRNA levels in liver. Severe iron deficiency reduced brain ferritin H protein levels significantly in all regions, whereas only ferritin L levels in striatum, substantia nigra and pons were affected by iron deficiency. Supplemental dietary iron increased both ferritin subunits, with the largest increase (50%) in the hippocampus. These data indicate that ferritin H and L subunits within the brain respond differently to iron status and suggest post transcription regulation as a key event.

Animals↗

Transferrin is required for normal distribution of 59Fe and 54Mn in mouse brain.

Hypotransferrinemia (hpx/hpx) is a genetic defect in mice resulting in <1% of normal plasma transferrin (Tf) concentrations; heterozygotes for this mutation (+/hpx) have low circulating Tf concentrations. These mice provide a unique opportunity to examine the role of Tf in Fe and Mn transport in the brain. Twenty weanling wild-type BALB/cJ mice, 15 +/hpx mice, and 12 hpx/hpx mice of both sexes were injected i.v. with either 54MnCl(2) or 59FeCl(3) either 1 h or 1 week before killing at 12 weeks of age. Total brain counts of 54Mn and 59Fe were measured, and regional brain distributions were assessed by autoradiography. Hypotransferrinemia did not affect total brain Mn uptake. However, 1 week after i.v. injection, hpx/hpx mice had less 54Mn in forebrain structures including cerebral cortex, corpus callosum, striatum, and substantia nigra. The +/hpx mice had the highest total brain 59Fe accumulation 1 h after i.v. injection. A striking effect of regional distribution of 59Fe was noted 1 week after injection; in hpx/hpx mice, 59Fe was located primarily in choroid plexus, whereas in +/+ and +/hpx mice 59Fe was widely distributed, with relatively high amounts in cerebral cortex and cerebellum. We interpret these data to mean that Tf is necessary for the transport of Fe but not Mn across the blood-brain barrier, and that there is a Tf-independent uptake mechanism for iron in the choroid plexus. Additionally, these data suggest that endogenous synthesis of Tf is necessary for Fe transport from the choroid plexus.

Animals↗

Existing and emerging mechanisms for transport of iron and manganese to the brain.

The metals iron (Fe) and manganese (Mn) are essential for normal functioning of the brain. This review focuses on recent developments in the literature pertaining to Fe and Mn transport. These metals are treated together because they appear to share several transport mechanisms. In addition, several neurological diseases such as Alzheimer's Disease, Parkinson's Disease, and Huntington's Disease are all associated with Fe mismanagement in the brain, particularly in the striatum and basal ganglia. Similarly, Mn accumulation in brain also appears to target the same brain regions. Therefore, stringent regulation of the concentration of these metals in the brain is essential. The homeostatic mechanisms for these metals must be understood in order to design neurotoxicity prevention strategies.

Animals↗

New insights into the mechanism and actions of growth hormone (GH) in poultry.

Despite well documented anabolic effects of GH in mammals, a clear demonstration of such responses in domestic poultry is lacking. Recently, comprehensive dose-response studies of GH have been conducted in broilers during late post-hatch development (8 to 9 weeks of age). GH reduced feed intake (FI) and body weight gain in a dose-dependent manner, whereas birds pair-fed to the level of voluntary FI of GH-infused birds did not differ from controls. The reduction in voluntary FI may involve centrally mediated mechanisms, as hypothalamic neuropeptide Y protein and mRNA were reduced with GH, coincident with the maximal depression in FI. Growth of breast muscle was also reduced in a dose-dependent manner. Circulating IGF-I was not enhanced by GH, despite evidence that early events in the GH signaling pathway were intact. A GH dose-dependent increase in circulating 3,3',5-triiodothyronine(T3) paralleled decreases in hepatic 5D-III monodeiodinase activity, whereas 5'D-I activity was not altered. This confirms that a marked hyperthyroid response to GH occurs in late posthatch chickens, resulting from a decrease in the degradative pathway of T3 metabolism. This secondary hyperthyroidism would account for the decreased skeletal muscle mass (52) and lack of enhanced IGF-I (53) in GH-treated birds. Based upon these studies, it is now evident that GH does in fact have significant effects in poultry, but metabolic responses may confound the anabolic potential of the hormone.

Animals↗

A genetic developmental model of iron deficiency: biological aspects.

Numerous studies have demonstrated the negative impact of iron deficiency on growth and development. The present study expands on the published literature by exploring the role of genetics and developmental timing on the impact of iron deficiency on development in two strains of mice. Growth rates, organ weights, and hematological responses to an iron-deficient diet differed by strain and sex. The results from this study provided novel insight into iron metabolism and the impact of iron deficiency in C57 and DBA strains of mice. Future studies should continue to examine the contributions of both genetics and sex to the development of iron deficiency.

Animals↗

Effects of an omnivorous diet compared with a lactoovovegetarian diet on resistance-training-induced changes in body composition and skeletal muscle in older men.

BACKGROUND: Very limited data suggest that meat consumption by older people may promote skeletal muscle hypertrophy in response to resistance training (RT). OBJECTIVE: The objective of this study was to assess whether the consumption of an omnivorous (meat-containing) diet would influence RT-induced changes in whole-body composition and skeletal muscle size in older men compared with a lactoovovegetarian (LOV) (meat-free) diet. DESIGN: Nineteen men aged 51-69 y participated in the study. During a 12-wk period of RT, 9 men consumed their habitual omnivorous diets, which provided approximately 50% of total dietary protein from meat sources (beef, poultry, pork, and fish) (mixed-diet group). Another 10 men were counseled to self-select an LOV diet (LOV-diet group). RESULTS: Maximal strength of the upper- and lower-body muscle groups that were exercised during RT increased by 10-38% (P < 0.001), independent of diet. The RT-induced changes in whole-body composition and skeletal muscle size differed significantly between the mixed- and LOV-diet groups (time-by-group interactions, P < 0. 05). With RT, whole-body density, fat-free mass, and whole-body muscle mass increased in the mixed diet group but decreased in the LOV- diet group. Type II muscle fiber area of the vastus lateralis muscle increased with RT for all men combined (P < 0.01), and the increase tended to be greater in the mixed-diet group (16.2 +/- 4.4 %) than in the LOV diet group (7.3 +/- 5.1%). Type I fiber area was unchanged with RT in both diet groups. CONCLUSION: Consumption of a meat-containing diet contributed to greater gains in fat-free mass and skeletal muscle mass with RT in older men than did an LOV diet.

Aged↗

Iron deficiency in young rats alters the distribution of vitamin A between plasma and liver and between hepatic retinol and retinyl esters.

We assessed whether iron deficiency alters the concentration of vitamin A (VA) in plasma or liver and the chemical distribution between hepatic unesterified and esterified retinol. Weanling male Sprague-Dawley rats (n = 10/group) were allocated to one of four diet groups: low iron (ID3, 3 mg of elemental iron/kg diet), marginal iron (ID15, 15 mg/kg), control diet food-restricted to the ID3 group (FR, 35 mg/kg), and control diet ad libitum consumption (AD, 35 mg/kg). Both ID3 and FR rats grew less than AD and ID15 rats. At the end of 5.5 wk, plasma retinol concentrations of the ID3 and FR rats were reduced >40% compared to ID15 and AD rats [Kruskal-Wallis test (K-W), P < 0.0042)]. Paradoxically, the hepatic VA concentration was greater in FR rats, with accumulation of more retinyl esters and retinol compared to the other dietary groups. Concentrations of hepatic retinyl esters and retinol did not differ among the other groups, but the molar ratio of hepatic retinyl esters to retinol was greater in ID3 rats (20.1 +/- 1.4) compared to ID15 rats (13.8 +/- 1.6, P = 0.02), AD (11.3 +/- 2.1, P < 0.0042) and FR (9.5 +/- 1.1, P < 0.0042). Iron deficiency may cause changes in liver and plasma VA that are refractory to VA intake, and thus a benefit may be derived from combining iron and VA supplements during nutrition interventions.

Animals↗

Iron deficiency and neural development: an update.

In Latin America, 10-30% of reproductive age females and upwards of 40-70% of pregnant women may be iron deficient. The true prevalence in young children and infants is often hard to determine because of problems in survey design, data collection, or sampling. There is little doubt, however, that iron deficiency anemia is a significant nutritional problem in many infants within the first 5 years of life. Numerous intervention studies have been performed across the world with varying success and it is clear that in nearly all situations it is a preventable disease with preventable consequences. One such consequence is the alteration in cognition that occurs in iron deficient individuals during the early parts of their life cycle and perhaps at later times as well. While iron deficiency was once presumed to exert most of its deleterious effects only if anemia was present, it is now clear that many organs show morphologic, physiologic, and biochemical changes before there is any drop in hemoglobin concentration. Iron deficiency is associated with alterations in many metabolic processes that may impact brain functioning; among them are mitochondria electron transport, neurotransmitter synthesis and degradation, protein synthesis, organogenesis, and others. It is necessary to separate the developmental aspects of iron deficiency and neural functioning from the aspects of iron deficiency that could occur at any time in life. A number of reviews have discussed the links between brain iron and neuropathology, brain iron, nutrition, and development, and iron status and cognition. New knowledge concerning the acquisition of iron by the brain in early life is being generated by numerous research groups. In the next decade a much clearer understanding of the role of brain iron on neural functioning will probably emerge.

Animals↗

Selective ablation of human T-cell lymphotropic virus type 1 p12I reduces viral infectivity in vivo.

Human T-cell lymphotropic virus type 1 (HTLV-1) is the etiologic agent of adult T-cell leukemia and HTLV-1-associated myelopathy. Novel, yet conserved RNA transcripts encoded from open reading frames (ORFs) I and II of the viral pX region are expressed both in vitro and in infected individuals. The ORF I mRNA encodes the protein p12(I), which has been shown to localize to cellular endomembranes, cooperate with bovine papillomavirus E5 in transformation, as well as bind to the IL-2 receptor beta and gamma chains and the H+ vacuolar ATPase. It is unknown what role p12(I) plays in the viral life cycle. Using an infectious molecular clone of HTLV-1 (ACH) and a derivative clone, ACH.p12(I), which fails to produce the p12(I) message, we investigated the importance of p12(I) in infected primary cells and in a rabbit model of the infection. ACH.p12(I) was infectious in vitro as shown by viral passage in culture and no qualitative or quantitative differences were noted between ACH and ACH.p12(I) in posttransfection viral antigen production. However, in contrast to ACH, ACH.p12(I) failed to establish persistent infection in vivo as indicated by reduced anti-HTLV-1 antibody responses, failure to demonstrate viral p19 antigen production in peripheral blood mononuclear cell (PBMC) cultures, and only transient detection of provirus by polymerase chain reaction in PBMC from ACH.p12(I)-inoculated rabbits. These results are the first to show the essential role of HTLV-1 p12(I) in the establishment of persistent viral infection in vivo and suggest potential new targets in antiviral strategies to prevent HTLV-1 infection.

Animals↗

Transferrin response in normal and iron-deficient mice heterozygotic for hypotransferrinemia; effects on iron and manganese accumulation.

Hypotransferrinemia is a genetic defect in mice resulting < 1% of normal plasma transferrin (Tf) concentrations; heterozygotes for this mutation (+/hpx) have low circulating Tf concentrations. These mice provide a unique opportunity to examine the developmental pattern and response of Tf to iron-deficient diets, and furthermore, to address the controversial role of Tf in Mn transport. Twenty-three weanling +/hpx mice and forty-five wild-type BALB/cJ mice were either killed at weaning or fed diets containing either 13 or 72 mg kg-1 Fe, and killed after four or eight weeks. Plasma Tf concentrations were lower in +/hpx mice, plasma Tf nearly doubled and liver Tf was only 50% of normal in response to iron deficiency. Brain iron concentration did not correlate significantly with either plasma Tf or TIBC. However, iron accumulation into brain continued with iron deficiency whereas most other organs had less iron. These results imply that either there is a selected targeting of iron to the brain by plasma Tf or there is an alternative iron delivery system to the brain. Furthermore, we observed no differences in tissue distribution of 54Mn despite the differences in circulating Tf concentrations and body iron stores; this suggests that there are non-Tf dependent mechanisms for Mn transport.

Animals↗