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H McCoy

Publications and source records attributed to H McCoy.

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The effects of dietary boric acid on bone strength in rats.

The effects of dietary boron (B) (from boric acid [BA]) on bone strength were evaluated using male F344 rats. B was administered by dietary admixture of BA to NIH-07 feed at concentrations of 200, 1000, 3000, and 9000 ppm. The latter two levels were found in previous studies to be reproductively toxic to both males and the developing fetus. The first two levels are below and just at, respectively, the levels for producing fetal malformations, and are below the dose required to produce male reproductive toxicity. Resistance to destructive testing was measured on femora, tibiae, and lumbar vertebrae. Although femur and tibia resistance to bending force were not affected by any amount of dietary B, vertebral resistance to a crushing force was increased by approximately 10%, at all dose levels (200-9000 ppm). These data show that even levels of BA that are not reproductively toxic can affect the strength of the axial skeleton in rats.

Animals↗

The effects of dietary boron on bone strength in rats.

Previous studies from our laboratory found that when boric acid (BA) was administered in the diet to rats, boron levels in bone were approximately fourfold greater than serum levels. The current studies were undertaken to determine if these elevations produced adverse effects on several bone-related measures, including serum electrolyte levels, bone structure, and bone strength. Data from two studies are presented: in the first study, young adult male rats consumed a powdered diet containing 0, 3000, 4500, 6000, or 9000 ppm BA for 9 weeks. Endpoints were serum calcium, phosphorous, potassium, and chloride, as well as blood and bone boron concentrations ([B]) measured weekly during the 9-week exposure period, and at 8, 16, 24, and 32 weeks after the end of exposure. In the second study, the male and female young adult rats diet contained 0, 200, 1000, 3000, or 9000 ppm BA for 12 weeks; endpoints measured weekly were serum levels of calcium, phosphorous, and magnesium, bone [B], and bone structure (humerus) and strength (tibia, femur, and lumbar vertebrae). In treated rats, calcium was reduced in the first study but not the second. Serum phosphorous was reduced in both studies; potassium was unchanged, chloride was increased by 1%, and magnesium was reduced in all BA-exposed groups in the second study, to a maximal 19% reduction. Bone [B] was consistently increased in all treated groups, to concentrations approximately fourfold those of serum. After cessation of exposure, serum and urinary boron concentrations dropped to within control values within a week. However, even 32 weeks after the end of exposure, bone [B] remained threefold greater than controls. Male tibia and femur resistance to bending was unchanged. However, vertebral strength in compression was significantly increased by 5-10% in all dose groups (200 to 9000 ppm). The pattern was substantially similar in females. Only the humerus was examined by light microscopy and was found to be unchanged at any level of BA consumption. These data show that, despite a reduction in some serum electrolyte levels, BA consumption increased vertebral resistance to crush force, without detectably altering the microscopic structure of the humerus or the resistance of femur and tibia to a bending load. This increase in compression resistance occurred at exposure levels substantially below those that were previously reported to be reproductively toxic.

Animals↗

Interactions between magnesium and vitamin D: possible implications in the immune system.

Evidence clearly shows that magnesium and vitamin D [1 alpha, 25-dihydroxyvitamin D3; 1,25(OH)2D3] independently affect numerous aspects of the immune system. Although no reports of interactive effects on components of immunity have been found, there is evidence that the two nutrients interact in other biosystems, sometimes involving calcium. Furthermore, this paper identifies numerous places in common where both magnesium and vitamin D reportedly affect immune function. Fundamental sites for possible interaction within the immune system include cell transformation, regulation of the cell cycle, stabilization of nuclear DNA/chromatin, production of reactive oxygen species (ROS), and effects on enzymatic and hormonal actions. The presence of different functional, chemical forms of both of the nutrients within biological systems, and the availability of synthetic drug relatives of both to introduce into such systems, complicate interactive studies because such differing forms may not necessarily interact similarly or interact at all within the immune system or elsewhere. Regardless, there are compelling reasons to believe that examining interactions between magnesium and vitamin D within the immune system could prove rewarding, especially since the physiological statuses of both nutrients in human populations are less than optimum. Such human populations include the elderly whose immune function may be compromised.

Animals↗

Effects of magnesium deficiency on strength, mass, and composition of rat femur.

Magnesium (Mg) participates in the normal formation and remodeling of bone. However, little is known about effects of Mg status on the biomechanical function of bone. We examined gross morphometry and composition as well as biomechanical properties of the femurs of male rats fed diets adequate or deficient in Mg. Comparison of deficient animals and controls yielded a number of differences (all significant at P < 0.05). Mg-depleted animals exhibited slow growth, inefficient food utilization, and greatly reduced concentrations of Mg in both serum and femur ash. Compared with controls, femurs from depleted animals were shorter, but wet weights, diameters, and midfemoral cross-sectional areas showed no differences. Bone length was reduced to a greater degree than could be accounted for by differences in body weights between the groups. Bones of Mg-deficient rats contained less dry matter and less ash (which contained more Ca/g) than those of controls, along with a higher percentage of moisture. Significantly reduced bone strength in depleted animals was evident from the lighter loads supported at the elastic limit (yield point) and at fracture and from decreased stresses accompanying those loads. Modulus of elasticity, however, was not affected by Mg depletion. Different yield and breaking loads were related to different body weights of groups, but stresses were reduced for deficient bones even after adjusting for body size. Our data establish abnormal biomechanical behavior of cortical bone in Mg-deficient animals and emphasize the importance of measuring such functional properties of bone in the assessment of responses to altered metabolic conditions under experimental conditions.

Animals↗

Relation of boron to the composition and mechanical properties of bone.

A review of the experimental studies relating boron to biological effects on appendicular and axial bones in animal models suggests that numerous influences, known and unknown, affect the responsiveness of bone to dietary boron. Degrees of skeletal response to boron are modified by other nutritional variables that include calcium, magnesium, vitamin D, and fluoride. Evidence suggests that appendicular and axial bones may differ in their responses. Tests of the mechanical properties of bones may provide useful criteria for assessing the impacts of boron status on bone. These tests might resolve questions about optimal intakes of boron because mechanical properties sometimes respond to boron when composition of bones does not. Difficulty in interpreting some of the existing research arises because of the incipient state of knowledge regarding boron nutriture, to analytical problems associated with determining accurately the small quantities of boron in feed and tissues, and to technological difficulties in controlling extraneous exposure of experimental animals to boron. Yet there is considerable evidence that both compositional and functional properties of bone are affected by boron status.

Animals↗

Effects of dietary magnesium and nickel on growth and bone characteristics in rats.

We examined the interaction of dietary magnesium (Mg) and nickel (Ni) on growth and, in particular, the size, composition and mechanical properties of bones in weanling rats. Male rats were fed a diet with 0.3, 1.0 or 2.0 times the recommended concentration of Mg and adequate amounts of other nutrients. After a week, groups fed the low- and high-Mg diets were subdivided and fed the same concentration of Mg plus 0 or 500 mg Ni/kg diet (from Ni chloride) for the remaining 7 weeks. Rats fed low Mg with added Ni grew slowly and had smaller femurs and vertebrae that contained less ash and withstood less force before breaking or compression than did bones of rats fed the low-Mg diet without Ni. However, the breaking stress calculated for femurs from Mg-depleted, Ni-supplemented animals was increased. Ni did not produce these effects when added to a diet high in Mg. Compared with high dietary concentrations, the low-Mg intake had little effect unless Ni was added.

Animals↗

Magnesium and immune function: recent findings.

Recent findings regarding roles for magnesium in immunocompetence confirm and extend previous knowledge of its participation in natural and adaptive immunity. The detrimental effects of severe magnesium deficiency have been confirmed. There is better comprehension of how magnesium relates to mechanisms that control cellular activities and regulate interactions among cells that affect immune functions. Insight has been gained into how magnesium status affects susceptibility to physiological disorders, such as cardiomyopathy and cancer, that are exacerbated by inflammation and by the chemical mediators of anaphylaxis. More information is needed about the impact of less severe magnesium deficiency and of supplemental magnesium on indicators of immune function. Future studies should explore interactive relationships between Mg and such nutrients as vitamin D to elucidate more completely the roles that Mg can play in optimizing immune function.

Animals↗

A review of biointeractions of Ni and Mg. I. Enzyme, endocrine, transport, and skeletal systems.

Magnesium (Mg) and nickel (Ni) are biologically active elements in higher animals. Recent studies in vivo as well as in vitro point to interactions of Ni and Mg; non-immunological roles of these elements are reviewed here. Ni and Mg play roles in some of the same enzyme and endocrine systems, body and cell structures, and transport systems. Mg status has determined some responses to dietary Ni. Information available at this time is inadequate to permit assessment of all functions of Mg and Ni and their interactions in human populations. Evidence to date, however, warrants further investigation of the nutritional and metabolic relationships between these elements, over wide ranges of dietary intakes or exposure levels.

Animal Nutritional Physiological Phenomena↗

A review of biointeractions of Ni and Mg. II. Immune system and oncology.

Reports of interactions, in vivo and in vitro, between Ni and Mg in humoral and cellular immunity, hypersensitivity and inflammation, and in tumourigenesis are explored from a mechanistic viewpoint. Although Mg is present in much larger concentrations in normal mammalian systems than Ni, similar chemical and physical properties may allow Ni to exchange for Mg at reactive sites with damaging consequences to living organisms. Consequences of such exchanges could involve reduced immunocompetence and related carcinogenic transformation of cells. Mg status and environmental exposure to Ni are conceivable antecedents to possible biological sequelae in humans.

Animals↗

Self-esteem of adolescent females as related to race, economic status, and area of residence.

The Rosenberg Self-esteem Scale was used to measure the self-esteem of 109 14- and 16-yr.-old (+/- 6 mo.) girls. The self-esteem scores were categorized by economic status, race, and area of residence. For urban girls mean self-esteem of upper economic status subjects was significantly higher than that of those at the lower economic status. The self-esteem of upper economic status urban girls was significantly higher than the self-esteem of their rural peers. Finally, the self-esteem of the urban black girls was significantly higher than the self-esteem of the urban white girls.

Adolescent↗

Vitamin B-6 status of southern adolescent girls.

The vitamin B-6 status of 583 white and black adolescent girls living in Alabama, Arkansas, North Carolina, Oklahoma, and Virginia was assessed using the parameters coenzyme stimulation of erythrocyte alanine aminotransferase activities and dietary intakes of the vitamin. The sample included 382 white and 201 black girls who were 12, 14, or 16 years of age; the sample was also divided into low, medium, and high per capita income groups. The height and weight measurements of the subjects were within normal ranges. The mean estimated daily vitamin B-6 intake of the girls from food sources was 1.20 mg daily, as indicated by evaluation of data obtained via two nonsequential 24-hour food recalls; about half of the subjects reported consuming less than 66% of the Recommended Dietary Allowance for the vitamin. Approximately 20% of the girls had marginal vitamin B-6 status and 13%, deficient status, as indicated by coenzyme stimulation values. Coenzyme stimulation and dietary values of the race, age, and income groups were similar. Vitamin B-6 inadequacy appears to be fairly prevalent among white and black southern adolescent girls.

Adolescent↗

Nutrient intakes of female adolescents from eight southern states.

Nutrient intakes were calculated from two 24-hour recalls for 1,247 adolescent black and white girls. Whites consumed more vitamins E, C, and B-12, niacin, folacin, calcium, phosphorus, magnesium, and zinc and had higher intakes per 1,000 kcal of those nutrients, protein, vitamin D, and iron than blacks. Intakes of calcium (whites) and magnesium (both races) decreased with age. Urban girls consumed more energy and magnesium than rural ones. Folacin intake increased with income. Folacin intakes were most frequently below 67% RDAs, followed by intakes of iodine, vitamin D, iron, calcium, vitamin B-6, zinc, magnesium, and vitamin A. The majority of diets met or exceeded RDAs for protein, vitamins E, C, and B-12, riboflavin, and thiamin. Intakes are reported for most nutrients for which safe ranges have been set.

Adolescent↗

Turnbuckle orthotic correction of elbow-flexion contractures after acute injuries.

Fifteen patients with acute flexion contractures of the elbow after injuries or operations were treated with a turnbuckle splint. Satisfactory correction was achieved in twelve patients. An average reduction in deformity of about 37 degrees was recorded after an average treatment period of twenty weeks. The treatment was unsuccessful in three patients with severe intra-articular damage because the splint caused excessive discomfort. The average improvement in the arc of motion of the elbow was approximately 43 degrees.

Adolescent↗

Adding zinc reduces bone strength of rats fed a low-calcium diet.

This experiment examined skeletal effects of moderate zinc (Zn) supplementation of a low-calcium diet. Male weanling rats were fed experimental diets for about 4 wk. One diet was adequate (control), whereas two others were calcium-deficient, but otherwise adequate. One of the low-calcium (Ca) diets was supplemented with Zn. Dimensions, weight, mineral content, and mechanical properties of femurs were measured. Ca deficiency reduced bone mineral content and strength markedly. Adding Zn to the low-Ca diet further reduced bone strength and elasticity, compared with the unsupplemented low-Ca diet. When the Ca intake is low, possible benefits of Zn supplements should be weighted against risk of deterioration of mechanical properties of bone.

Animals↗

Methamphetamine concentrations in fetal and maternal brain following prenatal exposure.

Levels of methamphetamine in maternal striatum and whole fetal mouse brain were assessed at 0.5, 1, 2, and 4 h postinjection on gestational day 14 (GD14) following a single, subcutaneous injection of 40 mg/kg (+)-methamphetamine hydrochloride to pregnant mice. In the dams, striatal concentrations of methamphetamine peaked at 1 h postinjection, reaching levels of approximately 510 ng/mg protein. Amphetamine, the primary metabolite of methamphetamine, increased to 77 ng/mg protein at 2 h and remained elevated by 4 h postinjection. In the fetal brain, peak methamphetamine concentrations of approximately 122 ng/mg protein were attained at 1 h. Amphetamine was only detectable in fetal brain at 2 and 4 h postinjection. Regional analysis of methamphetamine levels in fetal striatum, cortex, and brainstem revealed that the drug was not uniformly distributed. Maternal administration of methamphetamine results in fetal brain drug concentrations, which approximate those reported in human infants whose mother abused methamphetamine. This dosage regimen, therefore, serves as an appropriate animal model for assessing the potential risks to human offspring exposed to methamphetamine in utero.

Animals↗

Hemodialysis clearance of total and unbound lidocaine.

The hemodialysis clearance and protein binding of lidocaine was determined in two acutely ill patients with end-stage renal disease. Patient A was a 74-year-old white man admitted for severe thrombocytopenia; lidocaine was started to control ventricular tachycardia. Patient B was a 66-year-old white man admitted for a myocardial infarction (MI); prophylactic treatment with lidocaine was begun after a second MI. Lidocaine hemodialysis clearance was evaluated during a five-hour dialysis procedure. Paired arterial and venous blood samples for lidocaine concentrations were collected at the midpoint of each hour of dialysis. Before dialysis and two hours after dialysis, venous samples were collected and assayed for alpha-1-acid glycoprotein (AAG) and lidocaine. The hemodialysis clearance of total and unbound lidocaine was calculated. The total amount of lidocaine removed was 8.9 and 12.5 mg for patients A and B, respectively. These amounts represented the removal of 5.6 and 2.8% of the total lidocaine dose administered to patients A and B, respectively, during the dialysis procedure. For patient A, the mean plasma dialysis clearance (Clp) was 28.2 +/- 6.3 ml/min for total lidocaine and 41.3 +/- 15.6 ml/min for unbound lidocaine. The Clp could not be calculated for patient B. The mean dialysate clearance (Cld) of total lidocaine was 28.6 +/- 7.8 and 26.3 +/- 6.5 ml/min for patients A and B, respectively. The Cld of unbound lidocaine was 42.7 +/- 6.7 and 44.5 +/- 9.9 for patients A and B, respectively. Although both patients A and B had substantial elevations in AAG concentrations (254 and 247 mg/dl, respectively), they exhibited high lidocaine unbound fractions of 0.55 and 0.68 before dialysis. The lidocaine unbound fraction was further increased in patient A after fat emulsion infusion to 0.80 and in patient B after heparin administration to 0.90. The clearance of lidocaine by hemodialysis in these two patients was negligible and clinically unimportant. No dose adjustment or supplementation was required after hemodialysis.

Aged↗