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H H Draper

Publications and source records attributed to H H Draper.

At least 55 records · Page 3Linked to original sources
PubMed1983

Long-term effects of excess protein and phosphorus on bone homeostasis in adult mice.

In adult human subjects, an interaction between dietary protein and phosphorus has been reported, in which the hypercalciuric effect of excess protein is counteracted by the hypocalciuric effect of phosphorus, with restoration of calcium balance. In adult rodents, bone homeostasis is maintained over a wide range of protein intakes, whereas high phosphorus diets cause bone loss, despite their hypocalciuric effect, as the result of an overriding increase in the excretion of endogenous fecal calcium. The present study was designed to determine whether there is an interaction between dietary protein and phosphorus with respect to bone homeostasis in adult mice. Four-month-old 45Ca-labeled B6D2F1 female mice were fed for 52 weeks the following diets (in percent): control, Ca, 0.6; P, 0.3; protein, 15; high P, Ca. 0.6; P, 1.2; protein, 15; high protein, Ca, 0.6; P, 0.3; protein, 30; and high P + high protein, Ca, 0.6; P, 1.2; protein, 30. Urinary calcium was persistently increased in the high protein group, depressed in the high P group and transiently depressed in the high P + high protein group. Excess dietary protein prevented phosphorus-induced kidney calcinosis. 45Ca loss was increased in the high P groups, but not in the high protein group. There were significant decreases in the mass of the femurs and tibias in both high P groups, whereas there was no effect of high protein intake. These results show that bone homeostasis in adult mice is sensitive to excess dietary phosphorus but not to excess protein, and that there is no interaction between these nutrients with respect to their effects on bone.

Animals↗
PubMed1982

Metabolism of malonaldehyde in vivo and in vitro.

The metabolism of malonaldehyde (MA) was investigated in vivo using male Wistar rats and in vitro using rat liver mitochondria. Twelve hr after intubation with [1,3-14C] MA, 60-70%, 5-15% and 9-17% of administered radioactivity was recovered in expired CO2, feces and urine, respectively. In rats intubated with [1,2-14C) acetate, the corresponding values were 68-82%, 1-2% and 2.3%. 14CO2 evolution was initially slower after 14C-MA administration than after 14C-acetate administration and more radioactivity was excreted in the feces and urine. In vitro experiments using [1,3-14C] MA showed that MA is metabolized primarily in the mitochondria via reactions involving O2 utilization and 14CO2 production. The apparent Km and Vmax were 0.5 mM and 9.3 nmol/min/mg protein for O2 uptake, respectively, and 2.0 mM and 2.4 nmol/min/mg protein for 14CO2 production. Addition of malonic acid to mitochondrial incubates at concentrations inhibitory to succinate dehydrogenase did not affect MA-induced O2 uptake but enhanced 14CO2 production from 14C-MA. 14C-Acetate appeared to be the major accumulating metabolite in rat liver mitochondrial preparations following a 120-min incubation with 14C-MA. A probable biochemical route for MA metabolism involves oxidation of MA by mitochondrial aldehyde dehydrogenase followed by decarboxylation to produce CO2 and acetate.

Acetates↗
PubMed1982

Uptake and oxidation of malonaldehyde by cultured mammalian cells.

Primary cultures of rat skin fibroblasts were used as a model system to investigate the cellular uptake and oxidation of malonaldehyde (MA). The cells were grown in a medium containing 10(-5) M, 10(-4) M or 10(-3) M concentrations of [1,3-14C]MA. There was a limited, concentration-dependent uptake of MA by 24 hr (approximately 4% at all concentrations). The uptake of [1,2-14C]acetate by 24 hr was in the major lipids. Despite its low uptake and rapid oxidation to CO2, pretreatment of the cells with 10(-3) M MA for 24 hr produced a latent inhibition of [14C]glucose oxidation. Limited cellular uptake of MA may explain the tolerance of cells grown in culture to relatively high MA concentrations.

Acetates↗
PubMed1982

Effect of malonaldehyde and acetaldehyde on cultured mammalian cells. Production of micronuclei and chromosomal aberrations.

The genotoxic effects of malonaldehyde (MA) and acetaldehyde (AA) were investigated using primary cultures of rat skin fibroblasts. Exposure to MA at 10(-4) to 10(-3) M concentrations resulted in dose-dependent production of micronuclei. MA was approx. 10 times as potent as AA with respect to micronuclei formation. Treatment with 10(-4) and 10(-3) M concentrations of MA for 12 h produced chromosomal aberrations (chromosomal fragments, achromatic lesions and chromatid breaks) in 14 and 34% of metaphases, respectively. At 24 h the corresponding frequencies were 46 and 52%. AA at analogous concentrations produced aberrations in 4 and 14% of metaphases at 12 h, and 20 and 40% at 24 h. Dose-dependent increases in aneuploidy were seen at 10(-4) M and higher concentrations of both aldehydes, with incidences twice as high for MA as for AA.

Acetaldehyde↗
PubMed1982

Toxicological evaluation of malonaldehyde: a 12-month study of mice.

The chronic toxicity of malonaldehyde (MA) was evaluated using Swiss female mice. Beginning at 10 wk of age, MA was administered in the drinking water for 12 mo to groups of 50 animals at levels of 0.1, 1, and 10 micrograms/g body wt.d with 100 controls. The highest dose was associated with increased mortality (28% versus 12-14%). MA had no effect on body weight, organ weight, hematological indices, or the incidence of lesions in 27 tissues examined. More liver lesions were observed in the three treatment groups than in the controls (p less than 0.05), and the histopathologic scores for severity of lesions were significantly increased in the groups that received the two higher levels of MA. The liver lesions included anisokaryosis, changes in cytoplasmic volume with architectural derangements, necrosis and neoplastic changes (nodular hyperplasia, hepatoma, and hemangioma). There was no significant increase in specific neoplasms in the treated groups, but the incidence of total neoplasms and neoplastic lesions was dose-dependent (4%, 8%, and 12%, respectively) (p less than 0.01). There was only one neoplasm (a hemangioma) among the controls (1%). Three animals (6%) given the highest dose of MA developed stomach neoplasms. In terms of human dietary exposure to MA, the lowest level of MA used in this study is about 10 times the estimated average daily intake of MA by the Canadian population on a body weight basis.

Animals↗
PubMed1981

Increased 1,25-dihydroxyvitamin D3 synthesis in rats fed a high-phosphorus diet.

Rats fed vitamin D-deficient diets containing 0.6% Ca and 0.3%, 0.6%, 1.2%, or 1.8% P exhibited progressive increments of hypocalcemia and hyperphosphatemia. In vitro assay of 25-hydroxyvitamin D3-1-alpha-hydroxylase (1-alpha-hydroxylase) activity in isolated kidney cortical mitochondria showed that hyperphosphatemia in the presence of hypocalcemia was associated with an increase in enzyme activity. The results indicate that the stimulation of 1-alpha-hydroxylase associated with depressed plasma Ca in rats fed a high-P diet overrides any inhibition of the enzyme that may be caused by excess plasma phosphate.

25-Hydroxyvitamin D3 1-alpha-Hydroxylase↗
PubMed1981

Effect of chronic high protein feeding on bone composition in the adult rat.

A study of the effect of feeding a high protein diet on bone metabolism was conducted using adult rats deep-labeled with 45Ca. A control diet (15% soy protein plus 0.2% methionine) and a high protein diet (control plus 20% lactalbumin) were fed for 10 months. Rats fed the high protein diet exhibited increases in urinary Ca, 45Ca, sulfate and volume. Total 45Ca excretion, urine calcium specific activity and urine phosphorus initially were depressed indicating an increase in the intestinal absorption of calcium, then were not significantly different from control values. After 10 months, analysis of the femur, tibia and mandible revealed no differences in wet weight, dry fat-free or ash weight, calcium, phosphorus, magnesium, or residual 45Ca content. Specific gravity and ash density also were unaffected by protein intake, as were femur length and midshaft cortical thickness. No changes in bone composition were found which would indicate that high protein diets promote bone loss in this species. The adult rat appears to be capable of compensating for the increased urinary loss of Ca associated with an increment in acid load (whether derived from an increase in diet acidity or in metabolic acid production) by reducing the fractional loss of endogenous Ca in the feces.

Animals↗
PubMed1981

Effect of a chronic acid load as sulfate or sulfur amino acids on bone metabolism in adult rats.

Diets containing an acid load as either sulfur amino acids (SAA) or inorganic sulfate were fed to 45Ca-labeled adult male rats for 10 months. Radioisotope excretion and bone composition data (femur, tibia, mandibles) were compared with those for rats fed a control (15% soy protein) diet. Rats fed the SAA supplement (1.28% cystine plus 0.19% methionine) exhibited a significant reduction in femoral weight and A:R ratio and a tendency toward lower specific gravity, dry weight, fat-free weight and calcium content. Femoral radioautographs indicated a reduction in metaphyseal bone density in six of eight animals. We have postulated that the osteopenia produced by feeding excess free SAA may be due to decreased bone formation caused by a reaction between homocysteine and the aldehyde groups of collagen, as in genetic homo-cystinuric osteoporosis. Sulfate feeding (1.42% of the diet) produced a significant increase in 45Ca excretion, indicative of enhanced bone resorption, lasting about 2 months. There was a tendency for bone mass measurements to be lower than controls after 10 months, but the differences were not significant. Two of eight sulfate-fed rats showed radiographic evidence of osteopenia. No evidence of osteopenia was seen in the controls or in rats previously fed a high protein diet containing the same concentration of SAA.

Amino Acids, Sulfur↗
PubMed1981

Occurrence of vitamin D sulfate in human milk whey.

Following reports that vitamin D sulfate is the major source of vitamin D activity in human milk, we investigated the presence of this compound in milk whey using a modification of techniques for the determination of vitamin D metabolites in plasma. Synthetic cholecalciferol sulfate, ergocalciferol sulfate an [3H]cholecalciferol sulfate were prepared by reacting radioactive cholecalciferol or nonradioactive cholecalciferol or ergocalciferol with sulfamic acid in pyridine. The products were purified sequentially by Sephadex LH-20 and high pressure liquid chromatography. The purified products were chromatographically homogeneous, exhibited an ultraviolet absorption spectrum identical to that of standard cholecalciferol, demonstrated a sulfonate ester linkage and upon saponification yielded the parent vitamin. Milk whey was extracted with methanol:methylene chloride (1:2 v/v) using [3H]cholecalciferol sulfate to estimate recovery of the compound. The extract was purified by chromatography on silica cartridges an reverse phase high pressure liquid chromatography and was quantitated by ultraviolet absorption (UV). Although added cholecalciferol sulfate was readily detected in human milk whey samples, no endogenous vitamin D sulfate was found (detection limit 1 ng/ml). The results indicate that vitamin D sulfate is not a major source of vitamin D activity in human milk.

Cholecalciferol↗
PubMed1981

Vitamin D and its metabolites in human and bovine milk.

Human and bovine milk were analyzed for vitamin D, 25-hydroxyvitamin D, 24,25-dihydroxyvitamin D, 25,26-dihydroxyvitamin D and 1,25-dihydroxyvitamin D using exhaustive chromatographic purification procedures coupled with ligand binding assays. Human milk contained the following amounts of antirachitic sterols (pg/ml, mean +/- SD, n = 5): 39 +/- 9 vitamin D; 311 +/- 31 25-hydroxyvitamin D; 52 +/- 8 24,25-hydroxyvitamin D; 32 +/- 9 25,26-dihydroxyvitamin D; 5.1 +/- 0.3 1,25-dihydroxyvitamin D. Normal bovine milk contained levels of these sterols comparable to those found in human milk. Increasing the oral dose of vitamin D to the cows was reflected by an increase of the parent vitamin and 25-hydroxyvitamin D in the milk. Vitamin D-binding protein concentration in human milk whey, determined by Ouchterlony immunodiffusion and radioimmunoassay, was 1--2% of the levels observed in the plasma and was dependent on the stage of lactation. Vitamin D and its metabolites were shown initially to be present in the whey portion but with time migrated into the fat portion of milk. The antirachitic sterols detected account for approximately 25 IU/liter and 27 IU/liter of antirachitic activity in human and bovine milk, respectively. In both species 25-hydroxyvitamin D comprised the majority of the antirachitic sterols detected in normal milk.

24,25-Dihydroxyvitamin D 3↗
PubMed1981

Self-regulation of phosphate intake by growing rats.

Groups of growing rats (100-150 g) were offered a choice of two diets, one containing a deficient concentration of phosphorus (0.1%) and the other containing 0.3, 0.6, 1.2 or 1.8% phosphorus. All diets contained 0.6% Ca and were isocaloric. Except for the groups that were offered the 0.1 and 0.3% phosphorus diets, all the animals selected mixtures of diets containing nearly identical phosphorus contents (0.33-0.36%). The group offered the two diets lowest in phosphorus selected 83% of their food from the higher (0.3%) phosphorus diet to obtain a mixture containing 0.25% phosphorus. Irrespective of the phosphorus content of the diets available, all groups ate similar amounts of food, made similar weight gains and maintained normal plasma levels of calcium and phosphorus. The experiment demonstrates the existence of a feedback mechanism by which growing rats regulate their phosphorus intake within narrow limits when allowed to self-select among diets of markedly different phosphorus contents. It is postulated that feedback regulation of phosphorus intake is mediated by changes in plasma calcium homeostasis.

Animals↗
PubMed1981

A hormonal assessment of bovine parturient paresis: evidence for a role of oestrogen.

A comparative assessment was made of the hormonal control of calcium homeostasis in eight dairy cows which developed parturient paresis and in seven normal animals from the same herd. Plasma levels of calcium, phosphorus, magnesium, free hydroxyproline, 25-hydroxycholecalciferol (25-OHD), 1,25-dihydroxycholecalciferol (1,25-(OH)2D), parathyroid hormone, calcitonin, prolactin and oestrogen were monitored from 30 days prepartum to 15 days post partum. Prepartum levels of plasma calcium, hydroxyproline and calcitonin were depressed in the paretic animals, and plasma levels of phosphorus and oestrogen were elevated. Plasma levels of 25-OHD remained stable in both groups, whereas levels of 1,25-(OH)2D, parathyroid hormone and prolactin rose sharply at parturition. Plasma hydroxyproline, an index of bone resorption, began to rise 2 days prepartum in the control cows but not until 2 days post partum in the paretic cows. The data indicate that bone resorption was inhibited in the paretic group at the onset of lactation, and that a decreased capacity for bone resorption is a major factor in the susceptibility of some cows to this disease. The failure of the paretic animals to resorb bone was not associated with an inability to synthesize the calcium-mobilizing hormones parathyroid hormone or 1,25-(OH)2D, or to regulate the production of calcitonin. However, hypocalcaemia in the affected animals was associated with a significantly higher plasma level of oestrogen (a known inhibitor of bone resorption) in the immediate prepartum period. Following parturition, plasma levels of oestrogen fell rapidly and active bone resorption ensued in the paretic animals.

Animals↗
PubMed1981

Calcium, phosphorus, and osteoporosis.

Gross epidemiological data indicate there are no significant differences in rates of aging osteopenia among countries with substantially different amounts of Ca in their national food supplies. This-observation, plus the fact that Ca administration fails to reverse osteoporotic bone loss, has led some investigators to conclude that Ca nutrition is an insignificant factor in the etiology of osteoporosis. However, it has become apparent that a Ca intake that may be adequate for adults consuming a low protein, low P, neural, or alkaline cereal-based diet is not necessarily adequate for subjects consuming a high protein, high P, acidic mixed Western diet. Ca administration inhibits postmenopausal osteopenia and there is epidemiological evidence that a liberal Ca intake reduces bone loss in middle adulthood. Ca intakes in the United States and Canada appear generally satisfactory among children and young adults, but low intakes by many individuals of middle age is a cause for concern, especially among women. Although the Ca:P ratio for the average diet consumed in these countries (about 1:1.6) appears to be satisfactory, a low intake of dairy foods, coupled with a high intake of other foods rich in natural and added phosphorus, may raise the ratio above 1:2, a value beyond which animal studies indicate that there is a risk of increased bone loss.

Adult↗
PubMed1980

Effect of malonaldehyde and acetaldehyde on cultured mammalian cells: Growth, morphology, and synthesis of macromolecules.

Primary cultures of rat skin fibroblasts were used as a model system to investigate the biological effects of the lipid peroxidation product malonaldehyde (MA). Acetaldehyde (AA) was used as a reference compound. Cells exposed to 10-3 M MA for 120 h exhibited altered morphology, cytoplasmic vacuolization, karyorrhexis, micro- and multinucleation, and a marked reduciton in mitotic index and DNA-, RNA-, and protein-synthesizing capacity. At 10-4 M, MA also caused mitotic aberrations, micronucleation, and a reduction in mitotic index and DNA synthesis. At 10-5 and 10-6 M, MA induced only the formation of small and irregular nuclei. Acetaldehyde at 10-3 M had similar but less severe effects on nuclear morphology, mitotic index, and macromolecule synthesis. At 10-4 M AA, only mitotic aberrations and nuclear changes were observed. At 10-5 and 10-6 M, AA exerted no apparent effects on either the structure or anabolic activity of the cells. With respect to antimitotic activity, MA was approximately 10 times as toxic as AA.

Acetaldehyde↗
PubMed1980

Effects of protein deficiency on plasma levels of 25-hydroxyvitamin and 24,25-dihydroxyvitamin D in the rat.

The effect of protein deficiency on plasma 25-hydroxyvitamin and 24,25-dihydroxyvitamin D concentrations was determined in weanling rats. The concentrations of these metabolites did not differ in rats fed diet providing either 0.5 or 21% casein for 4 weeks postweaning. Also, no change was observed in plasma levels of these metabolites in rats fed the 21% casein diet in amounts restricted to those consumed by the 0.5% casein animals for the same period of time. The results indicate that the synthesis and transport of 25-hydroxyvitamin and 24,25-dihydroxyvitamin D are not significantly affected by either a protein deficiency or a total food striction during the early postweaning period. This finding may be relevant to the vitamin D status of children with kwashiorkor.

24,25-Dihydroxyvitamin D 3↗
PubMed1980

The role of sulfate in the calciuria of high protein diets in adult rats.

Diets containing different sources of protein were evaluated for their effect or urinary calcium (Ca) excretion in adult male rats. High protein diets were prepared by adding 24 g N/kg as lactalbumin (Hi-Lact), egg white (Hi-EW), casein (Hi-Cas) or gelatin (Hi-Gel) to a control diet containing 24 g N/kg ascasein (Cas). There were significant differences in the degree of hypercalciuria produced by different dietary protein mixtures. A peak in Ca excretion occurred at about 2 days, when the relative values were as follows (Cas = 100): Hi-Lact, 489; Hi-EW, 429; Hi-Cas, 340, and Hi-Gel, 263. Subsequently urinary Ca declined, but a moderate hypercalciuria persisted to the end of the 8-weekexperiment, when the corresponding values (% Cas) were 200, 183,160 and 136, respectively. The degree of hypercalciuria was proportional to the sulfur content of the diets, i.e., Hi-Lact greater than Hi-EW greater than Hi-Cas greater than Hi-Gel greater than Cas. Supplementing the Cas diet with sulfur amino acids to the level present in the Hi-Lact diet resulted in a comparable increase in Ca excretion. Supplementing the Cas diet with 1.42% sulfate produced a 570% increase in urinary Ca on day 2 and a 306% increase at 5 weeks. There was a linear relationship between Ca excretion and sulfate excretion. It is proposed that a major factor in the hypercalciuria of high protein feeding is the production and excretion of sulfate. Variability in the calciuric effect of different proteins appears to be related mainly to differences in their sulfur amino acid content.

Amino Acids, Sulfur↗
PubMed1980

Influence of adult age on the skeletal response to phosphate and estrogen in rats.

Sixteen-month-old ("aged") female rats were less susceptible than 6-month-old ("mature") females to parathyroid hormone (PTH)-mediated bone resorption induced by excess dietary phosphate. Ovariectomy enhanced 45Ca loss from the bones of mature rats but not of aged rats. In mature ovariectomized (OX) females, estradiol initially suppressed phosphate-induced bone resorption but its effectiveness decreased with continued administration. Diethylstilbestrol (DES) administered continuously or on a 3-weeks-on, 1-week-off schedule in the diet suppressed the increase in 45Ca loss in OX mature females fed a high (1.2%) P diet. In contrast, DES had no consistent effect on 45Ca loss by the aged animals. Urinary cyclic adenosine monophosphate (cAMP) was increased to a similar extent in both groups by feeding excess phosphate, indicating that the reduced effect of phosphate on 45Ca loss in the aged females was due to decreased bone response to PTH. Ovariectomies produced an increase in cAMP excretion which was suppressed by DES administration. DES also suppressed the increase in urinary cAMP induced by dietary phosphate, signifying that the decrease in bone resorption produced by estrogen is associated with an inhibition either of PTH synthesis or function.

Aging↗