Biomedical subjects

S U Toverud

Publications and source records attributed to S U Toverud.

At least 37 records · Page 2Linked to original sources

PubMed1989

Adverse effects of a high-glucose diet on body weight and plasma calcium and 1,25-dihydroxyvitamin D3 levels in calcium-deficient growing rats.

We tested the hypothesis that dietary calcium would lead to greater impairment of body weight gain and calcium homeostasis if rats are fed a diet with a high glucose content compared with our standard diet in which the carbohydrate is supplied by whole wheat flour. Groups of female rats at 21 days of age were given either of two equivalent calcium-deficient diets with carbohydrate supplied either by glucose (LCaG) or by wheat flour (LCaW). Control rats were fed the wheat-flour diet containing 0.4% calcium. Since previous studies indicated divergent effects of glucose-based and flour-based diets on body weight in vitamin D-deficient rats, we designed a parallel study with vitamin D-deprived rats. Compared with rats fed the LCaW diet, the rats fed the LCaG diet had inferior body weight gain and more severe hypocalcemia (1-2 mg/ml lower) over a 40-day period, and no significant elevation of the plasma 1,25(OH)2D3 level at 61 days of age. Rats fed the LCaW diet maintained a 3-fold elevation of plasma 1,25(OH)2D3 relative to the level of control rats fed the 0.4% calcium diet. The dry weight and percent ash of tibias were similarly reduced in the two calcium-restricted groups compared to the control group. Among the vitamin D-deprived rats, those fed the glucose diet had poorer weight gain than those fed the wheat flour diet. However, both groups had similarly depressed serum calcium level, tibia ash content and 1,25(OH)2D3 level. Thus, a glucose diet combined with calcium restriction or vitamin D deprivation appears to accentuate the impairment of body weight gain and, when combined with calcium restriction, it also accentuates the impairment of calcium homeostasis and interferes with the adaptive increase in plasma 1,25(OH)2D3.

Animals↗

PubMed1988

Modulation of serum parathyroid hormone and ionized calcium concentrations during reproduction in rats fed a low calcium diet.

Moderate dietary restriction of calcium (0.1% Ca) was used to accentuate the changes in serum immunoreactive parathyroid hormone (iPTH) that had been reported earlier in lactating rats fed 0.4% Ca diet. In addition, the effects of this low-Ca diet on serum total and ionized Ca and iPTH during pregnancy, extended lactation, and weaning were examined. The positive correlation between serum total and ionized Ca was highly significant (r = 0.88, p less than 0.001, n = 120). Serum iPTH was significantly higher (36%) in pregnant rats on the day of parturition compared to nonmated controls, and there was a concomitant decrease in both total and ionized serum Ca. Within 1 day after parturition, however, serum Ca had risen to the control level. Serum iPTH remained significantly elevated during the first 2 weeks of lactation, and increased further during the third week of lactation to a level more than twice that of nonlactating controls. Serum Ca fell gradually during the second week of lactation. The high serum iPTH levels were maintained for another 2 weeks when lactation was extended with foster litters. Within 6 hr of removal of the suckling pups on day 16 of lactation, maternal serum ionized and total Ca had risen and serum iPTH had fallen; all three parameters were at levels similar to those of nonmated controls by 24-48 hr after weaning. The data suggest that serum ionized Ca is a major factor contributing to the hyperparathyroid state during lactation in rats fed a low-Ca diet.

Aging↗

PubMed1987

Increase in serum parathyroid hormone concentration in the lactating rat: effects of dietary calcium and lactational intensity.

The change in circulating levels of immunoreactive parathyroid hormone (iPTH), measured with an N-terminal specific radioimmunoassay, was examined during lactation in rats. In lactating rats consuming a diet containing 0.4% Ca (basic diet), serum iPTH was a) increased by an average of 53% between days 10 and 18 compared to the level of age-matched nonlactating rats (24.7 +/- 2.1 pg/ml vs 16.1 +/- 0.8 pg/ml, mean +/- SE, p less than 0.01) and b) significantly higher in dams suckling large litters (10-15 pups) than in dams suckling small litters (3 pups) over the period 3-13 days of lactation. Lactating rats consuming a low calcium diet (0.04% Ca), had serum iPTH levels on days 16-18 of lactation approximately twice those of nonlactating rats fed the same diet and 73% higher than those of lactating rats fed the basic diet. Serum Ca concentrations were 22% and 10% lower in dams consuming the 0.04 and 0.4% Ca diets, respectively, than in the nonlactating controls fed the same diets. Regression analysis showed a significant (p less than 0.001) negative correlation between iPTH and total serum calcium. Compared with nonmated controls, net mineral loss from femurs of dams consuming the 0.4% Ca diet was a) insignificant at day 6, b) 27% at day 15, and c) 34% at day 21 of lactation. Our data demonstrate that lactation in the rat is characterized by hyperparathyroidism that appears to be related to lactational intensity and that is accentuated when dietary calcium intake is restricted.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1987

Regulation by dietary calcium of vitamin D-dependent calcium-binding protein and active calcium transport in the small intestine of lactating rats.

To test the hypothesis that vitamin D-dependent calcium-binding protein (CaBP) and active calcium (Ca) transport in the small intestine of vitamin D-replete lactating rats are regulated by dietary Ca intake, pregnant rats were given a high Ca (1.6% Ca and 1.4% phosphorus) or low Ca (0.1% Ca and 0.4% phosphorus) diet starting 3 days before delivery. Toward the end of lactation (days 16-23) the rats were killed, and active Ca transport (using everted gut sacs) and CaBP were determined in duodenum, jejunum, and ileum. The right tibiae were used for bone weight and ash determinations. The Ca transport ratios and CaBP concentrations in jejunum and ileum were significantly increased only in the low Ca group. In contrast, in the duodenum both parameters were equally high regardless of the diet. Nonlactating rats given the two diets for the same length of time had the expected increase in both parameters in the duodenum when fed the low Ca diet. Nonlactating rats, in contrast to lactating rats, had undetectable CaBP in jejunum and ileum regardless of diet. Lactating rats fed the high Ca diet had no net loss of bone at the end of lactation compared with rats on day 1 of lactation. In contrast, lactating rats fed the low Ca diet had a net loss of 44% of bone weight. Plasma 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] concentrations on the 21st day of lactation were (mean +/- SE) 538 +/- 96 and 46 +/- 18 pg/ml in rats consuming the low and high Ca diets, respectively. The comparable values for the nonlactating rats were 140 +/- 4 and 26 +/- 8 pg/ml. In conclusion, dietary Ca restriction during lactation can stimulate CaBP and active Ca transport in both jejunum and ileum, and both parameters appear to be modulated by dietary Ca via the circulating concentration of 1,25-(OH)2D3. In contrast, in the duodenum neither parameter appears to be related to dietary Ca, plasma 1,25-(OH)2D3 concentration, or lactation-associated bone loss.

Animals↗

PubMed1987

Effects of high dietary contents of calcium and phosphorus on mineral metabolism and growth of vitamin D-deficient suckling and weaned rats.

We have tested the hypothesis that normalization of the plasma calcium (Ca) and phosphorus (P) concentrations by dietary means in vitamin D-deficient rat pups will prevent rickets. From day 6 of pregnancy rats were given a vitamin D-free diet containing 1.6% Ca and 1.4% P (-D 1.6) which normalized plasma Ca during lactation. Pups weaned from these mothers, and continuing on the -D 1.6 diet until 56 days of age, had a mean plasma Ca value of 8.6 +/- 0.2 mg/dl and were not significantly different from pups fed a vitamin D-replete diet with 0.4% Ca and 0.4% P in the following parameters: body weight (mean +/- SE for -D 1.6 rats: 197 +/- 4 g), percent bone ash (53 +/- 0.5), and tibia epiphyseal cartilage width (385 +/- 26 micron). In contrast, pups consuming the vitamin D-free diet with 0.4% Ca and 0.4% P had plasma Ca of 4.9 +/- 0.2 mg/dl, body weight of 156 +/- 4 g, reduced bone ash (45 +/- 0.5%) and abnormally wide epiphyseal cartilage (727 +/- 113 micron). Thus, elevating the plasma Ca level of vitamin D-deficient rat pups by dietary means can normalize body weight, epiphyseal cartilage width and bone mineral content.

Animals↗

PubMed1986

Purification and characterization of purple acid phosphatase from developing rat bone.

Tartrate-resistant acid phosphatase active on nucleoside di- and triphosphate substrates was isolated from developing rat bone and purified 2500-fold. The enzyme concentration had a purple coloration and activity that was sensitive to reducing agents. Mild reducing agents such as ferrous ion and ascorbic acid caused loss of purple color and increased activity toward substrates severalfold; however, a strong reductant such as dithionite caused loss of both color and activity which were partially restored by addition of ferrous ion and ascorbic acid. Enzyme activity was homogeneous with protein during the final gel permeation steps of chromatography and gave an apparent molecular size of about 40,000 Da. Determination of iron in the most pure preparation revealed the presence of 1.3 atoms of iron per molecule of the tartrate-resistant enzyme E2. Other properties of the purified enzyme include a pI of approximately 9.5 and sensitivity to inhibition by ions of copper, zinc, fluoride, and molybdate. Antibody prepared to the pre-concanavalin A (Con A)-Sepharose purified enzyme reacted with all protein from the Con A step, but it did not react with tartrate-sensitive acid phosphatase from rat bone or with potato acid phosphatase. Purple acid phosphatase from rat bone has many properties that parallel the iron-containing purple acid phosphatases from rat spleen, bovine spleen, and pig uterine secretions.

Acid Phosphatase↗

PubMed1986

Immunocytochemical localization of a tartrate-resistant and vanadate-sensitive acid nucleotide tri- and diphosphatase.

Purified rabbit antiserum to a tartrate-resistant and vanadate-sensitive acid phosphatase (nucleotide tri- and diphosphatase) prepared from rat bone was used in immunocytochemical studies. The antigen was localized in sections of fixed, decalcified tissue (head from rat) using the peroxidase-antiperoxidase bridge (PAP) or the avidin-biotin-peroxidase complex (ABC) technique. Both techniques resulted in similar and specific immunostaining in the following cells and tissues: osteoclasts situated in resorption lacunae, epithelium overlying enamel-free areas of tips of cusps of unerupted molars, cilia of respiratory epithelium, and tissue macrophages. This distribution corresponds to the cellular sites of tartrate-resistant acid phosphatase activity, as revealed by enzyme histochemistry. With the ABC method, staining in osteoclasts was obtained with antiserum dilutions of up to 1:10,000. Biochemical studies revealed that vanadate-sensitive acid ATPase activity in liver subcellular fractions was almost exclusively confined to lysosomes. Thus, the immunostaining has revealed the presence of the tartrate-resistant and vanadate-sensitive nucleotide phosphatase in many cells associated with tissue resorption and phagocytosis.

Adenosine Triphosphatases↗

PubMed1986

Somatomedin-C/insulin-like growth factor I and vitamin D-induced growth.

We measured serum somatomedin-C/insulin-like growth factor I (Sm-C/IGF-I) concentrations in vitamin D-deficient (-D) rats from 3-7 weeks of age to evaluate the role of Sm-C/IGF-I in the growth effects of vitamin D. To exclude effects of alterations in food intake, feeding patterns, and plasma minerals, controls included the following groups: pair fed (PFC; n = 10), low calcium diet (LCa; n = 10), meal fed (MFC; n = 10), and ad libitum fed (AdLC; n = 5). The -D, LCa, and PFC groups had similarly depressed growth rates and Sm-C/IGF-I concentrations. The growth and Sm-C/IGF-I concentrations of the MFC group were less than those in the AdLC group, but greater than those in the -D, PFC, and LCa groups. In all groups Sm-C/IGF-I concentrations correlated well with food intake, indicating that calorie intake, and not vitamin D deficiency or hypocalcemia, was the primary factor in reducing Sm-C/IGF-I. In the final 4 days of the study, half of the -D rats were given 1,25-dihydroxyvitamin D3 (2 ng/g BW;-D/repleted), while half of the PFC rats were given excess food during the meal period (PFC/refed). The weight gain of -D/repleted rats surpassed that of the -D rats treated with vehicle (P less than 0.05); similarly, the weight gain of PFC/refed rats exceeded that of the PFC rats (P less than 0.01). In contrast, the food intake and Sm-C/IGF-I levels of PFC/refed rats were greater than those in PFC rats (P less than 0.01), while the -D/repleted rats did not have significantly altered food intake or Sm-C/IGF-I levels. We conclude 1) that alterations in Sm-C/IGF-I concentrations of young growing -D rats are not directly related to lack of vitamin D, but, rather, to poor nutrition resulting from reduced food intake; and 2) that serum Sm-C/IGF-I is not a primary mediator of growth in -D/repleted rats since improved weight gain resulting from 1,25-dihydroxyvitamin D3 treatment can occur, acutely, without changes in serum Sm-C/IGF-I concentrations.

Animals↗

PubMed1986

Effects of vitamin D deprivation and 1,25-dihydroxyvitamin D3 treatment on ion release from rat tibiae in vitro.

Skeletal effects of dietary vitamin D and of 1,25-dihydroxyvitamin D3[1,25(OH)2D3] in vivo and in vitro were investigated using bones from vitamin D-deficient suckling rats. Tibiae from 19- to 21-day-old pups were incubated for up to 8 h in a defined medium and the net releases of Ca, inorganic phosphate (Pi) and Mg into and from the bones were determined. The pups were delivered and nursed by mothers fed either a diet containing vitamin D3 (+D) or a D-free diet (-D) starting on the sixth day of pregnancy. Effects of metabolic inhibition with iodoacetic acid (IAA, 1 mM); of elevated medium Pi concentration (2 mM); and of 1,25(OH)2D3 in vitro (2 and 10 ng/ml of medium) or in vivo (500 ng/mother ip, 2x) were evaluated. Although no effects of vitamin D on glucose metabolism or net Pi release were seen, tibiae from -D pups showed a marked decrease in net Ca release (up to 70%), while net Mg release was increased by 27%. IAA completely inhibited net Ca release in this system, had no effect on net Pi release, and reduced lactate production and net Mg release by 86 and 33%, respectively. Elevating the medium Pi concentration from 1 to 2 mM did not affect the differences between +D and -D bones. Treatment with 1,25(OH)2D3 in vitro and in vivo returned ion releases by the -D tibiae partly or completely to the +D levels. The results support the following conclusions: (1) vitamin D deficiency during suckling reduces net Ca release and increases net Mg release from bone which may contribute to the changes in circulating concentrations of these ions seen in D deficiency; (2) these effects on bone appear to be specific for Ca and Mg, since the vitamin has little or no effect on net Pi release; (3) net Ca and Mg release from rat bone in vitro presumably are energy-dependent processes, while net Pi release is not; and (4) 1,25(OH)2D3 can affect net Ca and Mg release from -D bones by a direct action.

Animals↗

PubMed1986

Circulating parathyroid hormone concentrations in normal and vitamin D-deprived rat pups determined with an N-terminal-specific radioimmunoassay.

Plasma PTH concentrations were determined in rats with an antiserum to human PTH (1-34) that cross reacts with rat PTH in order to evaluate the effects of growth, vitamin D deficiency and dietary modulations of plasma calcium. Displacement curves for synthetic rat PTH (1-34) and diluted rat plasma were parallel with curves for the hPTH (1-34) standards and hPTH (1-84). Parathyroidectomy in 33-day-old rats resulted in a fall in iPTH from (mean +/- SE) 8.1 +/- 0.5 to 5.4 +/- 0.5 pg/ml in an assay in which the lowest detectable concentration was 3 pg/ml. Elevation of plasma Ca by 0.7 mg/dl by dietary calcium supplementation in 25-day-old pups led to a plasma iPTH level of 4.4 +/- 0.7 pg/ml compared with 9.9 +/- 0.7 pg/ml in controls. There were no significant changes in iPTH in control rats fed a complete diet containing 0.4% Ca and 0.4% P over the age range 14-56 days. Rat pups (-D) suckling vitamin D-deprived mothers had plasma Ca and iPTH values of 7.76 +/- 0.16 mg/dl and 173 +/- 27 pg/ml, respectively, at 25 days of age and 5.8 +/- 0.2 mg/dl and 677 +/- 85 pg/ml, respectively, at 56 days. The -D pups that had access to their mothers' calcium-supplemented diet (1.6% Ca and 1.4% P) had a mean plasma Ca value that was 0.5 mg/dl above that of the control group and a mean plasma iPTH level of 6.7 +/- 0.8 pg/ml. We suggest that the RIA for PTH measures mostly, if not entirely, bioactive PTH. We conclude that plasma iPTH (a) remains essentially unchanged in normal rats during the rapid growth period, (b) can increase up to 75-fold in hypocalcemic vitamin D-deficient rats, and (c) can be suppressed to barely detectable levels when plasma Ca is raised less than 1 mg/dl above the level of normal control rats.

Age Factors↗

PubMed1986

Development-related regulation of plasma 1,25(OH)2D3 concentration by calcium intake in rat pups.

Circulating 1,25(OH)2D3 was determined in female rats between ages 1 and 20 weeks and in male rats between ages 5 and 12 weeks while the rats consumed diets containing vitamin D (5 U/g diet) and calcium concentrations of either 0.04, 0.4 or 1.6% Ca. When consuming the 0.4% Ca diet female rats had mean (+/- SE, pg/ml) serum 1,25(OH)2D3 values of 45 +/- 7 at 2 weeks, 272 +/- 23 at 4 weeks, 221 +/- 18 at 5 weeks and 51 +/- 6 and 49 +/- 4 at 13 and 20 weeks, respectively. Circulating 1,25 (OH)2D3 levels in the males at 4.5, 8 and 12 weeks were insignificantly higher than the levels for the females at comparable ages. There were no significant changes in plasma calcium over the ages examined in either sex. In order to test the efficiency of regulation of circulating 1,25(OH)2D3, 3-week-old female rats were given the 0.04% Ca diet for 2 or 6 weeks. At ages 5 and 9 weeks, serum 1,25(OH)2D3 values were 640 +/- 82 and 604 +/- 39 pg/ml, respectively, and therefore at least 3-fold higher than the values in rats consuming the 0.4% Ca diet. Plasma Ca concentrations in the calcium-deprived rats were 8.7 +/- 0.2 and 6.5 +/- 0.1 at 5 and 9 weeks, respectively. When the 0.04% Ca diet was introduced at 5 weeks of age, plasma Ca fell only 0.5 mg/dl and plasma 1,25(OH)2D3 rose to 1265 +/- 48 pg/ml. In contrast, plasma 1,25(OH)2D3 rose to only 176 +/- 19 pg/ml and plasma Ca fell 0.5 mg/dl when 12-week-old rats were given the 0.04% Ca diet for 5 weeks. When suckling rats were given access to the 1.6% Ca diet and continued to consume this diet after weaning, circulating 1,25(OH)2D3 concentrations were approximately one half the value of the rats consuming the 0.4% Ca diet at 3,4,5 and 6 weeks. We conclude that rats have a biphasic serum 1,25(OH)2D3 curve between the ages of 2 and 16 weeks regardless of the dietary calcium content. Circulating plasma 1,25(OH)2D3 is regulated by dietary calcium as early as the third week of life, before weaning. We suggest that the high serum 1,25(OH)2D3 concentrations are due to increased 1 alpha-OHase activity. However, the factor(s) responsible for changes in the 1 alpha-OHase remain(s) unknown, since plasma Ca does not change, and since the plasma level of other regulators of 1,25(OH)2D3, such as phosphate and parathyroid hormone do not correlate with 1,25(OH)2D3.

Age Factors↗

PubMed1984

Effects of vitamin D and parathyroid hormone on cyclic AMP production by bone cells isolated from rat calvariae.

Studies presented here were designed to investigate further the basis for an impaired cAMP response to parathyroid hormone (PTH) in osteoblastlike calvarial bone cells isolated from vitamin D-deficient rat pups. The goal was to perturb Ca, PTH, and vitamin D in vivo in order to see which factors might be responsible for the impaired in vitro bone cell cAMP response. Pups either were parathyroidectomized (PTX) 3-5 days, implanted with osmotic minipumps delivering high doses of PTH, given repeated, high doses of 1,25(OH)2D3, or were D-deficient (-D, i.e., born and suckled by D-deficient mothers). Osteoblastlike bone cells, isolated by sequential enzyme digestion and centrifugation, were exposed to PTH for 5 min in the presence of a phosphodiesterase inhibitor. In bone cells isolated from -D rat pups, both basal and PTH-induced cAMP accumulation were significantly lower than in +D bone cells. Earlier, we had shown that two daily injections of -D pups with 50 ng 1,25(OH)2D3 restores this reduced bone cAMP response of -D pups toward normal. In the present study, neither basal nor PTH-induced bone cell cAMP accumulation was affected by subjecting D-replete pups to PTX, PTH infusion, or repeated high doses of 1,25(OH)2D3 despite the fact that each treatment markedly changed serum Ca or serum immunoreactive PTH. The results indicate that the impaired bone cell cAMP response seen in -D pups is not a direct result of chronic hypocalcemia and that the "heterologous desensitization" seen in vitro with added 1,25(OH)2D3 could not be duplicated by in vivo treatment of +D pups with supraphysiologic doses of 1,25(OH)2D3.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1984

Effect of vitamin D3 on duodenal calcium absorption in vivo during early development.

The effect of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] and vitamin D deficiency on duodenal calcium absorption in suckling and weaned rats was determined by an in situ loop technique. In vitamin D-replete (+D) rats, the linear, or nonsaturable, component of calcium absorption was very efficient in 14-day-old pups and decreased with age until 35 days. The saturable component, which was undetectable in 14-day-old pups, became detectable by 18 days of age and increased until 26 days of age. Calcium absorption was not reduced in vitamin D-deficient (-D) 14-day-old pups as compared with +D pups. A high dose of 1,25(OH)2D3 increased the plasma calcium level of +D suckling rats but had no effect on calcium absorption even with milk present in the loop. Weaned -D rats had a reduced saturable component of absorption (P less than 0.01) compared with +D rats. A high dose of 1,25(OH)2D3 significantly increased calcium absorption and plasma calcium levels of -D rats. Our results indicate that during suckling calcium absorption occurs by a process that is insensitive to vitamin D. After weaning both saturable and nonsaturable processes appear to contribute to calcium absorption, and the saturable component can be influenced by vitamin D status or a high dose of 1,25(OH)2D3.

Aging↗

PubMed1984

Renal calcification in suckling rats after high doses of calcitriol (1,25-dihydroxycholecalciferol).

Light and electron microscopic characteristics of renal calcification caused by high doses of calcitriol (1,25-dihydroxycholecalciferol) were examined in suckling rats. Four daily doses of calcitriol caused greater hypercalcemia and kidney calcification in 2-week-old than in 3-week-old rats. Calcium deposits, as localized with glyoxal bis(2-hydroxyanil), von Kossa's, or alizarin red S stains, were found primarily in the renal cortex. Glomeruli and tubules were calcified in younger pups, whereas only tubules were affected in older pups. Electron-dense deposits were found primarily in proximal tubules and consisted of needlelike crystals, large mitochondrial granules, and lamellar deposits along basal laminae. The location and appearance of the deposits were similar to those described in vitamin D-treated adult rats. The deposits probably resulted from the hypercalcemia and not from a direct toxic effect of calcitriol on the kidney.

Age Factors↗

PubMed1983

Enhanced sensitivity of young suckling rats to the toxic effects of 1,25-dihydroxyvitamin D3.

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Administration, Oral↗

PubMed1983

Circulating levels and function of 1,25-(OH)2D3 in lactation.

During lactation in the rat, vitamin D is required for maintenance of a normal serum calcium level and maximal enhancement of active calcium transport in the duodenum. Vitamin D does not appear to be required for part of the adaptive increase in intestinal calcium transport or for calcium transport into the milk. The functions of vitamin D appear to be mediated by 1,25-(OH)2D3, the circulating level of which increases during lactation. Two days after sudden weaning, the serum level of 1,25-(OH)2D3 falls to levels below the pre-pregnant control level in parallel with a sharp increase in serum calcium; normal levels of calcium and 1,25-(OH)2D3 are observed one week after weaning. The initial stimulus for the increase in circulating 1,25-(OH)2D3 during lactation appears to be a small decrease in serum calcium which stimulates parathyroid hormone secretion, which in turn enhances synthesis of 1,25-(OH)2D3. Vitamin D is also required by the lactating rat to insure normal development of the suckling pup, since vitamin D deprivation during pregnancy and lactation causes significant decreases in body weight gain, in serum levels of 25-OHD3, calcium and phosphorus, in bone ash content and clear evidence of histological rickets by 20 days of age.

Animals↗

PubMed1983

Inhibition by dithionite and reactivation by iron of the tartrate-resistant acid phosphatase in bone of osteopetrotic (ia) rats.

The staining intensity and inhibitor sensitivity of acid phosphatase activity was determined histochemically in various tissues of normal and ia rat pups by the use of freeze-dried whole body sections. Activity was determined using alpha-naphthylphosphate as substrate and hexazonium pararosaniline as coupler. Sections from ia rats (6 and 24 days old) showed markedly higher enzyme activity in bone than sections from normal littermates. However, there were no differences between ia and normal pups in acid phosphatase activity in soft tissues and developing teeth. Preincubation of sections with 1-100 mM sodium dithionite (an iron-binding agent) caused a dose-related inhibition of enzyme activity in bone of ia and normal pups, but only slight inhibition of activity in soft tissues. Partial restoration of the dithionite-inhibited activity in bone was achieved by subsequent preincubation in 1 mM FeCl2. Addition of 100 mM sodium tartrate to the staining solution of non-preincubated sections caused almost complete inhibition of activity in soft tissues and the developing teeth but no inhibition of the activity in bone that was sensitive to sodium dithionite. These data indicate a) that sodium dithionite can be used as a specific histochemical inhibitor of the tartrate-resistant acid phosphatase and b) that the source of increased acid phosphatase activity in bone from ia rats is mostly from the tartrate-resistant acid phosphatase.

Acid Phosphatase↗

PubMed1983

Effects of high doses of vitamin D3 and 1,25-dihydroxyvitamin D3 in lactating rats on milk composition and calcium homeostasis of the suckling pups.

Changes in serum Ca and phosphorus and in kidney Ca were determined in lactating rats and their suckling pups after the mothers received high doses of vitamin D3 or 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3]. High dietary vitamin D3 intake (300 IU/g diet) or daily oral doses of vitamin D3 (1 microgram/g BW) to vitamin I)-replete (+D) lactating rats for 8 or 12 days caused significant increases in serum Ca in the mothers (1-2 mg/dl) and in their suckling pups (1.5 mg/dl). Daily oral doses of 1,25-(OH)2D3 (2 ng/g BW) to +D lactating rats caused a similar increase in serum Ca in the mothers, but did not affect the serum Ca of the pups. The administration of a high dose of 1,25-(OH)2D3 to vitamin D-deficient lactating rats or high doses of vitamin D3 to +D rats, caused no change in milk Ca, Mg, or phosphorus. Milk from +D rats given high doses of [3H]vitamin D3 (1 microgram/g BW) contained mostly [3H]vitamin D3 (85%) and a small amount of [3H]25-hydroxyvitamin D3 (6%). The results indicate that high doses of vitamin D3, but not 1,25-(OH)2D3, given to +D lactating rats can cause hypercalcemia in the suckling pups. The hypercalcemic effect on the pups observed after vitamin D3 treatment of the mother is probably a result of transport of toxic amounts of primarily vitamin D3 into the milk and is not due to altered mineral composition of the milk.

Animals↗