bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of short-term glucocorticoids on serum osteocalcin in healthy young men
Authors: Godschalk Michael F. , Downs Robert W. 
Published: February 2010

Abstract
Young healthy men were studied during brief treatment with prednisone to determine the rapidity of the effects of glucocorticoids on serum osteocalcin. Seven subjects were given 60 mg of prednisone orally at 8 a.m. on 5 consecutive days. Serum osteocalcin fell to 68% of the pretreatment level within 24 hours after the first dose was administered (p &lt; 0.01) and reached a nadir of 37% of baseline between 48 and 96 hours after treatment was begun (p &lt; 0.005). When prednisone was discontinued, serum osteocalcin returned promptly to pretreatment levels. Similar, though less marked, effects were found with lower doses of prednisone. Serum osteocalcin was not different from baseline after 5 mg of prednisone in five subjects, but after treatment of five subjects each with 10, 15, or 20 mg of prednisone, osteocalcin levels were 83%, 78%, and 74% of baseline, respectively (p &lt; 0.05). Serum osteocalcin levels fell rapidly with glucocorticoid administration, indicating that the effects of glucocorticoids on bone cells may be demonstrated long before clinical evidence of osteoporosis becomes apparent.
Bone mineral and glycosaminoglycans in newborn and mature rabbits
Authors: Grynpas Marc D. , Hunter Graeme K. 
Published: February 2010

Abstract
The relation between bone mineralization and glycosaminoglycans (GAG) was investigated in newborn and mature rabbit diaphyseal bone. Using the density fractionation technique, the bone was separated into fractions of increasing density from 1.4 to 2.3 grams/ml. Each fraction was analyzed by X-ray diffraction to determine the average crystal size. The GAG content of each fraction and of the unfractionated bone was determined by direct extraction and on a few fractions by sequential extraction in guanidine hydrochloride and guanidine/EDTA. There was a decrease in the GAG content with animal age and with increasing fraction density in the newborn rabbit. In one overlapping fraction (2.0–2.1 grams/ml), the GAG content was twice as high in the newborn as in the mature animal. Finally, the crystal size substantially increased from newborn to mature rabbits. Therefore, calcification and maturation of bone is associated with a decrease in the proteoglycan content of the organic matrix.
Effects of fluoride on parathyroid hormone secretion and intracellular second messengers in bovine parathyroid cells
Authors: Chenl Chu J. , Anast Constantine S. , Brown Edward M. 
Published: February 2010

Abstract
Fluoride ion (F−) alone or in conjunction with aluminum (Al3+) has been shown to stimulate the activity of guanine nucleotide-binding proteins (G proteins) in cell membrane preparations from a variety of cell types and in intact hepatic cells. Several studies have indicated that G proteins are involved in the regulation of parathyroid hormone (PTH) secretion. Intracellular second messengers which modulate PTH secretion (e.g., cAMP) have also been found to be regulated by G proteins. We have, therefore, employed F− as a probe to investigate the possible role of G proteins in the modulation of PTH release and the intracellular second messengers that have been implicated in the control of PTH secretion. F− produces a dose-dependent inhibition of PTH release with a maximal inhibitory effect (67%) at 5 mM. F− exerts its inhibitory effect within 5 min and the degree of suppression of PTH secretion gradually increases over 1 hr. F− (5 mM) inhibits PTH secretion at 0.5 mM Ca2+ to the level observed with 2 mM Ca2+ alone; moreover, the effects of F− and high Ca2+ are not additive. While 1 mM F− suppresses PTH secretion by only 21%, and 10 μM Al3+ has virtually no effect at all, together they inhibit PTH release approximately to the level (63% inhibition) observed with 5 mM NaF alone. In the presence of 10−5M dopamine, F− produces a concentration-dependent inhibition of cAMP accumulation (0.684 ± 0.033 pmoles/105 cells at 0 mM F−vs. 0.256 ± 0.048 at 5 mM F−). However, the F−-induced decrease in cAMP cannot account for the inhibition of PTH release by this agent, since addition of methylisobutylxanthine (10−4M) by F− -treated cells raises intracellular cAMP content above that of control cells but fails to reverse the inhibition of PTH release. The cytosolic calcium concentration in Fura-2-loaded cells increases from 210 ± 20 nM to 340 ± 44 nM after 5 mM F− was added to incubation media. Prior removal of extracellular Ca2+ by EGTA totally blocks the F−-induced rise in cytosolic Ca2+ without preventing the inhibition of PTH release by NaF. F− also produces a time- and dose-dependent increase in the accumulation of IP, IP2, and IP3 in cells prelabeled with [3H]inositol and incubated with 10 mM Li+, consistent with activation of phospholipase C. We conclude that F− is a potent inhibitor of PTH secretion. Its action is potentiated by Al3+, consistent with mediation via G protein(s). F− also mimics the effects of high Ca2+ on several intracellular second messengers in parathyroid cells (e.g., cAMP, cytosolic Ca2+, and IP3), presumably through activating G proteins, although the changes in these mediators may not be directly linked to inhibition of secretion. The tumor promoter TPA, an activator of protein kinase C, reverses the inhibition of PTH release by 2 mM Ca2+ but has no effect on the inhibition of secretion by F−, suggesting that F− may also affect G proteins related to secretion at a locus distal to the protein kinase C system.
Characterization of isolated and cultured chick osteoclasts: The effects of acetazolamide, calcitonin, and parathyroid hormone on acid production
Authors: Hunter Susan J. , Schraer Harald , Dr. Gay Carol V. 
Published: February 2010

Abstract
The effects of acetazolamide, calcitonin (CT), and parathyroid hormone (PTH) on acid production in isolated osteoclasts has been investigated. Osteoclasts were isolated from the endosteum of 3-week chick tibias and were maintained under culture conditions for 5 days. The cells were treated with acetazolamide (10×4M and 10−7M), CT (1 mU/ml and 0.31 mU/ml) and PTH (6.5 U/ml and 0.40 U/ml) for 1, 3, 6, and 18 hr. The cells were stained with acridine orange and the intensity of fluorescence measured by a light microscope photometer. Acetazolamide treatment resulted in a steady decline in intracellular acidity, suggesting that carbonic anhydrase plays a major role in acid production in isolated osteoclasts. Treatment with PTH produced a decline in acidity at 1 hr, followed by a peak at 3 hr and then a decline at 6 and 18 hr. The transient increase in acidity may be due to activation of carbonic anhydrase by PTH. Calcitonin treatment also resulted in a decline in cell acidity which was similar, but less pronounced than that resulting from acetazolamide treatment. These results indicate that calcitonin may mediate osteoclast activity by alterations in intracellular acid production.
Modulation of serum parathyroid hormone and ionized calcium concentrations during reproduction in rats fed a low calcium diet
Authors: Garner Sanford C. , Peng Tai-Chan , Toverud Svein U. 
Published: February 2010

Abstract
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 &lt; 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.
Adenine, guanine, and inosine nucleotides of chick growth cartilage: Relationship between energy status and the mineralization process
Authors: Matsumoto Hidehiko , Debolt Kristine , Dr. Shapiro Irving M. 
Published: February 2010

Abstract
The major aim of this investigation was to measure the nucleotide content of the developing chick epiphysis and to relate changes in nucleotide levels to chondrocyte maturation and the development of mineralization. Using a cryostat, sections of cartilage were isolated from the proximal head of the tibial growth cartilage, care being taken to preserve the metabolic integrity of the tissue. Sections were identified microscopically, pooled, and the nucleotide and nucleoside content of each sample determined by HPLC. Procedures used for the study were shown to minimize degradation of nucleotides. Their effectiveness was assessed through an evaluation of the rapid freezing technique and by examination of the effects of apatite on the recovery of endogenous and added nucleotides. Analysis of nucleotide levels in the growth cartilage indicated that chondrocytes undergo a profound change in energy metabolism during development and maturation. Thus, in the premineralized resting and proliferative zones, ATP and, to a lesser extent, GTP values were high, suggesting that the chondrocytes obtained metabolic energy through both glycolytic and mitochondrial oxidative processes. In the hypertrophic zone and in calcified cartilage, there was a profound decrease in the ATP concentration and a corresponding fall in the energy charge and the ATP/ADP ratios. The nucleotide levels in this zone indicated that there was increased reliance on nonoxidative metabolism. Measurement of nucleoside levels in premineralized cartilage suggested that there was little resynthesis of nucleotides through the salvage pathway. These observed changes in nucleotide values are consistent with earlier observations concerning chondrocyte redox and the low pO2 tension of the hypertrophic zone. The decrease in the level of ATP at the site of cartilage calcification lends support to the notion that nucleotides may serve as a source of phosphate ions for the initiation of mineralization.
The effects of muscle-building exercise on Vitamin D and mineral metabolism
Authors: Dr. Bell Norman H. , Godsen Richard N. , Henry David P. , Shary Judith , Epstein Sol 
Published: February 2010

Abstract
Exercise and muscle strength are important determinants of bone mass. Studies were carried out in normal young adult white males to determine the effects of exercise on vitamin D and mineral metabolism. Fourteen men who had engaged in regular muscle-building exercises for at least 1 year and 14 age-matched controls (age range, 19–36 year) were hospitalized on a metabolic ward and were given a constant daily diet estimated to contain 400 mg of calcium, 900 mg of phosphorus, 110 mEq of sodium, 65 mEq of potassium, and 18 mEq of magnesium. Body weight averaged 78 ± 3 kg in the exercisers and 72 ± 2 kg in the controls (NS). Serum calcium, ionized calcium, phosphate, magnesium, somatomedin-C, and immunoreactive parathyroid hormone (PTH) were not different in the two groups, whereas serum Gla-protein (39 ± 5 vs. 24 ± 2 ng/ml, p &lt; 0.01), 25-hydroxyvitamin D (23 ± 2 vs. 16 ± 2, p &lt; 0.05) and 1,25-dihydroxyvitamin D [1,25(OH)2D] (40 ± 2 vs. 29 ± 2 pg/ml, p &lt; 0.01) were higher in the exercisers than in the controls. Urinary calcium, phosphorus, sodium, potassium, creatinine clearance, and norepinephrine were not different in the two groups, whereas urinary magnesium (12.6 ± 1.0 vs. 9.4 ± 0.5 mEq/d, p &lt; 0.01) and urinary cyclic adenosine 3′,5′-monophosphate (cyclic AMP) (2.52 ± 0.19 vs. 1.72 ± 0.20 nM/dl glomerular filtrate, p &lt; 0.01) were higher in the exercisers than in the controls. There were positive correlations between serum 1,25(OH)2D and urinary calcium (r = 0.544, p &lt; 0.01) and between serum 1,25(OH)2D and urinary magnesium (r = 0.407, p &lt; 0.05) in all subjects. The results indicate that muscle-building exercise is associated with increases in serum Gla-protein, serum 1,25(OH)2D, and urinary cyclic AMP. The increase in serum Gla-protein suggests that this form of exercise enhances bone formation.
Growth of rat osteoblast-like cells in a lipid-enriched culture medium and regulation of function by parathyroid hormone and 1,25-dihydroxyvitamin D
Authors: Dr. Catherwood Bayard D. , Addison Judy , Chapman Gail , Contreras Sue , Lorang Marge 
Published: February 2010

Abstract
To examine the role of lipid metabolism in the growth and function of osteoblast-like cells, we studied ROS 17/2.8 osteosarcoma cells and primary cultures of rat calvarial osteoblasts during growth in a serum-free medium supplemented by purified human lipoproteins or by liposomes. Increase in ROS cell number was measured in sparse (1–5 × 103/cm2) cultures over 6–8 days. Liposomes (0–300 μg/ml) and high (HDL), low (LDL), and very low density (VLDL) lipoprotein fractions (0–300 μg apoprotein) markedly stimulated cell growth. Cells plated at 5 × 103/cm2 achieved growth rates in the presence of LDL or HDL comparable to 10% fetal bovine serum. Serum-free culture with exogenous lipid maintained the response of cell cyclic AMP accumulation to parathyroid hormone. Cyclic AMP response to parathyroid hormone was enhanced by glucocorticosteroid, and was attenuated by 1,25-dihydroxyvitamin D (1,25(OH)2D) with an EC50 (10−10M) comparable to that previously observed in serum-cultured cells (J. Biol. Chem. 258:736, 1985). 1,25(OH)2D also increased the alkaline phosphatase activity in ROS cells cultured in lipid-supplemented serum-free culture. Lipoproteins or liposomes also markedly enhanced the proliferative response of sparse cultures of normal rat osteoblasts to polypeptide mitogens.
Hepatic handling of vitamin D3 in micronodular cirrhosis: A structure—function study in the rat
Authors: Plourde Victor , Gascon-Barré Marielle , Coulombe Pierre A. , Vallières Sylvie , Huet P.-Michel 
Published: February 2010

Abstract
The response to vitamin D3 (D3) was studied in a model of micronodular cirrhosis induced by CCl4. The uptake and C-25 hydroxylation of D3 were then studied in isolated-perfused liver preparations. CCl4-treated rats had a significantly lower fractional hepatic D3 uptake than controls; they also had lower 25-hydroxyvitamin D3 (25(OH)D3) concentrations in both liver and perfusate following 150 min of perfusion. CCl4 induced a wide spectrum of hepatic morphologic changes ranging from mild to large collagen infiltration, but micronodular cirrhosis was present in more than 90% of the animals. Histomorphometric analysis of the liver indicated an overall highly significant increase in the volume density (Vv) of collagen infiltration, and a reduction in the Vv normal hepatocytes following CCl4. Linear relationships were also observed between the Vv normal hepatocytes and the liver, perfusate, and total 25(OH)D3, while the 25(OH)D3 production decreased in a logarithmic fashion as the collagen infiltration of the liver parenchyma increased. These data show that the overall production of 25(OH)D3 is decreased in micronodular cirrhosis; they also indicate, however, that the D3-25 hydroxylase seems to stay unimpaired in the remaining hepatocytes of the diseased liver, and that the Vv normal hepatocytes constitute one of the major determinants of the 25(OH)D3 production by the cirrhotic rat liver.
Parathyroid hormone control of free cytosolic Ca2+ in the kidney
Authors: Fujii Yoshio , Fukase Masaaki , Tsutsumi Masaharu , Miyauchi Akimitsu , Tsunenari Toru , Fujita Takuo 
Published: February 2010

Abstract
We have established a perifusion system to monitor free cytosolic calcium concentrations ([Ca2+]i) in mouse kidney slices, which presumably reflects in vivo status more accurately than renal cells in culture, by means of the fluorescent calcium indicators quin-2 and fura-2. An increase in the extracellular calcium concentrations from 0 (no added Ca2+) to 3.0 mM resulted in an increase in [Ca2+]i from 52 to 239 nM. Replacement of 118 mM of extracellular Na+ with choline, or the addition of ouabain, an inhibitor of Na+, K+-ATPase, at 10−6 M in the perfusate caused an increase in [Ca2+]i from 161 ± 13 to 873 ± 78 nM (n = 10) and 161 ± 13 to 395 ± 68 nM (n = 4), respectively, suggesting the possible existence of a Na+, Ca2+ exchange mechanism in the kidney slice. We further examined the effects of PTH on [Ca2+]i mobilization in the kidney. Both human PTH-(1–34) and hPTH-(1-84) increased [Ca2+]i within 60 s at physiologic concentrations of 10−11-10−9 M in a dose-dependent manner. On the other hand, an increase in intracellular cAMP in the slice was also detected above 3 × 10−9 M hPTH-(1–34) [base 2.1 ± 0.4 pmol/mg, 3.2 ± 0.6 pmol/mg (p &lt; 0.05 versus control values) 5 minutes after the application of 3 × 10−9 M hPTH-(1–34) and 17.3 ± 4.3 pmol/mg (p &lt; 0.05 versus control values) 3 × 10−8 M hPTH-(1–34), mean ± SEM, n = 7, p &lt; 0.05 versus control values]. We found that the effects of PTH on [Ca2+]i in our system appear to be similar to those found in cells of isolated proximal tubular cells, suggesting the cAMP and Ca2+ dual second-messenger system in PTH action. Thus, this perifusion system may enable us to study intracellular Ca2+ homeostasis in the kidney.
Increased renal calcium reabsorption in an animal model of hypercalcemia of human malignancy
Authors: Shipley Pauline J. , Shevrin Daniel H. , Kukreja Subhash C. 
Published: February 2010

Abstract
The present studies examined renal calcium (Ca) clearance in an animal model of malignancy-associated humoral hypercalcemia (MAHH) (a human squamous cell lung carcinoma carried in athymic mice). Three groups of animals-controls, normocalcemic tumor-bearing animals and hypercalcemic tumor-bearing animals-were studied in the basal state and during Ca infusion. Baseline Ca clearance was slightly but significantly elevated in the tumor-bearing hypercalcemic animals compared with the other two groups of animals. This clearea value was, however, inappropriately low for the serum Ca value. In the control and in the normocalcemic tumor-bearing animals, Ca clearance increased markedly during Ca infusion. This increase in renal Ca clearance was markedly blunted in the hypercalcemic animals compared with both the controls and the normoclacemic tumor-bearing animals. We conclude that increased renal Ca resorption contributes significantly to the pathogenesis of hypercalcemia of malignancy.
Arachidonic acid metabolism by a vitamin D3-differentiated human leukemic cell line
Authors: Stenson William F. , Teitelbaum Steven L. , Bar-Shavit Zvi 
Published: February 2010

Abstract
HL-60 is a human promyelocytic cell line that differentiates along the granulocytic pathway when incubated with dimethylsulfoxide and along the monocytic pathway when incubated with 1,25-(OH)2D3. We compared arachidonic acid metabolism in undifferentiated, DMSO-differentiated, and 1,25-(OH)2D3-differentiated cells. DMSO- and 1,25-(OH)2D3-differentiated cells metabolized exogenous arachidonic acid to both cyclo-oxygenase products (predominantly thromboxane B2 and prostaglandin E2) and 5-lipoxygenase products, including leukotriene B4. Undifferentiated cells produce these metabolites in much smaller amounts. DMSO-differentiated cells released a large percentage of phospholipid-bound arachidonic acid in response to stimulation with the ionophore A23187, zymosan, or formylmethionylleucylphenylalanine (FMLP). DMSO-differentiated cells stimulated with A23187 converted released arachidonate to LTB4 and TxB2. In contrast, 1,25-(OH)2D3-differentiated cells released a smaller percentage of phospholipid-bound arachidonate in response to stimuli, and undifferentiated cells released none at all. The three cell types (undifferentiated, DMSO-differentiated, and 1,25-(OH)2D3-differentiated) were homogenized and the 10,000 × g supernatant incubated with [14C]arachidonic acid. The supernatants from the homogenates of the DMSO- and 1,25-(OH)2D3-differentiated cells metabolized [14C]arachidonic acid to cyclooxygenase and lipoxygenase products, but the supernatant from the homogenate of undifferentiated cells did not. These data indicate that differentiation of HL-60 cells with DMSO or 1,25-(OH)2D3 induces cyclooxygenase and 5-lipoxygenase and induces mechanisms for the release of arachidonate from phospholipids by soluble and particulate stimuli.
Rapid action of 1,25-dihydroxyvitamin D3 on hepatocyte phospholipids
Authors: Baran Daniel T. , Sorensen Ann Marie , Honeyman Thomas W. 
Published: February 2010

Abstract
Recent studies have reported cellular effects of 1,25-dihydroxyvitamin D3 within 15 minutes, a time period too rapid to be mediated by nuclear activation. The vitamin increases hepatocyte cytosolic calcium levels in the absence of extracellular calcium within 5 minutes. Since metabolites of phosphatidylinositol have been implicated as second messengers in the regulation of cytosolic calcium, we examined the effect of 1,25-dihy-droxyvitamin D3 on hepatocyte phosphatidylinositol turnover and compared these effects to those produced by vasopressin. In isolated hepatocytes labeled with [3H]inositol, 1,25-dihydroxyvitamin D3 (4 nM) increased [3H]glycerophosphoryIinositol by 16% (p &lt; 0.01) within 2.5 minutes, by 18% (p &lt; 0.01) after 5 minutes, and by 11% (p &lt; 0.05) after 10 minutes. At a concentration of 20 nM, 1,25-dihydroxyvitamin D3 increased [3H]glycerophosphorylinositol by 27% (p &lt; 0.01) after 5 minutes. Vitamin D did not affect [3H]inositol polyphosphates. Conversely, vasopressin had no effect on [3H]glycerophosphorylinositol but significantly increased [3H]inositol phosphate, [3H]inositol bisphosphate, and [3H]inositol trisphosphate. 1,25-Dihy-droxyvitamin D3 (4 nM) decreased [3H]phosphatidylinositol by 10% (p &lt; 0.05) after 5 minutes and by 16% (p &lt; 0.01) after 10 minutes. At a concentration of 20 nM, 1,25-dihydroxyvitamin D decreased [3H]phosphatidylinositol by 18% (p &lt; 0.01) after 5 minutes. The vitamin did not affect [3H]phosphatidylinositol bis-phosphate or [3H]phosphatidylinositol trisphosphate. 24,25-Dihydroxyvitamin D had no effect on inositol phospholipids. The effects of 1,25-dihydroxyvitamin D3 on inositol phospholipids were blocked by quinacrine. Bromophenacylbromide inhibited the effects of 1,25-dihydroxyvitamin D3 on inositol phospholipids and also blocked the vitamin-induced increments in cytosolic calcium. In isolated hepatocytes labeled with [3H]arachidonic acid, 1,25-dihydroxyvitamin D3 (20 nM) decreased 3H-labeled phosphatidylcholine and phosphatidylethanolamine, as well as phosphatidylinositol. The data indicate that 1,25-dihydroxyvitamin D3 may enhance deacylation of hepatocyte phospholipids, perhaps by activation of phospholipase A activity. The ability of vitamin D to increase cytosolic calcium requires activation of phospholipase A. Although both 1,25-dihydroxyvitamin D and vasopressin rapidly affect phospholipid metabolism, their mechanisms of action differ.