bluuebunny/crossref_metadata_2025_split huggingface dataset:
A single-day treatment of tumor-induced hypercalcemia by intravenous amino-hydroxypropylidene bisphosphonate
Authors: Dr. Thiébaud D. , Jaeger P. , Jacquet A.F. , Burckhardt P. 
Published: February 2010

Abstract
Twenty patients with malignant hypercalcemia were treated with amino-hydroxypropylidene bisphosphonate (AHPrBP, previously APD), a potent inhibitor of osteoclast-mediated bone resorption. To assess the efficacy of a single-day treatment and determine the optimal dose of this compound, all patients received AHPrBP intravenously over 24 h, but they were divided into two subsequent groups of 10 patients: Group A received a single dose of 60 mg AHPrBP and group B received a single dose of 30 mg. In both groups all patients responded to AHPrBP with a decrease in plasma calcium concentration after a mean time lag of 1 day. Within 6 days, plasma calcium (corrected for serum proteins) fell from 3.24 ± 0.14 to 2.24 ± 0.06 mmol/liter in group A (p &lt; .001), but only from 3.22 ± 0.15 to 2.49 ± 0.10 mmol/liter in group B (p &lt; .005). Whereas in all patients from group A plasma calcium was within the normal range at days 9 and 14, in 4 patients of group B it was still above the normal range at day 9, and in 5 patients at day 14. There was a significant difference in plasma calcium between group A and group B from days 5 to 14 (p &lt; .005). In both groups, urinary calcium excretion fell dramatically and similarly, and plasma phosphate concentration decreased significantly (p &lt; .01) to values slightly below the normal range from days 4 to 6. A similar and significant decrement in TmP/GFR was noted at days 4 and 6 (p &lt; .01) which was related to the rise (p &lt; .01) in plasma parathyroid hormone concentration from days 4 to 9. Urinary hydroxyproline excretion decreased significantly (p &lt; .01) in both groups from days 0 to 9, with a trend to reincrease from day 6 on in group B. We conclude that a single intravenous dose of AHPrBP is effective in the treatment of tumor-induced hypercalcemia; but 60 mg has a more pronounced and prolonged effect than 30 mg, achieving normocalcemia in al patients, while 30 mg normalized plasma calcium only in moderately hypercalcemic patients. The decrease in plasma calcium after a single day infusion of 60 mg is similar to that previously observed during treatment of 30 mg per day during 6 days.
Paget's disease of bone treated in five days with AHPrBP (APD) per Os
Authors: Dr. Thiébaud D. , Jaeger P. , Burckhardt P. 
Published: February 2010

Abstract
Amino-hydroxypropylidene bisphosphonic acid (AHPrBP, previously APD) is a potent inhibitor of bone resorption. Since it remains in bone for a long time, and since it was not found to impair bone mineralization, it could be administered at high dose over a short period of time. Therefore, 11 patients with symptomatic Paget's disease received AHPrBP orally at 1200 mg/day over 5 consecutive days. Controls were performed after 1 month in all patients, 6 months in 8 patients, and one year in 4 patients. Clinical improvement and biochemical remission was observed in all patients, except one with severe disease.
Side effects were negligible. Disease activity at bone scintigram decreased over 6 months. Plasma alkaline phosphatase activity fell progressively and significantly from 210 ± 26 U/I (x̄ ± SEM) to 103 ± 10 U/I after 6 months (nl &lt; 120 U/I).
Urinary excretion of hydroxyproline decreased immediately and became normal (nl &lt; 2.3 μmol/IGF) as a mean at day 5 (from 4.6 ± 0.4 μmol/IGF to 2.1 ± 0.3 μmol/IGF). Thereafter it remained within the normal range (2.0 ± 0.2 μmol/l at day 180). Plasma calcium and phosphate concentrations fell transiently between day 4 and 15, whereas plasma PTH levels increased over this period of time. In conclusion, a short course of AHPrBP given per os at high dose induces a rapid decline in activity and remission of moderate Paget's disease, without significant side effects.
Synthetic parathyroid hormone fragments shortened at the amino terminus stimulate glucose-6-phosphate dehydrogenase activity in the distal renal tubule
Authors: Sakaguchi Kazushige , Fukase Masaaki , Kobayashi Ikuo , Kimura Terutoshi , Sakakibara Shumpei , Katsuragi Shigeo , Morita Kaoru , Noda Toshiharu , Fujita Takuo 
Published: February 2010

Abstract
The cytochemical bioassay, using glucose-6-phosphate dehydrogenase (G6PD) activity in the distal convoluted tubule of a guinea pig as an index, is specific and the most sensitive method of evaluating the biological activity of parathyroid hormone (PTH). Using this method, biological activities of the amino- or carboxylterminal PTH fragments and analogues, human (h) PTH-(3–34), [Tyr34]hPTH-(7–34)amide(NH2), [Tyr34]hPTH-(13–34)NH2, hPTH-(39–84), hPTH-(51–84), hPTH-(69–84), were tested over a concentration range of 10−16 to 10−13M. In addition, the combined effect of these hormones with human or bovine PTH-(1–84) and the effect of dibutyryl ((Bu)2) cAMP were also evaluated.
In the 14-min time-course study, amino-terminal PTH fragments and analogues induced cyclic changes of G6PD activity with shorter cycle lengths in higher concentrations and with constant peak heights regardless of the concentrations. Human and bovine PTH-(1–84) showed the same activity on G6PD activation at 6 min. hPTH-(3–34), [Tyr34]hPTH-(7–34)NH2, and [Tyr34]hPTH-(13–34)NH2 were equipotent with PTH-(1–84) on a molar basis, and none of these analogues inhibited PTH-(1–84) even with doses up to 240 times that of PTH-(1–84). Carboxyl-terminal PTH showed no effect. (Bu)2cAMP mimicked the effect of PTH-(1–84) on G6PD activation in time course and dose response.
We conclude that the amino terminus is not essential for the biological activity of PTH in the cytochemical bioassay.
Healing of rachitic lesions in chicks by 24R,25-dihydroxycholecalciferol administered locally into bone
Authors: Lidor Cobi , Atkin Isaac , Prof. Ornoy Asher , Dekel Samuel , Edelstein Samuel 
Published: February 2010

Abstract
In an attempt to further define the nature of the active metabolite in bone formation, a series of experiments were conducted whereby vitamin D metabolites were administered locally in vivo into the proximal epiphyseal growth plate of the tibiae of rachitic chicks. Local administration of 3 μg of 24,25(OH)2D3in vivo to D-deficient chicks resulted in disappearance of the rachitic lesions in the same leg. Administration of 1 μg 1,25(OH)2D3 in a similar manner failed to show any sign of healing. Injection of 5 μg 25(OH)D3 was followed by recovery from rickets in both the injected right leg and in the vehicle-injected left tibia, although the recovery was more pronounced in the injected leg. Lower doses of 0.3 or 1 μg 24,25(OH)2D3 failed to reverse the rachitic lesions and induced only minimal recovery. These findings suggest that 24,25(OH)2D3 at the higher doses has a direct local effect on cartilage and bone, while 1,25(OH)2D3 has no such effect in chicks. 25(OH)D3 is probably absorbed from the epiphyses into the blood stream and converted into the active metabolites, which were indeed detected in the blood to exert its systemic effects.
Computer modeling and analysis of cross-sectional bone density studies with respect to age and the menopause
Authors: Dr. Sambrook Philip N. , Eisman John A. , Furler Stuart M. , Pocock Nicholas A. 
Published: February 2010

Abstract
Controversy exists about rates of bone mineral loss from the lumbar spine at the menopause. Cross-sectional studies of lumbar bone mineral against age have been interpreted as evidence for or against a menopause-related change in lumbar bone loss, depending on their goodness of fit to either linear or nonlinear equations. To investigate the ability of cross-sectional studies to detect accelerated lumbar bone loss at the menopause, we constructed models of different patterns of loss and evaluated the findings in cross-sectional analyses of computer-simulated populations of normal women. A sample size of &gt;300 was needed to distinguish between linear and nonlinear patterns of bone loss with a power of 90% when the data was analyzed throughout life. Examining for differences between the slopes of the regressions of pre- and postmenopausal women was more useful for detecting nonlinear bone loss under some circumstances. A difference between slopes was apparent in studies containing 100 subjects if lumbar bone density (BMD) was assumed to be unchanged prior to the menopause, but a larger study size was needed (&gt; 1000) if BMD was assumed to fall before the menopause.
We also measured lumbar BMD by dual photon absorptiometry in 141 normal females. When the data was analyzed against age throughout life, a nonlinear pattern of bone loss was found, and comparison of preand postmenopausal subjects showed a significant difference in the slopes of the linear regressions.
Our patient data support the concept of a relatively stable lumbar BMD prior to the menopause with a rapid but transient decline postmenopausally. The modeling studies emphasize the importance of an adequate study size in cross-sectional studies to identify accelerated lumbar bone loss at the menopause.
Synergism between parathyroid hormone and interleukin 1 in stimulating bone resorption in organ culture
Authors: Dr. Dewhirst Floyd E. , Ago Joanne M. , Peros William J. , Stashenko Philip 
Published: February 2010

Abstract
The interaction of interleukin 1 (IL-1), a locally produced factor, and parathyroid hormone (PTH), a systemic factor, in stimulating bone resorption was examined using fetal rat long bone organ culture. Concentrations of IL-1 and PTH, which stimulated little bone resorption when present singly, produced marked resorption when present simultaneously. This synergistic interaction of IL-1 and PTH was not affected by the presence of the prostaglandin synthetase inhibitor indomethacin. Both interleukin 1α and interleukin 1β were capable of producing synergy. Synergy was not produced by sequential exposure of bone to IL-1 and PTH, but required the simultaneous presence of both mediators. The leftward shift in the dose response curve of PTH produced by IL-1 may be an important mechanism controlling localized bone resorption. A role for IL-1 in stimulating bone resorption in pathologic conditions, such as arthritis and periodontal disease, is strengthened by the finding that even low concentrations of IL-1 can produce resorptive effects by synergistic interaction with PTH.
Modulation of 1,25-dihydroxyvitamin D3 receptor binding and action by sodium butyrate in cultured pig kidney cells (LLC-PK1)
Authors: Costa M. Elizabeth , Feldman David 
Published: February 2010

Abstract
We have studied the effects of sodium butyrate (SB) on 1,25(OH)2D3 receptors in the pig kidney cell line (LLC-PK1). In this system, we have shown that 1,25(OH)2D3 induction of 25-hydroxyvitamin D3-24-hydroxylase (24-hydroxylase) activity is dependent on the level of 1,25(OH)2D3 receptors. Treatment of confluent cells with SB (5 mM/48 h) caused an -50% decrease in total receptors, whereas the affinity for 1,25(OH)2D3 was unchanged. At 5 mm, the action of SB on these receptors required more than 24 h to be detected. The effect of the decrease in receptors on the functional response to the hormone was studied by measuring the 1,25(OH)2D3 induction of 24-hydroxylase activity after treatment with SB. The induction of 24-hydroxylase activity at higher doses of hormone paralleled the reduction in receptors and was diminished by 25–50%. At low doses of hormone, the cells appear to be more sensitive to 1,25(OH)2D3 induction, exhibiting an unexplained increase in 24-hydroxylase activity compared to cells not exposed to SB. An additional effect of SB was also noted: SB decreased cell proliferation and inhibited [3H]thymidine incorporation by 75% when added to cells prior to confluence. At confluence, SB caused a less drastic effect on protein and DNA synthesis. Therefore, most binding experiments were conducted at confluence when the SB effect on cell proliferation was less. Other short chain fatty acids in addition to SB were also tested. The action to decrease 1,25(OH)2D3 receptors was more specific upon exposure to SB. We have previously demonstrated up-regulation of 1,25(OH)2D3 receptors in LLC-PK1 cells after treatment with various vitamin D metabolites. After 24–48 h of treatment, 24,25(OH)2D3 induced a 2-5-fold increase in receptors levels. When added together with 24,25(OH)2D3, SB prevented the up-regulation whether measured at 24 or 48 h. The blockade of up-regulation was not observed if SB was added only in the last hour of exposure to 24,25(OH)2D3. In summary, we describe an effect of SB to decrease both 1,25(OH)2D3 receptors and the functional response to hormone. SB was also found to inhibit cell growth and proliferation.
cDNA cloning of alkaline phosphatase from rat osteosarcoma (ROS 17/2.8) cells
Authors: Noda M. , Yoon K. , Thiede M. , Buenaga R. , Weiss M. , Henthorn P. , Harris H. , Rodan G.A. 
Published: February 2010

Abstract
Two cDNA clones of rat alkaline phosphatase (AP) were isolated from a rat osteosarcoma λgt 11 cDNA library (ROS 17/2.8) utilizing a human bone-liver-kidney (BLK) type AP cDNA. These clones contain overlapping DNA sequences of 597 and 520 bp, respectively, corresponding to the 3' noncoding region of AP mRNA. The sequence homology with the human BLK AP cDNA is 61%. In Northern blot analysis the rat cDNA hybridizes to a single band of 2.5 kb mRNA from ROS 17/2.8 and rat liver, under highly stringent conditions. Steady state levels of AP mRNAs measured in several rat osteosarcoma cell lines (ROS 17/2.8, ROS 2/3, ROS 25/1, UMR 106) correlate with the level of AP enzymatic activity in these cells. Dexamethasone, which stimulates AP enzymatic activity in ROS 17/2.8 cells, increases the relative abundance of AP mRNA in a dose-dependent manner. This probe can be used to study AP expression in rat tissues and cells.
The calcium-buffering phase of bone mineral: Some clues to its form and formation
Authors: Neuman Margaret W. , Imai K. , Kawase T. , Saito S. 
Published: February 2010

AbstractDevitalized, neonatal, rat calvariae incubated in a buffered solution release Ca2+ and P1 during the first day into the medium until levels reach 1.2 mM and 2.6 mM, respectively. Thereafter levels gradually decrease to stabilize by the fifth day at 0.5 mM and 2 mM. Comparison of these solubility changes with those of known calcium phosphate salts suggests that calvarial solubility is controlled by a mixture of impure, soluble, apatite precursors, which at cell death transform to an impure apatite. Increasing concentrations of Mg2+ increased the rate of Ca2+ release and, at 3 mM, stabilized Ca2+ by the fifth day at 0.9 mM. Decreasing the pH from 7.4 to 7.2 produced similar solubility changes as did the addition of citrate at 0.3 mM, phosphocitrate at 0.3 mM, ATP at 0.1 mM, and the bisphosphonate, HEBP, at 0.1 mM. Osteocalcin did not increase calvarial solubility but was able to slow the rate of calcium phosphate phase transition if present at the time of in vitro crystal formation. Phosphocitrate and HEBP were also more effective when present during in vitro crystal formation. HEBP was most effective when present during biological crystal formation, as shown by the increased solubility of devitalized calvariae removed after in vivo administration of HEBP.In vivo manipulations of osteoclast activity produced changes in plasma calcium which correlated with the solubility of the corresponding calvariae after removal and devitalization. Low milk intake increased calvarial solubility. Increasing doses of 1,25(OH)2D3 increased plasma calcium and calvarial solubility, both of which were reversed by injection of acetazolamide.It was concluded from this survey of devitalized bone solubility that calcium exchange between bone and body fluids can buffer calcium homeostasis in the young rat. The exchange is passive. The active components appear to be osteoblastic formation of soluble apatite precursors and their stabilizers and, in reverse, osteoclastic transformation of apatite to precursors by H2CO3 secretion.
Inhibition by citrate of spontaneous precipitation of calcium oxalate in vitro
Authors: Nicar Michael J. , Hill Kathy , Pak Charles Y.C. 
Published: February 2010

Abstract
Effect of citrate on the spontaneous precipitation of calcium oxalate was examined in synthetic media. Citrate significantly increased the formation product of calcium oxalate. This “direct” measure of inhibitor activity, representing activity product at the point of nucleation, rose by 76% by the addition of citrate sufficient to provide trivalent citrate concentration of 1.49 mM. Moreover, citrate inhibited calcium oxalate crystallization by complexing calcium and lowering calcium oxalate saturation. This “indirect” measure of inhibitor activity was assessed from the concentration product of calcium oxalate at the point of nucleation, since this measure should provide a reflection of both ion pair formation and direct inhibitor activity of citrate. The concentration product exceeded the formation product at all ionic (trivalent) citrate concentrations, particularly at high ionic citrate levels. At the ionic citrate concentration of 1.49 mM, the rise in the concentration product was 373%, which was nearly fivefold that observed for the formation product. The presence of ferric or aluminum cations at a physiologic concentration of 2 mg/l did not modify the increase in formation product produced by citrate. Thus, citrate inhibits calcium oxalate crystallization, largely by complexing citrate, but also by directly affecting nucleation. Presence of ferric or aluminum cations at a physiological concentration does not modify the inhibitor action of citrate.
The proportion of trabecular bone in human vertebrae
Authors: Nottestad Sheri Y. , Baumel Julian J. , Kimmel Donald B. , Recker Robert R. , Heaney Robert P. 
Published: February 2010

Abstract
The proportion of trabecular bone in human cadaver vertebrae was assessed by anatomic dissection. Thirty-two whole thoracic and lumbar vertebrae were obtained from 10 normal human postmenopausal female cadavers, 14 from 4 normal adult human male cadavers of similar age, and 8 from one female osteoporotic cadaver. Each vertebra was opened by saw cuts and separated into four tissue types: (1) body trabecular bone and marrow; (2) body cortical bone; (3) vertebral arch trabecular bone and marrow; and (4) vertebral arch cortical bone. Calcium was determined in each tissue type for each vertebra by ashing and atomic absorption spectrophotometry.
Trabeculae accounted for 24.4 ± 4.5% of the total calcium in whole female vertebrae, and 18.8 ± 4.4% in whole male vertebrae (p &lt; 0.001). The body averaged 41.8% trabecular bone in females and 33.5% in males. The arch averaged 9.7% trabecular bone in females and 4.9% in males. The proportion of trabecular bone in the whole vertebrae in the single osteoporotic spine was 28.5 ± 3.2%, a value not significantly different from the trabecular fraction in normal females.
These data indicate that whole human thoraco-lumbar vertebrae are composed of a substantially lower proportion of trabecular bone than is usually assumed, and they suggest that cortical and trabecular bone are eventually lost in equal proportion from the vertebrae during the development of spinal osteoporosis. These results are important for the interpretation of data from noninvasive bone measurement techniques that evaluate the spine, and they suggest that studies of this type are important for any site where noninvasive bone mass measurement is done.
Intravenous aminopropylidene bisphosphonate (APD) in the treatment of paget's bone disease
Authors: Vega Eduardo , Gonzalez Diana , Ghiringhelli Gualterio , Mautalen Carlos 
Published: February 2010

Abstract
We studied the effect of the intravenous administration of the bisphosphonate APD in 9 patients with Paget's bone disease. The medication was given in a daily dose of 25 mg for 7 days in 0.9% saline infusion over 2 hours. At the end of treatment a significant fall of serum calcium and phosphate was observed. The urinary excretion of calcium decreased markedly and the serum levels of the mid-molecule PTH fragment increased from (mean ± SE) 85 ± 11 to 122 ± 16 pg/ml (p &lt; 0.05). A marked and rapid decline in the hydroxyprolinuria was observed from 297 ± 61 mg/24 h to 194 ± 51 mg/24 h (p &lt; 0.01); meanwhile the serum alkaline phosphatase decreased from 102 ± 22 to 84 ± 21 KAU (p &lt; 0.05). The effect of ADP on suppression of hydroxyprolinuria varied markedly from +1 to -81% and was negatively related to the basal hydroxyprolinuria (r = -0.90; p &lt; 0.001). The duration of the bone turnover suppression was short. A relapse greater than 30% in hydroxyprolinuria was observed in 6 of 8 patients 2 to 3 months after APD withdrawal.
The short-term intravenous administration of ADP is a useful means to rapidly suppress the activity of Paget's bone disease. However, further studies should determine the optimum dose, the length of treatment, and the need to associate oral therapy to induce a prolonged remission.
Calcium/phosphatidylserine-stimulated protein phosphorylation in bone: Effect of parathyroid hormone
Authors: Stewart Pamela J. , Stern Paula H. 
Published: February 2010

Abstract
The calcium/phosphatidylserine (PS)-stimulated phosphorylation of endogenous proteins in the 100,000 × g particulate fraction from neonatal mouse calvaria was investigated. EGTA selectively inhibited the phosphorylation of a 20K protein. The phosphorylation of this 20K protein was stimulated by calcium and by PS. The combination of calcium plus PS increased the phosphorylation of the 20K protein more markedly than either calcium or PS alone. Parathyroid hormone (PTH) (100 nM) treatment of calvaria rapidly altered the phosphorylation of the 20K protein in a time-dependent manner. The PTH treatment time course demonstrated that after 5 minutes the in vitro phosphorylation of the 20K protein was markedly enhanced, after 15 minutes the 20K protein was not as heavily phosphorylated, and after 30 minutes the in vitro phosphorylation of the 20K was less than control. Our results demonstrate the presence of calcium/PS-stimulated phosphorylation in bone tissue and a rapid effect of PTH on this phosphorylation.
Effect of dietary acid and calcium on 25-hydroxyvitamin D metabolism by chick kidney
Authors: Dr. Cunningham John , Bikle Daniel D. , Avioli Louis V. 
Published: February 2010

Abstract
Studies of the effects of acidosis and dietary calcium on 25-hydroxyvitamin D3 (25OHD3) metabolism were conducted utilizing assays of mitochondrial 1-hydroxylase and 24-hydroxylase activity following 96 hours of acid loading. The results showed decreased 1-hydroxylase (206 ± 6 vs. 132 ± 22 fmol min−1 mg/mitochondrial protein−1, p &lt; 0.01), augmented 24-hydroxylase (48 ± 14 vs. 180 ± 30 fmol min−1 mg−1, p &lt; 0.001) and increments in plasma calcium and phosphate following acidosis. High calcium diet also increased 24-hydroxylase activity (48 ± 14 vs. 160 ± 24 fmol min−1 mg−1, p &lt; 0.001) and plasma calcium, but decreased plasma phosphate. The extramitochondrial concentrations of calcium, potassium, and phosphate which maximally stimulated the hydroxylases in vitro were not altered by the in vivo dietary perturbations. The increments in 1-hydroxylase and 24-hydroxylase resulting from the presence of calcium, potassium, or phosphate in optimal concentrations (10−5M, 100 mM, and 100 mM, respectively) were changed by both acid loading and high calcium diet, decreasing in the case of 1-hydroxylase and increasing in that of 24-hydroxylase. The data indicate that the suppression of 1-hydroxylase and augmentation of 24-hydroxylase following these dietary perturbations may depend on both changed total enzyme capacity and altered enzyme sensitivity to extramitochondrial ions and are consistent with mediation by calcium of the effects of acidosis.