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Transient Increased Calcium and Calcitriol Requirements After Discontinuation of Human Synthetic Parathyroid Hormone 1-34 (hPTH 1-34) Replacement Therapy in Hypoparathyroidism.

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Gafni, Rachel I; Guthrie, Lori C; Kelly, Marilyn H; Brillante, Beth A; Christie, C Michele; Reynolds, James C; Yovetich, Nancy A; James, Robert; Collins, Michael T

2015-11-01

Synthetic human PTH 1-34 (hPTH 1-34) replacement therapy in hypoparathyroidism maintains eucalcemia and converts quiescent bone to high-turnover bone. However, the skeletal and metabolic effects of drug discontinuation have not been reported. Nine subjects with hypoparathyroidism received subcutaneous injections of hPTH 1-34 two to three times daily for 19.8 to 61.3 months and then transitioned back to calcium and calcitriol. Biochemistries and bone mineral density (BMD) by dual-energy X-ray absorptiometry (DXA) were assessed at baseline, while on treatment, and at follow-up 3 to 12 months after drug discontinuation. Two subjects developed hypocalcemia when hPTH 1-34 was abruptly discontinued. Thus, to avoid hypocalcemia, subjects were slowly weaned from hPTH 1-34 over several weeks. When hPTH 1-34 was stopped, subjects were requiring two to three times pretreatment doses of calcitriol and calcium to maintain blood calcium levels. Doses were gradually reduced over many weeks until calcium levels were stable on doses similar to baseline. Bone-specific alkaline phosphatase (BSAP), N-telopeptide (NTX), and osteocalcin (OC) increased significantly with hPTH 1-34; at follow-up, BSAP and NTX had returned to baseline while OC was still slightly elevated. During treatment, BMD was unchanged at the hip and lateral spine but declined at the anterior-posterior (AP) spine, radius, and total body. During weaning, BMD increased, with the hip and lateral spine exceeding pre-hPTH 1-34 values and the whole body returning to baseline. AP spine was increased non-significantly compared to baseline at follow-up. hPTH 1-34 must be gradually weaned in hypoparathyroid patients with high doses of oral medications given to avoid hypocalcemia. The transient increased requirements accompanied by increased BMD after long-term hPTH 1-34 therapy suggest a reversal of the expanded remodeling space favoring bone formation as the skeleton returns to a low-turnover state, reminiscent of the hungry
High dose teriparatide (rPTH1-34) therapy increases callus volume and enhances radiographic healing at 8-weeks in a massive canine femoral allograft model.

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Nishitani, Kohei; Mietus, Zachary; Beck, Christopher A; Ito, Hiromu; Matsuda, Shuichi; Awad, Hani A; Ehrhart, Nicole; Schwarz, Edward M

2017-01-01

Small animal studies have demonstrated significant high-dose recombinant parathyroid hormone1-34 (rPTH1-34) effects on intercalary allograft healing. Towards a human adjuvant therapy to decrease non-unions, we evaluated rPTH1-34 safety and efficacy in a clinically relevant canine femoral allograft model. Adult female mongrel hounds (n = 20) received a 5cm mid-diaphyseal osteotomy reconstructed with a plated allograft, and were randomized to: 1) Placebo (n = 5; daily saline), 2) Continuous rPTH1-34 (n = 7; 5 μg/kg/day s.c. from day 1-55 post-op), or 3) Delayed rPTH1-34 (n = 8; 5 μg/kg/day s.c. from day 14-28 post-op). Safety was assessed by physical behavior and blood calcium monitoring. Cone beam CT (CB-CT) was performed on days 14, 28 and 56 post-op to assess 2D cortical healing, 3D bone volume, and Union Ratio. Biomechanical testing and dynamic histomorphometry were also performed. The high drug dose was poorly tolerated, as most dogs receiving rPTH1-34 had to be given intravenous saline, and one dog died from hypercalcemia. Continuous rPTH1-34 significantly increased 2D healing and callus volumes at 4-weeks versus Placebo, and sustained the significant increase in cortical union at 8-week (p<0.05). These rPTH1-34 effects were confirmed by histomorphometry, revealing significant increases in mineral apposition rates (MAR) on host bone and graft-host junctions (p<0.05). Delayed rPTH1-34 significantly increased callus volume and MAR at 8 weeks (p<0.05). Although no biomechanical differences were observed, as expected for early healing, the results demonstrated that 2D RUST scoring significantly correlated with torsional biomechanics (p<0.01). In conclusion, 8-weeks of intermittent high-dose rPTH1-34 treatment significantly increases callus formation and accelerates bony union of intercalary massive allografts in a clinically relevant canine model, but with serious side-effects from hypercalcemia.
High dose teriparatide (rPTH1-34 therapy increases callus volume and enhances radiographic healing at 8-weeks in a massive canine femoral allograft model.

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Kohei Nishitani

Full Text Available Small animal studies have demonstrated significant high-dose recombinant parathyroid hormone1-34 (rPTH1-34 effects on intercalary allograft healing. Towards a human adjuvant therapy to decrease non-unions, we evaluated rPTH1-34 safety and efficacy in a clinically relevant canine femoral allograft model. Adult female mongrel hounds (n = 20 received a 5cm mid-diaphyseal osteotomy reconstructed with a plated allograft, and were randomized to: 1 Placebo (n = 5; daily saline, 2 Continuous rPTH1-34 (n = 7; 5 μg/kg/day s.c. from day 1-55 post-op, or 3 Delayed rPTH1-34 (n = 8; 5 μg/kg/day s.c. from day 14-28 post-op. Safety was assessed by physical behavior and blood calcium monitoring. Cone beam CT (CB-CT was performed on days 14, 28 and 56 post-op to assess 2D cortical healing, 3D bone volume, and Union Ratio. Biomechanical testing and dynamic histomorphometry were also performed. The high drug dose was poorly tolerated, as most dogs receiving rPTH1-34 had to be given intravenous saline, and one dog died from hypercalcemia. Continuous rPTH1-34 significantly increased 2D healing and callus volumes at 4-weeks versus Placebo, and sustained the significant increase in cortical union at 8-week (p<0.05. These rPTH1-34 effects were confirmed by histomorphometry, revealing significant increases in mineral apposition rates (MAR on host bone and graft-host junctions (p<0.05. Delayed rPTH1-34 significantly increased callus volume and MAR at 8 weeks (p<0.05. Although no biomechanical differences were observed, as expected for early healing, the results demonstrated that 2D RUST scoring significantly correlated with torsional biomechanics (p<0.01. In conclusion, 8-weeks of intermittent high-dose rPTH1-34 treatment significantly increases callus formation and accelerates bony union of intercalary massive allografts in a clinically relevant canine model, but with serious side-effects from hypercalcemia.
Down-regulation of parathyroid hormone (PTH) receptors in cultured bone cells is associated with agonist-specific intracellular processing of PTH-receptor complexes.

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Teitelbaum, A P; Silve, C M; Nyiredy, K O; Arnaud, C D

1986-02-01

Exposure of cultured embryonic chicken bone cells to the PTH agonists bovine (b) PTH-(1-34) and [8Nle, 18Nle, 34Tyr]bPTH-(1-34)amide [bPTH-(1-34)A] reduces the subsequent cAMP response to the hormone and decreases the specific binding of 125I-labeled PTH to these cultures. To determine whether PTH receptor down-regulation in cultured bone cells is mediated by cellular internalization of PTH-receptor complexes, we measured the uptake of [125I]bPTH-(1-34) into an acid-resistant compartment. Uptake of radioactivity into this compartment was inhibited by incubating cells at 4 C with phenylarsineoxide and unlabeled bPTH-(1-34). Tracer uptake into the acid-resistant compartment at any time was directly proportional to total cell binding at 22 C. Thus, it is likely that PTH-receptor complexes are internalized by bone cells. This mechanism may explain the loss of cell surface receptors after PTH pretreatment. To determine whether internalized PTH-receptor complexes are reinserted into the plasma membrane, we measured PTH binding and PTH stimulation of cAMP production after cells were exposed to monensin, a known inhibitor of receptor recycling. Monensin (25 microM) had no effect on PTH receptor number or affinity and did not alter PTH-stimulated cAMP accumulation. However, monensin (25 microM) incubated with cells pretreated with various concentrations of bPTH-(1-34) for 1 h potentiated the effect of the hormone to reduce subsequent [125I]bPTH-(1-34) binding and PTH-stimulated cAMP accumulation by more than 2 orders of magnitude. Chloroquine also potentiated PTH-induced down-regulation of PTH receptors. By contrast, neither agent influenced PTH binding or PTH-stimulated cAMP production in cells pretreated with the antagonist bPTH-(3-34)A. Thus, monensin potentiated PTH receptor loss only in cells pretreated with PTH agonists, indicating that antagonist-occupied receptors may be processed differently from agonist-occupied receptors in bone cells. The data further suggest
Endogenous PTH deficiency impairs fracture healing and impedes the fracture-healing efficacy of exogenous PTH(1-34.

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Yongxin Ren

Full Text Available Although the capacity of exogenous PTH1-34 to enhance the rate of bone repair is well established in animal models, our understanding of the mechanism(s whereby PTH induces an anabolic response during skeletal repair remains limited. Furthermore it is unknown whether endogenous PTH is required for fracture healing and how the absence of endogenous PTH would influence the fracture-healing capacity of exogenous PTH.Closed mid-diaphyseal femur fractures were created and stabilized with an intramedullary pin in 8-week-old wild-type and Pth null (Pth(-/- mice. Mice received daily injections of vehicle or of PTH1-34 (80 µg/kg for 1-4 weeks post-fracture, and callus tissue properties were analyzed at 1, 2 and 4 weeks post-fracture. Cartilaginous callus areas were reduced at 1 week post-fracture, but were increased at 2 weeks post-fracture in vehicle-treated and PTH-treated Pth(-/- mice compared to vehicle-treated and PTH-treated wild-type mice respectively. The mineralized callus areas, bony callus areas, osteoblast number and activity, osteoclast number and surface in callus tissues were all reduced in vehicle-treated and PTH-treated Pth(-/- mice compared to vehicle-treated and PTH-treated wild-type mice, but were increased in PTH-treated wild-type and Pth(-/- mice compared to vehicle-treated wild-type and Pth(-/- mice.Absence of endogenous PTH1-84 impedes bone fracture healing. Exogenous PTH1-34 can act in the absence of endogenous PTH but callus formation, including accelerated endochondral bone formation and callus remodeling as well as mechanical strength of the bone are greater when endogenous PTH is present. Results of this study suggest a complementary role for endogenous PTH1-84 and exogenous PTH1-34 in accelerating fracture healing.
Endogenous PTH deficiency impairs fracture healing and impedes the fracture-healing efficacy of exogenous PTH(1-34).

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Ren, Yongxin; Liu, Bo; Feng, Yuxu; Shu, Lei; Cao, Xiaojian; Karaplis, Andrew; Goltzman, David; Miao, Dengshun

2011-01-01

Although the capacity of exogenous PTH1-34 to enhance the rate of bone repair is well established in animal models, our understanding of the mechanism(s) whereby PTH induces an anabolic response during skeletal repair remains limited. Furthermore it is unknown whether endogenous PTH is required for fracture healing and how the absence of endogenous PTH would influence the fracture-healing capacity of exogenous PTH. Closed mid-diaphyseal femur fractures were created and stabilized with an intramedullary pin in 8-week-old wild-type and Pth null (Pth(-/-)) mice. Mice received daily injections of vehicle or of PTH1-34 (80 µg/kg) for 1-4 weeks post-fracture, and callus tissue properties were analyzed at 1, 2 and 4 weeks post-fracture. Cartilaginous callus areas were reduced at 1 week post-fracture, but were increased at 2 weeks post-fracture in vehicle-treated and PTH-treated Pth(-/-) mice compared to vehicle-treated and PTH-treated wild-type mice respectively. The mineralized callus areas, bony callus areas, osteoblast number and activity, osteoclast number and surface in callus tissues were all reduced in vehicle-treated and PTH-treated Pth(-/-) mice compared to vehicle-treated and PTH-treated wild-type mice, but were increased in PTH-treated wild-type and Pth(-/-) mice compared to vehicle-treated wild-type and Pth(-/-) mice. Absence of endogenous PTH1-84 impedes bone fracture healing. Exogenous PTH1-34 can act in the absence of endogenous PTH but callus formation, including accelerated endochondral bone formation and callus remodeling as well as mechanical strength of the bone are greater when endogenous PTH is present. Results of this study suggest a complementary role for endogenous PTH1-84 and exogenous PTH1-34 in accelerating fracture healing.
All-atom simulation study of protein PTH(1-34) by using the Wang-Landau sampling method

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Kim, Seung-Yeon [Korea National University of Transportation, Chungju (Korea, Republic of); Kwak, Woo-Seop [Chosun University, Gwangju (Korea, Republic of)

2014-12-15

We perform simulations of the N-terminal 34-residue protein fragment PTH(1-34), consisting of 581 atoms, of the 84-residue human parathyroid hormone by using the all-atom ECEPP/3 force field and the Wang-Landau sampling method. Through a massive high-performance computation, the density of states and the partition function Z(T), as a continuous function of T, are obtained for PTH(1-34). From the continuous partition function Z(T), the partition function zeros of PTH(1-34) are evaluated for the first time. From both the specific heat and the partition function zeros, two characteristic transition temperatures are obtained for the all-atom protein PTH(1-34). The higher transition temperature T{sub 1} and the lower transition temperature T{sub 2} of PTH(1-34) can be interpreted as the collapse temperature T{sub θ} and the folding temperature T{sub f} , respectively.
Recombinant human parathyroid hormone (PTH 1-34) and low-intensity pulsed ultrasound have contrasting additive effects during fracture healing.

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Warden, Stuart J; Komatsu, David E; Rydberg, Johanna; Bond, Julie L; Hassett, Sean M

2009-03-01

Fracture healing is thought to be naturally optimized; however, recent evidence indicates that it may be manipulated to occur at a faster rate. This has implications for the duration of morbidity associated with bone injuries. Two interventions found to accelerate fracture healing processes are recombinant human parathyroid hormone [1-34] (PTH) and low-intensity pulsed ultrasound (LIPUS). This study aimed to investigate the individual and combined effects of PTH and LIPUS on fracture healing. Bilateral midshaft femur fractures were created in Sprague-Dawley rats, and the animals treated 7 days/week with PTH (10 microg/kg) or a vehicle solution. Each animal also had one fracture treated for 20 min/day with active-LIPUS (spatial-averaged, temporal-averaged intensity [I(SATA)]=100 mW/cm(2)) and the contralateral fracture treated with inactive-LIPUS (placebo). Femurs were harvested 35 days following injury to permit micro-computed tomography, mechanical property and histological assessments of the fracture calluses. There were no interactions between PTH and LIPUS indicating that their effects were additive rather than synergistic. These additive effects were contrasting with LIPUS primarily increasing total callus volume (TV) without influencing bone mineral content (BMC), and PTH having the opposite effect of increasing BMC without influencing TV. As a consequence of the effect of LIPUS on TV but not BMC, it decreased volumetric bone mineral density (vBMD) resulting in a less mature callus. The decreased maturity and persistence of cartilage at the fracture site when harvested offset any beneficial mechanical effects of the increased callus size with LIPUS. In contrast, the effect of PTH on callus BMC but not TV resulted in increased callus vBMD and a more mature callus. This resulted in PTH increasing fracture site mechanical strength and stiffness. These data suggest that PTH may have utility in the treatment of acute bone fractures, whereas LIPUS at an I(SATA) of
Pharmacokinetic and Pharmacodynamic Characteristics of Subcutaneously Applied PTH-1-37

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Wolf-Georg Forssmann

2016-08-01

Full Text Available Background/Aims: Parathyroid hormone (PTH derivatives exert pronounced renal and osteoanabolic properties when given intermittently. The current study was performed to assess the pharmacokinetic and pharmacodynamic properties as well as safety of subcutaneously applied PTH-1-37 after repeated dosing in healthy subjects. Methods: This randomized, double-blind, dose-escalating, placebo and active comparator controlled study was conducted in 33 healthy postmenopausal women. Subjects were allocated to one of five treatment options: 10, 20, or 40 µg PTH-1-37, 20 µg PTH-1-34 or placebo, administered as once daily subcutaneous doses for three days. Plasma drug concentrations and serum levels of endogenous PTH-1-84, and calcium as markers of biological activity were monitored during the treatment. Results: PTH was absorbed rapidly from the subcutaneous tissue with a median tmax of 30 minutes for 20 and 40 µg of PTH-1-37. tmax was 45 minutes for 20 µg PTH-1-34. Elimination half-lives were estimated as 76 ± 34 min and 70 ± 13 min for 20 µg and 40 µg PTH-1-37 (mean ± SD, and 78 ± 34 for 20 µg PTH-1-34. Both PTH fragments (PTH-1-37 and PTH-1-34 increased serum calcium. For PTH-1-37 the effect on serum calcium was dose-dependent. Suppression of endogenous PTH-1-84 was seen after the application of both PTH-1-37 and PTH-1-34. During the study period, the subjects experienced no unexpected or serious adverse events. Conclusions: PTH-1-37 is rapidly absorbed after s.c. injection, has a short plasma elimination half-life, and does not accumulate during multiple dosing. Biological activity was demonstrated by rising serum calcium and decreasing endogenous PTH-1-84 in blood plasma. The study drugs were well tolerated and safe. Our investigation presents data that PTH-1-37 is an excellent drug candidate for intervening with syndromes of dysregulation of calcium metabolism.
In vitro and preclinical assessment of an intranasal spray\\ud formulation of parathyroid hormone PTH 1-34 for the treatment of osteoporosis

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Williams, Allan J.; Jordan, Faron; King, Gareth; Lewis, Andrew L.; Illum, Lisbeth; Masud, Tahir; Perkins, Alan C.; Pearson, Richard G.

2017-01-01

Osteoporosis treatment with PTH 1-34 injections significantly reduces the incidence of bone fracture. Potential further reductions in fracture rate should be observed through nasal spray delivery to address the poor compliance associated with patient dislike of repeated PTH 1-34 subcutaneous injections. In vitro human osteoblast-like Saos-2 cell intracellular cAMP levels were used to define PTH 1-34 nasal spray formulation bioactivity. The chemically synthesised PTH 1-34 had an EC50 of 0.76nM...
In vitro and preclinical assessment of an intranasal spray formulation of parathyroid hormone PTH 1-34 for the treatment of osteoporosis.

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Williams, Allan J; Jordan, Faron; King, Gareth; Lewis, Andrew L; Illum, Lisbeth; Masud, Tahir; Perkins, Alan C; Pearson, Richard G

2018-01-15

Osteoporosis treatment with PTH 1-34 injections significantly reduces the incidence of bone fracture. Potential further reductions in fracture rate should be observed through nasal spray delivery to address the poor compliance associated with patient dislike of repeated PTH 1-34 subcutaneous injections. In vitro human osteoblast-like Saos-2 cell intracellular cAMP levels were used to define PTH 1-34 nasal spray formulation bioactivity. The chemically synthesised PTH 1-34 had an EC 50 of 0.76nM. Absorption enhancers polyethylene glycol (15)-hydroxystearate (Solutol ® HS15), poloxamer 407, chitosan or sodium hyaluronate did not diminish the bioactivity of PTH 1-34 within an in vitro cell culture model (p >0.05). We also demonstrated the effectiveness of the transmucosal absorption enhancer Solutol ® HS15 in a nasal spray formulation using a preclinical pharmacokinetic model. In Sprague-Dawley rats without the absorption enhancer the uptake of PTH 1-34 into the blood via intranasal delivery produced a Cmax of 2.1±0.5ng/ml compared to 13.7±1.6ng/ml with Solutol ® HS15 enhancer (p=0.016) and a Cmax14.8±8ng/ml in subcutaneous injections. Together these data illustrate that the nasal spray formulation bioactivity in vitro is not affected by the nasal spray absorption enhancers investigated, and the Solutol ® HS15 nasal spray formulation had an equivalent pharmacokinetic profile to subcutaneous injection in the rat model. The Solutol ® HS15 formulation therefore demonstrated potential as a PTH 1-34 nasal spray formulation for the treatment of osteoporosis. Copyright © 2017. Published by Elsevier B.V.
Intermittent Administration of Parathyroid Hormone [1-34] Prevents Particle-Induced Periprosthetic Osteolysis in a Rat Model.

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Fanggang Bi

Full Text Available We examined whether intermittent administration of parathyroid hormone [1-34] (PTH[1-34]; 60 μg/kg/day can prevent the negative effects of titanium (Ti particles on implant fixation and periprosthetic osteolysis in a rat model. Eighteen adult male rats (12 weeks old, bones still growing received intramedullary Ti implants in their bilateral femurs; 6 rats from the blank group received vehicle injections, and 12 rats from the control group and PTH treatment group received Ti particle injections at the time of operation and intra-articular injections 2 and 4 weeks postoperatively. Six of the rats that received Ti particles from the PTH group also received PTH[1-34] treatment. Six weeks postoperatively, all specimens were collected for assessment by X-ray, micro-CT, biomechanical, scanning electron microscopy (SEM, and dynamic histomorphometry. A lower BMD, BV/TV, Tb.N, maximal fixation strength, and mineral apposition rate were observed in the control group compared to the blank group, demonstrating that a periprosthetic osteolysis model had been successfully established. Administration of PTH[1-34] significantly increased the bone mineral density of the distal femur, BV/TV, Tb.N, Tb.Th, Tb.Sp, Con.D, SMI, and maximal fixation strength in the PTH group compared to that in the control group. SEM revealed higher bone-implant contact, thicker lamellar bone, and larger trabecular bone area in the PTH group than in the control group. A higher mineral apposition rate was observed in the PTH group compared to both the blank and control groups. These findings imply that intermittent administration of PTH[1-34] prevents periprosthetic osteolysis by promoting bone formation. The effects of PTH[1-34] were evaluated at a suprapharmacological dosage to the human equivalent in rats; therefore, additional studies are required to demonstrate its therapeutic potential in periprosthetic osteolysis.
Rat parathyroid hormone (rPTH) ELISAs specific for regions (2-7), (22-34) and (40-60) of the rat PTH structure: influence of sex and age.

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D'Amour, Pierre; Rousseau, Louise; Hornyak, Stephen; Yang, Zan; Cantor, Tom

2010-09-15

Rat (r) PTH ELISAs were used to study the influence of age and sex on rPTH levels and circulating PTH molecular forms separated by HPLC. Standard curves and saturation analysis were undertaken to define epitopes. Rats were sacrificed at approximately 27, 47 and 75days. Relevant biochemical parameters and 25(OH) vitamin D were measured. Differences between sexes were analyzed by Kruskal-Wallis ANOVA, followed by Dunn's test. Epitopes were localized in regions 2-7, 22-34 and 40-60 of rPTH structure for whole (W), total (T) and carboxyl (C) rPTH ELISAs. The W-rPTH assay only detected rPTH(1-84) and N-PTH in circulation while the T-PTH assay further detected large C-rPTH fragments. The C-rPTH assay detected all circulating rPTH molecular forms including smaller C-rPTH fragments. In both sexes, weight (p<0.001), ionized calcium, creatinine, albumin and 25(OH)D values (p<0.001) increased with age, while phosphate and alkaline phosphatase decreased (p<0.001). In male rats, W-rPTH remained unchanged, while T-rPTH rose slightly (p<0.05) and C-rPTH declined by half with time (p<0.001). In female rats, W-rPTH (p<0.05), T-rPTH (p<0.001) and C-rPTH (p<0.01) all increased in older animals. In both sexes, C-rPTH/W-rPTH and C-rPTH/T-rPTH ratios decreased between 25 and 47 days, to rise again between 47 and 75 days. The initial decrease may represent an adaptation to weaning and a change of diet between 25 and 47 days while the rise corresponds to higher calcium and 25(OH)D levels between 47 and 75 days. These changes were more pronounced in female rats, indicating an influence of sex on PTH molecular form secretion or metabolism. Copyright (c) 2010 Elsevier Inc. All rights reserved.
PTH1 receptor is involved in mediating cellular response to long-chain polyunsaturated fatty acids.

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Jose Candelario

Full Text Available The molecular pathways by which long chain polyunsaturated fatty acids (LCPUFA influence skeletal health remain elusive. Both LCPUFA and parathyroid hormone type 1 receptor (PTH1R are known to be involved in bone metabolism while any direct link between the two is yet to be established. Here we report that LCPUFA are capable of direct, PTH1R dependent activation of extracellular ligand-regulated kinases (ERK. From a wide range of fatty acids studied, varying in chain length, saturation, and position of double bonds, eicosapentaenoic (EPA and docosahexaenoic fatty acids (DHA caused the highest ERK phosphorylation. Moreover, EPA potentiated the effect of parathyroid hormone (PTH(1-34 in a superagonistic manner. EPA or DHA dependent ERK phosphorylation was inhibited by the PTH1R antagonist and by knockdown of PTH1R. Inhibition of PTH1R downstream signaling molecules, protein kinases A (PKA and C (PKC, reduced EPA and DHA dependent ERK phosphorylation indicating that fatty acids predominantly activate G-protein pathway and not the β-arrestin pathway. Using picosecond time-resolved fluorescence microscopy and a genetically engineered PTH1R sensor (PTH-CC, we detected conformational responses to EPA similar to those caused by PTH(1-34. PTH1R antagonist blocked the EPA induced conformational response of the PTH-CC. Competitive binding studies using fluorescence anisotropy technique showed that EPA and DHA competitively bind to and alter the affinity of PTH1 receptor to PTH(1-34 leading to a superagonistic response. Finally, we showed that EPA stimulates protein kinase B (Akt phosphorylation in a PTH1R-dependent manner and affects the osteoblast survival pathway, by inhibiting glucocorticoid-induced cell death. Our findings demonstrate for the first time that LCPUFAs, EPA and DHA, can activate PTH1R receptor at nanomolar concentrations and consequently provide a putative molecular mechanism for the action of fatty acids in bone.
Acute regulation of circulating parathyroid hormone (PTH) molecular forms by calcium: utility of PTH fragments/PTH(1-84) ratios derived from three generations of PTH assays.

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D'Amour, Pierre; Räkel, Agnès; Brossard, Jean-Hugues; Rousseau, Louise; Albert, Caroline; Cantor, Tom

2006-01-01

The quantitative evaluation of circulating PTH peaks revealed by PTH assays after HPLC separation constitutes the best way to study the behavior of PTH molecular forms, but it is also impractical. The objective of the study was to investigate the regulation of circulating PTH molecular forms by calcium through the use of PTH fragments/PTH (1-84) ratios derived from PTH assays with different specificities before and after HPLC separation of circulating PTH. CaCl2 and Na citrate were infused in eight volunteers. PTH was measured in serum and HPLC fractions at different calcium concentrations in PTH assays reacting with regions 1-2 (CA), 12-18 (T), and 65-69 (C) of the PTH structure. From hypo- to hypercalcemia, the C/CA ratio had the highest range (1.92 to 9.75; P < 0.001), and the C/T ratio had a higher range (1.69 to 6.11; P < 0.01) than the T/CA ratio (1.15 to 1.86). Human (h) PTH (1-84) represented 32.7 and 4.3% of circulating PTH in hypo- and hypercalcemic HPLC profiles, respectively. These numbers were 5 and 0.9% for amino-terminal (N)-PTH, an amino-terminal form of PTH distinct from hPTH (1-84), 7.3 and 6.8% for non-(1-84) PTH or large C-PTH fragments with a partially preserved N structure, and 54.9 and 88.1% for C-PTH fragments missing a N structure. The HPLC C-PTH fragments to hPTH (1-84) ratio had the most extensive range (1.67 to 20.58). Despite their quantitative differences, all ratios identified identical behavior of PTH fragments relative to PTH (1-84). PTH assay ratios are an adequate tool to investigate the modulation of PTH molecular forms, even if all PTH assays show some undesirable cross-reactivity with certain circulating forms of PTH.
The combined effect of Parathyroid hormone (1-34) and whole-body Vibration exercise in the treatment of OSteoporosis (PaVOS)- study protocol for a randomized controlled trial

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Jepsen, Ditte Beck; Ryg, Jesper; Jørgensen, Niklas Rye

2018-01-01

Background: PaVOS is a randomized controlled trial (RCT) which aims to address the use of whole-body vibration exercise (WBV) in combination with parathyroid hormone 1-34 fragment teriparatide (PTH 1-34) treatment in patients with osteoporosis. PTH 1-34 is an effective but expensive anabolic...... fracture risk. Methods/design: PaVOS is a multicenter, assessor-blinded, superiority, two-armed randomized controlled trial (RCT). Postmenopausal women (n = 40, aged 50 years and older) starting taking PTH 1-34 from outpatient clinics will be randomized and assigned to a PTH 1-34 + WBV-exercise group...... (intervention group), or a PTH 1-34-alone group (control group). The intervention group will undergo WBV three sessions a week (12 min each, including 1:1 ratio of exercise: rest, 30 Hz, 1 mm amplitude) for a 12-month intervention period. Both the intervention and the control group will receive PTH 1...
Parathyroid Hormone (1-34 Might Not Improve Early Bone Healing after Sinus Augmentation in Healthy Rabbits

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Jisun Huh

2017-01-01

Full Text Available Purpose. This study evaluated the effect of administering intermittent parathyroid hormone [PTH (1-34, henceforth PTH] on the early-stage bone healing of maxillary sinus augmentation in healthy rabbits. Materials and Methods. Bovine bone mineral was grafted on the sinuses of 20 female New Zealand white rabbits. The animals were randomly divided into two groups, PTH (n=10 or saline (n=10, in which either PTH or saline was injected subcutaneously 5 days a week for 2 weeks. Half of the animals in each group were killed at 2 weeks postoperatively and the other half were killed at 4 weeks postoperatively. The dosage of PTH was 10 μg/kg/day. Radiographic and histomorphometric analyses were performed. Result. The new bone area (NBA did not differ significantly between the PTH and saline groups. The NBA in the PTH group in the total augmented area and in the demarcated window, center, and Schneiderian membrane regions increased significantly from 2 to 4 weeks. The number of osteoclasts decreased significantly from 2 to 4 weeks in both groups, with no difference between the two groups. Conclusion. Intermittent PTH might not stimulate new bone formation in healthy rabbits during the first 4 weeks of healing.
Comparison of renal and osseous binding of parathyroid hormone and hormonal fragments

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Demay, M.; Mitchell, J.; Goltzman, D.

1985-01-01

The authors compared receptor binding and adenylate cyclase stimulation of intact bovine parathyroid hormone (bPTH)-(1-84) and the synthetic amino-terminal fragments, bPTH-(1-34) and rat PTH (rPTH)-(1-34). In both canine renal membranes and cloned rat osteosarcoma cells the amino-terminal fragments bound to a single order of sites; the affinity of rPTH-(1-34) exceeded that of bPTH-(1-34), correlating with its higher potency in stimulating adenylate cyclase. In studies with oxidized bPTH-(1--84), the middle and carboxyl regions of intact PTH were found to bind to both tissues but with higher affinity to osteosarcoma cells than to renal membranes. Our results demonstrate that rPTH-(1--34) is the most favorable probe of amino-terminal PTH binding and the most potent of the PTH peptides in stimulating renal and osseous adenylate cyclase. The results also show that midregion and carboxyl determinants within intact PTH contribute to hormone binding, which does not correlate with adenylate cyclase activation and appears more significant for skeletal than for renal binding
Long-term effects of intermittent equine parathyroid hormone fragment (ePTH-1-37) administration on bone metabolism in healthy horses.

Science.gov (United States)

Weisrock, Katharina U; Winkelsett, Sarah; Martin-Rosset, William; Forssmann, Wolf-Georg; Parvizi, Nahid; Coenen, Manfred; Vervuert, Ingrid

2011-11-01

Intermittent administration of parathyroid hormone (PTH) is an anabolic therapy for osteoporotic conditions in humans. This study evaluated the effects of equine PTH fragment (ePTH-1-37) administration on bone metabolism in 12 healthy horses. Six horses each were treated once daily for 120days with subcutaneous injections of 0.5μg/kg ePTH-1-37 or placebo. Blood was collected to determine ionized calcium (Ca(++)), total Ca (Ca(T)), inorganic phosphorus, serum equine osteocalcin (eOC), carboxy-terminal telopeptide of type I collagen (ICTP), bone-specific alkaline phosphatase, and carboxy-terminal cross-linked telopeptide of type I collagen. Bone mineral density (BMD) was determined with dual X-ray absorptiometry of the metacarpus and calcaneus. Significantly higher blood Ca(++) and plasma Ca(T) concentrations were measured 5h after ePTH-1-37 administration compared to placebo. Higher serum eOC concentrations were found for ePTH-1-37 treatment at days 90 (P<0.05) and 120 (P=0.05). Significantly higher serum ICTP levels were observed with ePTH-1-37 treatment at days 60 and 90. For both study groups, BMD increased significantly in the calcaneus. Long-term use of ePTH-1-37 seemed to have no negative effects on bone metabolism in healthy horses. The absence of undesirable side effects is the premise to ensure safety for further clinical investigations in horses with increased bone resorption processes. Copyright © 2011 Elsevier Ltd. All rights reserved.
Effects of growth hormone administration on bone mineral metabolism, PTH sensitivity and PTH secretory rhythm in postmenopausal women with established osteoporosis.

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Joseph, Franklin; Ahmad, Aftab M; Ul-Haq, Mazhar; Durham, Brian H; Whittingham, Pauline; Fraser, William D; Vora, Jiten P

2008-05-01

Growth hormone (GH) replacement improves target organ sensitivity to PTH, PTH circadian rhythm, calcium and phosphate metabolism, bone turnover, and BMD in adult GH-deficient (AGHD) patients. In postmenopausal women with established osteoporosis, GH and insulin like growth factor-1 (IGF-1) concentrations are low, and administration of GH has been shown to increase bone turnover and BMD, but the mechanisms remain unclear. We studied the effects of GH administration on PTH sensitivity, PTH circadian rhythm, and bone mineral metabolism in postmenopausal women with established osteoporosis. Fourteen postmenopausal women with osteoporosis were compared with 14 healthy premenopausal controls at baseline that then received GH for a period of 12 mo. Patients were hospitalized for 24 h before and 1, 3, 6, and 12 mo after GH administration and half-hourly blood and 3-h urine samples were collected. PTH, calcium (Ca), phosphate (PO(4)), nephrogenous cyclic AMP (NcAMP), beta C-telopeptide of type 1 collagen (betaCTX), procollagen type I amino-terminal propeptide (PINP), and 1,25-dihydroxyvitamin D [1,25(OH)(2)D] were measured. Circadian rhythm analysis was performed using Chronolab 3.0 and Student's t-test and general linear model ANOVAs for repeated measures were used where appropriate. IGF-1 concentration was significantly lower in the women with established osteoporosis compared with controls (101.5 +/- 8.9 versus 140.9 +/- 10.8 mug/liter; p bone mineral metabolism. GH administration to postmenopausal osteoporotic women improves target organ sensitivity to PTH and bone mineral metabolism and alters PTH secretory pattern with greater increases in bone formation than resorption. These changes, resulting in a net positive bone balance, may partly explain the mechanism causing the increase in BMD after long-term administration of GH in postmenopausal women with osteoporosis shown in previous studies and proposes a further component in the development of age

ALX 111: ALX1-11, parathyroid hormone (1-84) - NPS Allelix, PREOS, PTH, recombinant human parathyroid hormone, rhPTH (1-84).

Science.gov (United States)

2003-01-01

ALX 111 [parathyroid hormone (1-84) - NPS Allelix, recombinant human parathyroid hormone, rhPTH (1-84), PREOS] is a full-length, recombinant human parathyroid hormone. It has potential as an anti-osteoporotic agent, due to its properties as a bone formation stimulant. This profile has been selected from R&D Insight, a pharmaceutical intelligence database produced by Adis International Ltd. It has been recommended that ALX 111 should be given for 1 to 2 years and may be given in combination with an antiresorptive agent, such as estrogen or a bisphosphonate. In December 1999, Allelix Biopharmaceuticals merged with NPS Pharmaceuticals. This combined company is operating as NPS Pharmaceuticals in the US and as NPS Allelix in Canada. The merger has enabled a phase III study of ALX 111 to begin in the US, Europe and South America. NPS harmaceuticals has signed an agreement with Bio-Imaging Technologies, which will provide all image handling and analysis for this trial. Until 1994, Allelix Biopharmaceuticals and Glaxo in Canada were involved in a joint venture to investigate the efficacy of ALX 111 in osteoporosis. Allelix was subsequently, until September 1998, collaborating with Astra of Sweden in developing ALX 111. Astra had acquired exclusive worldwide rights to ALX 111 and was responsible for development of the agent. However, Astra returned all rights to ALX 111 to Allelix as a result of its merger with Zeneca to form AstraZeneca. In December 1999, Allelix Biopharmaceuticals merged with NPS Pharmaceuticals. This combined company is operating as NPS Pharmaceuticals in the US and as NPS Allelix in Canada. The merger has enabled a phase III study of ALX 111 to begin in the US, Europe and South America. The phase III trial of ALX 111 for the treatment of osteoporosis has completed patient enrolment, and phase II trials have been completed in Canada and the Netherlands. The 18-month, phase III, multicentre, placebo-controlled trial (Treatment of Osteoporosis with
Cellular effects and delivery propensity of penetratin is influenced by conjugation to parathyroid hormone fragment 1-34 in synergy with pH

DEFF Research Database (Denmark)

Kristensen, Mie; Nielsen, Line Hagner; Zor, Kinga

2018-01-01

The cell-penetrating peptide (CPP) penetratin, has demonstrated potential as a carrier for transepithelial delivery of cargo peptides, such as the therapeutically relevant part of parathyroid hormone, i.e. PTH(1-34). The purpose of the present study was to elucidate the relevance of modifying the pH...... evaluated by using the Real-Time-GLO assay as well as by microscopy following Tryphan blue staining. Morphological Caco-2 cell changes were studied exploiting the impedance-based xCELLigence system as well as optically using the oCelloscope setup. Finally, the effect of pH on the folding propensity...... the conjugation approach, the PTH(1-34) permeation was significantly enhanced by lowering the pH from 7.4 to 5, but also associated with a compromised barrier and a lowering of the cellular viability. The negative effects on the cellular viability following cellular incubation with the PTH(1-34)-penetratin...
Effects of increasing age, dosage, and duration of PTH treatment on BMD increase--a meta-analysis

DEFF Research Database (Denmark)

Schwarz, Peter; Jorgensen, Niklas Rye; Mosekilde, Leif

2012-01-01

were included. By metaregression analysis, we found that the increase in spine BMD (Z-score) after PTH treatment was blunted by increasing age (R (2) = 0.27; 2p = 0.01, slope -0.023 Z-scores per year, 11 studies). By increasing PTH dosage (μg/d), spine BMD increased significantly (2p = 0.......002) with a slope of +0.011 Z-scores/μg/d of teriparatide. Furthermore, the duration of treatment was positively correlated to spine BMD (P ......We studied the effects of increasing age, dosage, and duration of parathyroid hormone (PTH) treatment on changes in bone mineral density (BMD). Randomized placebo controlled trials on PTH treatment in men or women were retrieved from PubMed (1951 to present), Web of Science (1945 to present...
Regional myocardial blood flow distribution during intracoronary infusion of parathyroid hormone

International Nuclear Information System (INIS)

Crass, M.F. III; Lust, R.M.

1986-01-01

Although low doses of the biologically-active fragment of parathyroid hormone PTH-(1-34), have been shown to produce potent dilation of the coronary circulation specific regional and transmural (endo/epi) myocardial blood flow (MBF) responses to the hormone have not been described. Anesthetized open-chest mongrel dogs were instrumented to quantitate coronary blood flow and other cardiodynamic parameters. PTH-(1-34) was infused into the left circumflex artery (.008 nmol kg -1 min -1 ). Using the reference withdrawal method, radionuclide-labeled microspheres were injected before (basal flow), during (8 min after new steady-state flow), and after (restoration of basal flow) a 20 min infusion of PTH-(1-34). MFB increased from 76 +- 1.9 to 152 +- 3.5 ml min -1 100 g -1 (P < .001) during PTH-(1-34) infusion. No differences in endo/epi flow ratio or regional coronary blood flow within the left ventricle were detected. Thus, in anesthetized dogs, the increase in MBF observed secondary to the PTH-(1-34)-induced decrease in coronary resistance appeared to be uniform transmurally and regionally, and is probably not the result of a shunting or steal phenomenon
Parathyroid hormone (PTH) blood test

Science.gov (United States)

... PTH) intact molecule; Intact PTH; Hyperparathyroidism - PTH blood test; Hypoparathyroidism - PTH blood test ... drinking for some period of time before the test. Most often, you will not need to fast ...
Dopamine enhances the phosphaturic effect of PTH during acute respiratory alkalosis.

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Berndt, T J; Tucker, R R; Kent, P D; Streiff, P C; Tyce, G M; Knox, F G

1999-12-01

The phosphaturic response to parathyroid hormone (PTH) is blunted during acute respiratory alkalosis. The objective of the present study was to determine the effect of dopamine on the blunted phosphaturic response to PTH during acute respiratory alkalosis. The phosphaturic response to PTH was determined in thyroparathyroidectomized (TPTX) normocapnic and respiratory alkalotic rats in the absence and presence of the infusion of exogenous dopamine (25 microg/kg/min) or of 3,4-dihydroxyphenylalanine (L-DOPA, 250 microg/kg/min) to increase endogenous dopamine synthesis. In normocapnic rats, PTH infusion (33 U/kg plus 1 U/kg/min) significantly increased the fractional excretion of phosphate (FE(Pi)), from 1.5%+/-0.5% to 28.4%+/-4.0%, (deltaFE(Pi) 26.9%+/-4.1%, n = 11, Prespiratory alkalotic rats, the increase was from 0.4%+/-0.1% to 11.4%+/-1.7% (deltaFE(Pi) 11.0%+/-1.8%, n = 13, Prespiratory alkalotic rats (deltaFE(Pi) 26.9%+/-4.1% vs 11.0%+/-1.9%, Prespiratory alkalotic rats, in the presence of dopamine infusion, PTH significantly increased the FE(Pi), from 0.6%+/-0.2% to 19.3%+/-3.3% (deltaFE(Pi) 18.7%+/-3.3%, n = 6); in the presence of L-DOPA infusion it increased from 1.0%+/-0.3% to 20.5%+/-2.8% (deltaFE(Pi) 19.5%+/-2.9%, n = 8, Prespiratory alkalotic rats was enhanced by stimulation of endogenous dopamine synthesis by the infusion of L-DOPA.
Desensitization of parathyroid hormone receptors on cultured bone cells

International Nuclear Information System (INIS)

Pun, K.K.; Ho, P.W.; Nissenson, R.A.; Arnaud, C.D.

1990-01-01

Administration of excessive amounts of parathyroid hormone (PTH) in the treatment of osteoporosis can reverse the beneficial effects of a low-dose, intermittent regime. To investigate the direct actions and the possible cellular mechanisms of PTH in inducing desensitization of PTH receptors, we studied the effects of desensitization on rat osteoblastic UMR-106 cells. When the osteoblasts were preincubated with bPTH-(1-34), complete refractoriness to a subsequent challenge with the hormone developed within 1 h and at hormone concentrations as low as 5 nM. When osteoblasts thus desensitized were incubated in hormone-free medium, recovery of the cAMP responses began within 2 h and reached maximum after 16 h. Cycloheximide did not affect the process of desensitization. [Nle8,Nle18,Tyr34]bPTH-(3-34)amide significantly impaired the desensitization process by PTH-(1-34) but did not have stimulatory effect on cAMP responses. No significant heterologous desensitization was obvious after preincubation with isoprenaline (50 microM), prostaglandin E1 (50 microM), or prostaglandin E2 (50 microM) for 2 h. Binding experiments with [125I]PLP-(1-36)amide after desensitization revealed that there was an approximate twofold decrease in receptor affinities as analyzed by Scatchard analysis, showing that the decrease in affinity was prominent in the process of desensitization. When the cells were treated with monensin during desensitization, PTH challenge after desensitization produced significantly lower cyclic AMP responses. Recovery after desensitization occurred over a period of 16 h. Inclusion of monensin, but not cycloheximide, impaired the recovery. The results show that homologous desensitization of rat osteoblasts to PTH is brought about by the occupancy of receptors by PTH-(1-34) but not by cAMP generation itself
Modeling of Oxidized PTH (oxPTH and Non-oxidized PTH (n-oxPTH Receptor Binding and Relationship of Oxidized to Non-Oxidized PTH in Children with Chronic Renal Failure, Adult Patients on Hemodialysis and Kidney Transplant Recipients

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Berthold Hocher

2013-07-01

PTH. Conclusion: A huge proportion of circulating PTH measured by current state-of-the-art assay systems is oxidized and thus not biologically active. The relationship between oxPTH and n-oxPTH of individual patients varied substantially. Non-oxidized PTH concentrations are 1.5 - 2.25 fold higher in patients with renal failure as compared to health controls. Measurements of n-oxPTH may reflect the hormone status more precise. The iPTH measures describes most likely oxidative stress in patients with renal failure rather than the PTH hormone status. This, however, needs to be demonstrated in further clinical studies.
Effects of Intermittent Administration of Parathyroid Hormone (1-34 on Bone Differentiation in Stromal Precursor Antigen-1 Positive Human Periodontal Ligament Stem Cells

Directory of Open Access Journals (Sweden)

Xiaoxiao Wang

2016-01-01

Full Text Available Periodontitis is the most common cause of tooth loss and bone destruction in adults worldwide. Human periodontal ligament stem cells (hPDLSCs may represent promising new therapeutic biomaterials for tissue engineering applications. Stromal precursor antigen-1 (STRO-1 has been shown to have roles in adherence, proliferation, and multipotency. Parathyroid hormone (PTH has been shown to enhance proliferation in osteoblasts. Therefore, in this study, we aimed to compare the functions of STRO-1(+ and STRO-1(− hPDLSCs and to investigate the effects of PTH on the osteogenic capacity of STRO-1(+ hPDLSCs in order to evaluate their potential applications in the treatment of periodontitis. Our data showed that STRO-1(+ hPDLSCs expressed higher levels of the PTH-1 receptor (PTH1R than STRO-1(− hPDLSCs. In addition, intermittent PTH treatment enhanced the expression of PTH1R and osteogenesis-related genes in STRO-1(+ hPDLSCs. PTH-treated cells also exhibited increased alkaline phosphatase activity and mineralization ability. Therefore, STRO-1(+ hPDLSCs represented a more promising cell resource for biomaterials and tissue engineering applications. Intermittent PTH treatment improved the capacity for STRO-1(+ hPDLSCs to repair damaged tissue and ameliorate the symptoms of periodontitis.
Effects of continuous and pulsatile PTH treatments on rat bone marrow stromal cells

International Nuclear Information System (INIS)

Yang Chiming; Frei, Hanspeter; Burt, Helen M.; Rossi, Fabio

2009-01-01

Bone marrow stromal cells (MSCs) differentiation and proliferation are controlled by numerous growth factors and hormones. Continuous parathyroid hormone (PTH) treatment has been shown to decrease osteoblast differentiation, whereas pulsatile PTH increases osteoblast differentiation. However, the effects of PTH treatments on MSCs have not been investigated. This study showed continuous PTH treatment in the presence of dexamethasone (DEX) promoted osteogenic differentiation of rat MSCs in vitro, as demonstrated by increased alkaline phosphatase (ALP) activity, number of ALP expressing cells, and up-regulation of PTH receptor-1, ALP, and osteocalcin mRNA expressions. In contrast, pulsatile PTH treatment was found to suppress osteogenesis of rat MSCs, possibly by promoting the maintenance of undifferentiated cells. Additionally, the observed effects of PTH were strongly dependent on the presence of DEX. MSC proliferation however was not influenced by PTH independent of treatment regimen and presence or absence of DEX. Furthermore, our work raised the possibility that PTH treatment may modulate stem/progenitor cell activity within MSC cultures.
The metabolism of parathyroid hormone in kidney

International Nuclear Information System (INIS)

Hanao, Yasuhisa

1978-01-01

In order to investigate the mechanism and localization of parathyroid hormone (PTH), the degradation and the effects of calcium ion to PTH degradation in kidney, bovine PTH (b-PTH 1 - 84) and its synthetic N-terminal peptide (b-PTH 1 - 34) labeled with 125 I by Chloramine T methods ( 125 I-b-PTH 1 - 84 and 125 I-b-PTH 1 - 34) or labeled with horse radish peroxidase ( 125 I-POX-b-PTH 1 - 84 and 125 I-POX-bPTH 1-34) were used to study the disappearance from the blood stream and degradation and retention in the kidney after intravenous injections in male Wistar rats, weighing approximately 350 - 450 g. Degradation of PTH was studied in vitro, using isolated cells and homogenates of the kidney, and the effects of calcium ion to PTH degradation were furthermore studied, using our kidney perfusion system. PTH labeled with 125 I and POX was less degraded by the kidney than PTH labeled with 125 I alone. PTH 1 - 34 was more delayed in blood stream than PTH 1 - 84. Isolated intact kidney cells degrade PTH less efficiently than homogenates, indicating the prominance of microsomal degradative system in the kidney. The degradation of PTH in kidney was supposed to be controlled by calcium ion in our kidney perfusion system. (author)
Role of acidosis-induced increases in calcium on PTH secretion in acute metabolic and respiratory acidosis in the dog.

Science.gov (United States)

López, Ignacio; Aguilera-Tejero, Escolástico; Estepa, José Carlos; Rodríguez, Mariano; Felsenfeld, Arnold J

2004-05-01

Recently, we showed that both acute metabolic acidosis and respiratory acidosis stimulate parathyroid hormone (PTH) secretion in the dog. To evaluate the specific effect of acidosis, ionized calcium (iCa) was clamped at a normal value. Because iCa values normally increase during acute acidosis, we now have studied the PTH response to acute metabolic and respiratory acidosis in dogs in which the iCa concentration was allowed to increase (nonclamped) compared with dogs with a normal iCa concentration (clamped). Five groups of dogs were studied: control, metabolic (clamped and nonclamped), and respiratory (clamped and nonclamped) acidosis. Metabolic (HCl infusion) and respiratory (hypoventilation) acidosis was progressively induced during 60 min. In the two clamped groups, iCa was maintained at a normal value with an EDTA infusion. Both metabolic and respiratory acidosis increased (P acidosis, the increase in iCa was progressive and greater (P respiratory acidosis, in which iCa increased by 0.04 mM and then remained constant despite further pH reductions. The increase in PTH values was greater (P respiratory acidosis). In the nonclamped metabolic acidosis group, PTH values first increased and then decreased from peak values when iCa increased by > 0.1 mM. In the nonclamped respiratory acidosis group, PTH values exceeded (P acidosis. In conclusion, 1) both metabolic acidosis and respiratory acidosis stimulate PTH secretion; 2) the physiological increase in the iCa concentration during the induction of metabolic and respiratory acidosis reduces the magnitude of the PTH increase; 3) in metabolic acidosis, the increase in the iCa concentration can be of sufficient magnitude to reverse the increase in PTH values; and 4) for the same degree of acidosis-induced hypercalcemia, the increase in PTH values is greater in metabolic than in respiratory acidosis.
The measurement of serum human parathyroid hormone (h-PTH53-84) and effect of exercise on calcium metabolism

International Nuclear Information System (INIS)

Torizumi, Kazutami; Taniguchi, Yoshiyuki; Aibata, Hirofumi; Kiji, Shigeyuki; Ueyoshi, Akitaka; Shimizu, Eiji; Okamoto, Yukiharu; Tuda, Tadaaki; Ota, Kiichiro

1987-01-01

This study was focussed our attention on the measurement within the upper physiological level of human serum parathyroid hormone (PTH), using kits of human PTH 53 - 84. This assay kit was able to detect serum PTH in sera with suble changes of serum calcium concentrations before and after short term exercise. These serum PTH levels before and after exercise seemed to be changed within the upper physiological levels of PTH. Thus, this study suggested that the assay kit was likely to become a useful tool of the measurement of the physiological level of serum PTH in humans. (author)
Modeling of Oxidized PTH (oxPTH) and Non-oxidized PTH (n-oxPTH) Receptor Binding and Relationship of Oxidized to Non-Oxidized PTH in Children with Chronic Renal Failure, Adult Patients on Hemodialysis and Kidney Transplant Recipients

DEFF Research Database (Denmark)

Hocher, Berthold; Oberthür, Dominik; Slowinski, Torsten

2013-01-01

Background: The biological properties of oxidized and non-oxidized PTH are substantially different. Oxidized PTH (oxPTH) loses its PTH receptor-stimulating properties, whereas non-oxidized PTH (n-oxPTH) is a full agonist of the receptor. This was described in more than 20 well published studies i......PTH measures describes most likely oxidative stress in patients with renal failure rather than the PTH hormone status. This, however, needs to be demonstrated in further clinical studies. © 2013 S. Karger AG, Basel......., we performed modeling of the interaction of either oxPTH or n-oxPTH with the PTH receptor using biophysical structure approaches. Results: The children had the highest mean as well as maximum n-oxPTH concentrations as compared to adult patients (both patients on dialysis as well as kidney transplant......-oxPTH. This indicated that PTH oxidation may induce refolding of PTH and hence alters PTH-PTH receptor interaction via oxidation induced three-dimensional structure alteration of PTH. Conclusion: A huge proportion of circulating PTH measured by current state-of-the-art assay systems is oxidized and thus...
Structure of non-(1-84) PTH fragments secreted by parathyroid glands in primary and secondary hyperparathyroidism.

Science.gov (United States)

D'Amour, Pierre; Brossard, Jean-Hugues; Rousseau, Louise; Nguyen-Yamamoto, Loan; Nassif, Edgard; Lazure, Claude; Gauthier, Dany; Lavigne, Jeffrey R; Zahradnik, Richard J

2005-09-01

Non-(1-84) parathyroid hormone (PTH) fragments are large circulating carboxyl-terminal (C) fragments with a partially preserved amino-terminal (N) structure. hPTH (7-84), a synthetic surrogate, has been demonstrated to exert biologic effects in vivo and in vitro which are opposite to those of hPTH (1-34) on the PTH/PTHrP type I receptor through a C-PTH receptor. We wanted to determine the N structure of non-(1-84) PTH fragments. Parathyroid cells isolated from glands obtained at surgery from three patients with primary hyperparathyroidism and three patients with secondary hyperparathyroidism were incubated with 35S-methionine to internally label their secretion products. Incubations were performed for 8 hours at the patient-ionized calcium concentration and in the presence of various protease inhibitors. The supernatant was fractionated by high-performance liquid chromatography (HPLC) and fractions were analyzed with PTH assays having (1 to 4) and (12 to 23) epitopes, respectively. The serum of each patient was similarly analyzed. Peaks of immunoreactivity identified were submitted to sequence analysis to recover the 35S-methionine residues in positions 8 and 18. Three regions of interest were identified with PTH assays. They corresponded to non-(1-84) PTH fragments (further divided in regions 3 and 4), a peak of N-PTH migrating in front of hPTH (1-84) (region 2) and a peak of immunoreactivity corresponding to the elution position of hPTH (1-84) (region 1). The last corresponded to a single sequence starting at position 1. Region 2 gave similar results in all cases (a major signal starting at position 1) but also sometimes minor sequences starting at position 4 or 7. Regions 3 and 4 always identified a major sequence starting at positions 7 and minor sequences starting at positions 8, 10, and 15. Surprisingly, a major signal starting at position 1 was also present in region 3. The HPLC profile obtained from a given patient's parathyroid cells was qualitatively
Calciotrophic hormones and hyperglycemia modulate vitamin D receptor and 25 hydroxyy vitamin D 1-α hydroxylase mRNA expression in human vascular smooth muscle cells.

Science.gov (United States)

Somjen, D; Knoll, E; Sharon, O; Many, A; Stern, N

2015-04-01

Estrogen receptors (ERα and ERβ), the vitamin D receptor (VDR) and 25 hydroxyy vitamin D 1-α hydroxylase (1OHase) mRNA are expressed in vascular smooth muscle cells (VSMC). In these cells estrogenic hormones modulate cell proliferation as measured by DNA synthesis (DNA). In the present study we determined whether or not the calciotrophic hormones PTH 1-34 (PTH) and less- calcemic vitamin D analog QW as well as hyperglycemia can regulate DNA synthesis and CK. E2 had a bimodal effect on VSMC DNA synthesis, such that proliferation was inhibited at 30nM but stimulated at 0.3nM. PTH at 50nM increased, whereas QW at 10nM inhibited DNA synthesis. Hyperglycemia inhibited the effects on high E2, QW and PTH on DNA only. Both QW and PTH increased ERα mRNA expression, but only PTH increased ERβ expression. Likewise, both PTH and QW stimulated VDR and 1OHase expression and activity. ERβ, VDR and 1OHase expression and activity were inhibited by hyperglycemia, but ERα expression was unaffected by hyperglycemia. In conclusion, calcitrophic hormones modify VSMC growth and concomitantly affect ER expression in these cells as well as the endogenous VSMC vitamin D system elements, including VDR and 1OHase. Some of the later changes may likely participate in growth effects. Of importance in the observation is that several regulatory effects are deranged in the presence of hyperglycemia, particularly the PTH- and vitamin D-dependent up regulation of VDR and 1OHase in these cells. The implications of these effects require further studies. This article is part of a Special Issue entitled '17th Vitamin D Workshop'. Copyright © 2014 Elsevier Ltd. All rights reserved.
Carboxyl-terminal parathyroid hormone fragments: role in parathyroid hormone physiopathology.

Science.gov (United States)

D'Amour, Pierre; Brossard, Jean-Hugues

2005-07-01

Carboxyl-terminal parathyroid hormone (C-PTH) fragments constitute 80% of circulating PTH. Since the first 34 amino acids of the PTH structure are sufficient to explain PTH classical biological effects on the type I PTH/PTHrP receptor and since C-PTH fragments do not bind to this receptor, they have long been considered inactive. Recent data suggest the existence of a C-PTH receptor through which C-PTH fragments exert biological effects opposite to those of human PTH(1-84) on the type I PTH/PTHrP receptor. This is why a lot of attention has been paid to these fragments recently. In vivo, synthetic C-PTH fragments are able to decrease calcium concentration, to antagonize the calcemic response to human PTH(1-34) and human PTH(1-84) and to decrease the high bone turnover rate induced by human PTH(1-84). In vitro, they inhibit bone resorption, promote osteocyte apoptosis and exert a variety of effects on bone and cartilaginous cells. These effects are opposite to those of human PTH(1-84) on the PTH/PTHrP type I receptor. This suggests that the molecular forms of circulating PTH may control bone participation in calcium homeostasis via two different receptors. Clinically, the accumulation of C-PTH fragments in renal failure patients may cause PTH resistance and may be associated with adynamic bone disease. Rare parathyroid tumors, without a set point error, overproduce C-PTH fragments. The implication of C-PTH fragments in osteoporosis is still to be explored. C-PTH fragments represent a new field of investigation in PTH biology. More studies are necessary to disclose their real importance in calcium and bone homeostasis in health and disease.
Anabolic action of parathyroid hormone (PTH) does not compromise bone matrix mineral composition or maturation.

Science.gov (United States)

Vrahnas, Christina; Pearson, Thomas A; Brunt, Athena R; Forwood, Mark R; Bambery, Keith R; Tobin, Mark J; Martin, T John; Sims, Natalie A

2016-12-01

Intermittent administration of parathyroid hormone (PTH) is used to stimulate bone formation in patients with osteoporosis. A reduction in the degree of matrix mineralisation has been reported during treatment, which may reflect either production of undermineralised matrix or a greater proportion of new matrix within the bone samples assessed. To explore these alternatives, high resolution synchrotron-based Fourier Transform Infrared Microspectroscopy (sFTIRM) coupled with calcein labelling was used in a region of non-remodelling cortical bone to determine bone composition during anabolic PTH treatment compared with region-matched samples from controls. 8week old male C57BL/6 mice were treated with vehicle or 50μg/kg PTH, 5 times/week for 4weeks (n=7-9/group). Histomorphometry confirmed greater trabecular and periosteal bone formation and 3-point bending tests confirmed greater femoral strength in PTH-treated mice. Dual calcein labels were used to match bone regions by time-since-mineralisation (bone age) and composition was measured by sFTIRM in six 15μm 2 regions at increasing depth perpendicular to the most immature bone on the medial periosteal edge; this allowed in situ measurement of progressive changes in bone matrix during its maturation. The sFTIRM method was validated in vehicle-treated bones where the expected progressive increases in mineral:matrix ratio and collagen crosslink type ratio were detected with increasing bone maturity. We also observed a gradual increase in carbonate content that strongly correlated with an increase in longitudinal stretch of the collagen triple helix (amide I:amide II ratio). PTH treatment did not alter the progressive changes in any of these parameters from the periosteal edge through to the more mature bone. These data provide new information about how the bone matrix matures in situ and confirm that bone deposited during PTH treatment undergoes normal collagen maturation and normal mineral accrual. Copyright © 2016
Gene structure, transcripts and calciotropic effects of the PTH family of peptides in Xenopus and chicken

Directory of Open Access Journals (Sweden)

Power Deborah M

2010-12-01

Full Text Available Abstract Background Parathyroid hormone (PTH and PTH-related peptide (PTHrP belong to a family of endocrine factors that share a highly conserved N-terminal region (amino acids 1-34 and play key roles in calcium homeostasis, bone formation and skeletal development. Recently, PTH-like peptide (PTH-L was identified in teleost fish raising questions about the evolution of these proteins. Although PTH and PTHrP have been intensively studied in mammals their function in other vertebrates is poorly documented. Amphibians and birds occupy unique phylogenetic positions, the former at the transition of aquatic to terrestrial life and the latter at the transition to homeothermy. Moreover, both organisms have characteristics indicative of a complex system in calcium regulation. This study investigated PTH family evolution in vertebrates with special emphasis on Xenopus and chicken. Results The PTH-L gene is present throughout the vertebrates with the exception of placental mammals. Gene structure of PTH and PTH-L seems to be conserved in vertebrates while PTHrP gene structure is divergent and has acquired new exons and alternative promoters. Splice variants of PTHrP and PTH-L are common in Xenopus and chicken and transcripts of the former have a widespread tissue distribution, although PTH-L is more restricted. PTH is widely expressed in fish tissue but from Xenopus to mammals becomes largely restricted to the parathyroid gland. The N-terminal (1-34 region of PTH, PTHrP and PTH-L in Xenopus and chicken share high sequence conservation and the capacity to modify calcium fluxes across epithelia suggesting a conserved role in calcium metabolism possibly via similar receptors. Conclusions The parathyroid hormone family contains 3 principal members, PTH, PTHrP and the recently identified PTH-L. In teleosts there are 5 genes which encode PTHrP (2, PTH (2 and PTH-L and in tetrapods there are 3 genes (PTHrP, PTH and PTH-L, the exception is placental mammals which
Acute and chronic regulation of circulating PTH: significance in health and in disease.

Science.gov (United States)

D'Amour, Pierre

2012-08-01

Circulating human parathyroid hormone (PTH) is immunoheterogenous. It is composed of 80% carboxyl-terminal (C) fragments and of 20% PTH(1-84). This composition contrasts with the biological activity of the hormone, which is only related to PTH(1-84), creating a paradox between circulating PTH composition and PTH bioactivity. PTH molecular forms are either secreted by the parathyroid glands or generated by the peripheral metabolism of PTH(1-84) in the liver. The kidney has a major role in the disposal of C-PTH fragments. Secretion of PTH molecular forms by the parathyroid glands is highly regulated under a variety of clinical conditions, suggesting that C-PTH fragments could exert some biological effects of their own. Recent data suggest that C-PTH fragments can exert biological actions opposite to those of PTH(1-84) by acting on a C-PTH receptor not yet cloned. They can decrease calcium concentration, phosphate excretion, bone resorption and 1,25(OH)₂ synthesis. The clinical implications of this new concept are reviewed. Copyright © 2012 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

[The replacement therapy of rPTH(1-84) in established rat model of hypothyroidism].

Science.gov (United States)

Ding, Zhiwei; Li, Tiancheng; Liu, Yuhe; Xiao, Shuifang

2015-12-01

To investigate the replacement therapy of rPTH(1-84) (recombinant human parathyroid hormone (1-84)) to hypothyroidism in established rat model. Rat model of hypothyroidism was established by resecting parathyroids. A total of 30 rats with removal of parathyroids were divided into 6 groups randomly, 5 in each group, and applied respectively with saline injection (negative control group), calcitriol treatment (positive control group) and quadripartite PTH administration with dose of 20, 40, 80 and 160 µg/kg (experimental groups). Saline and rPTH(1-84) were injected subcutaneously daily. Calcitriol was gavaged once a day. Sham-operation was conducted in 5 rats of negative control group. To verify the authenticity of the rat model with hypothyroidism, the serum was insolated centrifugally from rat blood that was obtained from angular vein at specific time to measure calcium and phosphorus concentration. Urine in 12 hours was collected by metabolic cages and the calcium concentration was measured. After 10-week drug treatment, the experiment was terminated and bilateral femoral bone and L2-5 lumbar vertebra were removed from rats. Bone mineral density (BMD)of bilateral femoral bone and lumbar vertebra was analyzed by dual X-ray absorptiometry (DXA). The concentration of bone alkaline phosphatase (BALP) in serum was determined by radioimmunoassay. The rat model with hypothyroidism was obtained by excising parathyroid gland and was verified by monitoring calcium and phosphorus concentration subsequently. Administration of rPTH(1-84) in the dose of 80 or 160 µg/kg made serum calcium and phosphorus back to normal levels, with no significant difference between the doses (P>0.05). The BMD in each group of rats with rPTH(1-84) administration was increased significantly (P0.05). Calcium and phosphorus return to normal level by administration of rPTH(1-84) in the dose of 80 µg/kg or 160 µg/kg, with increase in BMD. Calcitriol can return the level of calcium to normal and
Monitoring of intermittent PTH(1-34) treatment by serum PINP in adult ovariectomized osteopenic rats

DEFF Research Database (Denmark)

Halleen, Jussi; Peng, ZhiQi; Fagerlund, Katja

-operated control group receiving vehicle, and OVX-operated groups receiving daily subcutaneous injections of 1.2, 4.0, 12.0, 40.0 and 120.0 µg/kg human PTH(1-34). Each group contained 12 animals that were 6 months of age at the time of the operations. Dosing was started at 7 weeks after OVX and continued for 6...... weeks. Before the start of treatment, the animals were randomized to groups based on their body weights and trabecular bone mineral density values obtained by peripheral quantitative computed tomography (pQCT). PINP values were determined from serum samples collected before the start of treatment, at 2...
Teriparatida (PTH[1-34]rh: uma nova perspectiva no tratamento da osteoporose

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Oliveira Juliana Helena Abreu de

2003-01-01

Full Text Available No momento, as medicações aprovadas para tratamento da osteoporose agem reduzindo a taxa de perda óssea e diminuindo a reabsorção óssea. A teriparatida é um fragmento recombinante sintético de 34 aminoácidos do hormônio paratireóide humano. A teriparatida se liga ao receptor de PTH da proteína G e estimula a formação e a ação dos osteoblastos, que são as células responsáveis pela formação dos ossos. Assim, a principal diferença entre o tratamento da osteoporose com teriparatida e o tratamento anti-reabsorção é que a teriparatida promove o crescimento de osso novo. Em estudos pré-clínicos, o uso intermitente de PTH foi associado com um aumento significativo da massa óssea gradeada em diversos locais. A exposição intermitente ao PTH durante 4 a 6 semanas em modelos de animais ovariectomizados leva a um aumento da espessura do osso gradeado. Há estudos clínicos que mostram que a teriparatida aumenta significativamente a densidade óssea e diminui a incidência de fraturas osteoporóticas vertebrais e não-vertebrais nas mulheres com osteoporose pós-menopáusica e têm risco alto de fratura, e aumenta a densidade óssea nos homens com osteoporose, tanto hipogonádica como idiopática. A teriparatida é dada por injeção subcutânea diária e foi associada com um mínimo de efeitos colaterais, além de não apresentar interações medicamentosas. Sendo assim, a teriparatida surge como uma abordagem completamente nova no tratamento da osteoporose, estimulando diretamente a formação do osso.
Comparison of Intact PTH and Bio-Intact PTH Assays Among Non-Dialysis Dependent Chronic Kidney Disease Patients.

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Einbinder, Yael; Benchetrit, Sydney; Golan, Eliezer; Zitman-Gal, Tali

2017-09-01

The third-generation bio-intact parathyroid hormone (PTH) (1-84) assay was designed to overcome problems associated with the detection of C-terminal fragments by the second-generation intact PTH assay. The two assays have been compared primarily among dialysis populations. The present study evaluated the correlations and differences between these two PTH assays among patients with chronic kidney disease (CKD) stages 3 to 5 not yet on dialysis. Blood samples were collected from 98 patients with CKD stages 3 to 5. PTH concentrations were measured simultaneously by using the second-generation - PTH intact-STAT and third-generation bio-intact 1-84 PTH assays. Other serum biomarkers of bone mineral disorders were also assessed. CKD stage was calculated by using the CKD-Epidemiology Collaboration (EPI) formula. Serum bio-intact PTH concentrations were strongly correlated but significantly lower than the intact PTH concentrations (r=0.963, Pbio-intact PTH) positively correlated with urea (r=0.523, r=0.504; P=0.002, respectively), phosphorus (r=0.532, r=0.521; Pbio-intact PTH assay detected significantly lower PTH concentrations compared with intact PTH assay. Additional studies that correlate the diagnosis and management of CKD mineral and bone disorders with bone histomorphometric findings are needed to determine whether bio-intact PTH assay results are better surrogate markers in these early stages of CKD. © The Korean Society for Laboratory Medicine
Radioimmunological assay of the biologically active fragment of the human parathyroid hormone

International Nuclear Information System (INIS)

Desplan, C.; Jullienne, A.; Raulais, D.; Rivaille, P.; Barlet, J.P.; Moukthar, M.S.; Milhaud, G.

1977-01-01

The authors describe a RIA of the biologically active fraction (N-terminal) of human parathyroid hormone. This homologous test uses antibodies obtained in goats against a N-terminal 1-34 fragment of hPTH synthetised according to the method of Niall and Coll. In this system, natural hPTH of different origin (extracts from parathyroid adenomas, adenomal culture medium, hyperparathyroid plasma, adsorption chromatography extract of normal human plasma) behaved in the same manner as the synthetic reference hormone 1-34 hPTHN. The RIA detected PTH in 65% of the normal subjects and distinguished the normal values from the values of hyperparathyroid patients, which makes it suitable for clinical practice. (AJ) [de
Cell Cycle and Apoptosis Regulatory Protein (CARP)-1 is Expressed inOsteoblasts and Regulated by PTH

International Nuclear Information System (INIS)

Sharma, Sonali; Mahalingam, Chandrika D.; Das, Varsha; Jamal, Shazia; Levi, Edi; Rishi, Arun K.; Datta, Nabanita S.

2013-01-01

Highlights: •CARP-1 is identified for the first time in bone cells. •PTH downregulates CARP-1 expression in differentiated osteoblasts. •PTH displaces CARP-1 from nucleus to the cytoplasm in differentiated osteoblasts. •Downregulation of CARP-1 by PTH involves PKA, PKC and P-p38 MAPK pathways. -- Abstract: Bone mass is dependent on osteoblast proliferation, differentiation and life-span of osteoblasts. Parathyroid hormone (PTH) controls osteoblast cell cycle regulatory proteins and suppresses mature osteoblasts apoptosis. Intermittent administration of PTH increases bone mass but the mechanism of action are complex and incompletely understood. Cell Cycle and Apoptosis Regulatory Protein (CARP)-1 (aka CCAR1) is a novel transducer of signaling by diverse agents including cell growth and differentiation factors. To gain further insight into the molecular mechanism, we investigated involvement of CARP-1 in PTH signaling in osteoblasts. Immunostaining studies revealed presence of CARP-1 in osteoblasts and osteocytes, while a minimal to absent levels were noted in the chondrocytes of femora from 10 to 12-week old mice. Treatment of 7-day differentiated MC3T3-E1 clone-4 (MC-4) mouse osteoblastic cells and primary calvarial osteoblasts with PTH for 30 min to 5 h followed by Western blot analysis showed 2- to 3-fold down-regulation of CARP-1 protein expression in a dose- and time-dependent manner compared to the respective vehicle treated control cells. H-89, a Protein Kinase A (PKA) inhibitor, suppressed PTH action on CARP-1 protein expression indicating PKA-dependent mechanism. PMA, a Protein Kinase C (PKC) agonist, mimicked PTH action, and the PKC inhibitor, GF109203X, partially blocked PTH-dependent downregulation of CARP-1, implying involvement of PKC. U0126, a Mitogen-Activated Protein Kinase (MAPK) Kinase (MEK) inhibitor, failed to interfere with CARP-1 suppression by PTH. In contrast, SB203580, p38 inhibitor, attenuated PTH down-regulation of CARP-1
Cell Cycle and Apoptosis Regulatory Protein (CARP)-1 is Expressed inOsteoblasts and Regulated by PTH

Energy Technology Data Exchange (ETDEWEB)

Sharma, Sonali; Mahalingam, Chandrika D.; Das, Varsha [Department of Internal Medicine/Endocrinology, Wayne State University School of Medicine, Detroit, MI 48201 (United States); Jamal, Shazia [Department of Oncology, Wayne State University School of Medicine, Detroit, MI 48201 (United States); Levi, Edi [Department of Oncology, Wayne State University School of Medicine, Detroit, MI 48201 (United States); Department of Pathology, Wayne State University School of Medicine, Detroit, MI 48201 (United States); Rishi, Arun K. [Department of Oncology, Wayne State University School of Medicine, Detroit, MI 48201 (United States); Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI 48201 (United States); VA Medical Center, Wayne State University School of Medicine, Detroit, MI 48201 (United States); Datta, Nabanita S., E-mail: ndatta@med.wayne.edu [Department of Internal Medicine/Endocrinology, Wayne State University School of Medicine, Detroit, MI 48201 (United States); Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI 48201 (United States); Cardiovascular Research Institute, Wayne State University School of Medicine, Detroit, MI 48201 (United States)

2013-07-12

Highlights: •CARP-1 is identified for the first time in bone cells. •PTH downregulates CARP-1 expression in differentiated osteoblasts. •PTH displaces CARP-1 from nucleus to the cytoplasm in differentiated osteoblasts. •Downregulation of CARP-1 by PTH involves PKA, PKC and P-p38 MAPK pathways. -- Abstract: Bone mass is dependent on osteoblast proliferation, differentiation and life-span of osteoblasts. Parathyroid hormone (PTH) controls osteoblast cell cycle regulatory proteins and suppresses mature osteoblasts apoptosis. Intermittent administration of PTH increases bone mass but the mechanism of action are complex and incompletely understood. Cell Cycle and Apoptosis Regulatory Protein (CARP)-1 (aka CCAR1) is a novel transducer of signaling by diverse agents including cell growth and differentiation factors. To gain further insight into the molecular mechanism, we investigated involvement of CARP-1 in PTH signaling in osteoblasts. Immunostaining studies revealed presence of CARP-1 in osteoblasts and osteocytes, while a minimal to absent levels were noted in the chondrocytes of femora from 10 to 12-week old mice. Treatment of 7-day differentiated MC3T3-E1 clone-4 (MC-4) mouse osteoblastic cells and primary calvarial osteoblasts with PTH for 30 min to 5 h followed by Western blot analysis showed 2- to 3-fold down-regulation of CARP-1 protein expression in a dose- and time-dependent manner compared to the respective vehicle treated control cells. H-89, a Protein Kinase A (PKA) inhibitor, suppressed PTH action on CARP-1 protein expression indicating PKA-dependent mechanism. PMA, a Protein Kinase C (PKC) agonist, mimicked PTH action, and the PKC inhibitor, GF109203X, partially blocked PTH-dependent downregulation of CARP-1, implying involvement of PKC. U0126, a Mitogen-Activated Protein Kinase (MAPK) Kinase (MEK) inhibitor, failed to interfere with CARP-1 suppression by PTH. In contrast, SB203580, p38 inhibitor, attenuated PTH down-regulation of CARP-1
Enhanced chondrogenesis and Wnt signaling in PTH-treated fractures.

Science.gov (United States)

Kakar, Sanjeev; Einhorn, Thomas A; Vora, Siddharth; Miara, Lincoln J; Hon, Gregory; Wigner, Nathan A; Toben, Daniel; Jacobsen, Kimberly A; Al-Sebaei, Maisa O; Song, Michael; Trackman, Philip C; Morgan, Elise F; Gerstenfeld, Louis C; Barnes, George L

2007-12-01

Studies have shown that systemic PTH treatment enhanced the rate of bone repair in rodent models. However, the mechanisms through which PTH affects bone repair have not been elucidated. In these studies we show that PTH primarily enhanced the earliest stages of endochondral bone repair by increasing chondrocyte recruitment and rate of differentiation. In coordination with these cellular events, we observed an increased level of canonical Wnt-signaling in PTH-treated bones at multiple time-points across the time-course of fracture repair, supporting the conclusion that PTH responses are at least in part mediated through Wnt signaling. Since FDA approval of PTH [PTH(1-34); Forteo] as a treatment for osteoporosis, there has been interest in its use in other musculoskeletal conditions. Fracture repair is one area in which PTH may have a significant clinical impact. Multiple animal studies have shown that systemic PTH treatment of healing fractures increased both callus volume and return of mechanical competence in models of fracture healing. Whereas the potential for PTH has been established, the mechanism(s) by which PTH produces these effects remain elusive. Closed femoral fractures were generated in 8-wk-old male C57Bl/6 mice followed by daily systemic injections of either saline (control) or 30 microg/kg PTH(1-34) for 14 days after fracture. Bones were harvested at days 2, 3, 5, 7, 10, 14, 21, and 28 after fracture and analyzed at the tissue level by radiography and histomorphometry and at the molecular and biochemical levels level by RNase protection assay (RPA), real-time PCR, and Western blot analysis. Quantitative muCT analysis showed that PTH treatment induced a larger callus cross-sectional area, length, and total volume compared with controls. Molecular analysis of the expression of extracellular matrix genes associated with chondrogenesis and osteogenesis showed that PTH treated fractures displayed a 3-fold greater increase in chondrogenesis relative to
Conjugation of a cell-penetrating peptide to parathyroid hormone affects its structure, potency, and transepithelial permeation

DEFF Research Database (Denmark)

Kristensen, Mie; de Groot, Anne Marit; Berthelsen, Jens

2015-01-01

hormone, i.e. PTH(1-34), and to evaluate the effect with regards to secondary structure, potency in Saos-2 cells, immunogenicity, safety as well as the transepithelial permeation across monolayers by using the Caco-2 cell culture model. Further, co-administration of CPP and PTH(1-34) as an alternative...
Hypoparathyroidism: Replacement Therapy with Parathyroid Hormone

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Lars Rejnmark

2015-12-01

Full Text Available Hypoparathyroidism (HypoPT is characterized by low serum calcium levels caused by an insufficient secretion of parathyroid hormone (PTH. Despite normalization of serum calcium levels by treatment with activated vitamin D analogues and calcium supplementation, patients are suffering from impaired quality of life (QoL and are at increased risk of a number of comorbidities. Thus, despite normalization of calcium levels in response to conventional therapy, this should only be considered as an apparent normalization, as patients are suffering from a number of complications and calcium-phosphate homeostasis is not normalized in a physiological manner. In a number of recent studies, replacement therapy with recombinant human PTH (rhPTH(1-84 as well as therapy with the N-terminal PTH fragment (rhPTH(1-34 have been investigated. Both drugs have been shown to normalize serum calcium while reducing needs for activated vitamin D and calcium supplements. However, once a day injections cause large fluctuations in serum calcium. Twice a day injections diminish fluctuations, but don't restore the normal physiology of calcium homeostasis. Recent studies using pump-delivery have shown promising results on maintaining normocalcemia with minimal fluctuations in calcium levels. Further studies are needed to determine whether this may improve QoL and lower risk of complications. Such data are needed before replacement with the missing hormone can be recommended as standard therapy.
Blocking the expression of both bone sialoprotein (BSP) and osteopontin (OPN) impairs the anabolic action of PTH in mouse calvaria bone.

Science.gov (United States)

Bouleftour, Wafa; Bouet, Guenaelle; Granito, Renata Neves; Thomas, Mireille; Linossier, Marie-Thérèse; Vanden-Bossche, Arnaud; Aubin, Jane E; Lafage-Proust, Marie-Hélène; Vico, Laurence; Malaval, Luc

2015-03-01

Osteopontin (OPN) and bone sialoprotein (BSP) are coexpressed in osteoblasts and osteoclasts, and display overlapping properties. We used daily injection of parathyroid hormone 1-84 (iPTH) over the calvaria of BSP knockout (-/-) mice to investigate further their functional specificity and redundancy. iPTH stimulated bone formation in both +/+ and -/- mice, increasing to the same degree periosteum, osteoid and total bone thickness. Expression of OPN, osterix, osteocalcin (OCN) and DMP1 was also increased by iPTH in both genotypes. In contrast to +/+, calvaria cell cultures from -/- mice revealed few osteoblast colonies, no mineralization and little expression of OCN, MEPE or DMP1. In contrast, OPN levels were 5× higher in -/- versus +/+ cultures. iPTH increased alkaline phosphatase (ALP) activity in cell cultures of both genotypes, with higher OCN and the induction of mineralization in -/- cultures. siRNA blocking of OPN expression did not alter the anabolic action of the hormone in BSP +/+ calvaria, while it blunted iPTH effects in -/- mice, reduced to a modest increase in periosteum thickness. In -/- (not +/+) cell cultures, siOPN blocked the stimulation by iPTH of ALP activity and OCN expression, as well as the induction of mineralization. Thus, full expression of either OPN or BSP is necessary for the anabolic effect of PTH at least in the ectopic calvaria injection model. This suggests that OPN may compensate for the lack of BSP in the response to this hormonal challenge, and provides evidence of functional overlap between these cognate proteins. © 2014 Wiley Periodicals, Inc., A Wiley Company.
Oxidation of PTH: in vivo feature or effect of preanalytical conditions?

NARCIS (Netherlands)

Ursem, Stan R.; Vervloet, Marc G.; Hillebrand, Jacquelien J. G.; de Jongh, Renate T.; Heijboer, Annemieke C.

2018-01-01

Background: Posttranslational oxidation of parathyroid hormone (PTH) modifies its biological activity. Measurement of non-oxidized PTH (n-oxPTH) could be an improvement in assessing PTH status, as intact PTH may rather reflect oxidative stress. However, it is debated whether oxidation of PTH occurs
Mobilization of endogenous bone marrow derived endothelial progenitor cells and therapeutic potential of parathyroid hormone after ischemic stroke in mice.

Directory of Open Access Journals (Sweden)

Li-Li Wang

Full Text Available Stroke is a major neurovascular disorder threatening human life and health. Very limited clinical treatments are currently available for stroke patients. Stem cell transplantation has shown promising potential as a regenerative treatment after ischemic stroke. The present investigation explores a new concept of mobilizing endogenous stem cells/progenitor cells from the bone marrow using a parathyroid hormone (PTH therapy after ischemic stroke in adult mice. PTH 1-34 (80 µg/kg, i.p. was administered 1 hour after focal ischemia and then daily for 6 consecutive days. After 6 days of PTH treatment, there was a significant increase in bone marrow derived CD-34/Fetal liver kinase-1 (Flk-1 positive endothelial progenitor cells (EPCs in the peripheral blood. PTH treatment significantly increased the expression of trophic/regenerative factors including VEGF, SDF-1, BDNF and Tie-1 in the brain peri-infarct region. Angiogenesis, assessed by co-labeled Glut-1 and BrdU vessels, was significantly increased in PTH-treated ischemic brain compared to vehicle controls. PTH treatment also promoted neuroblast migration from the subventricular zone (SVZ and increased the number of newly formed neurons in the peri-infarct cortex. PTH-treated mice showed significantly better sensorimotor functional recovery compared to stroke controls. Our data suggests that PTH therapy improves endogenous repair mechanisms after ischemic stroke with functional benefits. Mobilizing endogenous bone marrow-derived stem cells/progenitor cells using PTH and other mobilizers appears an effective and feasible regenerative treatment after ischemic stroke.
PTH Assays: Understanding What We Have and Forecasting What We Will Have

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Jose Gilberto H. Vieira

2012-01-01

Full Text Available Parathyroid hormone (PTH assays have evolved continuously for the last 50 years. Since the first radioimmunoassay was described in 1963, several assays based on immunological identification have been published (first generation assays. The routine assays used nowadays are immunometric “sandwich-type”. They are based on two different monoclonal antibodies, one amino-terminal and the other carboxyl terminal specific. These second generation assays are widely available and adapted to most of the automation platforms. The specificity of the amino terminal antibody defines if the immunometric assay measures only the bioactive PTH circulating form (including the first amino terminal amino acids or the “intact” PTH, which includes, besides bioactive PTH, other “long” carboxyl-terminal forms, for example, 7–84-PTH. Assays for “intact” PTH are the most commonly available and the potential advantage of the bioactive PTH assays is still debatable. Next generation of assays will be based on different principles, mainly mass spectrometry in samples submitted to a prior purification and fragmentation steps. These assays will provide information about the whole spectra of PTH peptides in circulation, with a significant increase of the information regarding this biologically important peptide hormone.
Thiazide increases serum calcium in anuric patients: the role of parathyroid hormone.

Science.gov (United States)

Vasco, Raquel F V; Reis, Eduardo T; Moyses, Rosa M A; Elias, Rosilene M

2017-12-01

We evaluated the effect of hydrochlorothiazide in a sample of anuric patients on hemodialysis and found an increase in serum calcium, which occurred only in those with parathyroid hormone >300 pg/ml. This finding highlights the extra-renal effect of this diuretic and a possible role of parathyroid hormone in the mechanism. Thiazide diuretics are commonly used in patients with chronic kidney disease to treat hypertension. Their effects on calcium and bone metabolism are not well established, once calciuria may not fully explain levels of calcium and parathyroid hormone (PTH) in this population. A previous study has suggested that thiazides require the presence of PTH as a permissive condition for its renal action. In anuric patients, however, the role of PTH, if any, in the thiazide effect is unknown. To assess thiazide extra renal effect on serum calcium and whether such an effect is reliant on PTH, hydrochlorothiazide (HCTZ) 100 mg was given orally once a day to a sample of 19 anuric patients on hemodialysis for 2 weeks. Laboratories' analyses were obtained in three phases: baseline, after diuretic use, and after a 2-week washout phase. We demonstrated that serum calcium (Ca) increased in ten patients (52.6%) after HCTZ use, returning to previous levels after the washout period. Out of the 19 patients, ten presented PTH ≥ 300 pg/ml, and Ca has increased in eight of them, whereas in the other nine patients with PTH < 300 pg/ml, serum Ca has increased only in two individuals (RR risk of increase Ca 3.9; p = 0.012). HCTZ was capable of increasing serum Ca in a sample of anuric patients on hemodialysis and seems this effect is highly dependent on PTH levels. Caution is required while interpreting this result, as the small sample size might implicate in a finding caused by chance.
New aspects of radioimmunochemical measurement of human parathyroid hormone using the labelled antibody technique

International Nuclear Information System (INIS)

Hesch, R.D.; McIntosh, C.H.S.; Woodhead, J.S.; Welsh National School of Medicine, Cardiff

1975-01-01

Two forms of heterogeneity of parathyroid hormone (PTH) have given rise to conflicting results: one due to the heterogeneity of the secreted species from the gland and their peripheral metabolism and the other representing the immunochemical heterogeneity of the available antibodies. We have developed sequence specific assays using the technique of labelled antibodies. Therefore, results of assays measuring the C-terminal part and the (1-34)-N-terminal part of the molecule could be compared to those of an assay for hormone bearing both N- and C-terminal antigenic determinants. This assay is supposed to detect predominantly (1-84)-intact hormone. The immunoradiometric assay of (1-34)-PTH has a sensitivity of 0.04 ng/ml. This technique avoids the critical iodination of the hormone fragment containing no tyrosine. There is the expected overlap between normal subjects and patients with primary and secondary hyperparathyroidism. The most important finding are results from patients undergoing neck catheterization. We demonstrated nonuniform secretion of different species of PTH by parathyroid adenomata and normal glands. This supports the hypothesis of cleavage of the (1-84)-molecule in the gland. (orig.) [de
Response of induced bone defects in horses to collagen matrix containing the human parathyroid hormone gene.

Science.gov (United States)

Backstrom, Kristin C; Bertone, Alicia L; Wisner, Erik R; Weisbrode, Stephen E

2004-09-01

To determine whether human parathyroid hormone (hPTH) gene in collagen matrix could safely promote bone formation in diaphyseal or subchondral bones of horses. 8 clinically normal adult horses. Amount, rate, and quality of bone healing for 13 weeks were determined by use of radiography, quantitative computed tomography, and histomorphometric analysis. Diaphyseal cortex and subchondral bone defects of metacarpi were filled with hPTH(1-34) gene-activated matrix (GAM) or remained untreated. Joints were assessed on the basis of circumference, synovial fluid analysis, pain on flexion, lameness, and gross and histologic examination. Bone volume index was greater for cortical defects treated with hPTH(1-34) GAM, compared with untreated defects. Bone production in cortical defects treated with hPTH(1-34) GAM positively correlated with native bone formation in untreated defects. In contrast, less bone was detected in hPTH(1-34) GAM-treated subchondral bone defects, compared with untreated defects, and histology confirmed poorer healing and residual collagen sponge. Use of hPTH(1-34) GAM induced greater total bone, specifically periosteal bone, after 13 weeks of healing in cortical defects of horses. The hPTH(1-34) GAM impeded healing of subchondral bone but was biocompatible with joint tissues. Promotion of periosteal bone formation may be beneficial for healing of cortical fractures in horses, but the delay in onset of bone formation may negate benefits. The hPTH(1-34) GAM used in this study should not be placed in articular subchondral bone defects, but contact with articular surfaces is unlikely to cause short-term adverse effects.
Synthesis, characterization, and cytocompatibility of potential cockle shell aragonite nanocrystals for osteoporosis therapy and hormonal delivery

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Jaji AZ

2017-01-01

Full Text Available Alhaji Zubair Jaji,1,2 Md Zuki Bin Abu Bakar,1,3 Rozi Mahmud,4 Mohamad Yusof Loqman,5 Mohamad Noor Mohamad Hezmee,1 Tijani Isa,3 Fu Wenliang,3 Nahidah Ibrahim Hammadi1 1Department of Veterinary Pre-Clinical Science, Universiti Putra Malaysia, Serdang, Selangor, Malaysia; 2Department of Veterinary Anatomy, Faculty of Veterinary Medicine, University of Ilorin, Ilorin, Kwara, Nigeria; 3Molecular Biomedicine Laboratory, Institute of Bioscience, Universiti Putra Malaysia, Serdang, Selangor, Malaysia; 4Department of Imaging, Faculty of Medicine and Health Science, Universiti Putra Malaysia, Serdang, Selangor, Malaysia; 5Department of Companion Animal Medicine and Surgery, Universiti Putra Malaysia, Serdang, Selangor, Malaysia Abstract: Calcium carbonate is a porous inorganic nanomaterial with huge potential in biomedical applications and controlled drug delivery. This study aimed at evaluating the physicochemical properties and in vitro efficacy and safety of cockle shell aragonite calcium carbonate nanocrystals (ANC as a potential therapeutic and hormonal delivery vehicle for osteoporosis management. Free and human recombinant parathyroid hormone 1-34 (PTH 1-34-loaded cockle shell aragonite calcium carbonate nanocrystals (PTH-ANC were synthesized and evaluated using standard procedures. Transmission electron microscopy and field emission scanning electron microscopy results demonstrated highly homogenized spherical-shaped aragonite nanocrystals of 30±5 nm diameter. PTH-ANC had a zeta potential of −27.6 ± 8.9 mV. The encapsulation efficiency of the formulation was found to be directly proportional to the concentrations of the drug fed. The X-ray diffraction patterns revealed strong crystallizations with no positional change of peaks before and after PTH-ANC synthesis. Fourier transform infrared spectroscopy demonstrated no detectable interactions between micron-sized aragonite and surfactant at molecular level. PTH-ANC formulation was stabilized
Functional characterization and evolution of PTH/PTHrP receptors: insights from the chicken

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Pinheiro Pedro LC

2012-07-01

Full Text Available Abstract Background The parathyroid hormone (PTH-family consists of a group of structurally related factors that regulate calcium and bone homeostasis and are also involved in development of organs such as the heart, mammary gland and immune system. They interact with specific members of family 2 B1 G-protein coupled receptors (GPCRs, which have been characterised in teleosts and mammals. Two PTH/PTHrP receptors, PTH1R and PTH2R exist in mammals and in teleost fish a further receptor PTH3R has also been identified. Recently in chicken, PTH-family members involved in calcium transport were characterized and specific PTHRs are suggested to exist although they have not yet been isolated or functionally characterized. The aim of this study is to further explore the evolution and function of the vertebrate PTH/PTHrP system through the isolation, phylogenetic analysis and functional characterization of the chicken receptors. Results Two PTHRs were isolated in chicken and sequence comparison and phylogenetic analysis indicate that the chicken receptors correspond to PTH1R and PTH3R, which emerged prior to the teleost/tetrapod divergence since they are present in cartilaginous fish. The vertebrate PTH2R receptor and its ligand TIP39 have been lost from bird genomes. Chicken PTH1R and PTH3R have a divergent and widespread tissue expression and are also evident in very early embryonic stages of development. Receptor stimulation studies using HEK293 cells stably expressing the chicken PTH1R and PTH3R and monitoring cAMP production revealed they are activated by chicken 1–34 N-terminal PTH-family peptides in a dose dependent manner. PTH-L and PTHrP were the most effective peptides in activating PTH1R (EC50 = 7.7 nM and EC50 = 22.7 nM, respectively. In contrast, PTH-L (100 nM produced a small cAMP accumulation on activation of PTH3R but PTHrP and PTH (EC50 = 2.5 nM and EC50 = 22.1 nM, respectively readily activated the receptor. PTHr
Parathyroid hormone in sodium-dependent hypertension

International Nuclear Information System (INIS)

Doris, P.A.; Harvey, S.; Pang, P.K.T.

1987-01-01

Plasma parathyroid hormone (pPTH) levels have been assessed in three separate radioimmunoassay systems in samples from Wistar-Kyoto rats. The animals were subjected to one of three dietary regimens throughout the study period: Group 1 animals consumed normal rat chow and drank tap water; Group 2 animals consumed normal rat chow and tap water was replaced with 0.05% saline solution; Group 3 animals consumed normal rat chow to which 2.5% CaCO 3 had been added and also drank 0.5% saline solution. Three assay systems were used to measure pPTH levels from trunk blood samples obtained by guillotine decapitation. One assay used an antiserum directed toward the vasoactive N terminal fragment 1-34 and produced pPTH measurements of 0.74 +/- 0.05 ng/ml in Gp 1 animals, 1.04 +/- 0.07 ng/ml in Gp 2 animals and 1.12 +/- 0.08 ng/ml in Gp 3 animals. This pattern was consistent with that obtained by another antiserum which had been raised against the intact 1-84 PTH molecule and produced values of 0.25 +/- 0.03 ng/ml in Gp 1 animals, 0.55 +/- 0.07 ng/ml in Gp 2 animals and 0.74 +/- 0.04 ng/ml in Gp 3 animals. Antiserum raised against the C-terminal did not show any difference in pPTH across groups. The authors conclude that saline consumption may increase some portions of circulating PTH. 26 references, 2 tables

Down-regulation of ABCG2, a urate exporter, by parathyroid hormone enhances urate accumulation in secondary hyperparathyroidism.

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Sugimoto, Ryusei; Watanabe, Hiroshi; Ikegami, Komei; Enoki, Yuki; Imafuku, Tadashi; Sakaguchi, Yoshiaki; Murata, Michiya; Nishida, Kento; Miyamura, Shigeyuki; Ishima, Yu; Tanaka, Motoko; Matsushita, Kazutaka; Komaba, Hirotaka; Fukagawa, Masafumi; Otagiri, Masaki; Maruyama, Toru

2017-03-01

Hyperuricemia occurs with increasing frequency among patients with hyperparathyroidism. However, the molecular mechanism by which the serum parathyroid hormone (PTH) affects serum urate levels remains unknown. This was studied in uremic rats with secondary hyperparathyroidism where serum urate levels were found to be increased and urate excretion in the intestine and kidney decreased, presumably due to down-regulation of the expression of the urate exporter ABCG2 in intestinal and renal epithelial membranes. These effects were prevented by administration of the calcimimetic cinacalcet, a PTH suppressor, suggesting that PTH may down-regulate ABCG2 expression. This was directly tested in intestinal Caco-2 cells where the expression of ABCG2 on the plasma membrane was down-regulated by PTH (1-34) while its mRNA level remained unchanged. Interestingly, an inactive PTH derivative (13-34) had no effect, suggesting that a posttranscriptional regulatory system acts through the PTH receptor to regulate ABCG2 plasma membrane expression. As found in an animal study, additional clinical investigations showed that treatment with cinacalcet resulted in significant reductions in serum urate levels together with decreases in PTH levels in patients with secondary hyperparathyroidism undergoing dialysis. Thus, PTH down-regulates ABCG2 expression on the plasma membrane to suppress intestinal and renal urate excretion, and the effects of PTH can be prevented by cinacalcet treatment. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.
A new human NHERF1 mutation decreases renal phosphate transporter NPT2a expression by a PTH-independent mechanism.

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Marie Courbebaisse

Full Text Available BACKGROUND: The sodium-hydrogen exchanger regulatory factor 1 (NHERF1 binds to the main renal phosphate transporter NPT2a and to the parathyroid hormone (PTH receptor. We have recently identified mutations in NHERF1 that decrease renal phosphate reabsorption by increasing PTH-induced cAMP production in the renal proximal tubule. METHODS: We compared relevant parameters of phosphate homeostasis in a patient with a previously undescribed mutation in NHERF1 and in control subjects. We expressed the mutant NHERF1 protein in Xenopus Oocytes and in cultured cells to study its effects on phosphate transport and PTH-induced cAMP production. RESULTS: We identified in a patient with inappropriate renal phosphate reabsorption a previously unidentified mutation (E68A located in the PDZ1 domain of NHERF1.We report the consequences of this mutation on NHERF1 function. E68A mutation did not modify cAMP production in the patient. PTH-induced cAMP synthesis and PKC activity were not altered by E68A mutation in renal cells in culture. In contrast to wild-type NHERF1, expression of the E68A mutant in Xenopus oocytes and in human cells failed to increase phosphate transport. Pull down experiments showed that E68A mutant did not interact with NPT2a, which robustly interacted with wild type NHERF1 and previously identified mutants. Biotinylation studies revealed that E68A mutant was unable to increase cell surface expression of NPT2a. CONCLUSIONS: Our results indicate that the PDZ1 domain is critical for NHERF1-NPT2a interaction in humans and for the control of NPT2a expression at the plasma membrane. Thus we have identified a new mechanism of renal phosphate loss and shown that different mutations in NHERF1 can alter renal phosphate reabsorption via distinct mechanisms.
Circulating PTH molecular forms: what we know and what we don't.

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D'Amour, P

2006-07-01

Circulating parathyroid hormone (PTH) molecular forms have been identified by three generations of PTH assays after gel chromatography or high-performance liquid chromatography fractionation of serum. Carboxyl-terminal (C) fragments missing the amino-terminal (N) structure of PTH(1-84) were identified first. They represent 80% of circulating PTH in normal individuals and up to 95% in renal failure patients. They are regulated by calcium (Ca) slightly differently than PTH(1-84), occurring in a relatively smaller proportion relative to the latter in hypocalcemia but in a much larger proportion in hypercalcemia. Synthetic C-PTH fragments do not bind to the PTH/PTHrP type I receptor and are not implicated in the classical biological effect of PTH(1-84). They bind to a different C-PTH receptor and exert biological actions on bone that are opposite to those of PTH(1-84). The integrity of the distal C-structure appears to be important for these biological effects, and it is uncertain if all C-PTH fragments are intact up to position 84. A second category of C-PTH fragment has a partially preserved N-structure. They are called non-(1-84) PTH or N-truncated fragments. They react in Intact (I)-PTH assays but not in PTH assays with a 1-4 epitope. They are acutely regulated by Ca(2+) concentration. They also exert similar hypocalcemic and antiresorptive effects but have 10-fold greater affinity for the C-PTH receptor compared to other C-PTH fragments. Even if they represent only 10% of all C-PTH fragments, they could be as relevant biologically. An N form of PTH other than PTH(1-84) has been identified in the circulation. It reacts very well in PTH assays with a 1-4 epitope but poorly in I-PTH assay with a 12-18 epitope. It is oversecreted in severe primary and secondary hyperparathyroidism and in parathyroid cancers. Its biological activity is still unknown. Overall, these studies suggest that PTH(1-84) and C-PTH fragments are regulated differently to exert opposite biological
Decrease in the expression of the type 1 PTH/PTHrP receptor (PTH1R on chondrocytes in animals with osteoarthritis

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Skwara Adrian

2010-04-01

Full Text Available Abstract Background To evaluate the expression of the type 1 PTH/PTHrP receptor (PTH1R on chondrocytes from hyaline cartilage over the course of osteoarthritis (OA. Methods In 12 NZW rabbits, the anterior cruciate ligament (ACL was resected to create anterior instability of the knee. In 12 control rabbits, only a sham operation, without resection of the ACL, was performed. Four animals from each group were killed at 3, 6, and 12 weeks. After opening the knee joint, OA was macroscopically graded and hyaline cartilage of the load-bearing area was evaluated histologically according to the Mankin scale and by immunostaining for PTH1R. Results There was a positive linear correlation between the time after surgery and the macroscopic and histologic OA scores. The scores in the control group were constant over the time course. Immunostaining showed significantly less expression of PTH1R in the experimental compared to the control group after 6 (P Conclusions The results show an in vivo decrease in the expression of PTH1R on chondrocytes over the time course of OA. Further studies are needed to evaluate whether new treatment approaches could evolve from this knowledge.
Role of the metabolism of parathyroid hormone

International Nuclear Information System (INIS)

Teitelbaum, A.P.

1978-01-01

The heterogeneity of parathyroid hormone (PTH) in plasma has prompted investigations of the metabolism of PTH and its relationship to hormone action. The time course of tissue distribution and metabolism of electrolytically iodinated PTH (E-PTH) previously shown to retain biological activity was compared with that of inactive PTH iodinated with Chloramine-T (CT-PTH). Labeled PTH (0.4 μg) was injected in the saphenous veins of anesthetized rats which were sacrificed at 1, 3, 5, 10, and 20 min. Tissue extracts from kidney, liver, and serum were chromatographed to separate intact PTH from its metabolites. In the kidney, the initial rate of degradation of E-PTH was greater than that of CT-PTH. The difference in initial rates of metabolism may be due, in part, to receptor-specific hydrolysis on peritubular cell membranes which selectively act on biologically active PTH molecules. PTH-responsive adenyl cyclase activity in isolated kidney cortex plasma membranes was measured and PTH metabolism was monitored simultaneously. When degradation was completely blocked by histone f 3 (1 mg/ml), adenyl cyclase activity was significantly increased over control. In addition, when adenyl cyclase activity was negligible, the rate of PTH degradation by the membranes was not significantly diminished. Consistent with the in vivo data was the observation that E-PTH is metabolized by these membranes at a greater rate than CT-PTH. The data demonstrate the existence of a receptor-specific metabolism at sites which are independent of PTH receptor mediated adenyl cyclase activity
Sequential treatment with basic fibroblast growth factor and PTH is more efficacious than treatment with PTH alone for increasing vertebral bone mass and strength in osteopenic ovariectomized rats

DEFF Research Database (Denmark)

Iwaniec, U.T.; Mosekilde, Li.; Mitova-Caneva, N.G.

2002-01-01

The study was designed 1) to determine whether treatment with basic fibroblast growth factor (bFGF) and PTH is more efficacious than treatment with PTH alone for increasing bone mass and strength and improving trabecular microarchitecture in osteopenic ovariectomized rats, and 2) to assess whethe...
Effects of PTH and Ca2+ on renal adenyl cyclase

International Nuclear Information System (INIS)

Nielsen, S.T.; Neuman, W.F.

1978-01-01

The effects of calcium ion on the adenylate cyclase system was studied in isolated, renal basal-lateral plasma membranes of the rat. Bovine parathyroid hormone (bPTH) and a guanyl triphosphate analogue, Gpp(NH)p were used to stimulate cyclase activity. Under conditions of maximal stimulation, calcium ions inhibited cyclic adenosine monophosphate (cAMP) formation, the formation rate falling exponentially with the calcium concentration. Fifty percent inhibition of either bPTH- or Gpp(NH)p-stimulated activity was given by approximately 50 μM Ca 2+ . Also the Hill coefficient for the inhibition was close to unity in both cases. The concentration of bPTH giving half-maximal stimulation of cAMP formation (1.8 x 10 -8 M) was unchanged by the presence of calcium. These data suggest that calcium acts at some point other than the initial hormone-receptor interaction, presumably decreasing the catalytic efficiency of the enzymic moiety of the membrane complex
Identification of six novel PTH1R mutations in families with a history of primary failure of tooth eruption.

Science.gov (United States)

Risom, Lotte; Christoffersen, Line; Daugaard-Jensen, Jette; Hove, Hanne Dahlgaard; Andersen, Henriette Skovgaard; Andresen, Brage Storstein; Kreiborg, Sven; Duno, Morten

2013-01-01

Primary Failure of tooth Eruption (PFE) is a non-syndromic disorder which can be caused by mutations in the parathyroid hormone receptor 1 gene (PTH1R). Traditionally, the disorder has been identified clinically based on post-emergent failure of eruption of permanent molars. However, patients with PTH1R mutations will not benefit from surgical and/or orthodontic treatment and it is therefore clinically important to establish whether a given failure of tooth eruption is caused by a PTH1R defect or not. We analyzed the PTH1R gene in six patients clinically diagnosed with PFE, all of which had undergone surgical and/or orthodontic interventions, and identified novel PTH1R mutations in all. Four of the six mutations were predicted to abolish correct mRNA maturation either through introduction of premature stop codons (c.947C>A and c.1082G>A), or by altering correct mRNA splicing (c.544-26_544-23del and c.989G>T). The latter was validated by transfection of minigenes. The six novel mutations expand the mutation spectrum for PFE from eight to 14 pathogenic mutations. Loss-of-function mutations in PTH1R are also associated with recessively inherited Blomstrand chondrodysplasia. We compiled all published PTH1R mutations and identified a mutational overlap between Blomstrand chondrodysplasia and PFE. The results suggest that a genetic approach to preclinical diagnosis will have important implication for surgical and orthodontic treatment of patients with failure of tooth eruption.
Identification of six novel PTH1R mutations in families with a history of primary failure of tooth eruption.

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Lotte Risom

Full Text Available Primary Failure of tooth Eruption (PFE is a non-syndromic disorder which can be caused by mutations in the parathyroid hormone receptor 1 gene (PTH1R. Traditionally, the disorder has been identified clinically based on post-emergent failure of eruption of permanent molars. However, patients with PTH1R mutations will not benefit from surgical and/or orthodontic treatment and it is therefore clinically important to establish whether a given failure of tooth eruption is caused by a PTH1R defect or not. We analyzed the PTH1R gene in six patients clinically diagnosed with PFE, all of which had undergone surgical and/or orthodontic interventions, and identified novel PTH1R mutations in all. Four of the six mutations were predicted to abolish correct mRNA maturation either through introduction of premature stop codons (c.947C>A and c.1082G>A, or by altering correct mRNA splicing (c.544-26_544-23del and c.989G>T. The latter was validated by transfection of minigenes. The six novel mutations expand the mutation spectrum for PFE from eight to 14 pathogenic mutations. Loss-of-function mutations in PTH1R are also associated with recessively inherited Blomstrand chondrodysplasia. We compiled all published PTH1R mutations and identified a mutational overlap between Blomstrand chondrodysplasia and PFE. The results suggest that a genetic approach to preclinical diagnosis will have important implication for surgical and orthodontic treatment of patients with failure of tooth eruption.
Overproduction of an amino-terminal form of PTH distinct from human PTH(1-84) in a case of severe primary hyperparathyroidism: influence of medical treatment and surgery.

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Räkel, Agnès; Brossard, Jean-Hugues; Patenaude, Jean-Victor; Albert, Caroline; Nassif, Edgard; Cantor, Tom; Rousseau, Louise; D'Amour, Pierre

2005-06-01

Rare patients with severe primary hyperparathyroidism present with large parathyroid tumours, severe hypercalcaemia, very high PTH levels and osteitis fibrosa cystica. Some of these patients display a large amount of C-PTH fragments in circulation and present with a higher C-PTH/I-PTH ratio than seen in less severe cases of primary hyperparathyroidism. We wanted to determine how PTH levels and circulating PTH high-performance liquid chromatography (HPLC) profiles analysed with PTH assays having different epitopes could be affected by medical and surgical treatment in such patients. A 55-year-old man with severe hypercalcaemia (Ca(2+): 2.01 mmol/l), very high PTH levels (CA-PTH 82.1 and T-PTH 72 pmol/l) caused by a large parathyroid tumour (7.35 g) and accompanied by significant bone involvement (alkaline phosphatase of 185 UI/l and subperiostal bone resorption of hands) was referred to us. Blood was obtained at various time points during his medical treatment, before and after surgery, to measure parameters of calcium and phosphorus metabolism, and of bone turnover. HPLC separations of circulating PTH molecular forms were performed and analysed with PTH assays having 1-4 (CA), 12-18 (T), 26-32 (E) and 65-84 (C) epitopes. Before surgery, serum Ca2+ was nearly normalized with hydratation, intravenous (IV) pamidronate and oral vitamin D administration. Despite a decrease in Ca2+ to 1.31 mmol/l, CA-PTH and T-PTH levels decreased by half in relation to a threefold increase in basal 1,25-dihydroxyvitamin D [1,25(OH)2D] level (94 to 337 pmol/l). After this initial positive response, hypercalcaemia and elevated CA- and T-PTH levels recurred even if 1,25(OH)2D levels remained elevated. The tumour was removed surgically and proved to be poorly differentiated with nuclear atypia and mitosis. After surgery, the Ca2+ level and PTH secretion normalized. The higher CA-PTH level relative to the T-PTH level observed before surgery in this patient was related to the oversecretion of
PTH Gene Polymorphism and Breast Cancer Risk in Kazakhstan

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Nurgul Sikhayeva

2014-12-01

Full Text Available Introduction. Breast cancer is the most common type of cancer among women. In Kazakhstan, breast cancer holds first place among causes of women death caused by cancer in the 45-55 year age group . Many studies have shown that the risk of acquiring breast cancer may be related to the level of calcium in the blood serum. One of the important regulators of calcium metabolism in the body is the parathyroid hormone. Single nucleotide polymorphisms in the gene encoding the parathyroid hormone (PTH are associated with breast cancer development risk, and may modify the associative interaction between the levels of calcium intake and breast cancer. Experimental studies have shown that PTH gene has a carcinogenic effect. At least three studies showed a weak positive correlation between the risk of acquiring breast cancer and primary hyperparathyroidism, a state with high levels of PTH and often high levels of calcium. The aim of this investigation was to evaluate potential association between PTH gene polymorphism and breast cancer risk among Kazakhstani women.Methods. Female breast cancer patients (n = 429 and matched control women (n = 373 were recruited into a case – control study,. Genomic DNA was extracted from peripheral venous blood of study participants using Wizard® Genomic DNA Purification Kit (Promega, USA. Detection of PTH gene polymorphism (rs1459015 was done by means of the TaqMan® SNP Genotyping Assay of real-time PCR. Statistical analysis was conducted using SPSS 19.0.Results. PTH gene alleles were in Hardy–Weinberg equilibrium (p > 0.05. Distribution was 59% CC, 35% CT, 6% TT in the group with breast cancer and 50% CC, 43% CT, 6% TT in the control group. Total difference (between the group with breast cancer and the control group in allele frequencies for PTH polymorphism was not significant (p > 0.05. No association was found between rs1459015 TT and breast cancer risk (OR = 1.039; 95%, CI 0.740 - 1.297; p = 0.893.Conclusion. We
A low plasma 1,25(OH)2 vitamin D/PTH (1-84) ratio predicts worsening of renal function in patients with chronic heart failure.

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Masson, Serge; Barlera, Simona; Colotta, Francesco; Magnoli, Michela; Bonelli, Fabrizio; Moro, Milena; Marchioli, Roberto; Tavazzi, Luigi; Tognoni, Gianni; Latini, Roberto

2016-12-01

Dysregulation of the vitamin D system promotes renal dysfunction and has direct detrimental effects on the heart. Progressive deterioration of renal function is common in patients with chronic heart failure (HF) and is invariably associated with unfavorable outcomes which can be improved by early identification and timely interventions. We examined the relation between two plasma markers of vitamin D metabolism and worsening of renal function (WRF) in a large cohort of patients with chronic HF. Plasma levels of 1,25-dihydroxyvitamin D (1,25(OH) 2 D) and parathyroid hormone PTH (1-84) were measured in 1237 patients with clinical evidence of chronic and stable HF enrolled in the multicentre GISSI-HF trial and followed for 3.9years. We examined the relation of 1,25(OH) 2 D, PTH(1-84), and their ratio with WRF, defined as first increase in serum creatinine concentration ≥0.3mg/dL and ≥25% at two consecutive measurements at any time during the study. Lower 1,25(OH) 2 D/PTH(1-84) ratio was associated with a higher baseline serum concentration of creatinine, winter season, female sex and older age; 335 patients (29.6%) experienced an episode of WRF. After adjustment, a lower 1,25(OH) 2 D/PTH(1-84) ratio remained significantly associated with a higher risk of WRF (HR=0.75 [0.62-0.90], p=0.002) and correctly reclassified events. This ratio also independently predicted mortality and admission to hospital for cardiovascular reasons. The plasma 1,25(OH) 2 D/PTH(1-84) ratio is a promising indicator of future risk of deterioration of renal function in patients with chronic HF and mild renal impairment, that may serve to optimize therapies and improve outcomes. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
PTH(1-84) Replacement Therapy in Hypoparathyroidism (HypoPT): a Randomized Controlled Trial on Pharmacokinetics and Dynamic effects Following 24 Weeks of treatment

DEFF Research Database (Denmark)

Sikjær, Tanja Tvistholm; Amstrup, Anne Kristine; Rolighed, Lars

In HypoPT, lack of PTH necessitates treatment with calcium and vitamin D analogues in order to avoid hypocalcemia. To study if replacement with the missing hormone possesses advantages, we randomized 62 patients with HypoPT to 24-wks with a daily SC injection in the thigh of PTH(1-84) 100 μg...... or similar placebo, as add to conventional therapy. At end of study, we performed a 24h biochemical monitoring on 39 patients (22 on PTH) in order to assess effects on diurnal variations in calcium-phosphate homeostasis. Following injection, blood samples were obtained at 0.25, 0.5, 1.0, 1.5, 2, 3, 4, 5, 6...
Role of the metabolism of parathyroid hormone. [Rats

Energy Technology Data Exchange (ETDEWEB)

Teitelbaum, Anne P. [Univ. of Rochester, NY (United States)

1978-01-01

The heterogeneity of parathyroid hormone (PTH) in plasma has prompted investigations of the metabolism of PTH and its relationship to hormone action. The time course of tissue distribution and metabolism of electrolytically iodinated PTH (E-PTH) previously shown to retain biological activity was compared with that of inactive PTH iodinated with Chloramine-T (CT-PTH). Labeled PTH (0.4 μg) was injected in the saphenous veins of anesthetized rats which were sacrificed at 1, 3, 5, 10, and 20 min. Tissue extracts from kidney, liver, and serum were chromatographed to separate intact PTH from its metabolites. In the kidney, the initial rate of degradation of E-PTH was greater than that of CT-PTH. The difference in initial rates of metabolism may be due, in part, to receptor-specific hydrolysis on peritubular cell membranes which selectively act on biologically active PTH molecules. PTH-responsive adenyl cyclase activity in isolated kidney cortex plasma membranes was measured and PTH metabolism was monitored simultaneously. When degradation was completely blocked by histone f₃ (1 mg/ml), adenyl cyclase activity was significantly increased over control. In addition, when adenyl cyclase activity was negligible, the rate of PTH degradation by the membranes was not significantly diminished. Consistent with the in vivo data was the observation that E-PTH is metabolized by these membranes at a greater rate than CT-PTH. The data demonstrate the existence of a receptor-specific metabolism at sites which are independent of PTH receptor mediated adenyl cyclase activity.
Synergistic effect of parathyroid hormone and growth hormone on trabecular and cortical bone formation in hypophysectomized rats.

Science.gov (United States)

Guevarra, Maria Sarah N; Yeh, James K; Castro Magana, Mariano; Aloia, John F

2010-01-01

Growth hormone (GH) deficiency in pediatric patients results in short stature and osteopenia. We postulated that the GH and parathyroid hormone (PTH) combination would result in improvement in bone growth and bone formation. Forty hypophysectomized female rats at age 8 weeks were divided into hypophysectomy (HX), HX + PTH (62.5 microg/kg, s.c. daily), HX + GH (3.33 mg/kg, s.c. daily), and HX + PTH + GH for a 4-week study. GH increased body weight, bone growth, bone mineral content (BMC) and bone mineral density (BMD), whereas PTH increased BMC and BMD without a significant effect on bone size. GH increased both periosteal and endocortical bone formation and cortical size, while PTH increased only endocortical bone formation. GH mitigated the trabecular bone loss by increasing bone formation, while PTH increased bone mass by increasing bone formation and suppressing osteoclast number per bone area. The result of combined intervention shows an increase in trabecular, periosteal and endocortical bone formation and suppression of bone resorption resulting in a synergistic effect on increasing trabecular and cortical bone volume and BMD. The combination treatment of PTH and GH increases bone growth, bone formation, decreases bone resorption and has a synergistic effect on increasing bone density and bone mass. Copyright (c) 2010 S. Karger AG, Basel.
Parathyroid hormone depresses cytosolic pH and DNA synthesis in osteoblast-like cells

International Nuclear Information System (INIS)

Reid, I.R.; Civitelli, R.; Avioli, L.V.; Hruska, K.A.

1988-01-01

It has recently become apparent that a number of hormones and growth factors modulate cytosolic pH (pH i ) and there is some evidence that this in turn may influence cell growth. The authors have examined the effects of parathyroid hormone (PTH) on both these parameters in an osteoblast-like cell line, UMR 106. Preliminary studies, using the pH-sensitive fluorescent probe 2',7'-bis(2-carboxyethyl)-5,(6)-carboxyfluorescein indicated that these cells regulate pH i by means of an amiloride-inhibitable Na + -H + exchanger. Rat PTH-(1-34) (rPTH) caused a progressive dose-related decrease in pH i with a half-maximal effect at 10 -11 M. The diacylglycerol analogue, phorbol 12-myristate 13-acetate, increased both pH i and [ 3 H]thymidine incorporation, and amiloride reduced both indexes. However, rPTH remained a potent inhibitor of [ 3 H]thymidine incorporation in the presence of amiloride, even though it did not affect pH i in these circumstances. It is concluded that PTH decreases pH i and growth in UMR 106 cells but that these changes can be dissociated. Depression of pH i may have other important effects on bone metabolism, such as reducing cell-cell communication, and may be associated with alkalinization of the bone fluid compartment
Identification of Six Novel PTH1R Mutations in Families with a History of Primary Failure of Tooth Eruption

DEFF Research Database (Denmark)

Risom, Lotte; Christoffersen, Line Borck; Daugaard-Jensen, Jette

2013-01-01

Primary Failure of tooth Eruption (PFE) is a non-syndromic disorder which can be caused by mutations in the parathyroid hormone receptor 1 gene (PTH1R). Traditionally, the disorder has been identified clinically based on post-emergent failure of eruption of permanent molars. However, patients...... undergone surgical and/or orthodontic interventions, and identified novel PTH1R mutations in all. Four of the six mutations were predicted to abolish correct mRNA maturation either through introduction of premature stop codons (c.947C>A and c.1082G>A), or by altering correct mRNA splicing (c.544......-26_544-23del and c.989G>T). The latter was validated by transfection of minigenes. The six novel mutations expand the mutation spectrum for PFE from eight to 14 pathogenic mutations. Loss-of-function mutations in PTH1R are also associated with recessively inherited Blomstrand chondrodysplasia. We compiled all...
The study in the relationship between serum calcium and serum parathyroid hormone (PTH) by employing the various kits of PTH assay

International Nuclear Information System (INIS)

Torizumi, Kazutami; Aibata, Hirofumi; Taniguchi, Yoshiyuki; Kiji, Shigeyuki; Ueyoshi, Akitaka; Shimizu, Eiji; Okamoto, Yukiharu; Tuda, Tadaaki; Ota, Kiichiro

1987-01-01

In order to evaluate the influences of serum PTH assay in the various concentrations of serum calcium, we divided into three groups which serum calcium had below 8.0 mg/dl, 8.2 mg/dl to 9.8 mg/dl and above 10.0 mg/dl at random samples and assayed PTH in serum sample, using various kits of PTH assay obtained from commercial sources. Our results suggested that the measurement of serum PTH influenced by the concentration of serum calcium and therefore, should be taken an attention of serum calcium in each sample. (author)
[Parathyroid hormone and its analogues - molecular mechanisms of action and efficacy of osteoporosis therapy].

Science.gov (United States)

Misiorowski, Waldemar

2011-01-01

Most medical agents currently applied in osteoporosis therapy act by inhibiting bone resorption and reducing bone remodelling, i.e. they inhibit the process of bone mass loss by suppressing bone resorption processes. These drugs provide an ideal therapeutic option to prevent osteoporosis progression. They however have a rather limited usefulness when the disease has already reached its advanced stages with distinctive bone architecture lesions. The fracture risk reduction rate, achieved in the course of anti-resorptive therapy, is insufficient for patients with severe osteoporosis to stop the downward spiral of their quality of life (QoL) with a simultaneously increasing threat of premature death. The activity of the N-terminal fragment of 1-34 human parathormone (teriparatide - 1-34 rhPTH), a parathyroid hormone (PTH) analogue obtained via genetic engineering , is expressed by increased bone metabolism, while promoting new bone tissue formation by stimulating the activity of osteoblasts more than that of osteoclasts. The anabolic activity of PTH includes both its direct effect on the osteoblast cell line, and its indirect actions exerted via its regulatory effects on selected growth factors, e.g. IGF-1 or sclerostin. However, the molecular mechanisms responsible for the actual anabolic effects of PTH remain mostly still unclear. Clinical studies have demonstrated that therapeutic protocols with the application of PTH analogues provide an effective protection against all osteoporotic fracture types in post-menopausal women and in elderly men with advanced osteoporosis. Particular hopes are pinned on the possibility of applying PTH in the therapy of post-steroid osteoporosis, mainly to suppress bone formation, the most important pathological process in this regard. The relatively short therapy period with a PTH analogue (24 months) should then be replaced and continued by anti-resorptive treatment.
Parathyroid hormone and its analogues--molecular mechanisms of action and efficacy in osteoporosis therapy.

Science.gov (United States)

Misiorowski, Waldemar

2011-01-01

Most medical agents currently applied in osteoporosis therapy act by inhibiting bone resorption and reducing bone remodelling, i.e. they inhibit the process of bone mass loss by suppressing bone resorption processes. These drugs provide an ideal therapeutic option to prevent osteoporosis progression. They however have a rather limited usefulness when the disease has already reached its advanced stages with distinctive bone architecture lesions. The fracture risk reduction rate, achieved in the course of anti-resorptive therapy, is insufficient for patients with severe osteoporosis to stop the downward spiral of their quality of life (QoL) with a simultaneously increasing threat of premature death. The activity of the N-terminal fragment of 1-34 human parathormone (teriparatide - 1-34 rhPTH), a parathyroid hormone (PTH) analogue obtained via genetic engineering , is expressed by increased bone metabolism, while promoting new bone tissue formation by stimulating the activity of osteoblasts more than that of osteoclasts. The anabolic activity of PTH includes both its direct effect on the osteoblast cell line, and its indirect actions exerted via its regulatory effects on selected growth factors, e.g. IGF-1 or sclerostin. However, the molecular mechanisms responsible for the actual anabolic effects of PTH remain mostly still unclear. Clinical studies have demonstrated that therapeutic protocols with the application of PTH analogues provide an effective protection against all osteoporotic fracture types in post-menopausal women and in elderly men with advanced osteoporosis. Particular hopes are pinned on the possibility of applying PTH in the therapy of post-steroid osteoporosis, mainly to suppress bone formation, the most important pathological process in this regard. The relatively short therapy period with a PTH analogue (24 months) should then be replaced and continued by anti-resorptive treatment.

Effects of intermittent versus continuous parathyroid hormone administration on condylar chondrocyte proliferation and differentiation

International Nuclear Information System (INIS)

Liu, Qi; Wan, Qilong; Yang, Rongtao; Zhou, Haihua; Li, Zubing

2012-01-01

Highlights: ► Different PTH administration exerts different effects on condylar chondrocyte. ► Intermittent PTH administration suppresses condylar chondrocyte proliferation. ► Continuous PTH administration maintains condylar chondrocyte proliferating. ► Intermittent PTH administration enhances condylar chondrocyte differentiation. -- Abstract: Endochondral ossification is a complex process involving chondrogenesis and osteogenesis regulated by many hormones and growth factors. Parathyroid hormone (PTH), one of the key hormones regulating bone metabolism, promotes osteoblast differentiation and osteogenesis by intermittent administration, whereas continuous PTH administration inhibits bone formation. However, the effects of PTH on chondrocyte proliferation and differentiation are still unclear. In this study, intermittent PTH administration presented enhanced effects on condylar chondrocyte differentiation and bone formation, as demonstrated by increased mineral nodule formation and alkaline phosphatase (ALP) activity, up-regulated runt-related transcription factor 2 (RUNX2), ALP, collagen type X (COL10a1), collagen type I (COL1a1), osteocalcin (OCN), bone sialoprotein (BSP), bone morphogenetic protein 2 (BMP2) and osterix (OSX) mRNA and/or protein expression. On the contrary, continuous PTH administration promoted condylar chondrocyte proliferation and suppressed its differentiation, as demonstrated by up-regulated collagen type II (COL2a1) mRNA expression, reduced mineral nodule formation and down-regulated expression of the mRNAs and/or proteins mentioned above. Our data suggest that PTH can regulate condylar chondrocyte proliferation and differentiation, depending on the type of PTH administration. These results provide new insight into the effects of PTH on condylar chondrocytes and new evidence for using local PTH administration to cure mandibular asymmetry.
Nuclear medicine diagnostic experience for 25 patients with parathyroid disease accompanied elevated serum PTH level

International Nuclear Information System (INIS)

Su Li; Huang Chenggang; Niu Wenqiang; Wu Liwen

2010-01-01

Objective: To explore nuclear medicine diagnostic method for parathyroid disease accompanied elevated serum parathyroid hormone (PTH) level. Methods: The images of 25 patients with parathyroid disease were obtained by SPECT 99 Tc m -MIBI double-phase parathyroid imaging and 99 Tc m -methylene diphosphonate ( 99 Tc m -MDP) whole-body static bone imaging. All subject were measured serum PTH, calcium, phosphorus and alkaline phosphatase. Results: (1) Serum PTH level increased to varying degrees in patients with primary hyperparathyroidism (PHPT), secondary hyperparathyroidism (SHPT). (2) PHPT and SHPT showed significant change before and after surgery (t=6.24 and t=6.85, P 99 Tc m -MIBI were above 90%. (4) Whole-body bone imaging results of SHPT patients showed complex and diverse caused by high background, increased uptakes mainly. 99 Tc m -MIBI dual-phase parathyroid imaging showed hyperparathyroidism in varying degree, up to 56% or more. Conclusion: Determination of serum PTH combined SPECT for parathyroid and whole-body bone imaging showed high clinical value in diagnosis and treatment of parathyroid disease. (authors)
Effects of intermittent versus continuous parathyroid hormone administration on condylar chondrocyte proliferation and differentiation

Energy Technology Data Exchange (ETDEWEB)

Liu, Qi; Wan, Qilong; Yang, Rongtao; Zhou, Haihua [The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, 237 Luoyu Road, Wuhan 430079 (China); Li, Zubing, E-mail: lizubing0827@163.com [The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, 237 Luoyu Road, Wuhan 430079 (China); Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Wuhan University, 237 Luoyu Road, Wuhan 430079 (China)

2012-07-20

Highlights: Black-Right-Pointing-Pointer Different PTH administration exerts different effects on condylar chondrocyte. Black-Right-Pointing-Pointer Intermittent PTH administration suppresses condylar chondrocyte proliferation. Black-Right-Pointing-Pointer Continuous PTH administration maintains condylar chondrocyte proliferating. Black-Right-Pointing-Pointer Intermittent PTH administration enhances condylar chondrocyte differentiation. -- Abstract: Endochondral ossification is a complex process involving chondrogenesis and osteogenesis regulated by many hormones and growth factors. Parathyroid hormone (PTH), one of the key hormones regulating bone metabolism, promotes osteoblast differentiation and osteogenesis by intermittent administration, whereas continuous PTH administration inhibits bone formation. However, the effects of PTH on chondrocyte proliferation and differentiation are still unclear. In this study, intermittent PTH administration presented enhanced effects on condylar chondrocyte differentiation and bone formation, as demonstrated by increased mineral nodule formation and alkaline phosphatase (ALP) activity, up-regulated runt-related transcription factor 2 (RUNX2), ALP, collagen type X (COL10a1), collagen type I (COL1a1), osteocalcin (OCN), bone sialoprotein (BSP), bone morphogenetic protein 2 (BMP2) and osterix (OSX) mRNA and/or protein expression. On the contrary, continuous PTH administration promoted condylar chondrocyte proliferation and suppressed its differentiation, as demonstrated by up-regulated collagen type II (COL2a1) mRNA expression, reduced mineral nodule formation and down-regulated expression of the mRNAs and/or proteins mentioned above. Our data suggest that PTH can regulate condylar chondrocyte proliferation and differentiation, depending on the type of PTH administration. These results provide new insight into the effects of PTH on condylar chondrocytes and new evidence for using local PTH administration to cure mandibular
Pregnancy-associated plasma protein-A modulates the anabolic effects of parathyroid hormone in mouse bone.

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Clifton, Kari B; Conover, Cheryl A

2015-12-01

Intermittent parathyroid hormone (PTH) is a potent anabolic therapy for bone, and several studies have implicated local insulin-like growth factor (IGF) signaling in mediating this effect. The IGF system is complex and includes ligands and receptors, as well as IGF binding proteins (IGFBPs) and IGFBP proteases. Pregnancy-associated plasma protein-A (PAPP-A) is a metalloprotease expressed by osteoblasts in vitro that has been shown to enhance local IGF action through cleavage of inhibitory IGFBP-4. This study was set up to test two specific hypotheses: 1) Intermittent PTH treatment increases the expression of IGF-I, IGFBP-4 and PAPP-A in bone in vivo, thereby increasing local IGF activity. 2) In the absence of PAPP-A, local IGF activity and the anabolic effects of PTH on bone are reduced. Wild-type (WT) and PAPP-A knock-out (KO) mice were treated with 80 μg/kg human PTH 1-34 or vehicle by subcutaneous injection five days per week for six weeks. IGF-I, IGFBP-4 and PAPP-A mRNA expression in bone were significantly increased in response to PTH treatment. PTH treatment of WT mice, but not PAPP-A KO mice, significantly increased expression of an IGF-responsive gene. Bone mineral density (BMD), as measured by DEXA, was significantly decreased in femurs of PAPP-A KO compared to WT mice with PTH treatment. Volumetric BMD, as measured by pQCT, was significantly decreased in femoral midshaft (primarily cortical bone), but not metaphysis (primarily trabecular bone), of PAPP-A KO compared to WT mice with PTH treatment. These data suggest that stimulation of PAPP-A expression by intermittent PTH treatment contributes to PTH bone anabolism in mice. Copyright © 2015 Elsevier Inc. All rights reserved.
PTH prevents the adverse effects of focal radiation on bone architecture in young rats.

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Chandra, Abhishek; Lan, Shenghui; Zhu, Ji; Lin, Tiao; Zhang, Xianrong; Siclari, Valerie A; Altman, Allison R; Cengel, Keith A; Liu, X Sherry; Qin, Ling

2013-08-01

Radiation therapy is a common treatment regimen for cancer patients. However, its adverse effects on the neighboring bone could lead to fractures with a great impact on quality of life. The underlying mechanism is still elusive and there is no preventive or curative solution for this bone loss. Parathyroid hormone (PTH) is a current therapy for osteoporosis that has potent anabolic effects on bone. In this study, we found that focal radiation from frequent scans of the right tibiae in 1-month-old rats by micro-computed tomography severely decreased trabecular bone mass and deteriorated bone structure. Interestingly, PTH daily injections remarkably improved trabecular bone in the radiated tibiae with increases in trabecular number, thickness, connectivity, structure model index and stiffness, and a decrease in trabecular separation. Histomorphometric analysis revealed that radiation mainly decreased the number of osteoblasts and impaired their mineralization activity but had little effects on osteoclasts. PTH reversed these adverse effects and greatly increased bone formation to a similar level in both radiated and non-radiated bones. Furthermore, PTH protects bone marrow mesenchymal stem cells from radiation-induced damage, including a decrease in number and an increase in adipogenic differentiation. While radiation generated the same amount of free radicals in the bone marrow of vehicle-treated and PTH-treated animals, the percentage of apoptotic bone marrow cells was significantly attenuated in the PTH group. Taken together, our data demonstrate a radioprotective effect of PTH on bone structure and bone marrow and shed new light on a possible clinical application of anabolic treatment in radiotherapy. Copyright © 2013 Elsevier Inc. All rights reserved.
AN OPEN-LABEL EXTENSION STUDY OF PARATHYROID HORMONE RHPTH(1-84) IN ADULTS WITH HYPOPARATHYROIDISM.

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Lakatos, Peter; Bajnok, Laszlo; Lagast, Hjalmar; Valkusz, Zsuzsanna

2016-05-01

Hypoparathyroidism is characterized by inadequate parathyroid hormone (PTH), resulting in hypocalcemia, hyperphosphatemia, and bone abnormalities. Adults with hypoparathyroidism treated with recombinant human PTH, rhPTH(1-84), in the 24-week, phase III REPLACE study maintained serum calcium despite reductions in oral calcium and active vitamin D. This study assessed the long-term efficacy and safety of rhPTH(1-84) for hypoparathyroidism. This was a 24-week, open-label, flexible-dose extension study of REPLACE (REPEAT) conducted in 3 outpatient centers in Hungary. Patients who previously completed or enrolled in REPLACE received 50 μg/day rhPTH(1-84), escalated to 75 and then to 100 μg/day, if needed, to reduce active vitamin D and oral calcium. The primary endpoint was ≥50% reduction in oral calcium (or ≤500 mg/day) and active vitamin D (or calcitriol ≤0.25 μg/day or alfacalcidol ≤0.50 μg/day) with normocalcemia. Twenty-four patients (n = 16 previously treated with rhPTH[1-84]; n = 8 rhPTH[1-84]-naïve) were enrolled and completed the study. At Week 24, 75% of patients (95% confidence interval [CI], 53.3-90.2%) achieved the study endpoint; 58% eliminated oral calcium and active vitamin D. Urinary calcium, serum phosphate, and calcium × phosphate (Ca × P) product decreased by Week 24. Mean serum bone turnover markers increased with rhPTH(1-84). Treatment-emergent adverse events (TEAEs) were reported by 92% of patients. No serious adverse events (AEs) occurred. This study used a simplified treatment algorithm intended to better mimic typical clinical practice and demonstrated the extended efficacy and safety of rhPTH(1-84) in patients with hypoparathyroidism and confirmed the REPLACE findings. Sustained rhPTH(1-84) efficacy up to 48 weeks was observed despite treatment interruption between studies.
Expanding the net: The re-evaluation of the multidimensional nomogram calculating the upper limit of normal PTH (maxPTH) in the setting of secondary hyperparathyroidism and the development of the MultIdimensional Predictive hyperparaTHyroid model (Mi-PTH).

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Rajhbeharrysingh, Uma; El Youssef, Joseph; Leon, Enrique; Lasarev, Michael R; Klein, Robert; Vanek, Chaim; Mattar, Samer; Berber, Eren; Siperstein, Allan; Shindo, Maisie; Milas, Mira

2016-01-01

The multidimensional nomogram calculating the upper limit of normal PTH (maxPTH) model identifies a personalized upper limit of normal parathyroid hormone (PTH) and successfully predicts classical primary hyperparathyroidism (PHP). We aimed to assess whether maxPTH can distinguish normocalcemic PHP (NCPHP) from secondary hyperparathyroidism (SHP), including subjects who underwent bariatric surgery (BrS). A total of 172 subjects with 359 complete datasets of serum calcium (Ca), 25-OH vitamin D, and intact PTH from Oregon were analyzed: 123 subjects (212 datasets) with PHP and 47 (143) with SHP, including 28 (100) with previous BrS. An improved prediction model, MultIdimensional evaluation for Primary hyperparaTHyroidism (Mi-PTH), was created with the same variables as maxPTH by the use of a combined cohort (995 subjects) including participants from previous studies. In the Oregon cohort, maxPTH's sensitivity was 100% for classical PHP and 89% for NCPHP, but only 50% for normohormonal PHP (NHPHP) and 40% specific for SHP. In comparison, although sensitivity for NCPHP was similar (89%), Mi-PTH vastly improved SHP specificity (85%). In the combined cohort, Mi-PTH had better sensitivity of 98.5% (vs 95%) and specificity 97% (vs 85%). MaxPTH was sensitive in detecting PHP; however, there was low specificity for SHP, especially in patients who underwent BrS. The creation of Mi-PTH provided improved performance measures but requires further prospective evaluation. Copyright © 2016 Elsevier Inc. All rights reserved.
Low dose PTH improves metaphyseal bone healing more when muscles are paralyzed.

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Sandberg, Olof; Macias, Brandon R; Aspenberg, Per

2014-06-01

Stimulation of bone formation by PTH is related to mechanosensitivity. The response to PTH treatment in intact bone could therefore be blunted by unloading. We studied the effects of mechanical loading on the response to PTH treatment in bone healing. Most fractures occur in the metaphyses, therefor we used a model for metaphyseal bone injury. One hind leg of 20 male SD rats was unloaded via intramuscular botulinum toxin injections. Two weeks later, the proximal unloaded tibia had lost 78% of its trabecular contents. At this time-point, the rats received bilateral proximal tibiae screw implants. Ten of the 20 rats were given daily injections of 5 μg/kg PTH (1-34). After two weeks of healing, screw fixation was measured by pull-out, and microCT of the distal femur cancellous compartment was performed. Pull-out force provided an estimate for cancellous bone formation after trauma. PTH more than doubled the pull-out force in the unloaded limbs (from 14 to 30 N), but increased it by less than half in the loaded ones (from 30 to 44 N). In relative terms, PTH had a stronger effect on pull-out force in unloaded bone than in loaded bone (p=0.03). The results suggest that PTH treatment for stimulation of bone healing does not require simultaneous mechanical stimulation. Copyright © 2014 Elsevier Inc. All rights reserved.
Treatment of postmenopausal women with osteoporosis with PTH(1-84) for 36 months: treatment extension study

NARCIS (Netherlands)

Zanchetta, J.R.; Bogado, C.E.; Cisari, C.; Aslanidis, S.; Greisen, H.; Fox, J.; Lems, W.F.

2010-01-01

Objective: To determine the safety and efficacy of full-length parathyroid hormone, PTH(184), treatment for up to 36 months by evaluating bone mineral density (BMD) changes, bone histomorphometric indices, and clinical fracture incidence in postmenopausal women with osteoporosis. Background: The TOP
Levels of parathyroid hormone and calcitonin in serum among atomic bomb survivors

International Nuclear Information System (INIS)

Fujiwara, Saeko; Yokoyama, Naokata; Sasaki, Hideo; Kodama, Kazunori; Sposto, R.; Shimaoka, Katsutaro; Shiraki, Mastaka

1994-01-01

To examines the potential causes of increased levels of calcium in serum with increasing dose of atomic bomb radiation, which was obtained from the previous preliminary analysis, levels of parathyroid hormone (PTH) and calcitonin in serum were examined among 1459 subjects in Hiroshima and Nagasaki. A significant effect of radiation on levels of calcium, PTH and calcitonin in serum was found, even after patients with hyperparathyroidism were excluded. The level of calcium in serum increased with radiation dose; this can be explained partly by the increase in the level of PTH with radiation dose. However, the dose effect on calcium remained even after adjustment for PTH, calcitonin and confounding factors such as renal function, serum albumin level and medication. Parathyroid hormone increased initially by 6.8% per gray, but the dose response leveled off after about 1 Gy. The level of calcitonin increased with radiation dose, probably in part due to feedback mechanisms stimulated by the increase in calcium. However, after adjustment for the level of calcium, the increase in the level of calcitonin with dose was still found. Although the etiological mechanisms of the effect of radiation on serum levels of calcium, PTH and calcitonin are unclear, radiation exposure may affect secretion of PTH and calcitonin and regulation of calcium a long time after atomic bomb exposure. 21 refs., 3 figs., 6 tabs
Deletion of PTH rescues skeletal abnormalities and high osteopontin levels in Klotho-/- mice.

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Quan Yuan

Full Text Available Maintenance of normal mineral ion homeostasis is crucial for many biological activities, including proper mineralization of the skeleton. Parathyroid hormone (PTH, Klotho, and FGF23 have been shown to act as key regulators of serum calcium and phosphate homeostasis through a complex feedback mechanism. The phenotypes of Fgf23(-/- and Klotho(-/- (Kl(-/- mice are very similar and include hypercalcemia, hyperphosphatemia, hypervitaminosis D, suppressed PTH levels, and severe osteomalacia/osteoidosis. We recently reported that complete ablation of PTH from Fgf23(-/- mice ameliorated the phenotype in Fgf23(-/-/PTH(-/- mice by suppressing serum vitamin D and calcium levels. The severe osteomalacia in Fgf23(-/- mice, however, persisted, suggesting that a different mechanism is responsible for this mineralization defect. In the current study, we demonstrate that deletion of PTH from Kl(-/- (Kl(-/-/PTH(-/- or DKO mice corrects the abnormal skeletal phenotype. Bone turnover markers are restored to wild-type levels; and, more importantly, the skeletal mineralization defect is completely rescued in Kl(-/-/PTH(-/- mice. Interestingly, the correction of the osteomalacia is accompanied by a reduction in the high levels of osteopontin (Opn in bone and serum. Such a reduction in Opn levels could not be observed in Fgf23(-/-/PTH(-/- mice, and these mice showed sustained osteomalacia. This significant in vivo finding is corroborated by in vitro studies using calvarial osteoblast cultures that show normalized Opn expression and rescued mineralization in Kl(-/-/PTH(-/- mice. Moreover, continuous PTH infusion of Kl(-/- mice significantly increased Opn levels and osteoid volume, and decreased trabecular bone volume. In summary, our results demonstrate for the first time that PTH directly impacts the mineralization disorders and skeletal deformities of Kl(-/-, but not of Fgf23(-/- mice, possibly by regulating Opn expression. These are significant new perceptions into
Calcitonin impairs the anabolic effect of PTH in young rats and stimulates expression of sclerostin by osteocytes.

Science.gov (United States)

Gooi, J H; Pompolo, S; Karsdal, M A; Kulkarni, N H; Kalajzic, I; McAhren, S H M; Han, B; Onyia, J E; Ho, P W M; Gillespie, M T; Walsh, N C; Chia, L Y; Quinn, J M W; Martin, T J; Sims, N A

2010-06-01

The therapeutic goal of increasing bone mass by co-treatment of parathyroid hormone (PTH) and an osteoclast inhibitor has been complicated by the undefined contribution of osteoclasts to the anabolic activity of PTH. To determine whether active osteoclasts are required at the time of PTH administration, we administered a low dose of the transient osteoclast inhibitor salmon calcitonin (sCT) to young rats receiving an anabolic PTH regimen. Co-administration of sCT significantly blunted the anabolic effect of PTH as measured by peripheral quantitative computer tomography (pQCT) and histomorphometry in the femur and tibia, respectively. To determine gene targets of sCT, we carried out quantitative real time PCR and microarray analysis of metaphyseal samples 1.5, 4 and 6.5h after administration of a single injection of PTH, sCT or PTH+sCT. Known targets of PTH action, IL-6, ephrinB2 and RANKL, were not modified by co-administration with sCT. Surprisingly, at all time points, we noted a significant upregulation of sclerostin mRNA by sCT treatment, as well as down-regulation of two other osteocyte gene products, MEPE and DMP1. Immunohistochemistry confirmed that sCT administration increased the percentage of osteocytes expressing sclerostin, suggesting a mechanism by which sCT reduced the anabolic effect of PTH. Neither mRNA for CT receptor (Calcr) nor labeled CT binding could be detected in sclerostin-enriched cells differentiated from primary calvarial osteoblasts. In contrast, osteocytes freshly isolated from calvariae expressed a high level of Calcr mRNA. Furthermore immunohistochemistry revealed co-localization of CT receptor (CTR) and sclerostin in some osteocytes in calvarial sections. Taken together these data indicate that co-treatment with sCT can blunt the anabolic effect of PTH and this may involve direct stimulation of sclerostin production by osteocytes. These data directly implicate calcitonin as a negative regulator of bone formation through a previously
Blood-pressure-independent wall thickening of intramyocardial arterioles in experimental uraemia: evidence for a permissive action of PTH.

Science.gov (United States)

Amann, K; Törnig, J; Flechtenmacher, C; Nabokov, A; Mall, G; Ritz, E

1995-11-01

Abnormalities in cardiovascular structures, e.g. LV hypertrophy and thickening of vessels (arteries, arterioles, veins) are hallmarks of renal failure. They are in part independent of elevated blood pressure. Parathyroid hormone (PTH) has been shown to affect cardiac function and has also been identified as a permissive factor in the genesis of cardiac fibrosis. The present study in rats with experimental renal failure was designed to examine whether PTH was permissive for wall thickening of intramyocardial arterioles as well. Male SD rats were sham operated or subtotally nephrectomized and maintained for 2 weeks. Subgroups of subtotally nephrectomized (SNX) rats were parathyroidectomized (PTX). Saline or rat 1, 34 PTH was administered by osmotic minipump. Eucalcaemia was maintained in PTX animals by a high-calcium diet (3%). Serum calcium was not statistically different between the groups. After perfusion fixation, intramyocardial arterioles were assessed using stereological techniques (wall thickness; wall/lumen ratio; minimal lumen diameter; length density). In random samples of the left ventricle, wall thickness of arterioles was 2.2 +/- 0.25 microns in sham-op controls and 2.76 +/- 0.41 in SNX (n = at least 8 animals per group). SNX-PTX animals+solvent did not differ significantly from sham-op controls (2.08 +/- 0.42 microns), while SNX-PTX animals+PTH had values not significantly different from SNX (2.59 +/- 0.54 microns). Differences in wall thickness were not paralleled by differences in systolic blood pressure (sham-op 110 +/- 13.3 mmHg; SNX 138 +/- 8.4 mmHg, SNX-PTX+solvent 142 +/- 5.2 mmHg; SNX-PTX+PTH 148 +/- 5.7 mmHg). PTH treated animals showed signs of marked vascular smooth-muscle cell and endothelial-cell activation. The data suggest that wall thickening of intramyocardial arterioles in short-term experimental uraemia is dependent upon the presence of PTH (permissive effect).
99mTc-HMDP Bone Uptake Quantification and Plasma Osteocalcin, PTH Levels in Hemodialysis Patients

International Nuclear Information System (INIS)

Kim, Euy Neyng; Sohn, Hyung Sun; Bang, Chan Young; Chung, Soo Kyo; Kim, Choon Yul; Shinn, Kyung Sub; Park, Chul Whee; Chang, Yoon Sik

1996-01-01

In this preliminary study, plasma osteocalcin, PTH level and Tc-99m-HMDP (hydro-xymetylene diphosphonate) bone uptake(BU) were measured in 14 patients with chronic end-stage renal failure who were on maintenance hemodialysis. The aim of this study was to determine the difference of bone uptake between renal failure patients and normal volunteers, and to determine the correlation between bone uptake and osteocalcin a sensitive and specific marker of osteoblastic activity and PTH-a important hormone of bone metabolism. There was a statistically significant increase in 180 minute uptake in the patient group when compared to the normal volunteers while there was no statistically significant difference in 20 minute uptake. Plasma osteocalcin and PTH levels were also significantly elevated compared to normal values. But the correlation between osteocalcin, PTH and 20 and 180 minute bone uptake was not significant. In conclusion, our preliminary study suggests that, in chronic renal failure patients, 180 minute Tc-99m-HMDP bone uptake is increased significantly without direct correlation with serum osteocalcin or PTH levels. It seems that further study is needed to evaluate other unknown factors that may influence the direct correlation between bone uptake and plasma osteocalcin and PTH in patients with chronic renal failure.
A PTH/PTHrP receptor antagonist blocks the hypercalcemic response to estradiol-17b

OpenAIRE

Fuentes, J.; Guerreiro, P. M.; Modesto, Teresa; Rotllant, J.; Canario, Adelino V. M.; Power, Deborah

2007-01-01

Estradiol (E2) increases circulating calcium and phosphate levels in fish, thus acting as a hypercalcemic and hyperphosphatemic factor during periods of high calcium requirements, such as during vitellogenesis. Since parathyroid hormone (PTH)-related protein (PTHrP) has been shown to be calciotropic in fish, we hypothesized that the two hormones could be mediating the same process. Sea bream (Sparus auratus) juveniles receiving a single intraperitoneal injection of piscin...
Marker of Bone Resorption in Acute Response to Exogenous or Endogenous Parathyroid Hormone

Directory of Open Access Journals (Sweden)

Vit Zikan

2008-01-01

Full Text Available Parathyroid hormone (PTH changes morphology of osteoclasts within minutes after its systemic administration. The aim of our study was to test in healthy men whether both exogenous and endogenous PTH could change acutely (minutes to hours the serum cross-linked C-telopeptide of type I collagen (beta CTX, which is released during osteoclastic resorption of bone. Twelve healthy men (age range 24–34 yr were each studied during 180 min on a control period, after a single subcutaneous injection of teriparatide, and after 30 min EDTA infusion to stimulate endogenous PTH secretion. The tests were started after overnight fast, 3 h after a standard calcium load. The EDTA infusion induced a significant decrease in serum ionized calcium (by 8.5% at 33 min and a significant increase in plasma PTH (by 305% at 33 min. Both the EDTA and teriparatide resulted in a significant increase in beta CTX (p < 0.001 with maximum increases of 64% and 80%, respectively. A mild, but significant decrease in beta CTX was observed during the control test period. In conclusion, single-dose teriparatide injection as well as a stimulation of endogenous PTH in healthy men results in an acute increase of the bone resorption marker.
Stimulation by parathyroid hormone of sup 45 Ca sup 2+ uptake in osteoblast-like cells: Possible involvement of alkaline phosphatase

Energy Technology Data Exchange (ETDEWEB)

Fukayama, S.; Tashjian, A.H. Jr. (Harvard School of Public Health, Boston, MA (USA))

1990-04-01

We have investigated the actions of human PTH (hPTH-(1-34)) on the association of 45Ca2+ with two human (SaOS-2 and MG-63) and two rat (ROS 17/2.8 and UMR-106) osteoblast-like cell types. In SaOS-2 cells, hPTH-(1-34) binds to specific membrane receptors to activate adenylate cyclase. Treatment of SaOS-2 cells with hPTH-(1-34) resulted in an increase in 45Ca2+ uptake, in a dose-dependent fashion, up to 2- to 4-fold above control values. The increase was first evident at 10 min and persisted for at least 30 min. Treatment with nimodipine, a calcium channel antagonist, was without effect on the stimulatory action of PTH. A similar enhancement of cell-associated 45Ca2+ was observed when the cells were incubated with vasoactive intestinal peptide, which acts via different receptors to activate adenylate cyclase in SaOS-2 cells. Treatment with (Bu)2cAMP also induced an increase in cell-associated 45Ca2+. Pretreatment of SaOS-2 cells with hPTH-(1-34) for 4 h, which induced homologous desensitization to a second challenge with the same peptide for stimulation of cAMP production, did not attenuate the further enhancement of cell-associated 45Ca2+ by a second treatment with hPTH-(1-34). We then examined a possible relationship between alkaline phosphatase (ALPase) and 45Ca2+ uptake. SaOS-2 cells contained high levels of alkaline phosphatase activity and continuously released the enzyme into the medium. Release was enhanced by treatment with hPTH-(1-34) for 10 min. Incubation of cells with levamisole (an inhibitor of the liver/bone/kidney type of ALPase) resulted in a rapid decrease in basal and PTH-stimulated 45Ca2+ uptake, while treatment with L-Phe-Gly-Gly was without effect. Treatment of the cells with ALPase (bovine kidney) enhanced 45Ca2+ uptake. In MG-63 cells, a stimulatory effect of hPTH-(1-34) on cell-associated 45Ca2+ was also observed; however, hPTH-(1-34) did not stimulate cAMP production in MG-63 cells.
Parathyroid Hormone Activates Phospholipase C (PLC)-Independent Protein Kinase C Signaling Pathway via Protein Kinase A (PKA)-Dependent Mechanism: A New Defined Signaling Route Would Induce Alternative Consideration to Previous Conceptions.

Science.gov (United States)

Tong, Guojun; Meng, Yue; Hao, Song; Hu, Shaoyu; He, Youhua; Yan, Wenjuan; Yang, Dehong

2017-04-20

BACKGROUND Parathyroid hormone (PTH) is an effective anti-osteoporosis agent, after binding to its receptor PTHR1, several signaling pathways, including cAMP/protein kinase A (PKA) and phospholipase C (PLC)/protein kinase C (PKC), are initiated through G proteins; with the cAMP/PKA pathway as the major pathway. Earlier studies have reported that PTHR1 might also activate PKC via a PLC-independent mechanism, but this pathway remains unclear. MATERIAL AND METHODS In HEK293 cells, cAMP accumulation was measured with ELISA and PKC was measured with fluorescence resonance energy transfer (FRET) analysis using CKAR plasmid. In MC3T3-E1 cells, real-time PCR was performed to examine gene expressions. Then assays for cell apoptosis, cell differentiation, alkaline phosphatase activity, and mineralization were performed. RESULTS The FRET analysis found that PTH(1-34), [G1,R19]PTH(1-34) (GR(1-34), and [G1,R19]PTH(1-28) (GR(1-28) were all activated by PKC. The PKC activation ability of GR(1-28) was blocked by cAMP inhibitor (Rp-cAMP) and rescued with the addition of active PKA-α and PKA-β. The PKC activation ability of GR(1-34) was partially inhibited by Rp-cAMP. In MC3T3-E1 cells, gene expressions of ALP, CITED1, NR4a2, and OSX that was regulated by GR(1-28) were significantly changed by the pan-PKC inhibitor Go6983. After pretreatment with Rp-cAMP, the gene expressions of ALP, CITED1, and OPG were differentially regulated by GR(1-28) or GR(1-34), and the difference was blunted by Go6983. PTH(1-34), GR(1-28), and GR(1-34) significantly decreased early apoptosis and augmented osteoblastic differentiation in accordance with the activities of PKA and PKC. CONCLUSIONS PLC-independent PKC activation induced by PTH could be divided into two potential mechanisms: one was PKA-dependent and associated with PTH(1-28); the other was PKA-independent and associated with PTH(29-34). We also found that PTH could activate PLC-independent PKC via PKA-dependent mechanisms.
Recombinant human parathyroid hormone related protein 1-34 and 1-84 and their roles in osteoporosis treatment.

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Hua Wang

Full Text Available Osteoporosis is a common disorder characterized by compromised bone strength that predisposes patients to increased fracture risk. Parathyroid hormone related protein (PTHrP is one of the candidates for clinical osteoporosis treatment. In this study, GST Gene Fusion System was used to express recombinant human PTHrP (hPTHrP 1-34 and 1-84. To determine whether the recombinant hPTHrP1-34 and 1-84 can enhance renal calcium reabsorption and promote bone formation, we examined effects of recombinant hPTHrP1-34 and 1-84 on osteogenic lineage commitment in a primary bone marrow cell culture system and on osteoporosis treatment. Results revealed that both of recombinant hPTHrP1-34 and 1-84 increased colony formation and osteogenic cell differentiation and mineralization in vitro; however, the effect of recombinant hPTHrP1-84 is a little stronger than that of hPTHrP1-34. Next, ovariectomy was used to construct osteoporosis animal model (OVX to test activities of these two recombinants in vivo. HPTHrP1-84 administration elevated serum calcium by up-regulating the expression of renal calcium transporters, which resulted in stimulation of osteoblastic bone formation. These factors contributed to augmented bone mass in hPTHrP1-84 treated OVX mice but did not affect bone resorption. There was no obvious bone mass alteration in hPTHrP1-34 treated OVX mice, which may be, at least partly, associated with shorter half-life of hPTHrP1-34 compared to hPTHrP1-84 in vivo. This study implies that recombinant hPTHrP1-84 is more effective than hPTHrP1-34 to enhance renal calcium reabsorption and to stimulate bone formation in vivo.
Parathyroid hormone induces the Nrna family of nuclear orphan receptors in vivo

International Nuclear Information System (INIS)

Pirih, Flavia Q.; Aghaloo, Tara L.; Bezouglaia, Olga; Nervina, Jeanne M.; Tetradis, Sotirios

2005-01-01

Parathyroid hormone (PTH) has both anabolic and catabolic effects on bone metabolism, although the molecular mechanisms mediating these effects are largely unknown. Among the transcription factors induced by Pth in osteoblasts are the nerve growth factor-inducible factor B (NR4A; NGFI-B) family of orphan nuclear receptors: Nurr1, Nur77, and NOR-1. PTH induces NR4A members through the cAMP-protein kinase A (PKA) pathway in vitro. We report here that PTH rapidly and transiently induced expression of all three NR4A genes in PTH-target tissues in vivo. In calvaria, long bones, and kidneys, NR4A induction was maximal 0.5-1 h after a single intraperitoneal (i.p.) injection of 80 μg/kg PTH. Nur77 demonstrated the highest expression, followed, in order, by Nurr1 and NOR-1. In calvaria and long bone, PTH-induced expression of each NR4A gene was detectable at 10 μg/kg i.p. with maximum induction at 40-80 μg/kg. PTH (3-34) did not induce NR4A mRNA levels in calvaria, long bone, and kidney in vivo, confirming our in vitro results that NR4A genes are induced primarily through the cAMP-PKA pathway. The magnitude of PTH-induced NR4A expression was comparable in vivo and in vitro. However, NR4A mRNA levels peaked and returned to baseline faster in vivo. Both in vivo and in vitro, PTH induced NR4A pre-mRNA levels suggesting that induction of these genes is, at least in part, through activation of mRNA synthesis. The in vivo induction of the NR4A family members by PTH suggests their involvement in, at least some, PTH-induced changes in bone metabolism

Measurement of human serum parathyroid hormone in disorders of calcium metabolism and during administration of certain gut hormones

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Coetzee, J.; Klaff, L.J.; Epstein, S.

1980-01-01

A sensitive radio-immunoassay for parathyroid hormone (PTH) using the commercially available antisera AS 211/32 and AS 211/41 has been established. The lower limit of sensitivity of the assay is 0,25 ng/ml. Seventy-nine per cent of normal subjects have PTH levels in the measurable range, with a mean of 0,49 ng/ml (SD more or less 0,26 ng/ml). Only 1 of 9 patients with proven primary hyperparathyroidism had a normal serum PTH value. The mean serum PTH value in this group was 3,0 more or less 0,26 ng/ml, which differed significantly from that in the normal group (P<0,001). The serum PTH level of 33 patients on chronic haemodialysis was uniformly raised, while in 8 patients with hypoparathyroidism PTH levels were undetectable. Patients with malignant disease presented a mixed picture, with raised, normal or undetectable PTH levels. We investigated a possible relationship between the gut hormones, gastrin, secretin and cholecystokininpancreozymin (CCK-PZ) and PTH secretion in human volunteers. No effect was found, although the investigations were conducted over relatively short time periods
Effect of parathyroid hormone on transport by toad and turtle bladder

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Sabatini, S.; Kurtzman, N.A.

1987-01-01

The authors recently demonstrated that parathyroid hormone (PTH) inhibited both vasopressin- and cyclic AMP-stimulated water transport in the toad bladder. This was associated with an increase in calcium uptake by isolated epithelial cells. They postulated that PTH exerts its action on H 2 O transport by directly stimulating calcium uptake. The current study was designed to compare the effects of PTH and the calcium ionophore, A23187, on H 2 O and Na transport and Hμ secretion in toad and turtle bladders. In toad bladder, PTH and A23187 decreased arginine vasopressin (AVP)-stimulated H 2 O flow and short-circuit current (SCC) after 60 min serosal incubation. In turtle bladder A23187 decreased SCC to 79.3 +/- 3.6% of base line (P + secretion in turtle bladders. Both PTH and A23187 increased 45 Ca uptake in toad bladder epithelial cells; only A23187 increased 45 Ca uptake in the turtle bladder. The different action of PTH in these two membranes, compared with that of the calcium ionophore, illustrates the selectivity of PTH on membrane transport. PTH increases calcium uptake and decreases transport only in a hormone-sensitive epithelium, whereas the ionophore works in virtually all living membranes. The mode of action of these two agents to increase calcium uptake is, therefore likely different
Therapy of Hypoparathyroidism by Replacement with Parathyroid Hormone

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Lars Rejnmark

2014-01-01

Full Text Available Hypoparathyroidism (HypoPT is a state of hypocalcemia due to inappropriate low levels of parathyroid hormone (PTH. HypoPT is normally treated by calcium supplements and activated vitamin D analogues. Although plasma calcium is normalized in response to conventional therapy, quality of life (QoL seems impaired and patients are at increased risk of renal complications. A number of studies have suggested subcutaneous injections with PTH as an alternative therapy. By replacement with the missing hormone, urinary calcium may be lowered and QoL may improve. PTH replacement therapy (PTH-RT possesses, nevertheless, a number of challenges. If PTH is injected only once a day, fluctuations in calcium levels may occur resulting in hypercalcemia in the hours following an injection. Twice-a-day injections seem to cause less fluctuation in plasma calcium but do stimulate bone turnover to above normal. Most recently, continuous delivery of PTH by pump has appeared as a feasible alternative to injections. Plasma calcium levels do not fluctuate, urinary calcium is lowered, and bone turnover is only stimulated modestly (into the normal range. Further studies are needed to assess the long-term effects. If beneficial, it seems likely that standard treatment of HypoPT in the future will change into replacement therapy with the missing hormone.
Sequential treatment with basic fibroblast growth factor and parathyroid hormone restores lost cancellous bone mass and strength in the proximal tibia of aged ovariectomized rats

DEFF Research Database (Denmark)

Wronski, T.J.; Ratkus, A.M.; Thomsen, Jesper Skovhus

2001-01-01

This study was designed to determine whether sequential treatment with basic fibroblast growth factor (bFGF) and parathyroid hormone (PTH) can restore lost cancellous bone mass and strength at a severely osteopenic skeletal site in aged ovariectomized (OVX) rats. Female Sprague-Dawley rats were...... intravenously (iv) daily with bFGF for 14 days at a dose of 200 microg/kg body weight. At the end of bFGF treatment, one group was killed whereas the other group was subjected to 8 weeks of treatment with synthetic human PTH 1-34 [hPTH(1-34)] consisting of subcutaneous (sc) injections 5 days/week at a dose...... of 80 microg/kg. Another group of OVX rats was treated iv with vehicle for 2 weeks followed by treatment with PTH alone for 8 weeks. Other groups of sham-operated control rats and OVX rats were treated iv and sc with vehicle alone. The right proximal tibia from each rat was processed undecalcified...
In vivo PTH provokes apical NHE3 and NaPi2 redistribution and Na-K-ATPase inhibition

DEFF Research Database (Denmark)

Zhang, Y; Norian, J M; Magyar, C E

1999-01-01

and to determine whether the same cellular signals drive the changes in apical and basolateral transporters. PTH-(1-34) (20 U), which couples to adenylate cyclase (AC), phospholipase C (PLC), and phospholipase A2 (PLA2), or [Nle8,18,Tyr34]PTH-(3-34) (10 U), which couples to PLC and PLA2 but not AC, were given....../diuresis and NHE3 and NaPi2 internalization, and that Na-K-ATPase inhibition is not secondary to depressed apical Na+ transport....
Second messenger production in avian medullary nephron segments in response to peptide hormones.

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Goldstein, D L; Reddy, V; Plaga, K

1999-03-01

We examined the sites of peptide hormone activation within medullary nephron segments of the house sparrow (Passer domesticus) kidney by measuring rates of hormone-induced generation of cyclic nucleotide second messenger. Thin descending limbs, thick ascending limbs, and collecting ducts had baseline activity of adenylyl cyclase that resulted in cAMP accumulation of 207 +/- 56, 147 +/- 31, and 151 +/- 41 fmol. mm-1. 30 min-1, respectively. In all segments, this activity increased 10- to 20-fold in response to forskolin. Activity of adenylyl cyclase in the thin descending limb was stimulated approximately twofold by parathyroid hormone (PTH) but not by any of the other hormones tested [arginine vasotocin (AVT), glucagon, atrial natriuretic peptide (ANP), or isoproterenol, each at 10(-6) M]. Thick ascending limb was stimulated two- to threefold by both AVT and PTH; however, glucagon and isoproterenol had no effect, and ANP stimulated neither cAMP nor cGMP accumulation. Adenylyl cyclase activity in the collecting duct was stimulated fourfold by AVT but not by the other hormones; likewise, ANP did not stimulate cGMP accumulation in this segment. These data support a tubular action of AVT and PTH in the avian renal medulla.
Parathyroid hormone contributes to the down-regulation of cytochrome P450 3A through the cAMP/PI3K/PKC/PKA/NF-κB signaling pathway in secondary hyperparathyroidism.

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Watanabe, Hiroshi; Sugimoto, Ryusei; Ikegami, Komei; Enoki, Yuki; Imafuku, Tadashi; Fujimura, Rui; Bi, Jing; Nishida, Kento; Sakaguchi, Yoshiaki; Murata, Michiya; Maeda, Hitoshi; Hirata, Kenshiro; Jingami, Sachiko; Ishima, Yu; Tanaka, Motoko; Matsushita, Kazutaka; Komaba, Hirotaka; Fukagawa, Masafumi; Otagiri, Masaki; Maruyama, Toru

2017-12-01

Chronic kidney disease (CKD), which affects, not only renal clearance, but also non-renal clearance, is accompanied by a decline in renal function. Although it has been suggested that humoral factors, such as uremic toxins that accumulate in the body under CKD conditions, could be involved in the changes associated with non-renal drug clearance, the overall process is not completely understood. In this study, we report on the role of parathyroid hormone (PTH), a middle molecule uremic toxin, on the expression of drug metabolizing or transporting proteins using rats with secondary hyperparathyroidism (SHPT) as models. In SHPT rats, hepatic and intestinal CYP3A expression was suppressed, but the changes were recovered by the administration of the calcimimetic cinacalcet, a PTH suppressor. Under the same experimental conditions, a pharmacokinetic study using orally administered midazolam, a substrate for CYP3A, showed that the AUC was increased by 5 times in SHPT rats, but that was partially recovered by a cinacalcet treatment. This was directly tested in rat primary hepatocytes and intestinal Caco-2 cells where the expression of the CYP3A protein was down-regulated by PTH (1-34). In Caco-2 cells, PTH (1-34) down-regulated the expression of CYP3A mRNA, but an inactive PTH derivative (13-34) had no effect. 8-Bromo-cyclic adenosine monophosphate, a membrane-permeable cAMP analog, reduced mRNA expression of CYP3A whereas the inhibitors of PI3K, NF-κB, PKC and PKA reversed the PTH-induced CYP3A down-regulation. These results suggest that PTH down-regulates CYP3A through multiple signaling pathways, including the PI3K/PKC/PKA/NF-κB pathway after the elevation of intracellular cAMP, and the effect of PTH can be prevented by cinacalcet treatment. Copyright © 2017 Elsevier Inc. All rights reserved.
Distribution of genes for parathyroid hormone (PTH)-related peptide, Indian hedgehog, PTH receptor and patched in the process of experimental spondylosis in mice.

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Nakase, Takanobu; Ariga, Kenta; Meng, Wenxiang; Iwasaki, Motoki; Tomita, Tetsuya; Myoui, Akira; Yonenobu, Kazuo; Yoshikawa, Hideki

2002-07-01

Little is known about the molecular mechanisms underlying the process of spondylosis. The authors determined the extent of genetic localization of major regulators of chondrogenesis such as Indian hedgehog (Ihh) and parathyroid hormone (PTH)-related peptide (PTHrP) and their receptors during the development of spondylosis in their previously established experimental mouse model. Experimental spondylosis was induced in 5-week-old ICR mice. The cervical spines were chronologically harvested, and histological sections were prepared. Messenger (m) RNA for PTHrP, Ihh, PTH receptor (PTHR; a receptor for PTHrP), patched (Ptc; a receptor for Ihh), bone morphogenetic protein (BMP)-6, and collagen type X (COL10; a marker for mature chondrocyte) was localized in the tissue sections by performing in situ hybridization. In the early stage, mRNA for COL10, Ihh, and BMP-6 was absent; however, mRNA for PTHrP, PTHR, and Ptc was detected in the anterior margin of the cervical discs. In the late stage, evidence of COL10 mRNA began to be detected, and transcripts for Ihh, PTHrP, and BMP-6 were localized in hypertrophic chondrocytes adjacent to the bone-forming area in osteophyte. Messenger RNA for Ptc and PTHR continued to localize at this stage. In control mice, expression of these genes was absent. The localization of PTHrP, Ihh, BMP-6, and the receptors PTHR and Ptc demonstrated in the present experimental model indicates the possible involvement of molecular signaling by PTHrP (through the PTHR), Ihh (through the Ptc), and BMP-6 in the regulation of chondrocyte maturation leading to endochondral ossification in spondylosis.
Role of paraoxonase-1 in bone anabolic effects of parathyroid hormone in hyperlipidemic mice

Energy Technology Data Exchange (ETDEWEB)

Lu, Jinxiu [Department of Physiology, University of California, Los Angeles (United States); Cheng, Henry [Department of Medicine, University of California, Los Angeles (United States); Atti, Elisa [Division of Diagnostic and Surgical Sciences, School of Dentistry, University of California, Los Angeles (United States); Shih, Diana M. [Department of Medicine, University of California, Los Angeles (United States); Demer, Linda L. [Department of Physiology, University of California, Los Angeles (United States); Department of Medicine, University of California, Los Angeles (United States); Department of Bioengineering, University of California, Los Angeles (United States); Tintut, Yin, E-mail: ytintut@mednet.ucla.edu [Department of Medicine, University of California, Los Angeles (United States)

2013-02-01

Highlights: ► Anabolic effects of PTH were tested in hyperlipidemic mice overexpressing PON1. ► Expression of antioxidant regulatory genes was induced in PON1 overexpression. ► Bone resorptive activity was reduced in PON1 overexpressing hyperlipidemic mice. ► PON1 restored responsiveness to intermittent PTH in bones of hyperlipidemic mice. -- Abstract: Hyperlipidemia blunts anabolic effects of intermittent parathyroid hormone (PTH) on cortical bone, and the responsiveness to PTH are restored in part by oral administration of the antioxidant ApoA-I mimetic peptide, D-4F. To evaluate the mechanism of this rescue, hyperlipidemic mice overexpressing the high-density lipoprotein-associated antioxidant enzyme, paraoxonase 1 (Ldlr{sup −/−}PON1{sup tg}) were generated, and daily PTH injections were administered to Ldlr{sup −/−}PON1{sup tg} and to littermate Ldlr{sup −/−} mice. Expression of bone regulatory genes was determined by realtime RT-qPCR, and cortical bone parameters of the femoral bones by micro-computed tomographic analyses. PTH-treated Ldlr{sup −/−}PON1{sup tg} mice had significantly greater expression of PTH receptor (PTH1R), activating transcription factor-4 (ATF4), and osteoprotegerin (OPG) in femoral cortical bone, as well as significantly greater cortical bone mineral content, thickness, and area in femoral diaphyses compared with untreated Ldlr{sup −/−}PON1{sup tg} mice. In contrast, in control mice (Ldlr{sup −/−}) without PON1 overexpression, PTH treatment did not induce these markers. Calvarial bone of PTH-treated Ldlr{sup −/−}PON1{sup tg} mice also had significantly greater expression of osteoblastic differentiation marker genes as well as BMP-2-target and Wnt-target genes. Untreated Ldlr{sup −/−}PON1{sup tg} mice had significantly greater expression of PTHR1 than untreated Ldlr{sup −/−} mice, whereas sclerostin expression was reduced. In femoral cortical bones, expression levels of transcription factors, Fox
Parathyroid hormone secretion in chronic human endogenous hypercortisolism

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Lanna C.M.M.

2002-01-01

Full Text Available Osteoporosis is a common manifestation of Cushing's syndrome, but the mechanisms responsible for this abnormality have not been defined. With the objective of analyzing parathyroid hormone (PTH secretion in chronic hypercortisolism (CH, we evaluated 11 healthy subjects and 8 patients with CH, 6 with Cushing's disease and 2 with adrenal adenoma. These volunteers were submitted to tests of PTH stimulation through hypocalcemia (EDTA, PTH suppression through hypercalcemia (iv and oral calcium, and evaluation of bone mineral density (BMD by DEXA. During the test of PTH stimulation, the calcium and magnesium concentrations of the normal and CH groups were similar. Patients with CH showed an increased PTH response to the hypocalcemic stimulus compared to controls. PTH values were significantly higher in the CH group at 70 (17.5 ± 3.5 vs 10.2 ± 1.3 pmol/l, P = 0.04, and 120 min (26.1 ± 5.9 vs 11.3 ± 1.9 pmol/l, P = 0.008 of EDTA infusion. The area under the curve for PTH during EDTA infusion was also significantly higher in patients with CH than in normal subjects (1867 ± 453 and 805 ± 148 pmol l-1 2 h-1, P = 0.02. During the test of PTH suppression, calcium, magnesium and PTH levels of the patients with hypercortisolism and controls were similar. BMD was decreased in patients with hypercortisolism in the spine (0.977 ± 0.052 vs 1.205 ± 0.038 g/cm² in controls, P<0.01. In conclusion, our results show that subjects with CH present decreased bone mass mainly in trabecular bone. The use of dynamic tests permitted the detection of increased PTH secretion in response to a hypocalcemic stimulus in CH patients that may probably be involved in the occurrence of osteoporosis in this state.
Small Molecule Binding, Docking, and Characterization of the Interaction between Pth1 and Peptidyl-tRNA

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Mary C. Hames

2013-11-01

Full Text Available Bacterial Pth1 is essential for viability. Pth1 cleaves the ester bond between the peptide and nucleotide of peptidyl-tRNA generated from aborted translation, expression of mini-genes, and short ORFs. We have determined the shape of the Pth1:peptidyl-tRNA complex using small angle neutron scattering. Binding of piperonylpiperazine, a small molecule constituent of a combinatorial synthetic library common to most compounds with inhibitory activity, was mapped to Pth1 via NMR spectroscopy. We also report computational docking results, modeling piperonylpiperazine binding based on chemical shift perturbation mapping. Overall these studies promote Pth1 as a novel antibiotic target, contribute to understanding how Pth1 interacts with its substrate, advance the current model for cleavage, and demonstrate feasibility of small molecule inhibition.
The Neuroendocrine Functions of the Parathyroid Hormone 2 Receptor

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Arpad eDobolyi

2012-10-01

Full Text Available The G-protein coupled parathyroid hormone 2 receptor (PTH2R is concentrated in endocrine and limbic regions in the forebrain. Its endogenous ligand,tuberoinfundibular peptide of 39 residues (TIP39, is synthesized in only 2 brain regions, within the posterior thalamus and the lateral pons. TIP39-expressing neurons have a widespread projection pattern, which matches the PTH2R distribution in the brain. Neuroendocrine centers including the preoptic area, the periventricular, paraventricular, and arcuate nuclei contain the highest density of PTH2R-positive networks. The administration of TIP39 and an antagonist of the PTH2R as well as the investigation of mice that lack functional TIP39 and PTH2R revealed the involvement of the PTH2R in a variety of neural and neuroendocrine functions. TIP39 acting via the PTH2R modulates several aspects of the stress response. It evokes corticosterone release by activating corticotropin-releasing hormone-containing neurons in the hypothalamic paraventricular nucleus. Block of TIP39 signaling elevates the anxiety state of animals and their fear response, and increases stress-induced analgesia. TIP39 has also been suggested to affect the release of additional pituitary hormones including arginine vasopressin and growth hormone. A role of the TIP39-PTH2R system in thermoregulation was also identified. TIP39 may play a role in maintaining body temperature in a cold environment via descending excitatory pathways from the preoptic area. Anatomical and functional studies also implicated the TIP39-PTH2R system in nociceptive information processing. Finally, TIP39 induced in postpartum dams may play a role in the release of prolactin during lactation. Potential mechanisms leading to the activation of TIP39 neurons and how they influence the neuroendocrine system are also described. The unique TIP39-PTH2R neuromodulator system provides the possibility for developing drugs with a novel mechanism of action to control
The biphasic effect of triiodothyronine compared to bone resorbing effect of PTH on bone modelling of mouse long bone in vitro

International Nuclear Information System (INIS)

Soskolne, W.A.; Schwartz, Z.; Goldstein, M.; Ornoy, A.

1990-01-01

To examine the effects of T3 on fetal long bone modelling the radii and ulnae of 16 day old fetal mice were grown in vitro for two days. Their growth, mineralization, and resorption were assessed by measuring diaphyseal length, calcium and phosphorus content, hydroxyproline content, and the release of incorporated 45 Ca. The effects of T3 were compared to the effects of 1-34 PTH, a known resorbing agent, on the same system. Devitalized bones were used as a control. The results showed that T3 had a biphasic effect. At high concentrations (10(-5) M-10(-6) M) T3 inhibited the growth of the bones as indicated by their diaphyseal length and hydroxyproline content. Calcium and phosphorus content were significantly decreased while 45 Ca release was increased. Similar effects were also found after the addition of 1-34 PTH to the media. However, T3, at lower concentrations (10(-7) M-10(-9) M), stimulated the growth and calcification of the bones as indicated by an increase in diaphyseal length and the hydroxyproline, calcium, and phosphorus content. 45 Ca release was significantly decreased at these concentrations. Neither T3 nor 1-34 PTH affected devitalized bones in the same system. The results suggest that at physiological concentrations, T3 has a direct, anabolic effect on bone, which may explain its major role in the growth process of various species. At high doses, however, T3 stimulates bone resorption in a way similar to PTH
Impact of Different Levels of iPTH on All-Cause Mortality in Dialysis Patients with Secondary Hyperparathyroidism after Parathyroidectomy.

Science.gov (United States)

Xi, Qiu Ping; Xie, Xi Sheng; Zhang, Ling; Zhang, Rui; Xiao, Yue Fei; Jin, Cheng Gang; Li, Yan Bo; Wang, Lin; Zhang, Xiao Xuan; Du, Shu Tong

2017-01-01

Secondary hyperparathyroidism (SHPT) usually required parathyroidectomy (PTX) when drugs treatment is invalid. Analysis was done on the impact of different intact parathyroid hormone (iPTH) after the PTX on all-cause mortality. An open, retrospective, multicenter cohort design was conducted. The sample included 525 dialysis patients with SHPT who had undergone PTX. 404 patients conformed to the standard, with 36 (8.91%) deaths during the 11 years of follow-up. One week postoperatively, different levels of serum iPTH were divided into four groups: A: ≤20 pg/mL; B: 21-150 pg/mL; C: 151-600 pg/mL; and D: >600 pg/mL. All-cause mortality in groups with different iPTH levels appeared as follows: A (8.29%), B (3.54%), C (10.91%), and D (29.03%). The all-cause mortality of B was the lowest, with D the highest. We used group A as reference (hazard ratio (HR) = 1) compared with the other groups, and HRs on groups B, C, and D appeared as 0.57, 1.43, and 3.45, respectively. The all-cause mortality was associated with different levels of iPTH after the PTX. We found that iPTH > 600 pg/mL appeared as a factor which increased the risk of all-cause mortality. When iPTH levels were positively and effectively reducing, the risk of all-cause mortality also decreased. The most appropriate level of postoperative iPTH seemed to be 21-150 pg/mL.
Endogenous Parathyroid Hormone Promotes Fracture Healing by Increasing Expression of BMPR2 through cAMP/PKA/CREB Pathway in Mice

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Wei Zhou

2017-06-01

Full Text Available Background/Aims: Endogenous parathyroid hormone (PTH plays an important role in fracture healing. This study investigated whether endogenous PTH regulates fracture healing by bone morphogenetic protein (BMP and/or the transforming growth factor-β (TGF-β signaling pathway. Methods: Eight-week-old wild-type (WT and PTH-knockout (PTH KO male mice were selected, and models of open right-femoral fracture were constructed. Fracture healing and callus characteristics of mice in the two groups were compared by X-ray, micro-computed tomography, histological, and immunohistochemical examinations. Bone marrow mesenchymal stem cells (BMMSCs of 8-week-old WT and PTHKO male mice were obtained and induced into osteoblasts and chondrocytes. Results: We found that expression levels of Runt-related transcription factor (RUNX2, bone morphogenetic protein-receptor-type Ⅱ (BMPR2, phosphorylated Smad 1/5/8, and phosphorylated cyclic adenosine monophosphate-responsive element binding protein (CREB in the callus of PTHKO mice were significantly decreased, whereas no significant difference in expression of SOX9, TGF-βR2,or pSMAD2/3 was observed between PTHKO and WT mice. Additionally, the activity of osteoblast alkaline phosphatase was low at 7 days post-induction, and was upregulated by addition of PTH or dibutyryl cyclic adenosine monophosphate (dbcAMP to the cell culture. Furthermore, H89 (protein kinase A inhibitoreliminated the simulating effects of PTH and dbcAMP, and a low concentration of cyclic adenosine monophosphate (cAMP was observed in PTHKO mouse BMMSCs. Conclusion: These results suggested that endogenous PTH enhanced BMPR2 expression by a cAMP/PKA/CREB pathway in osteoblasts, and increased RUNX2 expression through transduction of the BMP/pSMAD1/5/8 signaling pathway.
Metabolism of labeled parathyroid hormone. V. Collected biological studies

Energy Technology Data Exchange (ETDEWEB)

Neuman, W F; Neuman, M W; Lane, K; Miller, L; Sammon, P J

1975-01-01

Biologically active /sup 125/I-labeled parathyroid hormone (/sup 125/I-PTH) was used in a series of studies in dogs and chickens designed to confirm and augment earlier studies in rats. As in rats, a three exponential equation was required to describe disappearance of /sup 125/I-PTH from the blood in the dog. The first two ''half-lives'' (1.8 and 7 min) accounted for the bulk of the dose. Also as in rats, deposition of apparently intact hormone took place rapidly in kidney, liver and bone in both the dog and the chicken. Degradation occurred very rapidly in all three target organs. Three labeled hormones of different biological activities were compared in the rat. Inactive, oxidized hormone was rejected by the liver but showed markedly increased deposition in kidney and the higher the purity of the hormone the higher was its uptake by liver. Exploration of a wide range of dosages revealed few effects on distribution (smaller depositon in liver and kidney at highest dosages, 65 ..mu..g/rat). Fresh sera did not degrade hormone rapidly or extensively. There was no deposition of hormone in intestinal mucosa, marrow, and red cells. Nephrectomy increased deposition in liver and bone. Finally, the perfused liver was capable of extensive degradation of the hormone.
Verapamil reverses PTH- or CRF-induced abnormal fatty acid oxidation in muscle

International Nuclear Information System (INIS)

Perna, A.F.; Smogorzewski, M.; Massry, S.G.

1988-01-01

Chronic renal failure (CRF) is associated with impaired long chain fatty acids (LCFA) oxidation by skeletal muscle mitochondria. This is due to reduced activity of carnitine palmitoyl transferase (CPT). These derangements were attributed to the secondary hyperparathyroidism of CRF, since prior parathyroidectomy in CRF rats reversed these abnormalities and PTH administration to normal rats reproduced them. It was proposed that these effects of PTH are mediated by its ionophoric property leading to increased entry of calcium into skeletal muscle. A calcium channel blocker may, therefore, correct these derangements. The present study examined the effects of verapamil on LCFA oxidation, CPT activity by skeletal muscle mitochondria, and 45 Ca uptake by skeletal muscle obtained from CRF rats and normal animals treated with PTH with and without verapamil. Both four days of PTH administration and 21 days of CRF produced significant (P less than 0.01) reduction in LCFA oxidation and CPT activity of skeletal muscle mitochondria, and significant (P less than 0.01) increment in 45 Ca uptake by skeletal muscle. Simultaneous treatment with verapamil corrected all these derangements. Administration of verapamil alone to normal rats did not cause a significant change in any of these parameters. The data are consistent with the proposition that the alterations in LCFA in CRF or after PTH treatment are related to the ionophoric action of the hormone and could be reversed by a calcium channel blocker
Changes of blood levels of several hormones, catecholamines, prostaglandins, electrolytes and cAMP in man during emotional stress.

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Tigranian, R A; Orloff, L L; Kalita, N F; Davydova, N A; Pavlova, E A

1980-01-01

The levels of several hormones (ACTH, GH, TSH, FSH, LH, parathyroid hormone--PTH, insulin, thyroxine--T4, triiodothyronine--T3, cortisol, testosterone, aldosterone, renin), catecholamines (epinephrine, norepinephrine, dopamin), prostaglandins (F1 alpha, F2 alpha, A + E), electrolytes (Na, K, Ca, Mg), cAMP and glucose in blood were measured before and immediately after the examination in 15 male students aged 28 to 35 years. Simultaneously the blood pressure was measured and hemodynamic measures were registered with the aid of echocardiography. A remarkable increase of catecholamines, ACTH, renin, T3, PTH, cAMP, PG F1 alpha, PG F2 alpha and Ca was found before the examination together with the increase of blood pressure. After the examination the levels of catecholamines, renin, aldosterone, T3, PTH, GH, FSH, LH, testosterone, PG A + E, glucose and Ca were found to be increased, while these of insulin, Na, PG F1 alpha, PG F2 alpha were decreased. The decrease of blood pressure was also found.
Parathyroid Hormone Measurement in Prediction of Hypocalcaemia following Thyroidectomy

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Mehrvarz, S.; Mohebbi, H. A.; Motamedi, M. H. K.; Khatami, S. M.; Reazie, R.; Rasouli, H. R.

2014-01-01

Objective: To determine the risk of postthyroidectomy hypocalcaemia by measuring parathyroid hormone (PTH) level after thyroidectomy. Study Design: Cross-sectional study. Place and Duration of Study: Baqiyatallah Hospital, Tehran, Iran, from March 2008 to July 2010. Methodology: All included patients were referred for total or near bilateral thyroidectomy. Serum Calcium (Ca) and PTH levels were measured before and 24 hours after surgery. In low Ca cases or development of hypocalcaemia symptoms, daily monitoring of Ca levels were continued. Data were analyzed using SPSS 20 software (SPSS, Chicago, IL, USA). A p-value less than 0.05 were considered statistically significant. To assess the standard value of useful predictive factors, we used receiver operating characteristic (ROC) curves. Results: Of total 99 patients who underwent bilateral thyroidectomy, 47 patients (47.5%) developed hypocalcaemia, out of them, 12 (25.5%) became symptomatic while 2 patients developed permanent hypoparathyroidism. After surgery, mean rank of PTH level within the normocalcaemic and hypocalcaemic patients was 55.34 and 44.1 respectively, p=0.052. Twenty four hours after surgery, 62% drop in PTH was associated with 83.3% of symptomatic hypocalcaemic. For diagnosis of symptomatic hypocalcaemia, 62% PTH drop had sensitivity and specificity were 83.3% and 90.80%. The area under the ROC curve for the PTH postoperative and PTH drop for diagnostic symptomatic hypocalcaemia were 0.835 and 0.873 respectively. Conclusion: Measuring PTH levels after 24 hours postthyroidectomy is not reliable factor for predicting hypocalcaemia itself. For predicting the risk of hypocalcaemia after thyroidectomy it is more reliable to measure the serum PTH level before and after operation and compare the reduction level of percentage of PTH drop for predicting the risk of hypocalcaemia. (author)
Effect of parathyroid hormone and calcium ions on substrate oxidation by isolated glomeruli of the rat.

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Wang, M S; Kurokawa, K

1981-11-05

Effect of Ca2+ and parathyroid hormone (PTH) on 14 CO2 production from certain metabolic substrates by isolated glomeruli of rat kidney were examined. Increasing calcium concentration in the incubation medium inhibited 14CO2 production from 14C-labeled alpha-ketoglutarate and succinate, stimulated 14CO2 production from [1-14C]glucose and [1-14C]glutamate, but was without effect on that from [6-14C]glucose. PTH in the presence but not in the absence of Ca2+ inhibited 14CO2 production from labeled alpha-ketoglutarate and glutamate but not from labeled glucose. Additions of cyclic AMP as well as hormonal agents known to act directly on the glomureli, such as histamine, epinephrine, prostaglandin E2, vasopressin, angiotensin II and insulin, did not alter 14 CO2 production from labeled alpha-ketoglutarate. These data show the presence of calcium-dependent inhibitory actions on PTH on oxidation of alpha-ketoglutarate and glutamate which may be independent of cyclic AMP. These metabolic effects of PTH may underlie the alteration in the glomerular ultrafiltration coefficient and glomerular filtration induced by the hormone.

Overproduction and secretion of a novel amino-terminal form of parathyroid hormone from a severe type of parathyroid hyperplasia in uremia.

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Arakawa, Toshio; D'Amour, Pierre; Rousseau, Louise; Brossard, Jean-Hugues; Sakai, Makoto; Kasumoto, Hiroomi; Igaki, Naoya; Goto, Takeo; Cantor, Tom; Fukagawa, Masafumi

2006-05-01

Measurement of bioactive parathyroid hormone (PTH) is essential for optimal management of bone abnormalities in dialysis patients. This can be accomplished by PTH measurements using third-generation PTH assays, which detect more or less of the first six amino acids of the PTH structure. Such assays do not detect non-(1-84) PTH fragments, such as human PTH (7-84), which are recognized by the second-generation PTH assays that use a detection antibody that recognizes an epitope within the 13-34 region of the PTH structure. Therefore, third-generation PTH results are expected to be lower than those that are obtained with second-generation PTH assays. Rare exceptions to this rule have been reported for patients with severe primary hyperparathyroidism or parathyroid cancer. Sera and gland extracts were analyzed from a dialysis patient with high bone turnover disease and with surprising higher PTH levels by a third-generation assay than by a second-generation assay. This finding normalized after the surgical removal of an enlarged gland with a single nodule, an advanced type of nodular hyperplasia. HPLC fractionation of sera and gland extracts revealed the overproduction and secretion of a PTH molecule with an intact amino-terminus structure distinct from (1-84) PTH. This form of PTH was readily detectable by third-generation PTH assays but was poorly reactive in second-generation PTH assays. Therefore, parathyroid glands with advanced uremic nodular hyperplasia may overproduce and secrete a novel, biologically active form of PTH with an intact 1-6 region but a presumably modified 12-18 region required for the detection in second-generation PTH assays.
PTH treatment activates intracortical bone remodeling in patients with hypoparathyroidism

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Sikjær, Tanja Tvistholm; Rejnmark, Lars; Thomsen, Jesper Skovhus

2017-01-01

Hypoparathyroidism (hypoPT) is characterized by a state of low bone turnover and high BMD. We have previously shown that hypoPT patients treated with PTH(1-84) for six months have highly increased bone turnover markers and a decrease in aBMD at the hip and spine(1). The present study aims...... to investigate the effect of PTH(1-84) on cortical bone and intracortical bone remodeling in hypoPT. The study was conducted on 20 transiliac bone biopsies from hypoPT patients after six months of treatment with either PTH(1-84) 100 µg s.c./day N=10 or placebo N=10. The groups were age- (±6 years) and gender...... and diameter were measured. Cortical porosity and pore density did not differ between groups, but PTH treatment had a marked effect on the remodeling status of the pores. The percentage of pores undergoing remodeling was higher in the PTH-group than in placebo-group reported as median values (IQR[25-75%]) (52...
Detection of parathyroid hormone using an electrochemical impedance biosensor based on PAMAM dendrimers.

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Özcan, Hakkı Mevlüt; Sezgintürk, Mustafa Kemal

2015-01-01

This paper presents a novel hormone-based impedimetric biosensor to determine parathyroid hormone (PTH) level in serum for diagnosis and monitoring treatment of hyperparathyroidism, hypoparathyroidism and thyroid cancer. The interaction between PTH and the biosensor was investigated by an electrochemical method. The biosensor was based on the gold electrode modified by 12-mercapto dodecanoic (12MDDA). Antiparathyroid hormone (anti-PTH) was covalently immobilized on to poly amidoamine dendrimer (PAMAM) which was bound to a 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide/N-hydroxysuccinimide (EDC/NHS) couple, self-assembled monolayer structure from one of the other NH2 sites. The immobilization of anti-PTH was monitored by electrochemical impedance spectroscopy, cyclic voltammetry and scanning electron microscope techniques. After the optimization studies of immobilization materials such as 12MDDA, EDC-NHS, PAMAM, and glutaraldehyde, the performance of the biosensor was investigated in terms of linearity, sensitivity, repeatability, and reproducibility. PTH was detected within a linear range of 10-60 fg/mL. Finally the described biosensor was used to monitor PTH levels in artificial serum samples. © 2015 American Institute of Chemical Engineers.
Genetic Variants Associated with Circulating Parathyroid Hormone.

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Robinson-Cohen, Cassianne; Lutsey, Pamela L; Kleber, Marcus E; Nielson, Carrie M; Mitchell, Braxton D; Bis, Joshua C; Eny, Karen M; Portas, Laura; Eriksson, Joel; Lorentzon, Mattias; Koller, Daniel L; Milaneschi, Yuri; Teumer, Alexander; Pilz, Stefan; Nethander, Maria; Selvin, Elizabeth; Tang, Weihong; Weng, Lu-Chen; Wong, Hoi Suen; Lai, Dongbing; Peacock, Munro; Hannemann, Anke; Völker, Uwe; Homuth, Georg; Nauk, Matthias; Murgia, Federico; Pattee, Jack W; Orwoll, Eric; Zmuda, Joseph M; Riancho, Jose Antonio; Wolf, Myles; Williams, Frances; Penninx, Brenda; Econs, Michael J; Ryan, Kathleen A; Ohlsson, Claes; Paterson, Andrew D; Psaty, Bruce M; Siscovick, David S; Rotter, Jerome I; Pirastu, Mario; Streeten, Elizabeth; März, Winfried; Fox, Caroline; Coresh, Josef; Wallaschofski, Henri; Pankow, James S; de Boer, Ian H; Kestenbaum, Bryan

2017-05-01

Parathyroid hormone (PTH) is a primary calcium regulatory hormone. Elevated serum PTH concentrations in primary and secondary hyperparathyroidism have been associated with bone disease, hypertension, and in some studies, cardiovascular mortality. Genetic causes of variation in circulating PTH concentrations are incompletely understood. We performed a genome-wide association study of serum PTH concentrations among 29,155 participants of European ancestry from 13 cohort studies ( n =22,653 and n =6502 in discovery and replication analyses, respectively). We evaluated the association of single nucleotide polymorphisms (SNPs) with natural log-transformed PTH concentration adjusted for age, sex, season, study site, and principal components of ancestry. We discovered associations of SNPs from five independent regions with serum PTH concentration, including the strongest association with rs6127099 upstream of CYP24A1 ( P =4.2 × 10 -53 ), a gene that encodes the primary catabolic enzyme for 1,25-dihydroxyvitamin D and 25-dihydroxyvitamin D. Each additional copy of the minor allele at this SNP associated with 7% higher serum PTH concentration. The other SNPs associated with serum PTH concentration included rs4074995 within RGS14 ( P =6.6 × 10 -17 ), rs219779 adjacent to CLDN14 ( P =3.5 × 10 -16 ), rs4443100 near RTDR1 ( P =8.7 × 10 -9 ), and rs73186030 near CASR ( P =4.8 × 10 -8 ). Of these five SNPs, rs6127099, rs4074995, and rs219779 replicated. Thus, common genetic variants located near genes involved in vitamin D metabolism and calcium and renal phosphate transport associated with differences in circulating PTH concentrations. Future studies could identify the causal variants at these loci, and the clinical and functional relevance of these variants should be pursued. Copyright © 2017 by the American Society of Nephrology.
Effectiveness of Intraoperative Parathyroid Monitoring (ioPTH) in predicting a multiglandular or malignant parathyroid disease.

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Dobrinja, C; Santandrea, G; Giacca, M; Stenner, Elisabetta; Ruscio, Maurizio; de Manzini, Nicolò

2017-05-01

The main goal of our study was to confirm the usefulness of intra-operative parathyroid hormone (PTH) monitoring (ioPTH) when using minimally invasive techniques for treatment of sporadic Primary hyperparathyroidism (pHTP). Furthermore, we aimed to evaluate if ioPTH monitoring may help to predict the etiology of primary hyperparathyroidism, especially in malignant or multiglandular parathyroid disease. A retrospective review of 125 consecutive patients with pHPT who underwent parathyroidectomy between 2001 and 2016 at the Department of General Surgery was performed. For each patient, the specific preoperative work-up consisted of: high-resolution US of the neck by a skilled sonographer, sestamibi parathyroid scan, laryngoscopy, and serum measurement of PTH, serum calcium levels, and serum 25(OH)D levels. The study included 125 consecutive patients who underwent surgery for pHPT. At the histological examination, we registered 113 patients with simple adenomatous pathology (90,4%), 5 atypical adenomas (4%), 3 cases of parathyroid carcinoma (2,4%),, , and 4 histological exams of different nature (3,2%). Overall, 6 cases (4,8%) of multiglandular disease were found. We reported 10 cases (8%) of recurrent/persistent hyperparathyroidism: 1/10 in a patient affected by atypical adenoma, 9/10 in patients with benign pathology. Regarding these 10 cases, in three (30%) patients, ioPTH wasn't dosed (only frozen section (FS) exam was taken), in 5 cases (50%) ioPTH dropped more than 50% compared to basal value (false negative results), and in 2 (20%) cases, ioPTH did not drop >50% from the first samples taken, the extemporary exam had confirmed the presence of adenoma and the probable second hyperfunctioning adenoma was not found. IoPTH determinations ensure operative success of surgical resection in almost all hyperfunctioning tissue; in particular it is very important during minimally invasive parathyroidectomy, as it allows avoiding bilateral neck exploration. The use of ioPTH
Vitamin D, PTH, and calcium in relation to survival following prostate cancer.

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Brändstedt, Johan; Almquist, Martin; Manjer, Jonas; Malm, Johan

2016-05-01

Epidemiological studies suggest that low levels of vitamin D constitute a risk factor for prostate cancer. However, the results are conflicting, perhaps because prostate cancer is a very heterogeneous disease. More recent studies have focused on cancer progression and mortality. Vitamin D is closely related to both calcium metabolism and parathyroid hormone (PTH) levels, and all three factors have been implicated in prostate cancer. We examined the associations between pre-diagnostic serum levels of vitamin D (25OHD), PTH, and calcium and mortality among 943 participants within the Malmö Diet and Cancer Study, who were diagnosed with prostate cancer. The mean time from diagnosis until the end of followup was 9.1 years (SD 4.5), and the mean time from inclusion until end of follow-up was 16.6 years (SD 4.9). The analytes were divided into quartiles, and the risk of death from prostate cancer was analyzed using Cox proportional hazard analysis, yielding hazards ratios (HR) with 95 % confidence intervals. The models were adjusted for season and year of inclusion, age at baseline, age at diagnosis, body mass index (BMI), and tumor characteristics (TNM and Gleason score). We observed a trend toward a lower prostate-specific mortality with 25OHD >85 nmol/L in the unadjusted analysis. This became statistically significantly in the third quartile of 25OHD (85-102 nmol/L) compared to the first (L), HR 0.54 (0.34-0.85) when adjusting for age, time of inclusion, and BMI. The association was further strengthened when adjusted for age at diagnosis, Gleason score, and TNM classification with a HR in Q3 0.36 (0.22-0.60). p for trend was 0.03. Regarding calcium, there was a significantly lower HR for the second quartile (2.35-2.39 mmol/L) compared to the first (≤2.34 mmol/L) with a HR of 0.54 (0.32-0.86) in the unadjusted analysis. However, this association disappeared when adjusting for tumor characteristics. There were no associations between levels of PTH and prostate cancer
Additive Effects of Mechanical Marrow Ablation and PTH Treatment on de Novo Bone Formation in Mature Adult Rats

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Jodi A. Carlson Scholz

2012-12-01

Full Text Available Mechanical ablation of bone marrow in young rats induces rapid but transient bone growth, which can be enhanced and maintained for three weeks by the administration of parathyroid hormone (PTH. Additionally, marrow ablation, followed by PTH treatment for three months leads to increased cortical thickness. In this study, we sought to determine whether PTH enhances bone formation after marrow ablation in aged rats. Aged rats underwent unilateral femoral marrow ablation and treatment with PTH or vehicle for four weeks. Both femurs from each rat were analyzed by X-ray and pQCT, then analyzed either by microCT, histology or biomechanical testing. Marrow ablation alone induced transient bone formation of low abundance that persisted over four weeks, while marrow ablation followed by PTH induced bone formation of high abundance that also persisted over four weeks. Our data confirms that the osteo-inducive effect of marrow ablation and the additive effect of marrow ablation, followed by PTH, occurs in aged rats. Our observations open new avenues of investigations in the field of tissue regeneration. Local marrow ablation, in conjunction with an anabolic agent, might provide a new platform for rapid site-directed bone growth in areas of high bone loss, such as in the hip and wrist, which are subject to fracture.
Benefits resulting from 1- and 6-hour parathyroid hormone and calcium levels after thyroidectomy.

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Payne, Richard J; Tewfik, Marc A; Hier, Michael P; Tamilia, Michael; Mac Namara, Elizabeth; Young, Jonathan; Black, Martin J

2005-09-01

Previous studies have established the efficacy of post-thyroidectomy hypocalcemia monitoring using parathyroid hormone (PTH) and corrected calcium levels at 1 and 6 hours. The goal of this study was to measure the impact of managing patients based on the above findings with respect to: duration of hospital stays, rates of transient hypocalcemia, number of blood tests, cost savings, and discharge from the hospital as early as 8 hours post-thyroidectomy without compromising safety. This is a prospective study involving 95 total thyroidectomy patients using historical data as controls. The previous protocol was modified in that all blood tests ceased for patients meeting the 6-hour critical level of PTH > or = 28 ng/L and simultaneous corrected calcium > or = 2.14 mmol/L (8.56 mg/dL). Furthermore, patients with 1-hour PTH levels cost savings of 766 Canadian dollars per patient. The new algorithm resulting from PTH and corrected calcium monitoring at 1 and 6 hours post-thyroidectomy has led to significant cost savings for our institution. It has also translated into greater patient satisfaction as a result of fewer blood tests, a lower incidence of transient hypocalcemia, and significantly shorter hospital stays.
Effectiveness of an i-PTH Measurement in Predicting Post Thyroidectomy Hypocalcemia: Prospective Controlled Study

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Kim, Jin Pyeong; Park, Jung Je; Son, Hee Young; Kim, Rock Bum; Kim, Ho Youp

2013-01-01

Purpose Hypocalcemia is the most common complication after total thyroidectomy. The purpose of this study was to determine whether measurement of intact parathyroid hormone (i-PTH) level in thyroidectomy patients could predict hypocalcemia. Materials and Methods We performed a prospective study of patients undergoing total thyroidectomy. Serum concentration of i-PTH, total calcium (Ca), ionized calcium (Ca2+), phosphate (P), magnesium (Mg), and albumin were measured preoperatively and at 0 hour, 6 hours, 12 hours, 24 hours, 48 hours, and 72 hours postoperatively. Results 108 patients were recruited to the study. A total of 50 patients (46%) experienced hypocalcemia. The serum i-PTH concentration was linearly related to the time of measurement, while concentrations of P, Mg, albumin, Ca, and Ca2+ were not. We compared odds ratios, and found that the concentration of i-PTH at 6 hours post operation was the most closely related to the occurrence of hypocalcemic symptom. On ROC analysis using i-PTH level at 6 hours, an i-PTH level of 10.6 mg/dL was found to maximize both sensitivity and specificity at the same time point. Conclusion We found that i-PTH was a predictor of hypocalcemia, and that the earliest predictor of hypocalcemic symptoms was an i-PTH concentration lower than 10.6 mg/dL obtained 6 hours after total thyroidectomy. PMID:23549808
An iPTH based protocol for the prevention and treatment of symptomatic hypocalcemia after thyroidectomy

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Carter, Yvette; Chen, Herbert; Sippel, Rebecca S.

2013-01-01

Background Symptomatic hypocalcemia after thyroidectomy is a barrier to same day surgery, and the cause of ER visits. A standard protocol of calcium and vitamin D supplementation, dependent on intact parathyroid hormone (iPTH) levels, can address this issue. How effective is it? When does it fail? Methods We performed a retrospective review of the prospective Thyroid Database from January 2006 to December 2010. 620 patients underwent completion (CT) or total thyroidectomy (TT), and followed our post-operative protocol of calcium carbonate administration for iPTH levels ≥10pg/ml and calcium carbonate and 0.25μg calcitriol BID for iPTH hypocalcemia. The symptomatic (SX) and asymptomatic (ASX) groups were similar with regard to gender, cancer diagnosis, and pre-operative calcium and iPTH. The symptomatic group was significantly younger (39.6 ± 2.8 vs. 49 ± 0.6 years, p=0.01), with lower post-operative iPTH levels. 33% (n=8) of SX patients had an iPTH ≤5 pg/ml vs. only 6% (n=37) of ASX patients. While the majority of patients with a PTH hypocalcemia after thyroidectomy. An iPTH ≤ 5pg/ml may warrant higher initial doses of calcitriol in order to prevent symptoms. PMID:24144426
Effects of add on PTH(1-84) substitution therapy in hypoparathyroidism: results from a double-blind randomised controlled study

DEFF Research Database (Denmark)

Sikjær, Tanja Tvistholm; Rejnmark, Lars; Mosekilde, Leif

-phosphate levels within the physiological range. Compared with placebo, participants randomised to PTH (1-84) reduced their daily dose of calcium supplements by 68 % (pvitamin D dose by 53% (pneed of calcium supplements...... and 7 were not in need of active vitamin D. With the actual add on therapy there were no change in renal calcium excretion in response to treatment. Compared with placebo, bone mineral density (BMD) decreased significantly at the hip (-1.59 ± 0.57%), lumbar spine (-1.76 ± 1.03%) and whole body (-1...... bone packets. In conclusion, PTH substitution therapy is capable of maintaining normal p-calcium levels with a significantly reduced need for calcium supplements and active vitamin D. In contrast to the effect of PTH(1-84) treatment in patients with osteoporosis, causing an increase in BMD...
Bariatric Roux-En-Y Gastric Bypass Surgery: Adipocyte Proteins Involved in Increased Bone Remodeling in Humans.

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Biagioni, Maria Fernanda G; Mendes, Adriana L; Nogueira, Célia Regina; Leite, Celso V; Gollino, Loraine; Mazeto, Gláucia Mfs

2017-07-01

Bariatric surgery has been associated with bone remodeling changes. The action of adipokines on the expression of receptor activator of nuclear factor kappa β ligand (RANKL) and osteoprotegerin (OPG) and on an increase in sclerostin could be related to these changes. This study aimed to assess the repercussions of weight loss, fat mass (FM), and fat-free mass (FFM) loss and biochemical and hormonal changes on bone remodeling markers after Roux-en-Y gastric bypass (RYGB). Anthropometric data, parathyroid hormone (PTH), bone-specific alkaline phosphatase (BSAP), collagen type 1 C-telopeptide (CTX), 25-hydroxy vitamin D (25-OH-VitD), leptin, adiponectin, RANKL, OPG, and sclerostin of 30 menstruating women were measured preoperatively (Pre), and 3, 12, and 24 months (m) after RYGB. Leptin (34.4 (14.7; 51.9) vs. 22.5 (1.9; 52.7) ng/mL) and OPG (3.6 (1.1; 11.5) vs. 3.4 (1.5; 6) pmol/L) decreased, and adiponectin (7.4 (1.7; 18.4) vs. 13.8 (3.0; 34.6) μg/mL), CTX (0.2 (0.1; 2.2) vs. 0.6 (0.4; 6.0) ng/mL), RANKL (0.1 (0.0; 0.5) vs. 0.3 (0.0; 2.0) pmol/L), and sclerostin (21.7 (3.2; 75.1) vs. 34.8 (6.4; 80.5) pmol/L) increased after 3 m. BSAP increased after 12 m (10.1 (5.4; 18.9) vs. 13.9 (6.9; 30.2) μg/mL) (p < 0.005). CTX correlated positively with adiponectin at 24 m and inversely with leptin Pre; OPG at 3 m; weight, FM, FFM, and leptin at 24 m. RANKL correlated directly with weight at 3 m. Sclerostin correlated inversely with weight Pre and FM at 3 m. BSAP correlated negatively with 25-OH-VitD at 12 m, and positively with PTH at 24 m. RYGB induced weight loss, and biochemical, hormonal, and body composition changes are associated with higher bone remodeling.
Influence of a low calcium and phosphorus diet on the anabolic effect of human parathyroid hormone (1-38) in female rats

DEFF Research Database (Denmark)

Steiner, P.D.; Forrer, R.; Kneissel, Michaela

2001-01-01

Parathyroid hormone (PTH) or synthetic N-terminal PTH fragments administered intermittently have been established as anabolic agents in animal and human bones. In the present study, the influence of a low calcium diet on the anabolic effect of human PTH(1-38) [hPTH(1-38)] was investigated. Forty......-eight 10-week-old female Sprague-Dawley rats were randomly assigned to a diet with a low calcium content (LCa) or a diet with the recommended amount of calcium (RCa). After an adaptation period of 15 days, the rats were randomly assigned to hPTH(1-38) treatment (+LCa/+RCa) or vehicle only (-LCa....../-RCa) for an additional 14 days. Total bone mineral density (BMD) values of several bones were determined using quantitative computed tomography and from ratios of ash weight to volume. Biomechanical competence of the fourth lumbar vertebrae and of the right femora was assessed. An anabolic effect could be detected...
Significant association between parathyroid hormone and uric acid level in men

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Chin KY

2015-08-01

Full Text Available Kok-Yong Chin,1 Soelaiman Ima Nirwana,1 Wan Zurinah Wan Ngah21Department of Pharmacology, 2Department of Biochemistry, Faculty of Medicine, Universiti Kebangsaan Malaysia Medical Centre, Kuala Lumpur, MalaysiaBackground: Previous reports of patients undergoing parathyroidectomy and of patients receiving teriparatide as antiosteoporotic treatment have suggested a plausible relationship between parathyroid hormone (PTH and uric acid. However, similar data at population level were lacking. The current study aimed to determine the relationship between PTH and uric acid in a group of apparently healthy Malaysian men.Methods: A cross-sectional study was conducted among 380 Malay and Chinese men aged 20 years and above, residing in the Klang Valley, Malaysia. Their body anthropometry was measured, and their fasting blood samples were collected for biochemical analysis. The relationship between PTH and uric acid was analyzed using regression analysis.Results: Increased serum PTH level was significantly associated with increased serum uric acid level (β=0.165; P=0.001. Increased PTH level was also significantly associated with the condition of hyperuricemia in the study population (odds ratio [OR], 1.045; 95% confidence interval [CI], 1.017–1.075; P=0.002. All analyses were adjusted for age, body mass index, vitamin D, total calcium, inorganic phosphate, blood urea nitrogen and creatinine levels.Conclusion: There is a significant positive relationship between PTH level and uric acid level in Malaysian men. This relationship and its clinical significance should be further investigated in a larger longitudinal study. Keywords: hyperuricemia, Asian, cross-sectional study, uric acid, urate
Are PTH levels related to oxidative stress and inflammation in chronic kidney disease patients on hemodialysis?

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Marcel Jaqueto

Full Text Available Abstract Introduction: Patients at end stage renal disease have higher levels of inflammation and oxidative stress than the general population. Many factors contribute to these issues, and the parathyroid hormone (PTH is also implicated. Objective: The study was conducted in order to assess the relationship between PTH levels and inflammation and oxidative stress in hemodialysis patients. Methods: Cross-sectional study with patients of two hemodialysis facilities in Londrina, Brazil. Patients with other conditions known to generate oxidative stress and inflammation were excluded. Blood levels of PTH and biochemical parameters of inflammation (interleukins 1 and 6, tumor necrosis factor-alpha and oxidative stress (total plasma antioxidant capacity, malonic dialdehyde, lipid hydroperoxidation, advanced oxidation protein products, quantification of nitric oxide metabolites, and 8-isoprostane were measured before a dialysis session. Then, we made correlation analyses between PTH levels - either as the continuous variable or categorized into tertiles-, and inflammatory and oxidative stress biomarkers. Results: PTH did not show any correlation with the tested inflammation and oxidative stress parameters, nor as continuous variable neither as categorical variable. Conclusion: In this descriptive study, the results suggest that the inflammation and oxidative stress of hemodialysis patients probably arise from mechanisms other than secondary hyperparathyroidism.
Parathyroid hormone and vitamin D--markers for cardiovascular and all cause mortality in heart failure

DEFF Research Database (Denmark)

Schierbeck, Louise Lind; Jensen, Torben Slott; Bang, Ulrich

2011-01-01

To investigate levels of vitamin D and parathyroid hormone (PTH) in a population of heart failure (HF) patients, and to evaluate whether vitamin D and PTH are related to prognosis.......To investigate levels of vitamin D and parathyroid hormone (PTH) in a population of heart failure (HF) patients, and to evaluate whether vitamin D and PTH are related to prognosis....
Parathyroid hormone-related peptide plasma concentrations in patients on hemodialysis

DEFF Research Database (Denmark)

Nordholm, Anders; Rix, M.; Olgaard, K.

2014-01-01

the same receptor, the PTH1R, and it has been shown experimentally that PTHrP enhances the PTH secretory response to hypocalcemia, indicating a link between the two hormones. METHODS: Together with a number of parameters involved in mineral homeostasis plasma PTHrP was measured before hemodialysis in 90...
Fundamental and clinical study for PHT (parathyroid hormone) kit 'Yamasa'

International Nuclear Information System (INIS)

Fukunaga, Masao; Otsuka, Nobuaki; Furukawa, Takako; Morita, Rikushi

1987-01-01

A commercially available radioimmunoassay kit (Yamasa) for parathyroid hormone (PTH) is the midregion-specific assay system. Fundamental study of the PTH kit gave favorable results for specificity, reproducibility, dilution, and recovery. The serum PTH concentration was detectable among all 41 normal volunteers. The upper and lower limits of normal for PTH in serum were found to be 600 pg/ml and 184 pg/ml, respectively. PTH values were high for chronic renal failure (6/7) and primary hyperparathyroidism (41/41), and low for malignancy associated with hypercalcemia (5/25). It seems possible to discriminate hypercalcemic from normal subjects. The serum PTH concentration from the present assay system was significantly correlated with that from conventional carboxyl-terminal PTH, midregion PTH, amino-terminal PTH, and (1 - 84) PTH assay systems. The results indicate the potential of the Yamasa kit in evaluating calcium metabolism, as well as in detecting the presence of secondary hyperparathyroidism. (Namekawa, K.)
Parathyroid hormone promotes the disassembly of cytoskeletal actin and myosin in cultured osteoblastic cells: Mediation by cyclic AMP

International Nuclear Information System (INIS)

Egan, J.J.; Gronowicz, G.; Rodan, G.A.

1991-01-01

Parathyroid hormone (PTH) alters the shape of osteoblastic cells both in vivo and in vitro. In this study, we examined the effect of PTH on cytoskeletal actin and myosin, estimated by polyacrylamide gel electrophoresis of Triton X-100 (1%) nonextractable proteins. After 2-5 minutes, PTH caused a rapid and transient decrease of 50-60% in polymerized actin and myosin associated with the Triton X-100 nonextractable cytoskeleton. Polymerized actin returned to control levels by 30 min. The PTH effect was dose-dependent with an IC50 of about 1 nM, and was partially inhibited by the (3-34) PTH antagonist. PTH caused a rapid transient rise in cyclic AMP (cAMP) in these cells that peaked at 4 min, while the nadir in cytoskeletal actin and myosin was recorded around 5 min. The intracellular calcium chelator Quin-2/AM (10 microM) also decreased cytoskeletal actin and myosin, to the same extent as did PTH (100 nM). To distinguish between cAMP elevation and Ca++ reduction as mediators of PTH action, we measured the phosphorylation of the 20 kD (PI 4.9) myosin light chain in cells preincubated with [32P]-orthophosphate. The phosphorylation of this protein decreased within 2-3 min after PTH addition and returned to control levels after 5 min. The calcium ionophore A-23187 did not antagonize this PTH effect. Visualization of microfilaments with rhodamine-conjugated phalloidin showed that PTH altered the cytoskeleton by decreasing the number of stress fibers. These changes in the cytoskeleton paralleled changes in the shape of the cells from a spread configuration to a stellate form with retracting processes. The above findings indicate that the alteration in osteoblast shape produced by PTH involve relatively rapid and transient changes in cytoskeletal organization that appear to be mediated by cAMP
Changes in bone geometry and microarchitecture caused by intermittent administration of PTH. Comparison with those by exercise load

International Nuclear Information System (INIS)

Mori, Keiya

2010-01-01

There have been several studies showing that periodical intermittent medication with parathyroid hormone (PTH) causes increases in cancellous bone mass. However, there have been almost no reports comparing the effects of periodical intermittent PTH medication on bone microarchitecture with changes caused by physiological stimulation such as exercise load. In this study, we compared the effects of these two interventions on the microarchitecturural deterioration of femoral cancellous bone associated with unloading, using micro-computed tomography (micro-CT), and the effects of PTH administration and motion loading on improvement of the deteriorated structure. In the study, 32 eight-week-old male Wistar rats were divided into four groups: a control group without tail suspension (CON), a control recovery group after suspension (S+C), a suspension/PTH group (S+P), and a suspension/jumping exercise group (S+J). Periodical intermittent human PTH (1-34) was given periodically to the S+P group rats at a dose of 75 μg/kg/day five times a week for five weeks, after two weeks of exercise with suspension of the tail. The rats in the S+J group performed 40 cm-high jumping 10 times/day five times a week for five weeks. After this conditioning, upon examination, bilateral femurs were removed and the right distal metaphysis was scanned using micro-CT to obtain images of the cancellous bone region of the femur. Based on the tomographic data, indices of cancellous bone microarchitecture was the index of trabecular bone structure were determined by using three-dimensional image analysis system. In addition, to examine the geometric properties of the diaphysis, mid-portion images of the bone shaft of the left femur were obtained by micro-CT, and then the mechanical bone strength of the left femur was determined by performing a three-point bending test. Compared to the S+C group, the S+P and S+J groups showed significantly higher bone volume, bone surface mass values, superficial bone

Human interleukin 1β (IL-1β), a more powerful inducer of bone demineralization than interleukin 1α (IL-1α), parathyroid hormone (PTH) or prostaglandin E2 (PGE2) in vitro

International Nuclear Information System (INIS)

Chin, R.C.; Hodges, Y.C.; Allison, A.C.

1986-01-01

Effects of human IL-1α and IL-1β, prepared by recombinant DNA technology on cultures of rat fetal long bones, prelabelled with 45 Ca were studied. IL-1β was found to be the most powerful inducer of bone calcium loss so far known. Maximal activity (2.5 times the control rate of calcium loss) was induced by IL-1β at concentrations between 1 x 10 -10 M to 6 x 10 -12 M. With IL-1α maximal activity (1.5 times the control rate of calcium loss) was obtained at 6 x 10 -10 M. With bovine PTH (1-34) maximal activity (1.8 times the control rate of calcium loss) was obtained at 1 x 10 -8 M. With PGE 2 maximal activity (1.6 times the control rate of calcium loss) was obtained at 1 x 10 -7 M. The calcium loss induced by IL-1β was inhibited in the presence of 1 x 10 -7 M indomethacin, 5 x 10 -5 M naproxen or ketorolac, or 5 x 10 -6 M cyclohexamide. These findings suggest that protein synthesis and prostaglandin formation are required to mediate bone demineralization induced by IL-1β
μCT-based, in vivo dynamic bone histomorphometry allows 3D evaluation of the early responses of bone resorption and formation to PTH and alendronate combination therapy.

Science.gov (United States)

de Bakker, Chantal M J; Altman, Allison R; Tseng, Wei-Ju; Tribble, Mary Beth; Li, Connie; Chandra, Abhishek; Qin, Ling; Liu, X Sherry

2015-04-01

Current osteoporosis treatments improve bone mass by increasing net bone formation: anti-resorptive drugs such as bisphosphonates block osteoclast activity, while anabolic agents such as parathyroid hormone (PTH) increase bone remodeling, with a greater effect on formation. Although these drugs are widely used, their role in modulating formation and resorption is not fully understood, due in part to technical limitations in the ability to longitudinally assess bone remodeling. Importantly, it is not known whether or not PTH-induced bone formation is independent of resorption, resulting in controversy over the effectiveness of combination therapies that use both PTH and an anti-resorptive. In this study, we developed a μCT-based, in vivo dynamic bone histomorphometry technique for rat tibiae, and applied this method to longitudinally track changes in bone resorption and formation as a result of treatment with alendronate (ALN), PTH, or combination therapy of both PTH and ALN (PTH+ALN). Correlations between our μCT-based measures of bone formation and measures of bone formation based on calcein-labeled histology (r=0.72-0.83) confirm the accuracy of this method. Bone remodeling parameters measured through μCT-based in vivo dynamic bone histomorphometry indicate an increased rate of bone formation in rats treated with PTH and PTH+ALN, together with a decrease in bone resorption measures in rats treated with ALN and PTH+ALN. These results were further supported by traditional histology-based measurements, suggesting that PTH was able to induce bone formation while bone resorption was suppressed. Copyright © 2014 Elsevier Inc. All rights reserved.
Black bear parathyroid hormone has greater anabolic effects on trabecular bone in dystrophin-deficient mice than in wild type mice.

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Gray, Sarah K; McGee-Lawrence, Meghan E; Sanders, Jennifer L; Condon, Keith W; Tsai, Chung-Jui; Donahue, Seth W

2012-09-01

Duchenne muscular dystrophy (DMD) is an X-linked neuromuscular disease that has deleterious consequences in muscle and bone, leading to decreased mobility, progressive osteoporosis, and premature death. Patients with DMD experience a higher-than-average fracture rate, particularly in the proximal and distal femur and proximal tibia. The dystrophin-deficient mdx mouse is a model of DMD that demonstrates muscle degeneration and fibrosis and osteoporosis. Parathyroid hormone, an effective anabolic agent for post-menopausal and glucocorticoid-induced osteoporosis, has not been explored for DMD. Black bear parathyroid hormone (bbPTH) has been implicated in the maintenance of bone properties during extended periods of disuse (hibernation). We cloned bbPTH and found 9 amino acid residue differences from human PTH. Apoptosis was mitigated and cAMP was activated by bbPTH in osteoblast cultures. We administered 28nmol/kg of bbPTH 1-84 to 4-week old male mdx and wild type mice via daily (5×/week) subcutaneous injection for 6 weeks. Vehicle-treated mdx mice had 44% lower trabecular bone volume fraction than wild type mice. No changes were found in femoral cortical bone geometry or mechanical properties with bbPTH treatment in wild type mice, and only medio-lateral moment of inertia changed with bbPTH treatment in mdx femurs. However, μCT analyses of the trabecular regions of the distal femur and proximal tibia showed marked increases in bone volume fraction with bbPTH treatment, with a greater anabolic response (7-fold increase) in mdx mice than wild type mice (2-fold increase). Trabecular number increased in mdx long bone, but not wild type bone. Additionally, greater osteoblast area and decreased osteoclast area were observed with bbPTH treatment in mdx mice. The heightened response to PTH in mdx bone compared to wild type suggests a link between dystrophin deficiency, altered calcium signaling, and bone. These findings support further investigation of PTH as an anabolic
Parathyroid hormone and bone healing

DEFF Research Database (Denmark)

Ellegaard, M; JÃ¸rgensen, N R; Schwarz, P

2010-01-01

, no pharmacological treatments are available. There is therefore an unmet need for medications that can stimulate bone healing. Parathyroid hormone (PTH) is the first bone anabolic drug approved for the treatment of osteoporosis, and intriguingly a number of animal studies suggest that PTH could be beneficial...
Parathyroid hormone impairs extrarenal potassium tolerance in the rat

International Nuclear Information System (INIS)

Sugarman, A.; Kahn, T.

1988-01-01

The effect of parathyroid hormone (PTH) on the extrarenal disposition of an acute potassium load was examined in acutely nephrectomized rats infused with KCl alone or in combination with PTH, with serial monitoring of plasma potassium every 10 min. The rise in plasma potassium concentration (ΔPK) in the PTH group was higher than control. PTH was then administered along with KCl to two groups of nephrectomized and acutely thyroparathyroidectomized (TPTX) rats in doses of 1 and 0.25 U · kg -1 · min -1 for 90 min. ΔPK with PTH in both groups was higher than TPTX control. The two higher doses of PTH resulted in a decrease in mean arterial pressure from their respective controls. A similar reduction in arterial pressure in three groups of nephrectomized rats by administration of hydralazine or nitroprusside or by acute blood loss did not change ΔPK subsequent to potassium infusion from that in control rats. Furthermore, the lowest dose of PTH did not lower arterial pressure from its respective control. Therefore, hypotension is not a cause for the PTH-induced potassium intolerance. Serum levels of insulin, aldosterone, catecholamines, calcium, plasma HCO 3 concentration, and pH were not different in PTH-infused vs. respective control rats. These data suggest that PTH impairs extrarenal potassium disposal in the rat. The effect of PTH may relate to enhanced calcium entry into cells
Increasing Goat Productivity Through the Improvement of Endogenous Secretion of Pregnant Hormones Using Follicle Stimulating Hormone

Directory of Open Access Journals (Sweden)

Andriyanto Andriyanto

2011-05-01

Full Text Available Abstract. Previous studies reported that the improvement of endogenous estrogen and progesterone secretions during gestation improved fetal prenatal growth, birth weight, mammary gland growth and development, milk production, litter size, pre- and post-weaning growths. An experiment was conducted to apply the improvement of endogenous secretion of pregnant hormones during pregnancy to increase goat productivity. Thirty-six female ettawah-cross does were divided into 2 groups. Group 1 (control: 18 does included does without improvement of endogenous secretion of pregnant hormones and Group 2 (treatment: 18 does included does with improvement of endogenous secretion of pregnant hormones using follicle stimulating hormones to stimulate super ovulation. The application of this technology increased total offspring born (control: 25 offspring; treatment: 42 offspring, average litter size (control: 1.88; treatment: 2.33, offspring birth weight (control: 2.85±0.50 kg; treatment: 3.82±0.40 kg, and does milk production (control: 1.36±0.34 L/does/day; treatment: 2.10±0.21 L/does/day. Offspring born to does with improved endogenous secretion of pregnant hormones had better weaning weight (control: 11.17±1.99 kg/offspring; treatment: 14.5±1.11 kg/offspring. At weaning period, does with improved endogenous secretion of pregnant hormones produced offspring with total weaning weight twice as heavy as control does (control: 189.9 kg; treatment: 403.6 kg. By a simple calculation of economic analysis, this technology application could increase gross revenue per does until weaning by Rp. 432.888,89. It was concluded that this technology is economically feasible to be applied in small-scale farm. Key Words: follicle stimulating hormone, pregnant hormones, endogenous secretion, super ovulation, ettawah-cross does
Clinical application of determination of plasma intact parathyroid hormone content in kidney disease

International Nuclear Information System (INIS)

Zhu Mei; Wang Zhaohui; Zhou Xiaoli; Ren Chunling; Chen Huaqian

2011-01-01

Objective: To observe intact parathyroid hormone in kidney disease with clinical application. Methods: Plasma i-PTH level was measured in 46 patients with chronic renal insufficiency lose compensation stage, 39 patients with chronic renal failure, 35 patients with uremia. Besides, control group (n=41) was established. Results: Result shown that plasma i-PTH levels were experiment group and control group were obvious difference (P<0.01), among experiment group plasma i-PTH level was obvious difference (P<0.01). Conclusion: Results suggested along with renal function were worsen that plasma i-PTH level increasing gradually during renal insufficiency. (authors)
[Bone Cell Biology Assessed by Microscopic Approach. The effect of parathyroid hormone and teriparatide on bone].

Science.gov (United States)

Takahata, Masahiko

2015-10-01

Continuous exposure to parathyroid hormone (PTH) leads to hypercalcemia and a decrease in bone volume, which is referred to as its catabolic effect, while intermittent exogenously administered PTH leads to an anabolic effect on bone. Intermittent administration of PTH dramatically increases bone remodeling and modeling through their direct and indirect effects on the functional cells of bone remodeling units and their precursors. These effects on bone metabolism differ according to dosing frequency of PTH. Therefore, different dosing frequency of PTH shows different therapeutic effects on bone in terms of bone volume and bone quality in patients with osteoporosis.
Reduction of parathyoid hormone levels

DEFF Research Database (Denmark)

2011-01-01

A method of acutely reducing the plasma level of PTH of a patient having an elevated PTH comprising the administration of a pharmaceutical composition comprising a GLP-2, or a variant, an analogue, or derivative of GLP-2 having the ability to bind and activate a GLP-2 receptor such as GLP-2 1-34...
A comparative study of the bone metabolic response to dried plum supplementation and PTH treatment in adult, osteopenic ovariectomized rat.

Science.gov (United States)

Smith, Brenda J; Bu, So Young; Wang, Yan; Rendina, Elizabeth; Lim, Yin F; Marlow, Denver; Clarke, Stephen L; Cullen, Diane M; Lucas, Edralin A

2014-01-01

Dried plum has been reported to have potent effects on bone in osteopenic animal models, but the mechanisms through which bone metabolism is altered in vivo remain unclear. To address this issue, a study comparing the metabolic response of dried plum to the anabolic agent, parathyroid hormone (PTH), was undertaken. Six month-old female Sprague Dawley rats (n=84) were sham-operated (SHAM) or ovariectomized (OVX) and maintained on a control diet for 6wks until osteopenia was confirmed. Treatments were initiated consisting of a control diet (AIN-93M) supplemented with dried plum (0, 5, 15 or 25%; w/w) or a positive control group receiving PTH. At the end of 6wks of treatment, whole body and femoral bone mineral density (BMD) were restored by the two higher doses of dried plum to the level of the SHAM group. Trabecular bone volume and cortical thickness were also improved with these two doses of dried plum. Dried plum suppressed the OVX-induced increase in bone turnover as indicated by systemic biomarkers of bone metabolism, N-terminal procollagen type 1 (P1NP) and deoxypyridinoline (DPD). Dynamic bone histomorphometric analysis of the tibial metaphysis revealed that dried plum restored the OVX-induced increase in cancellous bone formation rate (BFR) and mineralizing surface (MS/BS) to the SHAM group, but some doses of dried plum increased endocortical mineral apposition rate (MAR). As expected, PTH significantly increased endocortical MAR and BFR, periosteal BFR, and trabecular MAR and BFR beyond that of the OVX and maintained the accelerated rate of bone resorption associated with OVX. Dried plum up-regulated bone morphogenetic protein 4 (Bmp4) and insulin-like growth factor 1 (Igf1) while down-regulating nuclear factor T cell activator 1 (Nfatc1). These findings demonstrate that in the adult osteopenic OVX animal, the effects of dried plum differ from that of PTH in that dried plum primarily suppressed bone turnover with the exception of the indices of bone
Arsenic may be involved in fluoride-induced bone toxicity through PTH/PKA/AP1 signaling pathway.

Science.gov (United States)

Zeng, Qi-bing; Xu, Yu-yan; Yu, Xian; Yang, Jun; Hong, Feng; Zhang, Ai-hua

2014-01-01

Chronic exposure to combined fluoride and arsenic continues to be a major public health problem worldwide, affecting thousands of people. In recent years, more and more researchers began to focus on the interaction between the fluorine and the arsenic. In this study, the selected investigation site was located in China. The study group was selected from people living in fluoride-arsenic polluted areas due to burning coal. The total number of participants was 196; including the fluoride-arsenic anomaly group (130) and the fluoride-arsenic normal group (63). By observing the changes in gene and protein expression of PTH/PKA/AP1 signaling pathway, the results show that fluoride can increase the expression levels of PTH, PKA, and AP1, but arsenic can only affect the expression of AP1; fluoride and arsenic have an interaction on the expression of AP1. Further study found that fluoride and arsenic can affect the mRNA expression level of c-fos gene (AP1 family members), and have an interaction on the expression of c-fos, but not c-jun. The results indicate that PTH/PKA/AP1 signaling pathway may play an important role in bone toxicity of fluoride. Arsenic can affect the expression of c-fos, thereby affecting the expression of transcription factor AP1, indirectly involved in fluoride-induced bone toxicity. Copyright © 2013. Published by Elsevier B.V.
Normal epidermal growth factor receptor signaling is dispensable for bone anabolic effects of parathyroid hormone.

Science.gov (United States)

Schneider, Marlon R; Dahlhoff, Maik; Andrukhova, Olena; Grill, Jessica; Glösmann, Martin; Schüler, Christiane; Weber, Karin; Wolf, Eckhard; Erben, Reinhold G

2012-01-01

Although the bone anabolic properties of intermittent parathyroid hormone (PTH) have long been employed in the treatment of osteoporosis, the molecular mechanisms behind this action remain largely unknown. Previous studies showed that PTH increases the expression and the activity of epidermal growth factor receptor (EGFR) in osteoblasts, and activation of ERK1/2 by PTH in osteoblasts was demonstrated to induce the proteolytical release of EGFR ligands and EGFR transactivation. However, conclusive evidence for an important role of the EGFR system in mediating the anabolic actions of intermittent PTH on bone in vivo is lacking. Here, we evaluated the effects of intermittent PTH on bone in Waved-5 (Wa5) mice which carry an antimorphic Egfr allele whose product acts as a dominant negative receptor. Heterozygous Wa5 females and control littermates received a subcutaneous injection of PTH (80 μg/kg) or buffer on 5 days per week for 4 weeks. Wa5 mice had slightly lower total bone mineral density (BMD), but normal cancellous bone volume and turnover in the distal femoral metaphysis. The presence of the antimorphic Egfr allele neither influenced the PTH-induced increase in serum osteocalcin nor the increases in distal femoral BMD, cortical thickness, cancellous bone volume, and cancellous bone formation rate. Similarly, the PTH-induced rise in lumbar vertebral BMD was unchanged in Wa5 relative to wild-type mice. Wa5-derived osteoblasts showed considerably lower basal extracellular signal-regulated kinase 1/2 (ERK1/2) activation as compared to control osteoblasts. Whereas activation of ERK1/2 by the EGFR ligand amphiregulin was largely blocked in Wa5 osteoblasts, treatment with PTH induced ERK1/2 activation comparable to that observed in control osteoblasts, relative to baseline levels. Our data indicate that impairment of EGFR signaling does not affect the anabolic action of intermittent PTH on cancellous and cortical bone. Copyright © 2011. Published by Elsevier Inc.
ATF4, A Novel Mediator of the Anabolic Actions of PTH on Bone

Science.gov (United States)

2008-07-01

pathways. Lastly, PTH stimulation of Ocn expres- sion was lost by silent interfering RNA down-regulation of ATF4 in MC-4 cells and Atf4/ bone marrow...M 2000 Para- thyroid hormone-related protein downregulates bone sialoprotein gene ex- pression in cementoblasts: role of the protein kinase A pathway
Relationship Between Aldosterone and Parathyroid Hormone, and the Effect of Angiotensin and Aldosterone Inhibition on Bone Health

DEFF Research Database (Denmark)

L.S., Bislev; T., Sikjaer; L., Rolighed

2015-01-01

Emerging evidence suggests a stimulating effect of parathyroid hormone (PTH) on the reninnullangiotensinnullaldosterone system (RAAS). In primary hyperparathyroidism, chronic-elevated PTH levels seem to stimulate the RAAS which may explain the increased risk of cardiovascular disease (CVD......). In addition to increased PTH levels, low vitamin D levels may also directly increase risk of CVD, as vitamin D, itself, has been shown to inhibit the RAAS. Angiotensin II, aldosterone and cortisol all negatively impact bone health. Hyperaldosteronism is associated with a reversible secondary...... hyperparathyroidism due to increased renal calcium excretion. Moreover, the angiotensin II receptor is expressed by human parathyroid tissue, and angiotensin may therefore directly stimulates PTH secretion. An increased bone loss is found in patients with hyperaldosteronism. The angiotensin II receptor seems main...
Radioimmunoassay of parathyroid hormone: past and future

International Nuclear Information System (INIS)

Yalow, R.S.

1986-01-01

In this report on radioimmunoassay of parathyroid hormone (iPTH) it was shown that the rate of disappearance of iPTH from plasma differed markedly in patients with primary hyperthyroidism or those with uremia and secondary hyperparathyroidism and that for each patient the rate of disappearance depended on the antiserum used for assay. The heterogeneity of iPTH in plasma was soon rapidly confirmed in many laboratories. (Auth.)
Gene therapy of hypoparathyroidism with TheraCyte-encapsulated stem cells

OpenAIRE

Fong Choulu; Shun-Chen Huang; Kun-Chou Hsieh; Shun-Yu Chi; Pei-Hua Hung; Feng-Sheng Wang

2010-01-01

The parathyroid hormone (PTH) (1-34) gene was inserted into a pcDNA3 promoter and E. coli competent cells were used to amplify the cDNA. C3H/10T1/2 stem cells were transfected with PTH (1-34) cDNA using Lipofectamine reagents. After G418 treatment live cells at a density of 4x107 were loaded onto a TheraCyte unit. After parathyroidectomy, rats were either the implanted with 4x107 TheraCyte-encapsulated cells (group A), subcutaneously injected with 4x107 live cells containing PTH (1-34) cDNA (...
Determination of hormone parathyroid by radioimmunoassay

International Nuclear Information System (INIS)

Fisher-Ferraro, Catalina; Moos de Ephraim, Monica; Mautalen, Carlos; Mitta, A.E.A.

1978-10-01

The labelling of bovine parathyroid hormone and its employment for the determination of seric PTH by radioimmunoanalysis is described. The specific activity of 131 I PTH is 200-350mCi/mg and the damage 3-5%. The method used for radioimmunoanalysis was that of C.D. Arnaud and coworkers. (author) [es
Intra-operative parathyroid hormone measurements – experience of ...

African Journals Online (AJOL)

Background. Surgery is the treatment of choice for symptomatic primary hyperparathyroidism. The majority of research concerning intra-operative parathyroid hormone (ioPTH) measurements is conducted in university hospitals. Whether ioPTH measurements are feasible and useful in predicting the presence of remaining ...
CaPTHUS scoring model in primary hyperparathyroidism: can it eliminate the need for ioPTH testing?

Science.gov (United States)

Elfenbein, Dawn M; Weber, Sara; Schneider, David F; Sippel, Rebecca S; Chen, Herbert

2015-04-01

The CaPTHUS model was reported to have a positive predictive value of 100 % to correctly predict single-gland disease in patients with primary hyperparathyroidism, thus obviating the need for intraoperative parathyroid hormone (ioPTH) testing. We sought to apply the CaPTHUS scoring model in our patient population and assess its utility in predicting long-term biochemical cure. We retrospective reviewed all parathyroidectomies for primary hyperparathyroidism performed at our university hospital from 2003 to 2012. We routinely perform ioPTH testing. Biochemical cure was defined as a normal calcium level at 6 months. A total of 1,421 patients met the inclusion criteria: 78 % of patients had a single adenoma at the time of surgery, 98 % had a normal serum calcium at 1 week postoperatively, and 96 % had a normal serum calcium level 6 months postoperatively. Using the CaPTHUS scoring model, 307 patients (22.5 %) had a score of ≥ 3, with a positive predictive value of 91 % for single adenoma. A CaPTHUS score of ≥ 3 had a positive predictive value of 98 % for biochemical cure at 1 week as well as at 6 months. In our population, where ioPTH testing is used routinely to guide use of bilateral exploration, patients with a preoperative CaPTHUS score of ≥ 3 had good long-term biochemical cure rates. However, the model only predicted adenoma in 91 % of cases. If minimally invasive parathyroidectomy without ioPTH testing had been done for these patients, the cure rate would have dropped from 98 % to an unacceptable 89 %. Even in these patients with high CaPTHUS scores, multigland disease is present in almost 10 %, and ioPTH testing is necessary.
Radioimmunoassays specific for the midregion (44-68) of parathyroid hormone

International Nuclear Information System (INIS)

Mallette, L.E.

1984-01-01

A lot of research has been done for characterization of the regional specificity of radioimunnoassays for Parathyroid Hormone (PTH). The main portion of plasma PTH consists of biologically inactive fragments, with a long half-life compared to active PTH. In this article a midregion-specific radioimmunoassay for PTH is described, the non-specific binding values and plasma creatinine influence are discussed. Finally some plasma measurements of hypo-, hyperparathyroid and hypercalcemic patients are presented. (Auth.)

Parathyroid Hormone Induces Bone Cell Motility and Loss of Mature Osteocyte Phenotype through L-Calcium Channel Dependent and Independent Mechanisms.

Directory of Open Access Journals (Sweden)

Matthew Prideaux

Full Text Available Parathyroid Hormone (PTH can exert both anabolic and catabolic effects on the skeleton, potentially through expression of the PTH type1 receptor (PTH1R, which is highly expressed in osteocytes. To determine the cellular and molecular mechanisms responsible, we examined the effects of PTH on osteoblast to osteocyte differentiation using primary osteocytes and the IDG-SW3 murine cell line, which differentiate from osteoblast to osteocyte-like cells in vitro and express GFP under control of the dentin matrix 1 (Dmp1 promoter. PTH treatment resulted in an increase in some osteoblast and early osteocyte markers and a decrease in mature osteocyte marker expression. The gene expression profile of PTH-treated Day 28 IDG-SW3 cells was similar to PTH treated primary osteocytes. PTH treatment induced striking changes in the morphology of the Dmp1-GFP positive cells in IDG-SW3 cultures and primary cells from Dmp1-GFP transgenic mice. The cells changed from a more dendritic to an elongated morphology and showed increased cell motility. E11/gp38 has been shown to be important for cell migration, however, deletion of the E11/gp38/podoplanin gene had no effect on PTH-induced motility. The effects of PTH on motility were reproduced using cAMP, but not with protein kinase A (PKA, exchange proteins activated by cAMP (Epac, protein kinase C (PKC or phosphatidylinositol-4,5-bisphosphonate 3-kinase (Pi3K agonists nor were they blocked by their antagonists. However, the effects of PTH were mediated through calcium signaling, specifically through L-type channels normally expressed in osteoblasts but decreased in osteocytes. PTH was shown to increase expression of this channel, but decrease the T-type channel that is normally more highly expressed in osteocytes. Inhibition of L-type calcium channel activity attenuated the effects of PTH on cell morphology and motility but did not prevent the downregulation of mature osteocyte marker expression. Taken together, these
Serum ionized calcium, intact PTH and novel markers of bone turnover in bedridden elderly patients.

Science.gov (United States)

Sorva, A; Välimäki, M; Risteli, J; Risteli, L; Elfving, S; Takkunen, H; Tilvis, R

1994-12-01

Chronic immobilization could markedly affect calcium and bone metabolism in elderly people. To investigate this, and to test the theory of 'type II' osteoporosis in bedridden elderly patients with low vitamin D status, 55 such subjects were examined. Serum concentrations of ionized calcium (Ca++), intact parathyrin (PTH) and two novel markers of bone collagen formation (carboxyterminal propeptide of type I procollagen; PICP) and resorption (carboxyterminal crosslinked telopeptide of type I collagen; ICTP) were measured. The effects on these parameters after 40 weeks of supplementation with vitamin D (1000 IU d-1) and/or calcium (1 g d-1) were subsequently prospectively evaluated. Despite low (mean 11.6 nmoll-1) serum 25-hydroxyvitamin D levels (25-OHD), those of 1,25-dihydroxy-vitamin D (1,25-(OH)2D) were mostly normal. Neither correlated with Ca++ or PTH. PTH correlated negatively not only with Ca++ (r = -0.328, P r = -0.306, P r = 0.268, P = 0.06). Vitamin D supplementation did not change PICP or ICTP considerably, despite slightly increased 1,25-(OH)2D and slightly decreased PTH. Ca++ values were normal and remained stable. In conclusion, Ca++ and PTH are poor indicators of vitamin D status in chronically immobilized elderly subjects. Furthermore, the results suggest that the increased bone resorption is not due to 'type II' secondary hyperparathyroidism; rather the resorption is primarily increased. Correction of vitamin D deficiency does not seem to benefit ageing bones unless adequate mechanical loading is provided.
Comparison of calcium carbonate and aluminium hydroxide as phosphate binders on biochemical bone markers, PTH(1-84), and bone mineral content in dialysis patients

DEFF Research Database (Denmark)

Jespersen, B; Jensen, J D; Nielsen, H K

1991-01-01

Bone mineral content, estimated by single-photon absorptiometry of the forearm, serum values of intact parathyroid hormone (PTH(1-84], osteocalcin, alkaline phosphatase, 1,25-dihydroxycholecalciferol (1,25(OH)2D3), and aluminium were determined during treatment with calcium carbonate (CaCO3......) or aluminium hydroxide (Al(OH)3) in 11 dialysis patients participating in a randomised cross-over study. Each treatment period lasted 6 months. Serum phosphorus was maintained in the range 1.5-2.0 mmol/l. During Al(OH)3 treatment bone mineral content (BMC) decreased by 11% per half-year (mean), but only by 3...... 0.05), osteocalcin decreased (89% versus 117%, P less than 0.01), alkaline phosphatase decreased (92% versus 116%, P less than 0.05), and aluminium decreased (56% versus 189%, P less than 0.05). 1,25(OH)2D3 remained unchanged in both periods. No increase in soft-tissue calcification was demonstrated...
Relationship between parathyroid mass and parathyroid hormone level in hemodialysis patients with secondary hyperparathyroidism.

Science.gov (United States)

Fang, Li; Tang, Bing; Hou, Dawei; Meng, Meijuan; Xiong, Mingxia; Yang, Junwei

2015-06-10

To evaluate the influence of parathyroid mass on the regulation of parathyroid hormone (PTH) secretion, we investigated the relationship between the resected parathyroid gland in total parathyroidectomy and the parathyroid hormone level in hemodialysis patients with secondary hyperparathyroidism. From January 2009 to July 2014, 223 patients undergoing total parathyroidectomy were included. The size and the weight of parathyroid gland were measured during the operation. 874 parathyroid glands were removed. A positive correlation was identified between the size and the weight of resected parathyroid glands. We found that both the preoperative PTH and the reduction of PTH were significantly correlated with the size and the weight of parathyroid glands in a positive manner. However, in the subgroup of patients with PTH < 1000 pg/ml, no significant correlation was found. Larger parathyroid gland secretes more PTH and high level of serum PTH usually indicated that surgical removal might be required. However, since PTH levels could be influenced by the pharmaceutical drug, the large size of parathyroid gland might be used as a much more appropriate guide that indicates the requirement of surgery treatment even when the parathyroid hormone was less than 1000 pg/ml.
Parathyroid hormone inhibition of Na{sup +}/H{sup +} exchanger 3 transcription: Intracellular signaling pathways and transcription factor expression

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Neri, Elida Adalgisa; Bezerra, Camila Nogueira Alves, E-mail: camilab@icb.usp.br; Queiroz-Leite, Gabriella Duarte; Polidoro, Juliano Zequini; Rebouças, Nancy Amaral

2015-06-12

The main transport mechanism of reabsorption of sodium bicarbonate and fluid in the renal proximal tubules involves Na{sup +}/H{sup +} exchanger 3 (NHE3), which is acutely and chronically downregulated by parathyroid hormone (PTH). Although PTH is known to exert an inhibitory effect on NHE3 expression and transcription, the molecular mechanisms involved remain unclear. Here, we demonstrated that, in opossum kidney proximal tubule (OKP) cells, PTH-induced inhibition of Nhe3 gene promoter occurs even in the core promoter that controls expression of the reporter gene. We found that inhibition of the protein kinase A (PKA) and Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathways transformed PTH from an inhibitor of promoter activity into an activator of that same activity, as did point mutations in the EGR1, Sp1, and Sp3 binding consensus elements in the promoter. In nuclear extracts of PTH-treated OKP cells, we also observed increased expression of EGR1 mRNA and of some Sp3 isoforms. Electrophoretic mobility shift assay showed a supershift of the −61 to −42-bp probe with an anti-EGR1 antibody in PTH-treated cells, suggesting that EGR1 binding is relevant for the inhibitory activity of PTH. We conclude that PTH-induced inhibition of NHE3 transcription is related to higher EGR1 expression; to EGR1 binding to the proximal and core promoters; and to PKA and JAK/STAT pathway activation. This mechanism might be responsible, at least in part, for lower NHE3 expression and sodium reabsorption in renal proximal tubules in the presence of high PTH levels. - Highlights: • PTH regulation of Nhe3 promoter depends on EGR1 binding. • EGR1, PKA and JAK/STAT are involved in PTH inhibition of the Nhe3 promoter. • PTH alters expression of EGR1 and Sp3. • PTH inhibits the Nhe3 promoter by regulating PKA and JAK/STAT signaling.
Effect of intravenous 1-alpha-hydroxyvitamin D3 on secondary hyperparathyroidism in chronic uremic patients on maintenance hemodialysis

DEFF Research Database (Denmark)

Brandi, L; Daugaard, H; Tvedegaard, E

1989-01-01

The effect of intravenous 1 alpha(OH)D3 on circulating intact parathyroid hormone (PTH) and COOH-terminal immunoreactive PTH was examined in 21 patients on chronic hemodialysis. The patients were treated for 3 months with increasing doses of 1 alpha(OH)D3 under careful control of serum Ca2+. 1 al...
Aldosterone and parathyroid hormone: a precarious couple for cardiovascular disease

NARCIS (Netherlands)

Tomaschitz, A.; Ritz, E.; Pieske, B.; Fahrleitner-Pammer, A.; Kienreich, K.; Horina, J.H.; Drechsler, C.; Marz, W.; Ofner, M.; Pieber, T.R.; Pilz, S.

2012-01-01

Animal and human studies support a clinically relevant interaction between aldosterone and parathyroid hormone (PTH) levels and suggest an impact of the interaction on cardiovascular (CV) health. This review focuses on mechanisms behind the bidirectional interactions between aldosterone and PTH and
Threshold levels of 25-hydroxyvitamin D and parathyroid hormone for impaired bone health in children with congenital ichthyosis and type IV and V skin.

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Sethuraman, G; Sreenivas, V; Yenamandra, V K; Gupta, N; Sharma, V K; Marwaha, R K; Bhari, N; Irshad, M; Kabra, M; Thulkar, S

2015-01-01

Patients with congenital ichthyosis, especially those with darker skin types, are at increased risk of developing vitamin D deficiency and rickets. The relationships between 25-hydroxyvitamin D [25(OH)D], parathyroid hormone (PTH) and bone health have not been studied previously, in ichthyosis. To determine the threshold levels of 25(OH)D and PTH for impaired bone health in children with congenital ichthyosis. In this cross-sectional study, 119 children with ichthyosis and 168 controls were recruited. Serum 25(OH)D, PTH, calcium, phosphate and alkaline phosphatase (ALP) were measured. Radiological screening for rickets was carried out only in children with ichthyosis. Forty-seven children with ichthyosis had either clinical or radiological evidence of rickets. The correlation between serum 25(OH)D and PTH showed that a serum level of 25(OH)D 8 ng mL(-1) was associated with a significant increase in PTH. The correlation between PTH and ALP showed that a serum PTH level of 75 pg mL(-1) was associated with a significant increase in ALP levels. Of the different clinical phenotypes of ichthyosis, both autosomal recessive congenital ichthyosis (ARCI) and epidermolytic ichthyosis (EI) were found to have significantly increased PTH, ALP and radiological rickets scores compared with common ichthyosis. Serum levels of 25(OH)D ≤ 8 ng mL(-1) and PTH ≥ 75 pg mL(-1) significantly increases the risk for development of rickets [odds ratio (OR) 2·8; 95% confidence interval (CI) 1·05-7·40; P = 0·04] in ichthyosis. Among the different types, patients with ARCI (OR 4·83; 95% CI 1·74-13·45; P < 0·01) and EI (OR 5·71; 95% CI 1·74-18·79; P < 0·01) are at an increased risk of developing rickets. © 2014 British Association of Dermatologists.
Serum levels of parathyroid hormone and markers of bone metabolism in patients with rheumatoid arthritis. Relationship to disease activity and glucocorticoid treatment

DEFF Research Database (Denmark)

Jensen, Tonny Joran; Hansen, M; Madsen, J C

2001-01-01

OBJECTIVE: To evaluate the influence of inflammatory activity and glucocorticoid (GC) treatment on serum parathyroid hormone (s-PTH) and bone metabolism in patients with rheumatoid arthritis (RA). Furthermore, in patients with active RA, to examine the PTH secretion and Ca2+ set point before and ....... The increased levels of markers of type I collagen metabolism (s-ICTP, Pyr) and s-AlbCorrCa2+ in patients with active disease and patients treated with GC may be a result of increased degradation in synovium, cartilage and bone due to the inflammatory process.......OBJECTIVE: To evaluate the influence of inflammatory activity and glucocorticoid (GC) treatment on serum parathyroid hormone (s-PTH) and bone metabolism in patients with rheumatoid arthritis (RA). Furthermore, in patients with active RA, to examine the PTH secretion and Ca2+ set point before...... groups. The levels of urine pyridinoline (Pyr) and s-albumin-corrected calcium (s-AlbCorrCa2+) were elevated in patients with active disease and patients treated with GC. S-PTH and s-phosphate were within normal ranges. S-TAP, s-ICTP, Pyr and s-AlbCorrCa2+ correlated positively with indices of disease...
Teriparatide - Indications beyond osteoporosis

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Marilyn Lee Cheng

2012-01-01

Full Text Available Osteoporosis is a condition of impaired bone strength that results in an increased risk of fracture. The current and most popular pharmacological options for the treatment of osteoporosis include antiresorptive therapy, in particular, oral bisphosphonates (alendronate, risedronate, ibandronate. Anabolic agents like teriparatide have widened our therapeutic options. They act by directly stimulating bone formation and improving bone mass quantity and quality. Two forms of recombinant human parathyroid hormone (PTH are available : full-length PTH (PTH 1-84; approved in the EU only and the 1-34 N-terminal active fragment of PTH (teriparatide, US FDA approved. This review aims to discuss the benefits of teriparatide beyond the currently licensed indications like fracture healing, dental stability, osteonecrosis of jaw, hypoparathyroidism, and hypocalcemia.
Nontruncated amino-terminal parathyroid hormone overproduction in two patients with parathyroid carcinoma: a possible link to HRPT2 gene inactivation.

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Caron, Philippe; Simonds, William F; Maiza, Jean-Christophe; Rubin, Mishaela; Cantor, Tom; Rousseau, Louise; Bilezikian, John P; Souberbielle, Jean-Claude; D'Amour, Pierre

2011-06-01

Some patients with parathyroid carcinoma present with an over-production of nontruncated amino-terminal (NT-N) parathyroid hormone (PTH), a post-transcriptionally modified form of PTH(1-84). This is usually picked up on an elevated whole (W) PTH (third-generation)/total (T) (second-generation) PTH assay ratio (N > 0·8). Two parathyroid cancer patients with several episodes of hypercalcaemia and multiple surgeries are described. In both patients, W-PTH, T-PTH and circulating PTH molecular forms separated by high-pressure liquid chromatography (HPLC) were measured with the same assays. qPCR was used to study HRPT2 gene mutation. The first patient had total calcium of 3·8 and 3·22 mmol/l before the fourth and fifth surgeries, and third/second-generation PTH ratios of 2·95 and 3·6, respectively. After the fourth surgery, the ratio remained normal for 1 year and increased progressively to 3·6 over 15 months. This preceded hypercalcaemia by 6 months. The ratio became normal after the fifth surgery. HPLC analysis disclosed an over-expression of NT-N PTH to 82·2% (N < 10%) relative to hPTH(1-84) before the fifth surgery. A deletion of all the tested exons of the HRPT2 gene was identified. In the second patient, W-PTH/T-PTH ratio was 0·89 when serum calcium was 3·3 mmol/l. NT-N PTH was also over-expressed at 51·9%. An inactivating mutation of the HRPT2 gene was also identified. This may suggest that a progressive rise in third/second-generation ratio may have possible clinical utility to monitor parathyroid cancer recurrence. A possible association between NT-N PTH overproduction and HRPT2 gene inactivation is also suggested. © 2011 Blackwell Publishing Ltd.
Serum uric acid is associated with left ventricular hypertrophy independent of serum parathyroid hormone in male cardiac patients.

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Shu-ichi Fujita

Full Text Available BACKGROUND: Several studies have shown that serum uric acid (UA is associated with left ventricular (LV hypertrophy. Serum levels of parathyroid hormone (PTH, which has bbe shown to be correlated with UA, is also known to be associated with cardiac hypertrophy; however, whether the association between UA and cardiac hypertrophy is independent of PTH remains unknown. PURPOSE: We investigated whether the relationship between serum uric acid (UA and LV hypertrophy is independent of intact PTH and other calcium-phosphate metabolism-related factors in cardiac patients. METHODS AND RESULTS: In a retrospective study, the association between UA and left ventricular mass index was assessed among 116 male cardiac patients (mean age 65 ± 12 years who were not taking UA lowering drugs. The median UA value was 5.9 mg/dL. Neither age nor body mass index differed significantly among the UA quartile groups. Patients with higher UA levels were more likely to be taking loop diuretics. UA showed a significant correlation with intact PTH (R = 0.34, P<0.001 but not with other calcium-phosphate metabolism-related factors. Linear regression analysis showed that log-transformed UA showed a significant association with left ventricular mass index, and this relationship was found to be significant exclusively in patients who were not taking loop and/or thiazide diuretics. Multivariate logistic regression analysis showed that log-transformed UA was independently associated with LV hypertrophy with an odds ratio of 2.79 (95% confidence interval 1.48-5.28, P = 0.002 per one standard deviation increase. CONCLUSIONS: Among cardiac patients, serum UA was associated with LV hypertrophy, and this relationship was, at least in part, independent of intact PTH levels, which showed a significant correlation with UA in the same population.
Falls relate to vitamin D and parathyroid hormone in an Australian nursing home and hostel.

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Stein, M S; Wark, J D; Scherer, S C; Walton, S L; Chick, P; Di Carlantonio, M; Zajac, J D; Flicker, L

1999-10-01

To determine whether falling relates to serum levels of vitamin D and parathyroid hormone. A cross-sectional study with retrospective analysis. An aged-care institution in Melbourne Australia. Ambulant nursing home and hostel residents (n = 83). Frequency of falling, frequency of going outdoors, use of cane or walker, age, sex, weight, type of accommodation, and duration of residence. Serum concentrations of 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, and parathyroid hormone (PTH). Plasma concentrations of albumin, calcium, phosphate, and creatinine. Use of furosemide or non-benzodiazepine anticonvulsants. Median age of residents was 84 years. The cohort was vitamin D deficient with a median (interquartile range) 25-hydroxyvitamin D level of 27 (18-37) nmol/L (one-third the reference range median), P falling, higher serum PTH remained independently associated with falling, with an odds ratio (95% confidence interval) for falling of 5.6 (1.7-18.5) per unit of the natural logarithm of serum PTH. Other terms in the regression were hostel accommodation, odds ratio .04 (.01-.25), and ability to walk without aids, odds ratio .07 (.01-.37). In ambulant nursing home and hostel residents, residents who fall have lower serum 25-hydroxyvitamin D and higher serum parathyroid hormone levels than other residents. The association between falling and serum PTH persists after adjustment for other variables.
Parathyroid Hormone Levels and Cognition

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Burnett, J.; Smith, S.M.; Aung, K.; Dyer, C.

2009-01-01

Hyperparathyroidism is a well-recognized cause of impaired cognition due to hypercalcemia. However, recent studies have suggested that perhaps parathyroid hormone itself plays a role in cognition, especially executive dysfunction. The purpose of this study was to explore the relationship of parathyroid hormone levels in a study cohort of elders with impaied cognition. Methods: Sixty community-living adults, 65 years of age and older, reported to Adult Protective Services for self-neglect and 55 controls matched (on age, ethnicity, gender and socio-economic status) consented and participated in this study. The research team conducted in-home comprehensive geriatric assessments which included the Mini-mental state exam (MMSE), the 15-item geriatric depression scale (GDS) , the Wolf-Klein clock test and a comprehensive nutritional panel, which included parathyroid hormone and ionized calcium. Students t tests and linear regression analyses were performed to assess for bivariate associations. Results: Self-neglecters (M = 73.73, sd=48.4) had significantly higher PTH levels compared to controls (M =47.59, sd=28.7; t=3.59, df=98.94, plevels. Overall, PTH was correlated with the MMSE (r=-.323, p=.001). Individual regression analyses revealed a statistically significant correlation between PTH and MMSE in the self-neglect group (r=-.298, p=.024) and this remained significant after controlling for ionized calcium levels in the regression. No significant associations were revealed in the control group or among any of the other cognitive measures. Conclusion: Parathyroid hormone may be associated with cognitive performance.
Role of parathyroid hormone in determination of fat mass in patients with Vitamin D deficiency

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Raman K Marwaha

2017-01-01

Full Text Available Background: Obesity has become a global epidemic and it is rising is Asia. Vitamin D deficiency (VDD is widely prevalent in the Indian subcontinent. Studies have linked VDD to obesity and shown correlation between parathyroid hormone (PTH, 25-hydroxy Vitamin D (25(OHD, and fat mass (FM. However, studies on the role of PTH among subjects with VDD are lacking. Objective: The objective of this study is to study the role of PTH in the determination of FM in participants with VDD. Subjects: Five hundred and fifty-one adults (m:247, f:304 were included in this study. Materials and Methods: Total and regional (trunk, arm, and leg FM was assessed by dual X-ray absorptometry. Biochemical and hormonal parameters such as calcium, phosphorus, alkaline phosphatase, ionic calcium, 25(OHD, and PTH were also analyzed. Results: The mean age of the study population was 58.8 ± 15.8 years (Male: [63.3 ± 13.1], Female: [55.2 ± 16.9]. FM and body mass index were significantly lower in females with higher levels of serum 25(OHD. Total FM was negatively correlated with serum 25(OHD (r = −0.363, P < 0.0001 and positively correlated with serum PTH (r: 0.262, P < 0.0001 in females only. Females with VDD and secondary hyperparathyroidism had higher FM than those with normal PTH. Conclusions: Females with VDD had higher total and regional FM. However, this correlation was evident only in those with high serum PTH levels, suggesting a potential role of PTH in the accumulation of FM.
Current Nomenclature of Pseudohypoparathyroidism: Inactivating Parathyroid Hormone/Parathyroid Hormone-Related Protein Signaling Disorder.

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Turan, Serap

2017-12-30

Disorders related to parathyroid hormone (PTH) resistance and PTH signaling pathway impairment are historically classified under the term of pseudohypoparathyroidism (PHP). The disease was first described and named by Fuller Albright and colleagues in 1942. Albright hereditary osteodystrophy (AHO) is described as an associated clinical entity with PHP, characterized by brachydactyly, subcutaneous ossifications, round face, short stature and a stocky build. The classification of PHP is further divided into PHP-Ia, pseudo-PHP (pPHP), PHP-Ib, PHP-Ic and PHP-II according to the presence or absence of AHO, together with an in vivo response to exogenous PTH and the measurement of Gsα protein activity in peripheral erythrocyte membranes in vitro. However, PHP classification fails to differentiate all patients with different clinical and molecular findings for PHP subtypes and classification become more complicated with more recent molecular characterization and new forms having been identified. So far, new classifications have been established by the EuroPHP network to cover all disorders of the PTH receptor and its signaling pathway. Inactivating PTH/PTH-related protein signaling disorder (iPPSD) is the new name proposed for a group of these disorders and which can be further divided into subtypes - iPPSD1 to iPPSD6. These are termed, starting from PTH receptor inactivation mutation (Eiken and Blomstrand dysplasia) as iPPSD1, inactivating Gsα mutations (PHP-Ia, PHP-Ic and pPHP) as iPPSD2, loss of methylation of GNAS DMRs (PHP-Ib) as iPPSD3, PRKAR1A mutations (acrodysostosis type 1) as iPPSD4, PDE4D mutations (acrodysostosis type 2) as iPPSD5 and PDE3A mutations (autosomal dominant hypertension with brachydactyly) as iPPSD6. iPPSDx is reserved for unknown molecular defects and iPPSDn+1 for new molecular defects which are yet to be described. With these new classifications, the aim is to clarify the borders of each different subtype of disease and make the classification
Parathyroid Hormone Levels and Cognition

Science.gov (United States)

Burnett, J.; Smith, S.M.; Aung, K.; Dyer, C.

2009-01-01

Hyperparathyroidism is a well-recognized cause of impaired cognition due to hypercalcemia. However, recent studies have suggested that perhaps parathyroid hormone itself plays a role in cognition, especially executive dysfunction. The purpose of this study was to explore the relationship of parathyroid hormone levels in a study cohort of elders with impaied cognition. Methods: Sixty community-living adults, 65 years of age and older, reported to Adult Protective Services for self-neglect and 55 controls matched (on age, ethnicity, gender and socio-economic status) consented and participated in this study. The research team conducted in-home comprehensive geriatric assessments which included the Mini-mental state exam (MMSE), the 15-item geriatric depression scale (GDS) , the Wolf-Klein clock test and a comprehensive nutritional panel, which included parathyroid hormone and ionized calcium. Students t tests and linear regression analyses were performed to assess for bivariate associations. Results: Self-neglecters (M = 73.73, sd=48.4) had significantly higher PTH levels compared to controls (M =47.59, sd=28.7; t=3.59, df=98.94, p<.01). There was no significant group difference in ionized calcium levels. Overall, PTH was correlated with the MMSE (r=-.323, p=.001). Individual regression analyses revealed a statistically significant correlation between PTH and MMSE in the self-neglect group (r=-.298, p=.024) and this remained significant after controlling for ionized calcium levels in the regression. No significant associations were revealed in the control group or among any of the other cognitive measures. Conclusion: Parathyroid hormone may be associated with cognitive performance.
Parathyroid hormone secretion in chronic renal failure

DEFF Research Database (Denmark)

Madsen, J C; Rasmussen, A Q; Ladefoged, S D

1996-01-01

The aim of study was to introduce and evaluate a method for quantifying the parathyroid hormone (PTH) secretion during hemodialysis in secondary hyperparathyroidism due to end-stage renal failure. We developed a method suitable for inducing sequential hypocalcemia and hypercalcemia during....../ionized calcium curves were constructed, and a mean calcium set-point of 1.16 mmol/liter was estimated compared to the normal mean of about 1.13 mmol/liter. In conclusion, we demonstrate that it is important to use a standardized method to evaluate parathyroid hormone dynamics in chronic renal failure. By the use...
Insulin-like growth factor I is required for the anabolic actions of parathyroid hormone on mouse bone

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Bikle, Daniel D.; Sakata, Takeshi; Leary, Colin; Elalieh, Hashem; Ginzinger, David; Rosen, Clifford J.; Beamer, Wesley; Majumdar, Sharmila; Halloran, Bernard P.

2002-01-01

Parathyroid hormone (PTH) is a potent anabolic agent for bone, but the mechanism(s) by which it works remains imperfectly understood. Previous studies have indicated that PTH stimulates insulin-like growth factor (IGF) I production, but it remains uncertain whether IGF-I mediates some or all of the skeletal actions of PTH. To address this question, we examined the skeletal response to PTH in IGF-I-deficient (knockout [k/o]) mice. These mice and their normal littermates (NLMs) were given daily injections of PTH (80 microg/kg) or vehicle for 2 weeks after which their tibias were examined for fat-free weight (FFW), bone mineral content, bone structure, and bone formation rate (BFR), and their femurs were assessed for mRNA levels of osteoblast differentiation markers. In wild-type mice, PTH increased FFW, periosteal BFR, and cortical thickness (C.Th) of the proximal tibia while reducing trabecular bone volume (BV); these responses were not seen in the k/o mice. The k/o mice had normal mRNA levels of the PTH receptor and increased mRNA levels of the IGF-I receptor but markedly reduced basal mRNA levels of the osteoblast markers. Surprisingly, these mRNAs in the k/o bones increased several-fold more in response to PTH than the mRNAs in the bones from their wild-type littermates. These results indicate that IGF-I is required for the anabolic actions of PTH on bone formation, but the defect lies distal to the initial response of the osteoblast to PTH.
Establishment of reference values in a healthy population and interpretation of serum PTH concentrations in hemodialyzed patients according to the KDIGO Guidelines using the Lumipulse® G whole PTH (3rd generation) assay.

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Cavalier, Etienne; Salsé, Margot; Dupuy, Anne-Marie; Bargnoux, Anne-Sophie; Watar, Florence; Souberbielle, Jean-Claude; Delanaye, Pierre; Cristol, Jean-Paul

2018-04-01

3rd generation PTH assays only detect the bioactive 1-84 fragment. Since standardization is still lacking, each new PTH assay requires to establish reference values and to assess the impact in the medical care of the mineral and bone disorders in hemodialyzed patients. Using Fujirebio Lumipulse G wPTH assay, serum PTH levels were measured in a population of 439 healthy subjects from France and Belgium PTH levels were also determined in 119 hemodialyzed patients. These patients were classified according to the KDIGO recommendation. Reference range was found to be 6.5 (90%CI: 6.0-7.0) - 41.8 (90% CI: 38.1-43.7). In hemodialysis patients, Passing-Bablock regression between 3rd generation PTH from Fujirebio and DiaSorin was DiaSorin = 1.01 xFujirebio-2.4 with a slope not different from 1.0(95%CI: 0.96-1.04) and a non-significant intercept, ranging from -6.0 to 0.1. Hemodialysis patients with a PTH concentration below 2-fold the Upper Limit of Normality (ULN), within the KDIGO range and upper 9-fold upper limit were respectively 33.6%, 54.6%, 11.8% (Fujirebio Lumipulse) and 36.1%, 51.3% and 12.6% (Diasorin Liaison). We determined a reference range with the 3rd generation PTH assay from Fujirebio. In a hemodialysis population, 3rd generation assays from Fujirebio and DiaSorin provide similar results. To the best of our knowledge, this is the first time that we can show similar PTH results obtained by 2 different 3rd generation PTH assays in healthy subjects and hemodialyzed patients without mathematically processing them. Copyright © 2018 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

High dose ESAs are associated with high iPTH levels in hemodialysis patients with end-stage kidney disease: a retrospective analysis

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Lan eChen

2015-11-01

Full Text Available Objective: Anemia and secondary hyperparathyroidism are the two most common complications associated with chronic kidney disease (CKD. Erythropoiesis-stimulating agents (ESAs are widely used in the management of anemia in hemodialysis patients. A reverse correlation has been established between hyperparathyroidism and hemoglobin levels. The aim of this retrospective study is to evaluate the relationship of high dose ESAs and hyperparathyroidism in hemodialysis patients with anemia. Methods: A total of 240 uremic patients maintained on regular hemodialysis were enrolled into this study. Among them, 142 patients were treated with Epiao® (epoetin-alfa and 98 patients were treated with Recormon® (epoetin-beta. The target hemoglobin concentration was 110-130 g/L. Laboratory measurements including hemoglobin, calcium, phosphorus, albumin, intact-parathyroid hormone (iPTH, serum ferritin and transferrin saturation were collected. Results: Hemoglobin concentration increased as iPTH level decreased by stratification. However, no significant association between anemia and calcium or phosphorus level was found. Patients with iPTH levels within 150-300 pg/mL had the highest levels of hemoglobin, serum ferritin and transferrin saturation. Patients treated with Recormon and Epiao had similar hemoglobin concentrations. However, the dose of Recormon for anemia treatment was significantly less than that the dose of Epiao (P<0.05. The level of iPTH in the Recormon group was significantly lower than in the Epiao group. In patients with hemoglobin levels between 110-130 g/L (P<0.05, iPTH level was found to be significantly lower in patients treated with lower doses of ESAs than in patients treated with higher doses of ESAs, no matter which ESA was used (Recormon or Epiao, P<0.05. Conclusions: The dose of ESAs might be positively associated with iPTH level, suggesting that a reasonable hemoglobin target can be achieved by using the lowest possible ESA dose.
Increased follicle-stimulating hormone is associated with higher assisted reproduction use after vasectomy reversal.

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Hsiao, Wayland; Sultan, Raymond; Lee, Richard; Goldstein, Marc

2011-06-01

Of men with vasectomy 6% elect to have more children. When considering vasectomy reversal vs in vitro fertilization/intracytoplasmic sperm injection, an elucidation of preoperative factors that predict surgical success would help determine appropriate management. We tested the hypothesis that preoperative follicle-stimulating hormone 10 U/l or greater predict a lower paternity rate after vasectomy reversal. Using preoperative follicle-stimulating hormone levels we retrospectively reviewed the records of patients who underwent vasectomy reversal. Follicle-stimulating hormone was measured in cases suspicious for impaired spermatogenesis. The final analysis included 206 men, who were divided by follicle-stimulating hormone less than 10 U/l (normal in 155) and 10 U/l or greater (high in 51). Nominal logistic regression was performed to evaluate assisted reproduction predictors. Mean ± SD follicle-stimulating hormone in the normal and high groups was 5.1 ± 2.2 and 16.2 ± 6.2 U/l, respectively. Postoperative semen parameters were similar. However, in the high hormone group there was greater use of any type of assisted reproduction (78.4% vs 54.8%, p = 0.0028). On multivariate analysis follicle-stimulating hormone 10 U/l or greater (OR 3.02, 95% CI 1.34-6.83) and vasoepididymostomy that was bilateral or to a solitary testis (OR 3.26, 95% CI 1.09-9.69) was associated with greater assisted reproduction use. We evaluated preoperative follicle-stimulating hormone as a predictor of reproductive outcome in men with suspected subfertility who underwent vasectomy reversal. Increased follicle-stimulating hormone was associated with a higher rate of assisted reproduction even after controlling for confounding covariates. Thus, men with increased follicle-stimulating hormone should be counseled on the increased likelihood of needing assisted reproduction to achieve pregnancy after vasectomy reversal. Copyright © 2011 American Urological Association Education and Research, Inc
Study of Red Cell Fragility in Different Stages of Chronic Kidney Disease in Relation to Parathyroid Hormone.

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Panda, Suchismita; Mishra, Anuva; Jena, Manoranjan; Rout, Sashi Bhusan; Mohapatra, Srikrushna

2017-08-01

Anaemia is one of the common complications associated with Chronic Kidney Disease (CKD) responsible for the increase in the morbidity and mortality in such patients. Several factors have been attributed to cause renal anaemia, amongst which hyperparathyroidism is one of the less recognised reasons. Most studies have been conducted in this regard in CKD patients undergoing haemodialysis. The level of PTH in early stages of chronic kidney disease has not been much studied. The excess amount of Parathyroid Hormone (PTH) secondary to CKD has been suggested to be a causative factor for anaemia. To evaluate the serum PTH level in CKD patients before haemodialysis and to study the association of the haemoglobin status with the parathyroid hormone. Forty CKD patients above 18 years of age before haemodialysis and 25 age and sex matched healthy controls were included in the study. Routine biochemical and haematological parameters such as Routine Blood Sugar (RBS), urea, creatinine, Na + , K + , Ca 2+ , PTH and Hb% were perfomed. Red cell osmotic fragility was measured by serial dilutions of whole blood with varying concentrations of sodium chloride ranging from 0.1% to 0.9%. The study revealed a significant fall in Hb%, along with a rise in Median Osmotic Fragility (MOF) and PTH in the CKD patients when compared to the control group. Linear regression of PTH with Hb% revealed significant negative association between both the parameters with a R 2 value of 0.677. Multilinear regression analysis of MOF and other independent variables such as Hb%, Na + , K + , Ca 2+ , urea, PTH and creatinine highlighted the variance of MOF by 72%, maximal variance contributed by PTH. Receiver Operating Curve (ROC) analysis revealed an area under the curve of 0.980 with a sensitivity of 100% and specificity of 87% in detecting osmotic fragility at a cut off value of PTH ≥100 pg/ml. The underlying cause of anaemia should be identified early in the CKD patients before haemodialysis. Secondary
Ihh and PTH1R signaling in limb mesenchyme is required for proper segmentation and subsequent formation and growth of digit bones.

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Amano, Katsuhiko; Densmore, Michael; Fan, Yi; Lanske, Beate

2016-02-01

Digit formation is a process, which requires the proper segmentation, formation and growth of phalangeal bones and is precisely regulated by several important factors. One such factor is Ihh, a gene linked to BDA1 and distal symphalangism in humans. In existing mouse models, mutations in Ihh have been shown to cause multiple synostosis in the digits but lead to perinatal lethality. To better study the exact biological and pathological events which occur in these fused digits, we used a more viable Prx1-Cre;Ihh(fl/fl) model in which Cre recombinase is expressed during mesenchymal condensation in the earliest limb buds at E9.5 dpc and found that mutant digits continuously fuse postnatally until phalanges are finally replaced by an unsegmented "one-stick bone". Mutant mice displayed osteocalcin-positive mature osteoblasts, but had reduced proliferation and abnormal osteogenesis. Because of the close interaction between Ihh and PTHrP during endochondral ossification, we also examined the digits of Prx1-Cre;PTH1R(fl/fl) mice, where the receptor for PTHrP was conditionally deleted. Surprisingly, we found PTH1R deletion caused symphalangism, demonstrating another novel function of PTH1R signaling in digit formation. We characterized the symphalangism process whereby initial cartilaginous fusion prevented epiphyseal growth plate formation, resulting in resorption and replacement of the remaining cartilage by bony tissue. Chondrocyte differentiation displayed abnormal directionality in both mutants. Lastly, Prx1-Cre;Ihh(fl/fl);Jansen Tg mice, in which a constitutively active PTH1R allele was introduced into Ihh mutants, were established to address the possible involvement of PTH1R signaling in Ihh mutant digits. These rescue mice failed to show significantly improved phenotype, suggesting that PTH1R signaling in chondrocytes is not sufficient to restore digit formation. Our results demonstrate that Ihh and PTH1R signaling in limb mesenchyme are both essential to regulate
Serum Parathyroid Hormone Is a New Potential Risk Factor in Multiple Myeloma

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Min-Gu Kang

2014-01-01

Full Text Available We hypothesized that serum PTH might be associated with various clinicopathological parameters in multiple myeloma (MM. So we investigated the implications of serum PTH in MM patients and the relationship with other risk factors of MM. A total of 115 patients who were newly diagnosed with MM were enrolled. Serum PTH level was 24.7 ± 34.9 (ranged 0.0–284.1 pg/mL. Serum levels of IgG, IgM, FLC-lambda, albumin, and LDH were in positive correlation with serum PTH. Compared to non-high PTH (<68.3 pg/mL group, the hazard ratio (HR for overall survival was higher for group with high PTH level (≥68.3 pg/mL (HR, 1.710. Furthermore, the patient group with high PTH level showed inferior progression-free survival than non-high PTH group (P=0.056. Interestingly, subgroup analysis showed that serum PTH level at diagnosis was associated with risk factors and clinical outcome in MM patients, especially in complete remission group, transplantation cases, ISS stage II cases, and cases without chromosome abnormality. In conclusion, this study showed that blood PTH level in MM at diagnosis was associated with risk factors and clinical outcome in MM patients.
Vitamin D and parathyroid hormone are associated with gait instability and poor balance performance in mid-age to older aged women.

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Bird, Marie-Louise; El Haber, Natalie; Batchelor, Frances; Hill, Keith; Wark, John D

2018-01-01

Vitamin D status and parathyroid hormone (PTH) levels influence the risk of accidental falls in older people, but the mechanisms underlying this effect remain unclear. Investigate the relationship between circulating PTH and 25 hydroxyvitamin D (25-OHD) levels and clinical tests of gait stability and balance as physical fall risk factors. We hypothesized that high levels of PTH and low 25-OHD levels would be significantly associated with gait stability and decreased balance performance. Observational cohort study. Australian community. 119 healthy, ambulatory female twin adults aged 47-80 years residing in Victoria, Australia. Serum PTH and 25-OHD levels with clinical tests of gait stability [double support duration (DSD)] and dynamic balance (Step Test). Associations were investigated by regression analysis and by comparing groups divided by tertiles of PTH (4.9pmol/L) and 25-OHD (75 nmol/L) using analysis of variance. Serum PTH was associated positively with DSD, with an increase of 10.6-15.7% when the mid and highest PTH tertiles were compared to the lowest tertile (p <0.025) when 25-OHD was included in the regression analysis. 25-OHD was significantly associated with DSD (greater by 10.6-11.1% when lowest and mid-tertiles compared with the highest 25-OHD tertile) (p <0.025) and dynamic balance (better performance by 12.6% in the highest compared with the lowest 25OHD tertile) (p <0.025). These findings reveal an important new relationship between parathyroid hormone and gait stability parameters and add to understanding of the role of 25-OHD in motor control of gait and dynamic balance in community-dwelling women across a wide age span. Copyright © 2017 Elsevier B.V. All rights reserved.
Parathyroid hormone blocks the stimulatory effect of insulin-like growth factor-I on collagen synthesis in cultured 21-day fetal rat calvariae

International Nuclear Information System (INIS)

Kream, B.E.; Petersen, D.N.; Raisz, L.G.

1990-01-01

We examined the interaction of parathyroid hormone (PTH) and recombinant human insulin-like growth factor I (IGF-I) on collagen synthesis in 21-day fetal rat calvariae as assessed by measuring the incorporation of [ 3 H]proline into collagenase-digestible protein. After 96 hours of culture, 10 nM PTH antagonized the stimulation of collagen synthesis and partially blocked the increase in dry weight produced by 10 nM IGF-I. The effect of PTH to block IGF-I stimulated collagen synthesis was observed in the central bone of calvariae and was mimicked by forskolin and phorbol 12-myristate 13-acetate, but not by 1,25-dihydroxyvitamin D3, transforming growth factor-alpha or dexamethasone. Our data are consistent with the concept that the direct effect of PTH is to inhibit basal CDP labeling and fully oppose IGF-I stimulated CDP labeling. The finding that this effect of PTH is mimicked by forskolin and PMA suggests that this block in IGF-I stimulation of CDP labeling involves both cAMP and protein kinase C mediated pathways
Parathyroid hormone in renal transplanted recipients; a single center study

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Nasri Hamid

2013-01-01

Full Text Available This investigation, aimed to study of intact parathormone (iPTH and calcium (Ca in a group of kidney transplanted patients and also we aimed to test the relationship of iPTH with various demographic data of kidney transplanted recipients. We studied 72 kidney transplanted persons with mean ages of 44±12 years. In this study, mean iPTH was 18.4±8.2 Pg/mL (median=16.5. A negative correlation of iPTH with creatinine clearance (r=-0.44, p0.05. In contrast to previous findings, in our patients, there was not secondary hyperparathyroidism. The results revealed suppressed PTH secretion. The reason may be due to excessive intake of calcium and Vitamin D analogues, which may suppress parathyroid hormone secretion.
[Relation between parathyroid hormone and cardiovascular risk in patients with vitamin D deficiency].

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Casado Cerrada, Jesús; Parra Caballero, Pedro; Vega Piris, Lorena; Suárez Fernández, Carmen

2013-10-05

Vitamin D deficiency and parathyroid hormone (PTH) are associated with an increased cardiovascular risk and arterial stiffness. The aim of our study is to compare the cardiovascular risk in subjects with low vitamin D, attending to the PTH concentration, as well as evaluating the response after administration of vitamin D. Prospective study of patients with a concentration of 25(OH)-vitamin D below 30nmol/l. We evaluated vascular risk parameters as blood pressure, arterial stiffness, lipid profile and glucose metabolism. Patients received vitamin D supplements for 3 months, after which the previous parameters were reassessed. A total of 32 patients were included. Those with PTH over 65pg/ml were older, had worse renal function, higher systolic blood pressure, pulse pressure and arterial stiffness. Treatment with vitamin D showed a statistically significant trend to lower blood pressure and pulse wave velocity. The increase in PTH in patients with low vitamin D involves poor control of blood pressure and increased vascular stiffness. Vitamin D replacement shows a tendency to reduce these parameters. Copyright © 2012 Elsevier España, S.L. All rights reserved.
Maximizing PTH Anabolic Osteoporosis Therapy

Science.gov (United States)

2015-09-01

to PTH might be weakened in these mice, it may not disappear since the persistent increased lymphocyte number would provide extra Wnt10b. We have...might be weakened in the Nmp4-/- mice, it may not disappear since the persistent 593 increased lymphocyte number might provide extra Wnt10b as a...loci including the chromosome number 965 and nucleotide interval are indicated. Read scales are indicated on the Y-axis. An arrow indicates the 966
Vitamin D, parathyroid hormone and cardiovascular risk: the good, the bad and the ugly.

Science.gov (United States)

Pascale, Antonietta V; Finelli, Rosa; Giannotti, Rocco; Visco, Valeria; Fabbricatore, Davide; Matula, Ida; Mazzeo, Pietro; Ragosa, Nicola; Massari, Angelo; Izzo, Raffaele; Coscioni, Enrico; Illario, Maddalena; Ciccarelli, Michele; Trimarco, Bruno; Iaccarino, Guido

2018-02-01

: 25-Hydroxyvitamin D insufficiency and increased cardiovascular risk (CVR) association is still debated. The vitamin D (VitD)-dependent parathyroid hormone (PTH) is considered as the possible actuator of VitD effects on CVR. To investigate the association of CVR, PTH and VitD, we carried out blood pressure measurements and blood samples and collected information on dietary habits, anamnestic, clinical and metabolic data of 451 participants in the Salerno area (Southern Italy) during the World Hypertension Day (17 May). CVR was calculated according to the Framingham CVR charts. The overall population mean age was 51.6 ± 0.7 years, and female sex was slightly prevalent (55%). VitD deficiency (<20 ng/ml) was most frequent (59.7%). In this population, VitD and CVR did not correlate. VitD and PTH inversely correlated (r = -0.265, P < 0.001) as expected. PTH was in direct correlation (r = 0.225, P < 0.001) with CVR. Elevated PTH (75 percentile; ≥49.5 pg/ml) levels identify a population with higher CVR (11.8 ± 0.5 vs. 8.5 ± 0.3, P < 0.001). In a multivariate analysis, both age and PTH correlate to CVR, but not VitD. In conclusion, VitD does not directly affect CVR in the overall population. Rather, increased PTH might be a better predictor of CVR.
BIOCHEMICAL MARKERS OF BONE RESORPTION AND HORMONAL REGULATION OF BONE METABOLISM FOLLOWING LIVER TRANSPLANTATION

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V. P. Buzulina

2013-01-01

Full Text Available Aim. Comparative evaluation of two biochemical markers of bone resorption and hormonal regulation of bone metabolism in liver recipients. Methods and results. Bоne densitometry of L2–L4 and neck of femur, serum level of some hormones (PTH, vitamin D3, estradiol, testosterone regulating osteoclastogenesis as well as com- parative analyses of two bone resorption markers β-crosslaps and tartrate-resistant acid phosphatase type 5b (TRAP-5b were fulfilled in patients after orthotopic liver transplantation (OLT. In 1 month after OLT bone density reduction of L2–L4 and neck of femur; decrease of vitamin D3, estradiol in women, testosterone in men and increase levels of bone resorption markers were observed. In 1 and 2 years after OLT the rise of bone density, increased levels of PTH, estradiol, testosterone and decreased β-crosslaps levels were revealed, while vitamin D3 and TRAP-5b levels remained stable. Conclusion. TRAP-5b was found to be a more speciffic marker of bone resorption, independent from collagen metabolism in liver. Osteoporosis defined in long-term period after OLT was associated with higher TRAP-5b and revialed in women with low estradiol level.
Mechanisms of Normalisation of Bone Metabolism during Recovery from Hyperthyroidism: Potential Role for Sclerostin and Parathyroid Hormone

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Elżbieta Skowrońska-Jóźwiak

2015-01-01

Full Text Available Sclerostin, a protein expressed by osteocytes, is a negative regulator of bone formation. The aim of the study was to investigate the relationship between parathyroid hormone (PTH and markers of bone metabolism and changes of sclerostin concentrations before and after treatment of hyperthyroidism. Patients and Methods. The study involved 33 patients (26 women, age (mean ± SD 48 ± 15 years, with hyperthyroidism. Serum sclerostin, PTH, calcium, and bone markers [osteocalcin (OC and collagen type I cross-linked C-telopeptide I (CTX] were measured at diagnosis of hyperthyroidism and after treatment with thiamazole. Results. After treatment of hyperthyroidism a significant decrease in free T3 (FT3 and free T4 (FT4 concentrations was accompanied by marked decrease of serum sclerostin (from 43.7 ± 29.3 to 28.1 ± 18.4 pmol/L; p<0.001, OC (from 35.6 ± 22.0 to 27.0 ± 14.3 ng/mL; p<0.001, and CTX (from 0.49 ± 0.35 to 0.35 ± 0.23 ng/dL; p<0.005, accompanied by an increase of PTH (from 29.3 ± 14.9 to 39.8 ± 19.8; p<0.001. During hyperthyroidism there was a positive correlation between sclerostin and CTX (rs=0.41, p<0.05 and between OC and thyroid hormones (with FT3 rs=0.42, with FT4 rs=0.45, p<0.05. Conclusions. Successful treatment of hyperthyroidism results in a significant decrease in serum sclerostin and bone markers concentrations, accompanied by an increase of PTH.
Differences between hospitals in attainment of parathyroid hormone treatment targets in chronic kidney disease do not reflect differences in quality of care.

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Peeters, Mieke J; van Zuilen, Arjan D; van den Brand, Jan A J G; Blankestijn, Peter J; ten Dam, Marc A G J; Wetzels, Jack F M

2012-08-06

Transparency in quality of care (QoC) is stimulated and hospitals are compared and judged on the basis of indicators of performance on specific treatment targets. In patients with chronic kidney disease, QoC differed significantly between hospitals. In this analysis we explored additional parameters to explain differences between centers in attainment of parathyroid hormone (PTH) treatment targets. Using MASTERPLAN baseline data, we selected one of the worst (center A) and one of the best (center B) performing hospitals. Differences between the two centers were analyzed from the year prior to start of the MASTERPLAN study until the baseline evaluation. Determinants of PTH were assessed. 101 patients from center A (median PTH 9.9 pmol/l, in 67 patients exceeding recommended levels) and 100 patients from center B (median PTH 6.5 pmol/l, in 34 patients exceeding recommended levels), were included. Analysis of clinical practice did not reveal differences in PTH management between the centers. Notably, hyperparathyroidism resulted in a change in therapy in less than 25% of patients. In multivariate analysis kidney transplant status, MDRD-4, and treatment center were independent predictors of PTH. However, when MDRD-6 (which accounts for serum urea and albumin) was used instead of MDRD-4, the center effect was reduced. Moreover, after calibration of the serum creatinine assays treatment center no longer influenced PTH. We show that differences in PTH control between centers are not explained by differences in treatment, but depend on incomparable patient populations and laboratory techniques. Therefore, results of hospital performance comparisons should be interpreted with great caution.
Long-term suppression of secondary hyperparathyroidism by intravenous 1 alpha-hydroxyvitamin D3 in patients on chronic hemodialysis

DEFF Research Database (Denmark)

Brandi, L; Daugaard, H; Tvedegaard, E

1992-01-01

The effect of intravenous 1 alpha-hydroxyvitamin D3 [1 alpha(OH)D3] on circulating levels of intact parathyroid hormone (PTH 1-84) and COOH-terminal immunoreactive PTH(PTH 53-84) was examined in 13 patients on chronic hemodialysis. Thirteen patients were treated for 300 days (10 months), 9 patien...
A threshold for low-protein-diet-induced elevations in parathyroid hormone

DEFF Research Database (Denmark)

Kerstetter, J E; Svastisalee, C M; Caseria, D M

2000-01-01

We reported previously that lowering dietary protein intake in young healthy women to 0.7 g/kg depressed intestinal calcium absorption and was accompanied by elevations in parathyroid hormone (PTH). Moderate amounts of dietary protein (1.0 g/kg) did not appear to perturb calcium homeostasis....
The Association between Depression and Vitamin D and Parathyroid Hormone Levels in Adolescents

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Müsemma Karabel

2016-02-01

Full Text Available Background Depression, a challenging disorder, affects 1–6% of adolescents and early onset often predicts more serious manifestations in later life. Elevated Parathyroid hormone (PTH, parathormone levels have reported among adults with depression. In this study, the roles of 25(OH D (vitamin D and parathormone during adolescence, in which the frequency of depression is high, were studied. Materials and Methods Patients who were followed-up jointly at both clinics and whose 25(OH D and PTH levels were evaluated and questioned "Depression Scale for Children" for depression at the same time, were included in the study. Cases’ socio-demographic data, 25(OH D and PTH levels and Depression Scale’ scores were recorded. Results Depression was diagnosed in 35 (25.3% of the 138 patients. No differences were found between vitamin D and parathormone in terms of age and gender in groups either with or without depression. Negative correlation was found between the vitamin D levels and depression score in the group with depression (r=-0.368; P=0.03. A significant and positive correlation was found between the PTH levels and depression score (r=0.399; P=0.018. A significant and negative correlation was found between 25(OH D and PTH levels. Conclusion Even if clinical depression is absent, the frequency of depressive symptoms is increased with decreased vitamin D levels and increased PTH levels, independent of other factors. The prevention of depression, specifically in adolescents, is important to decrease possible suicidal and homicidal thoughts that might arise during adulthood, and substance abuse. Maintaining vitamin D support during adolescence, as with the first year of life, is necessary for both the prevention and treatment of depression.
Direct suppressive effect of acute metabolic and respiratory alkalosis on parathyroid hormone secretion in the dog.

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Lopez, Ignacio; Rodriguez, Mariano; Felsenfeld, Arnold J; Estepa, Jose Carlos; Aguilera-Tejero, Escolastico

2003-08-01

Acute alkalosis may directly affect PTH secretion. The effect of acute metabolic and respiratory alkalosis was studied in 20 dogs. PTH values were lower in the metabolic (5.6 +/- 0.8 pg/ml) and respiratory (1.8 +/- 0.6 pg/ml) alkalosis groups than in the control group (27 +/- 5 pg/ml). Acute alkalosis is an independent factor that decreases PTH values during normocalcemia and delays the PTH response to hypocalcemia. We recently showed that acute metabolic and respiratory acidosis stimulated PTH secretion. This study was designed to evaluate whether acute metabolic and respiratory alkalosis suppressed parathyroid hormone (PTH) secretion. Three groups of 10 dogs were studied: control, acute metabolic alkalosis, and acute respiratory alkalosis. Metabolic alkalosis was induced with an infusion of sodium bicarbonate and respiratory alkalosis by hyperventilation. Calcium chloride was infused to prevent alkalosis-induced hypocalcemia during the first 60 minutes. During the next 30 minutes, disodium EDTA was infused to induce hypocalcemia and to evaluate the PTH response to hypocalcemia. Because the infusion of sodium bicarbonate resulted in hypernatremia, the effect of hypernatremia was studied in an additional group that received hypertonic saline. After 60 minutes of a normocalcemic clamp, PTH values were less (p respiratory (1.8 +/- 0.6 pg/ml) alkalosis groups than in the control group (27 +/- 5 pg/ml); the respective blood pH values were 7.61 +/- 0.01, 7.59 +/- 0.02, and 7.39 +/- 0.02. The maximal PTH response to hypocalcemia was similar among the three groups. However, the maximal PTH response was observed after a decrease in ionized calcium of 0.20 mM in the control group but not until a decrease of 0.40 mM in the metabolic and respiratory alkalosis groups. In contrast to the metabolic alkalosis group, hypernatremia (157 +/- 2 mEq/liter) in the hypertonic saline group was associated with an increased PTH value (46 +/- 4 pg/ml). Finally, the half-life of intact PTH
Aldosterone and parathyroid hormone interactions as mediators of metabolic and cardiovascular disease

NARCIS (Netherlands)

Tomaschitz, A.; Ritz, E.; Pieske, B.; Rus-Machan, J.; Kienreich, K.; Verheyen, N.; Gaksch, M.; Grubler, M.; Fahrleitner-Pammer, A.; Mrak, P.; Toplak, H.; Kraigher-Krainer, E.; Marz, W.; Pilz, S.

2014-01-01

Inappropriate aldosterone and parathyroid hormone (PTH) secretion is strongly linked with development and progression of cardiovascular (CV) disease. Accumulating evidence suggests a bidirectional interplay between parathyroid hormone and aldosterone. This interaction may lead to a disproportionally
Intermittent Parathyroid Hormone Enhances Cancellous Osseointegration of a Novel Murine Tibial Implant

Science.gov (United States)

Yang, Xu; Ricciardi, Benjamin F.; Dvorzhinskiy, Aleksey; Brial, Caroline; Lane, Zachary; Bhimani, Samrath; Burket, Jayme C.; Hu, Bin; Sarkisian, Alexander M.; Ross, F. Patrick; van der Meulen, Marjolein C.H.; Bostrom, Mathias P.G.

2015-01-01

Background: Long-term fixation of uncemented joint implants requires early mechanical stability and implant osseointegration. To date, osseointegration has been unreliable and remains a major challenge in cementless total knee arthroplasty. We developed a murine model in which an intra-articular proximal tibial titanium implant with a roughened stem can be loaded through the knee joint. Using this model, we tested the hypothesis that intermittent injection of parathyroid hormone (iPTH) would increase proximal tibial cancellous osseointegration. Methods: Ten-week-old female C57BL/6 mice received a subcutaneous injection of PTH (40 μg/kg/day) or a vehicle (n = 45 per treatment group) five days per week for six weeks, at which time the baseline group was killed (n = 6 per treatment group) and an implant was inserted into the proximal part of the tibiae of the remaining mice. Injections were continued until the animals were killed at one week (n = 7 per treatment group), two weeks (n = 14 per treatment group), or four weeks (n = 17 per treatment group) after implantation. Outcomes included peri-implant bone morphology as analyzed with micro-computed tomography (microCT), osseointegration percentage and bone area fraction as shown with backscattered electron microscopy, cellular composition as demonstrated by immunohistochemical analysis, and pullout strength as measured with mechanical testing. Results: Preimplantation iPTH increased the epiphyseal bone volume fraction by 31.6%. When the data at post-implantation weeks 1, 2, and 4 were averaged for the iPTH-treated mice, the bone volume fraction was 74.5% higher in the peri-implant region and 168% higher distal to the implant compared with the bone volume fractions in the same regions in the vehicle-treated mice. Additionally, the trabecular number was 84.8% greater in the peri-implant region and 74.3% greater distal to the implant. Metaphyseal osseointegration and bone area fraction were 28.1% and 70.1% higher

Vitamin D status and PTH in young men: a cross-sectional study on associations with bone mineral density, body composition and glucose metabolism

DEFF Research Database (Denmark)

Nielsen, Morten Frost; Abrahamsen, B; Nielsen, T L

2010-01-01

and the effects of vitamin D and parathyroid hormone (PTH) on bone mass, bone markers and metabolic function. Design and Participants The study population consisted of 783 men aged 20-29 years. Measurements Bone mineral density (BMD) of the total hip, femoral neck and lumbar spine was measured. dual-energy X......Objective Although vitamin D and bone metabolism are closely related, few studies have addressed the effects of vitamin D status on bone in men at time of peak bone mass. The objectives of this study were to evaluate the prevalence of vitamin D inadequacy in a cross-sectional study in young men...... (serum 25OHD bone-specific alkaline phosphatase and directly with carboxyterminal telopeptide of type-1-collagen. 25OHD and PTH were inversely associated with BFAT...
Parathyroid hormone: radioimmunoassay and clinical interpretation

International Nuclear Information System (INIS)

Hawker, C.D.

1975-01-01

A radioimmunoassay for serum immunoreactive parathyroid hormone (iPTH), which has had widespread clinical use for five years, is described in detail. The iPTH results in large groups of patients are reported, and are discussed in relation to the specificity of the assay and in relation to other assays. The assay has excellent precision and is highly proficient in discrimination of groups of patients. Ninety-three percent of 412 patients with surgically proven primary hyperparathyroidism were confidently separated from normal subjects or patients with hypercalcemia owing to other causes, while 86 percent of 160 patients with chronic renal failure and secondary hyperparathyroidism had iPTH values more than 2 S.D. above the normal mean. Results in patients with ectopic hyperparathyroidism were lower than in primary hyperparathyroidism although these groups showed considerable overlap. The antiserum used in this assay for iPTH appears to be specific for the carboxy-terminal region of the secreted or intact form of PTH but recognizes predominantly the secreted form rather than carboxy-terminal fragments believed to be in the circulation. It does not recognize amino terminal fragments. The assay is useful in selective venous catheterization for preoperative localization of hyperfunctioning parathyroid tissue
Assay-specific decision limits for two new automated parathyroid hormone and 25-hydroxyvitamin D assays.

Science.gov (United States)

Souberbielle, Jean-Claude; Fayol, Véronique; Sault, Corinne; Lawson-Body, Ethel; Kahan, André; Cormier, Catherine

2005-02-01

The recent development of nonradioactive automated assays for serum parathyroid hormone (PTH) and 25-hydroxyvitamin D (25OHD) has made measurement of these two hormones possible in many laboratories. In this study, we compared two new assays for PTH and 25OHD adapted on an automated analyzer, the LIAISON, with two manual immunoassays used worldwide. We studied 228 osteoporotic patients, 927 healthy individuals, 38 patients with primary hyperparathyroidism, and 167 hemodialyzed patients. Serum PTH was measured with the Allegro and the LIAISON assays, and 25OHD was measured with DiaSorin RIA and the LIAISON assay. Regression analysis was used to calculate decision thresholds for the LIAISON assays that were equivalent to those of the Allegro PTH and DiaSorin 25OHD assays. The 25OHD concentrations obtained with the LIAISON assay and the RIA in osteoporotic patients were well correlated (r = 0.83; P 50 nmol/L as eligible for the reference population for the LIAISON PTH assay. In this group, the 3rd-97th percentile interval for LIAISON PTH was 3-51 ng/L. Considering upper reference limits of 46 and 51 ng/L for the Allegro and LIAISON assays, respectively, the frequency of above-normal PTH concentrations in patients with primary hyperparathyroidism was similar in both assays. Regression analysis between serum PTH measured by the Allegro and LIAISON assays in 167 hemodialyzed patients and the corresponding Bland-Altman analysis of these data suggest that the LIAISON PTH assay tends to read higher than the Allegro assay at low concentrations but lower at high concentrations (>300 ng/L). Because clinical decision limits for both PTH and 25OHD should be assay specific, we propose equivalences between these assays and two manual assays used worldwide. These assay-specific decision limits should help potential users of the LIAISON PTH and 25OHD assays.
Bone Mineral Density in Patients with Growth Hormone Deficiency - Does a Gender Difference Exist?

DEFF Research Database (Denmark)

Hitz, Mette; Jensen, Jens-Erik Beck; Eskildsen, PC

2006-01-01

OBJECTIVE: The aim of the study was to clarify whether a gender difference exists with respect to bone mineral density (BMD) and bone mineral content (BMC) in adult patients with growth hormone deficiency (GHD). DESIGN: A case-control design. METHODS: Blood sampling for measurements of calcium......, phosphate, creatinine, PTH, vitamin D, IGF-1, markers of bone formation and bone resorption, and dual energy X-ray absorptiometry (DEXA), to determine BMD and BMC of the lumbar spine, hip, distal arm and total body, were performed in 34 patients with GHD (19 females) and 34 sex-, age- and weight...... identical BMD values at all regions. This gender difference was even more obvious when BMD values were expressed as Z-scores or as three-dimensional BMD of the total body. The bone formation and bone resorption markers, as well as calcium and vitamin D, were all at the same levels in GH...
Bone mineral density in patients with growth hormone deficiency: does a gender difference exist?

DEFF Research Database (Denmark)

Hitz, Mette Friberg; Jensen, Jens-Erik Beck; Eskildsen, Peter C

2006-01-01

OBJECTIVE: The aim of the study was to clarify whether a gender difference exists with respect to bone mineral density (BMD) and bone mineral content (BMC) in adult patients with growth hormone deficiency (GHD). DESIGN: A case-control design. METHODS: Blood sampling for measurements of calcium......, phosphate, creatinine, PTH, vitamin D, IGF-1, markers of bone formation and bone resorption, and dual energy X-ray absorptiometry (DEXA), to determine BMD and BMC of the lumbar spine, hip, distal arm and total body, were performed in 34 patients with GHD (19 females) and 34 sex-, age- and weight...... identical BMD values at all regions. This gender difference was even more obvious when BMD values were expressed as Z-scores or as three-dimensional BMD of the total body. The bone formation and bone resorption markers, as well as calcium and vitamin D, were all at the same levels in GH...
Increasing Dietary Phosphorus Intake from Food Additives: Potential for Negative Impact on Bone Health123

OpenAIRE

Takeda, Eiji; Yamamoto, Hironori; Yamanaka-Okumura, Hisami; Taketani, Yutaka

2014-01-01

It is important to consider whether habitual high phosphorus intake adversely affects bone health, because phosphorus intake has been increasing, whereas calcium intake has been decreasing in dietary patterns. A higher total habitual dietary phosphorus intake has been associated with higher serum parathyroid hormone (PTH) and lower serum calcium concentrations in healthy individuals. Higher serum PTH concentrations have been shown in those who consume foods with phosphorus additives. These fi...
Effects of phospho- and calciotropic hormones on electrolyte transport in the proximal tubule [version 1; referees: 2 approved

Directory of Open Access Journals (Sweden)

Justin J. Lee

2017-10-01

Full Text Available Calcium and phosphate are critical for a myriad of physiological and cellular processes within the organism. Consequently, plasma levels of calcium and phosphate are tightly regulated. This occurs through the combined effects of the phospho- and calciotropic hormones, parathyroid hormone (PTH, active vitamin D3, and fibroblast growth factor 23 (FGF23. The organs central to this are the kidneys, intestine, and bone. In the kidney, the proximal tubule reabsorbs the majority of filtered calcium and phosphate, which amounts to more than 60% and 90%, respectively. The basic molecular mechanisms responsible for phosphate reclamation are well described, and emerging work is delineating the molecular identity of the paracellular shunt wherein calcium permeates the proximal tubular epithelium. Significant experimental work has delineated the molecular effects of PTH and FGF23 on these processes as well as their regulation of active vitamin D3 synthesis in this nephron segment. The integrative effects of both phospho- and calciotropic hormones on proximal tubular solute transport and subsequently whole body calcium-phosphate balance thus have been further complicated. Here, we first review the molecular mechanisms of calcium and phosphate reabsorption from the proximal tubule and how they are influenced by the phospho- and calciotropic hormones acting on this segment and then consider the implications on both renal calcium and phosphate handling as well as whole body mineral balance.
Changes in calcitropic hormones, bone markers and insulin-like growth factor I (IGF-I) during pregnancy and postpartum: a controlled cohort study.

Science.gov (United States)

Møller, U K; Streym, S; Mosekilde, L; Heickendorff, L; Flyvbjerg, A; Frystyk, J; Jensen, L T; Rejnmark, L

2013-04-01

Pregnancy and lactation cause major changes in calcium homeostasis and bone metabolism. This population-based cohort study presents the physiological changes in biochemical indices of calcium homeostasis and bone metabolism during pregnancy and lactation We describe physiological changes in calcium homeostasis, calcitropic hormones and bone metabolism during pregnancy and lactation. We studied 153 women planning pregnancy (n=92 conceived) and 52 non-pregnant, age-matched female controls. Samples were collected prior to pregnancy, once each trimester and 2, 16 and 36 weeks postpartum. The controls were followed in parallel. P-estradiol (E2), prolactin and 1,25-dihydroxyvitamin D (1,25(OH)2D) increased (phormone (P-PTH) and calcitonin decreased (pgrowth factor I (IGF-I) was suppressed (pbone resorption and formation rose and fall, respectively (pbone formation markers increased in association with IGF-I changes (pbone turnover markers were associated with lactation status (pbone markers indicated a negative bone balance. The rise in bone formation in late pregnancy may be initiated by a spike in IGF-I levels. The high bone turnover in lactating women may be related to high prolactin and PTH levels, low E2 levels and perhaps increased parathyroid hormone-related protein levels.
Serum levels of parathyroid hormone-M, magnesium and calcium and their inter-relationship in patients with acute pancreatitis

International Nuclear Information System (INIS)

Liu Qi; Zhou Li; Lu Yuanhan; Wang Yan; Wang Yan; Liu Huarong

2002-01-01

Objective: To study the changes of serum parathyroid hormone-M, magnesium, and calcium levels and their interrelationships in patients with mild acute pancreatitis (MAP) and severe acute pancreatitis (SAP). Methods: Serum level of PTH-M was measured by means of radioimmunoassay, serum magnesium and calcium levels were determines with automatic biochemical analytical apparatus. Results: 1) Serum levels of PTH-M in acute period and daring recovery in patients with MAP and SAP were not significant different from those in controls (p > 0.05); serum levels of magnesium and calcium in cute period of patients with SAP were significantly lower than those in controls (p<0.01); 2) There was a linear positive correlation between serum levels of PTH-M and serum magnesium in acute-phase of SAP patients, correlation coefficient r = 0.413 (p<0.05). Conclusion: That presence of hypocalcemia in patients with severe acute pancreatitis did not lead to parathyroid hormone-M responsive rise, that might be due to the presence of hypomagnesemia
The paracrine feedback loop between vitamin D₃ (1,25(OH)₂D₃) and PTHrP in prehypertrophic chondrocytes

NARCIS (Netherlands)

Bach, Frances C; Rutten, Kirsten; Hendriks, Kristyanne; Riemers, Frank M; Cornelissen, Peter; de Bruin, Alain; Arkesteijn, Ger J; Wubbolts, Richard; Horton, William A; Penning, Louis C; Tryfonidou, Marianna A

2014-01-01

The endocrine feedback loop between vitamin D3(1,25(OH)2D3) and parathyroid hormone (PTH) plays a central role in skeletal development. PTH-related protein (PTHrP) shares homology and its receptor (PTHR1) with PTH. The aim of this study was to investigate whether there is a functional paracrine
Usefulness of a rapid immunometric assay for intraoperative parathyroid hormone measurements

Directory of Open Access Journals (Sweden)

M.N. Ohe

2003-06-01

Full Text Available Intraoperative parathyroid hormone (IO-PTH measurements have been proposed to improve operative success rates in primary, secondary and tertiary hyperparathyroidism (PHP, SHP and THP. Thirty-one patients requiring parathyroidectomy were evaluated retrospectively from June 2000 to January 2002. Sixteen had PHP, 7 SHP and 8 THP. Serum samples were taken at times 0 (before resection, 10, 20 and 30 min after resection of each abnormal parathyroid gland. Samples from 28 patients were frozen at -70ºC for subsequent tests, whereas samples from three patients were tested while surgery was being performed. IO-PTH was measured using the Elecsys immunochemiluminometric assay (Roche, Mannheim, Germany. The time necessary to perform the assay was 9 min. All samples had a second measurement taken by a conventional immunofluorimetric method. We considered as cured patients who presented normocalcemia in PHP and THP, and normal levels of PTH in SHP one month after surgery and who remained in this condition throughout the follow-up of 1 to 20 months. When rapid PTH assay was compared with a routine immunofluorimetric assay, excellent correlation was observed (r = 0.959, P < 0.0001. IO-PTH measurement showed a rapid average decline of 78.8% in PTH 10 min after adenoma resection in PHP and all patients were cured. SHP patients had an average IO-PTH decrease of 89% 30 min after total parathyroidectomy and cure was observed in 85.7%. THP showed an average IO-PTH decrease of 91.9%, and cure was obtained in 87.5% of patients. IO-PTH can be a useful tool that might improve the rate of successful treatment of PHP, SHP and THP.
Determining the Levels of Vitamin D and Parathyroid Hormone in Patients on Hemodialysis

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Mihaylov R.

2016-03-01

Full Text Available Vitamin D deficiency is fequently observed in chronic kidney disease. We conducted this study to determine the concentration of the above-mentioned parameters and the correlation between them in order to optimize therapy with vitamin D in patients with end-stage renal disease (ESRD on hemodialysis. In 53 patients on hemodialysis due to ESRD, vitamin D [Calcidiol (25(OHD], parathyroid hormone (PTH, calcium, phosphorus, albuminuria, albumin:creatinine ratio (ACR and other parameters have been followed up. Analysis of the levels of vitamin D has been carried out by High Performance Liquid Chromatography (HPLC, the PTH is determined by the system Centaur XP, Siemens Diagnostic, Electro-chemiluminescence immunoassay (ECLIA, and for albumin in urine we used immunological method [Miltigent microalbumin assay (Abbott Laboratories Diagnostics. We found out deficiency and insufficiency of vitamin D in 56.6% and 37.7%, as well as average 4.5 times increase in the PTH, hyperphosphatemia, hypocalcemia, albuminuria (A2 or A3, over 10 times increase in the ACR, secondary hyperparathyroidism. We registered a negative correlation between vitamin D and PTH. We confirmed the increase in creatinine and cystatin C in the patients on hemodialysis. There are few literature data for patients on hemodialysis, however, regarding the extent of the vitamin deficiency and its relationship with PTH, albuminuria, calcium, phosphorus, etc. Our data have indicated that patients on hemodialysis due to ESRD are associated with high incidence of vitamin D insufficiency or deficiency.
Influence of Secondary Hyperparathyroidism Induced by Low Dietary Calcium, Vitamin D Deficiency, and Renal Failure on Circulating Rat PTH Molecular Forms.

Science.gov (United States)

D'Amour, Pierre; Rousseau, Louise; Hornyak, Stephen; Yang, Zan; Cantor, Tom

2011-01-01

Rats(r) with secondary hyperparathyroidism were studied to define the relationship between vitamin D metabolites and rPTH levels measured by 3 different rat ELISAs. Controls and renal failure (RF) rats were on a normal diet, while 2 groups on a low-calcium (-Ca) or a vitamin D-deficient (-D) diet. RF was induced surgically. Mild RF rats had normal calcium and 25(OH)D but reduced 1,25(OH)(2)D levels (P < .001) with a 2.5-fold increased in rPTH (P < .001). Severe RF rats and those on a -Ca or -D diet had reduced calcium (P < .01) and 25(OH)D levels (P < .05), with rPTH increased by 2 (-Ca diet; P < .05), 4 (-D diet; P < .001), and 20-folds (RF; P < .001) while 1,25(OH)(2)D was high (-Ca diet: P < .001) or low (-D diet, RF: P < .001). 25(OH)D and 1,25(OH)(2)D were positively and negatively related on the -Ca and -D diets, respectively. rPTH molecular forms behaved as expected in RF and on -Ca diet, but not on -D diet with more C-rPTH fragments when less were expected. This may be related to the short-time course of this study compared to prior studies.
Effects of osteotropic hormones on the nitric oxide production in culture of ROS17/2.8 cells

International Nuclear Information System (INIS)

Ko, Seon Yil; Kim, Min Sung; Han, Won Jeong; Kim, Se Won; Kim, Jung Keun

2005-01-01

We performed the present study to investigate whether osteotropic hormones play roles on the nitric oxide (NO) production in culture of ROS17/2.8 osteoblastic cells. The osteoblastic cell line ROS17/2.8 cells were cultured in F12 medium supplemented with 5% fetal bovine serum (FBS) at 37.deg. C in a humidified atmosphere of 5% CO 2 in air. ROS17/2.8 cells were plated in 96-well plants at a density of 2-3 x 10 3 cells/well and grown to confluence. Then the cells were pretreated with osteotropic hormones (parathyroid hormone (PTH) 20-500 ng/mL, 1, 25-dihydroxycholecalciferol (1, 25[OH] 2 D 3 ) 1-100nM ; prostaglandin E 2 (PGE 2 ) 20-500 ng/mL) in the medium supplemented with 0.4% FBS for (72 hours and the cells were treated with cytokines (TNFα and IFNγ) in phenol red-free F12 medium for an additional 48 hours. NO synthesis was assessed by measuring the nitrite anion concentration, the reation product of NO, in the cell culture medium using Griess reagent. PTH and 1, 25[OH] 2 D 4 pretreatment induced a significant increase in NO production in the presence of TNFα and IFNγ. PGE 2 slightly induced NO production compared to the control group. But, PGE 2 pretreatment did not affect in NO production in the presence of TNFα and IFNγ. These results suggest that the actions of osteotropic hormones in bone metabolism may be partially mediated by NO in the presence of cytokines
Feasibility Study of a Standardized Novel Animal Model for Cervical Vertebral Augmentation in Sheep Using a PTH Derivate Bioactive Material

Directory of Open Access Journals (Sweden)

Karina Klein

2014-08-01

Full Text Available Prophylactic local treatment involving percutaneous vertebral augmentation using bioactive materials is a new treatment strategy in spine surgery in humans for vertebral bodies at risk. Standardized animal models for this procedure are almost non-existent. The purpose of this study was to: (i prove the efficacy of PTH derivate bioactive materials for new bone formation; and (ii create a new, highly standardized cervical vertebral augmentation model in sheep. Three different concentrations of a modified form of parathyroid hormone (PTH covalently bound to a fibrin matrix containing strontium carbonate were used. The same matrix without PTH and shams were used as controls. The bioactive materials were locally injected. Using a ventral surgical approach, a pre-set amount of material was injected under fluoroscopic guidance into the intertrabecular space of three vertebral bodies. Intravital fluorescent dyes were used to demonstrate new bone formation. After an observation period of four months, the animals were sacrificed, and vertebral bodies were processed for µCT, histomorphometry, histology and sequential fluorescence evaluation. Enhanced localized bone activity and new bone formation in the injected area could be determined for all experimental groups in comparison to the matrix alone and sham with the highest values detected for the group with a medium concentration of PTH.
Defective cancellous bone structure and abnormal response to PTH in cortical bone of mice lacking Cx43 cytoplasmic C-terminus domain

Science.gov (United States)

Pacheco-Costa, Rafael; Davis, Hannah M.; Sorenson, Chad; Hon, Mary C.; Hassan, Iraj; Reginato, Rejane D.; Allen, Matthew R.; Bellido, Teresita; Plotkin, Lilian I.

2015-01-01

Connexin43 (Cx43) forms gap junction channels and hemichannels that allow the communication among osteocytes, osteoblasts, and osteoclasts. Cx43 carboxy-terminal (CT) domain regulates channel opening and intracellular signaling by acting as a scaffold for structural and signaling proteins. To determine the role of Cx43 CT domain in bone, mice in which one allele of full length Cx43 was replaced by a mutant lacking the CT domain (Cx43ΔCT/fl) were studied. Cx43ΔCT/fl mice exhibit lower cancellous bone volume but higher cortical thickness than Cx43fl/fl controls, indicating that the CT domain is involved in normal cancellous bone gain but opposes cortical bone acquisition. Further, Cx43ΔCT is able to exert the functions of full length osteocytic Cx43 on cortical bone geometry and mechanical properties, demonstrating that domains other than the CT are responsible for Cx43 function in cortical bone. In addition, parathyroid hormone (PTH) failed to increase endocortical bone formation or energy to failure, a mechanical property that indicates resistance to fracture, in cortical bone in Cx43ΔCT mice with or without osteocytic full length Cx43. On the other hand, bone mass and bone formation markers were increased by the hormone in all mouse models, regardless of whether full length or Cx43ΔCT were or not expressed. We conclude that Cx43 CT domain is involved in proper bone acquisition; and that Cx43 expression in osteocytes is dispensable for some but not all PTH anabolic actions. PMID:26409319
A sensitive electrochemical sensor for in vitro detection of parathyroid hormone based on a MoS2-graphene composite

Science.gov (United States)

Kim, Hyeong-U.; Kim, Hye Youn; Kulkarni, Atul; Ahn, Chisung; Jin, Yinhua; Kim, Yeongseok; Lee, Kook-Nyung; Lee, Min-Ho; Kim, Taesung

2016-10-01

This paper reports a biosensor based on a MoS2-graphene (MG) composite that can measure the parathyroid hormone (PTH) concentration in serum samples from patients. The interaction between PTH and MG was analysed via an electrochemical sensing technique. The MG was functionalized using L-cysteine. Following this, PTH could be covalently immobilized on the MG sensing electrode. The properties of MG were evaluated using scanning electron microscopy, high-resolution transmission electron microscopy, X-ray diffraction, Raman spectroscopy, X-ray photoelectron spectroscopy, and Fourier transform infrared spectrometry. Following optimization of immobilized materials—such as MG, PTH, and alkaline phosphatase (ALP)—the performance of the MG sensor was investigated via cyclic voltammetry, to assess its linearity, repeatability, and reproducibility. Electrochemical impedance spectroscopy was performed on graphene oxide (GO) and MG-modified electrodes to confirm the capture of a monoclonal antibody (MAb) targeting PTH. Furthermore, the ALP-PTH-MG sensor exhibits a linear response towards PTH from artificial serum over a range of 1-50 pg mL-1. Moreover, patient sera (n = 30) were evaluated using the ALP-PTH-MG sensor and compared using standard equipment (Roche E 170). The P-value is less than 0.01 when evaluated with a t-test using Welch’s correction. This implies that the fabricated sensor can be deployed for medical diagnosis.
Effects of parathyroid hormone on cortical porosity, non-enzymatic glycation and bone tissue mechanics in rats with type 2 diabetes mellitus.

Science.gov (United States)

Campbell, G M; Tiwari, S; Hofbauer, C; Picke, A-K; Rauner, M; Huber, G; Peña, J A; Damm, T; Barkmann, R; Morlock, M M; Hofbauer, L C; Glüer, C-C

2016-01-01

Type 2 diabetes mellitus increases skeletal fragility; however, the contributing mechanisms and the efficacy of bone-forming agents are unclear. We studied diabetes and parathyroid hormone (PTH) treatment effects on cortical porosity (Ct.Po), non-enzymatic glycation (NEG) and bone mechanics in Zucker diabetic fatty (ZDF) rats. Eleven-week old ZDF diabetic (DB) and non-diabetic (ND) rats were given 75μg/kg PTH (1-84) or vehicle 5days per week over 12weeks. The right femora and L4 vertebrae were excised, micro-CT scanned, and tested in 3-point bending and uniaxial compression, respectively. NEG of the samples was determined using fluorescence. Diabetes increased Ct.Po (vertebra (vert): +40.6%, femur (fem): +15.5% vs. ND group, pbone tissue mechanics where reductions in vertebral maximum strain (-22%) and toughness (-42%) were observed in the DB vs. ND group (pbone mechanics, which were not improved with PTH treatment. PTH therapy alone may worsen diabetic bone mechanics through formation of new bone with high AGEs cross-linking. Optimal treatment regimens must address both improvements of bone mass and glycemic control in order to successfully reduce diabetic bone fragility. This article is part of a Special Issue entitled "Bone and diabetes". Copyright © 2015 Elsevier Inc. All rights reserved.
Increasing dietary phosphorus intake from food additives: potential for negative impact on bone health.

Science.gov (United States)

Takeda, Eiji; Yamamoto, Hironori; Yamanaka-Okumura, Hisami; Taketani, Yutaka

2014-01-01

It is important to consider whether habitual high phosphorus intake adversely affects bone health, because phosphorus intake has been increasing, whereas calcium intake has been decreasing in dietary patterns. A higher total habitual dietary phosphorus intake has been associated with higher serum parathyroid hormone (PTH) and lower serum calcium concentrations in healthy individuals. Higher serum PTH concentrations have been shown in those who consume foods with phosphorus additives. These findings suggest that long-term dietary phosphorus loads and long-term hyperphosphatemia may have important negative effects on bone health. In contrast, PTH concentrations did not increase as a result of high dietary phosphorus intake when phosphorus was provided with adequate amounts of calcium. Intake of foods with a ratio of calcium to phosphorus close to that found in dairy products led to positive effects on bone health. Several randomized controlled trials have shown positive relations between dairy intake and bone mineral density. In our loading test with a low-calcium, high-phosphorus lunch provided to healthy young men, serum PTH concentrations showed peaks at 1 and 6 h, and serum fibroblast growth factor 23 (FGF23) concentrations increased significantly at 8 h after the meal. In contrast, the high-calcium, high-phosphorus meal suppressed the second PTH and FGF23 elevations until 8 h after the meal. This implies that adequate dietary calcium intake is needed to overcome the interfering effects of high phosphorus intake on PTH and FGF23 secretion. FGF23 acts on the parathyroid gland to decrease PTH mRNA and PTH secretion in rats with normal kidney function. However, increased serum FGF23 is an early alteration of mineral metabolism in chronic kidney disease, causing secondary hyperthyroidism, and implying resistance of the parathyroid gland to the action of FGF23 in chronic kidney disease. These findings suggest that long-term high-phosphorus diets may impair bone health
Therapy of hypoparathyroidism by replacement with parathyroid hormone

DEFF Research Database (Denmark)

Rejnmark, Lars; Underbjerg, Line; Sikjaer, Tanja

2014-01-01

Hypoparathyroidism (HypoPT) is a state of hypocalcemia due to inappropriate low levels of parathyroid hormone (PTH). HypoPT is normally treated by calcium supplements and activated vitamin D analogues. Although plasma calcium is normalized in response to conventional therapy, quality of life (Qo...... recently, continuous delivery of PTH by pump has appeared as a feasible alternative to injections. Plasma calcium levels do not fluctuate, urinary calcium is lowered, and bone turnover is only stimulated modestly (into the normal range). Further studies are needed to assess the long-term effects...

Recessive mutations in PTHR1 cause contrasting skeletal dysplasias in Eiken and Blomstrand syndromes

DEFF Research Database (Denmark)

Duchatelet, Sabine; Ostergaard, Elsebet; Cortes, Dina

2005-01-01

Eiken syndrome is a rare autosomal recessive skeletal dysplasia. We identified a truncation mutation in the C-terminal cytoplasmic tail of the parathyroid hormone (PTH)/PTH-related peptide (PTHrP) type 1 receptor (PTHR1) gene as the cause of this syndrome. Eiken syndrome differs from Jansen...
Regulation of renal NaPi-2 expression and tubular phosphate reabsorption by growth hormone in the juvenile rat.

Science.gov (United States)

Woda, Craig B; Halaihel, Nabil; Wilson, Paul V; Haramati, Aviad; Levi, Moshe; Mulroney, Susan E

2004-07-01

Growth hormone (GH) is an important factor in the developmental adaptation to enhance P(i) reabsorption; however, the nephron sites and mechanisms by which GH regulates renal P(i) uptake remain unclear and are the focus of the present study. Micropuncture experiments were performed after acute thyroparathyroidectomy in the presence and absence of parathyroid hormone (PTH) in adult (14- to 17-wk old), juvenile (4-wk old), and GH-suppressed juvenile male rats. While the phosphaturic effect of PTH was blunted in the juvenile rat compared with the adult, suppression of GH in the juvenile restored fractional P(i) excretion to adult levels. In the presence or absence of PTH, GH suppression in the juvenile rat caused a significant increase in the fractional P(i) delivery to the late proximal convoluted (PCT) and early distal tubule, so that delivery was not different from that in adults. These data were confirmed by P(i) uptake studies into brush-border membrane (BBM) vesicles. Immunofluorescence studies indicate increased BBM type IIa NaP(i) cotransporter (NaPi-2) expression in the juvenile compared with adult rat, and GH suppression reduced NaPi-2 expression to levels observed in the adult. GH replacement in the [N-acetyl-Tyr(1)-d-Arg(2)]-GRF-(1-29)-NH(2)-treated juveniles restored high NaPi-2 expression and P(i) uptake. Together, these novel results demonstrate that the presence of GH in the juvenile animal is crucial for the early developmental upregulation of BBM NaPi-2 and, most importantly, describe the enhanced P(i) reabsorption along the PCT and proximal straight nephron segments in the juvenile rat.
Radiometrical, hormonal and biological correlates of skeletal growth in the female rat from birth to senescence.

Science.gov (United States)

del Pozo, Emilio; Janner, Marco; Mackenzie, Andrew R; Arampatzis, Spyridon; Dixon, Arnold K; Perrelet, Romain; Ruch, Walter; Lippuner, Kurt; Zapf, Juergen; Lamberts, Steven W; Mullis, Primus E

2014-01-01

We investigated the skeletal growth profile of female rats from birth to senescence (100weeks) on the basis of sequential radiometrical, hormonal and biochemical parameters. Weaning rats entered the study which was divided into two sections: a) sequential measurements of vertebral and tibial growths and bone mineral density (BMD), estimation of mineral content of the entire skeleton (BMC) and chemical analysis of vertebral Ca; and b) determination of basal and pulsatile growth hormone (rGH), insulin-like growth hormone (IGF-I), estradiol (E2), parathyroid hormone (PTH), osteocalcin (OC) and urinary d-pyridinoline (dp) throughout the experimental period. Vertebral and tibial growths ceased at week 25 whereas BMD and BMC as well as total vertebral Ca exhibited a peak bone mass at week 40. rGH pulsatile profiles were significantly higher in younger animals coinciding with the period of active growth and IGF-I peaked at 7weeks, slowly declining thereafter and stabilizing after week 60. OC and dp closely paralleled IGF-I coinciding with the period of enhanced skeletal growth, remaining thereafter in the low range indicative of reduced bone turnover. E2 increased during reproductive life but the lower values subsequently recorded were still in the physiological range, strongly suggesting a protective role of this steroid on bone remodeling. PTH followed a similar profile to E2, but the significance of this after completion of growth remains unclear. Mechanisms governing skeletal growth in the female rat appear similar to those in humans. Bone progression and attainment of peak bone mass are under simultaneous control of rGH, IGF-I and calciotropic hormones and are modulated by E2. This steroid seems to protect the skeleton from resorption before senescence whereas the role of PTH in this context remains uncertain. Copyright © 2014. Published by Elsevier Ltd.
Calcium, parathyroid hormone, oxytocin and pH profiles in the whelping bitch.

Science.gov (United States)

Hollinshead, F K; Hanlon, D W; Gilbert, R O; Verstegen, J P; Krekeler, N; Volkmann, D H

2010-06-01

Despite the high prevalence of primary uterine inertia in whelping bitches, the underlying pathogenesis remains unclear. The objectives were to i) determine serum concentrations of total calcium, ionized calcium (iCa), parathyroid hormone (PTH), and blood pH in normally whelping bitches throughout the peri-parturient period; and ii) investigate relationships among iCa, PTH, and acid-base status, and the role that they and oxytocin may have in the underlying pathogenesis of canine uterine inertia. Bitches were randomly selected from a population of German Shepherd Dog bitches with a history of uncomplicated parturition (Group 1; n=10), and from a population of Labrador bitches with a clinical history of an increased incidence of uterine inertia and stillbirths (Group 2; n=20). Jugular blood samples were collected daily from -4 d to the onset of whelping (t=0 h), and then every 4h until the last pup was born. Overall, bitches from Group 2 had higher mean+/-SEM serum concentrations of PTH (4.72+/-2.45 pmol/L, P<0.001), lower iCa (1.31+/-0.08 pmol/L, P<0.05), and higher venous pH (7.41+/-0.03, P<0.005) than bitches from Group 1 (2.9+/-1.44 pmol/L, 1.38+/-0.06 mmol/L, and 7.33+/-0.02, respectively) during the periparturient period. However, there was no significant difference between Groups 1 and 2 for serum oxytocin concentrations during the periparturient period (45.5+/-40 and 65.5+/-82 pg/mL). We inferred that low iCa resulting from a rising pH and decreasing PTH during the periparturient period may have contributed to decreased uterine contractility and increased risk of stillbirths. Therefore, manipulating the cationic/anionic difference in diets of pregnant bitches, similar to the bovine model for hypocalcamia, may reduce the incidence of stillbirths in the bitch. 2010 Elsevier Inc. All rights reserved.
Increasing Dietary Phosphorus Intake from Food Additives: Potential for Negative Impact on Bone Health123

Science.gov (United States)

Takeda, Eiji; Yamamoto, Hironori; Yamanaka-Okumura, Hisami; Taketani, Yutaka

2014-01-01

It is important to consider whether habitual high phosphorus intake adversely affects bone health, because phosphorus intake has been increasing, whereas calcium intake has been decreasing in dietary patterns. A higher total habitual dietary phosphorus intake has been associated with higher serum parathyroid hormone (PTH) and lower serum calcium concentrations in healthy individuals. Higher serum PTH concentrations have been shown in those who consume foods with phosphorus additives. These findings suggest that long-term dietary phosphorus loads and long-term hyperphosphatemia may have important negative effects on bone health. In contrast, PTH concentrations did not increase as a result of high dietary phosphorus intake when phosphorus was provided with adequate amounts of calcium. Intake of foods with a ratio of calcium to phosphorus close to that found in dairy products led to positive effects on bone health. Several randomized controlled trials have shown positive relations between dairy intake and bone mineral density. In our loading test with a low-calcium, high-phosphorus lunch provided to healthy young men, serum PTH concentrations showed peaks at 1 and 6 h, and serum fibroblast growth factor 23 (FGF23) concentrations increased significantly at 8 h after the meal. In contrast, the high-calcium, high-phosphorus meal suppressed the second PTH and FGF23 elevations until 8 h after the meal. This implies that adequate dietary calcium intake is needed to overcome the interfering effects of high phosphorus intake on PTH and FGF23 secretion. FGF23 acts on the parathyroid gland to decrease PTH mRNA and PTH secretion in rats with normal kidney function. However, increased serum FGF23 is an early alteration of mineral metabolism in chronic kidney disease, causing secondary hyperthyroidism, and implying resistance of the parathyroid gland to the action of FGF23 in chronic kidney disease. These findings suggest that long-term high-phosphorus diets may impair bone health
Intraoperative measurement of parathyroid hormone: A Copernican revolution in the surgical treatment of hyperparathyroidism.

Science.gov (United States)

Gioviale, Maria Concetta; Damiano, Giuseppe; Altomare, Roberta; Maione, Carolina; Buscemi, Salvatore; Buscemi, Giuseppe; Lo Monte, Attilio Ignazio

2016-04-01

Intraoperative parathyroid hormone (PTH) monitoring in the setting of the operating room represents a valuable example of the rationale use of the laboratory diagnostic in a patient-oriented approach. Rapid intraoperative PTH (ioPTH) assay is a valid tool for an accurate evaluation of the success of parathyroid surgery. The reliability of the user-friendly portable systems as well as the collaboration between operators and surgical staff allow the one-site monitoring of the ioPTH decrements on the course of the surgical management of hyperparathyroidism. The rapid answer provided by an effective decrement of PTH during parathyroidectomy contributes dramatically to the efficacy of parathyroid surgery and the reduction of the number of re-operations. Therefore the dose of ioPTH is a valid and reliable support for the success of the intervention of parathyroidectomy at controlled costs. Copyright © 2015 IJS Publishing Group Limited. Published by Elsevier Ltd. All rights reserved.
Parathyroid hormone secretion in chronic renal failure

DEFF Research Database (Denmark)

Madsen, J C; Rasmussen, A Q; Ladefoged, S D

1996-01-01

The aim of study was to introduce and evaluate a method for quantifying the parathyroid hormone (PTH) secretion during hemodialysis in secondary hyperparathyroidism due to end-stage renal failure. We developed a method suitable for inducing sequential hypocalcemia and hypercalcemia during....../ionized calcium curves were constructed, and a mean calcium set-point of 1.16 mmol/liter was estimated compared to the normal mean of about 1.13 mmol/liter. In conclusion, we demonstrate that it is important to use a standardized method to evaluate parathyroid hormone dynamics in chronic renal failure. By the use...... of a standardized method we show that the calcium set-point is normal or slightly elevated, indicating normal parathyroid reactivity to calcium in chronic renal failure....
Parathyroid hormone secretion in chronic renal failure

DEFF Research Database (Denmark)

Madsen, J C; Rasmussen, A Q; Ladefoged, S D

1996-01-01

/ionized calcium curves were constructed, and a mean calcium set-point of 1.16 mmol/liter was estimated compared to the normal mean of about 1.13 mmol/liter. In conclusion, we demonstrate that it is important to use a standardized method to evaluate parathyroid hormone dynamics in chronic renal failure. By the use...... of a standardized method we show that the calcium set-point is normal or slightly elevated, indicating normal parathyroid reactivity to calcium in chronic renal failure.......The aim of study was to introduce and evaluate a method for quantifying the parathyroid hormone (PTH) secretion during hemodialysis in secondary hyperparathyroidism due to end-stage renal failure. We developed a method suitable for inducing sequential hypocalcemia and hypercalcemia during...
Low parathyroid hormone levels in bedridden geriatric patients with vitamin D deficiency.

Science.gov (United States)

Björkman, Mikko P; Sorva, Antti J; Risteli, Juha; Tilvis, Reijo S

2009-06-01

To identify the clinical conditions associated with low parathyroid hormone (PTH) in patients with vitamin D deficiency and to evaluate the stability of the blunted PTH response to vitamin D deficiency over 6 months. Secondary analysis of a randomized double-blind controlled vitamin D supplementation trial. Four long-term care hospitals in Helsinki, Finland. Two hundred eighteen chronically bedridden patients. Plasma 25-hydroxyvitamin D (25-OHD), intact PTH, amino-terminal propeptide of type I procollagen (PINP), carboxy-terminal telopeptide of type I collagen (ICTP), activities of daily living (ADLs), and body mass index (BMI) were measured at baseline and at 6 months. Patient records were reviewed for demographic data. PTH was within reference values (8-73 ng/L) despite low 25-OHD level (bedridden patients with vitamin D deficiency. Attenuated parathyroid function appears to be associated with immobilization that causes accelerated bone resorption. Further studies addressing the possible adverse effects of low PTH are warranted.
ROL' POLOVYKh GORMONOV V REGULYaTsII KOSTNOGO OBMENA i mineral'noy plotnostikostnoy tkani u muzhchin v pozdnie sroki posle allotransplantatsii trupnoy pochki

Directory of Open Access Journals (Sweden)

I A PRONChENKO

2006-08-01

Full Text Available Lumbal spine and hip bone mineral density (BMD, bone turnover markers [bone alkaline phosphatase (bALP, osteocalcin (OC, aminoterminal procollagen I propeptide, bone acid phosphatase (bACP, ß-crosslaps (CTX], sex hormones [testosterone, estradiol (E2, sex hormone-binding globulin (SHBG, free androgen index (FAI, free estrogen index (FEI], parathyroid hormone (PTH, osteoprotegerin (OPG and insulin-like growth factor-1 (IGF-1] were determined in 39 men in age 42±10 years (33 with well renal function and 6 - with renal failure (RF 44±26 months following KT receiving triple immunosuppressive therapy (CysA, prednisolone and azathioprine. Increased CTX, bACP, OC and decreased bALP so as BMD were associated in men following KT with low testosterone, SHBG and IGF-1 and high E2, OPG and PTH. There was more degree of bone turnover disturbances, decreased BMD, PTH hypersecretion and low FAI in RF. There were significant positive relationships between serum testosterone and E2, FEI and FAI, bALP and E2, bALP and FEI, femur BMD and FAI, femur BMD and FEI, OPG and E2, IGF-1 and PTH. There were significant inverse correlations between serum CTX and FAI, CTX and FEI, hip (spine BMD and SHBG, hip (spine BMD and PTH so as between PTH and FAI, PTH and FEI. So bone turnover disturbances, hip BMD losses and PTH hypersecretion in men at late time following KT associated with sex hormone deficiency. Predictor of high bone turnover and as vertebral as femur bone losses after KT besides PTH hypersecretion was serum SHBG. Decreased IGF-1 was the reason of bone forming suppression and possibly was following cyclosporine hepatotoxicity. OPG increasing was associated partly with high estradiol and was compensatory to attenuation of bone resorption and bone losses.
Parathyroid Hormone Directs Bone Marrow Mesenchymal Cell Fate.

Science.gov (United States)

Fan, Yi; Hanai, Jun-Ichi; Le, Phuong T; Bi, Ruiye; Maridas, David; DeMambro, Victoria; Figueroa, Carolina A; Kir, Serkan; Zhou, Xuedong; Mannstadt, Michael; Baron, Roland; Bronson, Roderick T; Horowitz, Mark C; Wu, Joy Y; Bilezikian, John P; Dempster, David W; Rosen, Clifford J; Lanske, Beate

2017-03-07

Intermittent PTH administration builds bone mass and prevents fractures, but its mechanism of action is unclear. We genetically deleted the PTH/PTHrP receptor (PTH1R) in mesenchymal stem cells using Prx1Cre and found low bone formation, increased bone resorption, and high bone marrow adipose tissue (BMAT). Bone marrow adipocytes traced to Prx1 and expressed classic adipogenic markers and high receptor activator of nuclear factor kappa B ligand (Rankl) expression. RANKL levels were also elevated in bone marrow supernatant and serum, but undetectable in other adipose depots. By cell sorting, Pref1 + RANKL + marrow progenitors were twice as great in mutant versus control marrow. Intermittent PTH administration to control mice reduced BMAT significantly. A similar finding was noted in male osteoporotic patients. Thus, marrow adipocytes exhibit osteogenic and adipogenic characteristics, are uniquely responsive to PTH, and secrete RANKL. These studies reveal an important mechanism for PTH's therapeutic action through its ability to direct mesenchymal cell fate. Copyright © 2017 Elsevier Inc. All rights reserved.
Management of glucocorticoids-induced osteoporosis: role of teriparatide

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Silvia Migliaccio

2009-04-01

Full Text Available Silvia Migliaccio1, Marina Brama1, Nazzarena Malavolta21Dipartimento di Fisiopatologia Medica, Policlinico Umberto I, Università degli Studi Sapienza di Roma, Italy; 2Dipartimento di Medicina Interna, Policlinico S Orsola Malpighi, Bologna, ItalyAbstract: Glucocorticoids (GC-induced osteoporosis (GIOP is the most common cause of secondary osteoporosis, which leads to an increased fracture risk in patients. The normal bone turnover depends on a balance between osteoblasts and osteoclasts activity and GC can cause a rapid bone loss, decreasing bone formation and increasing bone resorption. The decreased bone formation is mainly due to the GC-induced apoptosis of both osteoblasts and osteocytes, while the increased bone resorption is due to the increased life-span of pre-existing osteoclasts. Bisphosphonates are clearly effective in preventing and treating GIOP but anabolic therapeutic strategies are the new promising therapeutic alternative. Experimental and clinical studies indicate that teriparatide, the active (1–34 parathyroid hormone (PTH molecule, is efficacious for the treatment of GIOP, being able to induce an increase in bone mass in these patients. Intermittent administration of human PTH (1–34 stimulates bone formation by increasing osteoblast number. Additionally, human PTH (1–34 modulates the level and/or activity of locally produced growth factors and cytokines. Teriparatide has been demonstrated in several clinical studies to significantly decrease the incidence of fractures in patients affected by GIOP. It has recently received an indication for GIOP and its label indication has also been expanded.Keywords: glucocorticoids, osteoblasts, osteoclasts, osteoporosis, teriparatide
The Effects of Liver Transplantation on the Bone Metabolism and Gonadal Functions

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Funda Atamaz

2005-06-01

Full Text Available The present study was designed to evaluate the effects of liver transplantation (LT on the bone mineral density (BMD, characteristics of bone turnover, mineral metabolism and sex hormons. Fifty one patients (34 men, 11 women aged 43.5 ± 12.1, who underwent LT were studied, assessing the following parameters: lumbar spine and proximal femur BMD, osteocalcin, deoxypyridinoline (DPD, parathyroid hormone (PTH, free testesterone (FT, gonadotropins (FSH, LH, tyroid hormones, growth hormone (GH and blood/ 24-hours urine Ca and P. All the measures were obtained at baseline and at 3rd month after LT. At baseline, 12 patients (%23.5 had osteoporosis, 22 patients (%43.1 had osteopenia and the mean BMD was 0.892 ± 0.1 for lumbar spine. Whereas, osteoporosis was seen less at femoral neck and total femur: 5 (%9.8 and 4 (%7.8, respectively. Three months after LT, 3.9% drop for lumbar spine, 5.3% drop for femur neck, 6.3% drop for total femur were observed, in BMD these decreases were statistically significant for all sites (p<0.05. The thyroid hormones, GH, PTH, blood Ca, P and osteocalcin levels and urinary DPD excretion were within normal range, while the levels of FSH and LH in women and level of FT in men were lower than normal range. After LT, statistically significant increases were observed in the PTH, osteocalcin, DPD, FSH, LH and FT levels (p<0.05. There was a highly significant negative correlation between duration of liver disease and all the BMD measures (p<0.01. Consequently, the increased osteoporosis ratio which was characterized by high bone turnover was found in patients who underwent LT in this study. The normalization of liver functions following LT was characterized by an early rise in sex hormones.
Vitamin D deficiency in Korean children: prevalence, risk factors, and the relationship with parathyroid hormone levels

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In Hyuk Chung

2014-06-01

Full Text Available PurposeThis study was performed to investigate the relationship between serum vitamin D and parathyroid hormone (PTH levels as well as to describe the prevalence and the risk factors of vitamin D deficiency (VDD in Korean children.MethodsParticipants were 1,212 children aged 4 to 15 years, who visited Bundang CHA Medical Center (located at 37°N between March 2012 and February 2013. Overweight was defined as body mass index≥85th percentile. Participants were divided into 4 age groups and 2 seasonal groups. VDD was defined by serum 25-hydroxyvitamin D (25OHD <20 ng/mL.ResultsThe level of 25OHD was significantly lower in overweight group than in normal weight group (17.1±5.1 ng/mL vs. 19.1±6.1 ng/mL, P<0.001. Winter-spring season (odds ratio [OR], 4.46; 95% confidence interval [CI], 3.45-5.77, older age group (OR, 1.60; 95% CI, 1.36-1.88, and overweight (OR, 2.21; 95% CI, 1.62-3.01 were independently related with VDD. The PTH levels were significantly higher in VDD group compared to vitamin D insufficiency and sufficiency group (P<0.001. In normal weight children, 25OHD (β=-0.007, P<0.001 and ionized calcium (β=-0.594, P=0.007 were independently related with PTH, however, these associations were not significant in overweight children.ConclusionVDD is very common in Korean children and its prevalence increases in winter-spring season, in overweight children and in older age groups. Further investigation on the vitamin D and PTH metabolism according to adiposity is required.
Hormonal alterations in PCOS and its influence on bone metabolism.

Science.gov (United States)

Krishnan, Abhaya; Muthusami, Sridhar

2017-02-01

According to the World Health Organization (WHO) polycystic ovary syndrome (PCOS) occurs in 4-8% of women worldwide. The prevalence of PCOS in Indian adolescents is 12.2% according to the Indian Council of Medical Research (ICMR). The National Institute of Health has documented that it affects approximately 5 million women of reproductive age in the United States. Hormonal imbalance is the characteristic of many women with polycystic ovarian syndrome (PCOS). The influence of various endocrine changes in PCOS women and their relevance to bone remains to be documented. Hormones, which include gonadotrophin-releasing hormone (GnRH), insulin, the leutinizing/follicle-stimulating hormone (LH/FSH) ratio, androgens, estrogens, growth hormones (GH), cortisol, parathyroid hormone (PTH) and calcitonin are disturbed in PCOS women. These hormones influence bone metabolism in human subjects directly as well as indirectly. The imbalance in these hormones results in increased prevalence of osteoporosis in PCOS women. Limited evidence suggests that the drugs taken during the treatment of PCOS increase the risk of bone fracture in PCOS patients through endocrine disruption. This review is aimed at the identification of the relationship between bone mineral density and hormonal changes in PCOS subjects and identifies potential areas to study bone-related disorders in PCOS women. © 2017 Society for Endocrinology.
Two Years of Cinacalcet Hydrochloride Treatment Decreased Parathyroid Gland Volume and Serum Parathyroid Hormone Level in Hemodialysis Patients With Advanced Secondary Hyperparathyroidism.

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Yamada, Shunsuke; Tokumoto, Masanori; Taniguchi, Masatomo; Toyonaga, Jiro; Suehiro, Takaichi; Eriguchi, Rieko; Fujimi, Satoru; Ooboshi, Hiroaki; Kitazono, Takanari; Tsuruya, Kazuhiko

2015-08-01

The long-term effect of cinacalcet hydrochloride treatment on parathyroid gland (PTG) volume has been scarcely investigated in patients with moderate to advanced secondary hyperparathyroidism (SHPT). The present study was a prospective observational study to determine the effect of cinacalcet treatment on PTG volume and serum biochemical parameters in 60 patients with renal SHPT, already treated with intravenous vitamin D receptor activator (VDRA). Measurement of biochemical parameters and PTG volumes were performed periodically, which were analyzed by stratification into tertiles across the baseline parathyroid hormone (PTH) level or PTG volume. We also determined the factors that can estimate the changes in PTG volume and the achievement of the target PTH range by multivariable analyses. Two years of cinacalcet treatment significantly decreased the serum levels of PTH, calcium, and phosphate, followed by the improvement of achieving the target ranges for these parameters recommended by the Japanese Society for Dialysis Therapy. Cinacalcet decreased the maximal and total PTG volume by about 30%, and also decreased the serum PTH level independent of the baseline serum PTH level and PTG volume. Ten out of 60 patients showed 30% increase in maximal PTG after 2 years. Multivariable analysis showed that patients with nodular PTG at baseline and patients with higher serum calcium and PTH levels at 1 year were likely to exceed the target range of PTH at two years. In conclusion, cinacalcet treatment with intravenous VDRA therapy decreased both PTG volume and serum intact PTH level, irrespective of the pretreatment PTG status and past treatment history. © 2015 The Authors. Therapeutic Apheresis and Dialysis © 2015 International Society for Apheresis.
Is calcitonin an active hormone in the onset and prevention of hypocalcemia in dairy cattle?

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Rodríguez, E M; Bach, A; Devant, M; Aris, A

2016-04-01

The objective of this study was to assess the potential importance of calcitonin (CALC) in the onset of subclinical hypocalcemia (experiment 1) and in the physiological mechanisms underlying the prevention of bovine hypocalcemia under metabolic acidosis (experiments 2 and 3). In experiment 1, 15 Holstein cows naturally incurring subclinical hypocalcemia during the first 5d postpartum were classified as low subclinical hypocalcemia (LSH) when blood Ca concentrations were between 7.5 and 8.5mg/dL, or as high subclinical hypocalcemia (HSH) when blood Ca concentrations were between 6.0 and 7.6 mg/dL. Blood samples were taken daily from d -5 to 5 relative to parturition to determine concentrations of parathyroid hormone (PTH), CALC, and 1,25(OH)2D3. In experiment 2, 24 Holstein bulls (497 ± 69 kg of body weight and 342 ± 10.5d of age) were assigned to 2 treatments (metabolic acidosis or control). Metabolic acidosis was induced by an oral administration of ammonium chloride (2.5 mEq/d) during 10 d, and animals were slaughtered thereafter. Blood samples were collected before slaughter to determine CALC, PTH, 1,25(OH)2D3, and samples of urine, kidney, parathyroid, and thyroid glands were obtained immediately after slaughter to determine expression of several genes in these tissues. Last, in experiment 3, we tested the activity of CALC under metabolic acidosis in vitro using breast cancer cell (T47D) cultures. Although PTH tended to be greater in HSH than in LSH, the levels of 1,25(OH)2D3 were lower in HSH cows (experiment 1). Blood CALC concentration was not affected by the severity of subclinical hypocalcemia, but it was influenced by days from calving (experiment 1). The expression of PTH receptor (PTHR) in the kidney was increased under metabolic acidosis (experiment 2). Furthermore, the activity of CALC was impaired under acidic blood pH (experiment 3). In conclusion, the CALC rise in HSH cows after calving impaired the recovery of blood Ca concentrations because the
Parathyroid hormone related to bone regeneration in grafted and nongrafted tooth extraction sockets in rats.

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Kuroshima, Shinichiro; Al-Salihi, Zeina; Yamashita, Junro

2013-02-01

The quality and quantity of bone formed in tooth extraction sockets impact implant therapy. Therefore, the establishment of a new approach to enhance bone formation and to minimize bone resorption is important for the success of implant therapy. In this study, we investigated whether intermittent parathyroid hormone (PTH) therapy enhanced bone formation in grafted sockets. Tooth extractions of the maxillary first molars were performed in rats, and the sockets were grafted with xenograft. Intermittent PTH was administered either for 7 days before extractions, for 14 days after extractions, or both. The effect of PTH therapy on bone formation in the grafted sockets was assessed using microcomputed tomography at 14 days after extractions. PTH therapy for 7 days before extractions was not effective to augment bone fill, whereas PTH therapy for 14 days after operation significantly augmented bone formation in the grafted sockets. Intermittent PTH therapy starting right after tooth extractions significantly enhanced bone fill in the grafted sockets, suggesting that PTH therapy can be a strong asset for the success of the ridge preservation procedure.
Vitamin D status and 5-year changes in urine albumin creatinine ratio and parathyroid hormone in a general population

DEFF Research Database (Denmark)

Skaaby, Tea; Husemoen, Lise Lotte Nystrup; Pisinger, Charlotta

2013-01-01

and negatively correlated with glomerular filtration rate. We investigated the association between vitamin D status and 5-year changes in urine albumin creatinine ratio (UACR) and parathyroid hormone (PTH). A random sample of 6,784 individuals aged 30-60 years from a general population participated in the Inter......99 study in 1999-2001. Vitamin D (serum-25-hydroxyvitamin D) was measured at baseline by high-performance liquid chromatography. UACR and PTH were measured at baseline and follow-up. Increased UACR was defined as UACR >4.0 mg/g reflecting the upper quartile at baseline. We included 4,330 individuals...
Let-7 and MicroRNA-148 Regulate Parathyroid Hormone Levels in Secondary Hyperparathyroidism.

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Shilo, Vitali; Mor-Yosef Levi, Irit; Abel, Roy; Mihailović, Aleksandra; Wasserman, Gilad; Naveh-Many, Tally; Ben-Dov, Iddo Z

2017-08-01

Secondary hyperparathyroidism commonly complicates CKD and associates with morbidity and mortality. We profiled microRNA (miRNA) in parathyroid glands from experimental hyperparathyroidism models and patients receiving dialysis and studied the function of specific miRNAs. miRNA deep-sequencing showed that human and rodent parathyroids share similar profiles. Parathyroids from uremic and normal rats segregated on the basis of their miRNA expression profiles, and a similar finding was observed in humans. We identified parathyroid miRNAs that were dysregulated in experimental hyperparathyroidism, including miR-29, miR-21, miR-148, miR-30, and miR-141 (upregulated); and miR-10, miR-125, and miR-25 (downregulated). Inhibition of the abundant let-7 family increased parathyroid hormone (PTH) secretion in normal and uremic rats, as well as in mouse parathyroid organ cultures. Conversely, inhibition of the upregulated miR-148 family prevented the increase in serum PTH level in uremic rats and decreased levels of secreted PTH in parathyroid cultures. The evolutionary conservation of abundant miRNAs in normal parathyroid glands and the regulation of these miRNAs in secondary hyperparathyroidism indicates their importance for parathyroid function and the development of hyperparathyroidism. Specifically, let-7 and miR-148 antagonism modified PTH secretion in vivo and in vitro , implying roles for these specific miRNAs. These findings may be utilized for therapeutic interventions aimed at altering PTH expression in diseases such as osteoporosis and secondary hyperparathyroidism. Copyright © 2017 by the American Society of Nephrology.

Serum vitamin D and parathormone (PTH) concentrations as ...

African Journals Online (AJOL)

Rania Naguib Abdel Mouteleb Abdel Reheem

2012-10-06

Oct 6, 2012 ... concentrations as predictors of the development and ... of vitamin D might be a risk marker of development or progression of ... 25(OH) 2 D3 may lead to increased, uncontrolled angio- ... PTH excess can reduce glucose tolerance16 and induce ... was separated and stored frozen at 20° C. Routine blood.
Novel, selective vitamin D analog suppresses parathyroid hormone in uremic animals and postmenopausal women.

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Zella, Julia B; Plum, Lori A; Plowchalk, David R; Potochoiba, Michael; Clagett-Dame, Margaret; DeLuca, Hector F

2014-01-01

The use of 1α-hydroxylated vitamin D therapy to control secondary hyperparathyroidism in renal failure patients has been a success story, culminating with the demonstration of increased life expectancy in patients treated with these compounds. However, hypercalcemic episodes have been a recurrent problem with these therapies and have resulted in the added use of calcium mimetics. Clearly there is good reason to search for improved vitamin D therapy. In our inventory of vitamin D compounds, 2-methylene-19-nor-(20S)-1α,25-dihydroxyvitamin D3 (2MD) surfaced as a potential candidate. This was based on its preferential localization in the parathyroid gland and a clear suppression of serum parathyroid hormone (PTH) levels without a change in serum calcium in a clinical trial in postmenopausal women. 2MD has now been tested in the rat 5/6-nephrectomy model of renal failure, and in postmenopausal women to determine if it can suppress serum PTH at doses that do not elevate serum calcium and serum phosphorus concentrations. Daily oral treatment of uremic rats on 2.5 ng/bw/day of 2MD dramatically suppressed PTH without a change in serum calcium or serum phosphorus. Further, PTH was suppressed in postmenopausal women after only 3 daily oral doses of 2MD that continued for 4 weeks with no change in serum calcium or serum phosphorus. These results coupled with a pharmacokinetic half-life of ~24 h suggest that 2MD given either daily or at the time of dialysis may be a superior therapy for secondary hyperparathyroidism in chronic renal failure patients.
Defective postnatal endochondral bone development by chondrocyte-specific targeted expression of parathyroid hormone type 2 receptor.

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Panda, Dibyendu Kumar; Goltzman, David; Karaplis, Andrew C

2012-12-15

The human parathyroid hormone type 2 receptor (PTH2R) is activated by PTH and by tuberoinfundibular peptide of 39 residues (TIP39), the latter likely acting as its natural ligand. Although the receptor is expressed at highest levels in the nervous system, we have observed that both PTH2R and TIP39 are expressed in the newborn mouse growth plate, with the receptor localizing in the resting zone and the ligand TIP39 localizing exclusively in prehypertrophic and hypertrophic chondrocytes. To address the role of PTH2R in postnatal skeletal growth and development, Col2a1-hPTH2R (PTH2R-Tg) transgenic mice were generated. The mice were viable and of nearly normal size at birth. Expression of the transgene in the growth plate was limited to chondrocytes. We found that chondrocyte proliferation was decreased, as determined by in vivo BrdU labeling of proliferating chondrocytes and CDK4 and p21 expression in the growth plate of Col2a1-hPTH2R transgenic mice. Similarly, the differentiation and maturation of chondrocytes was delayed, as characterized by decreased Sox9 expression and weaker immunostaining for the chondrocyte differentiation markers collagen type II and type X and proteoglycans. As well, there was altered expression of Gdf5, Wdr5, and β-catenin, factors implicated in chondrocyte maturation, proliferation, and differentiation.These effects impacted on the process of endochondral ossification, resulting in delayed formation of the secondary ossification center, and diminished trabecular bone volume. The findings substantiate a role for PTH2R signaling in postnatal growth plate development and subsequent bone mass acquisition.
Rapid intraoperative parathyroid hormone assay--more than just a comfort measure.

LENUS (Irish Health Repository)

Hanif, F

2012-02-03

BACKGROUND: Minimally invasive radio-guided parathyroidectomy (MIRP) has been embraced as an acceptable therapeutic approach to primary hyperparathyroidism. Preoperative sestamibi scanning has facilitated this technique. Here we evaluate the addition of a rapid intraoperative parathyroid hormone (iPTH) assay for patients undergoing MIRP. METHODS: A series of 51 patients underwent sestamibi localization of parathyroid glands followed by MIRP for primary hyperparathyroidism. Using peripheral venous samples, iPTH levels were measured prior to gland excision, as well as post-excision at 5, 10, and 15 minutes, taking a 50% reduction in iPTH level as indicative of complete excision. Next, changes in serum iPTH were compared with preoperative and postoperative changes in serum calcium, as well as levels of intraoperative ex-vivo radiation counts taken by hand-held gamma probe. RESULTS: In this series, a drop of greater than 50% in iPTH levels was observed in 94% of patients (n=48). Moreover, a significant drop in iPTH occurred within 10 minutes of excision in the majority (n=42) of cases (P<0.004). Changes in iPTH were comparable with the therapeutic reduction in calcium levels, as well as with the change in intraoperative ex-vivo gamma counts. CONCLUSIONS: This study demonstrates that the addition of an iPTH assay to MIRP provides a quick and reliable intraoperative diagnostic modality in confirming correct adenoma removal. Moreover, it precludes the requirement of frozen section.
Temporal trends and determinants of longitudinal change in 25-hydroxyvitamin D and parathyroid hormone levels.

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Berger, Claudie; Greene-Finestone, Linda S; Langsetmo, Lisa; Kreiger, Nancy; Joseph, Lawrence; Kovacs, Christopher S; Richards, J Brent; Hidiroglou, Nick; Sarafin, Kurtis; Davison, K Shawn; Adachi, Jonathan D; Brown, Jacques; Hanley, David A; Prior, Jerilynn C; Goltzman, David

2012-06-01

Vitamin D is essential for facilitating calcium absorption and preventing increases in parathyroid hormone (PTH), which can augment bone resorption. Our objectives were to examine serum levels of 25-hydroxyvitamin D [25(OH)D] and PTH, and factors related to longitudinal change in a population-based cohort. This is the first longitudinal population-based study looking at PTH and 25(OH)D levels. We analyzed 3896 blood samples from 1896 women and 829 men in the Canadian Multicentre Osteoporosis Study over a 10-year period starting in 1995 to 1997. We fit hierarchical models with all available data and adjusted for season. Over 10 years, vitamin D supplement intake increased by 317 (95% confidence interval [CI] 277 to 359) IU/day in women and by 193 (135 to 252) IU/day in men. Serum 25(OH)D (without adjustment) increased by 9.3 (7.3 to 11.4) nmol/L in women and by 3.5 (0.6 to 6.4) nmol/L in men but increased by 4.7 (2.4 to 7.0) nmol/L in women and by 2.7 (-0.6 to 6.2) nmol/L in men after adjustment for vitamin D supplements. The percentage of participants with 25(OH)D levels <50 nmol/L was 29.7% (26.2 to 33.2) at baseline and 19.8% (18.0 to 21.6) at year 10 follow-up. PTH decreased over 10 years by 7.9 (5.4 to 11.3) pg/mL in women and by 4.6 (0.2 to 9.0) pg/mL in men. Higher 25(OH)D levels were associated with summer, younger age, lower body mass index (BMI), regular physical activity, sun exposure, and higher total calcium intake. Lower PTH levels were associated with younger age and higher 25(OH)D levels in both women and men and with lower BMI and participation in regular physical activity in women only. We have observed concurrent increasing 25(OH)D levels and decreasing PTH levels over 10 years. Secular increases in supplemental vitamin D intake influenced both changes in serum 25(OH)D and PTH levels. Copyright © 2012 American Society for Bone and Mineral Research.
Radioimmunoassay for the middle region of human parathyroid hormone: comparison of two radioiodinated synthetic peptides

International Nuclear Information System (INIS)

Sharp, M.E.; Marx, S.J.

1985-01-01

Two synthetic peptides were evaluated to develop radioligands for midregion-specific radioimmunoassay (RIA) of human parathyroid hormone (hPTH). Both radioligands were tested using three anti-PTH sera of proven clinical utility. While each of these midregion-directed antisera showed unique specificity, they all reacted with high affinity with both radioligands and none of them discriminated significantly between the two synthetic midregion peptides. Analysis of data on the relation of serum calcium and hPTH midregion immunoreactivity showed a useful separation of groups (all nonazotemic) with primary hyperparathyroidism, secondary hyperparathyroidism, primary hypoparathyroidism and secondary hypoparathyroidism. (Auth.)
Effects of parathyroid hormone alone or in combination with antiresorptive therapy on bone mineral density and fracture risk--a meta-analysis

DEFF Research Database (Denmark)

Vestergaard, P; Jørgensen, Niklas R; Mosekilde, L

2007-01-01

AIM: The effects of parathyroid hormone (PTH) alone or in combination with antiresorptive therapy on changes in bone mineral density (BMD) and fracture risk were studied. MATERIALS AND METHODS: Randomised placebo controlled trials were retrieved from the PubMed, Web of Science or Embase databases......, nausea and discomfort at the injection sites. Only limited data are currently available on fracture risk reduction with PTH plus antiresorptive therapies. CONCLUSION: Although the number of studies on non-vertebral fractures is limited, our pooled analysis revealed that PTH alone or in combination...... are necessary. No studies comparing PTH, PTH plus antiresorptive drugs and antiresorptive drug versus placebo in a factorial design are available; consequently, we were unable to draw any conclusions on the superiority of PTH plus antiresorptive drug versus antiresorptive drug or PTH alone with respect to BMD...
Model of the complex of Parathyroid hormone-2 receptor and Tuberoinfundibular peptide of 39 residues

Directory of Open Access Journals (Sweden)

Persson Bengt

2010-10-01

Full Text Available Abstract Background We aim to propose interactions between the parathyroid hormone-2 receptor (PTH2R and its ligand the tuberoinfundibular peptide of 39 residues (TIP39 by constructing a homology model of their complex. The two related peptides parathyroid hormone (PTH and parathyroid hormone related protein (PTHrP are compared with the complex to examine their interactions. Findings In the model, the hydrophobic N-terminus of TIP39 is buried in a hydrophobic part of the central cavity between helices 3 and 7. Comparison of the peptide sequences indicates that the main discriminator between the agonistic peptides TIP39 and PTH and the inactive PTHrP is a tryptophan-phenylalanine replacement. The model indicates that the smaller phenylalanine in PTHrP does not completely occupy the binding site of the larger tryptophan residue in the other peptides. As only TIP39 causes internalisation of the receptor and the primary difference being an aspartic acid in position 7 of TIP39 that interacts with histidine 396 in the receptor, versus isoleucine/histidine residues in the related hormones, this might be a trigger interaction for the events that cause internalisation. Conclusions A model is constructed for the complex and a trigger interaction for full agonistic activation between aspartic acid 7 of TIP39 and histidine 396 in the receptor is proposed.
Increased risk of all-cause mortality and renal graft loss in stable renal transplant recipients with hyperparathyroidism.

Science.gov (United States)

Pihlstrøm, Hege; Dahle, Dag Olav; Mjøen, Geir; Pilz, Stefan; März, Winfried; Abedini, Sadollah; Holme, Ingar; Fellström, Bengt; Jardine, Alan G; Holdaas, Hallvard

2015-02-01

Hyperparathyroidism is reported in 10% to 66% of renal transplant recipients (RTR). The influence of persisting hyperparathyroidism on long-term clinical outcomes in RTR has not been examined in a large prospective study. We investigated the association between baseline parathyroid hormone (PTH) levels and major cardiovascular events, renal graft loss, and all-cause mortality by Cox Proportional Hazard survival analyses in 1840 stable RTR derived from the Assessment of LEscol in Renal Transplantation trial. Patients were recruited in a mean of 5.1 years after transplantation, and follow-up time was 6 to 7 years. Significant associations between PTH and all 3 outcomes were found in univariate analyses. When adjusting for a range of plausible confounders, including measures of renal function and serum mineral levels, PTH remained significantly associated with all-cause mortality (4% increased risk per 10 units; P=0.004), and with graft loss (6% increased risk per 10 units; PHyperparathyroidism is an independent, potentially remediable, risk factor for renal graft loss and all-cause mortality in RTR.
Parathyroid carcinoma survival: improvements in the era of intact parathyroid hormone monitoring?

Directory of Open Access Journals (Sweden)

Steve R. Martinez

2013-02-01

Full Text Available The intact parathyroid hormone (iPTH assay is a critical test in the diagnosis and management of PTH-mediated hypercalcemia, including parathyroid carcinoma (PCa. We hypothesized that the survival of patients diagnosed with PCa has improved since adoption of the iPTH assay into clinical practice. We identified all confirmed cases of PCa within the Surveillance, Epidemiology and End Results database from 1973 to 2006. Patients were categorized into two eras based upon introduction of the iPTH assay: 1973 to 1997 (era I and 1997 to 2006 (era II, when the iPTH assay was in standard use. We estimated overall survival (OS and disease-specific survival (DSS using the Kaplan-Meier method, with differences among survival curves assessed via log rank. Multivariate Cox proportional hazards models compared the survival rates between treatment eras while controlling for patient age, sex, race/ethnicity, tumor size, nodal status, extent of disease, and type of surgery. Multivariate models included patients undergoing potentially curative surgery and excluded those with dis- tant metastases. Risks of overall and disease-specific mortality were reported as hazard ratios with 95% confidence intervals. Study criteria were met by 370 patients. Median survival was 15.6 years. Five-year rates of OS and DSS were 78% and 88% for era I and 82% and 96% for era II. On multivariate analysis, age, black race, and unknown extent of disease predicted an increased risk of death from any cause. Treatment era did not predict OS. No factor predicted PCa-specific mortality. In multivariate analysis, neither OS nor DSS have improved in the current era that utilizes iPTH for the detection and management of PCa.
Serum Parathyroid Hormone Responses to Vitamin D Supplementation in Overweight/Obese Adults: A Systematic Review and Meta-Analysis of Randomized Clinical Trials

Directory of Open Access Journals (Sweden)

Ashley Lotito

2017-03-01

Full Text Available Obesity is often associated with vitamin D deficiency and secondary hyperparathyroidism. Vitamin D supplementation typically leads to the reductions in serum parathyroid hormone (PTH levels, as shown in normal weight individuals. Meanwhile, the dose of vitamin D supplementation for the suppression of PTH may differ in overweight and obese adults. We conducted a systematic review and meta-analysis of randomized controlled trials to determine the dose of vitamin D supplementation required to suppress PTH levels in overweight/obese individuals. We identified 18 studies that examined overweight or obese healthy adults who were supplemented with varying doses of vitamin D3. The primary outcomes examined were changes in PTH and serum 25-hydroxyvitamin D (25OHD levels from baseline to post-treatment. The results of the meta-analysis showed that there was a significant treatment effect of vitamin D supplementation on PTH, total standardized mean difference (SMD (random effects = −0.38 (95% CI = −0.56 to −0.20, t = −4.08, p < 0.001. A significant treatment effect of vitamin D supplementation was also found on 25OHD, total SMD (random effects = 2.27 (95% CI = 1.48 to 3.06 t = 5.62, p < 0.001. Data from available clinical trials that supplemented adults with D3 ranging from 400 IU to 5714 IU, showed that 1000 IU of vitamin D supplementation best suppressed serum PTH levels, total SMD = −0.58, while vitamin D supplementation with 4000 IU showed the greatest increase in serum 25OH levels. Vitamin D and calcium supplementation of 700 IU and 500 mg, respectively, also showed a significant treatment effect on the suppression of PTH with a total SMD = −5.30 (95% CI = −9.72 to −0.88. In conclusion, the meta analysis of available clinical trials indicates that 1000 IU vitamin D supplementation can suppress serum PTH levels, while 4000 IU of vitamin D was associated with the largest increase in serum 25OHD levels in the overweight and obese
Parathyroid hormone dependent T cell proliferation in uremic rats

DEFF Research Database (Denmark)

Lewin, E; Ladefoged, Jens; Brandi, L

1993-01-01

Chronic renal failure (CRF) is combined with an impairment of the immune system. The T cell may be a target for the action of parathyroid hormone (PTH). Rats with CRF have high blood levels of PTH. Therefore, the present investigation examined some aspects of the T cell function in both normal...... and CRF rats before and after parathyroidectomy and after an isogenic kidney transplantation. The T cell proliferative response to phytohemagglutinin (PHA) stimulation was significantly higher in peripheral blood mononuclear cell (PBMC) cultures obtained from CRF rats than from normal rats. After...... parathyroidectomy the T cells of normal as well as of uremic rats could still be significantly stimulated by PHA, but now no significant difference was seen. When CRF was reversed after an isogenic kidney transplantation and PTH reversed to levels in the normal range, the T cell proliferative response to PHA...
Negative regulation of human parathyroid hormone gene promoter by vitamin D3 through nuclear factor Y

International Nuclear Information System (INIS)

Jaeaeskelaeinen, T.; Huhtakangas, J.; Maeenpaeae, P.H.

2005-01-01

The negative regulation of the human parathyroid hormone (PTH) gene by biologically active vitamin D 3 (1,25-dihydroxyvitamin D 3 ; 1,25(OH) 2 D 3 ) was studied in rat pituitary GH4C1 cells, which express factors needed for the negative regulation. We report here that NF-Y binds to sequences downstream of the site previously reported to bind the vitamin D receptor (VDR). Additional binding sites for NF-Y reside in the near vicinity and were shown to be important for full activity of the PTH gene promoter. VDR and NF-Y were shown to exhibit mutually exclusive binding to the VDRE region. According to our results, sequestration of binding partners for NF-Y by VDR also affects transcription through a NF-Y consensus binding element in GH4C1 but not in ROS17/2.8 cells. These results indicate that 1,25(OH) 2 D 3 may affect transcription of the human PTH gene both by competitive binding of VDR and NF-Y, and by modulating transcriptional activity of NF-Y
Effects of continual intermittent administration of parathyroid hormone on implant stability in the presence of osteoporosis: an in vivo study using resonance frequency analysis in a rabbit model

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Yoshifumi Oki

Full Text Available Abstract Objective: This study aimed to evaluate the effects of continual intermittent administration of parathyroid hormone (PTH on implant stability in the presence of osteoporosis, using rabbit models. Material and Methods: Fifteen female New Zealand white rabbits underwent ovariectomy and were administered glucocorticoids to induce osteoporosis, following which they were divided into three groups. The first group received intermittent subcutaneous PTH for 4 weeks until implant placement (PTH1, while the second and third groups received PTH (PTH2 and saline (control, respectively, for 4 weeks before and after implant placement. After intermittent administration of PTH or saline, titanium implants were inserted into the left femoral epiphyses of all animals, and the implant stability quotient (ISQ was measured immediately after placement to assess the primary stability and at 2 and 4 weeks after implant placement to assess osseointegration. At 4 weeks after implant placement, histological and histomorphometric evaluations were conducted and the bone area around the implant socket was measured as a ratio of the total bone area to the total tissue area. Results: Regarding primary stability, the ISQ values for the PTH1 and PTH2 groups were significantly higher than those for the control group (p<0.05. Concerning osseointegration, the ISQ values at 2 and 4 weeks were significantly higher for the PTH2 group than for the PTH1 and control (p<0.05 groups. Histological assessments showed a thicker and more trabecular bone around the implant sockets in the PTH2 specimens than in the PTH1 and control specimens. The bone area around the implant socket was significantly greater in the PTH2 group than in the PTH1 and control groups (p<0.05. Conclusions: Our results suggest that continual intermittent PTH administration before and after dental implant placement is effective for the achievement of favorable stability and osseointegration in the presence of
Growth hormone-releasing hormone as an agonist of the ghrelin receptor GHS-R1a.

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Casanueva, Felipe F; Camiña, Jesus P; Carreira, Marcos C; Pazos, Yolanda; Varga, Jozsef L; Schally, Andrew V

2008-12-23

Ghrelin synergizes with growth hormone-releasing hormone (GHRH) to potentiate growth hormone (GH) response through a mechanism not yet fully characterized. This study was conducted to analyze the role of GHRH as a potential ligand of the ghrelin receptor, GHS-R1a. The results show that hGHRH(1-29)NH(2) (GHRH) induces a dose-dependent calcium mobilization in HEK 293 cells stably transfected with GHS-R1a an effect not observed in wild-type HEK 293 cells. This calcium rise is also observed using the GHRH receptor agonists JI-34 and JI-36. Radioligand binding and cross-linking studies revealed that calcium response to GHRH is mediated by the ghrelin receptor GHS-R1a. GHRH activates the signaling route of inositol phosphate and potentiates the maximal response to ghrelin measured in inositol phosphate turnover. The presence of GHRH increases the binding capacity of (125)I-ghrelin in a dose dependent-fashion showing a positive binding cooperativity. In addition, confocal microscopy in CHO cells transfected with GHS-R1a tagged with enhanced green fluorescent protein shows that GHRH activates the GHS-R1a endocytosis. Furthermore, the selective GHRH-R antagonists, JV-1-42 and JMR-132, act also as antagonists of the ghrelin receptor GHS-R1a. Our findings suggest that GHRH interacts with ghrelin receptor GHS-R1a, and, in consequence, modifies the ghrelin-associated intracellular signaling pathway. This interaction may represent a form of regulation, which could play a putative role in the physiology of GH regulation and appetite control.
Combination therapy of Nigella sativa and human parathyroid hormone on bone mass, biomechanical behavior and structure in streptozotocin-induced diabetic rats.

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Altan, Mehmet Fatih; Kanter, Mehmet; Donmez, Senayi; Kartal, Murat Emre; Buyukbas, Sadik

2007-01-01

Extracts of the seeds of Nigella sativa (NS), an annual herbaceous plant of the Ranunculaceae family, have been used for many years for therapeutic purposes, including their potential anti-diabetic properties. The aim of the present study was to test the hypothesis that combined treatment with NS and human parathyroid hormone (hPTH) is more effective than treatment with NS or hPTH alone in improving bone mass, connectivity, biomechanical behaviour and strength in insulin-dependent diabetic rats. Diabetes was induced by intraperitoneal injection of streptozotocin (STZ) at a single dose of 50mg/kg. The diabetic rats received NS (2ml/kg/day, i.p.), hPTH (6microg/kg/day, i.p.) or NS and hPTH combined for 4 weeks, starting 8 weeks after STZ injection. The beta-cells of the pancreatic islets of Langerhans were examined by immunohistochemical methods. In addition, bone sections of femora were processed for histomorphometry and biomechanical analysis. In diabetic rats, the beta-cells were essentially negative for insulin-immunoreactivity. NS treatment (alone or in combination with hPTH) significantly increased the area of insulin immunoreactive beta-cells in diabetic rats; however, hPTH treatment alone only led to a slightly increase in the insulin-immunoreactivity. These results suggest that NS might be used in a similar manner to insulin as a safe and effective therapy for diabetes and might be useful in the treatment of diabetic osteopenia.
Vitamin D supplementation has minor effects on parathyroid hormone and bone turnover markers in vitamin D-deficient bedridden older patients.

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Björkman, Mikko; Sorva, Antti; Risteli, Juha; Tilvis, Reijo

2008-01-01

to evaluate the effects of vitamin D supplementation on parathyroid function and bone turnover in aged, chronically immobile patients. a randomised double-blind controlled trial. two hundred and eighteen long-term inpatients aged over 65 years. the patients were randomised into treatment groups of I-III, each receiving 0 IU, 400 IU and 1200 IU cholecalciferol per day, respectively. In case of inadequate consumption of dairy products, patients received a daily calcium substitution of 500 mg. plasma concentrations of 25-hydroxyvitamin D (25-OHD), intact parathyroid hormone (PTH), amino-terminal propeptide of type I procollagen (PINP), a marker of bone formation, and carboxy-terminal telopeptide of type I collagen (ICTP), a marker of bone resorption, were measured at baseline and after 6 months. the patients (age 84.5 years) were chronically bedridden. The baseline 25-OHD was low (23 nmol/l), correlated inversely with PINP, and tended to associate inversely with PTH. The prevalence of vitamin D deficiency (VDD) (25-OHD < 50 nmol/l) was 98% and PTH was elevated in 23% of the patients. Vitamin D supplementation significantly increased 25-OHD concentrations (124% group II, 204% group III) and decreased PTH (-7% group II, -8% group III). PINP tended to decrease, but ICTP tended to increase, and only their ratio decreased significantly. The tendency of ICTP to increase was inconsistent. Changes in 25-OHD correlated inversely with those in PTH and PINP. vitamin D supplementation has minor effects on PTH and bone turnover in chronically immobilised aged patients with VDD. Further comparative studies and meta-analyses are warranted to elucidate the confounding effects of different mobility levels on the benefits of vitamin D supplementation in patients with differing baseline PTH levels.
Reciprocal changes in parathyroid hormone and thyroid function after radioiodine treatment of hyperthyroidism

International Nuclear Information System (INIS)

Ross, D.S.; Nussbaum, S.R.

1989-01-01

Hyperthyroidism is associated with negative calcium balance, normal to increased serum calcium concentrations, and decreased cortical bone mass. There is no agreement concerning serum PTH levels in such patients. In this study, we measured serum PTH concentrations using a newly developed sensitive 2-site immunoradiometric assay in 17 hyperthyroid patients before and after radioiodine therapy. The mean serum PTH and calcium concentrations were 28 +/- 15 (+/- SD) ng/L (normal range, 12-65 ng/L) and 2.4 +/- 0.5 mmol/L (normal range, 2.1-2.6 mmol/L) before therapy. After therapy serum PTH concentrations increased in 16 of the 17 patients. The increase in serum PTH was greater in the 9 patients who became hypothyroid rapidly (29 +/- 15 to 75 +/- 29 ng/L) compared with that in the 8 patients who became euthyroid gradually (26 +/- 16 to 45 +/- 24 ng/L). Serum PTH rose along with TSH as the patients became hypothyroid after radioiodine, and both serum PTH and TSH fell when L-T4 therapy was given. The reciprocal changes in serum PTH concentrations and thyroid function over time suggest a strong association of bone mineral metabolism and thyroid status
Reciprocal changes in parathyroid hormone and thyroid function after radioiodine treatment of hyperthyroidism

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Ross, D.S.; Nussbaum, S.R.

1989-06-01

Hyperthyroidism is associated with negative calcium balance, normal to increased serum calcium concentrations, and decreased cortical bone mass. There is no agreement concerning serum PTH levels in such patients. In this study, we measured serum PTH concentrations using a newly developed sensitive 2-site immunoradiometric assay in 17 hyperthyroid patients before and after radioiodine therapy. The mean serum PTH and calcium concentrations were 28 +/- 15 (+/- SD) ng/L (normal range, 12-65 ng/L) and 2.4 +/- 0.5 mmol/L (normal range, 2.1-2.6 mmol/L) before therapy. After therapy serum PTH concentrations increased in 16 of the 17 patients. The increase in serum PTH was greater in the 9 patients who became hypothyroid rapidly (29 +/- 15 to 75 +/- 29 ng/L) compared with that in the 8 patients who became euthyroid gradually (26 +/- 16 to 45 +/- 24 ng/L). Serum PTH rose along with TSH as the patients became hypothyroid after radioiodine, and both serum PTH and TSH fell when L-T4 therapy was given. The reciprocal changes in serum PTH concentrations and thyroid function over time suggest a strong association of bone mineral metabolism and thyroid status.
Increased and mistimed sex hormone production in night shift workers.

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Papantoniou, Kyriaki; Pozo, Oscar J; Espinosa, Ana; Marcos, Josep; Castaño-Vinyals, Gemma; Basagaña, Xavier; Juanola Pagès, Elena; Mirabent, Joan; Martín, Jordi; Such Faro, Patricia; Gascó Aparici, Amparo; Middleton, Benita; Skene, Debra J; Kogevinas, Manolis

2015-05-01

Night shift work has been associated with an increased risk for breast and prostate cancer. The effect of circadian disruption on sex steroid production is a possible underlying mechanism, underinvestigated in humans. We have assessed daily rhythms of sex hormones and melatonin in night and day shift workers of both sexes. We recruited 75 night and 42 day workers, ages 22 to 64 years, in different working settings. Participants collected urine samples from all voids over 24 hours on a working day. Urinary concentrations of 16 sex steroid hormones and metabolites (estrogens, progestagens, and androgens) and 6-sulfatoxymelatonin were measured in all samples. Mean levels and peak time of total and individual metabolite production were compared between night and day workers. Night workers had higher levels of total progestagens [geometric mean ratio (GMR) 1.65; 95% confidence intervals (CI), 1.17-2.32] and androgens (GMR: 1.44; 95% CI, 1.03-2.00), compared with day workers, after adjusting for potential confounders. The increased sex hormone levels among night shift workers were not related to the observed suppression of 6-sulfatoxymelatonin. Peak time of androgens was significantly later among night workers, compared with day workers (testosterone: 12:14 hours; 10:06-14:48 vs. 08:35 hours; 06:52-10:46). We found increased levels of progestagens and androgens as well as delayed peak androgen production in night shift workers compared with day workers. The increase and mistiming of sex hormone production may explain part of the increased risk for hormone-related cancers observed in night shift workers. ©2015 American Association for Cancer Research.

Serum 25(OHD Level and Parathyroid Hormone in Chinese Adult Population: A Cross-Sectional Study in Guiyang Urban Community from Southeast of China

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Zhang Qiao

2013-01-01

Full Text Available Objective. To evaluate vitamin D status and serum parathyroid hormone (IPTH of healthy adults living in Guiyang. Design and Participants. We conducted a cross-sectional evaluation in the General Community in Guiyang by cluster sampling method. The data was a part of 1510 participants (634 men, 876 women aged 20–79 years median 45.2 years from November 2009 to February 2010 in Guiyang Health Measures Survey. Measurements. Aradioimmunoassay was used to measure the level of 25-hydroxyvitamin D [25(OHD] and intact parathyroid hormone (iPTH. Results.The mean serum 25(OHD level was (20.4 ± 9.0 ng/mL and the highest level among participants aged 40–59 years (22.8 ng/mL. The mean serum PTH level was (32.1 ± 13.7 pg/mL and the lowest level among participants aged 40–50 years (30.8 ng/mL. Serum 25(OHD was below 50 nmol/liter in 52.3%, below 75 nmol/liter in 84.6%, and above 75 nmol/liter in 15.4% of the respondents. Secondary hyperparathyroidism was 5.4% (5.4% among men and 4.6% among women. The prevalence of secondary hyperparathyroidism increased (5.8%, 6.5%, and 7.1%, resp. with decreasing serum 25(OHD levels among subjects who were 30 to 20, 19.9 to 10, and <10 ng/mL, respectively. Serum 25(OHD was inversely associated with serum PTH. Conclusions. Vitamin D insufficiency and its complication of secondary hyperparathyroidism are common.
Delayed administration of recombinant human parathyroid hormone improves early biomechanical strength in a rat rotator cuff repair model.

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Duchman, Kyle R; Goetz, Jessica E; Uribe, Bastian U; Amendola, Andrew M; Barber, Joshua A; Malandra, Allison E; Fredericks, Douglas C; Hettrich, Carolyn M

2016-08-01

Despite advances in intraoperative techniques, rotator cuff repairs frequently do not heal. Recombinant human parathyroid hormone (rhPTH) has been shown to improve healing at the tendon-to-bone interface in an established acute rat rotator cuff repair model. We hypothesized that administration of rhPTH beginning on postoperative day 7 would result in improved early load to failure after acute rotator cuff repair in an established rat model. Acute rotator cuff repairs were performed in 108 male Sprague-Dawley rats. Fifty-four rats received daily injections of rhPTH beginning on postoperative day 7 until euthanasia or a maximum of 12 weeks postoperatively. The remaining 54 rats received no injections and served as the control group. Animals were euthanized at 2 and 16 weeks postoperatively and evaluated by gross inspection, biomechanical testing, and histologic analysis. At 2 weeks postoperatively, rats treated with rhPTH demonstrated significantly higher load to failure than controls (10.9 vs. 5.2 N; P = .003). No difference in load to failure was found between the 2 groups at 16 weeks postoperatively, although control repairs more frequently failed at the tendon-to-bone interface (45.5% vs. 22.7%; P = .111). Blood vessel density appeared equivalent between the 2 groups at both time points, but increased intracellular and extracellular vascular endothelial growth factor expression was noted in the rhPTH-treated group at 2 weeks. Delayed daily administration of rhPTH resulted in increased early load to failure and equivalent blood vessel density in an acute rotator cuff repair model. Copyright © 2016 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.
Intronic deletions in the SLC34A3 gene: A cautionary tale for mutation analysis of hereditary hypophosphatemic rickets with hypercalciuria

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Ichikawa, Shoji; Tuchman, Shamir; Padgett, Leah R.; Gray, Amie K.; Baluarte, H. Jorge; Econs, Michael J.

2013-01-01

Hereditary hypophosphatemic rickets with hypercalciuria (HHRH) is a rare metabolic disorder, characterized by hypophosphatemia, variable degrees of rickets/osteomalacia, and hypercalciuria secondary to increased serum 1,25-dihydroxyvitamin D [1,25(OH)2D] levels. HHRH is caused by mutations in the SLC34A3 gene, which encodes sodium-phosphate co-transporter type IIc. A 6 ½-year-old female presented with a history of nephrolithiasis. Her metabolic evaluation revealed increased 24- hour urine calcium excretion with high serum calcium, low intact parathyroid hormone (PTH) levels, and elevated 1,25(OH)2D level. In addition, the patient had low to low-normal serum phosphorus with high urine phosphorus. The patient had normal stature; without rachitic or boney deformities or a history of fractures. Genetic analysis of SLC34A3 revealed the patient to be a compound heterozygote for a novel single base pair deletion in exon 12 (c.1304delG) and 30-base pair deletion in intron 6 (g.1440–1469del). The single-base pair mutation causes a frameshift, which results in premature stop codon. The intronic deletion is likely caused by misalignment of the 4-basepair homologous repeats and results in the truncation of an already small intron to 63 bp, which would impair proper RNA splicing of the intron. This is the fourth unique intronic deletion identified in patients with HHRH, suggesting the frequent occurrence of sequence misalignments in SLC34A3 and the importance of screening introns in patients with HHRH. PMID:24176905
Solution Structure of Archaeoglobus fulgidis Peptidyl-tRNA Hydrolase(Pth2) Provides Evidence for an Extensive Conserved Family of Pth2 Enzymes in Archaea, Bacteria and Eukaryotes.

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Powers, Robert; Mirkovic, Nebojsa; Goldsmith-Fischman, Sharon; Acton, Thomas; Chiang, Yiwen; Huang, Yuanpeng; Ma, LiChung; Rajan, Paranji K.; Cort, John R.; Kennedy, Michael A.; Liu, Jinfeng; Rost, Burkhard; Honig, Barry; Murray, Diana; Montelione, Gaetano

2005-11-01

The solution structure of protein AF2095 from the thermophilic archaea Archaeglobus fulgidis, a 123-residue (13.6 kDa) protein, has been determined by NMR methods. The structure of AF2095 is comprised of four a-helices and a mixed b-sheet consisting of four parallel and anti-parallel b-strands, where the a-helices sandwich the b-sheet. Sequence and structural comparison of AF2095 with proteins from Homo sapiens, Methanocaldococcus jannaschii and Sulfolobus solfataricus, reveals that AF2095 is a peptidyl-tRNA hydrolase (Pth2). This structural comparison also identifies putative catalytic residues and a tRNA interaction region for AF2095. The structure of AF2095 is also similar to the structure of protein TA0108 from archaea Thermoplasma acidophilum, which is deposited in the Protein Database but not functionally annotated. The NMR structure of AF2095 has been further leveraged to obtain good quality structural models for 55 other proteins. Although earlier studies have proposed that the Pth2 protein family is restricted to archeal and eukaryotic organisms, the similarity of the AF2095 structure to human Pth2, the conservation of key active-site residues, and the good quality of the resulting homology models demonstrate a large family of homologous Pth2 proteins that are conserved in eukaryotic, archaeal and bacterial organisms, providing novel insights in the evolution of the Pth and Pth2 enzyme families.
Parathyroid diseases and animal models.

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Imanishi, Yasuo; Nagata, Yuki; Inaba, Masaaki

2012-01-01

CIRCULATING CALCIUM AND PHOSPHATE ARE TIGHTLY REGULATED BY THREE HORMONES: the active form of vitamin D (1,25-dihydroxyvitamin D), fibroblast growth factor (FGF)-23, and parathyroid hormone (PTH). PTH acts to stimulate a rapid increment in serum calcium and has a crucial role in calcium homeostasis. Major target organs of PTH are kidney and bone. The oversecretion of the hormone results in hypercalcemia, caused by increased intestinal calcium absorption, reduced renal calcium clearance, and mobilization of calcium from bone in primary hyperparathyroidism. In chronic kidney disease, secondary hyperparathyroidism of uremia is observed in its early stages, and this finally develops into the autonomous secretion of PTH during maintenance hemodialysis. Receptors in parathyroid cells, such as the calcium-sensing receptor, vitamin D receptor, and FGF receptor (FGFR)-Klotho complex have crucial roles in the regulation of PTH secretion. Genes such as Cyclin D1, RET, MEN1, HRPT2, and CDKN1B have been identified in parathyroid diseases. Genetically engineered animals with these receptors and the associated genes have provided us with valuable information on the patho-physiology of parathyroid diseases. The application of these animal models is significant for the development of new therapies.
Combination Therapy with Zoledronic Acid and Parathyroid Hormone Improves Bone Architecture and Strength following a Clinically-Relevant Dose of Stereotactic Radiation Therapy for the Local Treatment of Canine Osteosarcoma in Athymic Rats.

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Curtis, Ryan C; Custis, James T; Ehrhart, Nicole P; Ehrhart, E J; Condon, Keith W; Gookin, Sara E; Donahue, Seth W

2016-01-01

Clinical studies using definitive-intent stereotactic radiation therapy (SRT) for the local treatment of canine osteosarcoma (OSA) have shown canine patients achieving similar median survival times as the current standard of care (amputation and adjuvant chemotherapy). Despite this, there remains an unacceptable high risk of pathologic fracture following radiation treatment. Zoledronic acid (ZA) and parathyroid hormone (PTH) are therapeutic candidates for decreasing this fracture risk post-irradiation. Due to differing mechanisms, we hypothesized that the combined treatment with ZA and PTH would significantly improve bone healing more than ZA or PTH treatment alone. Using an orthotopic model of canine osteosarcoma in athymic rats, we evaluated bone healing following clinically-relevant doses of radiation therapy (12 Gy x 3 fractions, 36 Gy total). Groups included 36 Gy SRT only, 36 Gy SRT plus ZA, 36 Gy SRT plus ZA and PTH, 36 Gy SRT plus PTH, and 36 Gy SRT plus localized PTH treatment. Our study showed significant increases in bone volume and increased polar moments of inertia (in the distal femoral metaphysis) 8 weeks after radiation in the combined (ZA/PTH) treatment group as compared to radiation treatment alone. Histomorphometric analysis revealed evidence of active mineralization at the study endpoint as well as successful tumor-cell kill across all treatment groups. This work provides further evidence for the expanding potential indications for ZA and PTH therapy, including post-irradiated bone disease due to osteosarcoma.
Combination Therapy with Zoledronic Acid and Parathyroid Hormone Improves Bone Architecture and Strength following a Clinically-Relevant Dose of Stereotactic Radiation Therapy for the Local Treatment of Canine Osteosarcoma in Athymic Rats.

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Ryan C Curtis

Full Text Available Clinical studies using definitive-intent stereotactic radiation therapy (SRT for the local treatment of canine osteosarcoma (OSA have shown canine patients achieving similar median survival times as the current standard of care (amputation and adjuvant chemotherapy. Despite this, there remains an unacceptable high risk of pathologic fracture following radiation treatment. Zoledronic acid (ZA and parathyroid hormone (PTH are therapeutic candidates for decreasing this fracture risk post-irradiation. Due to differing mechanisms, we hypothesized that the combined treatment with ZA and PTH would significantly improve bone healing more than ZA or PTH treatment alone. Using an orthotopic model of canine osteosarcoma in athymic rats, we evaluated bone healing following clinically-relevant doses of radiation therapy (12 Gy x 3 fractions, 36 Gy total. Groups included 36 Gy SRT only, 36 Gy SRT plus ZA, 36 Gy SRT plus ZA and PTH, 36 Gy SRT plus PTH, and 36 Gy SRT plus localized PTH treatment. Our study showed significant increases in bone volume and increased polar moments of inertia (in the distal femoral metaphysis 8 weeks after radiation in the combined (ZA/PTH treatment group as compared to radiation treatment alone. Histomorphometric analysis revealed evidence of active mineralization at the study endpoint as well as successful tumor-cell kill across all treatment groups. This work provides further evidence for the expanding potential indications for ZA and PTH therapy, including post-irradiated bone disease due to osteosarcoma.
The study of calcitriol, cinacalcet combined with nursing intervention effect of SHPT, calcium, phosphorus metabolism and parathyroid hormone on MHD patients

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Le Chen

2017-06-01

Full Text Available Objective: To investigate calcitriol, cinacalcet plus comprehensive intervention on maintenance hemodialysis (MHD patients with secondary hyperparathyroidism (SHPT calcium (Ca, phosphorus (P metabolism and parathyroid hormone (PTH effect. Methods: A total of 80 cases of patients with SHPT from January 2014 to January 2016 in our hospital were randomly divided into observation group and control group, control group to eat the whole piece of cinacalcet hydrochloride oral tablets, the initial dose of 25 mg/d, every 2 to 4 weeks, according to Ca×P, parathyroid hormone (iPTH test results adjust the dose, the maximum dose of not more than 75 mg/d, the observation group in the control group on the basis of oral administration of Calcitriol Soft Capsules 0.25 g/d, 3 times/week, 2 groups were given comprehensive intervention measures, to evaluate the curative effect after 3 months of treatment. The 2 groups before and after treatment collected fasting peripheral venous blood, the determination of Ca, P and alkaline phosphatase by colorimetric method (ALP, Ca, P product calculation (Ca×P, to detect the level of iPTH before and after treatment by ELISA method; TY-6858-HI type ultrasound instrument, measuring length, width and thickness of the parathyroid glands, and calculate the parathyroid gland volume. Results: in the observation group after treatment, Ca, Ca×P increased degree, P, ALP, iPTH lower than the control group, the size of the parathyroid gland was better than the control group. Conclusion: calcitriol, cinacalcet combined intervention therapy has good clinical effect in patients with MHD SHPT, Ca, P can effectively improve the metabolism, reduce the level of iPTH, reduce the parathyroid gland volume is worthy of promotion.
A common polymorphism of the growth hormone receptor is associated with increased responsiveness to growth hormone.

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Dos Santos, Christine; Essioux, Laurent; Teinturier, Cécile; Tauber, Maïté; Goffin, Vincent; Bougnères, Pierre

2004-07-01

Growth hormone is used to increase height in short children who are not deficient in growth hormone, but its efficacy varies largely across individuals. The genetic factors responsible for this variation are entirely unknown. In two cohorts of short children treated with growth hormone, we found that an isoform of the growth hormone receptor gene that lacks exon 3 (d3-GHR) was associated with 1.7 to 2 times more growth acceleration induced by growth hormone than the full-length isoform (P < 0.0001). In transfection experiments, the transduction of growth hormone signaling through d3-GHR homo- or heterodimers was approximately 30% higher than through full-length GHR homodimers (P < 0.0001). One-half of Europeans are hetero- or homozygous with respect to the allele encoding the d3-GHR isoform, which is dominant over the full-length isoform. These observations suggest that the polymorphism in exon 3 of GHR is important in growth hormone pharmacogenetics.
Gene transfer of heterologous G protein-coupled receptors to cardiomyocytes: differential effects on contractility.

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Laugwitz, K L; Weig, H J; Moretti, A; Hoffmann, E; Ueblacker, P; Pragst, I; Rosport, K; Schömig, A; Ungerer, M

2001-04-13

In heart failure, reduced cardiac contractility is accompanied by blunted cAMP responses to beta-adrenergic stimulation. Parathyroid hormone (PTH)-related peptide and arginine vasopressin are released from the myocardium in response to increased wall stress but do not stimulate contractility or adenylyl cyclase at physiological concentrations. To bypass the defective beta-adrenergic signaling cascade, recombinant P1 PTH/PTH-related peptide receptors (rPTH1-Rs) and V(2) vasopressin receptors (rV(2)-Rs), which are normally not expressed in the myocardium and which are both strongly coupled to adenylyl cyclase, and recombinant beta(2)-adrenergic receptors (rbeta(2)-ARs) were overexpressed in cardiomyocytes by viral gene transfer. The capacity of endogenous hormones to increase contractility via the heterologous, recombinant receptors was compared. Whereas V(2)-Rs are uniquely coupled to Gs, PTH1-Rs and beta(2)-ARs are also coupled to other G proteins. Gene transfer of rPTH1-Rs or rbeta(2)-ARs to adult cardiomyocytes resulted in maximally increased basal contractility, which could not be further stimulated by adding receptor agonists. Agonists at rPTH1-Rs induced increased cAMP formation and phospholipase C activity. In contrast, healthy or failing rV(2)-R-expressing cardiomyocytes showed unaltered basal contractility. Their contractility and cAMP formation increased only at agonist exposure, which did not activate phospholipase C. In summary, we found that gene transfer of PTH1-Rs to cardiomyocytes results in constitutive activity of the transgene, as does that of beta(2)-ARS: In the absence of receptor agonists, rPTH1-Rs and rbeta(2)-ARs increase basal contractility, coupling to 2 G proteins simultaneously. In contrast, rV(2)-Rs are uniquely coupled to Gs and are not constitutively active, retaining their property to be activated exclusively on agonist stimulation. Therefore, gene transfer of V(2)-Rs might be more suited to test the effects of c
Vitamin D status and PTH in young men: a cross-sectional study on associations with bone mineral density, body composition and glucose metabolism

DEFF Research Database (Denmark)

Frost, M; Abrahamsen, B; Nielsen, T L

2010-01-01

Although vitamin D and bone metabolism are closely related, few studies have addressed the effects of vitamin D status on bone in men at time of peak bone mass. The objectives of this study were to evaluate the prevalence of vitamin D inadequacy in a cross-sectional study in young men...... and the effects of vitamin D and parathyroid hormone (PTH) on bone mass, bone markers and metabolic function....
Nonoxidized, biologically active parathyroid hormone determines mortality in hemodialysis patients

DEFF Research Database (Denmark)

Tepel, Martin; Armbruster, Franz Paul; Grön, Hans Jürgen

2013-01-01

Background: It was shown that nonoxidized PTH (n-oxPTH) is bioactive, whereas the oxidation of PTH results in a loss of biological activity. Methods: In this study we analyzed the association of n-oxPTH on mortality in hemodialysis patients using a recently developed assay system. Results......: Hemodialysis patients (224 men, 116 women) had a median age of 66 years. One hundred seventy patients (50%) died during the follow-up period of 5 years. Median n-oxPTH levels were higher in survivors (7.2 ng/L) compared with deceased patients (5.0 ng/L; P = .002). Survival analysis showed an increased survival...... in the highest n-oxPTH tertile compared with the lowest n-oxPTH tertile (χ(2), 14.3; P = .0008). Median survival was 1702 days in the highest n-oxPTH tertile, whereas it was only 453 days in the lowest n-oxPTH tertile. Multivariable-adjusted Cox regression showed that higher age increased odds for death, whereas...
Evaluation Of Hormone Profile And Dexa Values in Premenopausal, Perimenopausal and Postmenopausal Women

Directory of Open Access Journals (Sweden)

Esra Esen

2005-09-01

Full Text Available This study was carried out in 130 women, between 44-55 ages, admitted to outpatient clinic of Physical Medicine and Rehabilitation Department of Trakya University Medical Faculty in order to make. comparison of hormone profile and DEXA values of premenopausal, perimenopausal, and postmenopausal women . Three groups were allocated according to climacteric symptoms and menopause condition. Premenopausal group consisted of women who had regular menstruation and did not have any climacteric symptoms , perimenopausal group consisted of women who had menstruation disorder and climacteric symptoms within one year and postmenopausal group consisted of women who had last menstruation within more than one year and less than 5 years. Women who had prior osteoporosis diognosis and treatment, hormone replacement therapy, surgical menopause and menopause duration more than 5 years were excluded from the study. Age, body weight ,height, hormone profile including estradiol (E2, progesterone (P, follicule stimulating hormone (FSH, luteinizing hormone (LH, parathyroid hormone (PTH, thyroid hormones (T3, T4, thyroid stimulating hormone (TSH and DEXA values representing bone mineral density (BMD of both groups were evaluated. In peri and postmenopausal groups, E2, P, FSH and LH values were significantly lower, while there was no significant difference for PTH and thyroid hormone levels comparing to premenopausal group. For DEXA values, T scores of L2-L4, L2, L3, L4, femur neck, trochanter, Wards and Z scores of femur neck, Wards area were significantly lower in peri and postmenopausal groups. It was demonstrated paralel to literature that BMD decreased in peri and early postmenopausal women associated with hormone profile changes, mainly lower E2.
[Usefullness of intraoperatory parathyroid hormone measurement in surgical management of primary hyperparathyroidism due to a parathyroid adenoma].

Science.gov (United States)

Obiols, Gabriel; Catalán, Roberto; Alasà, Cristian; Baena, Juan Antonio; Fort, José Manuel; Gémar, Enrique; Mesa, Jordi

2003-09-13

Surgical neck exploration of the 4 parathyroid glands is quite an aggressive procedure for most patients with primary hyperparathyroidism (PHPT) due to a parathyroid adenoma. Intraoperatory measurement of parathyroid hormone (PTH) seems to be a useful tool for the management of these cases, allowing the use of minimally invasive surgical techniques with a lower morbidity. Our aims was to assess the usefulness of PTH intraoperatory measurement for the surgical management of PHPT. We studied 27 consecutive patients, diagnosed with PHPT secondary to parathyroid adenoma. Localization studies included neck ultrasonography and Tc-MIBI scintigraphy. PTH at the stage of anesthesia induction as well as 5 and 10 minutes after the removal of the adenoma was determined. A PTH decrement greater than 50% at 10 minutes was considered as curative. PTH was measured by an immunoluminometric method (Advantage, Nichols). In all cases, calcium levels were normal 24 hours after the operation, and therefore all them were considered as cured. PTH levels decreased more than 50% in all patients. In one case, PTH levels remained high after the exeresis of a preoperatively localized lesion. The pathologic study confirmed that it was a normal parathyroid gland. We then continued the surgical exploration which eventually allowed us to find a contralateral adenoma. A further PTH measurement showed an over 50% decrease. Therefore, PTH was predictive of surgical success in all 28 measurements. Intraoperatory determination of PTH is useful for the surgical management of PHPT and it could allow the use of minimally invasive surgical techniques.
Comparison of parathyroid hormone and G-CSF treatment after myocardial infarction on perfusion and stem cell homing.

Science.gov (United States)

Huber, Bruno C; Fischer, Rebekka; Brunner, Stefan; Groebner, Michael; Rischpler, Christoph; Segeth, Alexander; Zaruba, Marc M; Wollenweber, Tim; Hacker, Marcus; Franz, Wolfgang-Michael

2010-05-01

Mobilization of stem cells by granulocyte colony-stimulating factor (G-CSF) was shown to have protective effects after myocardial infarction (MI); however, clinical trials failed to be effective. In search for alternative cytokines, parathyroid hormone (PTH) was recently shown to promote cardiac repair by enhanced neovascularization and cell survival. To compare the impact of the two cytokines G-CSF and PTH on myocardial perfusion, mice were noninvasively and repetitively investigated by pinhole single-photon emission computed tomography (SPECT) after MI. Mobilization and homing of bone marrow-derived stem cells (BMCs) was analyzed by fluorescence-activated cell sorter (FACS) analysis. Mice (C57BL/6J) were infarcted by left anterior descending artery ligation. PTH (80 mug/kg) and G-CSF (100 mug/kg) were injected for 5 days. Perfusion defects were determined by (99m)Tc-sestamibi SPECT at days 6 and 30 after MI. The number of BMCs characterized by Lin(-)/Sca-1(+)/c-kit(+) cells in peripheral blood and heart was analyzed by FACS. Both G-CSF and PTH treatment resulted in an augmented mobilization of BMCs in the peripheral blood. Contrary to G-CSF and controls, PTH and the combination showed significant migration of BMCs in ischemic myocardium associated with a significant reduction of perfusion defects from day 6 to day 30. A combination of both cytokines had no additional effects on migration and perfusion. In our preclinical model, SPECT analyses revealed the functional potential of PTH reducing size of infarction together with an enhanced homing of BMCs to the myocardium in contrast to G-CSF. A combination of both cytokines did not improve the functional outcome, suggesting clinical applications of PTH in ischemic heart diseases.
Comparison of predictive accuracy of pre surgical serum parathormone (PTH) level with that of parathyroid scan in case of primary hyperparathyroidism

International Nuclear Information System (INIS)

Nasreen, F.; Yasmeen, S.; Ahsan, A.S.M.; Mandal, T.; Sultana, K.S.A.; Shirin, A.

2007-01-01

Full text: Aims and Objective: Parathyroid scintigraphy with Tc-99m Sestamibi is a sensitive and specific test for pre operative localization of parathyroid adenoma (PA) in patients with primary hyperparathyroidism. However false ve studies are not uncommon. Our aim was to find out the predictive accuracy of pre surgical parathormone (PTH) level with that of parathyroid scan in case of primary hyperparathyroidism. Materials And Method: A total of 54 patients (29 male, 25 female) with a mean age of 41. 24+14.26 years suspected of primary hyperparathyroidism were included in this study. All patients had serum PTH and calcium level higher than the normal limit. Parathyroid scintigraphy was done by subtraction method using 185 MBq of Tc-99m PO4 which was given first and images were taken by planar gamma camera after 20 minutes followed by Tc-99m Sestamibi (740MBq) injection without moving the patient. We calculated the sensitivity and specificity at different cut off values of PTH such as >70pg/ml, >80pg/ml, >90pg/ml and >100pg/ml and observed the changes in sensitivity, specificity, PPV and NPV against scintigraphic diagnosis of PA. Result: Parathyroid scintigraphy revealed 15 positive cases (27.8%) amongst 54 patients, which were surgically proven to be so. The sensitivity of PTH in predicting positive parathyroid scan revealed to be 86.7% at serum PTH level of 70-90pg/ml. Then the sensitivity declines steadily to 73.3% at PTH level of >100pg/ml. The specificity increases gradually from 20.5% at serum PTH level >70pg/ml to 53.8% at serum PTH level >100pg/ml. However, PPV and NPV of serum PTH did not experience significant change like sensitivity and specificity with the increase of cut off values. Conclusion: We can use a cut off value of pre surgical serum PTH level at 90pg/ml before doing parathyroid scan as this has maximum sensitivity and optimum specificity. It will help to predict the outcome of scan and avoid unnecessary parathyroid scan and false ve cases
34 CFR 377.1 - What is the Demonstration Projects to Increase Client Choice Program?

Science.gov (United States)

2010-07-01

... 34 Education 2 2010-07-01 2010-07-01 false What is the Demonstration Projects to Increase Client... PROJECTS TO INCREASE CLIENT CHOICE PROGRAM General § 377.1 What is the Demonstration Projects to Increase Client Choice Program? The Demonstration Projects to Increase Client Choice Program is designed to...
Systemic administration of mesenchymal stem cells combined with parathyroid hormone therapy synergistically regenerates multiple rib fractures.

Science.gov (United States)

Cohn Yakubovich, Doron; Sheyn, Dmitriy; Bez, Maxim; Schary, Yeshai; Yalon, Eran; Sirhan, Afeef; Amira, May; Yaya, Alin; De Mel, Sandra; Da, Xiaoyu; Ben-David, Shiran; Tawackoli, Wafa; Ley, Eric J; Gazit, Dan; Gazit, Zulma; Pelled, Gadi

2017-03-09

A devastating condition that leads to trauma-related morbidity, multiple rib fractures, remain a serious unmet clinical need. Systemic administration of mesenchymal stem cells (MSCs) has been shown to regenerate various tissues. We hypothesized that parathyroid hormone (PTH) therapy would enhance MSC homing and differentiation, ultimately leading to bone formation that would bridge rib fractures. The combination of human MSCs (hMSCs) and a clinically relevant PTH dose was studied using immunosuppressed rats. Segmental defects were created in animals' fifth and sixth ribs. The rats were divided into four groups: a negative control group, in which animals received vehicle alone; the PTH-only group, in which animals received daily subcutaneous injections of 4 μg/kg teriparatide, a pharmaceutical derivative of PTH; the hMSC-only group, in which each animal received five injections of 2 × 10 6 hMSCs; and the hMSC + PTH group, in which animals received both treatments. Longitudinal in vivo monitoring of bone formation was performed biweekly using micro-computed tomography (μCT), followed by histological analysis. Fluorescently-dyed hMSCs were counted using confocal microscopy imaging of histological samples harvested 8 weeks after surgery. PTH significantly augmented the number of hMSCs that homed to the fracture site. Immunofluorescence of osteogenic markers, osteocalcin and bone sialoprotein, showed that PTH induced cell differentiation in both exogenously administered cells and resident cells. μCT scans revealed a significant increase in bone volume only in the hMSC + PTH group, beginning by the 4 th week after surgery. Eight weeks after surgery, 35% of ribs in the hMSC + PTH group had complete bone bridging, whereas there was complete bridging in only 6.25% of ribs (one rib) in the PTH-only group and in none of the ribs in the other groups. Based on the μCT scans, biomechanical analysis using the micro-finite element method demonstrated that
Healthy looking hospital nurses showing vitamin d deficiency: correlation of vitamin d levels with their levels of parathhyroid hormone and bone turnover markers

International Nuclear Information System (INIS)

Nasim, A.; Salim, B.; Niazi, S.; Fatima, N.

2015-01-01

To evaluate the correlation of low vitamin D levels with parathyroid hormone (PTH) levels and bone turn over markers among apparently healthy hospital nurses. Methods: Screening was done on 50 recruited healthy female nursing staff, aged between 18 to 35 years, for vitamin D levels. Among them 31 were found to be deficient in vitamin D. These 31 nurses were selected for further evaluation in trance. Their vitamin D levels were calculated by using the electrochemiluminescence immunoassay. Blood samples were drawn to estimate serum PTH levels accordingly. Samples were also collected from these recruited subjects to evaluate their bone turn over markers, including, osteocalcin, procollagen type 1 N propeptide and Beta-Crosslaps. Results: Out of 50 subjects, 31 subjects were found to have Vitamin D levels below 50 nmol/l. Out of these 31 subjects, 13 subjects, 41.9%, showed vitamin D levels below 20 nmol/l. Among these 13 subjects, all had significantly raised PTH levels (p-value: <0.001, r-value: -0.781). In rest of all the subjects, including those having Vitamin D levels above 20nmol/l, inordinately, PTH levels were normal. No reciprocity was found between low Vitamin D and raised PTH levels with bone turnover markers, except with P1NP (r-value 0.022). Conclusion: PTH levels show a steep augmentation in serum, when vitamin D levels hit the trough below 20 nmol/l. These are the subjects who should be treated prior to the development of complications of bone resorption. Moreover we could not find any significant correlation of Vitamin D and PTH with any bone turnover marker except P1NP. (author)
Bone development in the fetus and neonate: role of the calciotropic hormones.

Science.gov (United States)

Kovacs, Christopher S

2011-12-01

During embryonic and fetal development much of the skeleton initiates as a cartilaginous scaffold, which is progressively resorbed and replaced by bone. Endochondral bone formation continues until the growth plates fuse during puberty. At all life stages adequate delivery of mineral is required for the skeleton to achieve and maintain appropriate mineral content and strength. During fetal development the placenta actively transports calcium, phosphorus, and magnesium. Postnatally passive and then active absorption from the intestines becomes the main supply of minerals to the skeleton. Animal and human data indicate that fetal bone development requires parathyroid hormone (PTH) and PTH-related protein but not vitamin D/calcitriol, calcitonin, or (possibly) sex steroids. During the postnatal period, when intestinal calcium absorption becomes an active process, skeletal development begins to depend upon vitamin D/calcitriol but this requirement can be bypassed by increasing the calcium content of the diet or by administering intermittent calcium infusions.

An evaluation of the incidence of hyperparathyroidism after {sup 131}I treatment for Basedow disease. Pt. 1

Energy Technology Data Exchange (ETDEWEB)

Tsuchiya, Takehiko; Ito, Kunihiko [Ito Hospital, Tokyo (Japan); Murata, Motoi

1996-07-01

It is known that external radiation can act as a developing factor in hyperparathyroidism (HPT). To clarify whether or not {sup 131}I acts as a factor of developing HPT or not, levels of calcium and parathyroid hormone in the blood were studied in 2,954 cases of patients treated with {sup 131}I (RI group) and 530 cases treated with antithyroid drugs (ATD group). The calcium level was measured in all cases treated with {sup 131}I and/or antithyroid drugs. PTH-M (parathyroid hormone) was measured in 262 cases of the RI group and 29 cases of the ATD group which showed levels over 10 mg/dl of calcium. Fifty-eight cases (2.50%) in the RI group and three cases (1.19%) in the ATD group showed over 560 pg/ml PTH-M, which is the highest normal value. The increase in incidence of cases with over 560 pg/ml PTH-M in the RI group versus that of the ATD group is statistically significant. However, there is no statistically significant difference in the annual incidence when the follow-up period is taken into account, because the follow-up period differed between the two groups. The incidence of cases with 560 pg/ml of PTH-M was higher in the older patients than in the younger patients. These results suggest that {sup 131}I treatment for Basedow disease affects increase in the development of HPT after treatment and that the age factor is also important in the above fact. (author)
Estradiol potentiation of gonadotropin-releasing hormone responsiveness in the anterior pituitary is mediated by an increase in gonadotropin-releasing hormone receptors

International Nuclear Information System (INIS)

Menon, M.; Peegel, H.; Katta, V.

1985-01-01

In order to investigate the mechanism by which 17 beta-estradiol potentiates the action of gonadotropin-releasing hormone on the anterior pituitary in vitro, cultured pituitary cells from immature female rats were used as the model system. Cultures exposed to estradiol at concentrations ranging from 10(-10) to 10(-6) mol/L exhibited a significant augmentation of luteinizing hormone release in response to a 4-hour gonadotropin-releasing hormone (10 mumol/L) challenge at a dose of 10(-9) mol/L compared to that of control cultures. The estradiol augmentation of luteinizing hormone release was also dependent on the duration of estradiol exposure. When these cultures were incubated with tritium-labeled L-leucine, an increase in incorporation of radiolabeled amino acid into total proteins greater than that in controls was observed. A parallel stimulatory effect of estradiol on iodine 125-labeled D-Ala6 gonadotropin-releasing hormone binding was observed. Cultures incubated with estradiol at different concentrations and various lengths of time showed a significant increase in gonadotropin-releasing hormone binding capacity and this increase was abrogated by cycloheximide. Analysis of the binding data showed that the increase in gonadotropin-releasing hormone binding activity was due to a change in the number of gonadotropin-releasing hormone binding sites rather than a change in the affinity. These results suggest that (1) estradiol treatment increases the number of pituitary receptors for gonadotropin-releasing hormone, (2) the augmentary effect of estradiol on luteinizing hormone release at the pituitary level might be mediated, at least in part, by the increase in the number of binding sites of gonadotropin-releasing hormone, and (3) new protein synthesis may be involved in estradiol-mediated gonadotropin-releasing hormone receptor induction
Intra-operative parathyroid hormone monitoring through central laboratory is accurate in renal secondary hyperparathyroidism.

Science.gov (United States)

Vulpio, Carlo; Bossola, Maurizio; Di Stasio, Enrico; Pepe, Gilda; Nure, Eda; Magalini, Sabina; Agnes, Salvatore

2016-05-01

The usefulness, the methods and the criteria of intra-operative monitoring of the parathyroid hormone (ioPTH) during parathyroidectomy (PTX) for renal secondary hyperparathyroidism (rSHPT) in patients on chronic hemodialysis remain still matter of debate. The present study aimed to evaluate the ability of a low cost central-laboratory second generation PTH assay to predict an incomplete resection of parathyroid glands (PTG). The ioPTH decay was determined In 42 consecutive patients undergoing PTX (15 subtotal and 27 total without auto-transplant of PTG) for rSHPT. The ioPTH monitoring included five samples: pre-intubation, post-manipulation of PTG and at 10, 20 and 30min post-PTG excision. The patients with PTH exceeding the normal value (65pg/ml) at the first postoperative week, 6 and 12months were classified as persistent rSHPT. The concentrations of ioPTH declined significantly over time in patients who received total or subtotal PTX; however, no difference was found between the two types of PTX. Irrespective of the type of PTX and the number of PTG removed, combining the absolute and percentage of ioPTH decay at 30min after PTG excision, we found high sensitivity (100%), specificity (92%), negative predictive value (100%) and accuracy (93%) in predicting the persistence of rSHPT. The monitoring of the ioPTH decline by a low cost central-laboratory second generation assay is extremely accurate in predicting the persistence of disease in patients on maintenance hemodialysis undergoing surgery for rSHPT. Copyright © 2016 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.
Nikkaji Dictionary: PTH-チロシン [MeCab user dictionary for science technology term[Archive

Lifescience Database Archive (English)

Full Text Available MeCab user dictionary for science technology term PTH-チロシン名詞一般 * * * * PTH-チロシン ... Nikkaji J53.640G 200906033314709367 C CA06 UNKNOWN_2 PTH - チロシン
Vitamin D Deficiency and a Blunted Parathyroid Hormone Response in Children with Attention-Deficit/Hyperactivity Disorder.

Science.gov (United States)

Avcil, Sibelnur; Uysal, Pinar; Yilmaz, Mustafa; Erge, Duygu; Demirkaya, Sevcan K; Eren, Esra

2017-03-01

Attention-deficit/hyperactivity disorder (ADHD) is the most frequently diagnosed neuropsychiatric disorder of childhood. The etiopathogenesis of ADHD has not been fully defined. Recent evidence has suggested a pathophysiological role of vitamin D deficiency in ADHD. In this study, we evaluated the serum levels of 25-hydroxy vitamin D (25(OH)D), parathyroid hormone (PTH), calcium (Ca), phosphate (P), and alkaline phosphatase (ALP) in children with ADHD. The study group consisted of 105 children diagnosed with ADHD according to DSM-IV-TR criteria. A control group, matched for age and gender, was composed of 95 healthy children. Venous blood samples were collected, and 25(OH)D, PTH, Ca, P, and ALP levels were measured. The mean serum 25(OH)D, Ca, and P levels of the children with ADHD were significantly lower than those of the healthy controls. There were no significant differences between the groups regarding PTH and ALP. Serum PTH levels were found to be normal, but vitamin D deficiency, hypocalcemia, and hypophosphatemia were observed in children with ADHD. There was no correlation between serum PTH and Ca levels in children with ADHD, whereas, there was a negative correlation between serum PTH and Ca levels in healthy controls. There was no correlation between serum 25(OH)D and PTH levels in children with ADHD, whereas, there was a negative correlation between serum 25(OH)D and PTH levels in healthy controls. There were no significant differences in all parameters' levels among the subtypes of ADHD. The findings suggest that ADHD is associated with vitamin D deficiency, blunted PTH response, and impaired Ca homeostasis in children.
Effect of metabolic control on parathyroid hormone secretion in diabetic patients

Directory of Open Access Journals (Sweden)

Paula F.J.A.

2001-01-01

Full Text Available The metabolic derangement caused by diabetes mellitus may potentially affect bone mineral metabolism. In the present study we evaluated the effect of diabetes metabolic control on parathyroid hormone (PTH secretion during stimulation with EDTA infusion. The study was conducted on 24 individuals, 8 of them normal subjects (group N: glycated hemoglobin - HbA1C = 4.2 ± 0.2%; range = 3.5-5.0%, 8 patients with good and regular metabolic control (group G-R: HbA1C = 7.3 ± 0.4%; range = 6.0-8.5%, and 8 patients with poor metabolic control (group P: HbA1C = 12.5 ± 1.0%; range: 10.0-18.8%. Blood samples were collected at 10-min intervals throughout the study (a basal period of 30 min and a 2-h period of EDTA infusion, 30 mg/kg body weight and used for the determination of ionized calcium, magnesium, glucose and intact PTH. Basal ionized calcium levels were slightly lower in group P (1.19 ± 0.01 mmol/l than in group N (1.21 ± 0.01 mmol/l and group G-R (1.22 ± 0.01 mmol/l. After EDTA infusion, the three groups presented a significant fall in calcium, but with no significant difference among them at any time. Basal magnesium levels and levels determined during EDTA infusion were significantly lower (P<0.01 in group P than in group N. The induction of hypocalcemia caused an elevation in PTH which was similar in groups N and G-R but significantly higher than in group P throughout the infusion period (+110 min, N = 11.9 ± 2.1 vs G-R = 13.7 ± 1.6 vs P = 7.5 ± 0.7 pmol/l; P<0.05 for P vs N and G-R. The present results show that PTH secretion is impaired in patients with poorly controlled diabetes.
Inhibition of parathyroid hormone release by maitotoxin, a calcium channel activator

International Nuclear Information System (INIS)

Fitzpatrick, L.A.; Yasumoto, T.; Aurbach, G.D.

1989-01-01

Maitotoxin, a toxin derived from a marine dinoflagellate, is a potent activator of voltage-sensitive calcium channels. To further test the hypothesis that inhibition of PTH secretion by calcium is mediated via a calcium channel we studied the effect of maitotoxin on dispersed bovine parathyroid cells. Maitotoxin inhibited PTH release in a dose-dependent fashion, and inhibition was maximal at 1 ng/ml. Chelation of extracellular calcium by EGTA blocked the inhibition of PTH by maitotoxin. Maitotoxin enhanced the effects of the dihydropyridine calcium channel agonist (+)202-791 and increased the rate of radiocalcium uptake in parathyroid cells. Pertussis toxin, which ADP-ribosylates and inactivates a guanine nucleotide regulatory protein that interacts with calcium channels in the parathyroid cell, did not affect the inhibition of PTH secretion by maitotoxin. Maitotoxin, by its action on calcium channels allows entry of extracellular calcium and inhibits PTH release. Our results suggest that calcium channels are involved in the release of PTH. Inhibition of PTH release by maitotoxin is not sensitive to pertussis toxin, suggesting that maitotoxin may act distal to the site interacting with a guanine nucleotide regulatory protein, or maitotoxin could interact with other ions or second messengers to inhibit PTH release
Radioimmunological determination of parathormone peptides in the plasma before and after gel filtration in hyperparathyroidic patients

International Nuclear Information System (INIS)

Juengst, U.

1983-01-01

Plasmas from different patients suffering from secondary renal hyperparathyroidism and from one patient suffering from primary hyperparathyroidism owing to a parathyroid adenoma, were studied and parathormone concentrations (total IPTH) were determined radio-immunologically. Plasmas were gel-filtered subsequently. Gelfiltration allows to separate intact PTH from PTH fragments which also occur in the plasma. These fragments also react with the antisera used in the PTH-radio-immuno-assay; thus it was possible to determine only the concentration of intact PTH after gel filtration. In patients in whose unfiltered plasma strongly increased PTH values had been measured (more than 100 pmol hPTH/l plasma), only 10 to 40% of total immunoreactivity were taken up by intact parathormone after gel filtration. Histological findings of iliac crest biopsies revealed marked changes corresponding to the increased concentration of biologically active hormone. Whereas unfiltered plasma revealed slightly increased PTH measurement values (below 100 pmol hPTH/l), 60 to 75% of total immuno reactivity was taken up by the intact hormone after gel filtration. Correspondingly, histological changes of the skeleton were less marked. Apparently, there is a correlation - though not a linear one - between total IPTH and the absolute concentration of intact PTH. If increased PTH values are measured with antiserum S478, it may be assumed in general that the concentration of intact and biologically active PTH has increased as well. (orig./MG) [de
Cinacalcet reduces plasma intact parathyroid hormone, serum phosphate and calcium levels in patients with secondary hyperparathyroidism irrespective of its severity.

LENUS (Irish Health Repository)

2011-09-01

To evaluate the relationship between the severity of secondary hyperparathyroidism (SHPT) - defined in terms of baseline plasma intact parathyroid hormone (iPTH) level - and the magnitude of response to cinacalcet.
Bone development and mineral homeostasis in the fetus and neonate: roles of the calciotropic and phosphotropic hormones.

Science.gov (United States)

Kovacs, Christopher S

2014-10-01

Mineral and bone metabolism are regulated differently in utero compared with the adult. The fetal kidneys, intestines, and skeleton are not dominant sources of mineral supply for the fetus. Instead, the placenta meets the fetal need for mineral by actively transporting calcium, phosphorus, and magnesium from the maternal circulation. These minerals are maintained in the fetal circulation at higher concentrations than in the mother and normal adult, and such high levels appear necessary for the developing skeleton to accrete a normal amount of mineral by term. Parathyroid hormone (PTH) and calcitriol circulate at low concentrations in the fetal circulation. Fetal bone development and the regulation of serum minerals are critically dependent on PTH and PTH-related protein, but not vitamin D/calcitriol, fibroblast growth factor-23, calcitonin, or the sex steroids. After birth, the serum calcium falls and phosphorus rises before gradually reaching adult values over the subsequent 24-48 h. The intestines are the main source of mineral for the neonate, while the kidneys reabsorb mineral, and bone turnover contributes mineral to the circulation. This switch in the regulation of mineral homeostasis is triggered by loss of the placenta and a postnatal fall in serum calcium, and is followed in sequence by a rise in PTH and then an increase in calcitriol. Intestinal calcium absorption is initially a passive process facilitated by lactose, but later becomes active and calcitriol-dependent. However, calcitriol's role can be bypassed by increasing the calcium content of the diet, or by parenteral administration of calcium. Copyright © 2014 the American Physiological Society.
Radioimmunological detection of parathormone

International Nuclear Information System (INIS)

Klueber, S.

1978-01-01

On the basis of the principle of competitive displacement of standard or proband hormone from the antibody by 125 I-labelled hormone, the structure of a radioimmunological PTH assay for humans is presented. In agreement with the pathophysiological knowledge gained during the last few years, i.e. that the C-terminal residual fragment-produced partly in the gland and partly by peripheral splitting of the total molecule secreted - circulates longer than the 1-34 N fragment containing the biologically active region, the C assay showed clearly increased hormone levels (more than 1 ng eq/ml) in the peripheral venous blood of HPT patients while the N assay showed a strong overlap of normal and HPT sera. The detection limit of 100pg eq/ml for both systems did not permit a discrimination between normal and reduced serum levels. (orig.) [de
A Convenient In Vivo Model Using Small Interfering RNA Silencing to Rapidly Assess Skeletal Gene Function.

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Wen Zhang

Full Text Available It is difficult to study bone in vitro because it contains various cell types that engage in cross-talk. Bone biologically links various organs, and it has thus become increasingly evident that skeletal physiology must be studied in an integrative manner in an intact animal. We developed a model using local intraosseous small interfering RNA (siRNA injection to rapidly assess the effects of a target gene on the local skeletal environment. In this model, 160-g male Sprague-Dawley rats were treated for 1-2 weeks. The left tibia received intraosseous injection of a parathyroid hormone 1 receptor (Pth1r or insulin-like growth factor 1 receptor (Igf-1r siRNA transfection complex loaded in poloxamer 407 hydrogel, and the right tibia received the same volume of control siRNA. All the tibias received an intraosseous injection of recombinant human parathyroid hormone (1-34 (rhPTH (1-34 or insulin-like growth factor-1 (IGF-1. Calcein green and alizarin red were injected 6 and 2 days before euthanasia, respectively. IGF-1R and PTH1R expression levels were detected via RT-PCR assays and immunohistochemistry. Bone mineral density (BMD, microstructure, mineral apposition rates (MARs, and strength were determined by dual-energy X-ray absorptiometry, micro-CT, histology and biomechanical tests. The RT-PCR and immunohistochemistry results revealed that IGF-1R and PTH1R expression levels were dramatically diminished in the siRNA-treated left tibias compared to the right tibias (both p<0.05. Using poloxamer 407 hydrogel as a controlled-release system prolonged the silencing effect of a single dose of siRNA; the mRNA expression levels of IGF-1R were lower at two weeks than at one week (p<0.01. The BMD, bone microstructure parameters, MAR and bone strength were significantly decreased in the left tibias compared to the right tibias (all p<0.05. This simple and convenient local intraosseous siRNA injection model achieved gene silencing with very small quantities of
Effect of high fat diet on pulmonary expression of parathyroid hormone-related protein and its downstream targets

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Learta Oruqaj

2016-10-01

Full Text Available Aims: Parathyroid hormone-related protein (PTHrP is involved in lung development and surfactant production. The latter one requires a paracrine interaction between type II alveolar cells and lipofibroblasts in which leptin triggers PTHrP-induced effects. Whether increased plasma leptin levels, as they occur in high fat diet, modify the expression of PTHrP remains unclear. Furthermore, the effect of high fat diet under conditions of forced pulmonary remodelling such as response to post myocardial infarction remains to be defined. Materials and methods: C57 bl/6 mice were randomized to either normal diet or high fat diet at an age of 6 weeks. Seven months later, the mice were euthanized and the lung was removed and frozen in fluid nitrogen until use. Samples were analyzed by real-time RT-PCR and western blot. Leptin deficient mice were used to investigate the effect of leptin on pulmonary expression of PTHrP more directly. A subgroup of mice with and without high fat diet underwent in vivo ischemia (45 min and reperfusion (4 weeks. Finally, experiments were repeated with prolonged high-fat diet. Key findings: High fat diet increased plasma leptin levels by 30.4% and the pulmonary mRNA expression of PTHrP (1,447-fold, PTH-1 receptor (4.21-fold, and PTHrP-downstream targets ADRP (7.54-fold and PPARγ (5.27-fold. Pulmonary PTHrP expression was reduced in leptin deficient mice by 88% indicating leptin dependent regulation. High fat diet further improved changes in pulmonary adaptation caused by ischemia/reperfusion (1.48-fold increased PTH-1 receptor protein expression. These effects were lost during prolonged high fat diet. Significance: This study established that physiological regulation of leptin plasma levels by high fat diet affects the pulmonary PTHrP expression and of PTHrP downstream targets. Modification of pulmonary expression of PTH-1 receptors by high fat diet after myocardial infarction suggests that the identified interaction may
Increased Procurement of Thoracic Donor Organs After Thyroid Hormone Therapy.

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Novitzky, Dimitri; Mi, Zhibao; Collins, Joseph F; Cooper, David K C

2015-01-01

Hormonal therapy to the brain-dead organ donor can include thyroid hormone (triiodothyronine [T3] or levothyroxine [T4]), antidiuretic hormone, corticosteroids, or insulin. There has been a controversy on whether thyroid hormone enables more organs to be procured. Data on 63,593 donors of hearts and lungs (2000-2009) were retrospectively reviewed. Documentation on T3/T4 was available in all donors (study 1), and in 40,124 details of all 4 hormones were recorded (study 2). In this cohort, group A (23,022) received T3/T4 and group B (17,102) no T3/T4. Univariate analyses and multiple regressions were performed. Posttransplant graft and recipient survival at 1 and 12 months were compared. In study 1, 30,962 donors received T3/T4, with 36.59% providing a heart and 20.05% providing 1 or both lungs. Of the 32,631 donors who did not receive T3/T4, only 29.62% provided a heart and 14.61% provided lungs, an increase of 6.97% hearts and 5.44% lungs from T3/T4-treated donors (both P donor was associated with either improved posttransplant graft and recipient survival or no difference in survival. T3/T4 therapy results in more transplantable hearts and lungs, with no detriment to posttransplant graft or recipient survival. Copyright © 2015 Elsevier Inc. All rights reserved.
Clinical significance of combined determination of serum BGP, PTH, CT in aged osteoporosis

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Wang Limin; Chen Kejing; Gu Weiguang; Zhu Weimin; Wang Hongfu

1997-01-01

Using radioimmunoassay to determine serum BGP, PTH and CT, the author showed that there are various changes of level of BGP, PTH, CT with respect to osteoporosis of different etiology. It suggested that the combined determination has certain reference value in clinical diagnosis, disease staging and treatment of the aged osteoporosis
The influence of abnormal thyroid function on sex hormones and bone metabolism in female patients

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Li Xiaohong; Chu Shaolin; Lei Qiufang; Ye Peihong; Chai Luhua

2001-01-01

Objectives: To explore the influence of hyperthyroidism and hypothyroidism on sex hormones and bone metabolism in female patients. Method: A single photon bone absorptiometry was used to measure calcareous bone mineral density (BMD) in 91 female patients with hyperthyroidism, and 37 female patients with hypothyroidism caused by Hashimoto's thyroiditis and 51 healthy female subjects with euthyroid. In addition the serum levels of BGP and PTH were determined by means of IRMA. Serum levels of FSH and E 2 were determined by RIA. Results: Serum levels of FSH , E 2 and BGP in hyperthyroidism group were significantly higher than those in control group. The serum levels of PTH were slightly lower than that in control group (P 2 and BGP were significantly lower than those in control group. The assessment of BMD showed that the prevalence rate of osteoporosis (OP) both in hyperthyroidism groups and in hypothyroidism groups was significantly higher than control group. The peak bone density in young and middle-aged female was decreased, and OP was more common in over 60-year-aged female with hypothyroidism. Conclusions: Female patients with abnormal thyroid function are often associated with abnormality of sex hormones. It leads to increasing the incidence of OP. The attack age of OP tends to be younger, especially aged patients with lymphocytic hypothyroidism increases more markedly. Therefore, BMD should be measured in all female patients with a variety of thyroid diseases
Parathyroid Hormone Levels and Cognition

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Burnett, J.; Smith, S.M.; Aung, K.; Dyer, C.

2009-01-01

Hyperparathyroidism is a well-recognized cause of impaired cognition due to hypercalcemia. However, recent studies have suggested that perhaps parathyroid hormone itself plays a role in cognition, especially executive dysfunction. The purpose of this study was to explore the relationship of parathyroid hormone levels in a study cohort of elders with impaied cognition. Methods: Sixty community-living adults, 65 years of age and older, reported to Adult Protective Services for self-neglect and 55 controls matched (on age, ethnicity, gender and socio-economic status) consented and participated in this study. The research team conducted in-home comprehensive geriatric assessments which included the Mini-mental state exam (MMSE), the 15-item geriatric depression scale (GDS) , the Wolf-Klein clock test and a comprehensive nutritional panel, which included parathyroid hormone and ionized calcium. Students t tests and linear regression analyses were performed to assess for bivariate associations. Results: Self-neglecters (M = 73.73, sd=48.4) had significantly higher PTH levels compared to controls (M =47.59, sd=28.7; t=3.59, df=98.94, pcognitive measures. Conclusion: Parathyroid hormone may be associated with cognitive performance.
Low vitamin D3 and high anti-Müllerian hormone serum levels in the polycystic ovary syndrome (PCOS): Is there a link?

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Cappy, Hélène; Giacobini, Paolo; Pigny, Pascal; Bruyneel, Aude; Leroy-Billiard, Maryse; Dewailly, Didier; Catteau-Jonard, Sophie

2016-10-01

Low vitamin D serum level has been reported in women with polycystic ovary syndrome (PCOS) compared to controls. A few in vitro studies showed that the bioactive form of vitamin D is able to modulate the expression of the anti-Müllerian hormone (AMH) gene. However, in vivo studies failed to demonstrate clearly whether low vitamin D3 serum level is involved in the AMH excess of PCOS. This prospective study evaluates serum vitamin D3 and AMH levels in women with PCOS and in controls, before and after vitamin D supplementation. Among vitamin D deficient patients, 23 patients with PCOS were compared to 27 women with normal ovarian reserve (NOR). The vitamin D deficient patients received a vitamin D supplementation according to the depth of their insufficiency. For the 23 patients with PCOS and the 27 controls, serum AMH assay and serum calciotropic hormone assays [25-hydroxyvitamin D (25[OH]D), 1,25 dihydroxyvitamin D (1,25[OH] 2 D) and parathyroid hormone (PTH)] were performed before and after supplementation. Serum 25(OH)D levels before treatment were statistically lower in PCOS women than in NOR patients (Ptreatment was observed neither in PCOS patients nor in NOR patients. In both groups, 25(OH)D serum levels were not related to serum AMH levels, serum 1,25(OH) 2 D and serum PTH levels, before and after treatment. We found no evidence that serum calciotropic hormones are linked to circulating AMH levels, particularly in PCOS. Copyright © 2016 Elsevier Masson SAS. All rights reserved.
Vitamin D, parathyroid hormone, and acroosteolysis in systemic sclerosis.

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Braun-Moscovici, Yolanda; Furst, Daniel E; Markovits, Doron; Rozin, Alexander; Clements, Philip J; Nahir, Abraham Menahem; Balbir-Gurman, Alexandra

2008-11-01

.Sclerodactyly with acroosteolysis (AO) and calcinosis are prominent features of systemic sclerosis (SSc), but the pathogenesis of these findings is poorly understood. Vitamin D and parathyroid hormone (PTH) have a crucial role in bone metabolism and resorption and may affect AO and calcinosis. We assessed vitamin D and PTH in patients with SSc. Medical records of 134 consecutive patients with SSc (American College of Rheumatology criteria) followed at the rheumatology department during the years 2003-2006 were reviewed for clinical assessment, laboratory evaluation [including 25(OH) vitamin D, calcium, phosphorus, alkaline phosphatase, PTH, creatinine, and albumin]; imaging data confirming AO and/or calcinosis. Patients followed routinely at least once a year were included (81 patients). Of these, 60 patients' medical records were found to have complete, relevant clinical, laboratory, and radiographic imaging. Thirteen patients had diffuse disease and 47 limited disease - 51 women and 9 men, 44 Jews and 16 Arabs; mean age 55 +/- 14 years; disease duration 8 +/- 6 years. AO with or without calcinosis was observed in 42 patients (70%). Vitamin D deficiency was found in 46% of patients (16 out of 44 Jewish patients, 10 out of 16 Arab patients). PTH was elevated in 21.7% of patients. Significant correlations were observed between acroosteolysis and PTH (p = 0.015), calcinosis (p = 0.009), and disease duration (p = 0.008), and between PTH and vitamin D levels (p = 0.01). All patients had normal serum concentrations of calcium, phosphorus, magnesium, and albumin, and liver and kidney functions. In this group of Mediterranean patients with SSc, the incidence of vitamin D deficiency and secondary hyperparathyroidism was surprisingly high. This finding correlated with the occurrence of AO and calcinosis. Low levels of vitamin D may reflect silent malabsorption and might be a risk factor for secondary hyperparathyroidism and bone resorption. Traditional dress habits and low
Prophylactic oral calcium supplementation therapy to prevent early post thyroidectomy hypocalcemia and evaluation of postoperative parathyroid hormone levels to detect hypocalcemia: A prospective randomized study.

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Arer, Ilker Murat; Kus, Murat; Akkapulu, Nezih; Aytac, Huseyin Ozgur; Yabanoglu, Hakan; Caliskan, Kenan; Tarim, Mehmet Akin

2017-02-01

Postoperative hypocalcemia is the most common complication after total thyroidectomy. Postoperative parathyroid hormone (PTH) measurement is one of the methods to detect or prevent postoperative hypocalcemia. Prophylactic oral calcium supplementation is another method to prevent early postoperative hypocalcemia. The aim of this study is to detect the accurate timing of PTH and evaluate efficacy of routine oral calcium supplementation for postoperative hypocalcemia. A total of 106 patients were performed total thyroidectomy. Rotuine oral calcium supplementation was given to group 1 and no treatment to group 2 according to randomization. Serum calcium and PTH level of patients in group 2 at postoperative 6, 12 and 24 h and patients in both groups at postoperative day 7 were evaluated. Patients were compared according to age, sex, operation findings, serum calcium and PTH levels and symptomatic hypocalcemia. Half of the patients (50%) were in group 1. Most of the patients were female (83%). The most common etiology of thyroid disease was multinodular goiter (64.1%). Oral calcium supplementation was given to 18 (33.9%) patients in group 2. Symptomatic hypocalcemia for group 1 and 2 was found to be 1.9 and 33.9% respectively (p hypocalcemia. Prophylactic oral calcium supplementation therapy can prevent early post-thyroidectomy hypocalcemia with advantages of being cost effective and safe. Copyright © 2016 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.

Lack of endogenous parathyroid hormone delays fracture healing by inhibiting vascular endothelial growth factor‑mediated angiogenesis.

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Ding, Qingfeng; Sun, Peng; Zhou, Hao; Wan, Bowen; Yin, Jian; Huang, Yao; Li, Qingqing; Yin, Guoyong; Fan, Jin

2018-07-01

Intermittent low‑dose injections of parathyroid hormone (PTH) have been reported to exert bone anabolic effects and to promote fracture healing. As an important proangiogenic cytokine, vascular endothelial growth factor (VEGF) is secreted by bone marrow mesenchymal stem cells (BMSCs) and osteoblasts, and serves a crucial regulatory role in the process of vascular development and regeneration. To investigate whether lack of endogenous PTH causes reduced angiogenic capacity and thereby delays the process of fracture healing by downregulating the VEGF signaling pathway, a PTH knockout (PTHKO) mouse fracture model was generated. Fracture healing was observed using X‑ray and micro‑computerized tomography. Bone anabolic and angiogenic markers were analyzed by immunohistochemistry and western blot analysis. The expression levels of VEGF and associated signaling pathways in murine BMSC‑derived osteoblasts were measured by quantitative polymerase chain reaction and western blot analysis. The expression levels of protein kinase A (PKA), phosphorylated‑serine/threonine protein kinase (pAKT), hypoxia‑inducible factor‑1α (HIF1α) and VEGF were significantly decreased in BMSC‑derived osteoblasts from PTHKO mice. In addition, positive platelet endothelial cell adhesion molecule staining was reduced in PTHKO mice, as determined by immunohistochemistry. The expression levels of HIF1α, VEGF, runt‑related transcription factor 2, osteocalcin and alkaline phosphatase were also decreased in PTHKO mice, and fracture healing was delayed. In conclusion, lack of endogenous PTH may reduce VEGF expression in BMSC‑derived osteoblasts by downregulating the activity of the PKA/pAKT/HIF1α/VEGF pathway, thus affecting endochondral bone formation by causing a reduction in angiogenesis and osteogenesis, ultimately leading to delayed fracture healing.
Alteração do teor de cálcio no banho de DP para 2,5 mEq/L é eficaz no reestabelecimento dos valores preconizados por diretrizes atuais em pacientes com PTH < 150 pg/dL Low-calcium peritoneal dialysis solution is effective in bringing PTH levels to the range recommended by current guidelines in patients with PTH levels < 150 pg/dL

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Thyago Proença de Moraes

2010-09-01

Full Text Available INTRODUÇÃO/OBJETIVO: A doença óssea adinâmica (DOA é um achado comum em diálise peritoneal (PD e é considerada fator de risco para desenvolvimento de fraturas e doença cardiovascular. Dados do BRAZPD apontam as soluções de cálcio a 3,5 mEq/L presentes na maioria das prescrições no país, que possui quase 9.000 pacientes em PD. É comum o balanço positivo de cálcio com concentrações a 3,5 mEq/L contribuindo para o desenvolvimento de DOA. Diretrizes atuais recomendam um PTHi na DRC V em diálise entre 2 e 9 vezes (150-500 pg/mL o valor máximo da normalidade. O objetivo deste estudo foi avaliar a resposta em 6 meses do PTH-i após a conversão para solução de cálcio a 2,5 mEq/L de pacientes que usavam soluções com cálcio a 3,5 mEq/L e com PTH-i basal INTRODUCTION/OBJECTIVE: Adinamic bone disease (ABD is a common finding in peritoneal dialysis (PD and is associated with higher risk of developing cardiovascular and bone disease. Data from BRAZPD indicates that 3.5 mEq/L calcium PD solutions represents the majority of PD prescriptions in the country. A positive calcium balance can contribute to ABD development. Currently guidelines suggest that PTH-i levels in end stage renal disease should be kept from 150-300 pg/mL. The purpose of this study is to evaluate 6 month PTH-i response after conversion to 2.5 mEq/L calcium PD solution in patients with baseline PTH-i levels < 150 pg/mL. METHODS: Prospective, observational study of all prevalent patients (at least 90 days on therapy on PD of a single Brazilian center from January 2008 to May 2009. Inclusion criteria (1 be in use of a PD solution with 3.5mEq/L of calcium; (2 baseline PTH leves < 150 pg/ mL. According to clinical practice patients could be switched to PD solutions with 2.5 mEq/L of calcium. RESULTS: 35 patients (age 62 ± 17 years were included. Of these 22 were converted to 2.5 mEq/L calcium solutions. Diabetic nephropathy (36% was the main cause of renal disease
Serum phosphorus reduction in dialysis patients treated with cinacalcet for secondary hyperparathyroidism results mainly from parathyroid hormone reduction

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Zitt, Emanuel; Fouque, Denis; Jacobson, Stefan H

2013-01-01

The calcimimetic cinacalcet lowers parathyroid hormone (PTH), calcium (Ca) and phosphorus (P) in dialysis patients with secondary hyperparathyroidism (SHPT). We explored serum P changes in dialysis patients treated with cinacalcet, while controlling for vitamin D sterol and phosphate binder (PB...
Endogenous PKI gamma limits the duration of the anti-apoptotic effects of PTH and beta-adrenergic agonists in osteoblasts.

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Chen, Xin; Song, In-Hwan; Dennis, James E; Greenfield, Edward M

2007-05-01

PKI gamma knockdown substantially extended the anti-apoptotic effects of PTH and beta-adrenergic agonists, whereas PKI gamma overexpression decreased these effects. Therefore, inhibition of PKI gamma activity may provide a useful co-therapy in combination with intermittent PTH or beta-adrenergic agonists for bone loss in conditions such as osteoporosis. PTH has both catabolic and anabolic effects on bone, which are primarily caused by cAMP/protein kinase A (PKA) signaling and regulation of gene expression. We previously showed that protein kinase inhibitor-gamma (PKI gamma) is required for efficient termination of cAMP/PKA signaling and gene expression after stimulation with PTH or beta-adrenergic agonists. Inhibition of osteoblast apoptosis is thought to be an important, but transient, mechanism partly responsible for the anabolic effects of intermittent PTH. Therefore, we hypothesized that endogenous PKI gamma also terminates the anti-apoptotic effect of PTH. PKI gamma knockdown by antisense transfection or siRNA was used to examine the ability of endogenous PKI gamma to modulate the anti-apoptotic effects of PTH and beta-adrenergic agonists in ROS 17/2.8 cells. Knockdown of PKI gamma substantially extended the anti-apoptotic effects of PTH, whether apoptosis was induced by etoposide or dexamethasone. In contrast, overexpression of PKI gamma decreased the anti-apoptotic effect of PTH pretreatment. This study is also the first demonstration that beta-adrenergic agonists mimic the anti-apoptotic effects of PTH in osteoblasts. Moreover, PKI gamma knockdown also substantially extended this anti-apoptotic effect of beta-adrenergic agonists. Taken together, these results show that endogenous PKI gamma limits the duration of the anti-apoptotic effects of cAMP/PKA signaling in osteoblasts. Because significant individual variability exists in the anabolic responses to PTH therapy in current clinical treatment of osteoporosis, inhibition of PKI gamma activity may provide a
Efficacy and safety of ultrasound-guided radiofrequency ablation of hyperplastic parathyroid gland for secondary hyperparathyroidism associated with chronic kidney disease.

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Peng, Chengzhong; Zhang, Zhengxian; Liu, Jibin; Chen, Hongyu; Tu, Xiao; Hu, Rihong; Ni, Jun; Weng, Ning; Pang, Haisu; Xue, Zhengmei

2017-03-01

The purpose of this study was to determine if ultrasound-guided radiofrequency ablation (RFA) of hyperplastic parathyroid glands could be used to treat secondary hyperparathyroidism (HPT) in patients with chronic kidney disease. RFA of the hyperplastic parathyroid glands was performed in 34 patients with secondary HPT. Intact parathyroid hormone (iPTH), calcium, and phosphorus were measured. The outcome was based on the ablation extent (ie, 4, 3, and 1-2 glands). The iPTH, calcium, and phosphorus levels decreased in all groups after RFA. One year after ablation, these parameters remained significantly lower in the 4-gland ablation group compared with the 3-gland and 1 to 2-gland groups. The same tendency was observed for the symptom score. The iPTH levels of secondary HPT is feasible in selected patients. © 2016 Wiley Periodicals, Inc. Head Neck 39: 564-571, 2017. © 2016 Wiley Periodicals, Inc.
Hormones and growth factors in the pathogenesis of spinal ligament ossification.

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Li, Hai; Jiang, Lei-Sheng; Dai, Li-Yang

2007-08-01

Ossification of the spinal ligaments (OSL) is a pathologic condition that causes ectopic bone formation and subsequently results in various degrees of neurological deficit, but the etiology of OSL remains almost unknown. Some systemic hormones, such as 1,25-dihydroxyvitamin D, parathyroid hormone (PTH), insulin and leptin, and local growth factors, such as transforming growth factor-beta (TGF-beta), and bone morphogenetic protein (BMP), have been studied and are thought to be involved in the initiation and development of OSL. This review article summarizes these studies, delineates the possible mechanisms, and puts forward doubts and new questions. The related findings from studies of genes and target cells in the ligament of OSL are also discussed. Although these findings may be helpful in understanding the pathogenesis of OSL, much more research needs to be conducted in order to investigate the nature of OSL.
The role of secondary hyperparathyroidism in left ventricular hypertrophy of patients under chronic hemodialysis

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Randon R.B.

2005-01-01

Full Text Available End-stage renal disease (ESRD patients frequently develop structural cardiac abnormalities, particularly left ventricular hypertrophy (LVH. The mechanisms involved in these processes are not completely understood. In the present study, we evaluated a possible association between parathyroid hormone (PTH levels and left ventricular mass (LVM in patients with ESRD. Stable uremic patients on intermittent hemodialysis treatment were evaluated by standard two-dimensional echocardiography and their sera were analyzed for intact PTH. Forty-one patients (mean age 45 years, range 18 to 61 years, 61% males, who had been on hemodialysis for 3 to 186 months, were evaluated. Patients were stratified into 3 groups according to serum PTH: low levels (280 pg/ml; group III = 21 patients. A positive statistically significant association between LVM index and PTH was identified (r = 0.34; P = 0.03, Pearson's correlation coefficient in the sample as a whole. In subgroup analyses, we did not observe significant associations in the low and intermediate PTH groups; nevertheless, PTH and LVM index were correlated in patients with high PTH levels (r = 0.62; P = 0.003. LVM index was also inversely associated with hemoglobin (r = -0.34; P = 0.03. In multivariate analysis, after adjustment for age, hemoglobin, body mass index, and blood pressure, the only independent predictor of LVM index was PTH level. Therefore, PTH is an independent predictor of LVH in patients undergoing chronic hemodialysis. Secondary hyperparathyroidism may contribute to the elevated cardiovascular morbidity associated with LVH in ESRD.
Cloning and regulation of rat tissue inhibitor of metalloproteinases-2 in osteoblastic cells

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Cook, T. F.; Burke, J. S.; Bergman, K. D.; Quinn, C. O.; Jeffrey, J. J.; Partridge, N. C.

1994-01-01

Rat tissue inhibitor of metalloproteinases-2 (TIMP-2) was cloned from a UMR 106-01 rat osteoblastic osteosarcoma cDNA library. The 969-bp full-length clone demonstrates 98 and 86% sequence identity to human TIMP-2 at the amino acid and nucleic acid levels, respectively. Parathyroid hormone (PTH), at 10(-8) M, stimulates an approximately twofold increase in both the 4.2- and 1.0-kb transcripts over basal levels in UMR cells after 24 h of exposure. The PTH stimulation of TIMP-2 transcripts was not affected by the inhibitor of protein synthesis, cycloheximide (10(-5) M), suggesting a primary effect of the hormone. This is in contradistinction to regulation of interstitial collagenase (matrix metalloproteinase-1) by PTH in these same cells. Nuclear run-on assays demonstrate that PTH causes an increase in TIMP-2 transcription that parallels the increase in message levels. Parathyroid hormone, in its stimulation of TIMP-2 mRNA, appears to act through a signal transduction pathway involving protein kinase A (PKA) since the increase in TIMP-2 mRNA is reproduced by treatment with the cAMP analogue, 8-bromo-cAMP (5 x 10(-3) M). The protein kinase C and calcium pathways do not appear to be involved due to the lack of effect of phorbol 12-myristate 13-acetate (2.6 x 10(-6) M) and the calcium ionophore, ionomycin (10(-7) M), on TIMP-2 transcript abundance. In this respect, regulation of TIMP-2 and collagenase in osteoblastic cells by PTH are similar. However, we conclude that since stimulation of TIMP-2 transcription is a primary event, the PKA pathway must be responsible for a direct increase in transcription of this gene.
Fibroblast Growth Factor-23 and Vitamin D Metabolism in Subjects with eGFR ≥60 ml/min/1.73 m².

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Nakatani, Shinya; Nakatani, Ayumi; Tsugawa, Naoko; Yamada, Shinsuke; Mori, Katsuhito; Imanishi, Yasuo; Ishimura, Eiji; Okano, Toshio; Inaba, Masaaki

2015-01-01

Fibroblast growth factor (FGF)-23 and parathyroid hormone (PTH) are both potent phosphaturic hormones. Since they exert opposite effects on vitamin D metabolism, the measurement of 3 vitamin D metabolites; 25-hydroxyvitamin D (25-OH-D), 1,25-dihydroxyvitamin D (1,25(OH)2D), and 24,25-dihydroxyvitamin D (24,25(OH)2D), allows the distinction of the effects of FGF-23 from those of PTH. The aim of this study was to elucidate which factor, FGF-23 or PTH, plays a more important role in the regulation of vitamin D metabolites in subjects with estimated glomerular filtration (eGFR) ≥60 ml/min/1.73 m(2). Subjects with eGFR ≥60 ml/min/1.73 m(2) (n = 20) were enrolled and their serum levels of FGF-23, intact PTH, and vitamin D metabolites were determined. Serum FGF-23 correlated inversely with 1,25(OH)2D (r = -0.717, p = 0.0004) and the 1,25(OH)2D/25-OH-D ratio (r = -0.518, p = 0.019), compared with a significant positive correlation between serum intact PTH and the 1,25(OH)2D/25-OH-D ratio (r = 0.562, p = 0.010). Multiple regression analyses revealed serum FGF-23 as a significant factor that was associated with serum 1,25(OH)2D (β = -0.593, p = 0.018), 1,25(OH)2D/25-OH-D ratio (β = -0.521, p = 0.025), and the 24,25(OH)2D/1,25(OH)2D ratio (β = 0.632, p = 0.008), and intact PTH as a significant factor associated with the 1,25(OH)2D/25-OH-D ratio (β = 0.445, p = 0.028). This study demonstrated that, even in subjects with eGFR ≥60 ml/min/1.73 m(2), FGF-23 might play an important role in the regulation of vitamin D metabolism. In addition to the established role of PTH, the association between FGF-23 and indices of vitamin D metabolism suggested the potential role of FGF-23 on phosphate metabolism in such patients. © 2015 S. Karger AG, Basel.
Effects of parathyroid hormone and calcitonin on alkaline phosphatase activity and matrix calcification in rabbit growth-plate chondrocyte cultures

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Kato, Y.; Shimazu, A.; Nakashima, K.; Suzuki, F.; Jikko, A.; Iwamoto, M. (Osaka Univ. (Japan))

1990-07-01

The effects of PTH and calcitonin (CT) on the expression of mineralization-related phenotypes by chondrocytes were examined. In cultures of pelleted growth-plate chondrocytes. PTH caused 60-90% decreases in alkaline phosphatase activity, the incorporation of {sup 45}Ca into insoluble material, and the calcium content during the post-mitotic stage. These effects of PTH were dose-dependent and reversible. In contrast, CT increased alkaline phosphatase activity, {sup 45}Ca incorporation into insoluble material, and the calcium content by 1.4- to 1.8-fold. These observations suggest that PTH directly inhibits the expression of the mineralization-related phenotypes by growth-plate chondrocytes, and that CT has the opposite effects.
Acute hypotension induced by aortic clamp vs. PTH provokes distinct proximal tubule Na+ transporter redistribution patterns

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Leong, Patrick K K; Yang, Li E; Lin, Harrison W

2004-01-01

. This study aimed to determine the effects of acute hypotension, induced by aortic clamp or by high-dose PTH (100 microg PTH/kg), on renal hemodynamics and proximal tubule Na/H exchanger isoform 3 (NHE3) and type IIa Na-P(i) cotransporter protein (NaPi2) distribution. Subcellular distribution was analyzed...... clearance. There was, however, no significant change in glomerular filtration rate (GFR) or subcellular distribution of NHE3 and NaPi2. In contrast, high-dose PTH rapidly (
Calcilytic Ameliorates Abnormalities of Mutant Calcium-Sensing Receptor (CaSR) Knock-In Mice Mimicking Autosomal Dominant Hypocalcemia (ADH).

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Dong, Bingzi; Endo, Itsuro; Ohnishi, Yukiyo; Kondo, Takeshi; Hasegawa, Tomoka; Amizuka, Norio; Kiyonari, Hiroshi; Shioi, Go; Abe, Masahiro; Fukumoto, Seiji; Matsumoto, Toshio

2015-11-01

Activating mutations of calcium-sensing receptor (CaSR) cause autosomal dominant hypocalcemia (ADH). ADH patients develop hypocalcemia, hyperphosphatemia, and hypercalciuria, similar to the clinical features of hypoparathyroidism. The current treatment of ADH is similar to the other forms of hypoparathyroidism, using active vitamin D3 or parathyroid hormone (PTH). However, these treatments aggravate hypercalciuria and renal calcification. Thus, new therapeutic strategies for ADH are needed. Calcilytics are allosteric antagonists of CaSR, and may be effective for the treatment of ADH caused by activating mutations of CaSR. In order to examine the effect of calcilytic JTT-305/MK-5442 on CaSR harboring activating mutations in the extracellular and transmembrane domains in vitro, we first transfected a mutated CaSR gene into HEK cells. JTT-305/MK-5442 suppressed the hypersensitivity to extracellular Ca(2+) of HEK cells transfected with the CaSR gene with activating mutations in the extracellular and transmembrane domains. We then selected two activating mutations locating in the extracellular (C129S) and transmembrane (A843E) domains, and generated two strains of CaSR knock-in mice to build an ADH mouse model. Both mutant mice mimicked almost all the clinical features of human ADH. JTT-305/MK-5442 treatment in vivo increased urinary cAMP excretion, improved serum and urinary calcium and phosphate levels by stimulating endogenous PTH secretion, and prevented renal calcification. In contrast, PTH(1-34) treatment normalized serum calcium and phosphate but could not reduce hypercalciuria or renal calcification. CaSR knock-in mice exhibited low bone turnover due to the deficiency of PTH, and JTT-305/MK-5442 as well as PTH(1-34) increased bone turnover and bone mineral density (BMD) in these mice. These results demonstrate that calcilytics can reverse almost all the phenotypes of ADH including hypercalciuria and renal calcification, and suggest that calcilytics can become a
Zebrafish Bone and General Physiology Are Differently Affected by Hormones or Changes in Gravity.

Science.gov (United States)

Aceto, Jessica; Nourizadeh-Lillabadi, Rasoul; Marée, Raphael; Dardenne, Nadia; Jeanray, Nathalie; Wehenkel, Louis; Aleström, Peter; van Loon, Jack J W A; Muller, Marc

2015-01-01

Teleost fish such as zebrafish (Danio rerio) are increasingly used for physiological, genetic and developmental studies. Our understanding of the physiological consequences of altered gravity in an entire organism is still incomplete. We used altered gravity and drug treatment experiments to evaluate their effects specifically on bone formation and more generally on whole genome gene expression. By combining morphometric tools with an objective scoring system for the state of development for each element in the head skeleton and specific gene expression analysis, we confirmed and characterized in detail the decrease or increase of bone formation caused by a 5 day treatment (from 5dpf to 10 dpf) of, respectively parathyroid hormone (PTH) or vitamin D3 (VitD3). Microarray transcriptome analysis after 24 hours treatment reveals a general effect on physiology upon VitD3 treatment, while PTH causes more specifically developmental effects. Hypergravity (3g from 5dpf to 9 dpf) exposure results in a significantly larger head and a significant increase in bone formation for a subset of the cranial bones. Gene expression analysis after 24 hrs at 3g revealed differential expression of genes involved in the development and function of the skeletal, muscular, nervous, endocrine and cardiovascular systems. Finally, we propose a novel type of experimental approach, the "Reduced Gravity Paradigm", by keeping the developing larvae at 3g hypergravity for the first 5 days before returning them to 1g for one additional day. 5 days exposure to 3g during these early stages also caused increased bone formation, while gene expression analysis revealed a central network of regulatory genes (hes5, sox10, lgals3bp, egr1, edn1, fos, fosb, klf2, gadd45ba and socs3a) whose expression was consistently affected by the transition from hyper- to normal gravity.
Zebrafish Bone and General Physiology Are Differently Affected by Hormones or Changes in Gravity.

Directory of Open Access Journals (Sweden)

Jessica Aceto

Full Text Available Teleost fish such as zebrafish (Danio rerio are increasingly used for physiological, genetic and developmental studies. Our understanding of the physiological consequences of altered gravity in an entire organism is still incomplete. We used altered gravity and drug treatment experiments to evaluate their effects specifically on bone formation and more generally on whole genome gene expression. By combining morphometric tools with an objective scoring system for the state of development for each element in the head skeleton and specific gene expression analysis, we confirmed and characterized in detail the decrease or increase of bone formation caused by a 5 day treatment (from 5dpf to 10 dpf of, respectively parathyroid hormone (PTH or vitamin D3 (VitD3. Microarray transcriptome analysis after 24 hours treatment reveals a general effect on physiology upon VitD3 treatment, while PTH causes more specifically developmental effects. Hypergravity (3g from 5dpf to 9 dpf exposure results in a significantly larger head and a significant increase in bone formation for a subset of the cranial bones. Gene expression analysis after 24 hrs at 3g revealed differential expression of genes involved in the development and function of the skeletal, muscular, nervous, endocrine and cardiovascular systems. Finally, we propose a novel type of experimental approach, the "Reduced Gravity Paradigm", by keeping the developing larvae at 3g hypergravity for the first 5 days before returning them to 1g for one additional day. 5 days exposure to 3g during these early stages also caused increased bone formation, while gene expression analysis revealed a central network of regulatory genes (hes5, sox10, lgals3bp, egr1, edn1, fos, fosb, klf2, gadd45ba and socs3a whose expression was consistently affected by the transition from hyper- to normal gravity.
Calcium and Bone Turnover Markers in Acromegaly: A Prospective, Controlled Study.

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Constantin, Tina; Tangpricha, Vin; Shah, Reshma; Oyesiku, Nelson M; Ioachimescu, Octavian C; Ritchie, James; Ioachimescu, Adriana G

2017-07-01

Acromegaly has been associated with calcium-phosphate and bone turnover alterations. Controlled studies of these interactions are sparse. To evaluate calcium and bone metabolism in active and treated acromegaly. We conducted a controlled, prospective study at a tertiary referral center. We studied 22 patients with acromegaly referred for surgical or medical therapy (ACM) and 22 with nonfunctioning pituitary adenomas referred for surgery (control). Calcium (serum and urine), phosphorus, parathyroid hormone (PTH), 25-hydroxy- and 1,25-dihydroxy-vitamin D, bone turnover markers [serum C-terminal telopeptide of type 1 collagen (CTX) and procollagen type 1 N-terminal propeptide (P1NP)], and cytokines [receptor activator of nuclear factor κB ligand (RANK-L) and osteoprotegerin (OPG)] at baseline and 3 to 6 months after treatment. At baseline, the ACM group had lower PTH levels than controls (36.3 ± 13.9 pg/mL vs 56.0 ± 19.9 pg/mL) and higher phosphorus (4.34 ± 0.71 mg/dL vs 3.55 ± 0.50 mg/dL) (P acromegaly, serum calcium (9.52 ± 0.43 mg/dL to 9.26 ± 0.28 mg/dL), phosphorus (4.34 ± 0.71 mg/dL to 3.90 ± 0.80 mg/dL), and CTX (0.91 ± 0.75 ng/mL to 0.63 ± 0.68 ng/mL) decreased, while PTH increased (36.3 ± 13.9 pg/mL to 48.9 ± 16.7 pg/mL) (P Acromegaly patients exhibited PTH-independent calcium-phosphate alterations and enhanced coupled bone formation and resorption. Within 6 months of treatment, bone resorption decreased, whereas RANK-L/OPG changes were inconsistent. Copyright © 2017 Endocrine Society
Control In Cellular Activity By Interaction Of Peptides | Umar Dikko ...

African Journals Online (AJOL)

An experiments was conducted in the previous years using EGF, PTH-rP and PTH(1-34) to investigate the interaction between these peptides on the proliferation of JAR human chariocarcinoma cells. Here the interaction between some of the fragments of hypercalcaemic factor PTH-rP and PTH(1-34) were considered with ...
Engraftment and bone mass are enhanced by PTHrP 1-34 in ectopically transplanted vertebrae (vossicle model) and can be non-invasively monitored with bioluminescence and fluorescence imaging.

Science.gov (United States)

Hildreth, Blake Eason; Williams, Michelle M; Dembek, Katarzyna A; Hernon, Krista M; Rosol, Thomas J; Toribio, Ramiro E

2015-12-01

Evidence exists that parathyroid hormone-related protein (PTHrP) 1-34 may be more anabolic in bone than parathyroid hormone 1-34. While optical imaging is growing in popularity, scant information exists on the relationships between traditional bone imaging and histology and bioluminescence (BLI) and fluorescence (FLI) imaging. We aimed to evaluate the effects of PTHrP 1-34 on bone mass and determine if relationships existed between radiographic and histologic findings in bone and BLI and FLI indices. Vertebrae (vossicles) from mice coexpressing luciferase and green fluorescent protein were implanted subcutaneously into allogenic nude mice. Transplant recipients were treated daily with saline or PTHrP 1-34 for 4 weeks. BLI, FLI, radiography, histology, and µCT of the vossicles were performed over time. PTHrP 1-34 increased bioluminescence the most after 2 weeks, fluorescence at all time points, and decreased the time to peak bioluminescence at 4 weeks (P ≤ 0.027), the latter of which suggesting enhanced engraftment. PTHrP 1-34 maximized vertebral body volume at 4 weeks (P bone observed histologically increased in both groups at 2 and 4 weeks (P ≤ 0.002); however, PTHrP 1-34 exceeded time-matched controls (P ≤ 0.044). A positive linear relationship existed between the percentage of trabecular bone and (1) total bioluminescence (r = 0.595; P = 0.019); (2) total fluorescence (r = 0.474; P = 0.074); and (3) max fluorescence (r = 0.587; P = 0.021). In conclusion, PTHrP 1-34 enhances engraftment and bone mass, which can be monitored non-invasively by BLI and FLI.
Interleukin-2 stimulates osteoclastic activity: Increased acid production and radioactive calcium release

International Nuclear Information System (INIS)

Ries, W.L.; Seeds, M.C.; Key, L.L.

1989-01-01

Recombinant human interleukin-2 (IL-2) was studied to determine effects on acid production by individual osteoclasts in situ on mouse calvarial bones. This analysis was performed using a microspectrofluorimetric technique to quantify acid production in individual cells. Radioactive calcium release was determined using calvarial bones in a standard tissue culture system. This allowed us to correlate changes in acid production with a measure of bone resorption. IL-2 stimulated acid production and bone resorbing activity. Both effects were inhibited by calcitonin. No stimulation of bone resorption occurred when IL-2-containing test media was incubated with a specific anti-IL-2 antibody and ultrafiltered. Our data demonstrated a correlation between acid production and bone resorbing activity in mouse calvaria exposed to parathyroid hormone (PTH). The data obtained from cultured mouse calvaria exposed to IL-2 demonstrated similar stimulatory effects to those seen during PTH exposure. These data suggest that calvaria exposed to IL-2 in vitro have increased osteoclastic acid production corresponding with increased bone resorption. (author)
Alterations in vitamin D metabolite, parathyroid hormone and fibroblast growth factor-23 concentrations in sclerostin-deficient mice permit the maintenance of a high bone mass.

Science.gov (United States)

Ryan, Zachary C; Craig, Theodore A; McGee-Lawrence, Meghan; Westendorf, Jennifer J; Kumar, Rajiv

2015-04-01

Humans with mutations of the sclerostin (SOST) gene, and knockout animals in which the Sost gene has been experimentally deleted, exhibit an increase in bone mass. We review the mechanisms by which Sost knockout mice are able to accrete increased amounts of calcium and phosphorus required for the maintenance of a high bone mass. Recently published information from our laboratory, shows that bone mass is increased in Sost-deficient mice through an increase in osteoblast and a decrease in osteoclast activity, which is mediated by activation of β-catenin and an increase in prostacyclin synthesis in osteocytes and osteoblasts. The increases in calcium and phosphorus retention required for enhanced bone mineral accretion are brought about by changes in the vitamin D endocrine system, parathyroid hormone (PTH) and fibroblast growth factor-23 (FGF-23). Thus, in Sost knockout mice, concentrations of serum 1,25-dihydroxyvitamin D (1,25(OH)2D) are increased and concentrations of FGF-23 are decreased thereby allowing a positive calcium and phosphorus balance. Additionally, in the absence of Sost expression, urinary calcium is decreased, either through a direct effect of sclerostin on renal calcium handling, or through its effect on the synthesis of 1,25(OH)2D. Adaptations in vitamin D, PTH and FGF-23 physiology occur in the absence of sclerostin expression and mediate increased calcium and phosphorus retention required for the increase in bone mineralization. This article is part of a Special Issue entitled '17th Vitamin D Workshop'. Copyright © 2014 Elsevier Ltd. All rights reserved.
Treatment with cinacalcet increases plasma sclerostin concentration in hemodialysis patients with secondary hyperparathyroidism.

Science.gov (United States)

Kuczera, Piotr; Adamczak, Marcin; Więcek, Andrzej

2016-11-15

Sclerostin is a paracrine acting factor, which is expressed in the osteocytes and articular chondrocytes. Sclerostin decreases the osteoblast-related bone formation through the inhibition of the Wnt/β-catenin pathway. Osteocytes also express the Calcium sensing receptor which is a target for cinacalcet. The aim of this study was to assess the influence of six-month cinacalcet treatment on plasma sclerostin concentration in hemodialysed patients with secondary hyperparathyroidism (sHPT). In 58 hemodialysed patients with sHPT (PTH > 300 pg/ml) plasma sclerostin and serum PTH, calcium and phosphate concentrations were assessed before the first dose of cinacalcet and after 3 and 6 months of treatment. Serum PTH concentration decreased after 3 and 6 month of treatment from 1138 (931-1345) pg/ml to 772 (551-992) pg/ml and to 635 (430-839) pg/ml, respectively. Mean serum calcium and phosphate concentrations remained stable. Plasma sclerostin concentration increased after 3 and 6 months of treatment from 1.66 (1.35-1.96) ng/ml, to 1.77 (1.43-2.12) ng/ml and to 1.87 (1.50-2.25) ng/ml, respectively. In 42 patients with cinacalcet induced serum PTH decrease plasma sclerostin concentration increased after 3 and 6 months of treatment from 1.51 (1.19-1.84) ng/ml to 1.59 (1.29-1.89) ng/ml and to 1.75 (1.42-2.01) ng/ml, respectively. Contrary, in the 16 patients without cinacalcet induced serum PTH decrease plasma sclerostin concentration was stable. Plasma sclerostin concentrations correlated inversely with serum PTH concentrations at the baseline and also after 6 months of treatment. 1. In hemodialysed patients with secondary hyperparathyroidism treatment with cinacalcet increases plasma sclerostin concentration 2. This effect seems to be related to decrease of serum PTH concentration.

Parathyroid hormone measurement and 99Tcm-MIBI imaging for hyperparathyroidism diagnosis

International Nuclear Information System (INIS)

Zhao Yunyun; Wang Qian; Li Yuan; Yue Minggang; Li Hebei

2011-01-01

Objective: To evaluate 99 Tc m -MIBI imaging in patients with hyperparathyroidism and its correlation with serum intact PTH level. Methods: Seventy patients with suspicious hyperparathyroidism underwent 99 Tc m -MIBI imaging and serum intact PTH measurement. Abnormal increased uptake lesion appeared at early phase and even more clearly at delayed phase was considered as the positive by 99 Tc m -MIBI imaging. A cut-off value of PTH >88 ng/L was taken as the criteria for hyperparathyroidism diagnosis. The diagnostic efficacy of 99 Tc m -MIBI imaging combined with serum PTH measurement was assessed according to post-surgical histopathology or clinical follow-up. For those operated patients, Pearson correlation coefficient between serum PTH and the gland volume was calculated. Results: Hyperparathyroidism was confirmed in 38 patients by histopathology (n=36) or follow-up (n=2). The overall diagnostic accuracy of 99 Tc m -MIBI imaging was 90.0% (63/70), in which the accuracy was 80.0% (12/15) for patients with normal serum PTH and 92.7% (51/55) for those with elevated serum PTH. False positive 99 Tc m -MIBI imaging were found in 3 patients with normal serum PTH. The diagnostic accuracy of abnormally high serum PTH combined with 99 Tc m -MIBI imaging was 94.3% (66/70). There was a positive correlation between serum PTH level and the volume of pathologic parathyroid glands (r=0.782, P<0.001). Conclusions: Serum PTH measurement may help to improve the diagnostic accuracy of 99 Tc m -MIBI imaging in patients with hyperparathyroidism. (authors)
Further studies on the intermediary metabolism of bone in vitro and a monoclonal cell line (MMB-1) derived from bone: effects of parathyroid hormone and acetazolamide

International Nuclear Information System (INIS)

Nichols, F.C.

1981-01-01

The mechanism/mechanisms by which PTH affects Ca homeostasis between blood and bone have not been clearly established. Most studies of metabolic acid production in bone took place during the late 1950s and early 1960s. Since that time, assay techniques for metabolic acid production have been improved for greater sensitivity, more has been learned as to how PTH mediates its cellular responses, and techniques for cell isolation and culture have dramatically improved. These improvements have made possible new approaches to the study of short term effects of PTH on metabolic acid production in bone. Chapter 1 explores the potential of bone to utilize substrates other than glucose for metabolic energy transfer. Chapter 2 characterizes glucose metabolism in mouse calvaria in vitro and explores effects of PTH, acetazolamide, and C1 13,850 on calvaria oxidative metabolism. Chapter 3 describes PTH effects on glucose metabolism of MMB-1 cells, a monoclonal cell line reported to possess osteoblast-like characteristics
Effect of enamel matrix derivative and parathyroid hormone on bone formation in standardized osseous defects: an experimental study in minipigs

DEFF Research Database (Denmark)

Jensen, Simon S; Chen, B; Bornstein, Michael M

2011-01-01

Previous experimental studies have indicated that locally administered enamel matrix derivative (EMD) and parathyroid hormone (PTH) may have a stimulatory effect on bone formation. However, it is not clear if the positive effect of EMD is related to its effect on the periodontium as a whole...
La proteína PthB de Xanthomonas axonopodis pv. manihotis es autoactiva en ensayos de doble hibrido

Directory of Open Access Journals (Sweden)

Juliana Gil

2011-01-01

Full Text Available La bacteriosis vascular de yuca producida por la bacteria Xanthomonas axonopodis pv. manihotis (Xam es uno de los factores limitantes para la producción de yuca. Dentro de los primeros factores de patogenicidad identificados en esta bacteria se encuentra el gen pthB. La proteína PthB pertenece a la familia de efectores PthA/AvrBs3, que se caracterizan por presentar dominios NLS (Nuclear Localization Signal y un dominio AAD (Acidic Activation Domain, lo cual sugiere que estas proteínas actúan como factores de transcripción. La identificación de las proteínas de yuca que interactúan con PthB permitiría dar luces sobre la función de esta proteína en la patogenicidad de esta bacteria. En este trabajo se clonó pthB en una fusión traduccional con el BD (Binding Domain del factor de transcripción GAL4. Después de transformar este constructo en una cepa de levadura, se observó autoactivación de los genes reporteros, incluso a concentraciones altas de 3-AT. La eliminación del primer, segundo o de los dos NLS y del AAD no eliminaron la capacidad de autoactivación de los genes reporteros mediada por PthB. Estos resultados indican la imposibilidad de su utilización en un tamizaje de una librería de ADNc de yuca para identificar las proteínas que interactúan con PthB.
Carriers of a VEGFA enhancer polymorphism selectively binding CHOP/DDIT3 are predisposed to increased circulating levels of thyroid-stimulating hormone

DEFF Research Database (Denmark)

Ahluwalia, Tarun Veer Singh; Troelsen, Jesper Thorvald; Balslev-Harder, Marie

2017-01-01

BACKGROUND: Levels of serum thyroid-stimulating hormone (TSH) indicate thyroid function, because thyroid hormone negatively controls TSH release. Genetic variants in the vascular endothelial growth factor A (VEGFA) gene are associated with TSH levels. The aim of this study was to characterise...... levels (p=0.0014). The SNP rs881858 is located in a binding site for CHOP (C/EBP homology protein) and c/EBPβ (ccaat enhancer binding protein β). Reporter-gene analysis showed increased basal enhancer activity of the rs881858 A-allele versus the G-allele (34.5±9.9% (average±SEM), p=0.0012), while co...
PTH/PTHrP Receptor Mediates Cachexia in Models of Kidney Failure and Cancer.

Science.gov (United States)

Kir, Serkan; Komaba, Hirotaka; Garcia, Ana P; Economopoulos, Konstantinos P; Liu, Wei; Lanske, Beate; Hodin, Richard A; Spiegelman, Bruce M

2016-02-09

Cachexia is a wasting syndrome associated with elevated basal energy expenditure and loss of adipose and muscle tissues. It accompanies many chronic diseases including renal failure and cancer and is an important risk factor for mortality. Our recent work demonstrated that tumor-derived PTHrP drives adipose tissue browning and cachexia. Here, we show that PTH is involved in stimulating a thermogenic gene program in 5/6 nephrectomized mice that suffer from cachexia. Fat-specific knockout of PTHR blocked adipose browning and wasting. Surprisingly, loss of PTHR in fat tissue also preserved muscle mass and improved muscle strength. Similarly, PTHR knockout mice were resistant to cachexia driven by tumors. Our results demonstrate that PTHrP and PTH mediate wasting through a common mechanism involving PTHR, and there exists an unexpected crosstalk mechanism between wasting of fat tissue and skeletal muscle. Targeting the PTH/PTHrP pathway may have therapeutic uses in humans with cachexia. Copyright © 2016 Elsevier Inc. All rights reserved.
Effects of high glucose and advanced glycation end products on the expressions of sclerostin and RANKL as well as apoptosis in osteocyte-like MLO-Y4-A2 cells

Energy Technology Data Exchange (ETDEWEB)

Tanaka, Ken-ichiro, E-mail: ken1nai@med.shimane-u.ac.jp; Yamaguchi, Toru, E-mail: yamaguch@med.shimane-u.ac.jp; Kanazawa, Ippei, E-mail: ippei.k@med.shimane-u.ac.jp; Sugimoto, Toshitsugu, E-mail: sugimoto@med.shimane-u.ac.jp

2015-05-29

In diabetes mellitus (DM), high glucose (HG) and advanced glycation end products (AGEs) are involved in bone quality deterioration. Osteocytes produce sclerostin and receptor activator of nuclear factor-kB ligand (RANKL) and regulate osteoblast and osteoclast function. However, whether HG or AGEs directly affect osteocytes and regulate sclerostin and RANKL production is unknown. Here, we examined the effects of HG, AGE2, and AGE3 on the expression of sclerostin and RANKL and on apoptosis in osteocyte-like MLO-Y4-A2 cells. Treatment of the cells with 22 mM glucose, 100 μg/mL either AGE2 or AGE3 significantly increased the expression of sclerostin protein and mRNA; however, both AGEs, but not glucose, significantly decreased the expression of RANKL protein and mRNA. Moreover, treatment of the cells with HG, AGE2, or AGE3 for 72 h induced significant apoptosis. These detrimental effects of HG, AGE2, and AGE3 on sclerostin and RANKL expressions and on apoptosis were antagonized by pretreatment of the cells with 10{sup −8} M human parathyroid hormone (PTH)-(1–34). Thus, HG and AGEs likely suppress bone formation by increasing sclerostin expression in osteocytes, whereas AGEs suppress bone resorption by decreasing RANKL expression. Together, these processes may cause low bone turnover in DM. In addition, HG and AGEs may cause cortical bone deterioration by inducing osteocyte apoptosis. PTH may effectively treat these pathological processes and improve osteocyte function. - Highlights: • AGEs are involved in bone quality deterioration in diabetes mellitus (DM). • AGEs increased sclerostin as well as apoptosis, and decreased RANKL in osteocytes. • The effects of AGEs on osteocyte function were antagonized by human PTH-(1–34). • AGEs may cause low bone turnover and cortical porosity in DM. • PTH may be effective in bone quality deterioration by improving osteocyte function.
Prolonged food deprivation increases mRNA expression of deiodinase 1 and 2, and thyroid hormone receptor β-1 in a fasting-adapted mammal.

Science.gov (United States)

Martinez, Bridget; Soñanez-Organis, José G; Vázquez-Medina, José Pablo; Viscarra, Jose A; MacKenzie, Duncan S; Crocker, Daniel E; Ortiz, Rudy M

2013-12-15

Food deprivation in mammals is typically associated with reduced thyroid hormone (TH) concentrations and deiodinase content and activity to suppress metabolism. However, in prolonged-fasted, metabolically active elephant seal pups, TH levels are maintained, if not elevated. The functional relevance of this apparent paradox is unknown and demonstrates variability in the regulation of TH levels, metabolism and function in food-deprived mammals. To address our hypothesis that cellular TH-mediated activity is upregulated with fasting duration, we quantified the mRNA expression and protein content of adipose and muscle deiodinase type I (DI1) and type II (DI2), and TH receptor beta-1 (THrβ-1) after 1, 3 and 7 weeks of fasting in northern elephant seal pups (N=5-7 per week). Fasting did not decrease the concentrations of plasma thyroid stimulating hormone, total triiodothyronine (tT3), free T3, total thyroxine (tT4) or free T4, suggesting that the hypothalamic-pituitary-thyroid axis is not suppressed, but rather maintained during fasting. Mean mRNA expression of adipose DI1 and DI2 increased threefold and fourfold, respectively, and 20- and 30-fold, respectively, in muscle. With the exception of adipose DI1, protein expression of adipose DI2 and muscle DI1 and DI2 increased twofold to fourfold. Fasting also increased adipose (fivefold) and muscle (fourfold) THrβ-1 mRNA expression, suggesting that the mechanisms mediating cellular TH activity are upregulated with prolonged fasting. The data demonstrate a unique, atypical mechanism of TH activity and regulation in mammals adapted to prolonged food deprivation in which the potential responsiveness of peripheral tissues and cellular TH activity are increased, which may contribute to their lipid-based metabolism.
The Role of PTHrP in Epithelial Stromal Interactions During Breast Development.

Science.gov (United States)

1999-07-01

development of skeletal muscle . Development 126:1621-1629. 12. Guo L, Degenstein L, and Fuchs E. (1996) Keratinocyte growth factor is required for hair...THE MEDICAL SCIENCES 287 Parathyroid Hormone-Related Protein L ’ ^-&#34 7«*.* %•** ’ • ». % Figure 1. Photomicrograph of a bone biopsy specimen...evident during development when PTHrP and the PTH/PTHrP receptor genes are expressed coordinately in adjacent cells begin- ning from the late morula
Mechanisms for the bone anabolic effect of parathyroid hormone treatment in humans

DEFF Research Database (Denmark)

Aslan, Derya; Dahl Andersen, Mille; Gede, Lene Bjerring

2012-01-01

. However, development of the biochemical measurement of PTH in the 1980s led us to understand the regulation of PTH secretion and calcium metabolism which subsequently paved the way for the use of PTH as an anabolic treatment of osteoporosis as, when given intermittently, it has strong anabolic effects...... in bone. This could not have taken place without the basic understanding achieved by the biochemical measurements of PTH. The stimulatory effects of PTH on bone formation have been explained by the so-called ‘anabolic window’, which means that during PTH treatment, bone formation is in excess over bone...... resorption during the first 6–18 months. This is due to the following: (1) PTH up-regulates c-fos expression in bone cells, (2) IGF is essential for PTH's anabolic effect, (3) bone lining cells are driven to differentiate into osteoblasts, (4) mesenchymal stem cells adhesion to bone surface is enhanced, (5...
Early prediction of post-thyroidectomy hypocalcemia by early parathyroid hormone measurement.

Science.gov (United States)

Yetkin, Gurkan; Citgez, Bulent; Yazici, Pinar; Mihmanli, Mehmet; Sit, Erhan; Uludag, Mehmet

2016-01-01

Hypoparathyroidism is the most common complication of total thyroidectomy (TT). Postthyroidectomy hypocalcemia occurs 24 to 48 hours after the operation. It prolongs the length of hospital stay, even though transient in most cases. The aim of this study was to predetermine the patients who may develop postthyroidectomy hypocalcemia by using early postoperative serum intact parathormone (iPTH) and calcium (Ca2+) measurements, and to investigate the effects of early initiated oral calcium and vitamin D treatments on the development of transient hypocalcemia. Patients who underwent TT after initiation of the early iPTH measurement protocol in January 2013 were included into the study group (Group 1, n=202). The control group (Group 2) was composed of 72 patients who underwent TT before the protocol. Prior to the initiation of the protocol, Ca2+ was measured instead of iPTH. In the study group, the serum Ca2+ and iPTH levels were measured before surgery, and 1 and 24-hours after. A calcium level below 8 mg/dL was accepted as biochemical hypocalcaemia, and a iPTH level under 15pg/mL was accepted as hypoparathyroidism. In the study group, patients with below normal iPTH levels were treated with prophylactic oral calcium and vitamin D. In Group 1, 15.8% (n=32) of the patients had hypoparathyroidism on the 1h and 24 h iPTH measurements. There was no statistically difference with regard to PTH levels measured in the postoperative 1st hour and at the 24th hour (p= 0.078). Biochemical hypocalcaemia developed in 16 (7.9%) and 13 (18%) patients in Groups 1 and 2, respectively, 24 hours after thyroidectomy (peffective management of plausible postthyroidectomic hypocalcemia. It yields significantly shorter hospital stay periods. Calcium, Hypoparathyroidism, Postoperative complication, Total thyroidectomy.
Growth hormone releasing hormone (GHRH) signaling modulates intermittent hypoxia-induced oxidative stress and cognitive deficits in mouse.

Science.gov (United States)

Nair, Deepti; Ramesh, Vijay; Li, Richard C; Schally, Andrew V; Gozal, David

2013-11-01

Intermittent hypoxia (IH) during sleep, such as occurs in obstructive sleep apnea (OSA), leads to degenerative changes in the hippocampus, and is associated with spatial learning deficits in adult mice. In both patients and murine models of OSA, the disease is associated with suppression of growth hormone (GH) secretion, which is actively involved in the growth, development, and function of the central nervous system (CNS). Recent work showed that exogenous GH therapy attenuated neurocognitive deficits elicited by IH during sleep in rats. Here, we show that administration of the Growth Hormone Releasing Hormone (GHRH) agonist JI-34 attenuates IH-induced neurocognitive deficits, anxiety, and depression in mice along with reduction in oxidative stress markers such as MDA and 8-hydroxydeoxyguanosine, and increases in hypoxia inducible factor-1α DNA binding and up-regulation of insulin growth factor-1 and erythropoietin expression. In contrast, treatment with a GHRH antagonist (MIA-602) during intermittent hypoxia did not affect any of the IH-induced deleterious effects in mice. Thus, exogenous GHRH administered as the formulation of a GHRH agonist may provide a viable therapeutic intervention to protect IH-vulnerable brain regions from OSA-associated neurocognitive dysfunction. Sleep apnea, characterized by chronic intermittent hypoxia (IH), is associated with substantial cognitive and behavioral deficits. Here, we show that administration of a GHRH agonist (JI-34) reduces oxidative stress, increases both HIF-1α nuclear binding and downstream expression of IGF1 and erythropoietin (EPO) in hippocampus and cortex, and markedly attenuates water maze performance deficits in mice exposed to intermittent hypoxia during sleep. © 2013 International Society for Neurochemistry.
Effect on thyroid function and serum PTH, BGP, CT of small dose of iodine 131 combined with Methimazole in patients with hyperthyroidism

Directory of Open Access Journals (Sweden)

Jia-Yin Qiu

2016-03-01

Full Text Available Objective: To observe the effect on thyroid function and serum PTH, BGP, CT of small dose of iodine 131 combined with Methimazole in patients with hyperthyroidism. Methods: A total of 104 patients with hyperthyroidism willing be incorporated into the study were randomly divided into the observation group (54 cases and the control group (50 cases. The control group was treated with Methimazole, and the observation group was given a small dose of iodine 131 the basised on the control group. For 2 months, to observe the changes of thyroid function (TT3, TT4, FT3, FT4 and TSH and bone metabolism related indexes (PTH, BGP and CT of the two groups. Results: (1 After treatment, TT3, FT3, TT4 and FT4 of the two groups decreased with before, and the observation group improved more significantly than the control group, with statistical difference; TSH of the two groups had no significant change. (2 After treatment, BGP and CT of the two groups decreased and PTH increased, the observation group improved more significantly than the control group, with statistical difference. Conclusion: small dose of iodine 131 combined with Methimazole can correct thyroid function and bone metabolism quickly in patients with hyperthyroidism.
Actin-Sorting Nexin 27 (SNX27)-Retromer Complex Mediates Rapid Parathyroid Hormone Receptor Recycling*

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McGarvey, Jennifer C.; Xiao, Kunhong; Bowman, Shanna L.; Mamonova, Tatyana; Zhang, Qiangmin; Bisello, Alessandro; Sneddon, W. Bruce; Ardura, Juan A.; Jean-Alphonse, Frederic; Vilardaga, Jean-Pierre; Puthenveedu, Manojkumar A.; Friedman, Peter A.

2016-01-01

The G protein-coupled parathyroid hormone receptor (PTHR) regulates mineral-ion homeostasis and bone remodeling. Upon parathyroid hormone (PTH) stimulation, the PTHR internalizes into early endosomes and subsequently traffics to the retromer complex, a sorting platform on early endosomes that promotes recycling of surface receptors. The C terminus of the PTHR contains a type I PDZ ligand that binds PDZ domain-containing proteins. Mass spectrometry identified sorting nexin 27 (SNX27) in isolated endosomes as a PTHR binding partner. PTH treatment enriched endosomal PTHR. SNX27 contains a PDZ domain and serves as a cargo selector for the retromer complex. VPS26, VPS29, and VPS35 retromer subunits were isolated with PTHR in endosomes from cells stimulated with PTH. Molecular dynamics and protein binding studies establish that PTHR and SNX27 interactions depend on the PDZ recognition motif in PTHR and the PDZ domain of SNX27. Depletion of either SNX27 or VPS35 or actin depolymerization decreased the rate of PTHR recycling following agonist stimulation. Mutating the PDZ ligand of PTHR abolished the interaction with SNX27 but did not affect the overall rate of recycling, suggesting that PTHR may directly engage the retromer complex. Coimmunoprecipitation and overlay experiments show that both intact and mutated PTHR bind retromer through the VPS26 protomer and sequentially assemble a ternary complex with PTHR and SNX27. SNX27-independent recycling may involve N-ethylmaleimide-sensitive factor, which binds both PDZ intact and mutant PTHRs. We conclude that PTHR recycles rapidly through at least two pathways, one involving the ASRT complex of actin, SNX27, and retromer and another possibly involving N-ethylmaleimide-sensitive factor. PMID:27008860
Interactions between calcium and phosphorus in the regulation of the production of fibroblast growth factor 23 in vivo

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Quinn, Stephen J.; Thomsen, Alex R. B.; Pang, Jian L.; Kantham, Lakshmi; Bräuner-Osborne, Hans; Pollak, Martin; Goltzman, David

2013-01-01

Calcium and phosphorus homeostasis are highly interrelated and share common regulatory hormones, including FGF23. However, little is known about calcium's role in the regulation of FGF23. We sought to investigate the regulatory roles of calcium and phosphorus in FGF23 production using genetic mouse models with targeted inactivation of PTH (PTH KO) or both PTH and the calcium-sensing receptor (CaSR; PTH-CaSR DKO). In wild-type, PTH KO, and PTH-CaSR DKO mice, elevation of either serum calcium or phosphorus by intraperitoneal injection increased serum FGF23 levels. In PTH KO and PTH-CaSR DKO mice, however, increases in serum phosphorus by dietary manipulation were accompanied by severe hypocalcemia, which appeared to blunt stimulation of FGF23 release. Increases in dietary phosphorus in PTH-CaSR DKO mice markedly decreased serum 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] despite no change in FGF23, suggesting direct regulation of 1,25(OH)2D3 synthesis by serum phosphorus. Calcium-mediated increases in serum FGF23 required a threshold level of serum phosphorus of about 5 mg/dl. Analogously, phosphorus-elicited increases in FGF23 were markedly blunted if serum calcium was less than 8 mg/dl. The best correlation between calcium and phosphorus and serum FGF23 was found between FGF23 and the calcium × phosphorus product. Since calcium stimulated FGF23 production in the PTH-CaSR DKO mice, this effect cannot be mediated by the full-length CaSR. Thus the regulation of FGF23 by both calcium and phosphorus appears to be fundamentally important in coordinating the serum levels of both mineral ions and ensuring that the calcium × phosphorus product remains within a physiological range. PMID:23233539
The Impact of Growth Hormone Therapy on the Apoptosis Assessment in CD34+ Hematopoietic Cells from Children with Growth Hormone Deficiency

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Miłosz Piotr Kawa

2017-01-01

Full Text Available Growth hormone (GH modulates hematopoietic cell homeostasis and is associated with apoptosis control, but with limited mechanistic insights. Aim of the study was to determine whether GH therapeutic supplementation (GH-TS could affect apoptosis of CD34+ cells enriched in hematopoietic progenitor cells of GH deficient (GHD children. CD34+ cells from peripheral blood of 40 GHD children were collected before and in 3rd and 6th month of GH-TS and compared to 60 controls adjusted for bone age, sex, and pubertal development. Next, apoptosis assessment via different molecular techniques was performed. Finally, to comprehensively characterize apoptosis process, global gene expression profile was determined using genome-wide RNA microarray technology. Results showed that GH-TS significantly reduced spontaneous apoptosis in CD34+ cells (p < 0.01 and results obtained using different methods to detect early and late apoptosis in analyzed cells population were consistent. GH-TS was also associated with significant downregulation of several members of TNF-alpha superfamily and other genes associated with apoptosis and stress response. Moreover, the significant overexpression of cyto-protective and cell cycle-associated genes was detected. These findings suggest that recombinant human GH has a direct anti-apoptotic activity in hematopoietic CD34+ cells derived from GHD subjects in course of GH-TS.
Fortification of Yogurts with Vitamin D and Calcium Enhances the Inhibition of Serum Parathyroid Hormone and Bone Resorption Markers: A Double Blind Randomized Controlled Trial in Women over 60 Living in a Community Dwelling Home.

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Bonjour, J-P; Benoit, V; Atkin, S; Walrand, S

2015-05-01

To evaluate whether fortification of yogurts with vitamin D and calcium exerts an additional lowering effect on serum parathyroid hormone (PTH) and bone resorption markers (BRM) as compared to iso-caloric and iso-protein dairy products in aged white women at risk of fragility fractures. A randomized double-blind controlled trial. A community dwelling home. Forty-eight women over 60 years (mean age 73.4). Consumption during 84 days of two 125 g servings of either vitamin D and calcium-fortified yogurts (FY) at supplemental levels of 10 µg vitamin D3/d and 520 mg/d of calcium (total=800 mg/d), or non fortified control yogurts (CY) providing 280 mg/d of calcium. Serum changes from baseline (D0) to D28, D56 and D84 in 25OHD, PTH and in two BRM: Tartrate-resistant-acid-phosphatase-isoform-5b (TRAP5b) and carboxy-terminal-cross-linked-telopeptide of type-I-collagen (CTX). The 10 years risk of major and hip fractures were 13.1 and 5.0%, and 12.9 and 4.2 %, in FY and CY groups, respectively. From D0 to D84, serum 25OHD increased (mean±SE) from 34.3±2.4 to 56.3±2.4 nmol/L in FY (n=24) and from 35.0±2.5 to 41.3±3.0 nmol/L in CY (n=24), (P=0.00001). The corresponding changes in PTH were from 64.1±5.1 to 47.4±3.8 ng/L in FY and from 63.5±4.6 to 60.7±4.2 ng/L in CY (P=0.0011). After D84, TRAP5b was reduced significantly (P=0.0228) and CTX fell though not significantly (P=0.0773) in FY compared to CY. This trial in aged white women living in a community dwelling home at risk for osteoporotic fractures confirms that fortification of dairy products with vitamin D3 and calcium should provide a greater prevention of secondary hyperparathyroidism and accelerated bone resorption as compared to non-fortified equivalent foods.
Action of specific thyroid hormone receptor α(1) and β(1) antagonists in the central and peripheral regulation of thyroid hormone metabolism in the rat.

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van Beeren, Hermina C; Kwakkel, Joan; Ackermans, Mariëtte T; Wiersinga, Wilmar M; Fliers, Eric; Boelen, Anita

2012-12-01

The iodine-containing drug amiodarone (Amio) and its noniodine containing analogue dronedarone (Dron) are potent antiarrhythmic drugs. Previous in vivo and in vitro studies have shown that the major metabolite of Amio, desethylamiodarone, acts as a thyroid hormone receptor (TR) α(1) and β(1) antagonist, whereas the major metabolite of Dron debutyldronedarone acts as a selective TRα(1) antagonist. In the present study, Amio and Dron were used as tools to discriminate between TRα(1) or TRβ(1) regulated genes in central and peripheral thyroid hormone metabolism. Three groups of male rats received either Amio, Dron, or vehicle by daily intragastric administration for 2 weeks. We assessed the effects of treatment on triiodothyronine (T(3)) and thyroxine (T(4)) plasma and tissue concentrations, deiodinase type 1, 2, and 3 mRNA expressions and activities, and thyroid hormone transporters monocarboxylate transporter 8 (MCT8), monocarboxylate transporter 10 (MCT10), and organic anion transporter 1C1 (OATP1C1). Amio treatment decreased serum T(3), while serum T(4) and thyrotropin (TSH) increased compared to Dron-treated and control rats. At the central level of the hypothalamus-pituitary-thyroid axis, Amio treatment decreased hypothalamic thyrotropin releasing hormone (TRH) expression, while increasing pituitary TSHβ and MCT10 mRNA expression. Amio decreased the pituitary D2 activity. By contrast, Dron treatment resulted in decreased hypothalamic TRH mRNA expression only. Upon Amio treatment, liver T(3) concentration decreased substantially compared to Dron and control rats (50%, p<0.01), but liver T(4) concentration was unaffected. In addition, liver D1, mRNA, and activity decreased, while the D3 activity and mRNA increased. Liver MCT8, MCT10, and OATP1C1 mRNA expression were similar between groups. Our results suggest an important role for TRα1 in the regulation of hypothalamic TRH mRNA expression, whereas TRβ plays a dominant role in pituitary and liver thyroid
Long-term effects of intravenous 1 alpha (OH)D3 combined with CaCO3 and low-calcium dialysis on secondary hyperparathyroidism and biochemical bone markers in patients on chronic hemodialysis

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Brandi, L; Daugaard, H; Nielsen, P K

1996-01-01

doses of CaCO3 and to reduce the doses of an aluminium-containing oral phosphate binder. A decrease in p-Ca2+ during dialysis was induced, and special care had to focus on the compliance to CaCO3, in order not to aggravate the secondary hyperparathyroidism. (2) The combination of 'low......The effects of intravenous administration of 1 alpha-hydroxycholecalciferol [1 alpha (OH)D3] in combination with CaCO3 and 'low-calcium dialysis' (1.25 mmol/l) on plasma (p) parathyroid hormone (PTH) and biochemical bone markers (osteocalcin, alkaline phosphatase, procollagen type 1 c......-terminal extension peptide) were examined in 54 patients on chronic hemodialysis with either normal or elevated PTH. Increasing doses of 1 alpha (OH)D3 were administered intravenously under careful control of p-Ca2+ and inorganic phosphate. Blood samples were obtained 1 week before the start of treatment...
The TAL effector PthA4 interacts with nuclear factors involved in RNA-dependent processes including a HMG protein that selectively binds poly(U RNA.

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Tiago Antonio de Souza

Full Text Available Plant pathogenic bacteria utilize an array of effector proteins to cause disease. Among them, transcriptional activator-like (TAL effectors are unusual in the sense that they modulate transcription in the host. Although target genes and DNA specificity of TAL effectors have been elucidated, how TAL proteins control host transcription is poorly understood. Previously, we showed that the Xanthomonas citri TAL effectors, PthAs 2 and 3, preferentially targeted a citrus protein complex associated with transcription control and DNA repair. To extend our knowledge on the mode of action of PthAs, we have identified new protein targets of the PthA4 variant, required to elicit canker on citrus. Here we show that all the PthA4-interacting proteins are DNA and/or RNA-binding factors implicated in chromatin remodeling and repair, gene regulation and mRNA stabilization/modification. The majority of these proteins, including a structural maintenance of chromosomes protein (CsSMC, a translin-associated factor X (CsTRAX, a VirE2-interacting protein (CsVIP2, a high mobility group (CsHMG and two poly(A-binding proteins (CsPABP1 and 2, interacted with each other, suggesting that they assemble into a multiprotein complex. CsHMG was shown to bind DNA and to interact with the invariable leucine-rich repeat region of PthAs. Surprisingly, both CsHMG and PthA4 interacted with PABP1 and 2 and showed selective binding to poly(U RNA, a property that is novel among HMGs and TAL effectors. Given that homologs of CsHMG, CsPABP1, CsPABP2, CsSMC and CsTRAX in other organisms assemble into protein complexes to regulate mRNA stability and translation, we suggest a novel role of TAL effectors in mRNA processing and translational control.

Mice lacking melanin-concentrating hormone receptor 1 demonstrate increased heart rate associated with altered autonomic activity.

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Astrand, Annika; Bohlooly-Y, Mohammad; Larsdotter, Sara; Mahlapuu, Margit; Andersén, Harriet; Tornell, Jan; Ohlsson, Claes; Snaith, Mike; Morgan, David G A

2004-10-01

Melanin-concentrating hormone (MCH) plays an important role in energy balance. The current studies were carried out on a new line of mice lacking the rodent MCH receptor (MCHR1(-/-) mice). These mice confirmed the previously reported lean phenotype characterized by increased energy expenditure and modestly increased caloric intake. Because MCH is expressed in the lateral hypothalamic area, which also has an important role in the regulation of the autonomic nervous system, heart rate and blood pressure were measured by a telemetric method to investigate whether the increased energy expenditure in these mice might be due to altered autonomic nervous system activity. Male MCHR1(-/-) mice demonstrated a significantly increased heart rate [24-h period: wild type 495 +/- 4 vs. MCHR1(-/-) 561 +/- 8 beats/min (P dark phase: wild type 506 +/- 8 vs. MCHR1(-/-) 582 +/- 9 beats/min (P light phase: wild type 484 +/- 13 vs. MCHR1(-/-) 539 +/- 9 beats/min (P vs. MCHR1(-/-) 113 +/- 0.4 mmHg (P > 0.05)]. Locomotor activity and core body temperature were higher in the MCHR1(-/-) mice during the dark phase only and thus temporally dissociated from heart rate differences. On fasting, wild-type animals rapidly downregulated body temperature and heart rate. MCHR1(-/-) mice displayed a distinct delay in the onset of this downregulation. To investigate the mechanism underlying these differences, autonomic blockade experiments were carried out. Administration of the adrenergic antagonist metoprolol completely reversed the tachycardia seen in MCHR1(-/-) mice, suggesting an increased sympathetic tone.
Metabolic and Hormonal Determinants of Glomerular Filtration Rate and Renal Hemodynamics in Severely Obese Individuals

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Edoardo Vitolo

2016-10-01

Full Text Available Objective: Renal function is often compromised in severe obesity. A true measurement of glomerular filtration rate (GFR is unusual, and how estimation formulae (EstForm perform in such individuals is unclear. We characterized renal function and hemodynamics in severely obese individuals, assessing the reliability of EstForm. Methods: We measured GFR (mGFR by iohexol plasma clearance, renal plasma flow (RPF by 123I-ortho-iodo-hippurate, basal and stimulated vascular renal indices, endothelium-dependent and -independent vasodilation using flow-mediated dilation (FMD as well as metabolic and hormonal profile in morbid, otherwise healthy, obese subjects. Results: Compared with mGFR, the better performing EstForm was CKD-EPI (5.3 ml/min/1.73 m2 bias by Bland-Altman analysis. mGFR was directly related with RPF, total and incremental glucose AUC, and inversely with PTH and h8 cortisol. Patients with mGFR below the median shown significantly higher PTH and lower vitamin D3. Basal or dynamic renal resistive index, FMD, pulse wave velocity were not related with mGFR. In an adjusted regression model, renal diameter and plasma flow remained related with mGFR (R2 = 0.67, accounting for 15% and 21% of mGFR variance, respectively. Conclusions: CKD-EPI formula should be preferred in morbid obesity; glucose increments during oral glucose tolerance test correlate with hyperfiltration; RPF and diameter are independent determinants of mGFR; slightly high PTH values, frequent in obesity, might influence mGFR.
Better functional mobility in community-dwelling elderly is related to D-hormone serum levels and to daily calcium intake.

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Dukas, L; Staehelin, H B; Schacht, E; Bischoff, H A

2005-01-01

The influence of calcitropic hormones on functional mobility has been studied in vitamin D (calcidiol) deficient elderly or elderly with a history of falls, however, data in community-dwelling independent vitamin D replete elderly are missing. We therefore assessed in an observational survey the association of calcidiol (25(OH)D3) and calcitriol (D-hormone / 1,25(OH)2D3) status as well as of daily calcium intake on functional mobility in older subjects We evaluated 192 women and 188 men, aged superior 70 years and living independently. Average Timed-up and go test (TUG-test) in seconds was taken as measure of functional mobility. Calcidiol and D-hormone serum concentrations and daily calcium intake were studied in multivariate controlled linear regression models with TUG-test performance as the dependent variable and/or as dichotomous variables (deficient vs. non-deficient, above vs. below the median, respectively). Subjects with low D-hormone serum concentrations took significantly more time to perform the TUG-test (low = 7.70s +/- 2.52 SD ; high = 6.70s +/- 1.29 SD; p = 0.004). In the linear multivariate controlled regression model increased D-hormone serum concentrations predicted better TUG-test performance (estimate -0.0007, p = 0.044). Participants with a calcium intake of > or =512 mg/day were significantly faster to perform the TUG-test than participants with a daily calcium intake of better TUG-test performance in both models were: male gender, less comorbid conditions, younger age, lower BMI, iPTH serum levels and creatinine clearance. Calcidiol serum levels were not associated with TUG-test performance. Higher D-hormone status and a calcium intake of > or =512 mg/day in community-dwelling independent older persons are significant determinants of better functional mobility. Therefore, to ensure optimal functional mobility, the care of older persons should address correction of D-hormone deficiency and increasing daily calcium intake.
The role of leptin and other hormones related to bone metabolism and appetite-regulation as determinants of gain in body fat and fat-free mass in 8-11 year old children

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Dalskov, Stine-Mathilde; Ritz, Christian; Larnkjær, Anni

2015-01-01

Background: Regulation of body composition during childhood is complex. Numerous hormones are potentially involved. Leptin has been proposed to restrain weight gain, but results are inconsistent. Objectives: We examined if baseline fasting levels of ghrelin, adiponectin, leptin, insulin, insulin......-like growth factor I (IGF-1), osteocalcin and intact parathyroid hormone (iPTH) were associated with body composition cross-sectionally and longitudinally in 633 8-11-year-olds. Design: Data on hormones and body composition by Dual-energy X-ray absorptiometry from OPUS School Meal Study were used. We looked...... at baseline hormones as predictors of baseline fat mass index (FMI) or fat-free mass index (FFMI), and also subsequent changes (three and six months) in FMI or FFMI using models with hormones individually or combined. Results: Cross-sectionally, baseline leptin was positively associated with FMI in girls (0...
Hormonal and echocardiographic abnormalities in adult patients with sickle-cell anemia in Bahrain

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Garadah TS

2016-12-01

Full Text Available Taysir S Garadah,1,2 Ahmed A Jaradat,3 Mohammed E Alalawi,1 Adla B Hassan2 1Cardiac Unit, Salmaniya Medical Complex, Ministry of Health, 2Department of Internal Medicine, College of Medicine and Medical Sciences, Arabian Gulf University, Manama, 3Department of Family and Community Medicine, Arabian Gulf University, Manama, Bahrain Background: Adrenal, thyroid, and parathyroid gland hormonal changes are recognized in children with homozygous (HbSS sickle-cell anemia (SCA, but are not clear in adult patients with SCA. Aim: To assess the metabolic and endocrine abnormalities in adult patients with SCA and evaluate left ventricular (LV systolic and diastolic functions compared with patients with no SCA and further study the relationship between serum levels of cortisol, free thyroxine (T4, and testosterone with serum ferritin. Materials and methods: The study was conducted on 82 patients with adult HbSS SCA compared with a sex- and age-matched control group. The serum levels of cortisol, parathyroid hormone (PTH, testosterone, thyroid-stimulating hormone (TSH, and free T4 were compared. Blood levels of hemoglobin, reticulocyte count, lactate dehydrogenase (LDH, calcium, alkaline phosphatase (ALP, vitamin D3, and ferritin were also compared. Pulsed Doppler echo was performed to evaluate the LV mass, wall thickness, and cavity dimensions with diastolic filling velocities of early (E and atria (A waves. Biometric data were analyzed as mean ± standard deviation between the two groups. Multiple regression analysis was performed between serum levels of ferritin as independent variable and testosterone, cortisol, and thyroid hormones. Results: A total of 82 adult patients with HbSS SCA were enrolled who had a mean age of 21±5.7 years, with 51 males (62%. Patients with SCA compared with the control group had significantly lower hemoglobin, body mass index, cortisol, vitamin D3, testosterone, and T4. Furthermore, there were significantly high levels of
Effects of phospho- and calciotropic hormones on electrolyte transport in the proximal tubule

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Lee, Justin J; Plain, Allein; Beggs, Megan R

2017-01-01

), active vitamin D 3, and fibroblast growth factor 23 (FGF23). The organs central to this are the kidneys, intestine, and bone. In the kidney, the proximal tubule reabsorbs the majority of filtered calcium and phosphate, which amounts to more than 60% and 90%, respectively. The basic molecular mechanisms......Calcium and phosphate are critical for a myriad of physiological and cellular processes within the organism. Consequently, plasma levels of calcium and phosphate are tightly regulated. This occurs through the combined effects of the phospho- and calciotropic hormones, parathyroid hormone (PTH...... as their regulation of active vitamin D 3 synthesis in this nephron segment. The integrative effects of both phospho- and calciotropic hormones on proximal tubular solute transport and subsequently whole body calcium-phosphate balance thus have been further complicated. Here, we first review the molecular mechanisms...
Effects of Lowering Dialysate Calcium Concentration on Mineral and Bone Disorders in Chronic Hemodialysis Patients: Conversion from 3.0 mEq/L to 2.75 mEq/L.

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Yamada, Shunsuke; Ueki, Kenji; Tokumoto, Masanori; Suehiro, Takaichi; Kimura, Hiroshi; Taniguchi, Masatomo; Fujimi, Satoru; Kitazono, Takanari; Tsuruya, Kazuhiko

2016-02-01

Selection of a lower dialysate calcium concentration (DCa) can reduce calcium burden and prevent vascular calcification in hemodialysis patients. However, decreased DCa can worsen mineral and bone disorders. This 1-year retrospective observational study evaluated 121 hemodialysis patients at Fukuoka Renal Clinic who underwent conversion of DCa from 3.0 mEq/L to 2.75 mEq/L. The primary outcomes were changes in serum levels of calcium, phosphate, and parathyroid hormone (PTH). The effects of baseline serum calcium and PTH levels on changes in biochemical parameters were also determined. One year after DCa conversion, mean serum calcium level decreased, while serum phosphate, alkaline phosphatase, and PTH concentrations increased. The rate of achievement of target PTH was higher in patients with lower serum PTH level at baseline, while patients with higher baseline serum PTH level tended to exceed the upper limit of the PTH target range. Patients with higher baseline serum calcium concentration showed a greater decrease in serum calcium level and a greater increase in serum PTH level at 1 year. Patients with a lower baseline serum PTH level can benefit from optimal PTH control following conversion of DCa from 3.0 mEq/L to 2.75 mEq/L. However, secondary hyperparathyroidism may be exacerbated in some patients with higher baseline serum calcium (Ca) and PTH levels. These results indicate that an individualized approach can maximize the benefits of Ca unloading after conversion to lower DCa. © 2015 International Society for Apheresis, Japanese Society for Apheresis, and Japanese Society for Dialysis Therapy.
Targeting sphingosine-1-phosphate lyase as an anabolic therapy for bone loss.

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Weske, Sarah; Vaidya, Mithila; Reese, Alina; von Wnuck Lipinski, Karin; Keul, Petra; Bayer, Julia K; Fischer, Jens W; Flögel, Ulrich; Nelsen, Jens; Epple, Matthias; Scatena, Marta; Schwedhelm, Edzard; Dörr, Marcus; Völzke, Henry; Moritz, Eileen; Hannemann, Anke; Rauch, Bernhard H; Gräler, Markus H; Heusch, Gerd; Levkau, Bodo

2018-05-01

Sphingosine-1-phosphate (S1P) signaling influences bone metabolism, but its therapeutic potential in bone disorders has remained unexplored. We show that raising S1P levels in adult mice through conditionally deleting or pharmacologically inhibiting S1P lyase, the sole enzyme responsible for irreversibly degrading S1P, markedly increased bone formation, mass and strength and substantially decreased white adipose tissue. S1P signaling through S1P 2 potently stimulated osteoblastogenesis at the expense of adipogenesis by inversely regulating osterix and PPAR-γ, and it simultaneously inhibited osteoclastogenesis by inducing osteoprotegerin through newly discovered p38-GSK3β-β-catenin and WNT5A-LRP5 pathways. Accordingly, S1P 2 -deficient mice were osteopenic and obese. In ovariectomy-induced osteopenia, S1P lyase inhibition was as effective as intermittent parathyroid hormone (iPTH) treatment in increasing bone mass and was superior to iPTH in enhancing bone strength. Furthermore, lyase inhibition in mice successfully corrected severe genetic osteoporosis caused by osteoprotegerin deficiency. Human data from 4,091 participants of the SHIP-Trend population-based study revealed a positive association between serum levels of S1P and bone formation markers, but not resorption markers. Furthermore, serum S1P levels were positively associated with serum calcium , negatively with PTH , and curvilinearly with body mass index. Bone stiffness, as determined through quantitative ultrasound, was inversely related to levels of both S1P and the bone formation marker PINP, suggesting that S1P stimulates osteoanabolic activity to counteract decreasing bone quality. S1P-based drugs should be considered as a promising therapeutic avenue for the treatment of osteoporotic diseases.
Efficacy of Ablation Therapy for Secondary Hyperparathyroidism by Ultrasound Guided Percutaneous Thermoablation.

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Zhao, Junfeng; Qian, Linxue; Zu, Yuan; Wei, Ying; Hu, Xiangdong

2016-05-01

The objective of this study was to explore the value of ultrasound-guided percutaneous microwave thermoablation to treat secondary hyperparathyroidism (SHPT). One hundred and thirty-eight parathyroid glands from 56 patients with SHPT were ablated in this study. All the parathyroid glands were evaluated by real-time contrast-enhanced ultrasound before, during and after ablation. Changes in serum parathyroid hormone (sPTH) levels were measured before treatment and at 1 h, 1 wk, 1 mo and 6 mo after thermoablation treatment. All 56 cases had a 1-mo follow-up, and 34 cases had a 6-mo follow-up. The sPTH level of the 54 cases 1 mo after ablation was significantly lower than that before (p 0.05). Ultrasound-guided percutaneous microwave thermoablation is a feasible and effective non-surgical alternative treatment for SHPT patients. Copyright © 2016. Published by Elsevier Inc.
How the reference values for serum parathyroid hormone concentration are (or should be) established?

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Souberbielle, J-C; Brazier, F; Piketty, M-L; Cormier, C; Minisola, S; Cavalier, E

2017-03-01

Well-validated reference values are necessary for a correct interpretation of a serum PTH concentration. Establishing PTH reference values needs recruiting a large reference population. Exclusion criteria for this population can be defined as any situation possibly inducing an increase or a decrease in PTH concentration. As recommended in the recent guidelines on the diagnosis and management of asymptomatic primary hyperparathyroidism, PTH reference values should be established in vitamin D-replete subjects with a normal renal function with possible stratification according to various factors such as age, gender, menopausal status, body mass index, and race. A consensus about analytical/pre-analytical aspects of PTH measurement is also needed with special emphasis on the nature of the sample (plasma or serum), the time and the fasting/non-fasting status of the blood sample. Our opinion is that blood sample for PTH measurement should be obtained in the morning after an overnight fast. Furthermore, despite longer stability of the PTH molecule in EDTA plasma, we prefer serum as it allows to measure calcium, a prerequisite for a correct interpretation of a PTH concentration, on the same sample. Once a consensus is reached, we believe an important international multicentre work should be performed to recruit a very extensive reference population of apparently healthy vitamin D-replete subjects with a normal renal function in order to establish the PTH normative data. Due to the huge inter-method variability in PTH measurement, a sufficient quantity of blood sample should be obtained to allow measurement with as many PTH kits as possible.
Brown tumor of the maxilla in patient with secondary hyperparathyroidism

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Jović Nebojša

2004-01-01

Full Text Available Brown tumor or parathyroid osteopathy is a kind of bony lesion caused by hyperparathyroidism. It appears as an expansive osteolytic lesion mostly in mandible, ribs, pelvis and femur, but rarely in the upper jaw. Bone resorption is the result of osteoclastic activity due to an increased activity of parathyroid hormone. A 25-years-old male patient was operated on due to clinicaly and radiographicaly obvious maxillary tumor and increased values of parathyroid hormon (PTH - 1 050 ng/l. The level of calcium in blood was normal (Ca 2.34 mEq/L. The patient was dialyzed for years because of the chronic renal failure. Histopathologic analysis confirmed brown tumor, that appeared as bony lesion of secondary hyperparathyroidism due to the chronic renal failure. The operation of the upper jaw had been performed before parathyroidectomy, due to an excessive growth of tumor followed by heavy epistaxes. The subsequent parathyroidectomy was followed by the regression of remaining bony lesions.
The Role of the Multiple Hormonal Dysregulation in the Onset of “Anemia of Aging”: Focus on Testosterone, IGF-1, and Thyroid Hormones

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Marcello Maggio

2015-01-01

Full Text Available Anemia is a multifactorial condition whose prevalence increases in both sexes after the fifth decade of life. It is a highly represented phenomenon in older adults and in one-third of cases is “unexplained.” Ageing process is also characterized by a “multiple hormonal dysregulation” with disruption in gonadal, adrenal, and somatotropic axes. Experimental studies suggest that anabolic hormones such as testosterone, IGF-1, and thyroid hormones are able to increase erythroid mass, erythropoietin synthesis, and iron bioavailability, underlining a potential role of multiple hormonal changes in the anemia of aging. Epidemiological data more consistently support an association between lower testosterone and anemia in adult-older individuals. Low IGF-1 has been especially associated with anemia in the pediatric population and in a wide range of disorders. There is also evidence of an association between thyroid hormones and abnormalities in hematological parameters under overt thyroid and euthyroid conditions, with limited data on subclinical statuses. Although RCTs have shown beneficial effects, stronger for testosterone and the GH-IGF-1 axis and less evident for thyroid hormones, in improving different hematological parameters, there is no clear evidence for the usefulness of hormonal treatment in improving anemia in older subjects. Thus, more clinical and research efforts are needed to investigate the hormonal contribution to anemia in the older individuals.
Low vitamin D and high parathyroid hormone levels as determinants of loss of muscle strength and muscle mass (sarcopenia) : the Longitudinal Aging Study Amsterdam

NARCIS (Netherlands)

Visser, Marjolein; Deeg, Dorly J H; Lips, Paul

2003-01-01

The age-related change in hormone concentrations has been hypothesized to play a role in the loss of muscle mass and muscle strength with aging, also called sarcopenia. The aim of this prospective study was to investigate whether low serum 25-hydroxyvitamin D (25-OHD) and high serum PTH
The effect of high-dose vitamin D supplementation on calciotropic hormones and bone mineral density in obese subjects with low levels of circulating 25-hydroxyvitamin d: results from a randomized controlled study.

Science.gov (United States)

Wamberg, Louise; Pedersen, Steen B; Richelsen, Bjørn; Rejnmark, Lars

2013-07-01

Low levels of 25-hydroxyvitamin D (25OHD) are associated with increased bone turnover and risk of fractures. Plasma 25OHD is inversely related to body mass index, and vitamin D deficiency is common in obesity. We aimed to determine whether vitamin D supplementation affects bone turnover and bone mineral density (BMD) in obese subjects. Fifty-two healthy obese men and women aged 18-50 years with plasma 25OHD levels below 50 nmol/L were randomized to 7,000 IU of cholecalciferol daily or placebo for 26 weeks. We measured plasma levels of 25OHD, parathyroid hormone (PTH), and markers of bone turnover, as well as BMD at the hip, spine, forearm, and whole body. Compared with placebo, treatment with cholecalciferol increased mean plasma 25OHD from 35 to 110 nmol/L (p importance to bone health in young obese subjects as increased levels of 25OHD are associated with a decrease in both PTH and bone turnover and with an increase in BMD at the forearm.
Urbanization of black South African women may increase risk of low bone mass due to low vitamin D status, low calcium intake, and high bone turnover.

Science.gov (United States)

Kruger, Marlena C; Kruger, Iolanthé M; Wentzel-Viljoen, Edelweiss; Kruger, Annamarie

2011-10-01

Globally, rural to urban migration is accompanied by changes in dietary patterns and lifestyle that have serious health implications, including development of low bone mass. We hypothesized that serum 25 (OH) vitamin D3 (25[OH]D3) levels will be lower, bone turnover higher, and nutrition inadequate in urban postmenopausal black women, increasing risk for low bone mass. We aimed to assess the prevalence of risk factors for low bone mass in 1261 black women from rural and urban areas in the North West Province of South Africa (Prospective Urban and Rural Epidemiology-South Africa project). Fasting blood samples were taken; and participants were interviewed to complete questionnaires on self-reported diseases, fractures, and dietary intakes. Bone health markers were assessed in a subgroup of 658 women older than 45 years. Specific lifestyle risk factors identified were inactivity, smoking, injectable progestin contraception use, and high alcohol consumption. Dietary risk factors identified were low calcium and high animal protein, phosphorous, and sodium intakes. The 25(OH)D3 and C-terminal telopeptide (CTX) levels were significantly higher in the rural vs the urban women older than 50 years. Parathyroid hormone (PTH) levels increased with age in both groups. The 25(OH)D levels were inversely correlated with CTX and PTH in rural women. In urban women, PTH and CTX were correlated while dietary calcium was inversely correlated with CTX and PTH with 25(OH)D3. The combination of low dietary calcium (<230 mg/d), marginally insufficient 25(OH)D3 status, and raised PTH may result in increased bone resorption. Further research is required to assess bone health and fracture risk in black African women. Copyright © 2011 Elsevier Inc. All rights reserved.
Recovery responses of testosterone, growth hormone, and IGF-1 after resistance exercise.

Science.gov (United States)

Kraemer, William J; Ratamess, Nicholas A; Nindl, Bradley C

2017-03-01

The complexity and redundancy of the endocrine pathways during recovery related to anabolic function in the body belie an oversimplistic approach to its study. The purpose of this review is to examine the role of resistance exercise (RE) on the recovery responses of three major anabolic hormones, testosterone, growth hormone(s), and insulin-like growth factor 1. Each hormone has a complexity related to differential pathways of action as well as interactions with binding proteins and receptor interactions. Testosterone is the primary anabolic hormone, and its concentration changes during the recovery period depending on the upregulation or downregulation of the androgen receptor. Multiple tissues beyond skeletal muscle are targeted under hormonal control and play critical roles in metabolism and physiological function. Growth hormone (GH) demonstrates differential increases in recovery with RE based on the type of GH being assayed and workout being used. IGF-1 shows variable increases in recovery with RE and is intimately linked to a host of binding proteins that are essential to its integrative actions and mediating targeting effects. The RE stress is related to recruitment of muscle tissue with the glandular release of hormones as signals to target tissues to support homeostatic mechanisms for metabolism and tissue repair during the recovery process. Anabolic hormones play a crucial role in the body's response to metabolism, repair, and adaptive capabilities especially in response to anabolic-type RE. Changes of these hormones following RE during recovery in the circulatory biocompartment of blood are reflective of the many mechanisms of action that are in play in the repair and recovery process. Copyright © 2017 the American Physiological Society.
Resistance exercise-induced increases in putative anabolic hormones do not enhance muscle protein synthesis or intracellular signalling in young men.

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West, Daniel W D; Kujbida, Gregory W; Moore, Daniel R; Atherton, Philip; Burd, Nicholas A; Padzik, Jan P; De Lisio, Michael; Tang, Jason E; Parise, Gianni; Rennie, Michael J; Baker, Steven K; Phillips, Stuart M

2009-11-01

We aimed to determine whether exercise-induced elevations in systemic concentration of testosterone, growth hormone (GH) and insulin-like growth factor-1 (IGF-1) enhanced post-exercise myofibrillar protein synthesis (MPS) and phosphorylation of signalling proteins important in regulating mRNA translation. Eight young men (20 +/- 1.1 years, BMI = 26 +/- 3.5 kg m(-2)) completed two exercise protocols designed to maintain basal hormone concentrations (low hormone, LH) or elicit increases in endogenous hormones (high hormone, HH). In the LH protocol, participants performed a bout of unilateral resistance exercise with the elbow flexors. The HH protocol consisted of the same elbow flexor exercise with the contralateral arm followed immediately by high-volume leg resistance exercise. Participants consumed 25 g of protein after arm exercise to maximize MPS. Muscle biopsies and blood samples were taken as appropriate. There were no changes in serum testosterone, GH or IGF-1 after the LH protocol, whereas there were marked elevations after HH (testosterone, P anabolic hormones do not enhance fed-state anabolic signalling or MPS following resistance exercise. Local mechanisms are likely to be of predominant importance for the post-exercise increase in MPS.
Premenstrual Symptoms in Dysmenorrheic College Students: Prevalence and Relation to Vitamin D and Parathyroid Hormone Levels

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Bayan A. Obeidat

2012-11-01

Full Text Available Objectives: To determine the prevalence of premenstrual symptoms (PMS due to primary dysmenorrhea among a sample of university female students, and to explore possible association with vitamin D and parathyroid (PTH levels, as well as frequency of consumption of dairy products. Design: A cross-sectional study. Setting: One Jordanian university. Subjects: A total of 177 female students aged between 18 and 24 years who experienced primary dysmenorrhea participated in the study and completed a self administered questionnaire to collect information concerning demographics, menstruation- related information, associated specified premenstrual symptoms, and consumption of dairy products. Plasma 25-hydroxyvitamin vitamin D level and intact parathyroid hormone level were measured. Results: Of the 177 participants 91.5% had two or more symptoms among which fatigue, mood swings, anxiety, abdominal bloating, and depression were the most prevalent symptoms. There was no evident association between presence of symptoms and vitamin D status, PTH level or dairy products consumption. Headaches and social withdrawal were significantly lower in those women who consumed high amounts of dairy products. Conclusion: Premenstrual symptoms are very common in young women with primary dysmenorrhea. PMS has no relation to levels of vitamin D, parathyroid hormone or dairy products consumption. Headache and social withdrawal may be affected by dairy product consumption.
Influence of exercise on bone remodeling-related hormones and cytokines in ovariectomized rats: a model of postmenopausal osteoporosis.

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Lihui Li

Full Text Available This study aims to explore the effects of exercise on postmenopausal osteoporosis and the mechanisms by which exercise affects bone remodeling. Sixty-three Wistar female rats were randomly divided into five groups: (1 control group, (2 sham-operated group, (3 OVX (Ovariectomy group, (4 DES-OVX (Diethylstilbestrol-OVX group, and (5 Ex-OVX (Exercise-OVX group. The rat osteoporosis model was established through ovariectomy. The Ex-OVX rats were made to run 251.2 meters every day, 6 d/wk for 3 months in a running wheel. Trabecular bone volume (TBV%, total resorption surface (TRS%, trabecular formation surface (TFS%, mineralization rate (MAR, bone cortex mineralization rate (mAR, and osteoid seam width (OSW were determined by bone histomorphometry. The mRNA and protein levels of interleukin-1β (IL-1β2, interleukin-6 (IL-6, and cyclooxygenase-2 (Cox-2 were determined by in situ hybridization and immunohistochemistry, respectively. Serum levels of estrogen estradiol (E2, calcitonin (CT, osteocalcin (BGP, and parathyroid hormone (PTH were determined by ELISA assays. The investigation revealed that compared to the control and the sham-operated groups, the OVX group showed significantly lower levels of TBV%, E2, and CT, but much higher levels of TRS%, TFS%, MAR, OSW, BGP, and PTH. The Ex-OVX group showed increased TBV% and serum levels of E2 and CT compared to the OVX group. Ovariectomy also led to a significant increase in IL-1β mRNA and protein levels in the bone marrow and IL-6 and Cox-2 protein levels in tibias. In addition, the Ex-OVX group showed lower levels of IL-1 mRNA and protein, IL-6 mRNA, and Cox-2 mRNA and protein than those in the OVX group. The upshot of the study suggests that exercise can significantly increase bone mass in postmenopausal osteoporosis rat models by inhibiting bone resorption and increasing bone formation, especially in trabecular bones.
miR-34 increases in vitro PANC-1 cell sensitivity to gemcitabine via targeting Slug/PUMA.

Science.gov (United States)

Zhang, Qing-An; Yang, Xu-Hai; Chen, Dong; Yan, Xiang; Jing, Fu-Chun; Liu, Hong-Qian; Zhang, Ronghua

2018-01-01

miR-34 was deregulated in tumor tissues compared with corresponding noncancerous tissue samples. Furthermore, miR-34 may contribute to cancer-stromal interaction associated with cancer progression. However, whether miR-34 could decrease chemoresistance of cancer cells to chemotherapeutic agent remains unclear. In our study, we examined whether overexpression of miR-34 could sensitize gemcitabine -mediated apoptosis in human pancreatic cancer PANC-1 cells. We found that miR-34 markedly induced gemcitabine -mediated apoptosis in PANC-1 cells. miR-34 induced down-regulation of Slug expression and upregulation of p53 up-regulated modulator of apoptosis (PUMA) expression. The over-expression of Slug or downregulation of PUMA by Slug cDNA or PUMA siRNA transfection markedly blocked miR-34-induced gemcitabine sensitization. Furthermore, miR-34 induced PUMA expression by downregulation of Slug. Taken together, our study demonstrates that miR-34 enhances sensitization against gemcitabine-mediated apoptosis through the down-regulation of Slug expression, and up-regulation of Slug-dependent PUMA expression.

Targeted Disruption of NF1 in Osteocytes Increases FGF23 and Osteoid With Osteomalacia-like Bone Phenotype.

Science.gov (United States)

Kamiya, Nobuhiro; Yamaguchi, Ryosuke; Aruwajoye, Olumide; Kim, Audrey J; Kuroyanagi, Gen; Phipps, Matthew; Adapala, Naga Suresh; Feng, Jian Q; Kim, Harry Kw

2017-08-01

Neurofibromatosis type 1 (NF1, OMIM 162200), caused by NF1 gene mutations, exhibits multi-system abnormalities, including skeletal deformities in humans. Osteocytes play critical roles in controlling bone modeling and remodeling. However, the role of neurofibromin, the protein product of the NF1 gene, in osteocytes is largely unknown. This study investigated the role of neurofibromin in osteocytes by disrupting Nf1 under the Dmp1-promoter. The conditional knockout (Nf1 cKO) mice displayed serum profile of a metabolic bone disorder with an osteomalacia-like bone phenotype. Serum FGF23 levels were 4 times increased in cKO mice compared with age-matched controls. In addition, calcium-phosphorus metabolism was significantly altered (calcium reduced; phosphorus reduced; parathyroid hormone [PTH] increased; 1,25(OH) 2 D decreased). Bone histomorphometry showed dramatically increased osteoid parameters, including osteoid volume, surface, and thickness. Dynamic bone histomorphometry revealed reduced bone formation rate and mineral apposition rate in the cKO mice. TRAP staining showed a reduced osteoclast number. Micro-CT demonstrated thinner and porous cortical bones in the cKO mice, in which osteocyte dendrites were disorganized as assessed by electron microscopy. Interestingly, the cKO mice exhibited spontaneous fractures in long bones, as found in NF1 patients. Mechanical testing of femora revealed significantly reduced maximum force and stiffness. Immunohistochemistry showed significantly increased FGF23 protein in the cKO bones. Moreover, primary osteocytes from cKO femora showed about eightfold increase in FGF23 mRNA levels compared with control cells. The upregulation of FGF23 was specifically and significantly inhibited by PI3K inhibitor Ly294002, indicating upregulation of FGF23 through PI3K in Nf1-deficient osteocytes. Taken together, these results indicate that Nf1 deficiency in osteocytes dramatically increases FGF23 production and causes a mineralization
Comparison of third and second generation parathyroid hormone assays and their use in chronic hemdialysis patients

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Alexis Muryan

2017-06-01

Full Text Available Introduction: This work’s objective is to compare third and second generation assays in patients with normal kidney function and in chronic hemodialysis patients, and the implications on the latter. Methods: 60 chronic hemodialysis patients and 40 patients with normal kidney function were studied and their PTH levels were measured for both assays. Results: In patients population with normal kidney function the average on PTH was 51.8 and 45.6 pg/ml with second and third generation assays respectively. In chronic hemodialysis patients the average PTH was 193.9 and 137.1 pg/ml with second and third generation assays respectively. The difference between assays was 11.3% and 29.3% in patients with normal kidney function and in hemodialysis patients respectively. Third generation assay caused a variation in the amount of patients that fall over seve ral PTH ranges according to KDIGO guidelines, for a lesser value of 2 times the reference upper limit: it changes from 20 to 25 patients, between 2 and 9 times: it changes from 31 to 32 patients, and more than 9 times: it changes from 9 to 3 patients. Conclusions: When PTH concentration increases the difference between both assays also increases, for this reason we cannot use them indiscriminately in a chronic hemodialysis patient population. With third generation assays 11 patients (18.3% changed their classification according to KDIGO guidelines, which will result in a change of treatment.
Artificially Increased Yolk Hormone Levels and Neophobia in Domestic Chicks

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Aline Bertin

2015-11-01

Full Text Available In birds there is compelling evidence that the development and expression of behavior is affected by maternal factors, particularly via variation in yolk hormone concentrations of maternal origin. In the present study we tested whether variation in yolk hormone levels lead to variation in the expression of neophobia in young domestic chicks. Understanding how the prenatal environment could predispose chicks to express fear-related behaviors is essential in order to propose preventive actions and improve animal welfare. We simulated the consequences of a maternal stress by experimentally enhancing yolk progesterone, testosterone and estradiol concentrations in hen eggs prior to incubation. The chicks from these hormone-treated eggs (H and from sham embryos (C that received the vehicle-only were exposed to novel food, novel object and novel environment tests. H chicks approached a novel object significantly faster and were significantly more active in a novel environment than controls, suggesting less fearfulness. Conversely, no effect of the treatment was found in food neophobia tests. Our study highlights a developmental influence of yolk hormones on a specific aspect of neophobia. The results suggest that increased yolk hormone levels modulate specifically the probability of exploring novel environments or novel objects in the environment.
A randomized, double-blind, placebo-controlled trial of calcium acetate on serum phosphorus concentrations in patients with advanced non-dialysis-dependent chronic kidney disease

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Ho Chiang-Hong

2011-02-01

Full Text Available Abstract Background Hyperphosphatemia in patients with chronic kidney disease (CKD contributes to secondary hyperparathyroidism, soft tissue calcification, and increased mortality risk. This trial was conducted to examine the efficacy and safety of calcium acetate in controlling serum phosphorus in pre-dialysis patients with CKD. Methods In this randomized, double-blind, placebo-controlled trial, 110 nondialyzed patients from 34 sites with estimated GFR 2 and serum phosphorus > 4.5 mg/dL were randomized to calcium acetate or placebo for 12 weeks. The dose of study drugs was titrated to achieve target serum phosphorus of 2.7-4.5 mg/dL. Serum phosphorus, calcium, iPTH, bicarbonate and serum albumin were measured at baseline and every 2 weeks for the 12 week study period. The primary efficacy endpoint was serum phosphorus at 12 weeks. Secondary endpoints were to measure serum calcium and intact parathyroid hormone (iPTH levels. Results At 12 weeks, serum phosphorus concentration was significantly lower in the calcium acetate group compared to the placebo group (4.4 ± 1.2 mg/dL vs. 5.1 ± 1.4 mg/dL; p = 0.04. The albumin-adjusted serum calcium concentration was significantly higher (9.5 ± 0.8 vs. 8.8 ± 0.8; p p Conclusions In CKD patients not yet on dialysis, calcium acetate was effective in reducing serum phosphorus and iPTH over a 12 week period. Trial Registration www.clinicaltrials.gov NCT00211978.
Hypocalcemic stimulation and nonselective venous sampling for localizing parathyroid adenomas: work in progress.

Science.gov (United States)

Doppman, J L; Skarulis, M C; Chang, R; Alexander, H R; Bartlett, D; Libutti, S K; Marx, S J; Spiegel, A M

1998-07-01

To evaluate whether the release of parathyroid hormone (PTH) from parathyroid tumors during selective parathyroid arteriography can help localize the tumors. In 20 patients (six men, 14 women; age range, 24-72 years) with parathyroid tumors undergoing parathyroid arteriography after failed surgery, serial measurements of PTH were obtained during selective arteriography with nonionic contrast material. PTH levels were measured in the superior vena cava (SVC) before and at varying times from 20 to 120 seconds after arteriography. A 1.4-fold increase in the PTH level of the postarteriographic SVC samples enabled correct prediction of the site of adenoma in 13 of the 20 patients (65%). Of nine patients with positive arteriograms, eight had positive results of postarteriographic sampling. Of 11 patients with negative arteriograms, five had positive results of postarteriographic sampling. Sampling the SVC for PTH gradients after selective parathyroid arteriography correctly indicated the site of the adenoma in 13 of 20 patients (65%).
Sensitive and rapid immunoassay for parathyroid hormone using magnetic particle labels and magnetic actuation.

Science.gov (United States)

Dittmer, W U; de Kievit, P; Prins, M W J; Vissers, J L M; Mersch, M E C; Martens, M F W C

2008-09-30

A rapid method for the sensitive detection of proteins using actuated magnetic particle labels, which are measured with a giant magneto-resistive (GMR) biosensor, is described. The technique involves a 1-step sandwich immunoassay with no fluid replacement steps. The various assay binding reactions as well as the bound/free separation are entirely controlled by magnetic forces induced by electromagnets above and below the sensor chip. During the assay, particles conjugated with tracer antibodies are actuated through the sample for target capture, and rapidly brought to the sensor surface where they bind to immobilized capture antibodies. Weakly or unbound labels are removed with a magnetic force oriented away from the GMR sensor surface. For the measurement of parathyroid hormone (PTH), a detection limit in the 10 pM range is obtained with a total assay time of 15 min when 300 nm particles are used. The same sensitivity can be achieved in 5 min when 500 nm particles are used. If 500 nm particles are employed in a 15-minute assay, then 0.8 pM of PTH is detectable. The low sample volume, high analytical performance and high speed of the test coupled with the compact GMR biosensor make the system especially suitable for sensitive testing outside of laboratory environments.
Effect of radiation on proteo-hormones activity

International Nuclear Information System (INIS)

Mikulaj, L.

1975-05-01

Samples of pituitary hormones were irradiated by a 60 Co source. A dose rate of 1.0-1.1 Mrad/hour and the doses of 0.5, 2.5 and 12.5 Mrad were used. The hormone preparations in the dry solid state or in solution were sealed into glass ampules. After sterilization they were kept at 4 0 C until the biological activity had been tested. The biological activity of thyroid stimulating hormone TSH, subjected to a sterilizing dose of 2.5 Mrad of gamma radiation, was found to have decreased when tested 3-5 months after irradiation. TSH remained fully active for up to 1 month after sterilization. The activity of vasopressin dropped off markedly during the 3-4 week period after irradiation. Biological activity of growth hormone tested shortly after irradiation was found to be unaffected. The activities of adrenocorticotropic hormone, human menopausal gonadotropin and luteinizing hormone were not affected. The experiments can be considered promising since they show that pituitary proteohorm, one preparations in the solid state may be sterilized. The stability on storage needs, however, to be carefully checked individually for every single hormone
Expansion of microsatellite in the thyroid hormone receptor-alpha1 gene linked to increased receptor expression and less aggressive thyroid cancer

DEFF Research Database (Denmark)

Onda, Masamitsu; Li, Daisy; Suzuki, Shinichi

2002-01-01

PURPOSE: The purpose of this study was to determine whether the length of the THRA1 microsatellite, which resides in a noncoding portion of the thyroid hormone receptor-alpha1 gene, affects receptor expression and is linked to clinicopathological parameters in thyroid cancer. EXPERIMENTAL DESIGN......: In 30 cases of surgically resected sporadic thyroid cancer, the length of the THRA1 microsatellite was determined by DNA sequence analysis, and expression of thyroid hormone receptor-alpha1 was assessed immunohistochemically in thin sections cut from tumor blocks. The length of THRA1 and expression...... of thyroid hormone receptor-alpha1 were also assessed in seven cancer cell lines. Regression analysis was used to gauge the correlation between the size of THRA1 and receptor expression. Multivariate analysis was used to test for links to the clinical parameters of gender, age, histology, stage, nodal...
In uncontrolled diabetes, thyroid hormone and sympathetic activators induce thermogenesis without increasing glucose uptake in brown adipose tissue.

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Matsen, Miles E; Thaler, Joshua P; Wisse, Brent E; Guyenet, Stephan J; Meek, Thomas H; Ogimoto, Kayoko; Cubelo, Alex; Fischer, Jonathan D; Kaiyala, Karl J; Schwartz, Michael W; Morton, Gregory J

2013-04-01

Recent advances in human brown adipose tissue (BAT) imaging technology have renewed interest in the identification of BAT activators for the treatment of obesity and diabetes. In uncontrolled diabetes (uDM), activation of BAT is implicated in glucose lowering mediated by intracerebroventricular (icv) administration of leptin, which normalizes blood glucose levels in streptozotocin (STZ)-induced diabetic rats. The potent effect of icv leptin to increase BAT glucose uptake in STZ-diabetes is accompanied by the return of reduced plasma thyroxine (T4) levels and BAT uncoupling protein-1 (Ucp1) mRNA levels to nondiabetic controls. We therefore sought to determine whether activation of thyroid hormone receptors is sufficient in and of itself to lower blood glucose levels in STZ-diabetes and whether this effect involves activation of BAT. We found that, although systemic administration of the thyroid hormone (TR)β-selective agonist GC-1 increases energy expenditure and induces further weight loss in STZ-diabetic rats, it neither increased BAT glucose uptake nor attenuated diabetic hyperglycemia. Even when GC-1 was administered in combination with a β(3)-adrenergic receptor agonist to mimic sympathetic nervous system activation, glucose uptake was not increased in STZ-diabetic rats, nor was blood glucose lowered, yet this intervention potently activated BAT. Similar results were observed in animals treated with active thyroid hormone (T3) instead of GC-1. Taken together, our data suggest that neither returning normal plasma thyroid hormone levels nor BAT activation has any impact on diabetic hyperglycemia, and that in BAT, increases of Ucp1 gene expression and glucose uptake are readily dissociated from one another in this setting.
Failure to Diagnose Hyperparathyroidism in 10,432 Patients With Hypercalcemia: Opportunities for System-level Intervention to Increase Surgical Referrals and Cure.

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Balentine, Courtney J; Xie, Rongbing; Kirklin, James K; Chen, Herbert

2017-10-01

To determine whether a significant number of patients with hyperparathyroidism remain undiagnosed and untreated. Failure to diagnose primary hyperparathyroidism and refer patients to surgeons leads to impaired quality of life and increased costs. We hypothesized that many patients with hyperparathyroidism would be untreated due to not considering the diagnosis, inadequate evaluation of hypercalcemia, and under-referral to surgeons. We reviewed administrative data on 682,704 patients from a tertiary referral center between 2011 and 2015, and identified hypercalcemia (>10.5 mg/dL) in 10,432 patients. We evaluated whether hypercalcemic patients underwent measurement of parathyroid hormone (PTH), had documentation of hypercalcemia/hyperparathyroidism, or were referred to surgeons. The mean age of our cohort was 54 years, with 61% females, and 56% whites. Only 3200 (31%) hypercalcemic patients had PTH levels measured, 2914 (28%) had a documented diagnosis of hypercalcemia, and 880 (8%) had a diagnosis of hyperparathyroidism in the medical record. Only 592 (22%) out of 2666 patients with classic hyperparathyroidism (abnormal calcium and PTH) were referred to surgeons. A significant proportion of patients with hyperparathyroidism do not undergo appropriate evaluation and surgical referral. System-level interventions which prompt further evaluation of hypercalcemia and raise physician awareness about hyperparathyroidism could improve outcomes and produce long-term cost savings.
Increased insulin sensitivity in intrauterine growth retarded newborns--do thyroid hormones play a role?

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Setia, Sajita; Sridhar, M G; Koner, B C; Bobby, Zachariah; Bhat, Vishnu; Chaturvedula, Lata

2007-02-01

Thyroid hormones are necessary for normal brain development. We studied thyroid hormone profile and insulin sensitivity in intrauterine growth retarded (IUGR) newborns to find correlation between insulin sensitivity and thyroid status in IUGR newborns. Fifty IUGR and fifty healthy control infants were studied at birth. Cord blood was collected for determination of T(3), T(4), TSH, glucose and insulin levels. IUGR newborns had significantly lower insulin, mean+/-S.D., 5.25+/-2.81 vs. 11.02+/-1.85microU/ml, but significantly higher insulin sensitivity measured as glucose to insulin ratio (G/I), 9.80+/-2.91 vs. 6.93+/-1.08 compared to healthy newborns. TSH was also significantly higher 6.0+/-2.70 vs. 2.99+/-1.05microU/ml with significantly lower T(4), 8.65+/-1.95 vs. 9.77+/-2.18microg/dl, but similar T(3) levels, 100.8+/-24.36 vs. 101.45+/-23.45ng/dl. On stepwise linear regression analysis in IUGR infants, insulin sensitivity was found to have a significant negative association with T(4) and significant positive association with TSH. Thyroid hormones may play a role in increased insulin sensitivity at birth in IUGR.
Hyperparathyroidism complicating CYP 24A1 mutations.

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Loyer, Camille; Leroy, Clara; Molin, Arnaud; Odou, Marie-Françoise; Huglo, Damien; Lion, Georges; Ernst, Olivier; Hoffmann, Maxime; Porchet, Nicole; Carnaille, Bruno; Pattou, François; Kottler, Marie-Laure; Vantyghem, Marie-Christine

2016-10-01

CYP24A1 gene mutations induce infantile hypercalcemia, with high 1,25(OH) 2 D contrasting with low PTH levels. The adult phenotype is not well known. Two unrelated adult patients were referred for nephrolithiasis, hypertension, hypercalcemia, hypercalciuria, normal 25-OHD levels, and inappropriate PTH levels (22 to 92pg/mL;N: 15-68) suggesting primary hyperparathyroidism, leading to surgery. Hypercalciuria improved despite persistent hypercalcemia, treated with cinacalcet. The ratio 25-OHD 3 /24-25-(OH)2D 3 >100 (Nhyperparathyroidism with moderately increased PTH level, adenoma and/or slightly increased parathyroid glands. Surgery decreased calciuria and improved kidney function. Cinacalcet was partially effective on hypercalcemia since PTH was inappropriate. This novel phenotype, a phenocopy of hyperparathyroidism, might evolve in few cases towards hyperparathyroidism despite random association of the 2 diseases cannot be excluded. Copyright © 2016. Published by Elsevier Masson SAS.
Brown tumor of mandible with primary hyperparathyroidism

International Nuclear Information System (INIS)

Ali, S.K.; Khan, F.A.; Siddiq, A.; Hanif, M.S.

2011-01-01

Parathyroid hormone (PTH) is secreted and released by the parathyroid glands, the activity of which is controlled by the ionized serum calcium level. Increased PTH secretion results in hyperparathyroidism. Hyperparathyroidism is classified as primary, secondary and tertiary types. Primary hyperparathyroidism is characterized by increased parathyroid hormone secretion occurring as a result of abnormality in one or more of the parathyroid glands. Brown tumors are non-neoplastic lesions as a result of abnormal bone metabolism in cases of hyperparathyroidism, creating a local destructive phenomenon. A rare case of a young female patient with brown tumors in her mandible associated with primary hyperparathyroidism, is reported. (author)
Overexpression of thyroid hormone beta1 nuclear receptor is associated with an increased proliferation of human hepatoma cells

International Nuclear Information System (INIS)

Lin, K.; Lin, Y.; McPhie, P.; Cheng S.

1994-01-01

It is evaluated the expression of thyroid hormone nuclear receptors (TRs) and their possible roles in the carcinogenesis of human hepatocarcinoma. The expression of TRβ and TRα genes was evaluated at both the mRNA and protein levels. The expression of TRβ1 and TRα1 mRNAs is similar to those found in normal liver. However, the expression of TR isoform proteins depends on the cell-type. The expression of TRα1 protein is low in all cell lines examined. However, TRβ1 protein is overexpressed in Mahlavu, SK-Hep-1, and HA22T, moderately expressed in J5, J7, and J328 and is very low in HepG2, Hep3B, and PLC/PRF/5 cells. The proliferation of cells in which TRβ1 is overexpressed is stimulated by the thyroid hormone, 3,3',5-triiodo-L-thyronine. These results suggest that TRβ1 not TRα1, is probably involved in the proliferation of hepatoma cells
Association of Drug Effects on Serum Parathyroid Hormone, Phosphorus, and Calcium Levels With Mortality in CKD: A Meta-analysis.

Science.gov (United States)

Palmer, Suetonia C; Teixeira-Pinto, Armando; Saglimbene, Valeria; Craig, Jonathan C; Macaskill, Petra; Tonelli, Marcello; de Berardis, Giorgia; Ruospo, Marinella; Strippoli, Giovanni F M

2015-12-01

Serum parathyroid hormone (PTH), phosphorus, and calcium levels are surrogate outcomes that are central to the evaluation of drug treatments in chronic kidney disease (CKD). This systematic review evaluates the evidence for the correlation between drug effects on biochemical (PTH, phosphorus, and calcium) and all-cause and cardiovascular mortality end points in adults with CKD. Systematic review and meta-analysis. Adults with CKD. Randomized trials reporting drug effects on biochemical and mortality end points. Drug interventions with effects on serum PTH, phosphorus, and calcium levels, including vitamin D compounds, phosphate binders, cinacalcet, bisphosphonates, and calcitonin. Correlation between drug effects on biochemical and all-cause and cardiovascular mortality. 28 studies (6,999 participants) reported both biochemical and mortality outcomes and were eligible for analysis. Associations between drug effects on surrogate biochemical end points and corresponding effects on mortality were weak and imprecise. All correlation coefficients were less than 0.70, and 95% credible intervals were generally wide and overlapped with zero, consistent with the possibility of no association. The exception was an inverse correlation between drug effects on serum PTH levels and all-cause mortality, which was nominally significant (-0.64; 95% credible interval, -0.85 to -0.15), but the strength of this association was very imprecise. Risk of bias within available trials was generally high, further reducing confidence in the summary correlations. Findings were robust to adjustment for age, baseline serum PTH level, allocation concealment, CKD stage, and drug class. Low power in analyses and combining evidence from many different drug comparisons with incomplete data across studies. Drug effects on serum PTH, phosphorus, and calcium levels are weakly and imprecisely correlated with all-cause and cardiovascular death in the setting of CKD. Risks of mortality (patient
Parathyroid Hormone Polymorphism RS6254 is Associated with the Development and Severity of Osteoporosis in Asymptomatic but not Normocalcemic Hyperthyroidism.

Science.gov (United States)

Díaz-Soto, G; Romero, E; Pérez-Castrillón, J L; Jauregui, O I; de Luis Román, D

2016-12-01

Although normocalcemic and asymptomatic hyperparathyroidism (HPT) are becoming more common, they remain only partially understood. Parathyroid hormone ( PTH ) polymorphisms have been associated with disease severity in classical HPT. The aim of the present study was to evaluate the clinical effect of PTH polymorphism (rs6254) in normocalcemic and asymptomatic HPT. A prospective study of 61 consecutive patients with normocalcemic or asymptomatic HPT was carried out. Secondary causes of HPT were ruled out. All patients were followed for≥1 year. Calcium and phosphorus metabolism parameters were assessed at least twice during the follow-up period to classify as normocalcemic or asymptomatic HPT. Bone mineral density (BMD) and the rs6254 polymorphism genotype were also assessed. Genotype rs6254GG was observed in 23 patients (37.7%) whereas GA and AA genotypes were presented in 29 (47.5%) and 9 (14.8%) patients, respectively. Age, sex and genotype distributions were comparable in both groups. In asymptomatic but not normocalcemic HPT patients, the GG genotype was associated with a significantly higher level of intact PTH [200.2 (SD 76.5) vs. 113.3 (SD 25.9) pg/ml; peffect of rs6254GA polymorphism on the development and severity of BMD complications in patients with asymptomatic but not normocalcemic HPT. Further studies are needed to confirm this finding and to assess the effect of other polymorphisms in normocalcemic and asymptomatic HPT. © Georg Thieme Verlag KG Stuttgart · New York.
TGF-beta1 expression in EL4 lymphoma cells overexpressing growth hormone.

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Farmer, John T; Weigent, Douglas A

2006-03-01

Our previous studies show that growth hormone overexpression (GHo) upregulates the expression of the IGF-1R and IGF-2R resulting in the protection of the EL4 lymphoma cell line from apoptosis. In this study, we report that GHo also increases TGF-beta1 protein expression measured by luciferase promoter assay, Western analysis, and ELISA. Further, the data show that antibody to TGF-betaR2 decreases TGF-beta1 promoter activity to the level of vector alone control cells. GHo cells treated with (125)I-rh-latent TGF-beta1 showed increased activation of latent TGF-beta1 as measured by an increase in the active 24kDa, TGF-beta1 compared to vector alone control cells. The ability of endogenous GH to increase TGF-beta1 expression is blocked in EL4 cells by antisense but not sense oligodeoxynucleotides or in cells cultured with antibody to growth hormone (GH). The data suggest that endogenous GH may protect from apoptosis through the IGF-1R receptor while limiting cellular growth through increased expression and activation of TGF-beta1.
Quality-of-life in patients with post-traumatic hypopituitarism.

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Nourollahi, Sabrina; Wille, Julia; Weiß, Verena; Wedekind, Christoph; Lippert-Grüner, Marcela

2014-01-01

Hypopituitarism is a frequent complication in patients after traumatic brain injury (TBI). Both TBI and hypopituitarism can lead to complex cognitive and affective deficits. This study was intended to examine the quality-of-life in patients with post-traumatic hypopituitarism (PTH) and to discern the effect of this endocrinological disorder on general outcome of patients after TBI including earning capacity. Research type: Retrospective analysis of clinical data. Ninety-seven symptomatic patients were screened after TBI for PTH. Their results were examined in the SF-36 [a standardized questionnaire for quality of life (QoL)] comparing the groups with or without PTH. After 6 months of hormone substitution (if necessary), patients were asked to repeat the SF-36. Forty-six patients were diagnosed with PTH (47.5%). All patients included had a significantly lower QoL compared to the standard population. QoL was significantly worse in patients with PTH. There was no significant difference with regard to earning capacity. After hormone substitution, patients achieved better SF-36-results, albeit the difference was lacking statistical significance. PTH is frequent after TBI. PTH turns out to further diminish QoL, without affecting earning capacity. Hormone substitution might improve QoL in patients with PTH, but future research is needed to confirm this hypothesis.
Associations of Sun Exposure with 25-Hydroxyvitamin D and Parathyroid Hormone Levels in a Cohort of Hypertensive Patients: The Graz Endocrine Causes of Hypertension (GECOH Study

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Stefan Pilz

2012-01-01

Full Text Available Sunlight-induced vitamin D, synthesis in the skin is the major source of vitamin D, but data on the relationship of sun-related behaviour with vitamin D and parathyroid hormone (PTH levels are relatively sparse. We evaluated whether habitual sun exposure is associated with 25-hydroxyvitamin D (25[OH]D and PTH levels and whether there exist seasonal variations. We examined 111 hypertensive patients in Austria (latitude 47° N. Frequent sunbathing at home and outdoor sports were associated with higher 25(OHD levels (P<0.05 for both. Red or blond scalp hair as a child, memory of sunburns, preferring sunbathing, frequent stays on the beach or in open-air pools, and solarium use were associated with lower PTH levels (P<0.05 for all. Multiple linear regression analyses including age, sex, and body mass index showed that sun exposure score was significantly associated with 25(OHD (beta coefficient=0.27; P=0.004 and by trend with PTH (beta coefficient=−0.16; P=0.09. These associations were more prominent in summer in which 25(OHD levels were significantly higher compared to winter. Translation of these findings into recommendations for the prevention and treatment of vitamin D deficiency remains a challenge for the future.
Fibroblast Growth Factor (FGF) 23 Regulates the Plasma Levels of Parathyroid Hormone In Vivo Through the FGF Receptor in Normocalcemia, But Not in Hypocalcemia

DEFF Research Database (Denmark)

Mace, Maria L; Gravesen, Eva; Nordholm, Anders

2018-01-01

hypocalcemia. We demonstrated that FGF23 rapidly inhibited PTH secretion and that this effect was completely blocked by inhibition of the FGF receptor. Furthermore, inhibition of the FGF receptor by itself significantly increased PTH levels, indicating that FGF23 has a suppressive tonus on the parathyroid...... gland's PTH secretion. In acute hypocalcemia, there was no effect of either recombinant FGF23 or FGF receptor inhibition on the physiological response to the low ionized calcium levels. In conclusion, FGF23 has an inhibitory tonus on PTH secretion in normocalcemia and signals through the FGF receptor....... In acute hypocalcemia, when increased PTH secretion is needed to restore the calcium homeostasis, this inhibitory effect of FGF23 is abolished....

Combined Treatment with Gonadotropin-releasing Hormone Analog and Anabolic Steroid Hormone Increased Pubertal Height Gain and Adult Height in Boys with Early Puberty for Height.

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Tanaka, Toshiaki; Naiki, Yasuhiro; Horikawa, Reiko

2012-04-01

Twenty-one boys with a height of 135 cm or less at onset of puberty were treated with a combination of GnRH analog and anabolic steroid hormone, and their pubertal height gain and adult height were compared with those of untreated 29 boys who enter puberty below 135 cm. The mean age at the start of treatment with a GnRH analog, leuprorelin acetate depot (Leuplin(®)) was 12.3 yr, a mean of 1.3 yr after the onset of puberty, and GnRH analog was administered every 3 to 5 wk thereafter for a mean duration of 4.1 yr. The anabolic steroid hormone was started approximately 1 yr after initiation of treatment with the GnRH analog. The mean pubertal height gain from onset of puberty till adult height was significantly greater in the combination treatment group (33.9 cm) than in the untreated group (26.4 cm) (ppenis and pubic hair is promoted by the anabolic steroid hormone, no psychosocial problems arose because of delayed puberty. No clinically significant adverse events appeared. Combined treatment with GnRH analog and anabolic steroid hormone significantly increased height gain during puberty and adult height in boys who entered puberty with a short stature, since the period until epiphyseal closure was extended due to deceleration of the bone age maturation by administration of the GnRH analog and the growth rate at this time was maintained by the anabolic steroid hormone.
Studies on endogenous circulating calcium entry blocker and stimulator

International Nuclear Information System (INIS)

Pang, P.K.T.; Yang, M.C.M.

1986-01-01

Several synthetic compounds have been studied extensively for their calcium entry blockade and stimulation in smooth muscles. It is hypothesized that there should be endogenous substances which control calcium entry into cells. We recently investigated the effect of some vasoactive hormones on calcium entry. Our studies on rat tail artery helical strip showed that the in vitro vasoconstriction produced by arginine vasopressin (AVP) decreased stepwise with decreasing concentration of both calcium. After exposure of the tail artery to calcium-free Ringer's solution for 1 minute or longer, the tissue lost its ability to respond to AVP. Subsequent addition of calcium to the medium produced immediate contraction. Measurements of low affinity lanthanum resistant pool of calcium with 45 Ca showed that AVP increased calcium uptake by tail artery in a dose-dependent manner. In another study rat tail artery helical strip indicated that the vasorelaxing action of parathyroid hormone (PTH) was related to an inhibition of calcium uptake. AVP or 60 mM potassium chloride increased the low affinity lanthanum resistant pool of calcium in rate tail artery and PTH inhibited the increase. In conclusion, AVP and PTH may behave like endogenous calcium entry stimulator and inhibitor respectively in vascular tissues
Age-related changes in bone in the dog: calcium homeostasis

International Nuclear Information System (INIS)

Williams, E.A.; Kelly, P.J.

1984-01-01

To explore the changes in the relationship between skeletal and Ca 2+ homeostasis with age, a study was made of 50 dogs divided into four age groups. The skeletal uptake of 85 Sr decreased markedly with age, and the immunoreactive parathyroid hormone (iPTH) level increased. There was a significant correlation between iPTH value and the calculated short-term exchange of Ca in bone. Bone formation and bone resorption decreased with age except that in the oldest group of dogs the resorption increased. The authors suggest that in aging dogs the skeletal exchange of Ca falls to a very low level that decreases the immediate effect of PTH and thus leads to a chronic net increase in circulating PTH. Concomitant with this is an increase in osteoclastic bone resorption and, over a long time, loss of skeletal mass
In Vitro Fertilization Using Luteinizing Hormone-Releasing Hormone Injections Resulted in Healthy Triplets without Increased Attack Rates in a Hereditary Angioedema Case

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Ceyda Tunakan Dalgıç

2018-01-01

Full Text Available Hereditary angioedema due to C1-inhibitor deficiency (C1-INH-HAE is a rare, autosomal dominant disorder. The management of pregnant patients with C1-INH-HAE is a challenge for the physician. Intravenous plasma-derived nanofiltered C1-INH (pdC1INH is the only recommended option throughout pregnancy, postpartum, and breastfeeding period. In order to increase pregnancy rates, physicians use fertilization therapies increasing endogen levels of estrogens. Therefore, these techniques can provoke an increase in the number and severity of edema attacks in C1-INH-HAE. Our patient is a 32-year-old female, diagnosed with C1-INH-HAE type 1 since 2004. She had been taking danazol 50–200 mg/day for 9 years. Due to her pregnancy plans in 2013, danazol was discontinued. PdC1INH was prescribed regularly for prophylactic purpose. Triplet pregnancy occurred by in vitro fertilization using luteinizing hormone-releasing hormone (LHRH injections. In our patient, LHRH injections were done four times without causing any severe attack during in vitro fertilization. Angioedema did not worsen during pregnancy and delivery due to the prophylactic use of intravenous pdC1INH in our patient. According to the attack frequency and severity, there was no difference between the three pregnancy trimesters. To our knowledge, this is the first published case of C1-INH-HAE receiving in vitro fertilization therapies without any angioedema attacks during pregnancy and delivery and eventually having healthy triplets with the prophylactic use of intravenous pdC1INH.
Disfunção hormonal em lesões não hipofisárias das regiões selar e periselar Hormonal dysfunction of nonpituitary lesions from midline and perisellar area

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Ana Luíza Vidal Fonseca

2001-12-01

Full Text Available OBJETIVO: Analisar a disfunção hormonal pré-operatória, clínica e/ou laboratorial, das lesões intracranianas não hipofisárias da linha média e região peri-selar. MÉTODO: Foram analisados 44 pacientes com lesões intracranianas não hipofisárias, com exames de imagem (tomografia computadorizada ou ressonância magnética e dosagens hormonais basais; 16 tinham provas de função hipotálamo-hipofisária (megateste pré-operatórios. Esses pacientes foram divididos em dois grupos: Grupo I - 34 lesões da linha média: 11 craniofaringiomas, 8 meningiomas, 3 germinomas, 3 tumores do seio esfenoidal, 2 síndromes sela vazia, 2 astrocitomas pilocíticos, 1 aneurisma gigante, 2 mucoceles, 1 divertículo do III ventrículo e 1 cisto da bolsa de Rathke; Grupo II - 10 lesões da região peri-selar: 9 meningiomas e 1 aneurisma gigante. RESULTADOS: No grupo I, 25/34 (73,5% pacientes apresentavam déficit hormonal laboratorial (14 sem clínica evidente, 18/34 (52,9% hiperprolactinemia (apenas 5 com galactorréia e, dos 15 megatestes realizados nesse grupo, 8 (53,3% mostraram deficiência do hormônio de crescimento (GH; 3 (8,8 % pacientes apresentaram diabetes insipidus central (DIC pré-operatório. No grupo II, 6/10 (60% pacientes apresentavam déficit hormonal laboratorial (5 sem clínica evidente, 1/10 (10% hiperprolactinemia e 1 deficiência de GH (único megateste feito nesse grupo; nenhum paciente apresentou DIC pré-operatório. CONCLUSÃO: A presença de manifestações clínicas inespecíficas ou pouco valorizadas não indica ausência de disfunção hormonal laboratorial; na presente série, 19/38 (50% pacientes com alterações laboratoriais, não apresentavam manifestações clínicas. Disfunção hormonal é frequente em lesões não hipofisárias selares e peri-selares, especialmente, aquelas envolvendo a linha média.OBJECTIVE: To analyse clinical and/or laboratorial preoperative hormonal dysfunction , of the nonpituitary
Overexpression of thyroid hormone beta1 nuclear receptor is associated with an increased proliferation of human hepatoma cells

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Lin, K; Lin, Y; McPhie, P [Chang-Gung College of Medicine and Technology, Graduate Institute of Clinical Medicine, Taoyuan (Taiwan, Province of China); Cheng, S [National Cancer Inst., Bethesda, MD (United States)

1994-12-31

It is evaluated the expression of thyroid hormone nuclear receptors (TRs) and their possible roles in the carcinogenesis of human hepatocarcinoma. The expression of TR{beta}1 and TR{alpha} genes was evaluated at both the mRNA and protein levels. The expression of TR{beta}1 and TR{alpha}1 mRNAs is similar to those found in normal liver. However, the expression of TR isoform proteins depends on the cell-type. The expression of TRaplha1 protein is low in all cell lines examined. However, TR{Beta}1 protein is overexpressed in Mahlavu, SK-Hep-1, and HA22T, moderately expressed in J5, J7, and J328 and is very low HepG2, Hep3B, and PLC/PRF/5 cells. The proliferation of cells in which TR{beta}1 is overexpressed is stimulated by the thyroid hormone, 3,3`,5- triiodo-L-thyronine. These results suggest that TR{beta}1, not TR{alpha}1, is probably involved in the prolifaration of hepatoma cells.
Relationship between fasting glucose, vitamin D and PTH in early postmenopausal women

DEFF Research Database (Denmark)

við Streym, Susanna; Rejnmark, Lars; Vestergaard, Peter

Abstract Relationship between fasting glucose, vitamin D and PTH in early postmenopausal women Súsanna við Streym Thomsen (1), Lars Rejnmark (1), Peter Vestergaard (1), Christine Brot (2), Pia Eiken (3), Pernille Hermann (4) Leif Mosekilde (1). (1) Department of Medicine and Endocrinology C...... postmenopausal Caucasian women (n=2016) aged 45 to 58 years old. Measurements: Fasting blood glucose was measured after an overnight fast by standard laboratory methods. Serum levels of 25OHD were measured by a competitive assay using rachitic rat binding protein. The fat and lean mass was measured by DXA...... between fasting blood glucose and 25OHD and all studied indices. In a multivariate linear regression analyzing fasting blood glucose was significantly associated with BMI (b=0.038 ±0.007 (SE), 2p
Phosphorylation of Ribosomal Protein S6 Mediates Mammalian Target of Rapamycin Complex 1-Induced Parathyroid Cell Proliferation in Secondary Hyperparathyroidism.

Science.gov (United States)

Volovelsky, Oded; Cohen, Gili; Kenig, Ariel; Wasserman, Gilad; Dreazen, Avigail; Meyuhas, Oded; Silver, Justin; Naveh-Many, Tally

2016-04-01

Secondary hyperparathyroidism is characterized by increased serum parathyroid hormone (PTH) level and parathyroid cell proliferation. However, the molecular pathways mediating the increased parathyroid cell proliferation remain undefined. Here, we found that the mTOR pathway was activated in the parathyroid of rats with secondary hyperparathyroidism induced by either chronic hypocalcemia or uremia, which was measured by increased phosphorylation of ribosomal protein S6 (rpS6), a downstream target of the mTOR pathway. This activation correlated with increased parathyroid cell proliferation. Inhibition of mTOR complex 1 by rapamycin decreased or prevented parathyroid cell proliferation in secondary hyperparathyroidism rats and in vitro in uremic rat parathyroid glands in organ culture. Knockin rpS6(p-/-) mice, in which rpS6 cannot be phosphorylated because of substitution of all five phosphorylatable serines with alanines, had impaired PTH secretion after experimental uremia- or folic acid-induced AKI. Uremic rpS6(p-/-) mice had no increase in parathyroid cell proliferation compared with a marked increase in uremic wild-type mice. These results underscore the importance of mTOR activation and rpS6 phosphorylation for the pathogenesis of secondary hyperparathyroidism and indicate that mTORC1 is a significant regulator of parathyroid cell proliferation through rpS6. Copyright © 2016 by the American Society of Nephrology.
The administration of intermittent parathyroid hormone affects functional recovery from trochanteric fractured neck of femur: a randomised prospective mixed method pilot study.

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Chesser, T J S; Fox, R; Harding, K; Halliday, R; Barnfield, S; Willett, K; Lamb, S; Yau, C; Javaid, M K; Gray, A C; Young, J; Taylor, H; Shah, K; Greenwood, R

2016-06-01

We wished to assess the feasibility of a future randomised controlled trial of parathyroid hormone (PTH) supplements to aid healing of trochanteric fractures of the hip, by an open label prospective feasibility and pilot study with a nested qualitative sub study. This aimed to inform the design of a future powered study comparing the functional recovery after trochanteric hip fracture in patients undergoing standard care, versus those who undergo administration of subcutaneous injection of PTH for six weeks. We undertook a pilot study comparing the functional recovery after trochanteric hip fracture in patients 60 years or older, admitted with a trochanteric hip fracture, and potentially eligible to be randomised to either standard care or the administration of subcutaneous PTH for six weeks. Our desired outcomes were functional testing and measures to assess the feasibility and acceptability of the study. A total of 724 patients were screened, of whom 143 (20%) were eligible for recruitment. Of these, 123 were approached and 29 (4%) elected to take part. However, seven patients did not complete the study. Compliance with the injections was 11 out of 15 (73%) showing the intervention to be acceptable and feasible in this patient population. Only 4% of patients who met the inclusion criteria were both eligible and willing to consent to a study involving injections of PTH, so delivering this study on a large scale would carry challenges in recruitment and retention. Methodological and sample size planning would have to take this into account. PTH administration to patients to enhance fracture healing should still be considered experimental. Cite this article: Bone Joint J 2016;98-B:840-5. ©2016 Chesser et al.
Vitamin D and its relation with ionic calcium, parathyroid hormone, maternal and neonatal characteristics in pregnancy after roux-en-Y gastric bypass.

Science.gov (United States)

Medeiros, Marina; Matos, Andréa C; Pereira, Silvia E; Saboya, Carlos; Ramalho, Andréa

2016-03-01

The objective of this study was to evaluate vitamin D nutritional status and its relation with ionic calcium, parathyroid hormone (PTH), maternal anthropometry and perinatal outcomes in pregnant women who previously underwent Roux-en-Y gastric bypass (RYGB) surgery. In a clinic specialized in obesity control located in the city of Rio de Janeiro (Brazil), the following information were collected for adult women who underwent RYGB before pregnancy: serum concentrations of vitamin D [25(OH)D], calcium and PTH per gestational trimester and data on maternal anthropometry, gestational intercurrences and perinatal outcomes. The present study included 46 post-RYGB pregnant women. The prevalence of pregnant women with deficiency (≤20 ng/mL) or insufficiency (≥21 and 29 ng/mL) of vitamin D was above 70% in all trimesters. The prevalence of calcium deficiency was 15.2% in the first and in the second trimesters and 20% in the third trimester, while the prevalence of excess PTH was 19.6, 30.4 and 32.6% in the first, the second and the third trimesters, respectively. In the second and the third trimesters, a significant difference was observed between concentrations of 25(OH)D, and a negative correlation was observed between concentrations of calcium and PTH. Association of 25(OH)D with urinary tract infection (UTI) was found, but there was no association with calcium, PTH, maternal anthropometry, type of delivery and weight and gestational age at birth The post-RYGB pregnant women showed an elevated serum inadequacy (deficiency or insufficiency) of 25(OH)D during pregnancy. Maternal vitamin D status showed no association with maternal variables, except UTI, and the neonatal variables analyzed.
Effect of Etelcalcetide vs Placebo on Serum Parathyroid Hormone in Patients Receiving Hemodialysis With Secondary Hyperparathyroidism: Two Randomized Clinical Trials.

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Block, Geoffrey A; Bushinsky, David A; Cunningham, John; Drueke, Tilman B; Ketteler, Markus; Kewalramani, Reshma; Martin, Kevin J; Mix, T Christian; Moe, Sharon M; Patel, Uptal D; Silver, Justin; Spiegel, David M; Sterling, Lulu; Walsh, Liron; Chertow, Glenn M

2017-01-10

Secondary hyperparathyroidism contributes to extraskeletal complications in chronic kidney disease. To evaluate the effect of the intravenous calcimimetic etelcalcetide on serum parathyroid hormone (PTH) concentrations in patients receiving hemodialysis. Two parallel, phase 3, randomized, placebo-controlled treatment trials were conducted in 1023 patients receiving hemodialysis with moderate to severe secondary hyperparathyroidism. Trial A was conducted in 508 patients at 111 sites in the United States, Canada, Europe, Israel, Russia, and Australia from March 12, 2013, to June 12, 2014; trial B was conducted in 515 patients at 97 sites in the same countries from March 12, 2013, to May 12, 2014. Intravenous administration of etelcalcetide (n = 503) or placebo (n = 513) after each hemodialysis session for 26 weeks. The primary efficacy end point was the proportion of patients achieving greater than 30% reduction from baseline in mean PTH during weeks 20-27. A secondary efficacy end point was the proportion of patients achieving mean PTH of 300 pg/mL or lower. The mean age of the 1023 patients was 58.2 (SD, 14.4) years and 60.4% were men. Mean PTH concentrations at baseline and during weeks 20-27 were 849 and 384 pg/mL vs 820 and 897 pg/mL in the etelcalcetide and placebo groups, respectively, in trial A; corresponding values were 845 and 363 pg/mL vs 852 and 960 pg/mL in trial B. Patients randomized to etelcalcetide were significantly more likely to achieve the primary efficacy end point: in trial A, 188 of 254 (74.0%) vs 21 of 254 (8.3%; P secondary hyperparathyroidism, use of etelcalcetide compared with placebo resulted in greater reduction in serum PTH over 26 weeks. Further studies are needed to assess clinical outcomes as well as longer-term efficacy and safety. clinicaltrials.gov Identifiers: NCT01788046.
The Anabolic Effect of PTH on Bone is Attenuated by Simultaneous Glucocorticoid Treatment

DEFF Research Database (Denmark)

Oxlund, Hans; Ørtoft, Gitte; Thomsen, Jesper Skovhus

2006-01-01

. The pronounced anabolic effect of PTH injections on the endocortical and trabecular bone surfaces and less pronounced anabolic effect on periosteal surfaces were partially inhibited, but not prevented, by simultaneous GC treatment in old rats. Both cortical and cancellous bone possessed full mechanical...
Osteoporosis and its association with non-gonadal hormones involved in hypertension, adiposity and hyperglycaemia.

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Poudyal, Hemant; Brown, Lindsay

2013-12-01

Osteoporosis is a high-prevalence disease, particularly in developed countries, and results in high costs both to the individual and to society through associated fragility fractures. There is an urgent need for identification of novel drug targets and development of new anti-osteoporotic agents. Between 30 and 80% of osteoporotic fractures cannot be prevented despite current treatments achieving relative fracture risk reduction of up to 20%, 50%, and 70% for non-vertebral, hip and spine fractures, respectively. Traditionally, the decline in gonadal hormones has been studied as the sole hormonal determinant for the loss of bone mineral density in osteoporosis. However, recent studies have identified receptors for numerous non-gonadal hormones such as PTH, angiotensin II, leptin, adiponectin, insulin and insulin-like growth factor-1 on the osteoblast lineage cells that directly regulate bone turnover. These hormones are also involved in the pathogenesis of metabolic syndrome risk factors, particularly hypertension, type-II diabetes and obesity. By activating their respective receptors on osteoblastic lineage cells, these hormones appear to act through a common mechanism by down-regulating receptors for activation of nuclear factor kappa B ligand (RANKL) and up-regulating osteoprotegerin (OPG) with inverse responses for adiponectin. Receptors for amylin, gastric inhibitory polypeptide and ghrelin and have also been identified on the osteoblast lineage cells although the roles of these receptors in bone turnover are controversial or poorly studied. Moreover, bone turnover may be independently regulated by modulation of osteoclast-osteoblast function and bone marrow adiposity. Leptin appears to be the only hormone that is a known regulator of both bone mineralisation and bone adiposity.
Vitamin D Status and Its Association with Parathyroid Hormone Concentration in Brazilians

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Juliana Sálvio Martins

2017-01-01

Full Text Available Vitamins are organic compounds that play a vital role in the control of metabolic processes. The D complex is considered a nutrient with a hormonal action and has an important participation in the constant maintenance of serum and extracellular calcium levels. The present study aims to analyze the results of 105.588 vitamin D (25(OHD measurements obtained from a database from a clinical analysis laboratory in Brazil, between the years of 2011 and 2013. The values of 25(OHD were correlated with age, gender, and values of PTH. The results show a high prevalence of values of 25(OHD considered inadequate, characterizing 76% of the studied population. It was observed that 26,5% of the individuals had deficiency and 49,5% had insufficiency of vitamin D. It was also shown that there was a negative correlation between 25(OHD and PTH levels. In conclusion, this study is in accordance with others that show a high prevalence of vitamin D deficiency in different populations and alerts us for the importance of these measurements and analysis in clinical practice and as a base for diagnosis and treatment of hypovitaminosis.
Are P.T.H. plasma levels useful for the selection of patients with secondary hyperparathyroidism for preoperative MIBI (99mTc)/123I dual-isotope scintigraphy?

International Nuclear Information System (INIS)

Balogova, S.; Sauer, A.M.; Dudczak, J.; Pascal, O.; Kerrou, K.; Huchet, V.; Montravers, F.; Talbot, J.N.; Perie, S.; Lacau St-Guily, J.; Nataf, V.; Balogova, S.

2010-01-01

The utility of preoperative scintigraphy in case of secondary hyperparathyroidism is questioned by some authors. Obviously, an imaging modality that will detect all hyperplastic glands, including the ectopic ones, would be of interest in those patients at high risk for surgery. However, scintigraphy has a limited detection rate in some patients. We investigated whether one of the following parameters would identify a subgroup of patients in whom the detection rate would be optimal: age, gender, hemodialysis and duration since its onset, and plasma levels of parathyrin (P.T.H.). Methods: Retrospective series of 38 patients referred for preoperative parathyroid scintigraphy due to secondary hyperparathyroidism who then underwent para thyroidectomy. Scintigraphy was performed 20 min and then 3 h after injection of 8 MBq/kg of sestamibi ( 99m Tc) with a previous ingestion of 0.1 MBq/kg iodine-123, 3 h before. Result: No significant correlation was observed between the number of glands detected on scintigraphy (and confirmed by postoperative histology) and plasma P.T.H. levels (r = -0.17). A weak positive correlation (r = +0.34) was noted in the group of six non-hemo dialysed patients. No significant relationship between this number of detected glands and a clinical parameter was observed. Conclusion: In our experience, these parameters do not permit to select, among patients with secondary hyperparathyroidism and scheduled for para thyroidectomy, those who will better benefit from parathyroid scintigraphy. (authors)
On the pth moment estimates of solutions to stochastic functional differential equations in the G-framework.

Science.gov (United States)

Faizullah, Faiz

2016-01-01

The aim of the current paper is to present the path-wise and moment estimates for solutions to stochastic functional differential equations with non-linear growth condition in the framework of G-expectation and G-Brownian motion. Under the nonlinear growth condition, the pth moment estimates for solutions to SFDEs driven by G-Brownian motion are proved. The properties of G-expectations, Hölder's inequality, Bihari's inequality, Gronwall's inequality and Burkholder-Davis-Gundy inequalities are used to develop the above mentioned theory. In addition, the path-wise asymptotic estimates and continuity of pth moment for the solutions to SFDEs in the G-framework, with non-linear growth condition are shown.
The effect of leptin replacement on parathyroid hormone, RANKL-osteoprotegerin axis, and Wnt inhibitors in young women with hypothalamic amenorrhea.

Science.gov (United States)

Foo, Joo-Pin; Polyzos, Stergios A; Anastasilakis, Athanasios D; Chou, Sharon; Mantzoros, Christos S

2014-11-01

Recombinant leptin (metreleptin) treatment restores bone mineral density in women with hypothalamic amenorrhea (HA), a condition characterized by hypoleptinemia, which has adverse impact on bone health. The objective of the study was to investigate how metreleptin exerts its positive effect on bone metabolism in humans. This was a randomized, double-blinded, placebo-controlled study. The study was conducted at Beth Israel Deaconess Medical Center (Boston, Massachusetts). Women (n = 18) with HA and hypoleptinemia for at least 6 months were randomized to receive either metreleptin or placebo for 36 weeks. Serum samples were obtained at baseline and 12, 24, and 36 weeks of treatment. Circulating levels of leptin, intact PTH (iPTH), receptor activator of nuclear factor-κB ligand (RANKL), osteoprotegerin (OPG), sclerostin, dickkopf-1, and fibroblast growth factor-23. Metreleptin administration significantly increased leptin levels throughout the treatment period (P = .001). iPTH decreased over the 36 weeks of treatment (P = .01). There was a trend toward a decrease in serum RANKL and increase in serum OPG in the metreleptin-treated group. The RANKL to OPG ratio was significantly decreased within the metreleptin (P = .04) but not the placebo group. Metreleptin had no effect on serum sclerostin, dickkopf-1, and fibroblast growth factor-23. Metreleptin treatment over 36 weeks decreases iPTH and RANKL to OPG ratio levels in hypoleptinemic women with HA.
Effect of Etelcalcetide vs Cinacalcet on Serum Parathyroid Hormone in Patients Receiving Hemodialysis With Secondary Hyperparathyroidism: A Randomized Clinical Trial.

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Block, Geoffrey A; Bushinsky, David A; Cheng, Sunfa; Cunningham, John; Dehmel, Bastian; Drueke, Tilman B; Ketteler, Markus; Kewalramani, Reshma; Martin, Kevin J; Moe, Sharon M; Patel, Uptal D; Silver, Justin; Sun, Yan; Wang, Hao; Chertow, Glenn M

2017-01-10

Secondary hyperparathyroidism contributes to extraskeletal calcification and is associated with all-cause and cardiovascular mortality. Control is suboptimal in the majority of patients receiving hemodialysis. An intravenously (IV) administered calcimimetic could improve adherence and reduce adverse gastrointestinal effects. To evaluate the relative efficacy and safety of the IV calcimimetic etelcalcetide and the oral calcimimetic cinacalcet. A randomized, double-blind, double-dummy active clinical trial was conducted comparing IV etelcalcetide vs oral placebo and oral cinacalcet vs IV placebo in 683 patients receiving hemodialysis with serum parathyroid hormone (PTH) concentrations higher than 500 pg/mL on active therapy at 164 sites in the United States, Canada, Europe, Russia, and New Zealand. Patients were enrolled from August 2013 to May 2014, with end of follow-up in January 2015. Etelcalcetide intravenously and oral placebo (n = 340) or oral cinacalcet and IV placebo (n = 343) for 26 weeks. The IV study drug was administered 3 times weekly with hemodialysis; the oral study drug was administered daily. The primary efficacy end point was noninferiority of etelcalcetide at achieving more than a 30% reduction from baseline in mean predialysis PTH concentrations during weeks 20-27 (noninferiority margin, 12.0%). Secondary end points included superiority in achieving biochemical end points (>50% and >30% reduction in PTH) and self-reported nausea or vomiting. The mean (SD) age of the trial participants was 54.7 (14.1) years and 56.2% were men. Etelcalcetide was noninferior to cinacalcet on the primary end point. The estimated difference in proportions of patients achieving reduction in PTH concentrations of more than 30% between the 198 of 343 patients (57.7%) randomized to receive cinacalcet and the 232 of 340 patients (68.2%) randomized to receive etelcalcetide was -10.5% (95% CI, -17.5% to -3.5%, P for noninferiority, secondary hyperparathyroidism, the
Effects of recombinant human growth hormone in the treatment of dwarfism and relationship between IGF-1, IGFBP-3 and thyroid hormone.

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Ren, Shanxiang; Nie, Yuxiang; Wang, Aihong

2016-12-01

The effects of recombinant human growth hormone (rhGH) in the treatment of dwarfism and the relationship between insulin-like growth factor (IGF)-1, IGF-binding protein (IGFBP)-3 and thyroid hormone were examined in the present study. For this purpose, 66 patients diagnosed with dwarfism were selected retrospectively, with 36 cases of growth hormone deficiency (GHD) and 30 cases of idiopathic short stature (ISS). The therapeutic dose of GHD 0.10 IU/kg·day and ISS 0.15 IU/kg·day were injected subcutaneously every night before sleep until adulthood. The average follow-up was 5 years, and the results were evaluated and measured every 3 months, including height, BA, secondary test of growth hormone (GH peak), IGF-1, IGFBP-3 and thyroid hormone (FT3, FT4 and TSH). After treatment, the height, BA, GH peak, IGF-A and IGFBP-3 of the GHD group were all increased, and the differences were statistically significant (P0.05). The results of the Pearson-related analysis suggested that GH peak of the GHD group, IGF-1 and IGFBP-3 were positively associated with height (P0.05). rhGH was effective for GHD and ISS, with the GHD effect being positively associated with the GH peak, IGF-1 and IGFBP-3. ISS had no obvious relationship with GH peak, IGF-1 and IGFBP-3 although other influencing factors may be involved.
The medical and surgical treatment in secondary and tertiary hyperparathyroidism. Review.

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Cocchiara, G; Fazzotta, S; Palumbo, V D; Damiano, G; Cajozzo, M; Maione, C; Buscemi, S; Spinelli, G; Ficarella, S; Maffongelli, A; Caternicchia, F; Ignazio Lo Monte, A; Buscemi, G

2017-01-01

Hyperparathyroidism is an alteration of the pathophysiological parathyroid hormone (PTH) secretion due or an independent and abnormal release (primary or tertiary hyperparathyroidism) by the parathyroid or an alteration of calcium homeostasis that stimulates the excessive production of parathyroid hormone (secondary hyperparathyroidism). There is not a standard, clinical or surgical, treatment for hyperparathyroidism. We review current diagnostic and therapeutic methods. In secondary hyperparathyroidism (2HPT) there is a progressive hyperplasia of the parathyroid glands and an increased production of parathyroid hormone. Several causes are proposed: chronic renal insufficiency, vitamin D deficiency, malabsorption syndrome. The tertiary hyperparathyroidism (3HPT) is considered a state of excessive autonomous secretion of PTH due to long-standing 2HPT and it's usually the result of a lack of suppression in the production of PTH. The pathophysiological implications are both skeletal and extraskeletal: it damages the cardiovascular system, nervous system, immune, hematopoietic and endocrine system. The introduction of new drugs has improved the survival of these patients, allowing the inhibition of the synthesis of PTH. Indication for surgical treatment is unresponsive medical therapy. There are no large prospective studies that comparing the medical and surgical treatment. The choice is not unique and we have to consider the singolar case and the clinical condition of the patient.

Circulating levels of sclerostin but not DKK1 associate with laboratory parameters of CKD-MBD.

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Geert J Behets

Full Text Available Mounting evidence indicates that a disturbed Wnt-β-catenin signaling may be involved in the pathogenesis of chronic kidney disease-mineral and bone and mineral disorder (CKD-MBD. Data on the impact of CKD on circulating levels of the Wnt antagonists sclerostin and Dickkopf related protein 1 (DKK1 and the relationship with laboratory parameters of CKD-MBD are incomplete.We analyzed serum sclerostin and DKK1 in 308 patients across the stages of chronic kidney disease (kDOQI stage 1-2 n = 41; CKD stage 3 n = 54; CKD stage 4-5 n = 54; hemodialysis n = 100; peritoneal dialysis n = 59 as well as in 49 healthy controls. We investigated associations with demographics, renal function, parameters of mineral metabolism including 25(OH vitamin D, 1,25(OH2 vitamin D, biointact fibroblast growth factor 23 (FGF23, and parathyroid hormone (PTH, and bone turnover markers.Serum sclerostin, but not DKK1, increases in more advanced stages of CKD and associates with PTH, phosphate, and 1,25(OH2 vitamin D concentrations. Bone turnover markers are highest in hemodialysis patients presenting the combination of high PTH with low sclerostin level. Serum DKK1 levels are lower in CKD patients than in controls and are not associated with laboratory parameters of mineral metabolism. Interestingly, a direct association between DKK1 and platelet count was observed.In CKD, serum levels of the Wnt inhibitors DKK1 and sclerostin are unrelated, indicating different sites of origin and/ or different regulatory mechanisms. Sclerostin, as opposed to DKK1, may qualify as a biomarker of CKD-MBD, particularly in dialysis patients. DKK1 serum levels, remarkably, correlate almost uniquely with blood platelet counts.
PTH levels and not serum phosphorus levels are a predictor of the progression of kidney disease in elderly patients with advanced chronic kidney disease.

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Toapanta Gaibor, Néstor Gabriel; Nava Pérez, Nathasha Carolina; Martínez Echevers, Yeleine; Montes Delgado, Rafael; Guerrero Riscos, María Ángeles

At present, there is a high incidence of elderly patients with advanced chronic kidney disease (CKD) and it is important to know the long term progression and the factors that influence it. To analyse the progression of advanced CKD in elderly patients and the influence of bone-mineral metabolism. Retrospective study of 125 patients ≥70years of age with CKD stages 4-5 who started follow-up from January 1, 2007 to December 31, 2008, showing the progression of CKD (measured by the slope of the regression line of the estimated glomerular filtration rate [eGFR] by MDRD-4) over 5years. Progression in the entire group (median and 25th and 75th percentiles): -1.15 (-2.8/0.17) ml/min/1.73m 2 /year, CKD-4: -1.3 (-2.8/0.03) ml/min/1.73m 2 /year, CKD-5: -1.03 (-3.0/0.8) ml/min/1.73m 2 /year; the slope of the regression line was positive in 35 patients (28%: CKD does not progress) and negative in 90 patients (72%: CKD progresses). Negative correlation (Spearman) (slower progression): PTH, albumin/Cr ratio and daily Na excretion (all baseline measurements). No correlation with eGFR, serum P, urinary P excretion, protein intake and intake of P (all baseline measurements). In the linear regression analysis (dependent variable: slope of progression): albuminuria and PTH (both at baseline measurements) influenced this variable independently. Logistic regression (progresses vs. does not progress): PTH, albuminuria and eGFR (all at baseline measurements) influenced significantly. In our group of elderly patients, impairment of renal function is slow, particularly in CKD-5 patients. Albuminuria and PTH at baseline levels are prognostic factors in the evolution of renal function. Copyright © 2016 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.
Incidensen af tertiaer hyperparatyroidisme efter nyretransplantation

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Nielsen, Tomas; Brixen, Kim T; Jespersen, Bente

2008-01-01

INTRODUCTION: Tertiary hyperparathyroidism (3 degrees HPT) is a condition characterized by autonomous secretion of parathyroid hormone (PTH) which develops as a consequence of secondary hyperparathyroidism in patients with chronic renal failure. Severe cases of 3 degrees HPT are treated with para......INTRODUCTION: Tertiary hyperparathyroidism (3 degrees HPT) is a condition characterized by autonomous secretion of parathyroid hormone (PTH) which develops as a consequence of secondary hyperparathyroidism in patients with chronic renal failure. Severe cases of 3 degrees HPT are treated...... consecutive patients who underwent Tx at Odense University Hospital from 1/1/2000 to 12/31/2004. We defined 3 degrees HPT as at least one elevated measurement of P-PTH concurrent with elevated S-Ca2+. Elevated S-Ca2+ was defined as at least 5 consecutive, elevated measurements from 14 days to six months after...
Intermittent PTHrP(1–34) Exposure Augments Chondrogenesis and Reduces Hypertrophy of Mesenchymal Stromal Cells

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Fischer, Jennifer; Aulmann, Antje; Dexheimer, Verena; Grossner, Tobias

2014-01-01

Phenotype instability and premature hypertrophy prevent the use of human mesenchymal stromal cells (MSCs) for cartilage regeneration. Aim of this study was to investigate whether intermittent supplementation of parathyroid hormone-related protein (PTHrP), as opposed to constant treatment, can beneficially influence MSC chondrogenesis and to explore molecular mechanisms below catabolic and anabolic responses. Human MSCs subjected to chondrogenic induction in high-density culture received PTHrP(1–34), forskolin, dbcAMP, or PTHrP(7–34) either constantly or via 6-h pulses (three times weekly), before proteoglycan, collagen type II, and X deposition; gene expression; and alkaline phosphatase (ALP) activity were assessed. While constant application of PTHrP(1–34) suppressed chondrogenesis of MSCs, pulsed application significantly increased collagen type 2 (COL2A1) gene expression and the collagen type II, proteoglycan, and DNA content of pellets after 6 weeks. Collagen type 10 (COL10A1) gene expression was little affected but Indian hedgehog (IHH) expression and ALP activity were significantly downregulated by pulsed PTHrP. A faster response to PTHrP exposure was recorded for ALP activity over COL2A1 regulation, suggesting that signal duration is critical for catabolic versus anabolic reactions. Stimulation of cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) signaling by forskolin reproduced major effects of both treatment modes, whereas application of PTHrP(7–34) capable of protein kinase C (PKC) signaling was ineffective. Pulsed PTHrP exposure of MSCs stimulated chondrogenesis and reduced endochondral differentiation apparently uncoupling chondrogenic matrix deposition from hypertrophic marker expression. cAMP/PKA was the major signaling pathway triggering the opposing effects of both treatment modes. Intermittent application of PTHrP represents an important novel means to improve chondrogenesis of MSCs and may be considered as a supporting clinical
Inositol metabolism in WRK-1 cells. Relationship of hormone-sensitive to -insensitive pools of phosphoinositides

International Nuclear Information System (INIS)

Monaco, M.E.

1987-01-01

Previous studies have indicated the existence of two separate pools of phosphoinositides in WRK-1 cells; one is labile and hormone-sensitive with respect to turnover, while the other is stable. Hormonal stimulation results in a rapid increase in 32 Pi incorporation into the sensitive pool, while in the absence of hormone, incorporation of 32 Pi into this pool is slow. Results are quite different when [ 3 H]inositol is the precursor utilized. Incorporation of [ 3 H]inositol into hormone-sensitive phosphoinositides is not stimulated in the presence of hormone, suggesting entry of this exogenous precursor into the cycle by a route other than the resynthetic phase of the cycle. Furthermore, failure of hormone to induce loss of [ 3 H]phosphoinositide in pulse-chase experiments in the absence of lithium suggests reutilization of the [ 3 H]inositol moiety generated by phosphodiesteratic cleavage of hormone-sensitive phosphoinositide. Time course studies indicate that the relative rates of incorporation of [ 3 H]inositol into sensitive and insensitive phosphoinositide remain constant from 2 to 24 h. Several factors are capable of increasing [ 3 H]inositol incorporation into hormone-insensitive phosphoinositide including vasopressin, calcium ionophores, and manganese. On the other hand, vasopressin treatment appears to decrease incorporation of [ 3 H]inositol into the hormone-sensitive pool, probably by shifting the equilibrium between phosphoinositides and inositol phosphates, since the decrease in radioactivity observed in the phosphoinositides is equaled by the increase observed in that in the inositol phosphates
IGF-1 and insulin as growth hormones.

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Laron, Zvi

2004-01-01

IGF-1 generated in the liver is the anabolic effector and linear growth promoting hormone of the pituitary growth hormone (GH). This is evidenced by dwarfism in states of congenital IGF-1 deficiency, Igf1 gene mutation/deletions or knockouts, and in Laron syndrome (LS), due to GH receptor gene mutations/deletions or IGF-1 receptor blocking. In a positive way, daily IGF-1 administration to stunted patients with LS or hGH gene deletion accelerates linear growth velocity. IGF-1 acts on the proliferative cells of the epiphyseal cartilage. IGF-1 also induces organ and tissue growth; its absence causing organomicria. Insulin shares a common ancestry with IGF-1 and with 45% amino acid homology, as well as very close relationships in the structure of its receptors and post-receptor cascade, also acts as a growth hormone. It has protein anabolic activity and stimulates IGF-1 synthesis. Pancreas agenesis causes short babies, and obese children with hyperinsulinism, with or without pituitary GH, have an accelerated growth rate and skeletal maturation; so do babies with macrosomia. Whether the insulin growth effect is direct, or mediated by IGF-1 or leptin is controversial.
Large artery stiffness and carotid intima-media thickness in relation to markers of calcium and bone mineral metabolism in African women older than 46 years.

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Gafane, L F; Schutte, R; Kruger, I M; Schutte, A E

2015-03-01

Vascular calcification and cardiovascular diseases have been associated with altered bone metabolism. We explored the relationships of arterial pressures and carotid intima-media thickness (CIMT) with parathyroid hormone, 25-hydroxycholecalciferol and their ratio (PTH:25(OH)D3) as well as a marker of bone resorption (CTX) in lean and overweight/obese African women. A population of 434 African women older than 46 years was divided into lean and overweight/obese groups. We assessed brachial blood pressure, central pulse pressure (cPP) and CIMT, and determined PTH, 25(OH)D3 and CTX concentrations. Overweight/obese women had elevated PTH and PTH:25(OH)D3 compared with lean women (both Pwomen had higher CTX (Pwomen CIMT was independently associated with PTH:25(OH)D3 (R(2)=0.22; β=0.26; P=0.003), whereas in obese women cPP was associated with both PTH:25(OH)D3 (R2=0.20; β=0.17; P=0.017) and CTX (R2=0.20; β=0.17; P=0.025). In conclusion, we found that in African women with increased adiposity, cPP (as a surrogate measure of arterial stiffness), was positively associated with alterations in bone metabolism and calciotropic hormones, whereas CIMT of lean women was positively associated with PTH:25(OH)D3. Our results suggest that alterations in bone and calcium metabolism may contribute to arterial calcification in older African women.
Long-term benefits and risks of parathyroid hormone treatment in compliant osteoporotic patients. A Danish national register based cohort study

DEFF Research Database (Denmark)

Thorsteinsson, Anne-Luise; Hansen, Louise; Vestergaard, Peter

2018-01-01

(n = 12,721) were selected. Incidence of fractures, drug consumption, and comorbidity were compared between the three cohorts. Mean follow-up of the PTH-treated patients was 4.3 years (range 1.8-8.7 years). RESULTS: Before initiation of treatment, PTH patients had a significantly higher Charlson...... comorbidity index score and more osteoporotic fractures than both BP patients and controls. No difference was detected in the incidence of fractures during PTH treatment or years after between PTH patients and BP patients. No significant difference in the use of drugs was seen between PTH and BP patients...
The secretory response of parathyroid hormone to acute hypocalcemia in vivo is independent of parathyroid glandular sodium/potassium-ATPase activity

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Martuseviciene, Giedre; Hofman-Bang, Jacob; Clausen, Torben

2011-01-01

increased in response to ethylene glycol tetraacetic acid-induced acute hypocalcemia and to the same extent in both vehicle and ouabain groups. The glands were removed, and inhibition of the ATPase was measured by (86)rubidium uptake, which was found to be significantly decreased in ouabain......-treated parathyroid glands, indicating inhibition of the ATPase. As ouabain induced systemic hyperkalemia, the effect of high potassium on hormone secretion was also examined but was found to have no effect. Thus, inhibition of the parathyroid gland sodium/potassium-ATPase activity in vivo had no effect...... on the secretory response to acute hypocalcemia. Hence, the suggested importance of this ATPase in the regulation of PTH secretion could not be confirmed in this in vivo model....
Pakistani Immigrant Children and Adults in Denmark Have Severely Low Vitamin D Status

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Andersen, Rikke; Mølgaard, C.; Skovgaard, L. T.

2008-01-01

association with S-25OHD for men (P = 0.04) and women (P = 0.0008). Twenty-one per cent of the women and 34% of the men had osteopenia. Neither S-25OHD nor S-iPTH was associated with lumbar spine or whole body bone mineral content. Conclusions: Severely low vitamin D status and elevated S-iPTH is common among......, Copenhagen (55 degrees N), January- November. Serum 25-hydroxyvitamin D (S-25OHD), serum intact parathyroid hormone (S-iPTH), bone turnover markers and whole body and lumbar spine bone mineral density were measured. Sun, smoking and clothing habits, age, body mass index (BMI), and vitamin D and calcium from......Objective: To determine vitamin D and bone status in adolescent girls, pre-menopausal women and men of Pakistani origin, to single out determinants of vitamin D status and to determine the association between vitamin D status, bone metabolism and bone status. Subjects/Methods: Cross-sectional study...
Parathyroid hormone, but not vitamin D, is associated with the metabolic syndrome in morbidly obese women and men: a cross-sectional study

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Hager Helle

2009-02-01

Full Text Available Abstract Background The prevalence of vitamin D insufficiency and secondary hyperparathyroidism is high among morbidly obese subjects. Further, low serum levels of 25-hydroxyvitamin D (25 [OH]D and magnesium have been associated with increased risk of the metabolic syndrome (MS, and recently, a possible link between PTH and MS has been reported. Although it is well known that the synthesis and secretion of PTH is regulated by serum levels of calcium, phosphate, magnesium and 25(OHD, less is known about the possible clustered affiliation of these parameters with MS. We aimed to explore whether MS is associated with abnormal serum levels of PTH, 25(OHD and magnesium in a population of morbidly obese patients. Methods Fasting serum levels of 25(OHD, PTH and magnesium were assessed in a cross-sectional cohort study of 1,017 consecutive morbidly obese patients (68% women. Multiple logistic regression analyses were used to assess the independent effect of PTH, 25(OHD and magnesium on the odds for MS (National Cholesterol Education Program [NCEP] after adjustment for confounding factors. Results Sixty-eight percent of the patients had MS. Patients with MS had lower mean serum magnesium (P Conclusion The PTH level, but not the vitamin D level, is an independent predictor of MS in treatment seeking morbidly obese Caucasian women and men. Randomized controlled clinical trials, including different therapeutic strategies to lower PTH, e.g. calcium/vitamin D supplementation and weight reduction, are necessary to explore any cause-and-effect relationship.
Multifactorial Hypercalcemia and Literature Review on Primary Hyperparathyroidism Associated with Lymphoma

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Jelena Maletkovic

2014-01-01

Full Text Available The most common cause of hypercalcemia in hospitalized patients is malignancy. Primary hyperparathyroidism most commonly causes hypercalcemia in the outpatient setting. These two account for over 90% of all cases of hypercalcemia. Hypercalcemia can be divided into PTH-mediated and PTH-independent variants. Primary hyperparathyroidism, familial hypocalciuric hypercalcemia, familial hyperparathyroidism, and secondary hyperparathyroidism are PTH mediated. The most common PTH-independent type of hypercalcemia is malignancy related. Several mechanisms lead to hypercalcemia in malignancy-direct osteolysis by metastatic disease or, more commonly, production of humoral factors by the primary tumor also known as humoral hypercalcemia of malignancy that accounts for about 80% of malignancy-related hypercalcemia. The majority of HHM is caused by tumor-produced parathyroid hormone-related protein and less frequently production of 1,25-dihydroxyvitamin D or parathyroid hormone by the tumor. We report the rare case of a patient with hypercalcemia and diagnosed primary hyperparathyroidism. The patient had persistent hypercalcemia after surgical removal of parathyroid adenoma with recorded significant decrease in PTH level. After continued investigation it was found that the patient also had elevated 1,25-dihydroxyvitamin D and further studies confirmed a large spleen mass that was later confirmed to be a lymphoma. This is a rare example of two concomitant causes of hypercalcemia requiring therapy.
Chronic food restriction and the circadian rhythms of pituitary-adrenal hormones, growth hormone and thyroid-stimulating hormone.

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Armario, A; Montero, J L; Jolin, T

1987-01-01

Adult male Sprague-Dawley rats were subjected to food restriction so that they ate 65% of food ingested by control rats. While control rats had free access to food over the 24-hour period, food-restricted rats were provided with food daily at 10 a.m. The experimental period lasted for 34 days. On day 35, rats from both experimental groups were killed at 08.00, 11.00, 14.00, 24.00 and 02.00 h. Food restriction modified the circadian rhythms of ACTH and corticosterone. In addition, total circulating corticosterone throughout the day was higher in food-restricted than in control rats. In contrast, food restriction resulted in depressed secretion of thyroid-stimulating hormone and growth hormone. The results indicate that time of food availability entrained circadian corticosterone rhythm but not thyroid-stimulating hormone and growth hormone rhythms.
Effect of different types of blood purification treatment (HD and HDF) on the serum PTH, leptin and Hcy levels in patients with chronic renal failure

International Nuclear Information System (INIS)

Yao Yongliang

2009-01-01

Objective: To investigate the effect of different type of blood purification treatment (hemodialysis and hemodiafiltration) on the serum PTH, Leptin and Hcy levels in patients with chronic renal failure(CRF). Methods: Serum levels of PTH(with ECLIA), Leptin(with RIA) and Hcy(with biochemistry) were measured in 30 patients treated with hemodialysis(HD) and 30 patients treated with hemodiafiltration(HDF) both before and after treatment. Results: The concentration of PTH decreased significantly from 60.8±32.5pmol/L to 28.2±17.2pmol/L in patients treated with HDF(P 0.05). Yet the concentration of Hcy also decreased significantly from 31.5μ10.5μmol/L to 20.4±8.5μmol/L(P<0.01) in patients treated HD. Conclusion: HDF can eliminate serum PTH, leptin and Hcy better than HD does. (authors)
Hormonal changes in 3-month-old cryptorchid boys

DEFF Research Database (Denmark)

Suomi, Anne-Maarit; Main, Katharina M; Kaleva, Marko M

2006-01-01

CONTEXT: Hormonal dysregulation has been suggested to be one of many etiological factors of cryptorchidism. OBJECTIVES: The objective of this study was to assess the hypothalamic-pituitary-testicular axis in cryptorchid boys during the postnatal hormonal surge. DESIGN: This was a prospective......, longitudinal, population-based study. SETTING: The study was performed at two primary obstetric centers. PARTICIPANTS: Study participants included 388 Finnish and 433 Danish boys (88 and 34 with cryptorchidism, respectively). INTERVENTIONS: Clinical examinations were performed at 0 and 3 months. Blood samples...... were taken at 3 months. MAIN OUTCOME MEASURES: The main outcome measures were testis position and reproductive hormone levels. RESULTS: Finnish cryptorchid boys had significantly higher FSH [1.59 (0.50-3.53) vs. 1.30 (0.49-2.92) IU/liter; P
Ozone Exposure Increases Circulating Stress Hormones and Lipid Metabolites in Humans

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RATIONALE: Air pollution has been associated with increased prevalence of type 2 diabetes; however, the mechanisms remain unknown. We have shown that acute ozone exposure in rats induces release of stress hormones, hyperglycemia, leptinemia, and gluoose intolerance that are assoc...
Measurement of the incretin hormones

DEFF Research Database (Denmark)

Kuhre, Rune Ehrenreich; Wewer Albrechtsen, Nicolai Jacob; Hartmann, Bolette

2015-01-01

The two incretin hormones, glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP), are secreted from the gastrointestinal tract in response to meals and contribute to the regulation of glucose homeostasis by increasing insulin secretion. Assessment of plasma concentrat......The two incretin hormones, glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP), are secreted from the gastrointestinal tract in response to meals and contribute to the regulation of glucose homeostasis by increasing insulin secretion. Assessment of plasma...... concentrations of GLP-1 and GIP is often an important endpoint in both clinical and preclinical studies and, therefore, accurate measurement of these hormones is important. Here, we provide an overview of current approaches for the measurement of the incretin hormones, with particular focus on immunological...
Using an electrocautery strategy or recombinant follicle stimulating hormone to induce ovulation in polycystic ovary syndrome: randomised controlled trial

Science.gov (United States)

Bayram, Neriman; van Wely, Madelon; Kaaijk, Eugenie M; Bossuyt, Patrick M M; van der Veen, Fulco

2004-01-01

Objective To compare the effectiveness of an electrocautery strategy with ovulation induction using recombinant follicle stimulating hormone in patients with polycystic ovary syndrome. Design Randomised controlled trial. Setting Secondary and tertiary hospitals in the Netherlands. Participants 168 patients with clomiphene citrate resistant polycystic ovary syndrome: 83 were allocated electrocautery and 85 were allocated recombinant follicle stimulating hormone. Intervention Laparoscopic electrocautery of the ovaries followed by clomiphene citrate and recombinant follicle stimulating hormone if anovulation persisted, or induction of ovulation with recombinant follicle stimulating hormone. Main outcome measure Ongoing pregnancy within 12 months. Results. The cumulative rate of ongoing pregnancy after recombinant follicle stimulating hormone was 67%. With only electrocautery it was 34%, which increased to 49% after clomiphene citrate was given. Subsequent recombinant follicle stimulating hormone increased the rate to 67% at 12 months (rate ratio 1.01, 95% confidence interval 0.81 to 1.24). No complications occurred from electrocautery with or without clomiphene citrate. Patients allocated to electrocautery had a significantly lower risk of multiple pregnancy (0.11, 0.01 to 0.86). Conclusion The ongoing pregnancy rate from ovulation induction with laparoscopic electrocautery followed by clomiphene citrate and recombinant follicle stimulating hormone if anovulation persisted, or recombinant follicle stimulating hormone, seems equivalent to ovulation induction with recombinant follicle stimulating hormone, but the former procedure carries a lower risk of multiple pregnancy. PMID:14739186
[Hormonal methods of increasing fertility in swine].

Science.gov (United States)

Kostov, L; Radev, G; Andreev, A

1976-01-01

Experiments were carried out to raise the conception rate in sows during the summer season under industrial conditions of breeding. Eight test groups of 365 animals were formed as well as four control ones with 137 pigs. The sucking period lasted 28 to 33 days. When in estrus the sows were mated with boars twice at a 24-hour interval. In five groups that were dried up from July to September was recorded the effect of several kinds of gonadotropic hormones administered alone or in combination with vitamin E and steroid hormones -- Gravohormone Tolligon, an oil emulsion of PMS (500 IU), with 250 Chorulon and 2 mg estradiol benzoicum; an oil solution of PMS (500 IU) with 2 mg estradiol, 25 mg testosterone and 30 mg vitamin E. During the same period three other groups of test sows were formed to use steroid hormones such as Gravignost, an oil solution of 2 mg estradiol benzoicum, and 40 mg testosterone propionate as well as the same preparation in combination with 30 mg vitamin E. The deterioration of the temperature and humidity regime in the summer at the industrial pig-breeding complexes was shown to inhibit the manifestation of estrus and lower the conception rate in sows. Either alone or in combination with vitamin E and estradiol the gonadotropic hormones largely raised the per cent of animals manifesting estrus for ten days in summer after weaning their piglets (89 to 100 per cent) as well as the number of lively born offsprings per sow (9.8 to 11.3). The optimal doses used were as follows: Gravohormone, 13--14 IU/kg liveweight; Folligon or PMS, 6--7 IU per kg; and choriogonadotropin at the rate of 500 IU per sow. One the other hand, the steroid hormonal preparations bring about estrus of a lower quality leading to a low conception rate and fertility at first insemination, disturb the sexual cyclicity. They should not be administered alone as cycle starters in pig-breeding.
Clinical, laboratory and instrumental methods of pre-surgical diagnosis of the parathyroid glands cancer

Directory of Open Access Journals (Sweden)

Natalia G. Mokrysheva

2017-12-01

Full Text Available Backgraund. When defining symptomatic primary hyperparathyroidism (PHPT, differential diagnosis between a benign and malignant neoplasm of parathyroid glands (PG may be challenging. The diagnosis of carcinoma or a benign tumor determines the extent of the surgical intervention and further observation tactics. Aims. The purpose of the study is to determine the clinical and laboratory and instrumental predictors of PG cancer. Materials and methods. A retrospective study included 385 patients with PHPT (273 with adenomas of the PG, 66 with hyperplasia, and 19 patients with cancer of the PG, who had been examined and operated from 2000 to 2014. The primary goal of the study was to define the level of ionized calcium (Ca++, parathyroid hormone (PTH, and the volume of the tumor PG specific for cancer of the PG. The level of parathyroid hormone (PTH was determined by electrochemoluminescent method on the Roche analyzer Cobas 6000; ionized calcium (Ca++ ion-selective method. The size of the PG was determined by the ellipse formula: V(cm3 = (A × B × C × 0.49 by ultrasound investigation using the Valuson E8 device from General Electric. Results. The group of patients with PG carcinoma showed the increased level of Ca++ of more than 1.60 mmol/l (p = 0.004 and increased level of PTH of more than 600 pg/ml (p = 0.03. The size of tumors of more than 6 cm3 is more typical to malignant neoplasm compared to the adenoma of the PG (p = 0.01. Conclusions. The group of patients with PHPT that are at risk of having PG carcinoma include individuals that have a combination of the following indicators: PTH levels of more than 600 pg/ml, an increase in ionized calcium of more than 1.60 mmol/l, the tumor size of more than 6 cm3.

Gut hormones and gastric bypass

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Holst, Jens J.

2016-01-01

Gut hormone secretion in response to nutrient ingestion appears to depend on membrane proteins expressed by the enteroendocrine cells. These include transporters (glucose and amino acid transporters), and, in this case, hormone secretion depends on metabolic and electrophysiological events elicited...... that determines hormone responses. It follows that operations that change intestinal exposure to and absorption of nutrients, such as gastric bypass operations, also change hormone secretion. This results in exaggerated increases in the secretion of particularly the distal small intestinal hormones, GLP-1, GLP-2......, oxyntomodulin, neurotensin and peptide YY (PYY). However, some proximal hormones also show changes probably reflecting that the distribution of these hormones is not restricted to the bypassed segments of the gut. Thus, cholecystokinin responses are increased, whereas gastric inhibitory polypeptide responses...
Cadmium-induced formation of multinucleated osteoclast-like cells in vitro

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Konz, R.P.; Choi, T.T.; Seed, T.M.

1990-01-01

Mononuclear, progenitor-enriched bone marrow cells fuse into multinucleated osteoclast-like (MN-OS) cells during 10 to 20 days of culture. As cadmium (Cd) exposure has been linked to increased bone resorption, we asked if Cd would increase (1) MN-OS cell formation and (2) 45 Ca release from bone, when marrow cells were cultured in the presence of 45 Ca-prelabeled dog femur slices. Results show that, on day 21, the percentage of MN-OS cells (≥3 nuclei/cell) was 1.4 ± 0.1% (mean ± SE, n=4) for control cultures (medium + bone slice + cells), 3.6 ± 0.1% for cultures with 10 nM parathyroid hormone (PTH) added, and 7.1 ± 1.5% with 10 nM Cd added. Starting on day 10, we found MN-OS cells with centrally located nuclei, a clear zone, and ruffled borders typical of activated osteoclasts; these activated cells appeared almost exclusively in the +Cd and +PTH cultures. During 21 days, 256 ± 9 CPM 45 Ca was released per well from the bone slices in cultures with cells, compared to 209 ± 11 CPM 45 Ca was released in cultures without cells (mean ± SE, n=16). However, neither Cd nor PTH significantly increased the cell-mediated release of 45 Ca. Thus, both Cd and PTH at 10 nM stimulated the formation of MN-OS cells; however, another factor may have been required to cause MN-OS cells of resorb bone
iagnostic accuracy study comparing total alkaline phosphatase with intact parathyroid hormone 1-84 for the diagnosis of high turnover renal osteodystrophy in chronic renal failure on hemodialysis

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Andrés Marcelo Rojas González

2014-09-01

Full Text Available INTRODUCTION High turnover renal osteodystrophy (HTRO is a highly prevalent complication in patients with chronic kidney disease and mineral bone disease (CKD-MBD, causing pain and significant fracture-associated morbidity and mortality. The diagnostic gold standard test is bone biopsy but there are other, more widely available screening tests such as 1-84 intact parathormone (1-84 iPTH and nonspecific markers such as total alkaline phosphatase (tALP. PURPOSE To determine the diagnostic value (ROC curve, predictive values and likelihood ratios of 1-84 iPTH and tALP for HTRO screening. METHODS A diagnostic accuracy study was performed on a sample of CKD-MDB patients, grouping them according to bone biopsy results and analyzing the results of the diagnostic tests as descriptive variables. RESULTS The study group comprised 188 patients with CKD-MDB, 36 of which had biopsy-confirmed HTRO (19.15%. The average age was 50.2 years in the biopsy group, and 53.4 years in the non-biopsy group (p=0.2385, most were male (63.8% and diabetic (80.5%. The mean time in dialysis was 5.02 years in the biopsy group, and 2.61 years for the non-biopsy group (p<0.001. The mean Kt/V was 1.44 in the biopsy group, and 1.40 in the non-biopsy group (p=0.5354. The mean tALP was 398.02 IU/L in the group with HTRO versus 141.76 IU/L in the group without HTRO (p<0.001. The best cut-off value for tALP was 300-350 IU/L with a near 80% post-test probability, but also with a 15-20% probability for HTRO if the test is negative. The mean 1-84 iPTH was 1248.01 pg/ml in the group with HTRO versus 350.76 pg/ml in the group without HTRO (p<0.001. The 1-84 iPTH cut-off reference value of 300 pg/ml was associated with a post-test probability of 30% for HTRO diagnosis and had a lower overall performance. The best cut-off value for iPTH 1-84 was 600 pg/ml with a post-test probability for HTRO of 70% if positive and less than 5% if the test results are negative. DISCUSSION Both markers show
Increased sensitivity of thyroid hormone-mediated signaling despite prolonged fasting.

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Martinez, Bridget; Scheibner, Michael; Soñanez-Organis, José G; Jaques, John T; Crocker, Daniel E; Ortiz, Rudy M

2017-10-01

Thyroid hormones (TH) can increase cellular metabolism. Food deprivation in mammals is typically associated with reduced thyroid gland responsiveness, in an effort to suppress cellular metabolism and abate starvation. However, in prolonged-fasted, elephant seal pups, cellular TH-mediated proteins are up-regulated and TH levels are maintained with fasting duration. The function and contribution of the thyroid gland to this apparent paradox is unknown and physiologically perplexing. Here we show that the thyroid gland remains responsive during prolonged food deprivation, and that its function and production of TH increase with fasting duration in elephant seals. We discovered that our modeled plasma TH data in response to exogenous thyroid stimulating hormone predicted cellular signaling, which was corroborated independently by the enzyme expression data. The data suggest that the regulation and function of the thyroid gland in the northern elephant seal is atypical for a fasted animal, and can be better described as, "adaptive fasting". Furthermore, the modeling data help substantiate the in vivo responses measured, providing unique insight on hormone clearance, production rates, and thyroid gland responsiveness. Because these unique endocrine responses occur simultaneously with a nearly strict reliance on the oxidation of lipid, these findings provide an intriguing model to better understand the TH-mediated reliance on lipid metabolism that is not otherwise present in morbidly obese humans. When coupled with cellular, tissue-specific responses, these data provide a more integrated assessment of thyroidal status that can be extrapolated for many fasting/food deprived mammals. Copyright © 2017 Elsevier Inc. All rights reserved.
OPG/RANKL/RANK cytokine system in renal osteodystrophy

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Ivica Avberšek-Lužnik

2007-11-01

Full Text Available Background: Renal osteodystrophy is one of the most common complications affecting patients with endstage renal disease treated with hemodialysis (HD. The action of calciotropic hormones in renal osteodystrophy is regulated by the OPG/RANKL/RANK system. Its function is modulated by interleukines, calcitriol and parathyroid hormone (PTH.The aim of our study was to confirm that this system is involved in the pathogenesis of renal osteodystrophy and supports the mechanism of PTH action on bone.Methods: 106 HD patients (mean age 60 years and 50 healthy volunteers (mean age 64 years were enrolled in the study. In serum samples of patients and controls we determined concentrations of OPG, RANKL, tartarat resistant acid phosphatase 5b (TRAP 5b, serum Cterminal telopeptide cross-links of type I collagen (CTx, bone specific alkaline phosphatase (BALP, osteocalcin (OC and parathyroid hormone (PTH. We compared serum measurements of HD patients and controls and assessed the correlation of OPG and RANKL with bone markers. The most frequent OPG promotor gene polymorphisms were also determined. SPSS 12.1 for Windows was used for statistical analysis.Results: Median OPG concentrations were approximately three times higher in HD patients (0.804 µg/l than in healthy volunteers (0.272 µg/l. Mean serum RANKL concentrations were 1.66- fold higher in HD patients (1.36 pmol/l than in controls (0.82 pmol/l. Serum RANKL levels significantly differed between patients with and without calcitriol therapy (p = 0.001. After dividing HD patients into tertiles according to PTH, we observed significantly higher OPG values in the lower and RANKL in the upper tertile (p < 0.001. OPG did not correlate with bone resorption markers. Only weak correlation of bone formation markers with osteocalcin was noted. In contrast to OPG, RANKL correlated well with PTH, OC and CTX. OPG promoter gene polymorphisms (149 T → C, 163 A → G, 950 T → C do not influence OPG expression and
Essential role of UCP1 modulating the central effects of thyroid hormones on energy balance

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Mayte Alvarez-Crespo

2016-04-01

Full Text Available Objective: Classically, metabolic effects of thyroid hormones (THs have been considered to be peripherally mediated, i.e. different tissues in the body respond directly to thyroid hormones with an increased metabolism. An alternative view is that the metabolic effects are centrally regulated. We have examined here the degree to which prolonged, centrally infused triiodothyronine (T3 could in itself induce total body metabolic effects and the degree to which brown adipose tissue (BAT thermogenesis was essential for such effects, by examining uncoupling protein 1 (UCP1 KO mice. Methods: Wildtype and UPC1 KO mice were centrally-treated with T3 by using minipumps. Metabolic measurements were analyzed by indirect calorimetry and expression analysis by RT-PCR or western blot. BAT morphology and histology were studied by immunohistochemistry. Results: We found that central T3-treatment led to reduced levels of hypothalamic AMP-activated protein kinase (AMPK and elevated body temperature (0.7 °C. UCP1 was essential for the T3-induced increased rate of energy expenditure, which was only observable at thermoneutrality and notably only during the active phase, for the increased body weight loss, for the increased hypothalamic levels of neuropeptide Y (NPY and agouti-related peptide (AgRP and for the increased food intake induced by central T3-treatment. Prolonged central T3-treatment also led to recruitment of BAT and britening/beiging (“browning” of inguinal white adipose tissue (iWAT. Conclusions: We conclude that UCP1 is essential for mediation of the central effects of thyroid hormones on energy balance, and we suggest that similar UCP1-dependent effects may underlie central energy balance effects of other agents. Keywords: AMPK, Brown adipose tissue, Hypothalamus, Thyroid hormones, UCP1
Release of Hormones from Conjugates: Chloroplast Expression of β-Glucosidase Results in Elevated Phytohormone Levels Associated with Significant Increase in Biomass and Protection from Aphids or Whiteflies Conferred by Sucrose Esters1[C][OA

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Jin, Shuangxia; Kanagaraj, Anderson; Verma, Dheeraj; Lange, Theo; Daniell, Henry

2011-01-01

Transplastomic tobacco (Nicotiana tabacum) plants expressing β-glucosidase (Bgl-1) show modified development. They flower 1 month earlier with an increase in biomass (1.9-fold), height (1.5-fold), and leaf area (1.6-fold) than untransformed plants. Trichome density on the upper and lower leaf surfaces of BGL-1 plants increase by 10- and 7-fold, respectively, harboring 5-fold more glandular trichomes (as determined by rhodamine B staining), suggesting that BGL-1 lines produce more sugar esters than control plants. Gibberellin (GA) levels were investigated because it is a known regulator of flowering time, plant height, and trichome development. Both GA1 and GA4 levels are 2-fold higher in BGL-1 leaves than in untransformed plants but do not increase in other organs. In addition, elevated levels of other plant hormones, including zeatin and indole-3-acetic acid, are observed in BGL-1 lines. Protoplasts from BGL-1 lines divide and form calli without exogenous hormones. Cell division in protoplasts is enhanced 7-fold in the presence of exogenously applied zeatin-O-glucoside conjugate, indicating the release of active hormones from their conjugates. Whitefly (Bemisia tabaci) and aphid (Myzus persicae) populations in control plants are 18 and 15 times higher than in transplastomic lines, respectively. Lethal dose to kill 50% of the test population values of 26.3 and 39.2 μg per whitefly and 23.1 and 35.2 μg per aphid for BGL-1 and untransformed control exudates, respectively, confirm the enhanced toxicity of transplastomic exudates. These data indicate that increase in sugar ester levels in BGL-1 lines might function as an effective biopesticide. This study provides a novel strategy for designing plants for enhanced biomass production and insect control by releasing plant hormones or sugar esters from their conjugates stored within their chloroplasts. PMID:21068365
Frequency of papillary tubal hyperplasia (PTH), salpingoliths and transition from adenoma to borderline ovarian tumors (BOT): A systematic analysis of 74 BOT with different histologic types.

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Horn, Lars-Christian; Angermann, Karolin; Hentschel, Bettina; Einenkel, Jens; Höhn, Anne Kathrin

2017-04-01

Borderline ovarian tumors (BOT) arise from cystadenomas and represent a transition step within the development of low-grade ovarian carcinomas (Type I tumors). That pathway mirrors the adenoma-to-carcinoma sequence known for colorectal cancer. It has been suggested that papillary tubal hyperplasia (PTH) and salpingoliths may be associated with the development of BOT. To evaluate the frequency of the presence of benign cystadenoma and its transition to BOT in a given patient as well as the presence of PTH and salpingoliths we re-valuated in 74 consecutive cases of BOT with different histologic types. The majority of cases represented serous-BOT (60.8%), followed by mucinous BOT (25.7%), other histologic types were rare. 86.5% showed an adenoma-BOT sequence, which was seen in all mucinous BOT but was missed in 15.6% of serous BOT. Two cases had salpingoliths without associated PTH. PTH was seen in four out of the 74 (5.4%) BOT and occurred only in cases with serous histology. The vast majority of BOT represent a transition from benign cystadenoma to BOT in cases with mucinous and serous histology. Salpingoliths are rarely seen in association with BOT and occurred exclusively in BOT with serous histology. PTH may represent a distinct lesion but is rarely seen in association with BOT, especially in those with non-serous histology. Further studies are needed to evaluate the frequency and pathogenetic association of PTH with BOT. Copyright © 2017 Elsevier GmbH. All rights reserved.
The effect of cholecalciferol and calcitriol on biochemical bone markers in HIV type 1-infected males: results of a clinical trial.

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Bang, Ulrich Christian; Kolte, Lilian; Hitz, Mette; Schierbeck, Louise Lind; Nielsen, Susanne Dam; Benfield, Thomas; Jensen, Jens-Erik Beck

2013-04-01

HIV-1-infected patients have an increased risk of osteoporosis and fractures. The main objective of this study was to evaluate the bone metabolism in HIV-1-infected patients exposed to calcitriol and cholecalciferol. We also investigated the relationship between T cells and bone markers. We conducted a placebo-controlled randomized study running for 16 weeks including 61 HIV-1-infected males, of whom 51 completed the protocol. Nineteen participants were randomized to daily treatment with (A) 0.5-1.0 μg calcitriol and 1,200 IU (30 μg) cholecalciferol, 17 participants to (B) 1,200 IU cholecalciferol, and 15 participants to (C) placebo. At baseline and after 16 weeks, we determined collagen type 1 trimeric cross-linked peptide (CTx), procollagen type 1 N-terminal peptide (P1NP), parathyroid hormone (PTH), ionized calcium, 25-hydroxyvitamin D (25OHD), and 1,25-dihydroxyvitamin D [1,25(OH)2D]. We determined naive CD4(+) and CD8(+), activated CD4(+) and CD8(+), and regulatory CD4(+)CD25(+)CD127(low) T lymphocytes. Baseline levels of P1NP and CTx correlated (coefficient 0.5, p<0.001) with each other but not with PTH, 25OHD, or 1,25(OH)2D. In patients receiving calcitriol and cholecalciferol, the mean levels of P1NP (p<0.001) and CTx (p= 0.002) declined significantly compared to our placebo group. Based on changes in P1NP and CTx, we estimated that net bone formation occurred more frequently in group A compared to groups B and C. PTH correlated inversely with naive CD4(+) and CD8(+) cells. Otherwise, no relationships between bone markers and T lymphocytes were demonstrated. Supplementation with calcitriol and cholecalciferol induced biochemical indications of bone formation in HIV-1 patients.
Age-related differences in hormonal and nutritional impact on lean anorexia nervosa bone turnover uncoupling.

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Galusca, B; Bossu, C; Germain, N; Kadem, M; Frere, D; Lafage-Proust, M H; Lang, F; Estour, B

2006-01-01

In anorexia nervosa (AN) patients osteoporosis occurs within a framework of multiple hormonal abnormalities as a result of bone turnover uncoupling, with decreased bone formation and increased bone resorption. The aim of study was to evaluate the hormonal and nutritional relationships with both of these bone remodeling compartments and their eventual modifications with age. In a cohort of 115 AN patients (mean BMI:14.6 kg/m2) that included 60 mature adolescents (age: 15.5-20 years) and 55 adult women (age: 20-37 years) and in 28 age-matched controls (12 mature adolescents and 16 adults) we assessed: bone markers [serum osteocalcin, skeletal alkaline phosphatase (sALP), C-telopeptide of type I collagen (sCTX) and tartrate-resistant acid phosphatase type 5b (TRAP 5b)], nutritional markers [ body mass index (BMI, fat and lean mass), hormones (free tri-iodothyronine (T3), free T4, thyroid stimulating hormone (TSH), luteinizing hormone (LH), follicle stimulating hormone (FSH), 17 beta estradiol, free testosterone index (FTI), dehydroepiandrosterone (DHEAS), insulin-like growth factor 1 (IGF-1), growth hormone (GH) and cortisol], plasma methoxyamines (metanephrine and normetanephrine) and calcium metabolism parameters [parathyroid hormone (PTH), Ca, vitamin D3]. Osteocalcin reached similar low levels in both AN age subgroups. sCTX levels were found to be elevated in all AN subjects and higher in mature adolescents than in adult AN (11,567+/-895 vs. 8976+/-805 pmol/l, psALP was significantly lower only in mature adolescent AN patients, while there were no significant differences in the levels of TRAP 5b between AN patients and age-matched control groups. Osteocalcin correlated with sCTX in the control subjects (r=0.65) but not in the AN patients, suggesting the independent regulation of these markers in AN patients. Osteocalcin levels strongly correlated with freeT3, IGF-I, 17 beta estradiol and cortisol, while sCTX correlated with IGF-I, GH and cortisol in both age
Clinicopathological Risk Factors and Biochemical Predictors of Safe Discharge after Total Thyroidectomy and Central Compartment Node Dissection for Thyroid Cancer: A Prospective Study

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Yu-mi Lee

2015-01-01

Full Text Available To determine the clinicopathological risk factors and reliable biochemical predictors of the development of hypocalcemic symptoms after total thyroidectomy on the basis of serum calcium and intact parathyroid hormone (PTH levels measured 1 hour after surgery, a prospective study was performed on 817 patients who underwent a total thyroidectomy with central compartment node dissection (CCND due to well-differentiated thyroid cancer. We evaluated the correlations between hypocalcemic symptom development and clinicopathological factors. And the predictability for hypocalcemic symptom development of intact PTH cut-offs (<10 pg/mL and <20 pg/mL, resp. according to serum calcium level subgroup was analyzed. Female gender (P<0.001 was the only independent risk factor for hypocalcemic symptom development in multivariate regression analysis. The negative predictive value (NPV of intact PTH, signifying nondevelopment of hypocalcemic symptoms, was higher than the positive predictive value (PPV which signified development of hypocalcemic symptoms. In addition, when we applied the different adoption of the intact PTH cut-off according to serum calcium level, we could obtain more increased NPVs. A female gender and the application of more specific cut-offs for intact PTH according to the serum calcium levels measured 1 hour after surgery may help the patients to be more safely discharged.
Dual-hormone treatment with insulin and glucagon in patients with type 1 diabetes

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Reiband, H K; Schmidt, S; Ranjan, Ajenthen

2015-01-01

Intensive insulin treatment in type 1 diabetes reduces the incidence and slows the progression of microvascular and macrovascular complications; however, it is associated with an increased risk of hypoglycaemia and weight gain. In this review, we propose dual-hormone treatment with insulin...... and glucagon as a method for achieving near normalization of blood glucose levels without increasing hypoglycaemia frequency and weight gain. We briefly summarize glucagon pathophysiology in type 1 diabetes as well as the current applications of glucagon for the treatment of hypoglycaemia. Until now, the use...... of glucagon has been limited by the need for reconstitution immediately before use, because of instability of the available compounds; however, stabile compounds are soon to be launched and will render long-term intensive dual-hormone treatment in type 1 diabetes possible....
Effects of general anaesthesia on endocrine system of body in paediatric patients during surgical intervention

International Nuclear Information System (INIS)

Mahmood, N.

1990-01-01

A total of 50 children (mean age 7, range 2-12 years), undergoing minor to major surgical operations were evaluated for hormonal changes induced by anaesthesia 15 hormones i.e. GH, ACTH, OH, FISH, TSH, PTH, FT4, T3, prolactin, insulin estradiol, testosterone, aldosterone, progesterone, and cortisol were studies results obtained showed significant increase in the levels of GH, cortisol, aldosterone, prolactin, progesterone, and PTH at the time of induction of anaesthesia. Of these GH, prolactin and aldosterone levels showed further increase during surgery (maintenance of anaesthesia). Values of TSH, LH, FSH, FT4 and testosterone levels remained essentially unaffected at induction of anaesthesia, but showed significant rise during surgery (maintenance of anaesthesia). Serum levels of ACTH, insulin, estradiol, and T3 were basically unaffected by anaesthesia and surgery. Furthermore, increase in cortisol and PTH levels was more prominent in patients anaesthetized with halothane alone. In this group ACTH level recorded a decrease while in thiopentone, halothane+nitrous oxide anaesthesia group ACTH showed a significantly rise. Growth hormone and insulin response was significantly more prominent in patients undergoing major surgery as compared to others. These findings under score the importance of stress response resulting from general anaesthesia and surgical trauma in children, and brings into focus the need of careful pre and post operative monitoring of patients in this age group. (author)
Insulin-like growth factor 1 (IGF-1): a growth hormone

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Laron, Z

2001-01-01

Aim—To contribute to the debate about whether growth hormone (GH) and insulin-like growth factor 1 (IGF-1) act independently on the growth process. Methods—To describe growth in human and animal models of isolated IGF-1 deficiency (IGHD), such as in Laron syndrome (LS; primary IGF-1 deficiency and GH resistance) and IGF-1 gene or GH receptor gene knockout (KO) mice. Results—Since the description of LS in 1966, 51 patients were followed, many since infancy. Newborns with LS are shorter (42–47 cm) than healthy babies (49–52 cm), suggesting that IGF-1 has some influence on intrauterine growth. Newborn mice with IGF-1 gene KO are 30% smaller. The postnatal growth rate of patients with LS is very slow, the distance from the lowest normal centile increasing progressively. If untreated, the final height is 100–136 cm for female and 109–138 cm for male patients. They have acromicia, organomicria including the brain, heart, gonads, genitalia, and retardation of skeletal maturation. The availability of biosynthetic IGF-1 since 1988 has enabled it to be administered to children with LS. It accelerated linear growth rates to 8–9 cm in the first year of treatment, compared with 10–12 cm/year during GH treatment of IGHD. The growth rate in following years was 5–6.5 cm/year. Conclusion—IGF-1 is an important growth hormone, mediating the protein anabolic and linear growth promoting effect of pituitary GH. It has a GH independent growth stimulating effect, which with respect to cartilage cells is possibly optimised by the synergistic action with GH. PMID:11577173
Adult growth hormone deficiency

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Vishal Gupta

2011-01-01

Full Text Available Adult growth hormone deficiency (AGHD is being recognized increasingly and has been thought to be associated with premature mortality. Pituitary tumors are the commonest cause for AGHD. Growth hormone deficiency (GHD has been associated with neuropsychiatric-cognitive, cardiovascular, neuromuscular, metabolic, and skeletal abnormalities. Most of these can be reversed with growth hormone therapy. The insulin tolerance test still remains the gold standard dynamic test to diagnose AGHD. Growth hormone is administered subcutaneously once a day, titrated to clinical symptoms, signs and IGF-1 (insulin like growth factor-1. It is generally well tolerated at the low-doses used in adults. Pegylated human growth hormone therapy is on the horizon, with a convenient once a week dosing.
Risk factors of post renal transplant hyperparathyroidism

International Nuclear Information System (INIS)

Jahromi, Alireza Hamidian; Roozbeh, Jamshid; Raiss-Jalali, Ghanbar Ali; Dabaghmanesh, Alireza; Jalaeian, Hamed; Bahador, Ali; Nikeghbalian, Saman; Salehipour, Mehdi; Salahi, Heshmat; Malek-Hosseini, Ali

2009-01-01

It is well recognized that patients with end stage renal diseases (ESRD) have hyper-plastic parathyroid glands. In most patients, a decrease in parathyroid hormone (PTH) occurs by about 1 year after renal transplantation. However, some renal transplant recipients continue to have elevated level of PTH. We prospectively evaluated 121 patients undergoing renal transplantation between August 2000 and 2002. The duration of dialysis, calcium (Ca), phosphorus (P), albumin, creatinine and iPTH levels were recorded prior to transplantation and three months and one year after transplantation. These 121 patients were on dialysis for an average period of 17.4 months prior to transplantation. An increase in the serum Ca and a decrease in serum P and iPTH level was seen in the patients after transplantation (P< 0.001). Hyperparathyroidism was in 12 (9.9%) and 7 (5.7%) patients three months and one year after transplantation respectively. Elderly patients and patients with longer duration on dialysis had an increased risk of developing post transplant hyperparathyroidism and hypercalcemia in the first year post transplant (P< 0.05). In conclusion age and duration on dialysis before transplantation seems to be important risk factors for post transplant hyperparathyroidism. (author)
Glucagon-related peptide 1 (GLP-1): hormone and neurotransmitter

DEFF Research Database (Denmark)

Larsen, Philip J; Holst, Jens Juul

2005-01-01

normal and pathophysiological role of GLP-1 have been published over the last two decades and our understanding of GLP-1 action has widened considerably. In the present review, we have tried to cover our current understanding of GLP-1 actions both as a peripheral hormone and as a central neurotransmitter...
Immunoassays for the incretin hormones GIP and GLP-1

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Deacon, Carolyn F; Holst, Jens J

2009-01-01

The measurement of the incretin hormones, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), using immunologically based assays is made difficult by the fact that the processing of the precursor molecules gives rise to a number of different peptides which cross......-react with antisera raised against the two hormones. For GLP-1, the picture is further complicated because of the necessity to differentiate between the intestinal and pancreatic proglucagon products. Finally, once secreted, both incretins are rapidly degraded by the enzyme dipeptidyl peptidase-4 (DPP-4) to generate....... The use of highly specific assays using well-characterised antisera and careful sample handling is therefore required for a reliable determination of incretin hormone concentrations....
Long-term effects of intermittent oral alphacalcidol, calcium carbonate and low-calcium dialysis (1.25 mmol L-1) on secondary hyperparathyroidism in patients on continuous ambulatory peritoneal dialysis

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Brandi, L; Nielsen, P K; Bro, S

1998-01-01

of the secondary hyperparathyroidism was seen. CONCLUSIONS: A calcium concentration of 1.25 mmol L-1 in the CAPD dialysate made it possible to reduce the amount of aluminium-containing phosphate binder, to increase the doses of CaCO3 and to use pulse oral 1 alpha(OH)D3 without causing severe hyper...... L-1 to 1.25 mmol L-1. Increasing doses of oral 1 alpha(OH)D3 were then administered under careful control of p-ionized calcium (p-Ca2+) and p-inorganic phosphate (p-P1). Blood samples were obtained every 2-4 weeks for 52 weeks. PET was performed using standard dialysis fluid and 1 week later using...... low-calcium dialysis fluid after a preceding overnight dwell. Two litres of glucose 22.7 mg mL-1 were used. MAIN OUTCOME MEASURES: Intact parathyroid hormone (PTH), p-Ca2+, p-P1, doses of CaCO3, doses of 1 alpha(OH)D3, peritoneal mass transfer for calcium, inorganic phosphate, magnesium, lactate...
Radiological diagnosis of renal osteodystrophy with reference to clinical features in patients undergoing maintenance hemodialysis

International Nuclear Information System (INIS)

Huebsch, P.; Trattnig, S.; Barton, P.; Seidl, G.

1989-01-01

Pathophysiological, histological and radiological findings in renal osteodystrophy are described. Special emphasis is laid on secondary hyperparathyroidism. Preliminary results of the authors' investigations show a good correlation between radiological findings in the phalanges of the hand and the concentration of parathyroid hormone (PTH) in 14 patients. The concentration of the hormone in the blood was measured by a new 'two-site' immunoradiometric assay, which is specific for the intact, biologically active hormone. Patients with high concentrations of PTH in the blood tended to have more severe radiological changes. In 4 patients for whom radiographs of the hands revealed no pathologic findings, normal PTH concentrations in the blood were measured by this method, whereas the conventional assay gave elevated hormone concentrations for the same patients. This is due to the lack of specificity of the conventional method for the intact, biologically active hormone. Nevertheless, further investigations are needed to confirm these findings. (orig.) [de

Deletion of the Intestinal Plasma Membrane Calcium Pump, Isoform 1, Atp2b1, in Mice is Associated with Decreased Bone Mineral Density and Impaired Responsiveness to 1, 25-Dihydroxyvitamin D3

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Ryan, Zachary C.; Craig, Theodore A.; Filoteo, Adelaida G.; Westendorf, Jennifer J.; Cartwright, Elizabeth J.; Neyses, Ludwig; Strehler, Emanuel E.; Kumar, Rajiv

2016-01-01

The physiological importance of the intestinal plasma membrane calcium pump, isoform 1, (Pmca1, Atp2b1), in calcium absorption and homeostasis has not been previously demonstrated in vivo. Since global germ-line deletion of the Pmca1 in mice is associated with embryonic lethality, we selectively deleted the Pmca1 in intestinal absorptive cells. Mice with loxP sites flanking exon 2 of the Pmca1 gene (Pmca1fl/fl) were crossed with mice expressing Cre recombinase in the intestine under control of the villin promoter to give mice in which the Pmca1 had been deleted in the intestine (Pmca1EKO mice). Pmca1EKO mice were born at a reduced frequency and were small at the time of birth when compared to wild-type (Wt) litter mates. At two months of age, Pmca1EKO mice fed a 0.81% calcium, 0.34% phosphorus, normal vitamin D diet had reduced whole body bone mineral density (P <0.037), and reduced femoral bone mineral density (P <0.015). There was a trend towards lower serum calcium and higher serum parathyroid hormone (PTH) and 1α,25-dihydroxyvitamin D3 (1α,25(OH)2D3) concentrations in Pmca1EKO mice compared to Wt mice but the changes were not statistically significant. The urinary phosphorus/creatinine ratio was increased in Pmca1EKO mice (P <0.004). Following the administration of 200 ng of 1α,25(OH)2D3 intraperitoneally to Wt mice, active intestinal calcium transport increased ∼2-fold, whereas Pmca1EKO mice administered an equal amount of 1α,25(OH)2D3 failed to show an increase in active calcium transport. Deletion of the Pmca1 in the intestine is associated with reduced growth and bone mineralization, and a failure to up-regulate calcium absorption in response to 1α,25(OH)2D3. PMID:26392310
Hormone replacement therapy increases the risk of cranial meningioma

DEFF Research Database (Denmark)

Andersen, Lene; Friis, Søren; Hallas, Jesper

2013-01-01

We investigated the influence of hormone replacement therapy (HRT) use on the risk of meningioma in a population-based setting.......We investigated the influence of hormone replacement therapy (HRT) use on the risk of meningioma in a population-based setting....
Influence of medication on the rate of orthodontic tooth movement (Part 1: hormons and corticosteroids

Directory of Open Access Journals (Sweden)

Mirhashemi Amirhossein

2015-05-01

Full Text Available The aim of this review article was to define the mechanism of action and effects of commonly used medications on the tissue remodeling and Orthodontic Tooth Movement (OTM. A review on the effects of medications and dietary supplements on the rate of experimental tooth movement was performed using Cochrane library, Embase and medline (1980-2013. 63 articles were included in this review. 34 of them were related to the effects of hormones and analgesics, were evaluated in this article but their interpretation was hindered by the variability in experimental design, magnitude of force applied during tooth movement and medication regimens. Non Steroidal Anti-Inflammatory Drugs (NSAIDs reduced the rate of tooth movement while non-NSAIDs such as acetaminophen had no effect on the rate of OTM. Corticosteroids, parathyroid hormone and thyroxin increased the rate of tooth movement. Sturgeons might slow OTM, but experimental studies are lacking. Medications might have an important influence on the rate of tooth movement and information on their consumption is necessary to adequately discuss treatment planning with patients.
Low calcium-phosphate intakes modulate the low-protein diet-related effect on peak bone mass acquisition: a hormonal and bone strength determinants study in female growing rats.

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Fournier, C; Rizzoli, R; Ammann, P

2014-11-01

Peak bone mass acquisition is influenced by environmental factors including dietary intake. A low-protein diet delays body and skeletal growth in association with a reduction in serum IGF-1 whereas serum FGF21 is increased by selective amino acid deprivation. Calcium (Ca) and phosphorous (P) are also key nutrients for skeletal health, and inadequate intakes reduce bone mass accrual in association with calciotropic hormone modulation. Besides, the effect of calcium supplementation on bone mass in prepubertal children appears to be influenced by protein intake. To further explore the interaction of dietary protein and Ca-P intake on bone growth, 1-month-old female rats were fed with an isocaloric 10%, 7.5%, or 5% casein diet containing normal or low Ca-P for an 8-week period (6 groups). Changes in tibia geometry, mineral content, microarchitecture, strength, and intrinsic bone quality were analyzed. At the hormonal level, serum IGF-1, fibroblast growth factor 21 (FGF21), PTH, 1,25-dihydroxyvitamin D3 (calcitriol), and FGF23 were investigated as well as the Ghr hepatic gene expression. In normal dietary Ca-P conditions, bone mineral content, trabecular and cortical bone volume, and bone strength were lower in the 5% casein group in association with a decrease in serum IGF-1 and an increase in FGF21 levels. Unexpectedly, the low-Ca-P diet attenuated the 5% casein diet-related reduction of serum IGF-1 and Ghr hepatic gene expression, as well as the low-protein diet-induced decrease in bone mass and strength. However, this was associated with lower cortical bone material level properties. The low-Ca-P diet increased serum calcitriol but decreased FGF23 levels. Calcitriol levels positively correlated with Ghr hepatic mRNA levels. These results suggest that hormonal modulation in response to a low-Ca-P diet may modify the low-protein diet-induced effect on Ghr hepatic mRNA levels and consequently the impact of low protein intakes on IGF-1 circulating levels and skeletal
Diminished parathyroid gland responsiveness to hypocalcemia in diabetic patients with uremia.

Science.gov (United States)

Heidbreder, E; Götz, R; Schafferhans, K; Heidland, A

1986-01-01

The parathyroid gland responsiveness to hypocalcemia induced by short-term calcium-free hemodialysis in patients with insulin-dependent diabetes mellitus was investigated in comparison with 10 nondiabetic uremic patients and compared with test results from the autonomic nervous system. Diabetic patients had lower C-terminal parathyroid hormone (cPTH) levels before hemodialysis than uremic control patients and showed a significantly smaller increase in cPTH during hypocalcemia. The neurological tests revealed severe disturbances of the autonomic functions in the diabetic group. In conclusion, the disturbances observed in the parathyroid secretory pattern are probably caused by gland dysfunction; it is hypothesized that the defective autonomic nervous system has an additional effect on the development of this hormonal dysfunction.
Urinary calcium and oxalate excretion in healthy adult cats are not affected by increasing dietary levels of bone meal in a canned diet.

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Nadine Passlack

Full Text Available This study aimed to investigate the impact of dietary calcium (Ca and phosphorus (P, derived from bone meal, on the feline urine composition and the urinary pH, allowing a risk assessment for the formation of calcium oxalate (CaOx uroliths in cats. Eight healthy adult cats received 3 canned diets, containing 12.2 (A, 18.5 (B and 27.0 g Ca/kg dry matter (C and 16.1 (A, 17.6 (B and 21.1 g P/kg dry matter (C. Each diet was fed over 17 days. After a 7 dayś adaptation period, urine and faeces were collected over 2×4 days (with a two-day rest between, and blood samples were taken. Urinary and faecal minerals, urinary oxalate (Ox, the urinary pH and the concentrations of serum Ca, phosphate and parathyroid hormone (PTH were analyzed. Moreover, the urine was microscopically examined for CaOx uroliths. The results demonstrated that increasing levels of dietary Ca led to decreased serum PTH and Ca and increased faecal Ca and P concentrations, but did not affect the urinary Ca or Ox concentrations or the urinary fasting pH. The urinary postprandial pH slightly increased when the diet C was compared to the diet B. No CaOx crystals were detected in the urine of the cats. In conclusion, urinary Ca excretion in cats seems to be widely independent of the dietary Ca levels when Ca is added as bone meal to a typical canned diet, implicating that raw materials with higher contents of bones are of subordinate importance as risk factors for the formation of urinary CaOx crystals.
SIAH1-induced p34SEI-1 polyubiquitination/degradation mediates p53 preferential vitamin C cytotoxicity.

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Lee, Soonduck; Kim, Jinsun; Jung, Samil; Li, Chengping; Yang, Young; Kim, Keun Il; Lim, Jong-Seok; Kim, Yonghwan; Cheon, Choong-Il; Lee, Myeong-Sok

2015-03-01

Vitamin C is considered as an important anticancer therapeutic agent although this view is debatable. In this study, we introduce a physiological mechanism demonstrating how vitamin C exerts anticancer activity that induces cell cycle arrest and apoptosis. Our previous and current data reveal that p53 tumor suppressor is the prerequisite factor for stronger anticancer effects of vitamin C. In addition, vitamin C-mediated cancer cell cytotoxicity appears to be achieved at least partly through the downregulation of the p34SEI-1 oncoprotein. Our previous study showed that p34SEI-1 increases the survival of various types of cancer cells by inhibiting their apoptosis. Present data suggest that vitamin C treatment decreases the p34SEI-1 expression at the protein level and therefore alleviates its anti-apoptotic activity. Of note, SIAH1, E3 ubiquitin ligase, appears to be responsible for the p34SEI-1 polyubiquitination and its subsequent degradation, which is dependent on p53. In summary, vitamin C increases cancer cell death by inducing SIAH1-mediated polyubiquitination/degradation of the p34SEI-1 oncoprotein in a p53-dependent manner.
Starting Hormone Therapy at Menopause Increases Breast Cancer Risk

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According to a January 28, 2011 article in the Journal of the National Cancer Institute, women who start taking menopausal hormone therapy around the time of menopause have a higher risk of breast cancer than women who begin taking hormones a few years later.
Intraoperative parathyroid hormone assay-cutting the Gordian knot

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Chandralekha Tampi

2014-01-01

Full Text Available Background: Hyperparathyroidism is treated by surgical excision of the hyperfunctioning parathyroid gland. In case of adenoma the single abnormal gland is removed, while in hyperplasias, a subtotal excision, that is, three-and-a-half of the four glands are removed. This therapeutic decision is made intraoperatively through frozen section evaluation and is sometimes problematic, due to a histological overlap between hyperplasia and the adenoma. The intraoperative parathyroid hormone (IOPTH assay, propogated in recent years, offers an elegant solution, with a high success rate, due to its ability to identify the removal of all hyperfunctioning parathyroid tissue. Aim: To study the feasibility of using IOPTH in our setting. Materials and Methods: Seven patients undergoing surgery for primary hyperparathyroidism had their IOPTH levels evaluated, along with the routine frozen and paraffin sections. Results: All seven patients showed more than a 50% intraoperative fall in serum PTH after excision of the abnormal gland. This was indicative of an adenoma and was confirmed by histopathological examination and normalization of serum calcium postoperatively. Conclusion: The intraoperative parathyroid hormone is a sensitive and specific guide to a complete removal of the abnormal parathyroid tissue. It can be incorporated without difficulty as an intraoperative guide and is superior to frozen section diagnosis in parathyroid surgery.
Stretching dependence of the vibration modes of a single-molecule Pt-H-2-Pt bridge

DEFF Research Database (Denmark)

Djukic, D.; Thygesen, Kristian Sommer; Untiedt, C.

2005-01-01

isotope substitution is obtained. The stretching dependence for each of the modes allows uniquely classifying them as longitudinal or transversal modes. The interpretation of the experiment in terms of a Pt-H-2-Pt bridge is verified by density-functional theory calculations for the stability, vibrational...
A van der Waals DFT study of PtH_2 systems absorbed on pristine and defective graphene

International Nuclear Information System (INIS)

López-Corral, Ignacio; Piriz, Sebastián; Faccio, Ricardo; Juan, Alfredo; Avena, Marcelo

2016-01-01

Highlights: • We performed DFT calculations including van der Waals interactions. • Kubas-type Pt-H2 complex is stable on defective graphene. • Carbon vacancy decreases the reactivity of the metal decoration. • The interaction between σ-H and π-C states favors the Kubas-type complex. - Abstract: We used a density functional that incorporates van der Waals interactions to study hydrogen adsorption onto Pt atoms attached to carbon-vacancies on graphene layers, considering molecular and dissociated hydrogen-platinum coordination structures. PtH_2 complexes adsorbed on several sites of pristine graphene were also studied for comparison. Our results indicate that both a Kubas-type dihydrogen complex and a classic hydride without H−H bond are the preferential PtH_2 systems on the vacancy site of graphene. In contrast, the Kubas complex is unstable onto pristine graphene and the hydride is obtained at all adsorption sites. Our simulations suggest that the C-vacancy decreases the reactivity of the metal decoration, allowing a non-dissociative hydrogen adsorption. The H_2 molecule is oriented almost perpendicular to the outermost C−Pt bond, interacting also with the graphene surface through σ-H and π-C states. This stabilization of the Kubas-type complex could play a very important role for hydrogen storage in Pt-decorated carbon adsorbents with vacancies.
Mechanisms of renal phosphate loss in liver resection-associated hypophosphatemia.

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Nafidi, Otmane; Lapointe, Real W; Lepage, Raymond; Kumar, Rajiv; D'Amour, Pierre

2009-05-01

To determine precisely the role of parathyroid hormone (PTH) and of phosphatonins in the genesis of posthepatectomy hypophosphatemia. Posthepatectomy hypophosphatemia has recently been related to increased renal fractional excretion of phosphate (FE P). To address the cause of hypophosphatemia, we measured serum concentrations of PTH, various phosphatonins, and the number of removed hepatic segment in patients with this disorder. Serum phosphate (PO4), ionized calcium (Ca++), HCO3-, pH and FE P, intact PTH (I-PTH), carboxyl-terminal fibroblast growth factor 23 (C-FGF-23) and intact fibroblast growth factor 23 (I-FGF-23), FGF-7, and secreted frizzled related-protein-4 (sFRP-4) were measured before and on postoperative (po) days 1, 2, 3, 5, and 7, in 18 patients undergoing liver resection. The number of removed hepatic segments was also assessed. Serum PO4 concentrations decreased within 24 hours, were lowest (0.66 +/- 0.03 mmol/L; P < 0.001) at 48 hours, and returned to normal within 5 days of the procedure. FE P peaked at 25.07% +/- 2.26% on po day 1 (P < 0.05). Decreased ionized calcium concentrations (1.10 +/- 0.01 mmol/L; P < 0.01) were observed on po day 1 and were negatively correlated with increased I-PTH concentrations (8.8 +/- 0.9 pmol/L; P < 0.01; correlation: r = -0.062, P = 0.016). FE P was positively related to I-PTH levels on po day 1 (r = 0.52, P = 0.047) and negatively related to PO4 concentrations (r = -0.56, P = 0.024). Severe hypophosphatemia and increased urinary phosphate excretion persisted for 72 hours even when I-PTH concentrations had returned to normal. I-FGF-23 decreased to its nadir of 7.8 +/- 6.9 pg/mL (P < 0.001) on po day 3 and was correlated with PO4 levels on po days 0, 3, 5, and 7 (P < 0.001). C-FGF-23, FGF-7 and sFRP-4 levels could not be related to either PO4 concentrations or FE P. Posthepatectomy hypophosphatemia is associated with increased FE P unrelated to I-FGF-23 or C-FGF-23, FGF-7, or sFRP-4. I-PTH contributes to excessive
The role of leptin and other hormones related to bone metabolism and appetite regulation as determinants of gain in body fat and fat-free mass in 8-11-year-old children.

Science.gov (United States)

Dalskov, Stine-Mathilde; Ritz, Christian; Larnkjær, Anni; Damsgaard, Camilla T; Petersen, Rikke A; Sørensen, Louise B; Ong, Ken K; Astrup, Arne; Mølgaard, Christian; Michaelsen, Kim F

2015-03-01

Regulation of body composition during childhood is complex. Numerous hormones are potentially involved. Leptin has been proposed to restrain weight gain, but results are inconsistent. We examined whether baseline fasting levels of ghrelin, adiponectin, leptin, insulin, IGF-I, osteocalcin, and intact parathyroid hormone (iPTH) were associated with body composition cross sectionally and longitudinally in 633 8-11-year-olds. Data on hormones and body composition by dual-energy x-ray absorptiometry from the OPUS School Meal Study were used. We looked at baseline hormones as predictors of baseline fat mass index (FMI) or fat-free mass index (FFMI), and also subsequent changes (3 and 6 months) in FMI or FFMI using models with hormones individually or combined. Cross-sectionally, baseline leptin was positively associated with FMI in girls (0.211 kg/m(2) pr. μg/mL; 97.5% confidence interval [CI],0.186-0.236; P < .001) and boys (0.231 kg/m(2) pr. μg/mL; 97.5% CI, 0.200-0.261; P < .001). IGF-I in both sexes and iPTH in boys were positively associated with FMI. An inverse association between adiponectin and FFMI in boys and a positive association between IGF-I and FFMI were found in girls. In longitudinal models, baseline leptin was inversely associated with subsequent changes in FMI (-0.018 kg/m(2) pr. μg/mL; 97.5% CI, -0.034 - -0.002; P = .028) and FFMI (-0.014 kg/m(2) pr. μg/mL; 97.5% CI, -0.024 - -0.003; P = .006) in girls. Cross-sectional findings support that leptin is produced in proportion to body fat mass, but the longitudinal observations support that leptin inhibits gains in FMI and FFMI in girls, a finding that may reflect preserved leptin sensitivity in this predominantly normal weight population.
Effects on bone geometry, density, and microarchitecture in the distal radius but not the tibia in women with primary hyperparathyroidism

DEFF Research Database (Denmark)

Hansen, Stinus; Beck Jensen, Jens-Erik; Rasmussen, Lars

2010-01-01

Patients with primary hyperparathyroidism (PHPT) have continuously elevated parathyroid hormone (PTH) and consequently increased bone turnover with negative effects on cortical (Ct) bone with preservation of trabecular (Tb) bone. High-resolution peripheral quantitative computed tomography (HR...
Effect of lowering dietary calcium intake on fractional whole body calcium retention

International Nuclear Information System (INIS)

Dawson-Hughes, B.; Stern, D.T.; Shipp, C.C.; Rasmussen, H.M.

1988-01-01

Although fractional calcium absorption is known to vary inversely with calcium intake, the extent and timing of individual hormonal and calcium absorption responses to altered calcium intake have not been defined. We measured fractional whole body retention of orally ingested 47 Ca, an index of calcium absorption, in nine normal women after they had eaten a 2000-mg calcium diet for 8 weeks and a 300-mg calcium diet for 1, 2, 4, and 8 weeks. After the diet change, serum intact PTH (32.2% increase; P = 0.005), serum 1,25-dihydroxyvitamin D [1,25-(OH)2D; 43.8% increase; P = 0.003], and fractional whole body calcium retention (42.8% increase; P = 0.004) increased within 1 week. Although the PTH and calcium retention responses remained fairly constant throughout the low calcium intake period, serum 1,25-(OH)2D concentrations declined toward baseline after week 1. Thus, the late increase in calcium retention may have resulted from calcium absorption that was independent of 1,25-(OH)2D stimulation
Acetylcholine Modulates the Hormones of the Growth Hormone/Insulinlike Growth Factor-1 Axis During Development in Mice.

Science.gov (United States)

Lecomte, Marie-José; Bertolus, Chloé; Ramanantsoa, Nélina; Saurini, Françoise; Callebert, Jacques; Sénamaud-Beaufort, Catherine; Ringot, Maud; Bourgeois, Thomas; Matrot, Boris; Collet, Corinne; Nardelli, Jeannette; Mallet, Jacques; Vodjdani, Guilan; Gallego, Jorge; Launay, Jean-Marie; Berrard, Sylvie

2018-04-01

Pituitary growth hormone (GH) and insulinlike growth factor (IGF)-1 are anabolic hormones whose physiological roles are particularly important during development. The activity of the GH/IGF-1 axis is controlled by complex neuroendocrine systems including two hypothalamic neuropeptides, GH-releasing hormone (GHRH) and somatostatin (SRIF), and a gastrointestinal hormone, ghrelin. The neurotransmitter acetylcholine (ACh) is involved in tuning GH secretion, and its GH-stimulatory action has mainly been shown in adults but is not clearly documented during development. ACh, together with these hormones and their receptors, is expressed before birth, and somatotroph cells are already responsive to GHRH, SRIF, and ghrelin. We thus hypothesized that ACh could contribute to the modulation of the main components of the somatotropic axis during development. In this study, we generated a choline acetyltransferase knockout mouse line and showed that heterozygous mice display a transient deficit in ACh from embryonic day 18.5 to postnatal day 10, and they recover normal ACh levels from the second postnatal week. This developmental ACh deficiency had no major impact on weight gain and cardiorespiratory status of newborn mice. Using this mouse model, we found that endogenous ACh levels determined the concentrations of circulating GH and IGF-1 at embryonic and postnatal stages. In particular, serum GH level was correlated with brain ACh content. ACh also modulated the levels of GHRH and SRIF in the hypothalamus and ghrelin in the stomach, and it affected the levels of these hormones in the circulation. This study identifies ACh as a potential regulator of the somatotropic axis during the developmental period.
Growth hormone increases vascular cell adhesion molecule 1 expression

DEFF Research Database (Denmark)

Hansen, Troels Krarup; Fisker, Sanne; Dall, Rolf

2004-01-01

We investigated the impact of GH administration on endothelial adhesion molecules, vascular cell adhesion molecule-1 (VCAM-1) and E-selectin, in vivo and in vitro. Soluble VCAM-1, E-selectin, and C-reactive protein concentrations were measured before and after treatment in 25 healthy subjects...... and 25 adult GH-deficient (GHD) patients randomized to GH treatment or placebo. Furthermore, we studied the direct effect of GH and IGF-I and serum from GH-treated subjects on basal and TNF alpha-stimulated expression of VCAM-1 and E-selectin on cultured human umbilical vein endothelial cells. Baseline......% confidence interval: 95.0-208.7 microg/liter); P cells, there was no direct stimulatory effect of either GH or IGF-I on the expression of VCAM-1 and E-selectin, but serum from GH-treated healthy subjects significantly increased the expression of VCAM-1 (P
Sex steroid hormones and sex hormone binding globulin levels, CYP17 MSP AI (-34T:C) and CYP19 codon 39 (Trp:Arg) variants in children with developmental stuttering.

Science.gov (United States)

Mohammadi, Hiwa; Joghataei, Mohammad Taghi; Rahimi, Zohreh; Faghihi, Faezeh; Khazaie, Habibolah; Farhangdoost, Hashem; Mehrpour, Masoud

2017-12-01

Developmental stuttering is known to be a sexually dimorphic and male-biased speech motor control disorder. In the present case-control study, we investigated the relationship between developmental stuttering and steroid hormones. Serum levels of testosterone, dihydrotestosterone (DHT), dehydroepiandrosterone (DHEA), oestradiol, progesterone, cortisol, and sex hormone binding globulin (SHBG), as well as the 2nd/4th digit ratio (2D:4D), an indicator of prenatal testosterone level, were compared between children who stutter (CWS) and children who do not stutter (CWNS). Moreover, two SNPs (CYP17 -34 T:C (MSP AI) and CYP19 T:C (Trp:Arg)) of cytochrome P450, which is involved in steroid metabolism pathways, were analysed between the groups. Our results showed significantly higher levels of testosterone, DHT, and oestradiol in CWS in comparison with CWNS. The severity of stuttering was positively correlated with the serum levels of testosterone, DHEA, and cortisol, whereas no association was seen between the stuttering and digit ratio, progesterone, or SHBG. The CYP17CC genotype was significantly associated with the disorder. Copyright © 2017 Elsevier Inc. All rights reserved.
A complete study on the ethiology of malign renal lithiasis based on the determination of other hormones and functional and metabolic parameters implied in these diases. Part of a coordinated programme on in vitro assay techniques

International Nuclear Information System (INIS)

Tiberiu, P.

1979-10-01

Plasma parathyroid hormone (PTH) and plasma calcitonin (CT) were measured by radioimmunoassay with commercial radioimmunoassay kits and corresponding biochemical and functional studies were carried out in 55 patients with unilateral or bilateral malignant lithiasis and in a group of 10 control subjects. Plasma PTH levels were found to be normal in 5 of the patients and slightly or markedly elevated in 50, whilst plasma CT levels were found to be normal in 52 and slightly elevated in 3. In a further analysis of the data, plasma PTH levels were found to be slightly elevated in 42 out of the 45 patients suffering from renal failure and markedly elevated in 3. The latter were suspected of primary hyperparathyroidism, but in none was any adenoma discovered, either scintigraphically or by other means. It is concluded that secondary reactive hyperparathyroidism may appear in malignant renal lithiasis, but that primary hyperparathyroidism is unlikely to be implicated in the recurrent nature of the disease, which is more likely to result from residual calculi. The significance of these findings in relation to the management of the disease is discussed
Association of Hormonal Contraception With Depression

DEFF Research Database (Denmark)

Skovlund, Charlotte Wessel; Mørch, Lina Steinrud; Kessing, Lars Vedel

2016-01-01

to those who never used hormonal contraception, the RR estimates for users of combined oral contraceptives increased to 1.7 (95% CI, 1.66-1.71). Conclusions and Relevance: Use of hormonal contraception, especially among adolescents, was associated with subsequent use of antidepressants and a first......Importance: Millions of women worldwide use hormonal contraception. Despite the clinical evidence of an influence of hormonal contraception on some women's mood, associations between the use of hormonal contraception and mood disturbances remain inadequately addressed. Objective: To investigate...... whether the use of hormonal contraception is positively associated with subsequent use of antidepressants and a diagnosis of depression at a psychiatric hospital. Design, Setting, and Participants: This nationwide prospective cohort study combined data from the National Prescription Register...

Diagnosis of secondary hyperparathyroidism with 99mTc-MIBI/131I parathyroid imaging in chronic renal failure

International Nuclear Information System (INIS)

Tang Anwu; Luo Yaowu; Wu Yongkang; Pan Jianzhong; Ji Liangyuan

1995-01-01

20 chronic renal failure (CRF) patients and 15 normals were investigated with radionuclide parathyroid imaging and parathyroid hormone (PTH) RIA measurement for the detection of hyperparathyroidism. The serum PTH concentrations were 800.47 +- 665.25 pmol/L and 82.81 +- 13.79 pmol/L in two groups respectively. The radionuclide parathyroid images revealed that 1∼4 enlarged parathyroid glands were visualized in the CRF patients, none in the normals
The growth hormone-insulin-like growth factor axis in glycogen storage disease type 1: evidence of different growth patterns and insulin-like growth factor levels in patients with glycogen storage disease type 1a and 1b.

Science.gov (United States)

Melis, Daniela; Pivonello, Rosario; Parenti, Giancarlo; Della Casa, Roberto; Salerno, Mariacarolina; Balivo, Francesca; Piccolo, Pasquale; Di Somma, Carolina; Colao, Annamaria; Andria, Generoso

2010-04-01

To investigate the growth hormone (GH)-insulin-like growth factor (IGF) system in patients with glycogen storage disease type 1 (GSD1). This was a prospective, case-control study. Ten patients with GSD1a and 7 patients with GSD1b who were given dietary treatment and 34 sex-, age-, body mass index-, and pubertal stage-matched control subjects entered the study. Auxological parameters were correlated with circulating GH, either at basal or after growth hormone releasing hormone plus arginine test, insulin-like growth factors (IGF-I and IGF-II), and anti-pituitary antibodies (APA). Short stature was detected in 10.0% of patients with GSD1a, 42.9% of patients with GSD1b (P = .02), and none of the control subjects. Serum IGF-I levels were lower in patients with GSD1b (P = .0001). An impaired GH secretion was found in 40% of patients with GSD1a (P = .008), 57.1% of patients with GSD1b (P = .006), and none of the control subjects. Short stature was demonstrated in 3 of 4 patients with GSD1b and GH deficiency. The prevalence of APA was significantly higher in patients with GSD1b than in patients with GSD1a (P = .02) and control subjects (P = .03). The GH response to the provocative test inversely correlated with the presence of APA (P = .003). Compared with levels in control subjects, serum IGF-II and insulin levels were higher in both groups of patients, in whom IGF-II levels directly correlated with height SD scores (P = .003). Patients with GSD1a have an impaired GH secretion associated with reference range serum IGF-I levels and normal stature, whereas in patients with GSD1b, the impaired GH secretion, probably because of the presence of APA, was associated with reduced IGF-I levels and increased prevalence of short stature. The increased IGF-II levels, probably caused by increased insulin levels, in patients with GSD1 are presumably responsible for the improved growth pattern observed in patients receiving strict dietary treatment. Copyright 2010 Mosby, Inc. All
The effect of growth hormone replacement on the thyroid axis in patients with hypopituitarism: in vivo and ex vivo studies.

Science.gov (United States)

Glynn, Nigel; Kenny, Helena; Quisenberry, Leah; Halsall, David J; Cook, Paul; Kyaw Tun, Tommy; McDermott, John H; Smith, Diarmuid; Thompson, Christopher J; O'Gorman, Donal J; Boelen, Anita; Lado-Abeal, Joaquin; Agha, Amar

2017-05-01

Alterations in the hypothalamic-pituitary-thyroid axis have been reported following growth hormone (GH) replacement. The aim was to examine the relationship between changes in serum concentration of thyroid hormones and deiodinase activity in subcutaneous adipose tissue, before and after GH replacement. A prospective, observational study of patients receiving GH replacement as part of routine clinical care. Twenty adult hypopituitary men. Serum TSH, thyroid hormones - free and total thyroxine (T4) and triiodothyronine (T3) and reverse T3, thyroglobulin and thyroid-binding globulin (TBG) levels were measured before and after GH substitution. Changes in serum hormone levels were compared to the activity of deiodinase isoenzymes (DIO1, DIO2 and DIO3) in subcutaneous adipose tissue. The mean daily dose of growth hormone (GH) was 0·34 ± 0·11 mg (range 0·15-0·5 mg). Following GH replacement, mean free T4 levels declined (-1·09 ± 1·99 pmol/l, P = 0·02). Reverse T3 levels also fell (-3·44 ± 1·42 ng/dl, P = 0·03) and free T3 levels increased significantly (+0·34 ± 0·15 pmol/l, P = 0·03). In subcutaneous fat, DIO2 enzyme activity declined; DIO1 and DIO3 activities remained unchanged following GH substitution. Serum TSH, thyroglobulin and TBG levels were unaltered by GH therapy. In vitro analysis of subcutaneous adipose tissue from hypopituitary human subjects demonstrates that GH replacement is associated with significant changes in deiodinase isoenzyme activity. However, the observed variation in enzyme activity does not explain the changes in the circulating concentration of thyroid hormones induced by GH replacement. It is possible that deiodinase isoenzymes are differentially regulated by GH in other tissues including liver and muscle. © 2016 John Wiley & Sons Ltd.
Growth hormone/IGF-1 axis longitudinal evaluation in clinically isolated syndrome patients on interferon β-1b therapy: stimulation tests and correlations with clinical and radiological conversion to multiple sclerosis.

Science.gov (United States)

Lanzillo, R; Di Somma, C; Quarantelli, M; Carotenuto, A; Pivonello, C; Moccia, M; Cianflone, A; Marsili, A; Puorro, G; Saccà, F; Russo, C V; De Luca Picione, C; Ausiello, F; Colao, A; Brescia Morra, V

2017-02-01

Growth hormone (GH)/insulin-like growth factor 1 (IGF-1) axis abnormalities in multiple sclerosis (MS) suggest their role in its pathogenesis. Interferon β (IFN-β) efficacy could be mediated also by an increase of IGF-1 levels. A 2-year longitudinal study was performed to estimate the prevalence of GH and/or IGF-1 deficiency in clinically isolated syndrome (CIS) patients and their correlation with conversion to MS in IFN treated patients. Clinical and demographic features of CIS patients were collected before the start of IFN-β-1b. IGF-1 levels and GH response after arginine and GH releasing hormone + arginine stimulation tests were assessed. Clinical and magnetic resonance imaging evaluations were performed at baseline, 1 year and 2 years. Thirty CIS patients (24 female) were enrolled. At baseline, four patients (13%) showed a hypothalamic GH deficiency (GHD), whilst no one had a pituitary GHD. Baseline demographic, clinical and radiological data were not related to GHD, whilst IGF-1 levels were inversely related to age (P IGF-1 serum mean levels were not significantly modified after 1 and 2 years of treatment in the whole group, although 3/4 GHD patients experienced a normalization of GH levels, whilst one dropped out. After 2 years of treatment 13/28 (46%) patients converted to MS. The presence of GHD and GH and IGF-1 levels were not predictive of relapses, new T2 lesions or conversion occurrence. Growth hormone/IGF-1 axis function was found to be frequently altered in CIS patients, but this was not related to MS conversion. Patients experienced an improvement of GHD during IFN therapy. Longer follow-up is necessary to assess its impact on disease progression. © 2016 EAN.
Effects of Different Dietary Interventions on Calcitriol, Parathyroid Hormone, Calcium, and Phosphorus: Results from the DASH Trial

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Ahmed Hassoon

2018-03-01

Full Text Available The “Dietary Approaches to Stop Hypertension” (DASH diet, rich in fiber and low-fat dairy, effectively lowers blood pressure. DASH’s effect on calcitriol and other markers of bone-mineral metabolism is unknown. This secondary analysis of the DASH trial aimed to determine the effect of dietary patterns on blood concentrations of calcitriol, parathyroid hormone (PTH, ionized calcium, and urinary excretion of calcium and phosphorus. Outcomes were available in 334 participants in the trial. After a 3-week run-in on the control diet, participants were randomized to control, fruits and vegetables (F&V, or DASH diets. Outcomes were assessed at the end of run-in, and during the last week of the intervention period. Mean age of participants was 45.7 ± 10.7 years, 46% female, and 57% African-American. Mean ± Standard Deviation(SD baseline serum concentrations of calcitriol, PTH, and ionized calcium were 37.8 ± 9.2 pg/mL, 46.1 ± 18.5 pg/mL and 5.2 ± 0.23 mg/dL, respectively. Mean (±SD urinary calcium and phosphorus excretions were 150.1 ± 77.8 and 708.0 ± 251.8 mg/24 h, respectively. Compared with control, DASH reduced calcitriol −3.32 pg/mL (p = 0.004. Otherwise, there was no significant effect on other biomarkers. DASH lowered serum calcitriol perhaps more among African-Americans. These results raise important questions about the interpretation and clinical significance of low calcitriol concentrations in the setting of recommended diets.
Influence of thyroid hormones and transforming growth factor-β1 on cystatin C concentrations.

Science.gov (United States)

Kotajima, N; Yanagawa, Y; Aoki, T; Tsunekawa, K; Morimura, T; Ogiwara, T; Nara, M; Murakami, M

2010-01-01

Serum cystatin C concentrations are reported to increase in the hyperthyroid state. Serum concentrations of cystatin C and transforming growth factor-β1 (TGF-β1) were measured in patients with thyroid dysfunction, and the effects of 3,5,3'-tri-iodothyronine (T(3)) and TGF-β1 on cystatin C production in human hepatoblastoma (Hep G2) cells were studied. Serum concentrations of cystatin C and TGF-β1 were significantly higher in patients with Graves' disease compared with control subjects. Significantly positive correlations were observed between thyroid hormones and cystatin C, thyroid hormones and TGF-β1, and TGF-β1 and cystatin C in patients with thyroid dysfunction. Serum concentrations of cystatin C and TGF-β1 decreased after treatment for hyperthyroidism. Cystatin C mRNA levels and cystatin C secretion were increased by T(3) and TGF-β1 in cultured Hep G2 cells. These results suggest that serum cystatin C concentrations increase in patients with hyperthyroidism. The mechanisms for this may involve elevation of serum TGF-β1 levels and the stimulatory effects of T(3) and TGF-β1 on cystatin C production.
Lipid Profile and Thyroid Hormones in Types 1 and 2 Diabetics ...

African Journals Online (AJOL)

Literature describing relationship between thyroid hormones and lipid levels in Types 1 and 2 diabetics is scanty. Medications used in treating each of the two classes of diabetes differ and the effect of the various hypoglycemic agents on thyroid hormones varies, while thyroid hormone levels relate inversely with cholesterol ...
Catch-up growth in early treated patients with growth hormone deficiency. Dutch Growth Hormone Working Group.

OpenAIRE

Boersma, B; Rikken, B; Wit, J M

1995-01-01

Catch-up growth of 26 children with growth hormone deficiency during four years of growth hormone treatment, which was started young (< 3 years), was compared with that of 16 children with coeliac disease on a gluten free diet. In children with growth hormone deficiency mean (SD) height SD score increased from -4.3 (1.8) to -1.9 (1.4) and in patients with coeliac disease from -1.8 (0.9) to -0.1 (0.8). Height SD score after four years correlated positively with injection frequency and height S...
Calcium concentration in the CAPD dialysate

DEFF Research Database (Denmark)

Bro, S; Brandi, L; Daugaard, H

1998-01-01

OBJECTIVE: To evaluate risk/benefit of various continuous ambulatory peritoneal dialysis (CAPD) dialysate calcium concentrations. DATA SOURCES: A review of the literature on the effects of various CAPD dialysate Ca concentrations on plasma Ca, plasma phosphate, plasma parathyroid hormone (PTH......), doses of calcium carbonate, doses of vitamin D analogs, and requirements of aluminum-containing phosphate binders. STUDY SELECTION: Eleven studies of nonselected CAPD patients, and 13 studies of CAPD patients with hypercalcemia were reviewed. RESULTS: In nonselected CAPD patients, treatment...... with a reduced dialysate Ca concentration (1.00, 1.25, or 1.35 mmol/L) improved the tolerance to calcium carbonate and/or vitamin D metabolites and reduced the need for Al-containing phosphate binders. When using dialysate Ca 1.25 or 1.35 mmol/L, the initial decrease of plasma Ca and increase of PTH could easily...
Increased and Mistimed Sex Hormone Production in Night Shift Workers

OpenAIRE

Papantoniou, K; Pozo, OJ; Espinosa, A; Marcos, J; Castano-Vinyals, G; Basagana, X; Juanola Pages, E; Mirabent, J; Martin, J; Such Faro, P; Gasco Aparici, A; Middleton, B; Skene, DJ; Kogevinas, M

2015-01-01

BACKGROUND: Night shift work has been associated with an increased risk for breast and prostate cancer. The effect of circadian disruption on sex steroid production is a possible underlying mechanism, underinvestigated in humans. We have assessed daily rhythms of sex hormones and melatonin in night and day shift workers of both sexes. METHODS: We recruited 75 night and 42 day workers, ages 22 to 64 years, in different working settings. Participants collected urine samples from all voids over ...
A possible role for reproductive hormones in newborn boys

DEFF Research Database (Denmark)

Main, K M; Schmidt, I M; Skakkebaek, N E

2000-01-01

Healthy boys have a considerable production of reproductive hormones during the first postnatal months, the biological significance of which is poorly understood. We report on cases of male infants with hypogonadism (hypogonadotropic hypogonadism, n = 1; panhypopituitarism, n = 2) who showed lack...... of penile growth and involution of the scrotum. In two boys, diagnoses were obtained in early infancy and hormonal measurements at 3-4 months of age showed serum testosterone levels below detection limits in both low inhibin B (37 and 199 pg/mL, respectively; normal range, 193-563 pg/mL) and low......RH. All cases required hormonal treatment with testosterone, administered as suppositories in daily doses between 1 and 5 mg, which reintroduced male genital development. Our observations suggest that normal phallic and scrotal development in humans is dependent on intact testosterone secretion during...
Phosphate homeostasis in Bartter syndrome: a case-control study.

Science.gov (United States)

Bettinelli, Alberto; Viganò, Cristina; Provero, Maria Cristina; Barretta, Francesco; Albisetti, Alessandra; Tedeschi, Silvana; Scicchitano, Barbara; Bianchetti, Mario G

2014-11-01

Bartter patients may be hypercalciuric. Additional abnormalities in the metabolism of calcium, phosphate, and calciotropic hormones have occasionally been reported. The metabolism of calcium, phosphate, and calciotropic hormones was investigated in 15 patients with Bartter syndrome and 15 healthy subjects. Compared to the controls, Bartter patients had significantly reduced plasma phosphate {mean [interquartile range]:1.29 [1.16-1.46] vs. 1.61 [1.54-1.67] mmol/L} and maximal tubular phosphate reabsorption (1.16 [1.00-1.35] vs. 1.41 [1.37-1.47] mmol/L) and significantly increased parathyroid hormone (PTH) level (6.1 [4.5-7.7] vs. 2.8 [2.2-4.4] pmol/L). However, patients and controls did not differ in blood calcium, 25-hydroxyvitamin D, alkaline phosphatase, and osteocalcin levels. In patients, an inverse correlation (P Bartter patients.
Essential role of UCP1 modulating the central effects of thyroid hormones on energy balance

Science.gov (United States)

Alvarez-Crespo, Mayte; Csikasz, Robert I.; Martínez-Sánchez, Noelia; Diéguez, Carlos; Cannon, Barbara; Nedergaard, Jan; López, Miguel

2016-01-01

Objective Classically, metabolic effects of thyroid hormones (THs) have been considered to be peripherally mediated, i.e. different tissues in the body respond directly to thyroid hormones with an increased metabolism. An alternative view is that the metabolic effects are centrally regulated. We have examined here the degree to which prolonged, centrally infused triiodothyronine (T3) could in itself induce total body metabolic effects and the degree to which brown adipose tissue (BAT) thermogenesis was essential for such effects, by examining uncoupling protein 1 (UCP1) KO mice. Methods Wildtype and UPC1 KO mice were centrally-treated with T3 by using minipumps. Metabolic measurements were analyzed by indirect calorimetry and expression analysis by RT-PCR or western blot. BAT morphology and histology were studied by immunohistochemistry. Results We found that central T3-treatment led to reduced levels of hypothalamic AMP-activated protein kinase (AMPK) and elevated body temperature (0.7 °C). UCP1 was essential for the T3-induced increased rate of energy expenditure, which was only observable at thermoneutrality and notably only during the active phase, for the increased body weight loss, for the increased hypothalamic levels of neuropeptide Y (NPY) and agouti-related peptide (AgRP) and for the increased food intake induced by central T3-treatment. Prolonged central T3-treatment also led to recruitment of BAT and britening/beiging (“browning”) of inguinal white adipose tissue (iWAT). Conclusions We conclude that UCP1 is essential for mediation of the central effects of thyroid hormones on energy balance, and we suggest that similar UCP1-dependent effects may underlie central energy balance effects of other agents. PMID:27069867
Pulse versus daily oral Alfacalcidol treatment of secondary hyperparathyroidism in hemodialysis patients: a randomized controlled trial

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Sawalmeh O

2018-01-01

Full Text Available Osama Sawalmeh,1 Shaheed Moala,1 Zakaria Hamdan,2 Huda Masri,3 Khubaib Ayoub,4 Emad Khazneh,2 Mujahed Shraim5 1Medicine Department, Faculty of Medicine and Health Sciences, An-Najah National University, Nablus, Palestine; 2Nephrology Department, 3Pharmacy Department, 4Internal Medicine Department, An-Najah National University Hospital, Nablus, Palestine; 5Public Health Department, College of Health Sciences, Qatar University, Doha, Qatar Background: Secondary hyperparathyroidism is a common complication of chronic kidney disease and is managed using vitamin D replacement therapy. Very few studies have examined the effectiveness of pulse alfacalcidol therapy in comparison to daily oral alfacalcidol therapy in suppressing serum parathyroid hormone (PTH levels in hemodialysis patients. The aim of this randomized controlled trial was to replicate the findings of prior studies comparing effectiveness of pulse oral alfacalcidol therapy versus daily oral alfacalcidol therapy in suppressing PTH after 13 weeks of therapy using a Palestinian sample of hemodialysis patients, and to identify demographic and biomedical characteristics of patients that are independently associated with PTH levels.Methods: One hundred and sixty-seven patients completed the study, 88 in the daily group and 79 in the pulse group. The pulse group had more clinically significant reduction in mean PTH level by 75 pg/dL at 13 weeks than the daily group, but this was not statistically significant.Results: The effect of alfacalcidol therapy on metabolism of phosphate and corrected calcium levels was comparable in both groups, and pulse therapy was not associated with increased risk of hypercalcemia and hyperphosphatemia. Serum PTH levels were independently and inversely associated with older age and diabetes.Conclusion: Switching daily alfacalcidol therapy to thrice-weekly alfacalcidol pulse therapy seems safe and convenient, especially for hemodialysis patients with poor compliance
Knockin mouse with mutant Gα11 mimics human inherited hypocalcemia and is rescued by pharmacologic inhibitors

DEFF Research Database (Denmark)

Roszko, Kelly L; Bi, Ruiye; Gorvin, Caroline M

2017-01-01

in patients with autosomal-dominant hypocalcemia type 2 (ADH2), an inherited disorder of hypocalcemia, low parathyroid hormone (PTH), and hyperphosphatemia. We have generated knockin mice harboring the point mutation GNA11 c.C178T (p.Arg60Cys) identified in ADH2 patients. The mutant mice faithfully replicated...... human ADH2. They also exhibited low bone mineral density and increased skin pigmentation. Treatment with NPS 2143, a negative allosteric modulator of the calcium-sensing receptor (CASR), increased PTH and calcium concentrations in WT and mutant mice, suggesting that the gain-of-function effect of GNA11...
Increased oxidative metabolism and neurotransmitter cycling in the brain of mice lacking the thyroid hormone transporter SLC16A2 (MCT8).

Science.gov (United States)

Rodrigues, Tiago B; Ceballos, Ainhoa; Grijota-Martínez, Carmen; Nuñez, Barbara; Refetoff, Samuel; Cerdán, Sebastian; Morte, Beatriz; Bernal, Juan

2013-01-01

Mutations of the monocarboxylate transporter 8 (MCT8) cause a severe X-linked intellectual deficit and neurological impairment. MCT8 is a specific thyroid hormone (T4 and T3) transporter and the patients also present unusual abnormalities in the serum profile of thyroid hormone concentrations due to altered secretion and metabolism of T4 and T3. Given the role of thyroid hormones in brain development, it is thought that the neurological impairment is due to restricted transport of thyroid hormones to the target neurons. In this work we have investigated cerebral metabolism in mice with Mct8 deficiency. Adult male mice were infused for 30 minutes with (1-(13)C) glucose and brain extracts prepared and analyzed by (13)C nuclear magnetic resonance spectroscopy. Genetic inactivation of Mct8 resulted in increased oxidative metabolism as reflected by increased glutamate C4 enrichment, and of glutamatergic and GABAergic neurotransmissions as observed by the increases in glutamine C4 and GABA C2 enrichments, respectively. These changes were distinct to those produced by hypothyroidism or hyperthyroidism. Similar increments in glutamate C4 enrichment and GABAergic neurotransmission were observed in the combined inactivation of Mct8 and D2, indicating that the increased neurotransmission and metabolic activity were not due to increased production of cerebral T3 by the D2-encoded type 2 deiodinase. In conclusion, Mct8 deficiency has important metabolic consequences in the brain that could not be correlated with deficiency or excess of thyroid hormone supply to the brain during adulthood.
Increased oxidative metabolism and neurotransmitter cycling in the brain of mice lacking the thyroid hormone transporter SLC16A2 (MCT8.

Directory of Open Access Journals (Sweden)

Tiago B Rodrigues

Full Text Available Mutations of the monocarboxylate transporter 8 (MCT8 cause a severe X-linked intellectual deficit and neurological impairment. MCT8 is a specific thyroid hormone (T4 and T3 transporter and the patients also present unusual abnormalities in the serum profile of thyroid hormone concentrations due to altered secretion and metabolism of T4 and T3. Given the role of thyroid hormones in brain development, it is thought that the neurological impairment is due to restricted transport of thyroid hormones to the target neurons. In this work we have investigated cerebral metabolism in mice with Mct8 deficiency. Adult male mice were infused for 30 minutes with (1-(13C glucose and brain extracts prepared and analyzed by (13C nuclear magnetic resonance spectroscopy. Genetic inactivation of Mct8 resulted in increased oxidative metabolism as reflected by increased glutamate C4 enrichment, and of glutamatergic and GABAergic neurotransmissions as observed by the increases in glutamine C4 and GABA C2 enrichments, respectively. These changes were distinct to those produced by hypothyroidism or hyperthyroidism. Similar increments in glutamate C4 enrichment and GABAergic neurotransmission were observed in the combined inactivation of Mct8 and D2, indicating that the increased neurotransmission and metabolic activity were not due to increased production of cerebral T3 by the D2-encoded type 2 deiodinase. In conclusion, Mct8 deficiency has important metabolic consequences in the brain that could not be correlated with deficiency or excess of thyroid hormone supply to the brain during adulthood.
Circulating FGF23 levels in response to acute changes in plasma Ca(2+)

DEFF Research Database (Denmark)

Gravesen, E; Mace, M.L.; Hofman-Bang, J.

2014-01-01

The regulation of fibroblast growth factor 23 (FGF23) synthesis and secretion is still incompletely understood. FGF23 is an important regulator of renal phosphate excretion and has regulatory effects on the calciotropic hormones calcitriol and parathyroid hormone (PTH). Calcium (Ca) and phosphate...... FGF23 levels and whether a close relationship, similar that known for Ca and PTH, exists between Ca and FGF23. Thus, the aim of the present study was to examine whether acute hypercalcemia and hypocalcemia regulate FGF23 levels in the rat. Acute hypercalcemia was induced by an intravenous Ca infusion...... and hypocalcemia by infusion of ethylene glycol tetraacetic acid (EGTA) in normal and acutely parathyroidectomized rats. Intact plasma FGF23 and intact plasma PTH and plasma Ca(2+) and phosphate were measured. Acute hypercalcemia and hypocalcemia resulted as expected in adequate PTH secretory responses. Plasma FGF...
Calcium-phosphate and parathyroid intradialytic profiles: A potential aid for tailoring the dialysate calcium content of patients on different hemodialysis schedules.

Science.gov (United States)

Ferraresi, Martina; Pia, Anna; Guzzo, Gabriella; Vigotti, Federica Neve; Mongilardi, Elena; Nazha, Marta; Aroasio, Emiliano; Gonella, Cinzia; Avagnina, Paolo; Piccoli, Giorgina Barbara

2015-10-01

Severe hyperparathyroidism is a challenge on hemodialysis. The definition of dialysate calcium (Ca) is a pending issue with renewed importance in cases of individualized dialysis schedules and of portable home dialysis machines with low-flow dialysate. Direct measurement of calcium mass transfer is complex and is imprecisely reflected by differences in start-to-end of dialysis Ca levels. The study was performed in a dialysis unit dedicated to home hemodialysis and to critical patients with wide use of daily and tailored schedules. The Ca-phosphate (P)-parathyroid hormone (PTH) profile includes creatinine, urea, total and ionized Ca, albumin, sodium, potassium, P, PTH levels at start, mid, and end of dialysis. "Severe" secondary hyperparathyroidism was defined as PTH > 300 pg/mL for ≥3 months. Four schedules were tested: conventional dialysis (polysulfone dialyzer 1.8-2.1 m(2) ), with dialysate Ca 1.5 or 1.75 mmol/L, NxStage (Ca 1.5 mmol/L), and NxStage plus intradialytic Ca infusion. Dosages of vitamin D, calcium, phosphate binders, and Ca mimetic agents were adjusted monthly. Eighty Ca-P-PTH profiles were collected in 12 patients. Serum phosphate was efficiently reduced by all techniques. No differences in start-to-end PTH and Ca levels on dialysis were observed in patients with PTH levels dialysis on all schedules except on Nxstage (P dialysis, in "severe" secondary hyperparathyroid patients in order to increase the therapeutic potentials of the new dialysis techniques. © 2015 International Society for Hemodialysis.
Endogenous ovarian hormones affect mitochondrial efficiency in cerebral endothelium via distinct regulation of PGC-1 isoforms.

Science.gov (United States)

Kemper, Martin F; Zhao, Yuanzi; Duckles, Sue P; Krause, Diana N

2013-01-01

Mitochondria support the energy-intensive functions of brain endothelium but also produce damaging-free radicals that lead to disease. Previously, we found that estrogen treatment protects cerebrovascular mitochondria, increasing capacity for ATP production while decreasing reactive oxygen species (ROS). To determine whether these effects occur specifically in endothelium in vivo and also explore underlying transcriptional mechanisms, we studied freshly isolated brain endothelial preparations from intact and ovariectomized female mice. This preparation reflects physiologic influences of circulating hormones, hemodynamic forces, and cell-cell interactions of the neurovascular unit. Loss of ovarian hormones affected endothelial expression of the key mitochondrial regulator family, peroxisome proliferator-activated receptor γ coactivator 1 (PGC-1), but in a unique way. Ovariectomy increased endothelial PGC-1α mRNA but decreased PGC-1β mRNA. The change in PGC-1β correlated with decreased mRNA for crucial downstream mitochondrial regulators, nuclear respiratory factor 1 and mitochondrial transcription factor A, as well as for ATP synthase and ROS protection enzymes, glutamate-cysteine ligase and manganese superoxide dismutase. Ovariectomy also decreased mitochondrial biogenesis (mitochondrial/nuclear DNA ratio). These results indicate ovarian hormones normally act through a distinctive regulatory pathway involving PGC-1β to support cerebral endothelial mitochondrial content and guide mitochondrial function to favor ATP coupling and ROS protection.

Growth hormone transgenic tilapia (Oreochromis sp.) compensate for increased metabolic rate to preserve exercise performance and hypoxia tolerance

DEFF Research Database (Denmark)

McKenzie, D.J.; Martínez, R.; Morales, A.

2001-01-01

Transgenic tilapia hybrids (Oreochromis mossambicus × O. hornorum) carrying a single copy of a homologous cDNA growth hormone exhibit higher growth rates than their wild-type conspecifics (Martinez et al. 1999). Swimming respirometry was employed to determine whether the increased growth rate...... higher in transgenics, such that aerobic scope was similar in both groups, and there was no difference in maximum sustainable U (5.2 ± 0.5 vs. 4.5 ± 0.7 bl s-1 in transgenics vs. wild-types, respectively). Following 2 h recovery from exercise, tilapia were exposed to progressive hypoxia (stepwise......Pa, respectively). The results indicate that stimulation of growth consequent to ectopic expression of growth hormone in transgenic tilapia (Martinez et al. 1999) is linked to increased rates of maintenance metabolism. The swimming and hypoxia experiments indicate, however, that the transgenics were able...
Prolonged inhibition of luteinizing hormone and testosterone levels in male rats with the luteinizing hormone-releasing hormone antagonist SB-75.

Science.gov (United States)

Bokser, L; Bajusz, S; Groot, K; Schally, A V

1990-09-01

Inhibitory effects of the potent antagonist of luteinizing hormone-releasing hormone N-Ac-[3-(2-naphthyl)-D-alanine1,4-chloro-D-phenylalanine2,3- (3-pyridyl)-D- alanine3,D-citrulline6,D-alanine10]luteinizing hormone-releasing hormone (SB-75) free of edematogenic effects were investigated in male rats. In a study to determine the effect on luteinizing hormone levels in castrated male rats, SB-75 was injected s.c. in doses of 0.625, 1.25, 2.5, 5.0, and 10 micrograms. Blood samples were taken at different intervals for 48 hr. All doses of SB-75 significantly decreased luteinizing hormone levels for greater than 6 hr (P less than 0.01); this inhibition lasted for greater than 24 hr (P less than 0.01) with a dose of 5.0 micrograms and greater than 48 hr with 10 micrograms (P less than 0.05). Serum testosterone levels were also measured in intact male rats injected with SB-75 in doses of 25, 50, and 100 micrograms. All doses produced a dramatic fall in testosterone to castration levels 6 hr after injection (P less than 0.01); this inhibition of serum testosterone was maintained for greater than 72 hr, but only the 100-micrograms dose could keep testosterone in the castration range for greater than 24 hr (P less than 0.01). In another study using a specific RIA, we obtained the pharmacokinetic release pattern of SB-75 from two sustained delivery formulations of SB-75 pamoate microgranules and examined their effect on serum testosterone. After a single i.m. injection of 20 mg of one batch of microgranules, a large peak corresponding to SB-75 at 45.8 ng/ml was observed, corresponding to the "burst" effect. Levels of the analog decreased to 19.6 ng/ml on day 2, gradually reached a concentration of 4.7 ng/ml on day 7, and kept declining thereafter. Testosterone levels were reduced on day 1 (P less than 0.01) and were maintained at low values for greater than 7 days (P less than 0.05). In rats injected with 10 mg of SB-75 pamoate microgranules of the second batch, SB-75 serum
The interrelationships of thyroid and growth hormones: effect of growth hormone releasing hormone in hypo- and hyperthyroid male rats.

Science.gov (United States)

Root, A W; Shulman, D; Root, J; Diamond, F

1986-01-01

Growth hormone (GH) and the thyroid hormones interact in the hypothalamus, pituitary and peripheral tissues. Thyroid hormone exerts a permissive effect upon the anabolic and metabolic effects of GH, and increases pituitary synthesis of this protein hormone. GH depresses the secretion of thyrotropin and the thyroid hormones and increases the peripheral conversion of thyroxine to triiodothyronine. In the adult male rat experimental hypothyroidism produced by ingestion of propylthiouracil depresses the GH secretory response to GH-releasing hormone in vivo and in vitro, reflecting the lowered pituitary stores of GH in the hypothyroid state. Short term administration of large amounts of thyroxine with induction of the hyperthyroid state does not affect the in vivo GH secretory response to GH-releasing hormone in this animal.
Mice deleted for cell division cycle 73 gene develop parathyroid and uterine tumours: model for the hyperparathyroidism-jaw tumour syndrome.

Science.gov (United States)

Walls, G V; Stevenson, M; Lines, K E; Newey, P J; Reed, A A C; Bowl, M R; Jeyabalan, J; Harding, B; Bradley, K J; Manek, S; Chen, J; Wang, P; Williams, B O; Teh, B T; Thakker, R V

2017-07-13

The hyperparathyroidism-jaw tumour (HPT-JT) syndrome is an autosomal dominant disorder characterized by occurrence of parathyroid tumours, often atypical adenomas and carcinomas, ossifying jaw fibromas, renal tumours and uterine benign and malignant neoplasms. HPT-JT is caused by mutations of the cell division cycle 73 (CDC73) gene, located on chromosome 1q31.2 and encodes a 531 amino acid protein, parafibromin. To facilitate in vivo studies of Cdc73 in tumourigenesis we generated conventional (Cdc73 +/- ) and conditional parathyroid-specific (Cdc73 +/L /PTH-Cre and Cdc73 L/L /PTH-Cre) mouse models. Mice were aged to 18-21 months and studied for survival, tumour development and proliferation, and serum biochemistry, and compared to age-matched wild-type (Cdc73 +/+ and Cdc73 +/+ /PTH-Cre) littermates. Survival of Cdc73 +/- mice, when compared to Cdc73 +/+ mice was reduced (Cdc73 +/- =80%; Cdc73 +/+ =90% at 18 months of age, Pfourfold higher than that in parathyroid glands of wild-type littermates (P<0.0001). Cdc73 +/- , Cdc73 +/L /PTH-Cre and Cdc73 L/L /PTH-Cre mice had higher mean serum calcium concentrations than wild-type littermates, and Cdc73 +/- mice also had increased mean serum parathyroid hormone (PTH) concentrations. Parathyroid tumour development, and elevations in serum calcium and PTH, were similar in males and females. Cdc73 +/- mice did not develop bone or renal tumours but female Cdc73 +/- mice, at 18 months of age, had uterine neoplasms comprising squamous metaplasia, adenofibroma and adenomyoma. Uterine neoplasms, myometria and jaw bones of Cdc73 +/- mice had increased proliferation rates that were 2-fold higher than in Cdc73 +/+ mice (P<0.05). Thus, our studies, which have established mouse models for parathyroid tumours and uterine neoplasms that develop in the HPT-JT syndrome, provide in vivo models for future studies of these tumours.
A patient with thyrotropinoma cosecreting growth hormone and follicle-stimulating hormone with low alpha-glycoprotein: a new subentity?

Science.gov (United States)

Elhadd, Tarik A; Ghosh, Sujoy; Teoh, Wei Leng; Trevethick, Katy Ann; Hanzely, Zoltan; Dunn, Laurence T; Malik, Iqbal A; Collier, Andrew

2009-08-01

Thyrotropinomas are rare pituitary tumors. In 25 percent of cases there is autonomous secretion of a second pituitary hormone, adding to the clinical complexity. We report a patient with thyrotropin (TSH)-dependant hyperthyroidism along with growth hormone (GH) and follicle-stimulating hormone (FSH) hypersecretion but low alpha-glycoprotein (alpha-subunit) concentrations, a hitherto unique constellation of findings. A 67-year-old Scottish lady presented with longstanding ankle edema, paroxysmal atrial fibrillation, uncontrolled hypertension, fine tremors, warm peripheries, and agitation. Initial findings were a small goiter, elevated serum TSH of 7.37 mU/L (normal range, 0.30-6.0 mU/L), a free-thyroxine concentration of 34.9 pmol/L (normal range, 9.0-24.0 pmol/L), a flat TSH response to TSH-releasing hormone, and serum alpha-subunit of 3.1 IU/L (normal, hormone beta receptor by genotyping. Serum FSH was 56.8 U/L, but the luteinizing hormone (LH) was 23.6 U/L (postmenopausal FSH and LH reference ranges both >30 U/L) Basal insulin-like growth factor I was elevated to 487 microg/L with the concomitant serum GH being 14.1 mU/L, and subsequent serum GH values 30 minutes after 75 g oral glucose being 19.1 mU/L and 150 minutes later being 13.7 mU/L. An magnetic resonance imaging pituitary revealed a macroadenoma. Pituitary adenomectomy was performed with the histology confirming a pituitary adenoma, and the immunohistochemistry staining showed positive reactivity for FSH with scattered cells staining for GH and TSH. Staining for other anterior pituitary hormones was negative. After pituitary surgery she became clinically and biochemically euthyroid, the serum IFG-1 became normal, but the pattern of serum FSH and LH did not change. This case of plurihormonal thyrotropinoma is unique in having hypersecretion of TSH, GH, and FSH with low alpha-subunit. Such a combination may represent a new subentity of TSHomas.
Thyroid Hormones and Moderate Exposure to Perchlorate during Pregnancy in Women in Southern California.

Science.gov (United States)

Steinmaus, Craig; Pearl, Michelle; Kharrazi, Martin; Blount, Benjamin C; Miller, Mark D; Pearce, Elizabeth N; Valentin-Blasini, Liza; DeLorenze, Gerald; Hoofnagle, Andrew N; Liaw, Jane

2016-06-01

Findings from national surveys suggest that everyone in the United States is exposed to perchlorate. At high doses, perchlorate, thiocyanate, and nitrate inhibit iodide uptake into the thyroid and decrease thyroid hormone production. Small changes in thyroid hormones during pregnancy, including changes within normal reference ranges, have been linked to cognitive function declines in the offspring. We evaluated the potential effects of low environmental exposures to perchlorate on thyroid function. Serum thyroid hormones and anti-thyroid antibodies and urinary perchlorate, thiocyanate, nitrate, and iodide concentrations were measured in 1,880 pregnant women from San Diego County, California, during 2000-2003, a period when much of the area's water supply was contaminated from an industrial plant with perchlorate at levels near the 2007 California regulatory standard of 6 μg/L. Linear regression was used to evaluate associations between urinary perchlorate and serum thyroid hormone concentrations in models adjusted for urinary creatinine and thiocyanate, maternal age and education, ethnicity, and gestational age at serum collection. The median urinary perchlorate concentration was 6.5 μg/L, about two times higher than in the general U.S. Adjusted associations were identified between increasing log10 perchlorate and decreasing total thyroxine (T4) [regression coefficient (β) = -0.70; 95% CI: -1.06, -0.34], decreasing free thyroxine (fT4) (β = -0.053; 95% CI: -0.092, -0.013), and increasing log10 thyroid-stimulating hormone (β = 0.071; 95% CI: 0.008, 0.133). These results suggest that environmental perchlorate exposures may affect thyroid hormone production during pregnancy. This could have implications for public health given widespread perchlorate exposure and the importance of thyroid hormone in fetal neurodevelopment. Steinmaus C, Pearl M, Kharrazi M, Blount BC, Miller MD, Pearce EN, Valentin-Blasini L, DeLorenze G, Hoofnagle AN, Liaw J. 2016. Thyroid
Hormonal, anthropometric and lipid factors associated with idiopathic pubertal gynecomastia.

Science.gov (United States)

Al Alwan, Ibrahim; Al Azkawi, Hanan; Badri, Motasim; Tamim, Hani; Al Dubayee, Mohammed; Tamimi, Waleed

2013-01-01

To determine factors associated with pubertal gynecomastia. A cross-sectional study among healthy male school children and adolescents in Riyadh, Saudi Arabia. Subjects were selected from diverse socioeconomic backgrounds. Tanner stage, height, weight, blood hormonal levels (leutilizing hormone [LH], follicle-stimulating hormone [FSH], total testosterone, and estradiol), and anthropometric and lipid parameters (body mass index [BMI], triglycerides, high-density lipoprotein [HDL], and low-density lipoprotein [LDL]), were collected and compared in children with and without gynecomastia. The study included 542 children and adolescents. Median (interquartile range) age in the whole group was 11(8-13) years. The prevalence of gynecomastia was 185/542 (34%), with a peak at age 14. The 2 groups compared had nonsignificant difference in cholesterol (P=.331), LH (P=.215) and FSH (P=.571) levels. Those with gynecomastia were significantly older, had lower gonad stage, had higher anthropometric (height, weight, and BMI), and lipid (triglycerides, HDL, and LDL) values. In multivariate regression analysis, factors significantly associated with gynecomastia were BMI (odds ratio [OR]=1.05; 95%CI 1.00-1.10; P=.013), HDL (OR=0.42; 95%CI 0.19-0.92; P=.03), and gonad (Stage II OR=2.23; 95%CI 1.27-3.92; P=.005, Stage III OR=6.40; 95%CI 2.70-15.0; P gynecomastia tends to increase in mid-puberty. In our setting, BMI, HDL, and gonad stage were the major factors associated with the development of pubertal gynecomastia.
Trajectories of CKD-MBD biochemical parameters over a 2-year period following diagnosis of secondary hyperparathyroidism: a pharmacoepidemiological study.

Science.gov (United States)

Filipozzi, Pierre; Ayav, Carole; Ngueyon Sime, Willy; Laurain, Emmanuelle; Kessler, Michèle; Brunaud, Laurent; Frimat, Luc

2017-03-27

To define groups of patients according to the changes of biochemical parameters, that is, serum calcium, phosphate and parathyroid hormone (PTH), over a 2-year follow-up period using group-based multi-trajectory modeling (GBMM) among a cohort of dialysis patients with newly diagnosed secondary hyperparathyroidism (SHPT) (ie, PTH≥500 ng/L for the first time) and to compare their patient characteristics and treatments. Pharmacoepidemiological study. In the 12 dialysis units located in the French region of Lorraine. A total of 269 dialysis patients with newly diagnosed SHPT were prospectively included from December 2009 to May 2012 and followed-up for 2 years. We identified four distinct trajectory groups: 'rapid PTH drop' experiencing a rapid and sharp decrease (over weeks) in PTH level associated with decreasing phosphate level within normal range (n=34; 12.7%), 'gradual PTH decrease' experiencing a gradual and continuous decrease (over months) in PTH level and maintaining phosphate at a middle level throughout the study (n=98; 36.4%), 'slow PTH decrease with high phosphate' experiencing a slow decrease in PTH level associated with a relatively high phosphate level (n=105; 39.0%) and 'uncontrolled SHPT' with high levels of PTH and phosphate throughout the study (n=32; 11.9%). Patients in the 'uncontrolled SHPT' group were significantly (p<0.00001) younger than patients in other groups. Kidney Disease Improving Global Outcomes (KDIGO) targets for PTH, phosphate and calcium were reached simultaneously for 14.9% of patients at baseline and 16.7% at the end of the study. Patients were given cinacalcet more frequently at months 3 and 6 in the 'rapid PTH drop' and at month 24 in the 'uncontrolled SHPT' groups. Over 2 years following a new SHPT diagnosis, a younger age and a higher rate of alkaline phosphatase were associated to a continuous uncontrolled SHPT. Patients with the lowest PTH at the end of the follow-up tended to receive more often cinacalcet. Clinical
[Human growth hormone and Turner syndrome].

Science.gov (United States)

Sánchez Marco, Silvia Beatriz; de Arriba Muñoz, Antonio; Ferrer Lozano, Marta; Labarta Aizpún, José Ignacio; Garagorri Otero, Jesús María

2017-02-01

The evaluation of clinical and analytical parameters as predictors of the final growth response in Turner syndrome patients treated with growth hormone. A retrospective study was performed on 25 girls with Turner syndrome (17 treated with growth hormone), followed-up until adult height. Auxological, analytical, genetic and pharmacological parameters were collected. A descriptive and analytical study was conducted to evaluate short (12 months) and long term response to treatment with growth hormone. A favourable treatment response was shown during the first year of treatment in terms of height velocity gain in 66.6% of cases (height-gain velocity >3cm/year). A favourable long-term treatment response was also observed in terms of adult height, which increased by 42.82±21.23cm (1.25±0.76 SDS), with an adult height gain of 9.59±5.39cm (1.68±1.51 SDS). Predictors of good response to growth hormone treatment are: A) initial growth hormone dose, B) time on growth hormone treatment until starting oestrogen therapy, C) increased IGF1 and IGFBP-3 levels in the first year of treatment, and D) height gain velocity in the first year of treatment. Copyright © 2015 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.
Ovarian stimulation with follicle-stimulating hormone under increasing or minimal concentration of progesterone in dairy cows.

Science.gov (United States)

El-Sherry, T M; Matsui, M; Kida, K; Miyamoto, A; Megahed, G A; Shehata, S H; Miyake, Y-I

2010-03-01

The objective of this study was to investigate the effect of the presence or absence of Corpus luteum (CL) on the follicular population during superstimulation in dairy cows (Holstein-Friesian cattle). Animals were divided into two groups as follows: (1) Growing CL group (G1): Cows (n=7) received a total dose of 28 Armour units (AU) follicle-stimulating hormone (FSH) through the first 4 d (twice daily) after spontaneous ovulation (Day 0). (2) CL Absence group (G2): Cows (n=10) received prostaglandin F(2alpha) (PGF(2alpha)) at 9 or 10 d after ovulation. After 36h, all the follicles (larger than 5mm) were aspirated (Day 0). The FSH treatment started 24h after aspiration and continued for 4 d. The number of small (3 to or = 8mm) follicles was examined on Days 1, 3, and 5 in all groups. Blood samples were collected daily for 5 d, and progesterone (P(4)), estradiol (E(2)), insulin-like growth factor-1 (IGF-1), and growth hormone (GH) in plasma were measured by enzyme immunoassays. The results showed that in G1, the P(4) level increased gradually from 0.5 ng/mL at Day 1 to 2 ng/mL at Day 5, whereas in G2, the P(4) level was completely below 0.5 ng/mL. All cows of the G2 group showed an increase of E(2) at Day 3 or Day 4 followed by an increase of IGF-1 within 24h, while GH increased concomitantly with the E(2) increase in 8 of 10 trials. On the other hand, cows of the G1 group showed neither E(2) nor IGF-1 increase. Moreover, at the end of the treatment, the number of follicles in the G2 group was significantly increased compared with that of the G1 group (22.8+/-2.0 vs. 11.6+/-2.0). In conclusion, low P(4) level during FSH treatment enhanced multiple follicular growth and E(2) secretion, which was followed by increase of IGF-1 and GH. Therefore, the absence of the CL may play a critical role in the superovulation response by controlling the number of growing follicles. Copyright 2010 Elsevier Inc. All rights reserved.
Continuous and intermittent exposure of neonatal rat calvarial cells to PTHrP (1-36 inhibits bone nodule mineralization in vitro by downregulating bone sialoprotein expression via the cAMP signaling pathway [v2; ref status: indexed, http://f1000r.es/18x

Directory of Open Access Journals (Sweden)

Suzan A Kamel

2013-06-01

Full Text Available The development and growth of the skeleton in the absence of parathyroid-hormone-related protein (PTHrP is abnormal. The shortening of appendicular bones in PTHrP gene null mice is explained by an effect of PTHrP on endochondral bone growth. Whether or not PTHrP influences intramembranous ossification is less clear. The purpose of this study was to determine the effect of exogenous PTHrP on intramembranous ossification in vitro. Neonatal rat calvarial cells maintained in primary cell culture conditions that permit spontaneous formation of woven bone nodules by intramembranous ossification were studied. The expression of PTHrP, parathyroid hormone 1 receptor (PTH1R, and alkaline phosphatase (AP by osteogenic cells in developing nodules and the effects of PTHrP (1-36 on nodule development was determined over 3-18 days. PTHrP and PTH1R were detected colonies of osteogenic cells on culture day three, and AP was detected on day six. PTHrP and its receptor were localized in pre-osteoblasts, osteoblasts, and osteocytes, and AP activity was detected in pre-osteoblasts and osteoblasts but not osteocytes. Continuous and intermittent exposure to PTHrP (1-36 decreased the number of mineralized bone nodules and bone sialoprotein (BSP mRNA and protein, but had no effect on the number of AP-positive osteogenic cell colonies, cell proliferation, apoptosis, or osteopontin (OPN mRNA. These results demonstrate that osteogenic cells that participate in the formation of woven bone nodules in vitro exhibit PTHrP and PTH1R before they demonstrate AP activity. Exogenous PTHrP (1-36 inhibits the mineralization of woven bone deposited during bone nodule formation in vitro, possibly by reducing the expression of BSP.
Effect of Ramadan fasting in Saudi Arabia on serum bone profile and immunoglobulins.

Science.gov (United States)

Bahijri, Suhard M; Ajabnoor, Ghada M; Borai, Anwar; Al-Aama, Jumana Y; Chrousos, George P

2015-10-01

Each year Muslims fast from dawn to sunset for 1 month (Ramadan). In Saudi Arabia, the sleep-wake cycle during Ramadan is severely disturbed and is associated with abolition of the circadian cortisol rhythm, exposing Saudis to continuously increased cortisol levels, which may influence the immune response. In addition to cortisol, sleep and fasting affect the secretion of parathyroid hormone (PTH) and hence bone metabolism. Our objective was to investigate the effect of Ramadan type fasting on secretory patterns of PTH, markers of bone metabolism, and serum immunoglobulins. Blood samples from healthy young volunteers were collected at 9 a.m. and 9 p.m. (± 1 hour) before (Shaban) and 2 weeks into Ramadan. Calcium, phosphorus, magnesium, albumin, alkaline phosphatase, 25-OH vitamin D, intact PTH (iPTH), and immunoglobulin (Ig) A, M and G were measured. During Ramadan, evening-adjusted calcium was higher (p = 0.036) and phosphate lower (p Ramadan mean morning phosphate was higher and the evening level lower was than Shabaan values (p = 0.010 and p Ramadan (p = 0.003 and p = 0.021 for morning and evening, respectively). Changes in dietary practices during Ramadan modulated PTH secretion to a pattern which might be beneficial to bone health. Combined effects of fasting and disturbed sleep led to a noted decrease in IgG level. Therefore, a possible beneficial effect of fasting on bone turnover is combined with decreased immune response.
Transepithelial resistance and claudin expression in trout RTgill-W1 cell line: effects of osmoregulatory hormones.

Science.gov (United States)

Trubitt, Rebecca T; Rabeneck, D Brett; Bujak, Joanna K; Bossus, Maryline C; Madsen, Steffen S; Tipsmark, Christian K

2015-04-01

In the present study, we examined the trout gill cell line RTgill-W1 as a possible tool for in vitro investigation of epithelial gill function in fish. After seeding in transwells, transepithelial resistance (TER) increased until reaching a plateau after 1-2 days (20-80Ω⋅cm(2)), which was then maintained for more than 6 days. Tetrabromocinnamic acid, a known stimulator of TER via casein kinase II inhibition, elevated TER in the cell line to 125% of control values after 2 and 6h. Treatment with ethylenediaminetetraacetic acid induced a decrease in TER to hormone (Gh). The effects of three osmoregulatory hormones, Gh, prolactin, and cortisol, on the mRNA expression of three tight junction proteins were examined: claudin-10e (Cldn-10e), Cldn-30, and zonula occludens-1 (Zo-1). The expression of cldn-10e was stimulated by all three hormones but with the strongest effect of Gh (50-fold). cldn-30 expression was stimulated especially by cortisol (20-fold) and also by Gh (4-fold). Finally, zo-1 was unresponsive to hormone treatment. Western blot analysis detected Cldn-10e and Cldn-30 immunoreactive proteins of expected molecular weight in samples from rainbow trout gills but not from RTgill-W1 cultures, possibly due to low expression levels. Collectively, these results show that the RTgill-W1 cell layers have tight junctions between cells, are sensitive to hormone treatments, and may provide a useful model for in vitro study of some in vivo gill phenomena. Copyright © 2014 Elsevier Inc. All rights reserved.
Osteoporotic cytokines and bone metabolism on rats with induced hyperthyroidism; changes as a result of reversal to euthyroidism.

Science.gov (United States)

Simsek, Gönül; Karter, Yesari; Aydin, Seval; Uzun, Hafize

2003-12-31

Hyperthyroidism is characterized by increased bone turnover and resorptive activity. Raised levels of serum osteoporotic cytokines, such as interleukin (IL) -1beta, IL-6 and tumor necrosis factor (TNF)-alpha have been demonstrated previously in hyperthyroidism. These elevations are controversial and it is difficult to differentiate the contribution of thyroid hormones to the elevation of cytokines from that of the autoimmune inflammation in Graves' disease (GD) and follicular cell damage in thyroiditis. Therefore, we investigated the effect of thyroid hormones on serum IL-1beta, IL-6, TNF-alpha levels and bone metabolism on L-thyroxine induced hyperthyroid rats and changes in cytokine levels and bone metabolism on the same rats after reversal to euthyroidism. Rats were treated with L-thyroxine for 5 weeks (0.4 mg/ 100 g food). Plasma T3, T4, TSH and serum IL-1beta, IL-6, TNFalpha, Calcium (Ca), phosphorous (P), parathyroid hormone (PTH), alkaline phosphatase (ALP), bone alkaline phosphatase (B-ALP) levels were measured and differential leucocyte counts were made initially, at the 5th week of the experiment (hyperthyroid state) and 5 weeks after quitting the administration of L-thyroxine (euthyroid state). Significant rises in serum IL-1beta, IL-6 and TNFalpha were noted in hyperthyroidism (P hyperthyroid state while there was no correlation in euthyroid states. Ca and P levels did not differ significantly while PTH levels declined significantly in the hyperthyroid state (P hyperthyroidism (P hyperthyroid state (P metabolism in hyperthyroidism might be mediated by cytokines and the increased bone turnover in hyperthyroidism failed to decrease despite euthyroidism.
Challenges and Pitfalls in the Management of Parathyroid Carcinoma: 17-Year Follow-Up of a Case and Review of the Literature

NARCIS (Netherlands)

Witteveen, Janneke E.; Haak, Harm R.; Kievit, Job; Morreau, Hans; Romijn, Johannes A.; Hamdy, Neveen A. T.

2010-01-01

A 29-year-old man presented to his primary care physician with nausea, severe weight loss and muscle weakness. He had a hard, fixed neck swelling. He was severely hypercalcaemic with 10-fold increased parathyroid hormone (PTH) concentrations. A diagnosis of primary hyperparathyroidism was
Effect of neonatal hypothyroidism on prepubertal mouse testis in relation to thyroid hormone receptor alpha 1 (THRα1).

Science.gov (United States)

Sarkar, Debarshi; Singh, Shio Kumar

2017-09-15

Thyroid hormones (THs) are important for growth and development of many tissues, and altered thyroid status affects various organs and systems. Testis also is considered as a thyroid hormone responsive organ. Though THs play an important role in regulation of testicular steroidogenesis and spermatogenesis, the exact mechanism of this regulation remains poorly understood. The present study, therefore, is designed to examine the effect of neonatal hypothyroidism on prepubertal Parkes (P) strain mice testis in relation to thyroid hormone receptor alpha 1 (THRα1). Hypothyroidism was induced by administration of 6-propyl-2-thiouracil (PTU) in mother's drinking water from birth to day 28; on postnatal day (PND) 21 only pups, and on PND 28, both pups and lactating dams were euthanized. Serum T 3 and T 4 were markedly reduced in pups at PND 28 and in lactating mothers, while serum and intra-testicular testosterone levels were considerably decreased in pups of both age groups. Further, serum and intra-testicular levels of estrogen were significantly increased in hypothyroid mice at PND 28 with concomitant increase in CYP19 expression. Histologically, marked changes were noticed in testes of PTU-treated mice; immunohistochemical and western blot analyses of testes in treated mice also revealed marked decrease in the expression of THRα1 at both age groups. Semiquantitative RT-PCR and western blot analyses also showed reductions in both testicular mRNA and protein levels of SF-1, StAR, CYP11A1 and 3β-HSD in these mice. In conclusion, our results suggest that neonatal hypothyroidism alters localization and expression of THRα1 and impairs testicular steroidogenesis by down-regulating the expression SF-1, thereby affecting spermatogenesis in prepubertal mice. Copyright © 2016 Elsevier Inc. All rights reserved.
Cycling G1 CD34+/CD38+ cells potentiate the motility and engraftment of quiescent G0 CD34+/CD38-/low severe combined immunodeficiency repopulating cells.

Science.gov (United States)

Byk, Tamara; Kahn, Joy; Kollet, Orit; Petit, Isabelle; Samira, Sarit; Shivtiel, Shoham; Ben-Hur, Herzl; Peled, Amnon; Piacibello, Wanda; Lapidot, Tsvee

2005-04-01

The mechanism of human stem cell expansion ex vivo is not fully understood. Furthermore, little is known about the mechanisms of human stem cell homing/repopulation and the role that differentiating progenitor cells may play in these processes. We report that 2- to 3-day in vitro cytokine stimulation of human cord blood CD34(+)-enriched cells induces the production of short-term repopulating, cycling G1 CD34(+)/CD38(+) cells with increased matrix metalloproteinase (MMP)-9 secretion as well as increased migration capacity to the chemokine stromal cell-derived factor-1 (SDF-1) and homing to the bone marrow of irradiated nonobese diabetic severe/combined immunodeficiency (NOD/SCID) mice. These cycling G1 cells enhance SDF-1-mediated in vitro migration and in vivo homing of quiescent G0 CD34(+) cells, which is partially abrogated after inhibition of MMP-2/-9 activity. Moreover, the engraftment potential of quiescent G0 SCID repopulating cells (SRCs) is also increased by the cycling G1 CD34(+)/CD38(+) cells. This effect is significantly abrogated after incubation of cycling G1 cells with a neutralizing anti-CXCR4 antibody. Our data suggest synergistic interactions between accessory cycling G1 CD34(+)/CD38(+) committed progenitor cells and quiescent, primitive G0 CD34(+)/CD38(-/low) SRC/stem cells, the former increasing the motility and engraftment potential of the latter, partly via secretion of MMP-9.
Gonadotropin-releasing hormone analogues inhibit leiomyoma extracellular matrix despite presence of gonadal hormones.

Science.gov (United States)

Malik, Minnie; Britten, Joy; Cox, Jeris; Patel, Amrita; Catherino, William H

2016-01-01

To determine the effect of GnRH analogues (GnRH-a) leuprolide acetate (LA) and cetrorelix acetate on gonadal hormone-regulated expression of extracellular matrix in uterine leiomyoma three-dimensional (3D) cultures. Laboratory study. University research laboratory. Women undergoing hysterectomy for symptomatic leiomyomas. The 3D cell cultures, protein analysis, Western blot, immunohistochemistry. Expression of extracellular matrix proteins, collagen 1, fibronectin, and versican in leiomyoma cells 3D cultures exposed to E2, P, LA, cetrorelix acetate, and combinations for 24- and 72-hour time points. The 3D leiomyoma cultures exposed to E2 for 24 hours demonstrated an increased expression of collagen-1 and fibronectin, which was maintained for up to 72 hours, a time point at which versican was up-regulated significantly. Although P up-regulated collagen-1 protein (1.29 ± 0.04) within 24 hours of exposure, significant increase in all extracellular matrix (ECM) proteins was observed when the gonadal hormones were used concomitantly. Significant decrease in the amount of ECM proteins was observed on use of GnRH-a, LA and cetrorelix, with 24-hour exposure. Both the compounds also significantly decreased ECM protein concentration despite the presence of E2 or both gonadal hormones. This study demonstrates that GnRH-a directly affect the gonadal hormone-regulated collagen-1, fibronectin, and versican production in their presence. These findings suggest that localized therapy with GnRH-a may inhibit leiomyoma growth even in the presence of endogenous gonadal hormone exposure, thereby providing a mechanism to eliminate the hypoestrogenic side effects associated with GnRH-a therapy. Published by Elsevier Inc.
Desethylamiodarone is a competitive inhibitor of the binding of thyroid hormone to the thyroid hormone alpha 1-receptor protein

NARCIS (Netherlands)

van Beeren, H. C.; Bakker, O.; Wiersinga, W. M.

1995-01-01

Desethylamiodarone (DEA), the major metabolite of the potent antiarrythmic drug amiodarone, is a non-competitive inhibitor of the binding of thyroid hormone (T3) to the beta 1-thyroid hormone receptor (T3R). In the present study, we investigated whether DEA acts in a similar way with respect to the
Molecular Dynamics and Bioactivity of a Novel Mutated Human ...

African Journals Online (AJOL)

Keywords: Parathyroid hormone, Mutation prediction, Molecular dynamics, RANKL/OPG, UAMS-32P cell. Tropical .... PTH1R were used as MD simulation starting points. A full-atom ... Values of RMSD, Rg, and potential energy evaluation ...

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