Low dose PTH improves metaphyseal bone healing more when muscles are paralyzed.

Science.gov (United States)

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.

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

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

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.

Science.gov (United States)

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.

Endogenous PTH deficiency impairs fracture healing and impedes the fracture-healing efficacy of exogenous PTH(1-34.

Directory of Open Access Journals (Sweden)

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).

Science.gov (United States)

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.

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...

Pharmacokinetic and Pharmacodynamic Characteristics of Subcutaneously Applied PTH-1-37

Directory of Open Access Journals (Sweden)

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.

PTH Gene Polymorphism and Breast Cancer Risk in Kazakhstan

Directory of Open Access Journals (Sweden)

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

Down-regulation of parathyroid hormone (PTH) receptors in cultured bone cells is associated with agonist-specific intracellular processing of PTH-receptor complexes.

Science.gov (United States)

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

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)

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

Directory of Open Access Journals (Sweden)

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

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)

PTH levels and not serum phosphorus levels are a predictor of the progression of kidney disease in elderly patients with advanced chronic kidney disease

Directory of Open Access Journals (Sweden)

Néstor Gabriel Toapanta Gaibor

2017-03-01

Conclusions: 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.

Serum steroid levels in intact and endocrine ablated BALB/c nude mice and their intact littermates

DEFF Research Database (Denmark)

Brünner, N; Svenstrup, B; Spang-Thomsen, M

1986-01-01

An investigation was made of the serum steroid levels found in intact and endocrine ablated nude mice of both sexes and in their intact homozygous littermates. The results showed that nude mice have a normal steroidogenesis, but with decreased levels of circulating steroids compared to those...

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.

Science.gov (United States)

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.

Serum of 25-Hydroxyvitamin D and Intact Parathyroid Hormone Levels in Postmenopausal Women with Hip and Upper Limb Fractures.

Science.gov (United States)

Lv, Jiang-Tao; Zhang, Ying-Ying; Tian, Shao-Qi; Sun, Kang

2016-05-01

To assess the serum of 25-hydroxyvitamin D (25(OH)D) and intact parathyroid hormone (iPTH) levels in postmenopausal women from northern China with hip and upper limb fractures. Case-control. Affiliated Hospital of Qingdao University. Postmenopausal women diagnosed with hip fracture (n = 335) and matched controls without fracture (n = 335). Between 2011 and 2013, fasting venous samples were analyzed for 25(OH)D, iPTH, alkaline phosphatase (ALP), calcium, and phosphorus. All women completed a standardized questionnaire designed to document putative risk factors for fractures. Eight percent of participants had vitamin D deficiency, and 66.0% had secondary hyperparathyroidism. Serum 25(OH)D levels were significantly (P lower in women with hip fracture than in controls. Multivariate logistic regression analysis adjusted for common risk factors showed that serum 25(OH)D of 20 ng/mL or less was an independent indicator of hip fracture (odds ratio (OR) = 2.98, 95% confidence interval (CI) = 2.11-4.20) and concomitant upper limb fracture in those with existing hip fractures (OR = 4.77, 95% CI = 1.60-10.12). The area under the receiver operating characteristic curve of 25(OH)D was 0.77 (95% CI = 0.68-0.84) for hip fracture and 0.80 (95% CI = 0.72-0.89) for hip and upper limb fractures. Vitamin D insufficiency and secondary hyperparathyroidism were a common problem in postmenopausal women who presented with concomitant hip and upper limb fractures, suggesting that they might contribute to the pathophysiology of fractures in postmenopausal women. © 2016, Copyright the Authors Journal compilation © 2016, The American Geriatrics Society.

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)

Clinical significance of combined determination of serum BGP, PTH, CT in aged osteoporosis

International Nuclear Information System (INIS)

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

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.

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.

Correlation of Serum Magnesium with Serum Parathormone Levels in Patients on Regular Hemodialysis

Directory of Open Access Journals (Sweden)

Baradaran Azar

2006-01-01

Full Text Available Secondary hyperparathyroidism (SHPT is a common, important, and treatable complication of end-stage renal disease. This study was conducted to investigate the role of serum magnesium (Mg in regulating the secretion of parathyroid hormone (PTH by the parathyroid gland in patients on maintenance hemodialysis (HD. Pre-dialysis serum levels of calcium (Ca, phosphorus (P, Mg, alkaline phosphatase (ALP, intact serum PTH (iPTH, serum 25-hydroxy Vitamin D (25-OH Vit D and plasma bicarbonate (HCO3 were measured. The Urea Reduction Rate as well as duration and dosage of HD treatment were noted. Our study did not show any significant correlation between serum Mg levels and duration of HD treatment, levels of serum ALP, and plasma HCO3, Ca and P. An inverse correlation, albeit insignificant, was found between the serum Mg levels and iPTH (r=-0.30 p=0.079; also, a significant positive correlation was found between serum Mg levels and serum 25-OH Vit D levels (r= 0.40 p= 0.009. Our findings are in agreement with previous data, which suggest that factors other than serum Mg are more important in the regulation of PTH secretion in HD patients. A positive and strong association between serum Mg with 25-OH Vit D needs to be studied in greater detail.

Effectiveness of Intraoperative Parathyroid Monitoring (ioPTH) in predicting a multiglandular or malignant parathyroid disease.

Science.gov (United States)

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

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.

Clinicopathological Risk Factors and Biochemical Predictors of Safe Discharge after Total Thyroidectomy and Central Compartment Node Dissection for Thyroid Cancer: A Prospective Study

Directory of Open Access Journals (Sweden)

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.

PTH levels and not serum phosphorus levels are a predictor of the progression of kidney disease in elderly patients with advanced chronic kidney disease.

Science.gov (United States)

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.

Functional characterization and evolution of PTH/PTHrP receptors: insights from the chicken

Directory of Open Access Journals (Sweden)

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

Effects of growth hormone administration on bone mineral metabolism, PTH sensitivity and PTH secretory rhythm in postmenopausal women with established osteoporosis.

Science.gov (United States)

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

Decrease in the expression of the type 1 PTH/PTHrP receptor (PTH1R on chondrocytes in animals with osteoarthritis

Directory of Open Access Journals (Sweden)

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.

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

[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

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.

PTH prevents the adverse effects of focal radiation on bone architecture in young rats.

Science.gov (United States)

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.

PTH Assays: Understanding What We Have and Forecasting What We Will Have

Directory of Open Access Journals (Sweden)

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.

PTH treatment activates intracortical bone remodeling in patients with hypoparathyroidism

DEFF Research Database (Denmark)

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...

Two Years of Cinacalcet Hydrochloride Treatment Decreased Parathyroid Gland Volume and Serum Parathyroid Hormone Level in Hemodialysis Patients With Advanced Secondary Hyperparathyroidism.

Science.gov (United States)

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.

In vitro and preclinical assessment of an intranasal spray\\ud formulation of parathyroid hormone PTH 1-34 for the treatment of osteoporosis

OpenAIRE

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...

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

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

PTH1 receptor is involved in mediating cellular response to long-chain polyunsaturated fatty acids.

Directory of Open Access Journals (Sweden)

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.

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.

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.

Solution Structure of Archaeoglobus fulgidis Peptidyl-tRNA Hydrolase(Pth2) Provides Evidence for an Extensive Conserved Family of Pth2 Enzymes in Archaea, Bacteria and Eukaryotes.

Energy Technology Data Exchange (ETDEWEB)

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.

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...

Serum intact parathyroid hormone levels in cats with chronic kidney disease

Directory of Open Access Journals (Sweden)

Luciano H. Giovaninni

2013-02-01

Full Text Available Chronic kidney disease (CKD is frequently observed in cats and it is characterized as a multisystemic illness, caused by several underlying metabolic changes, and secondary renal hyperparathyroidism (SRHPT is relatively common; usually it is associated with the progression of renal disease and poor prognosis. This study aimed at determining the frequency of SRHPT, and discussing possible mechanisms that could contribute to the development of SRHPT in cats at different stages of CKD through the evaluation of calcium and phosphorus metabolism, as well as acid-base status. Forty owned cats with CKD were included and divided into three groups, according to the stages of the disease, classified according to the International Renal Interest Society (IRIS as Stage II (n=12, Stage III (n=22 and Stage IV (n=6. Control group was composed of 21 clinically healthy cats. Increased serum intact parathyroid hormone (iPTH concentrations were observed in most CKD cats in all stages, and mainly in Stage IV, which hyperphosphatemia and ionized hypocalcemia were detected and associated to the cause for the development of SRHPT. In Stages II and III, however, ionized hypercalcemia was noticed suggesting that the development of SRHPT might be associated with other factors, and metabolic acidosis could be involved to the increase of serum ionized calcium. Therefore, causes for the development of SRHPT seem to be multifactorial and they must be further investigated, mainly in the early stages of CKD in cats, as hyperphosphatemia and ionized hypocalcemia could not be the only factors involved.

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...

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

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.

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

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...

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

Science.gov (United States)

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

Small Molecule Binding, Docking, and Characterization of the Interaction between Pth1 and Peptidyl-tRNA

Directory of Open Access Journals (Sweden)

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.

Secondary hyperparathyroidism prevalence and profile, between diabetic and non-diabetic patients with stage 3 to 4 chronic kidney disease attended in internal medicine wards. MiPTH study.

Science.gov (United States)

Arévalo-Lorido, José Carlos; Carretero-Gómez, Juana; García-Sánchez, Francisco; Maciá-Botejara, Enrique; Ramiro-Lozano, José Manuel; Masero-Carretero, Antonio; Robles, Nicolás Roberto; Bureo-Dacal, Juan Carlos

2016-01-01

Secondary hyperparathyroidism (SHPTH) is a leading cause of renal osteodystrophy, and an independent risk factor for all-cause and cardiovascular mortality. Our aim is to establish differences in prevalence and profile of SHPTH, regarding diabetics or non-diabetics with chronic kidney disease (CKD). Cross-sectional multicenter study which included patients with stages 3 to 4 CKD. SHPTH was considered when the intact PTH levels (iPTH) were equal or higher than 70pg/ml. We divided the sample into two groups (diabetics and non-diabetics). We used robust statistical methods. 409 patients (214 diabetics) were studied. HPTH was found in 60.4% of diabetics vs 65% of non-diabetics (P=0.42). Diabetics with HPTH were younger (79.5 vs 82.3 years-old, P=0.005), and had more hypertension (P=0.0014), dyslipidemia (P=0.0001) and comorbidities. In multivariate analysis, we found a significant relationship in case of diabetics, with age (OR: 1.04, 95%CI 1.005-1.09 P=0.02 ), and with statins treatment (OR 2.3, 95%CI 1.17-4.54, P=0.01). The prevalence of SHPTH between the groups was similar, however, diabetics had more presence of hypertension and dyslipidemia, and SHPTH in this case was also related with moderate microalbuminuria and lower levels of vitamin D. An association with statins was also found in this group. Copyright © 2016 Diabetes India. Published by Elsevier Ltd. All rights reserved.

Dopamine enhances the phosphaturic effect of PTH during acute respiratory alkalosis.

Science.gov (United States)

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.

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

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.

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

Comparison of renal and osseous binding of parathyroid hormone and hormonal fragments

International Nuclear Information System (INIS)

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

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

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)

Vitamin D, PTH, and calcium in relation to survival following prostate cancer.

Science.gov (United States)

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

In vitro and preclinical assessment of an intranasal spray formulation of parathyroid hormone PTH 1-34 for the treatment of osteoporosis.

Science.gov (United States)

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.

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

Assessment of therapeutic effect in patients with secondary hyperparathyroidism using bone scintigraphy

International Nuclear Information System (INIS)

Kaida, Hayato; Ishibashi, Masatoshi; Baba, Kenkichi; Okuda, Seiya; Hayabuchi, Naofumi; Nishida, Hidemi; Hiromatsu, Yuji

2005-01-01

The semi-quantitative method of bone scintigraphy [bone to soft tissue (B/ST) ratio] has been used in diagnosing and evaluating systemic metabolic bone diseases. The aim of this study is to evaluate of the therapeutic effect of secondary hyperparathyroidism (SHP). The subjects were ten hemodialysis patients with SHP. Seven patients underwent parathyroidectomy (PTX), and 22-Oxacalcitoriol (derivative of 1, 25-dihydroxyvitamin D 3 ) (OCT) was given to three patients. Bone scintigraphy and blood tests [intact parathyroid hormone (PTH), alkaline phosphatase (ALP), calcium (Ca), phosphorus (P), bone alkaline phosphatase (BALP), and deoxypridinoline (DPYD)] were performed before and after treatment. Regions of interest were drown around cranium, lumbar vertebrae, femoral neck and soft tissue of left medial thigh to calculate the B/ST ratio. The B/ST ratios of cranium, lumbar vertebrae, and femoral neck were reduced significantly after PTX (cranium, p=0.0079, lumbar vertebrae, p=0.0282, femoral neck, p=0.0252). Intact PTH, ALP, Ca, P, BALP and DPYD levels were reduced significantly after PTX (intact PTH, p=0.003, Ca, p=0.0005, P, p=0.0393, ALP, p=0.005 1, DPYD, p=0.0232, BALP, p=0.0324). After OCT administration, the B/ST ratio of each bony region showed tendency to diminish, although not significantly. Intact PTH levels were reduced significantly, although ALP, BALP, and DPYD levels were not. Ca and P levels were increased significantly because of the medicinal action of OCT. The B/ST ratio of cranium may be non-invasive method and have potential in evaluating the therapeutic effect of SHP. (author)

All-atom simulation study of protein PTH(1-34) by using the Wang-Landau sampling method

Energy Technology Data Exchange (ETDEWEB)

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.

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.

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

Science.gov (United States)

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.

Endogenous PKI gamma limits the duration of the anti-apoptotic effects of PTH and beta-adrenergic agonists in osteoblasts.

Science.gov (United States)

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

Acute hypotension induced by aortic clamp vs. PTH provokes distinct proximal tubule Na+ transporter redistribution patterns

DEFF Research Database (Denmark)

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 (

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...

IgG4-Related Disease Combined with Autoimmune Hemolytic Anemia and Steroid-Responsive Transient Hypercalcemia

Directory of Open Access Journals (Sweden)

Sho Hasegawa

2015-01-01

Full Text Available A 67-year-old man with elevated serum immunoglobulin G4 (IgG4 levels, systemic lymphadenopathy infiltrated by IgG4-positive plasma cells, and Coombs-positive autoimmune hemolytic anemia (AIHA showed marked hypercalcemia. Although the intact parathyroid hormone (PTH level was elevated, 99mTc-MIBI scintigraphy and thyroid ultrasonography revealed no evidence of primary hyperparathyroidism. Liver biopsy showed marked infiltration of IgG4-positive plasma cells, which confirmed the diagnosis of IgG4-related disease (IgG4-RD. Corticosteroid therapy was initiated, and subsequently, intact PTH and serum calcium levels gradually normalized. Transient hypercalcemia in a patient with AIHA may therefore be associated with IgG4-RD.

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.

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.

Additive Effects of Mechanical Marrow Ablation and PTH Treatment on de Novo Bone Formation in Mature Adult Rats

Directory of Open Access Journals (Sweden)

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.

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...

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.

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)

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.

Positive Youth Development, Life Satisfaction and Problem Behaviors of Adolescents in Intact and Non-Intact Families in Hong Kong

Directory of Open Access Journals (Sweden)

Daniel Tan Lei Shek

2013-08-01

Full Text Available This study investigated whether Chinese adolescents living in intact and non-intact families differed in their positive development, life satisfaction, and risk behavior. A total of 3,328 Secondary 1 students responded to measures of positive youth development (such as resilience and psychosocial competencies, life satisfaction, and risk behavior (substance abuse, delinquency, Internet addiction, consumption of pornographic materials, self-harm, and behavioral intention to engage in problem behavior. Findings revealed that adolescents growing up in intact families reported higher levels of positive developmental outcomes and life satisfaction as compared with adolescents from non-intact families. Adolescents in non-intact families also reported higher levels of risk behaviors than those growing up in intact families.

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

Premenstrual Symptoms in Dysmenorrheic College Students: Prevalence and Relation to Vitamin D and Parathyroid Hormone Levels

Directory of Open Access Journals (Sweden)

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.

Serum uric acid is associated with left ventricular hypertrophy independent of serum parathyroid hormone in male cardiac patients.

Directory of Open Access Journals (Sweden)

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.

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.

Directory of Open Access Journals (Sweden)

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.

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).

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)

Recombinant human parathyroid hormone (PTH 1-34) and low-intensity pulsed ultrasound have contrasting additive effects during fracture healing.

Science.gov (United States)

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

Clinical Expression of Calcium Sensing Receptor Polymorphism (A986S) in Normocalcemic and Asymptomatic Hyperparathyroidism.

Science.gov (United States)

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

2016-03-01

Normocalcemic and asymptomatic hyperparathyroidism diagnosis are becoming more common. However, their pathophysiology is incompletely known. The aim of the present study was to evaluate the clinical effect of calcium-sensing receptor polymorphism (A986S) in normocalcemic and asymtomatic HPT. Prospective study conducted with 61 consecutive normocalcemic and asymptomatic HPT patients was followed up during a minimum period of 1 year. Secondary causes of hyperparathyroidism were ruled out. Calcium and phosphorus metabolism parameters were evaluated in at least 2 determinations during follow-up to classify as normocalcemic or asymptomatic hyperparathyroidism. Bone mineral density and A986S polymorphism genotype were also analyzed. Thiry-eight patients (62.3%) had the genotype A986A, and 23 (36.7%) patients had A986S (20 patients, 32.8%) or S986S (3 patients, 4.9%). Age, sex, and genotype distributions were comparable in both normocalcemic and asymptomatic hyperparathyroidism. In normocalcemic patients, S allele genotype was associated to statistically significant higher level of intact PTH: 92.0 (SD 18.5) vs. 110.6 (SD 24.4) pg/ml, phyperparathyroidism, A986A genotype resulted in a statistically significant higher level of intact PTH, alkaline phosphatase and procollagen amino-terminal propeptide; but only serum calcium remained as an independent predictor of serum intact PTH levels after a multiple linear regression. Bone mineral densitometry between genotypes did not show statistically significant differences. A986S polymorphism of CaSR is an independent predictor of PTH level in normocalcemic hyperparathyroidism patients, but not in asymptomatic hyperparathyroidism. More studies are needed to evaluate the effect of other polymorphisms in normocalcemic and asymptomatic hyperparathyroidism. © Georg Thieme Verlag KG Stuttgart · New York.

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

Directory of Open Access Journals (Sweden)

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.

Profile of chronic kidney disease related-mineral bone disorders in newly diagnosed advanced predialysis diabetic kidney disease patients: A hospital based cross-sectional study.

Science.gov (United States)

Ray, S; Beatrice, A M; Ghosh, A; Pramanik, S; Bhattacharjee, R; Ghosh, S; Raychaudhury, A; Mukhopadhyay, S; Chowdhury, S

2017-12-01

Chronic kidney disease related-mineral bone disorder (CKD-MBD) has been poorly studied in pre-dialysis Indian CKD population. There are limited data on the pattern of these disturbances in diabetic CKD patients. Therefore, a study was conducted to find out the profile of mineral bone disorders in T2DM patients with pre-dialysis CKD. In this cross-sectional design, diabetic patients with newly-diagnosed stage 4 and 5 CKD were evaluated. Serum levels of calcium, phosphorus, intact parathyroid hormone (iPTH), 25 hydroxy vitamin D and total alkaline phosphatase (ALP) were measured in all patients. Bone mineral density (BMD) was measured using dual-energy X-ray absorptiometry (DXA). A total of 72 eligible patients participated (44 males, 28 females; age 54.2±11.7). Patients with CKD Stage 5 had a lower level of corrected serum calcium and significantly higher level of inorganic phosphorus, total ALP and iPTH as compared to stage 4 patients. Overall, 38.5% were hypocalcemic, 31.43% were hyperphosphatemic. 24.2% of CKD subjects were vitamin D deficient (110pg/ml) was detected in nearly 43% of patients. In stage 5, only 32% patients was found to have hyperparathyroidism (iPTH>300pg/ml). There was a good correlation between iPTH and total ALP (r=0.5, p=0.0001) in this cohort. 25 (OH) vitamin D was inversely correlated with ALP (r=-0.39, P=0.001) and showed negative correlation with urine ACR (r=-0.37, P=0.002). As a group, the osteoporotic CKD subjects exhibited higher iPTH (220.1±153.8 vs. 119±108pg/ml, p<0.05) as compared to those who were osteopenic or had normal bone density. There was significant correlation between BMD and iPTH (adjusted r=-0.436; P=0.001). In the multivariate regression model, we found intact PTH to predict BMD even after adjustment of all the confounders. The current study showed that adynamic bone disease is prevalent even in pre-dialysis CKD population. High bone turnover disease may not be the most prevalent type in diabetic CKD. However, it

Postmeal increment in intact glucagon-like peptide 1 level, but not intact glucose-dependent insulinotropic polypeptide levels, is inversely associated with metabolic syndrome in patients with type 2 diabetes.

Science.gov (United States)

Yoo, Soyeon; Yang, Eun-Jin; Lee, Sang Ah; Koh, Gwanpyo

2018-02-01

Metabolic syndrome increases the risk of cardiovascular disease. Recently glucagon-like peptide 1 (GLP-1) agonists proved to be effective in preventing cardiovascular disease (CVD) in patients with type 2 diabetes. We investigated the association of blood incretin levels with metabolic syndrome in patients with type 2 diabetes. This is a cross-sectional study involving 334 people with type 2 diabetes. Intact GLP-1 (iGLP-1) and intact glucose-dependent insulinotropic polypeptide (iGIP) levels were measured in a fasted state and 30 min after ingestion of a standard mixed meal. Metabolic syndrome was diagnosed based on the criteria of the International Diabetes Federation. Two hundred twenty-five (69%) of the subjects have metabolic syndrome. The fasting iGLP-1 level was no different between groups. Thirty-min postprandial iGLP-1 was non-significantly lower in the subjects who had metabolic syndrome. Incremental iGLP-1 (ΔiGLP-1, the difference between 30-min postmeal and fasting iGLP-1 levels) was significantly lower in those with metabolic syndrome. There were no significant differences in fasting iGIP, postprandial iGIP, and ΔiGIP between groups. The ΔiGLP-1, but not ΔiGIP levels decreased significantly as the number of metabolic syndrome components increased. In hierarchical logistic regression analysis, the ΔiGLP-1 level was found to be a significant contributor to metabolic syndrome even after adjusting for other covariates. Taken together, the iGLP-1 increment in the 30 min after meal ingestion is inversely associated with metabolic syndrome in patients with type 2 diabetes. This suggests that postmeal iGLP-1 increment could be useful in assessing cardiovascular risk in type 2 diabetes.

The role of secondary hyperparathyroidism in left ventricular hypertrophy of patients under chronic hemodialysis

Directory of Open Access Journals (Sweden)

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.

Pegvisomant-induced serum insulin-like growth factor-I normalization in patients with acromegaly returns elevated markers of bone turnover to normal

DEFF Research Database (Denmark)

Parkinson, C; Kassem, M; Heickendorff, Lene

2003-01-01

of bone and soft tissue turnover, as well as levels of PTH and vitamin D metabolites, in 16 patients (nine males; median age, 52 yr; range, 28-78 yr) with active acromegaly (serum IGF-I at least 30% above upper limit of an age-related reference range). Serum procollagen III amino-terminal propeptide...... (PIIINP) and type I procollagen amino-terminal propeptide, osteocalcin (OC), bone-related alkaline phosphatase, C-terminal cross-linked telopeptide of type I collagen (CTx), albumin-corrected calcium, intact PTH, 25-hydroxy vitamin D, 1,25-dihydroxy vitamin D [1,25-(OH)(2) vit D], urinary type 1 collagen...... (CTx and urinary type 1 collagen cross-linked N-telopeptide/creatinine ratio). 1,25-(OH)(2) vit D decreased and intact PTH increased significantly, but 25-hydroxy vitamin D was unaffected. A significant decline in calculated calcium clearance was observed. The decrease in serum IGF-I correlated...

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

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.

Intact glycopeptide characterization using mass spectrometry.

Science.gov (United States)

Cao, Li; Qu, Yi; Zhang, Zhaorui; Wang, Zhe; Prytkova, Iya; Wu, Si

2016-05-01

Glycosylation is one of the most prominent and extensively studied protein post-translational modifications. However, traditional proteomic studies at the peptide level (bottom-up) rarely characterize intact glycopeptides (glycosylated peptides without removing glycans), so no glycoprotein heterogeneity information is retained. Intact glycopeptide characterization, on the other hand, provides opportunities to simultaneously elucidate the glycan structure and the glycosylation site needed to reveal the actual biological function of protein glycosylation. Recently, significant improvements have been made in the characterization of intact glycopeptides, ranging from enrichment and separation, mass spectroscopy (MS) detection, to bioinformatics analysis. In this review, we recapitulated currently available intact glycopeptide characterization methods with respect to their advantages and limitations as well as their potential applications.

A low plasma 1,25(OH)2 vitamin D/PTH (1-84) ratio predicts worsening of renal function in patients with chronic heart failure.

Science.gov (United States)

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.

The Evaluation of Fibroblast Growth Factor 23 Levels in Hypogonadotropic Hypogonadism

Directory of Open Access Journals (Sweden)

Hakan Demirci

2016-01-01

Full Text Available Aim: Our aim in this study was to investigate serum FGF-23 levels and its relationship with PTH, Ca and P in male patients with hypogonadotropic hypogonadism. Material and Method: Thirty-one male patients with hypogonadotropic hypogonadism and twenty healthy controls were enrolled in the study. The periferic venous blood samples of all the subjects involved in the study were taken for routine laboratory tests and serum testosteron, FSH, LH, PTH, P and Ca levels analysis. The serum samples were collected and stored at deep-freezer for serum FGF-23 level analysis. Results: It was observed that there was increase in serum P levels and there was decrease in PTH levels in patients with hypogonadotropic hypogonadism when compared with control group, however there was no difference in Ca and FGF-23 levels. It was determined that there were statistically significant difference between FGF-23 with P levels and PTH with Ca levels in correlation analysis. Discussion: The previous clinical studies have shown that there were bone metabolism disorders, secondary osteoporosis, changes in serum P and PTH levels in male patients with hypogonadotropic hypogonadism. In this study, we have observed that there is no correlation between all of those changes and one of the major regulators serum P, FGF-23.

Spectrophotometric Evaluation of the Pulpal Peroxide Levels in Intact and Restored Teeth - An Invitro Study.

Science.gov (United States)

Patri, Gaurav; Acharya, Gourismita; Agrawal, Pratik; Panda, Vijeta

2016-08-01

Hydrogen peroxide (30%) is a commonly used "in office" bleaching agent. Deleterious effects of hydrogen peroxide on the pulp have been observed. The present study was conducted with the aim to evaluate the penetration of 30% hydrogen peroxide into the pulp chamber through intact teeth and through the surface of teeth, restored with either hybrid composite or Resin Modified Glass Ionomer Cement (RMGIC). Sixty extracted human maxillary central incisors were selected and divided into six groups. Two groups were restored with hybrid composite resin and two with RMGIC, while two groups were left intact. The teeth with acetate buffer solution in their pulp cavity were then immersed in either 30% hydrogen peroxide or distilled water depending upon the group, for 60 minutes at 37°C. Then horseradish peroxidase and leucocrystal violet were added to the acetate buffer solution present in the pulp chamber after it was transferred to a test tube and the optical density of the resultant blue solution obtained was measured spectrophotometrically. The data obtained were analyzed using one way ANOVA and Student's t-test. The data obtained established that hydrogen peroxide penetrated into the pulp from the bleaching agent used. Hydrogen peroxide (30%) showed the highest pulpal peroxide level in teeth restored with RMGIC followed by teeth restored with hybrid composite resin and the least amount of penetration was observed in intact teeth. The amount of peroxide penetration into the tooth is more through restored tooth than intact tooth and is also dependant on the type of restorative materials used.

Original Article

African Journals Online (AJOL)

Elevated intact parathyroid hormone (PTH) among patients maintained on regular HD (group II and IV) may be explained by secondary hyperparathyroidism. It occurs early in the course of CRF mainly because of decreased calcitriol level, low serum calcium level and phosphorus retention [20]. Table 1: Laboratory data of ...

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....

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...

Efficacy and its predictor in microwave ablation for severe secondary hyperparathyroidism in patients undergoing haemodialysis.

Science.gov (United States)

Diao, Zongli; Liu, Xu; Qian, Linxue; Liu, Jing; Liu, Sha; Liu, Wenhu

2016-09-01

Microwave ablation (MWA) can be used to treat severe secondary hyperparathyroidism; however, its efficacy and the predictor of its efficacy are unclear. In this retrospective study we determined the predictor of efficacy of MWA and compared the efficacy of MWA and parathyroidectomy. Patients with severe secondary hyperparathyroidism who had received MWA or parathyroidectomy were enrolled in the study. Participants with MWA were divided into response and no response groups based on efficacy. Possible predictors were analysed using logistic regression to determine efficacy predictors. The participants were divided into MWA and parathyroidectomy groups, and the efficacy (including rates of achieving recommended goals for intact parathyroid hormone (iPTH), calcium, and phosphorus levels) were compared between the two groups. Thirty-one participants were enrolled for predictor analysis. Only baseline iPTH level predicted efficacy (OR 0.997, P = 0.018). The optimal threshold value of iPTH for predicting efficacy was 1493.5 pg/mL. To compare efficacy, 30 patients were enrolled in MWA (18/30) and parathyroidectomy (12/30) groups. The rates of achieving recommended goals for iPTH levels varied between 0 and 60%; a significant difference was found between the groups at 5 months (P = 0.01). However, in the parathyroidectomy group, the iPTH level and rate of iPTH secondary hyperparathyroidism; parathyroidectomy is more effective for severe secondary hyperparathyroidism than MWA.

Intact glycopeptide characterization using mass spectrometry

OpenAIRE

Cao, Li; Qu, Yi; Zhang, Zhaorui; Wang, Zhe; Prykova, Iya; Wu, Si

2016-01-01

Glycosylation is one of the most prominent and extensively studied protein post-translational modifications. However, traditional proteomic studies at the peptide level (bottom-up) rarely characterize intact glycopeptides (glycosylated peptides without removing glycans), so no glycoprotein heterogeneity information is retained. Intact glycopeptide characterization, on the other hand, provides opportunities to simultaneously elucidate the glycan structure and the glycosylation site needed to r...

Significant association between parathyroid hormone and uric acid level in men

Directory of Open Access Journals (Sweden)

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

High dose teriparatide (rPTH1-34) therapy increases callus volume and enhances radiographic healing at 8-weeks in a massive canine femoral allograft model.

Science.gov (United States)

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.

Directory of Open Access Journals (Sweden)

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.

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

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...

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...

Ihh and PTH1R signaling in limb mesenchyme is required for proper segmentation and subsequent formation and growth of digit bones.

Science.gov (United States)

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

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

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.

Impact of secondary hyperparathyroidism on ventricular mass regression after aortic valve replacement for aortic stenosis in hemodialysis-dependent patients.

Science.gov (United States)

Takami, Yoshiyuki; Tajima, Kazuyoshi

2015-07-01

In hemodialysis (HD)-dependent patients, secondary hyperparathyroidism induces cardiac hypertrophy. This study investigated whether parathyroid hormone (PTH) levels affect the degree of left ventricular (LV) mass regression in HD patients after aortic valve replacement (AVR) for aortic stenosis (AS). We retrospectively obtained preoperative and 2-year postoperative echocardiography and intact PTH measurements in 88 HD patients who underwent AVR, with bioprostheses (n = 35, 40%) and mechanical valves (n = 53, 60%) of effective orifice area >0.80 cm2/m2, between January 1997 and December 2010. The LV mass decreased significantly from 308 ± 88 to 217 ± 68 g at follow-up of 28 ± 4 months after AVR (p regression at follow-up was inversely related to preoperative PTH values (R = 0.44, p = 0.001). The LV mass regression at follow-up was significantly smaller in the patients (n = 47) with PTH ≥100 pg/mL than in those (n = 41) with PTH regression at 2-year follow-up (β = 0.23, r2 = 0.24, p = 0.02). In conclusion, the HD patients with high levels of PTH presented with less LV mass regression after AVR for AS without patient-prosthesis mismatch. Secondary hyperparathyroidism may impair regression of cardiac hypertrophy after AVR in HD patients with AS.

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

Teriparatida (PTH[1-34]rh: uma nova perspectiva no tratamento da osteoporose

Directory of Open Access Journals (Sweden)

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.

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.

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...

Fibroblast Growth Factor-23 and Vitamin D Metabolism in Subjects with eGFR ≥60 ml/min/1.73 m².

Science.gov (United States)

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.

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.

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

Directory of Open Access Journals (Sweden)

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

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.

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...

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

Fetuin-A and vitamin D receptor gene polymorphisms in hemodialysis patients

Directory of Open Access Journals (Sweden)

Shahnam Valizadeh-Shahbazloo

2014-08-01

Full Text Available Introduction: Vascular calcification is a common complication in the chronic kidney disease (CKD patients and the leading cause of morbidity and mortality in this patient. The aim of the present study was to evaluate a possible correlation between vitamin D receptor (VDR gene FokI and ApaI polymorphisms with the expression of calcification biomarkers such as Fetuin-A and intact parathyroid hormone (iPTH in hemodialysis (HD patients. Methods: In this cross-sectional study, serums were obtained from 46 stable chronic HD patients. The serum levels of iPTH, Fetuin-A, vitamin D, calcium, phosphorus, and VDR genotyping were determined by standard methods. Results: Serum levels of Fetuin-A, calcium, and phosphorus did not differ between males and females, but significant differences in iPTH and vitamin D levels was found in the study patients [(336.8 ± 139.0 pg/dl vs. (414.7 ± 111.8 pg/dl, P = 0.040 and (24.5 ± 7.6 ng/ml vs. (19.9 ± 4.8 ng/ml, P = 0.020 respectively]. A significant correlations were found between serum phosphorus and levels of serum calcium (r = –0.4; P = 0.002, vitamin D (r = –0.5; P = 0.001 and iPTH (r = 0.4; P = 0.001. iPTH level in FokI polymorphism, were different between genotype groups in study patient (P = 0.020. There was a significant positive correlation between vitamin D and iPTH levels in patients with aa genotype (P = 0.020, r = 0.4. Conclusion: These findings suggest that FokI (rs2228570 polymorphism in exon-2 of the VDR gene may play a role in iPTH levels. Fetuin-A deficiency or high level of iPTH and its association with VDR gene polymorphisms may be useful to identify the high-risk group susceptible to renal failure and atherosclerosis. Although VDR gene FokI and ApaI polymorphisms could affect the levels of Fetuin-A and vitamin D, their direct role on atherosclerosis needs further studies in the future.

Mechanisms of renal phosphate loss in liver resection-associated hypophosphatemia.

Science.gov (United States)

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 Association between Depression and Vitamin D and Parathyroid Hormone Levels in Adolescents

Directory of Open Access Journals (Sweden)

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.

Efficacy and safety of ultrasound-guided radiofrequency ablation of hyperplastic parathyroid gland for secondary hyperparathyroidism associated with chronic kidney disease.

Science.gov (United States)

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.

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.

Science.gov (United States)

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.

Distribution of genes for parathyroid hormone (PTH)-related peptide, Indian hedgehog, PTH receptor and patched in the process of experimental spondylosis in mice.

Science.gov (United States)

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.

Effects of hemodialysis on serum fetuin-A levels

Directory of Open Access Journals (Sweden)

Roman Safranek

2012-06-01

Full Text Available Fetuin-A is a calcification inhibitor, negative acute phase response marker and cardiovascular mortality predictor in hemodialysis patients. Low levels of fetuin-A are associated with malnutrition, inflammation, decreased bone mass density, low-turnover bone and use of high calcium concentration dialysate. Hemodialysis procedure (HD has been shown to decrease fetuin-A levels by 20%, probably due to HD-induced inflammation or acute changes in calcium metabolism. The aim of our study was to investigate effects of HD on serum fetuin-A levels. Forty clinically and hemodynamically stable hemodialysis patients (21 females, 68 (38-85 years underwent routine bicarbonate hemodialysis or hemodiafiltration with polysulfone dialyzer. On consecutive HD dialysis solution with different calcium concentration with/without citric acid was used to assess influence of calcium shifts and parathyroid activity on fetuin-A changes during HD. All other parameters of HD were kept constant. Serum fetuin-A, calcium, phosphorus, iPTH, CRP and other biochemical parameters were measured before and after each HD. Our data show that predialysis serum fetuin-A levels have positive correlation with iPTH levels (p<0.05 and tendency to decrease with higher CRP levels. There was no change in fetuin-A levels during HD: 206 (167.1; 231.9 ug/ml before and 208.9 (170.3; 246.3 ug/ml after HD; respectively. When corrected for haemoconcentration, decrease in fetuin-A was only 2.8% (p<0.05. There was also no difference between effect of hemodialysis and hemodia-filtration procedure. The use of different calcium dialysate concentrations had distinct effect on iPTH levels during and after HD, however, we observed no associated changes in fetuin-A levels. The use of dialysate solution with citric acid had no effect on fetuin-A levels. In conclusion, standard bicarbonate HD with polysulfone dialyser and ultrapure dialysate induces only minor changes in fetuin-A and no changes in hsCRP levels

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.

The TAL effector PthA4 interacts with nuclear factors involved in RNA-dependent processes including a HMG protein that selectively binds poly(U RNA.

Directory of Open Access Journals (Sweden)

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.

Temporal trends and determinants of longitudinal change in 25-hydroxyvitamin D and parathyroid hormone levels.

Science.gov (United States)

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.

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....

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

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

Relation of bone mineral density with homocysteine and cathepsin K levels in postmenopausal women

Directory of Open Access Journals (Sweden)

Madhukar Mittal

2018-01-01

Full Text Available Background: Homocysteine (HCY interferes with collagen cross-linking in bones and stimulates osteoclast activity. The activated osteoclasts secrete cathepsin K (CathK, a cysteine protease, in eminent quantity during bone resorption. Hyperhomocysteinemia may effect bone mineral density (BMD through CathK. We, therefore, examined the relation between HCY and BMD along with CathK, 25-hydroxyvit-D (25[OH]D, intact parathyroid hormone (iPTH, and Vitamin B12. Materials and Methods: We recruited a total of 93 postmenopausal women between the age group of 45–60 years, attending the Endocrinology outpatient department at King George's Medical University, Lucknow. BMD was done by DXA scan using Hologic QDR1000 system. Based on the WHO criteria, patients were segregated into three groups as follows; normal bone mass, osteopenia, and osteoporosis. All women underwent routine biochemical laboratory parameters, HCY, Vitamin B12, and CathK levels. Results: Among 93 postmenopausal women, 56% (52 had osteoporosis. Nineteen percent (18 had normal BMD (mean age, 53.22 ± 8.5 years and 23 (25% had osteopenia (mean age 52.86 ± 6.67 years. The mean age in the osteoporetic group was 56.2 ± 6.9 years. The median (interquartile range levels of HCY in the three groups were 14.5 μmol/L (12.2–24.7, 15.05 μmol/L (12.1–19.9 and 13.2 μmol/L (10.3–17.0, respectively. CathK levels were similar in three groups 7.6 ng/ml (7.0–80.5, 8.3 ng/ml (7.3–8.5, and 8.6 ng/ml (7.2–8.9. Both HCY and CathK were found positively associated with serum phosphorus (r = 0.584, P < 2.01 and r = 0.249, P < 0.05, respectively. Levels of HCY positively correlate with PTH (r = 0.303, P < 0.01 and inversely with Vitamin B12 (r = −0.248, P < 0.05. No significant association was seen between CathK level and 25(OH D, iPTH, serum calcium. Conclusion: Low bone mass by DXA is a significant problem in postmenopausal females. HCY and CathK do not reliably correlate with bone loss in

A new human NHERF1 mutation decreases renal phosphate transporter NPT2a expression by a PTH-independent mechanism.

Directory of Open Access Journals (Sweden)

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.

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...

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.

Prevalence of secondary hyperparathyroidism in patients with stage 3 and 4 chronic kidney disease seen in internal medicine.

Science.gov (United States)

Bureo, Juan Carlos; Arévalo, Jose Carlos; Antón, Joaquín; Adrados, Gaspar; Jiménez Morales, Jose Luis; Robles, Nicolás Roberto

2015-01-01

Despite the high prevalence of chronic kidney disease in the elderly population, few data are available on the frequency of secondary hyperparathyroidism in the Spanish population affected by this problem. We undertook a study on this issue in patients attending the internal medicine departments in our area. An observational, cross-sectional survey performed at internal medicine departments on 415 patients with stage 3 and 4 chronic kidney disease. Clinical history and risk factors were collected using a standardized protocol. Serum creatinine, phosphate, calcium, intact parathormone (PTH) and 25-hydroxy-cholecalciferol (25-OH-vitD) levels were measured in all patients. Among stage 3 patients, 62.9% had PTH levels ≥70pg/mL and 32.7% levels ≥110pg/mL. Median PTH level in stage 4 patients was 120pg/mL (p <0.001), and 77.9% of these patients had PTH ≥70pg/mL (p <0.001) and 54.1% ≥110pg/mL (p=0.015). Adequate 25-hydroxy-cholecalciferol levels were found in only 7.2% of stage 3 patients and 4.1% of stage 4 patients. Only 7.2% of stage 3 patients had hyperphosphatemia, as compared to 25.4% of stage 4 patients (p <0.001). Hyperparathyroidism is a common complication of stage 3 and 4 chronic kidney disease which is not associated to detectable changes in serum calcium and phosphate levels. It is therefore advisable to measure PTH levels in all patients with decreased glomerular filtration rate. Copyright © 2015 SEEN. Published by Elsevier España, S.L.U. All rights reserved.

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

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)

Tolerance and efficacy of a low dose of the calcimimetic agent cinacalcet in controlling moderate to severe secondary hyperparathyroidism in hemodialysis patients.

Science.gov (United States)

Bashir, Salah O; Omer, Hayder A; Aamer, Mahmoud A; Somialy, Rashid; Morsy, Mohamed D

2015-11-01

Secondary hyperparathyroidism is almost a constant feature in chronic kidney disease (CKD) patients maintained on hemodialysis (HD). Calcimimetic agents appear to offer an alternative to surgery in controlling secondary hyperparathyroidism in these patients. Recent studies provide conflicting data on the benefits, efficacy and tolerance of cinacalcet as first-line therapy for the treatment of secondary hyperparathyroidism in CKD. This study was designed to investigate the efficacy and tolerance of a low dose of the calcimimetic agent cinacalcet in patients on long-term HD having moderate to severe secondary hyperparathyroidism. Twenty five adult male patients on HD for more than three years were included in the study. All had moderate to severe secondary hyperparathyroidism with serum intact parathyroid hormone (iPTH) >50 pmol/L, resistant to conventional treatment. We used the targets of Chronic Kidney Disease: Outcomes Quality Initiative (K/DOQI) clinical guidelines as optimal target of serum iPTH, calcium and phosphate. Patients were administered cinacalcet as a single oral daily dose of 30 mg and were followed-up for six months. Cinacalcet treatment for six months resulted in a significant reduction in the serum phosphate and iPTH levels while the serum calcium levels remained unchanged. Thirty-six percent of the patients attained the recommended serum iPTH levels, 40% achieved significant reduction of the serum iPTH levels and 24% showed no favorable response. Only one patient dropped out because of severe gastrointestinal symptoms. Our results suggest that treatment of CKD patients, having moderate to severe secondary hyperparathyroidism, with low-dose cinacalcet is effective and well tolerated.

Threshold levels of 25-hydroxyvitamin D and parathyroid hormone for impaired bone health in children with congenital ichthyosis and type IV and V skin.

Science.gov (United States)

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.

Plasma intact fibroblast growth factor 23 levels in women with anorexia nervosa

Directory of Open Access Journals (Sweden)

Otani Makoto

2008-04-01

Full Text Available Abstract Background Fibroblast growth factor (FGF23 is a novel phosphaturic factor associated with inorganic phosphate homeostasis. Previous human studies have shown that serum FGF23 levels increase in response to a high phosphate diet. For anorexia nervosa (AN patients, inorganic phosphate homeostasis is important in the clinical course, such as in refeeding syndrome. The purpose of this study was to determine plasma levels of intact FGF23 (iFGF23 in restricting-type AN (AN-R patients, binge-eating/purging-type AN (AN-BP patients, and healthy controls. Methods The subjects consisted of 6 female AN-R patients, 6 female AN-BP patients, and 11 healthy female controls; both inpatients and outpatients were included. Plasma iFGF23, 1,25-dihydroxyvitamin D (1,25-(OH2D, and 25-hydroxyvitamin D (25-OHD levels were measured. Data are presented as the median and the range. A two-tailed Mann-Whitney U-test with Bonferroni correction was used to assess differences among the three groups, and a value of p Results There were no differences between AN-R patients and controls in the iFGF23 and 1,25-(OH2D levels. In AN-BP patients, the iFGF23 level (41.3 pg/ml; range, 6.1–155.5 pg/ml was significantly higher than in controls (3.8 pg/ml; range, not detected-21.3 pg/ml; p = 0.001, and the 1,25-(OH2D was significantly lower in AN-BP patients (7.0 pg/ml; range, 4.2–33.7 pg/ml than in controls (39.7 pg/ml; range, 6.3–58.5 pg/ml; p = 0.015. No differences in plasma 25-OHD levels were observed among the groups. Conclusion This preliminary study is the first to show that plasma iFGF23 levels are increased in AN-BP patients, and that these elevated plasma FGF23 levels might be related to the decrease in plasma 1,25-(OH2D levels.

Pregnancy-associated plasma protein-A in patients on Maintenance Hemodialysis

International Nuclear Information System (INIS)

Abdel-Messeih, Ph.L.

2012-01-01

A high level of serum pregnancy associated plasma protein-A (PAPP-A) has been observed in patients suffering from renal impairment. The aim of the present study is to evaluate the level of PAPP-A and to elucidate its relationship with renal osteodystrophy and renal functions in patients maintained on hemodialysis (HD). Intact parathyroid hormone (i-PTH), calcium (Ca) and phosphorus (P) levels and alkaline phosphatase activity (ALP) were measured in the serum as markers of renal osteodystrophy while the level of blood urea and serum creatinine were evaluated as markers of renal functions. The results obtained showed that for patients maintained on HD, the levels of PAPP-A, i-PTH, P, urea and creatinine, were significantly higher than controls. Significant positive correlations were obtained between PAPP-A and each of i-PTH, ALP and creatinine in the same group. After dialysis session, the level of PAPP-A increased significantly, compared to its pre -dialysis level. According to the results obtained in the current study, it could be concluded that the increase in PAPP-A level in the serum of patients maintained on hemodialysis is probably the result of chronic inflammation and impairment of kidney functions rather than renal osteodystrophy

Autism Spectrum Disorder and intact executive functioning.

Science.gov (United States)

Ferrara, R; Ansermet, F; Massoni, F; Petrone, L; Onofri, E; Ricci, P; Archer, T; Ricci, S

2016-01-01

Earliest notions concerning autism (Autism Spectrum Disorders, ASD) describe the disturbance in executive functioning. Despite altered definition, executive functioning, expressed as higher cognitive skills required complex behaviors linked to the prefrontal cortex, are defective in autism. Specific difficulties in children presenting autism or verbal disabilities at executive functioning levels have been identified. Nevertheless, the developmental deficit of executive functioning in autism is highly diversified with huge individual variation and may even be absent. The aim of the present study to examine the current standing of intact executive functioning intact in ASD. Analysis of ASD populations, whether high-functioning, Asperger's or autism Broad Phenotype, studied over a range of executive functions including response inhibition, planning, cognitive flexibility, cognitive inhibition, and alerting networks indicates an absence of damage/impairment compared to the typically-developed normal control subjects. These findings of intact executive functioning in ASD subjects provide a strong foundation on which to construct applications for growth environments and the rehabilitation of autistic subjects.

Clinically Relevant Levels of 4-Aminopyridine Strengthen Physiological Responses in Intact Motor Circuits in Rats, Especially After Pyramidal Tract Injury.

Science.gov (United States)

Sindhurakar, Anil; Mishra, Asht M; Gupta, Disha; Iaci, Jennifer F; Parry, Tom J; Carmel, Jason B

2017-04-01

4-Aminopyridine (4-AP) is a Food and Drug Administration-approved drug to improve motor function in people with multiple sclerosis. Preliminary results suggest the drug may act on intact neural circuits and not just on demyelinated ones. To determine if 4-AP at clinically relevant levels alters the excitability of intact motor circuits. In anesthetized rats, electrodes were placed over motor cortex and the dorsal cervical spinal cord for electrical stimulation, and electromyogram electrodes were inserted into biceps muscle to measure responses. The motor responses to brain and spinal cord stimulation were measured before and for 5 hours after 4-AP administration both in uninjured rats and rats with a cut lesion of the pyramidal tract. Blood was collected at the same time as electrophysiology to determine drug plasma concentration with a goal of 20 to 100 ng/mL. We first determined that a bolus infusion of 0.32 mg/kg 4-AP was optimal: it produced on average 61.5 ± 1.8 ng/mL over the 5 hours after infusion. This dose of 4-AP increased responses to spinal cord stimulation by 1.3-fold in uninjured rats and 3-fold in rats with pyramidal tract lesion. Responses to cortical stimulation also increased by 2-fold in uninjured rats and up to 4-fold in the injured. Clinically relevant levels of 4-AP strongly augment physiological responses in intact circuits, an effect that was more robust after partial injury, demonstrating its broad potential in treating central nervous system injuries.

The spectrum of bone disease in Jordanian hemodialysis patients

International Nuclear Information System (INIS)

Younes, Nidal A.; Al-Mansour, M.; Sroujieh, Ahmad S.; Wahbeh, A.; Ailabouni, W.; Hamzah, Y.; Mahafzah, W.

2006-01-01

To evaluate the spectrum of mineral abnormalities and bone disease (BD) in hemodialysis patients at Jordan University Hospital (JUH), Amman, Jordan. A cross-sectional study was conducted among 63 patients (38 males and 25 females), mean age 44.19 years (range 17-76 years), with chronic kidney disease (CKD) on regular hemodialysis at JUH between November 2004 and April 2005. All patients have undergone complete blood count, chemistry profile, alkaline phosphatase, serum albumin, intact parathyroid hormone (iPTH) and plain x-rays. Bone disorders were identified in 45 patients on x-rays (70%). Osteopenia was found in 43 patients (68.3%), subperiosteal resorption in 24 patients (38.3%) and metastatic calcification in 22 patients (35%). Hypocalcemia was found in 28.6% and hypercalcemia in 7.9%. All patients were taking calcium carbonate, and 55.5% of patients were on vitamin D supplements. The calcium levels in 63.5% and the phosphorus levels in 50.8% of patients were within the recommended guidelines of the National Kidney Foundation Kidney Disease Outcomes Quality Initiative (K/DOQI). Serum i-PTH level was above 300 pg/ml high turnover bone disease in 24.6% of patients, 21.3% had iPTH of 150-300 pg/ml target, and 44.3% had i-PTH levels below 100 pg/mL suggesting a dynamic bone disease. Patients with severe bone disease had a statistically significant higher iPTH levels (p<0.005). Bone disease and mineral abnormalities are common in hemodialysis patients at JUH. Earlier detection of bone disease and better overall management strategy may reduce the frequency and severity of bone disease in CKD patients in Jordan. (author)

Benefits resulting from 1- and 6-hour parathyroid hormone and calcium levels after thyroidectomy.

Science.gov (United States)

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.

Parathyroid carcinoma in tertiary hyperparathyroidism.

Science.gov (United States)

Kim, Byung Seup; Ryu, Han Suk; Kang, Kyung Ho; Park, Sung Jun

2016-10-01

Parathyroid carcinoma is a rare disease of unknown etiology. This study presents a case of parathyroid carcinoma in a patient with tertiary hyperparathyroidism. Despite a successful kidney transplantation, the intact parathyroid hormone (iPTH) level of the patient was elevated consistently and could not be controlled by medical therapy. Due to the development of tertiary hyperparathyroidism with bone pain and osteoporosis, subtotal parathyroidectomy was performed 4 months after the kidney transplantation. Histological evaluation revealed that one of four parathyroid lesions was a parathyroid carcinoma, while the others were diffuse hyperplasia. Postoperative laboratory studies indicated a decreased level of iPTH. A positron emission tomography-computed tomography performed 6 months after the operation revealed no evidence of local recurrence or distant metastasis. Copyright © 2013. Published by Elsevier Taiwan.

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.

Ultrasound Detection of Parathyroid Hyperplasia and Correlation with Clinical and Laboratory Findings in Patients with Chronic Kidney Disease

International Nuclear Information System (INIS)

Restrepo Valencia, Cesar Augusto; Santacruz Pacheco, David; Castillo Pinilla, Campo Elias; Chacon Cardona, Jose Arnoby

2011-01-01

Objective: To determine whether there is any correlation between parathyroid hyperplasia, as detected by high-resolution ultrasound, and clinical and laboratory variables in patients with hyperparathyroidism secondary to stage-5 chronic kidney disease (CKD) on hemodialysis. Design: Descriptive. Location: RTS Ltda. Renal Unit in Caldas, Santa Sofia Hospital and Children's Hospital. Patients: All patients, 18 years of age, with stage- 5 CKD who were on dialysis therapy (hemodialysis or peritoneal dialysis), and with PTH levels greater than 400 pg/ml. Methods: After giving their written consent to participate in the study, all patients underwent high-resolution thyroid and parathyroid ultrasound (Phillips Team Enviisor CHD -12 MHz transducer) performed by a medical specialist in radiology. Variables such as etiology, duration of the CKD, time on dialysis therapy, type of dialysis, presence of symptoms related to hyperparathyroidism (bone pain, fractures, pruritus), and laboratory variables like an intact PTH, calcium, phosphorus, calcium x phosphorus, and alkaline phosphatase were analyzed in order to determine if there was a significant correlation between the variables and the detection of parathyroid hyperplasia documented by high resolution ultrasound. Results: Of 403 patients evaluated, 92 met the inclusion criteria, 86 were scanned and 6 were excluded. In these patients, the most common cause of CKD was hypertensive nephrosclerosis. Thirty-seven patients were on peritoneal dialysis and 49 on hemodialysis, with an average time on dialysis of 61.4 +- 36.6 months. The average levels of PTH in pg/mL were 829,465 +- 473,631. The most prevalent clinical symptom was bone pain, found in 52.2% of patients. Ultrasound showed enlarged parathyroid glands in 30 patients (34.88%), with single-gland hyperplasia in 23 (26.74%), two-gland hyperplasia in 4 (4.65%) and three-gland hyperplasia in 3 (3.48%). The correlation between laboratory variables and the presence of

Parathyroid hormone in renal transplanted recipients; a single center study

Directory of Open Access Journals (Sweden)

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.

Vitamin D supplementation has minor effects on parathyroid hormone and bone turnover markers in vitamin D-deficient bedridden older patients.

Science.gov (United States)

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.

Feasibility of photodynamic therapy for secondary hyperparathyroidism in chronic renal failure rats.

Science.gov (United States)

Miyakogawa, Takayo; Kanai, Genta; Tatsumi, Ryoko; Takahashi, Hiroo; Sawada, Kaichiro; Kakuta, Takatoshi; Fukagawa, Masafumi

2017-08-01

Feasibility of photodynamic therapy (PDT) for secondary hyperparathyroidism (SHPT) was examined in a rat model of SHPT. A photosensitizer, 5-aminolevulinic acid (5-ALA), was injected intraperitoneally, and the parathyroid glands were irradiated either after surgical exposure with 385-nm light or transdermally with 630-nm light from a light-emitting diode (LED) lamp. PDT with high 5-ALA and irradiation doses caused severe hypoparathyroidism in SHPT rats within two days. Low-dose invasive PDT reduced intact parathyroid hormone (iPTH) levels in all rats from 748.9 ± 462.6 pg/mL at baseline to 138.7 ± 117.5 pg/mL at week 6, followed by a further decrease to 80.5 ± 54.0 pg/mL at week 9 in 60 % of rats or an increase to 970.0 ± 215.6 pg/mL at week 9 in 40 % of rats. Low-dose noninvasive PDT reduced iPTH levels from 1612.5 ± 607.8 pg/mL at baseline to 591.9 ± 480.1 pg/mL at week 4 in all rats. Thereafter, iPTH levels remained low in 43 % of rats and were 233.7 ± 51.6 pg/mL at week 9, whereas 57 % showed an increase, reaching 3305.9 ± 107.3 pg/mL at week 9. Control SHPT rats had iPTH levels of 2487.8 ± 350.9 and 2974.6 ± 372.1 pg/mL at week 4 and 9, respectively. The parathyroid glands of the rats with low iPTH levels were atrophied and had few parathyroid cells surrounded by fibrotic materials and no recognizable blood vessels. Those of the rats with high iPTH levels showed well-preserved gland structure, clusters of parathyroid cells, and blood vessels. These results demonstrate that 5-ALA-mediated PDT for SHPT is feasible.

Magnetic resonance Imaging (MRI) and technetium-99m-methoxyisonitrile (MIBI) scintigraphy to evaluate the abnormal parathyroid gland and PEIT efficacy for secondary hyperparathyroidism

International Nuclear Information System (INIS)

Wada, Akihiko; Sugihara, Masaki; Sugimura, Kazuro; Kuroda, Hiroyuki

1999-01-01

Percutaneous ethanol injection therapy (PEIT) of the abnormal parathyroid gland is an effective treatment in patients with chronic renal failure with dialysis that tends to be unresponsive to medication. To evaluate the efficacy of PEIT, we investigated the correlation between serum intact PTH (iPTH), and the findings of MR imaging and 99m Tc-MIBI scintigraphy. PEIT was performed 32 times in 24 patients with secondary hyperparathyroidism. Both MR imaging and MIBI scintigraphy were performed before and after PEIT. The detectability of parathyroid lesions was evaluated by MRI and MIBI scintigraphy with reference to ultrasound (B-mode) findings (as a standard) and the comparison of each treatment was done between imaging changes and serum iPTH levels. In the small parathyroid glands ( 99m Tc-MIBI scintigraphy. The reduction of high signal intensity area after PEIT on T2-weighted MR images is considered an useful therapeutic evaluation guideline than the reduction of MIBI accumulation on scintigraphy. (author)

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.

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.

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

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, 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.

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

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

Predictors of attachment security in preschool children from intact and divorced families.

Science.gov (United States)

Nair, Hira; Murray, Ann D

2005-09-01

The authors selected 58 mother-child dyads from divorced and intact families to participate in a study on the impact of divorce on preschoolers' attachment security. The authors explored pathways that lead to security of attachment. They found that mothers from divorced families were younger, had lower income levels, and had lower levels of education compared with their intact counterparts. Divorced mothers also reported significantly higher levels of stress, depression, need for social support, and conflict with their spouses. Mothers from intact families were more likely to use positive (authoritative) parenting styles compared with divorced mothers. Children in the divorced group had lower security scores on the Attachment Q-Set instrument (E. Waters, 1995). Regression analyses indicated that parenting style made a direct (independent) contribution to attachment security. In addition, temperament was related to attachment security, but temperament did not diminish the association of parenting style with attachment security. Furthermore, regression analyses indicated that the relationship of divorce to attachment security was mediated by parenting style.

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.

Effects of draught load exercise and training on calcium homeostasis in horses.

Science.gov (United States)

Vervuert, I; Coenen, M; Zamhöfer, J

2005-01-01

This study was conducted to investigate the effects of draught load exercise on calcium (Ca) homeostasis in young horses. Five 2-year-old untrained Standardbred horses were studied in a 4-month training programme. All exercise workouts were performed on a treadmill at a 6% incline and with a constant draught load of 40 kg (0.44 kN). The training programme started with a standardized exercise test (SET 1; six incremental steps of 5 min duration each, first step 1.38 m/s, stepwise increase by 0.56 m/s). A training programme was then initiated which consisted of low-speed exercise sessions (LSE; constant velocity at 1.67 m/s for 60 min, 48 training sessions in total). After the 16th and 48th LSE sessions, SETs (SET 2: middle of training period, SET 3: finishing training period) were performed again under the identical test protocol of SET 1. Blood samples for blood lactate, plasma total Ca, blood ionized calcium (Ca(2+)), blood pH, plasma inorganic phosphorus (P(i)) and plasma intact parathyroid hormone (PTH) were collected before, during and after SETs, and before and after the first, 16th, 32nd and 48th LSE sessions. During SETs there was a decrease in ionized Ca(2+) and a rise in lactate, P(i) and intact PTH. The LSEs resulted in an increase in pH and P(i), whereas lactate, ionized Ca(2+), total Ca and intact PTH were not affected. No changes in Ca metabolism were detected in the course of training. Results of this study suggest that the type of exercise influences Ca homeostasis and intact PTH response, but that these effects are not influenced in the course of the training period.

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-level

Angiotensin II potentiates prostaglandin stimulation of cyclic AMP levels in intact bovine adrenal medulla cells but not adenylate cyclase in permeabilized cells.

Science.gov (United States)

Boarder, M R; Plevin, R; Marriott, D B

1988-10-25

The level of cyclic AMP in primary cultures of bovine adrenal medulla cells is elevated by prostaglandin E1. Angiotensin II is commonly reported to act on receptors linked to phosphoinositide metabolism or to inhibition of adenylate cyclase. We have investigated the effect of angiotensin II on prostaglandin E1-stimulated cyclic AMP levels in these primary cultures. Rather than reducing cyclic AMP levels, we have found that angiotensin II powerfully potentiates prostaglandin E1-stimulated cyclic AMP accumulation in intact cells, both in the presence and absence of phosphodiesterase inhibitors. The 50% maximal response was similar to that for stimulation of phosphoinositide breakdown by angiotensin II in these cultures. The potentiation of stimulated cyclic AMP levels was seen, although to a smaller maximum, with the protein kinase C (Ca2+/phospholipid-dependent enzyme) activating phorbol ester tetradecanoyl phorbolacetate and with the synthetic diacylglycerol 1-oleoyl-2-acetylglycerol; pretreatment (24 h) with active phorbol ester, which would be expected to diminish protein kinase C levels, attenuated the angiotensin II potentiation of cyclic AMP. Using digitonin-permeabilized cells we showed that adenylate cyclase activity was stimulated by prostaglandin E1 with the same dose-response relationship as was cyclic AMP accumulation in intact cells, but the permeabilized cells showed no response to angiotensin II. The results are discussed with respect to the hypothesis that the angiotensin II influence on cyclic AMP levels is mediated, in part, by diacylglycerol stimulation of protein kinase C.

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

Let-7 and MicroRNA-148 Regulate Parathyroid Hormone Levels in Secondary Hyperparathyroidism.

Science.gov (United States)

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.

Exploratory investigations of hypervelocity intact capture spectroscopy

Science.gov (United States)

Tsou, P.; Griffiths, D. J.

1993-01-01

The ability to capture hypervelocity projectiles intact opens a new technique available for hypervelocity research. A determination of the reactions taking place between the projectile and the capture medium during the process of intact capture is extremely important to an understanding of the intact capture phenomenon, to improving the capture technique, and to developing a theory describing the phenomenon. The intact capture of hypervelocity projectiles by underdense media generates spectra, characteristic of the material species of projectile and capture medium involved. Initial exploratory results into real-time characterization of hypervelocity intact capture techniques by spectroscopy include ultra-violet and visible spectra obtained by use of reflecting gratings, transmitting gratings, and prisms, and recorded by photographic and electronic means. Spectrometry proved to be a valuable real-time diagnostic tool for hypervelocity intact capture events, offering understanding of the interactions of the projectile and the capture medium during the initial period and providing information not obtainable by other characterizations. Preliminary results and analyses of spectra produced by the intact capture of hypervelocity aluminum spheres in polyethylene (PE), polystyrene (PS), and polyurethane (PU) foams are presented. Included are tentative emission species identifications, as well as gray body temperatures produced in the intact capture process.

Influence of four different PTH methods on the classification of chronic kidney disease patients according to the new KDIGO guideline

NARCIS (Netherlands)

ten, Boekel Edwin; van Veen, Merk C.; Vervloet, Marc G.; Fischer, Johan C.; Koopman, Marion G.; van Dam, Bastiaan

2012-01-01

Secondary hyperparathyroidism develops frequently with chronic kidney disease (CKD) and is associated with poor outcome. The new CKD-MBD guideline, Kidney Disease: Improving Global Outcomes (KDIGO), recommends a target range for PTH which is based on the locally used, upper reference range limit

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...

A Case of Primary Hyperparathyroidism due to Intrathyroidal Parathyroid Cyst

Directory of Open Access Journals (Sweden)

Yavuz Yalcin

2014-01-01

Full Text Available Parathyroid cysts constitute 0.08–3.41% of all parathyroid masses. Intrathyroidal parathyroid cysts, however, are rare conditions with only a few cases being reported. Most of the parathyroid cysts are found to be nonfunctional and functional cysts are generally thought to be due to cystic degeneration of parathyroid adenomas. A cystic, smooth contoured lesion of 24 × 19 × 16 mm was observed in left thyroid lobe of a 76-year-old woman during ultrasonography which was performed as routine workup for primary hyperparathyroidism. It was defined as a cystic thyroid nodule at first. Tc99m sestamibi scintigraphy was performed to see any parathyroid lesions, but no radioactive uptake was observed. Intact parathormone (iPTH level was found to be >600 pg/mL in cyst aspiration fluid. Left lobectomy was performed, with a diagnosis of primary hyperparathyroidism due to functional parathyroid cyst. Serum iPTH level was decreased >50% postoperatively and histopathological evaluation was consistent with an encapsulated parathyroid adenoma with a cystic center. Parathyroid cysts are among rare causes of primary hyperparathyroidism. Diagnosis is made by markedly increased iPTH level in cyst fluid and observation of parathyroid epithelium lining the cyst wall.

The impact of family intactness on family functioning, parental control and parent-child relational qualities in a Chinese context

Directory of Open Access Journals (Sweden)

Daniel Tan Lei Shek

2015-01-01

Full Text Available The current study investigated the differences between intact and non-intact families in family processes, including systematic family functioning, parental behavioral control, parental psychological control, and parent-child relational qualities. The participants were 3,328 Secondary One students, with a mean age of 12.59 years, recruited from 28 secondary schools in Hong Kong. Four validated scales were used to assess family processes. Results showed that adolescents in non-intact families perceived relatively poorer family functioning, lower level of paternal and maternal behavioral control, lower level of paternal psychological control and poorer parent-child relational qualities than did adolescents in intact families. This generally indicated that family processes were poorer in non-intact families, compared with those in intact families. The theoretical and practical implications of the findings were discussed.

Single-center open-label randomized study of anemia management improvement in ESRD patients with secondary hyperparathyroidism

Directory of Open Access Journals (Sweden)

Bellasi Antonio

2016-04-01

Full Text Available Whether anemia and mineral bone abnormalities (chronic kidney disease–mineral bone disorder [CKD-MBD] are associated still remains to be elucidated. Both anemia and CKD-MBD have been associated with adverse cardiovascular outcome and poor quality of life. However, recent evidence suggests that use of large doses of erythropoietin-stimulating agents (ESAs to correct hemoglobin (Hb may be detrimental in CKD. The Optimal Anemia Treatment in End Stage Renal Disease (ESRD (Optimal ESRD Treatment study will assess whether lowering of parathyroid hormone (PTH is associated with a reduction in ESA consumption. The Optimal ESRD Treatment study is a pilot single-center open-label study with blinded end point (a prospective randomized open blinded end-point [PROBE] design enrolling 50 patients on maintenance dialysis. Eligible patients with intact PTH (iPTH 300-540 pg/mL and Hb 10-11.5 g/dL will be randomized 1:1 to strict PTH control (150-300 pg/mL versus standard care (PTH range 300-540 pg/mL. Available drugs for CKD-MBD and anemia treatment will be managed by the attending physician to maintain the desired levels of PTH (according to study arm allocation and Hb (10-11.5 g/dL. Echocardiographic data for cardiac structure and function as well as arterial stiffness will be assessed at study inception and completion. The Optimal ESRD Treatment study should shed light on the complicated interplay of anemia and CKD-MBD and on the feasibility of clinical trials in this domain. The study results are expected in the spring of 2017.

Comparison of umbilical cord interleukin-6 in preterm infants with premature rupture of membranes and intact membranes

International Nuclear Information System (INIS)

Gharebaghi, Manizheh M.; Peirovifar, A.; Gharebaghi, Parvin M.

2008-01-01

Objective was to compare inflammatory mediators in the cord blood of premature newborn infants with premature rupture of membranes (PROM) and intact membranes. Eighty-nine premature neonates with gestational age of 27-34 weeks that delivered in Ghaem Hospital in Mashhad, Iran from June 2005 to March 2006 were enrolled in a prospective observational study and their umbilical cord plasma was collected at birth. They were allocated into 2 groups (45 patients with PROM and 44 neonates with intact membranes). Interleukin-6 (IL-6) and C-reactive protein (CRP) levels were measured in cord plasma by the enzyme linked immunoassay (ELISA) method. Mean cord plasma IL-6 levels in preterm neonates with PROM was 205.71 pg/ml and in neonates with intact membranes was 33.3 pg/ml for IL-6 (p=0.000). The mean cord blood CRP level in newborns was 10.2 ug/ml, and in those with intact membranes was 1.6 ug/ml and in those with intact membranes was 1.6 ug/ml (p=0.41). Early onset sepsis was more frequent in infants with PROM than premature infants with intact membrane (38% versus 10%, p=0.001). In neonates with PROM, the mean cord blood IL-6 level was significantly higher in septic newborns (414.28 versus 40.44 pg/ml, p=0.000). The premature newborn infants with PROM had increased IL-6 levels in cord blood, which was significantly higher in neonates that developed early onset sepsis. (author)

A 12-week dose-escalating study of etelcalcetide (ONO-5163/AMG 416), a novel intravenous calcimimetic, for secondary hyperparathyroidism in Japanese hemodialysis patients
.

Science.gov (United States)

Yokoyama, Keitaro; Fukagawa, Masafumi; Shigematsu, Takashi; Akiba, Takashi; Fujii, Akifumi; Odani, Motoi; Akizawa, Tadao

2017-08-01

To evaluate dose-escalation of etelcalcetide (ONO-5163/AMG 416), a novel, intravenous (IV), long-acting calcium-sensing receptor agonist, for treatment of secondary hyperparathyroidism (SHPT) in Japanese hemodialysis patients. In this multicenter study, IV injections of etelcalcetide (3 times a week for 12 weeks) were administered, with dose escalation every 4 weeks depending on changes in serum intact parathyroid hormone (iPTH) and corrected calcium (cCa). A total of 24 patients participated in this study. Serum iPTH was reduced in a time- and dose-dependent manner, with reductions (in pg/mL) at 12 weeks of -226.1 ± 125.3, -362.5 ± 161.5, and -412.4 ± 130.2, respectively, for maximum doses of 5, 10, and 15 mg. At the end of the treatment, 50% of patients had serum iPTH levels within the target range (60 - 240 pg/mL). Serum cCa and phosphorus were reduced in parallel with iPTH. Adverse events (AEs) occurred in 20 patients (83.3%). The most frequently observed AEs (> 10%) were either mild or moderate nasopharyngitis (29.2%), decreased serum calcium (16.7%), and vomiting (12.5%). Dose-escalated triweekly etelcalcetide was effective for SHPT in Japanese hemodialysis patients and was satisfactorily tolerated.
.

Efficacy of low-dose cinacalcet on alternate days for the treatment of secondary hyperparathyroidism in hemodialysis patients: a single-center study

Directory of Open Access Journals (Sweden)

Gojaseni P

2017-02-01

Full Text Available Pongsathorn Gojaseni, Dolnapa Pattarathitinan, Anutra Chittinandana Division of Nephrology, Department of Medicine, Bhumibol Adulyadej Hospital, Directorate of Medical Services, Royal Thai Air Force, Bangkok, Thailand Introduction: Cinacalcet is effective in reducing serum parathyroid hormone (PTH in patients with secondary hyperparathyroidism (HPT. This study focused on testing whether a prescription of low-dose cinacalcet on alternate days could be an option for treatment of secondary HPT.Materials and methods: A retrospective clinical study was conducted on chronic maintenance hemodialysis patients. Patients with secondary HPT who received cinacalcet at a starting dose of 25 mg on alternate days were reviewed (low-dose group. Patients who were being treated with a standard dose of cinacalcet in the same period of time were selected as the control group. The primary outcome was difference in the percentage of patients achieving >30% reduction of intact parathyroid hormone (iPTH levels at 16 weeks. The changes of serum iPTH and other biochemical data were also tested.Results: A total of 30 patients (16 low doses and 14 controls took part in the study. Baseline iPTH levels in the low-dose and control group were 1,065.9±477.7 and 1,214.1±497.6 pg/mL, respectively (p=0.413. The analysis showed that the percentage of patients who achieved the primary outcome showed little or no difference (33.3% in the low-dose group compared with 38.5% in the control group, p=1.0. Serum iPTH reduction during 16 weeks of study period in the low-dose and control group was 253.5±316.1 and 243.4±561.3 pg/mL, respectively (p=0.957. There was no difference in the adverse events between both groups.Conclusion: Among patients with secondary HPT, initial treatment with cinacalcet 25 mg on alternate days can decrease serum PTH levels. The role of low-dose cinacalcet in secondary HPT should be further determined in large-scale, randomized controlled trials. Keywords

(Photosynthesis in intact plants)

Energy Technology Data Exchange (ETDEWEB)

1990-01-01

Progress in the two years since the last renewal application has been excellent. We have made substantial contributions on both main fronts of the projects, and are particularly happy with the progress of our research on intact plants. The approach of basing our field work on a sound foundation of laboratory studies has enabled is to use methods which provide unambiguous assays of well characterized reactions. We have also made excellent progress in several laboratory studies which will have direct applications in future field work, and have introduced to the laboratory a range of molecular genetics techniques which will allow us to explore new options in the attempt to understand function at the level of molecular structure.

Correlation of Serum Parathormone with Hypertension in Chronic Renal Failure Patients Treated with Hemodialysis

International Nuclear Information System (INIS)

Baradaran, A.; Nasri, H.

2005-01-01

To consider the correlation of serum parathromone on severity of hypertension in end stage renal disease (ESRD) patients on hemodialysis (HD). A cross-sectional study was done on patients with ESRD on treatment with maintenance HD. Levels of serum calcium, phosphorous, alkaline phosphatase, albumin and intact parathormone (iPTH) were measured. Stratification of hypertensive patients was done from stage one to three. The total number of patients studied was 73 (Females=28, Males=45), consisting of 58 non-diabetic (F=22, M=36) and 15 diabetic patients (F=6, M=9). The mean age of the study patients was 46.5+-16 years. The mean duration on HD of the study patients was 21.5+-232.5 months. The mean serum PTH of the study patients was 309+-349 pg/ml and the mean serum alkaline phosphatase was 413+-348 IU/L. There was a significant positive correlation between the stage of hypertension and serum PTH levels (r=0.200, p=0.045). Also, there was a significant positive correlation between stage of hypertension and calcium-phosphorus product (r=0.231, p=0.027). There was no significant correlation between stage of hypertension and serum ALP (r=0.135, p=0.128). Relationship between serum PTH and severity of hypertension in patients on HD needs to be studied in more detail. Hypertension and secondary hyperparathyroidism interact in the process of accelerated atherosclerosis in HD patients thus warranting appropriate measures to control hyperparathyrodism vigorously. (author)

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...

The Serum Level of Fibroblast Growth Factor-23 and Calcium-Phosphate Homeostasis in Obese Perimenopausal Women

Directory of Open Access Journals (Sweden)

M. Holecki

2011-01-01

Full Text Available Plasma FGF-23 concentrations and its relationship with calcium-phosphate homeostasis were evaluated in 48 perimenopausal obese women and in 29 nonobese controls. Serum parathyroid hormone, 25-hydroxyvitamin D3, CTX1, osteocalcin, total calcium, phosphorus, creatinine, and plasma intact FGF-23 concentrations were assessed. DXA of lumbar spine and femoral neck was performed to determine bone mineral density (BMD. Plasma iFGF-23 concentration was significantly higher in obese patients (by 42% and correlated with age and BMD of proximal femur (R=-0.346; R=0.285, resp. but not with markers of bone turnover. However, serum phosphorus level in obese subjects was significantly lower. iFGF-23 concentration correlated significantly with body mass index (R=0.292 and fat content (R=0.259 in all study subjects. Moreover, a significant correlation between iFGF-23 and iPTH (R=0.254 was found. No correlation between serum phosphorus or eGFR and plasma iFGF-23 and between eGFR and serum phosphorus was found. Elevated serum iFGF-23 concentration may partially explain lower phosphorus levels in the obese and seems not to reflect bone turnover.

Preoperative evaluation of hyperparathyroidism. The role of dual-phase parathyroid scintigraphy and ultrasound imaging

International Nuclear Information System (INIS)

Sukan, A.; Reyhan, M.; Aydin, M.; Yapar, A.F.; Aktas, A.; Sert, Y.; Canpolat, T.

2008-01-01

The aim of this study was to evaluate the efficacy of dual-phase 99mTc-methoxyisobutylnitrile (MIBI) parathyroid scintigraphy (PS) and ultrasound (US) in primary (pHPT) and secondary (sHPT) hyperparathyroidism. A total of 69 patients (mean age 47±16; age range 14-79 years), including 19 patients with sHPT were enrolled in this study. Preoperative serum intact parathyroid hormone (iPTH) levels, calcium (Ca), phosphate (P), alkaline phosphatase, and 24-h urinary-free Ca measurements were obtained. Concomitant thyroid pathology was also recorded. Histopathology revealed 30 solitary adenomas and 71 hyperplastic glands in 55 patients. The remaining patients' histopathology revealed normal parathyroid, thyroid, or lymph nodes. The sensitivities of MIBI and US in pUPT were 70% and 60%, respectively. It was 60% for both procedures in sHPT. The overall sensitivity of combined US+MIBI in pHPT and sHPT was 81% and 71%, respectively. The overall specificity of MIBI and US was 87% and 91%; positive predictive value (PPV) was 94% and 92%, respectively. MIBI and US identified the parathyroid pathology in 92% and 85% of patients in the non-concomitant thyroid disease group, and in 53% and 47% of patients in the concomitant thyroid disease group, respectively. The weight of the gland between primary and secondary hyperparathyroidism did not reveal a significant difference (P=0.4). Significant differences were found with respect to age, PTH, Ca, and P levels between the pHPT and sHPT (P<0.001). Intact PTH levels showed significant differences between MIBI positive and negative patients (P=0.013), and also US positive and negative patients (P=0.012). A significant negative correlation was found between iPTH and Ca at sHPT (P<0.001). The concomitancy of thyroid disease greatly influences scintigraphic and ultrasonographic detection of parathyroid pathology in pHPT and sHPT. The combination of MIBI and US appears promising for localizing parathyroid pathology in patients with both

Effects of Denosumab and Calcitriol on Severe Secondary Hyperparathyroidism in Dialysis Patients With Low Bone Mass.

Science.gov (United States)

Chen, Chien-Liang; Chen, Nai-Ching; Liang, Huei-Lung; Hsu, Chih-Yang; Chou, Kang-Ju; Fang, Hua-Chang; Lee, Po-Tsang

2015-07-01

Secondary hyperparathyroidism (SHPT) may worsen with administration of denosumab in chronic renal failure patients with low bone mass. This study aimed to evaluate the short-term effect of coadministration of calcitriol and denosumab on PTH secretion and parathyroid structure and the incidence of adverse effects in patients with SHPT and low bone mass. This was a 24-week, open-label study at Kaohsiung Veterans General Hospital in Kaohsiung, Taiwan. Dialysis patients with SHPT (intact parathyroid hormone [iPTH] > 800 pg/mL) and low bone mass (T score < -2.5) were enrolled. Patients received denosumab (60 mg) and doses of calcitriol adjusted to achieve iPTH < 300 pg/mL. Parathyroid gland volume was assessed upon study initiation and completion. Serum calcium, phosphate, alkaline phosphatase, iPTH, and adverse effects were assessed at each visit (Day 7, 14, and 21, and every month thereafter). iPTH significantly decreased (mean decrease, 58.28 ± 6.12%) with denosumab/calcitriol administration (P < .01) but not in the controls (patients not receiving denosumab). Parathyroid gland volume decreased (mean decrease, 21.98 ± 5.54%) with denosumab/calcitriol administration (P < .01) and progressively increased (20.58 ± 4.48%) in the controls (P < .05). Serum alkaline phosphatase and iPTH levels were significantly correlated to decreased iPTH and regression of parathyroid hyperplasia (P < .05). The most common adverse events were hypocalcemia (33.33%) and respiratory tract infection (4.17%). Hypocalcemia rapidly resolved with calcium and calcitriol supplements. Denosumab allows for supra-physiologic doses of calcitriol resulting in decreased parathyroid secretion and parathyroid hyperplasia. Supervised administration and weekly laboratory and clinical monitoring of serum calcium are recommended during the first month to prevent hypocalcemia.

MoFi: A Software Tool for Annotating Glycoprotein Mass Spectra by Integrating Hybrid Data from the Intact Protein and Glycopeptide Level.

Science.gov (United States)

Skala, Wolfgang; Wohlschlager, Therese; Senn, Stefan; Huber, Gabriel E; Huber, Christian G

2018-04-18

Hybrid mass spectrometry (MS) is an emerging technique for characterizing glycoproteins, which typically display pronounced microheterogeneity. Since hybrid MS combines information from different experimental levels, it crucially depends on computational methods. Here, we describe a novel software tool, MoFi, which integrates hybrid MS data to assign glycans and other post-translational modifications (PTMs) in deconvoluted mass spectra of intact proteins. Its two-stage search algorithm first assigns monosaccharide/PTM compositions to each peak and then compiles a hierarchical list of glycan combinations compatible with these compositions. Importantly, the program only includes those combinations which are supported by a glycan library as derived from glycopeptide or released glycan analysis. By applying MoFi to mass spectra of rituximab, ado-trastuzumab emtansine, and recombinant human erythropoietin, we demonstrate how integration of bottom-up data may be used to refine information collected at the intact protein level. Accordingly, our software reveals that a single mass frequently can be explained by a considerable number of glycoforms. Yet, it simultaneously ranks proteoforms according to their probability, based on a score which is calculated from relative glycan abundances. Notably, glycoforms that comprise identical glycans may nevertheless differ in score if those glycans occupy different sites. Hence, MoFi exposes different layers of complexity that are present in the annotation of a glycoprotein mass spectrum.

Performance of intact and partially degraded concrete barriers in limiting fluid flow

International Nuclear Information System (INIS)

Walton, J.C.; Seitz, R.R.

1991-07-01

Concrete barriers will play a critical role in the long-term isolation of low-level radioactive wastes. Over time the barriers will degrade, and in many cases, the fundamental processes controlling performance of the barriers will be different for intact and degraded conditions. This document examines factors controlling fluid flow through intact and degraded concrete disposal facilities. Simplified models are presented fro predicting build up of fluid above a vault; fluid flow through and around intact vaults, through flaws in coatings/liners applied to a vault, and through cracks in a concrete vault; and the influence of different backfill materials around the outside of the vault. Example calculations are presented to illustrate the parameters and processes that influence fluid flow. 46 refs., 49 figs., 2 tabs

Treatment of renal osteopathy by Rocaltrol, with special reference to parathormone levels and X-ray examinations

International Nuclear Information System (INIS)

Schmitt, R.L.

1981-01-01

The effects of treatment of renal osteopathy with 1.25 (OH) 2 D 3 was evaluated in 24 chronic hemodialysis patients. The best results of treatment were displayed in patients in whom 1.25 (OH) 2 D 3 determined only a slow rise in plasma calcium levels. In these patients iPTH, alkaline phosphatase levels, and osteoblast counts in bone biopsies were initially high. Definite improvement of bone resorption was found on X-ray examination. In contrast in patients with low iPTH, low alkaline phosphatase levels, and low osteoblast counts, administration of 1.25 (OH) 2 D 3 determined a fast rise of plasma calcium levels. No X-ray modifications could be detected. (orig.) [de

Impact of mineral and bone disorder on healthcare resource use and associated costs in the European Fresenius medical care dialysis population: a retrospective cohort study.

Science.gov (United States)

Chiroli, Silvia; Mattin, Caroline; Belozeroff, Vasily; Perrault, Louise; Mitchell, Dominic; Gioni, Ioanna

2012-10-29

Secondary hyperparathyroidism (SHPT) is associated with mortality in patients with chronic kidney disease (CKD), but the economic consequences of SHPT have not been adequately studied in the European population. We assessed the relationship between SHPT parameters (intact parathyroid hormone [iPTH], calcium, and phosphate) and hospitalisations, medication use, and associated costs among CKD patients in Europe. The analysis of this retrospective cohort study used records of randomly selected patients who underwent haemodialysis between January 1, 2005 and December 31, 2006 at participating European Fresenius Medical Care facilities in 10 countries. Patients had ≥ 1 iPTH value recorded, and ≥ 1 month of follow-up after a 3-month baseline period during which SHPT parameters were assessed. Time at risk was post-baseline until death, successful renal transplantation, loss to follow-up, or the end of follow-up. Outcomes included cost per patient-month, rates of hospitalisations (cardiovascular disease [CVD], fractures, and parathyroidectomy [PTX]), and use of SHPT-, diabetes-, and CVD-related medications. National costs were applied to hospitalisations and medication use. Generalised linear models compared costs across strata of iPTH, total calcium, and phosphate, adjusting for baseline covariates. There were 6369 patients included in the analysis. Mean ± SD person-time at risk was 13.1 ± 6.4 months. Patients with iPTH > 600 pg/mL had a higher hospitalisation rate than those with lower iPTH. Hospitalisation rates varied little across calcium and phosphate levels. SHPT-related medication use varied with iPTH, calcium, and phosphate. After adjusting for demographic and clinical variables, patients with baseline iPTH > 600 pg/mL had 41% (95% CI: 25%, 59%) higher monthly total healthcare costs compared with those with iPTH in the K/DOQI target range (150-300 pg/mL). Patients with baseline phosphate and total calcium levels above target ranges (1.13-1.78 mmol/L and 2

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

Directory of Open Access Journals (Sweden)

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.

Intactness of cell wall structure controls the in vitro digestion of starch in legumes.

Science.gov (United States)

Dhital, Sushil; Bhattarai, Rewati R; Gorham, John; Gidley, Michael J

2016-03-01

Increasing the level of starch that is not digested by the end of the small intestine and therefore enters the colon ('resistant starch') is a major opportunity for improving the nutritional profile of foods. One mechanism that has been shown to be successful is entrapment of starch within an intact plant tissue structure. However, the level of tissue intactness required for resistance to amylase digestion has not been defined. In this study, intact cells were isolated from a range of legumes after thermal treatment at 60 °C (starch not gelatinised) or 95 °C (starch gelatinised) followed by hydrolysis using pancreatic alpha amylase. It was found that intact cells, isolated at either temperature, were impervious to amylase. However, application of mechanical force damaged the cell wall and made starch accessible to digestive enzymes. This shows that the access of enzymes to the entrapped swollen starch is the rate limiting step controlling hydrolysis of starch in cooked legumes. The results suggest that a single cell wall could be sufficient to provide an effective delivery of starch to the large intestine with consequent nutritional benefits, provided that mechanical damage during digestion is avoided.

Determining the Levels of Vitamin D and Parathyroid Hormone in Patients on Hemodialysis

Directory of Open Access Journals (Sweden)

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.

Treatment of renal osteopathy by Rocaltrol, with special reference to parathormone levels and X-ray examinations

Energy Technology Data Exchange (ETDEWEB)

Schmitt, R.L.

The effects of treatment of renal osteopathy with 1.25 (OH)/sub 2/D/sub 3/ was evaluated in 24 chronic hemodialysis patients. The best results of treatment were displayed in patients in whom 1.25 (OH)/sub 2/D/sub 3/ determined only a slow rise in plasma calcium levels. In these patients iPTH, alkaline phosphatase levels, and osteoblast counts in bone biopsies were initially high. Definite improvement of bone resorption was found on X-ray examination. In contrast in patients with low iPTH, low alkaline phosphatase levels, and low osteoblast counts, administration of 1.25 (OH)/sub 2/D/sub 3/ determined a fast rise of plasma calcium levels. No X-ray modifications could be detected.

Primary hyperparathyroidism with classic and severe skeletal involvement

OpenAIRE

Sandoval, Mark Anthony S; Paz-Pacheco, Elizabeth

2010-01-01

A 63-year-old woman has had multiple repeated fractures. A diagnosis of primary hyperparathyroidism (PHPT) was made after she was found to be hypercalcaemic with an elevated level of intact parathyroid hormone (iPTH). Radiographs revealed classic and severe bone findings in PHPT, features which were common in the past but are thought to be rare at this modern age. She also had nephrolithiasis and osteoporosis. An enlarged parathyroid gland was seen on ultrasound and CT scan, and hyperfunction...

Changes of blood levels of several hormones, catecholamines, prostaglandins, electrolytes and cAMP in man during emotional stress.

Science.gov (United States)

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.

[Cinacalcet in the management of normocalcaemic secondary hyperparathyroidism after kidney transplantation: one-year follow-up multicentre study].

Science.gov (United States)

Torregrosa, Josep V; Morales, Enrique; Díaz, Juan M; Crespo, Josep; Bravo, Juan; Gómez, Gonzalo; Gentil, Miguel A; Rodríguez-Benot, Alberto; Rodríguez-García, Minerva; López-Jiménez, Verónica; Gutiérrez-Dalmau, Álex; Jimeno, Luisa; Pérez-Sáez, M José; Romero, Rafael; Gómez-Alamillo, Carlos

2014-01-01

The effect of cinacalcet in patients with persistent secondary hyperparathyroidism (SHPT) after kidney transplantation (RT) has mainly been reported in patients with secondary hypercalcaemia. Our objective was to assess the long-term effect of cinacalcet on patients with a RT and normocalcaemic SHPT. A one-year multicentre, observational, retrospective study that included kidney recipients with SHPT (intact parathyroid hormone [iPTH] >120 pg/ml) and calcium levels within the normal range (8.4-10.2 mg/dl). Patients began treatment with cinacalcet in clinical practice. 32 patients with a mean age (standard deviation [SD]) of 54 (11) years, 56% male, were included in the study. Treatment with cinacalcet began a median of 16 months after RT (median dose of 30 mg/day). Levels of iPTH decreased from a median (P25, P75) of 364 (220, 531) pg/ml at the start of the study to 187 (98, 320) after 6 months (48.6% reduction, P=.001) and to 145 (91, 195) after 12 months (60.2% reduction, P=.001), without there being changes in calcium and phosphorus levels (P=.214 and P=.216, respectively). No changes were observed in kidney function or anti-calcineuric drug levels. 3.1% of patients discontinued cinacalcet due to intolerance and 6.2% due to a lack of efficacy. In patients with normocalcaemic SHPT after RT, cinacalcet improves the control of serum PTH values without causing changes to calcaemia, phosphataemia or kidney function. Cinacalcet showed good tolerability.

VITAMIN D DEFICIENCY IN JAMMU IN SUBJECTS WITH NO COMORBIDITY- A PRELIMINARY STUDY

Directory of Open Access Journals (Sweden)

Sidharth Kapoor

2017-11-01

Full Text Available BACKGROUND Deficiency of the vitamin D may result in metabolic bone diseases leading to rickets in children or osteomalacia in adults.1,2 The vitamin D may provide protection against hypertension, cancer and multiple sclerosis.3 The vitamin D level is regulated through the interaction of various factors including intestinal absorption, renal function, serum calcium level and Parathyroid Hormone (PTH.3 The 2 main sources for vitamin D are synthesis in the skin on exposure to Ultraviolet-B (UVB light from sunlight and dietary intake. The aim of the study is to evaluate status of the vitamin D of a cohort of Jammu population with no comorbidity. A questionnaire was given to 119 patients (77 males and 42 females where information regarding intake of calcium and vitamin D supplementation, intake of calcium rich food and exposure to vitamin D was sought. MATERIALS AND METHODS Estimation of serum 25-hydroxyvitamin D (25(OH3 and plasma Parathyroid Hormone (PTH intact levels was done the subjects. Serum 25 (OH 2D3 levels did not differ significantly between males and females, although the levels were low (males 9.72 ng/mL ± 4.2 and females 8.5 ng/mL ± 4.7. RESULTS The vitamin D was still in the deficiency range even after excluding the subjects with very high PTH levels. CONCLUSION There was a high prevalence of a vitamin D deficiency in this sample of Jammu despite >70% of participants having adequate exposure to sunlight and >80% reporting adequate intake of dairy products.

Toward best practices in data processing and analysis for intact biotherapeutics by MS in quantitative bioanalysis.

Science.gov (United States)

Kellie, John F; Kehler, Jonathan R; Karlinsey, Molly Z; Summerfield, Scott G

2017-12-01

Typically, quantitation of biotherapeutics from biological matrices by LC-MS is based on a surrogate peptide approach to determine molecule concentration. Recent efforts have focused on quantitation of the intact protein molecules or larger mass subunits of monoclonal antibodies. To date, there has been limited guidance for large or intact protein mass quantitation for quantitative bioanalysis. Intact- and subunit-level analyses of biotherapeutics from biological matrices are performed at 12-25 kDa mass range with quantitation data presented. Linearity, bias and other metrics are presented along with recommendations made on the viability of existing quantitation approaches. This communication is intended to start a discussion around intact protein data analysis and processing, recognizing that other published contributions will be required.

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...

Pegvisomant-induced serum insulin-like growth factor-I normalization in patients with acromegaly returns elevated markers of bone turnover to normal

DEFF Research Database (Denmark)

Parkinson, C; Kassem, M; Heickendorff, Lene

2003-01-01

Active acromegaly is associated with increased biochemical markers of bone turnover. Pegvisomant is a GH receptor antagonist that normalizes serum IGF-I in 97% of patients with active acromegaly. We evaluated the effects of pegvisomant-induced serum IGF-I normalization on biochemical markers...... of bone and soft tissue turnover, as well as levels of PTH and vitamin D metabolites, in 16 patients (nine males; median age, 52 yr; range, 28-78 yr) with active acromegaly (serum IGF-I at least 30% above upper limit of an age-related reference range). Serum procollagen III amino-terminal propeptide...... (PIIINP) and type I procollagen amino-terminal propeptide, osteocalcin (OC), bone-related alkaline phosphatase, C-terminal cross-linked telopeptide of type I collagen (CTx), albumin-corrected calcium, intact PTH, 25-hydroxy vitamin D, 1,25-dihydroxy vitamin D [1,25-(OH)(2) vit D], urinary type 1 collagen...

Predictors of Attachment Security in Preschool Children from Intact and Divorced Families

Science.gov (United States)

Nair, Hira; Murray, Ann D.

2005-01-01

The authors selected 58 mother-child dyads from divorced and intact families to participate in a study on the impact of divorce on preschoolers' attachment security. The authors explored pathways that lead to security of attachment. They found that mothers from divorced families were younger, had lower income levels, and had lower levels of…

Strategies for Analyzing Data from Intact Groups.

Science.gov (United States)

Cross, Lawrence H.; Lane, Carolyn E.

Action research often necessitates the use of intact groups for the comparison of educational treatments or programs. This paper considers several analytical methods that might be used for such situations when pretest scores indicate that these intact groups differ significantly initially. The methods considered include gain score analysis of…

Small Particles Intact Capture Experiment (SPICE)

Science.gov (United States)

Nishioka, Ken-Ji; Carle, G. C.; Bunch, T. E.; Mendez, David J.; Ryder, J. T.

1994-01-01

The Small Particles Intact Capture Experiment (SPICE) will develop technologies and engineering techniques necessary to capture nearly intact, uncontaminated cosmic and interplanetary dust particles (IDP's). Successful capture of such particles will benefit the exobiology and planetary science communities by providing particulate samples that may have survived unaltered since the formation of the solar system. Characterization of these particles may contribute fundamental data to our knowledge of how these particles could have formed into our planet Earth and, perhaps, contributed to the beginnings of life. The term 'uncontaminated' means that captured cosmic and IDP particles are free of organic contamination from the capture process and the term 'nearly intact capture' means that their chemical and elemental components are not materially altered during capture. The key to capturing cosmic and IDP particles that are organic-contamination free and nearly intact is the capture medium. Initial screening of capture media included organic foams, multiple thin foil layers, and aerogel (a silica gel); but, with the exception of aerogel, the requirements of no contamination or nearly intact capture were not met. To ensure no contamination of particles in the capture process, high-purity aerogel was chosen. High-purity aerogel results in high clarity (visual clearness), a useful quality in detection and recovery of embedded captured particles from the aerogel. P. Tsou at the Jet Propulsion Laboratory (JPL) originally described the use of aerogel for this purpose and reported laboratory test results. He has flown aerogel as a 'GAS-can Lid' payload on STS-47 and is evaluating the results. The Timeband Capture Cell Experiment (TICCE), a Eureca 1 experiment, is also flying aerogel and is scheduled for recovery in late April.

Relationship between nutritional profile, measures of adiposity, and bone mineral density in postmenopausal Saudi women.

Science.gov (United States)

Alissa, Eman M; Alnahdi, Wafa A; Alama, Nabeel; Ferns, Gordon A

2014-01-01

Osteoporosis remains a major health problem in all developed countries and is a condition in which several dietary factors have been implicated. To assess the nutritional status and levels of adiposity of postmenopausal women in relation to bone mineral density. A cross-sectional study in which dietary intake was estimated by a food frequency questionnaire in 300 Saudi postmenopausal women aged 46-88 years. Bone profile biochemistry (serum calcium, phosphate, parathyroid hormone [PTH], vitamin D) and bone mineral density (BMD) in 3 skeletal sites were determined for all participants. Overweight and obesity were highly prevalent among the study population. No significant correlation was found between dietary calcium and vitamin D and bone mass at any site. Dietary intake of calcium and vitamin D was significantly less than the recommended levels for a large proportion of the cohort. Energy-adjusted intakes of carbohydrates, fat, protein, and unsaturated fatty acids were associated with BMD in the postmenopausal women. Age, body weight, and residency type were predictors of BMD at all sites. Serum-intact PTH was a predictor of BMD at lumbar spine and femoral neck. Waist : hip ratio (WHR) was a predictor for BMD at femoral neck. These results suggest that BMD is influenced by dietary factors other than calcium and vitamin D. However, nondietary factors such as age, WHR, PTH, and body weight may be important determinants of BMD in postmenopausal women.

Spontaneous and light-induced photon emission from intact brains of chick embryos

Institute of Scientific and Technical Information of China (English)

张锦珠; 于文斗; 孙彤

1997-01-01

Photon emission (PE) and light-induced photon emission(LPE) of intact brains isolated from chick embryos have been measured by using the single photon counting device. Experimental results showed that the intensi-ty level of photon emission was detected to be higher from intact brain than from the medium in which the brain was immerged during measuring, and the emission intensity was related to the developmental stages, the healthy situation of the measured embryos, and the freshness of isolated brains as well. After white light illumination, a short-life de-layed emission from intact brains was observed, and its relaxation behavior followed a hyperbolic rather than an expo-nential law. According to the hypothesis of biophoton emission originating from a delocalized coherent electromagnetic field and Frohlich’s idea of coherent long-range interactions in biological systems, discussions were made on the signifi-cance of photon emission in studying cell communication, biological regulation, living system’

Vitamin D deficiency in Korean children: prevalence, risk factors, and the relationship with parathyroid hormone levels

Directory of Open Access Journals (Sweden)

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.

Adjacent level effects of bi level disc replacement, bi level fusion and disc replacement plus fusion in cervical spine--a finite element based study.

Science.gov (United States)

Faizan, Ahmad; Goel, Vijay K; Biyani, Ashok; Garfin, Steven R; Bono, Christopher M

2012-03-01

Studies delineating the adjacent level effect of single level disc replacement systems have been reported in literature. The aim of this study was to compare the adjacent level biomechanics of bi-level disc replacement, bi-level fusion and a construct having adjoining level disc replacement and fusion system. In total, biomechanics of four models- intact, bi level disc replacement, bi level fusion and fusion plus disc replacement at adjoining levels- was studied to gain insight into the effects of various instrumentation systems on cranial and caudal adjacent levels using finite element analysis (73.6N+varying moment). The bi-level fusion models are more than twice as stiff as compared to the intact model during flexion-extension, lateral bending and axial rotation. Bi-level disc replacement model required moments lower than intact model (1.5Nm). Fusion plus disc replacement model required moment 10-25% more than intact model, except in extension. Adjacent level motions, facet loads and endplate stresses increased substantially in the bi-level fusion model. On the other hand, adjacent level motions, facet loads and endplate stresses were similar to intact for the bi-level disc replacement model. For the fusion plus disc replacement model, adjacent level motions, facet loads and endplate stresses were closer to intact model rather than the bi-level fusion model, except in extension. Based on our finite element analysis, fusion plus disc replacement procedure has less severe biomechanical effects on adjacent levels when compared to bi-level fusion procedure. Bi-level disc replacement procedure did not have any adverse mechanical effects on adjacent levels. Copyright © 2011 Elsevier Ltd. All rights reserved.

Telopéptido carboxilo terminal del colágeno tipo I (b-CTX sérico y compromiso óseo en la insuficiencia renal crónica Serum b-Type I collagen carboxyterminal telopeptide (b-CTXs and bone involvement in chronic renal failure

Directory of Open Access Journals (Sweden)

Beatriz Oliveri

2005-08-01

Full Text Available La osteodistrofia renal (ODR se caracteriza por alteraciones óseas. Se evaluaron métodos bioquímicos alternativos a la biopsia ósea en pacientes renales para determinar cambios rápidos del remodelamiento óseo en 43 pacientes predialíticos (PD y 49 hemodializados (HD. Los PD presentaron fosfatemia, fosfatasa alcalina ósea (FAO, hormona paratiroidea intacta (PTHi y b-telopéptido carboxilo terminal del colágeno tipo I (bCTXs mayores y clearence de creatinina (Ccr menores (p40 ml/min. En PD, bCTXs (pAn increase in parathyroid hormone (PTH levels in chronic renal failure (CRF induces bone abnormalities known as renal osteodystrophy (ROD. The aim of the present study was to evaluate alternative biochemical methods to bone biopsy, to evaluate changes in bone remodeling in renal patients. Intact PTH (iPTH and bone markers were measured in 43 predialysis (PD, 49 hemodialysis patients (HD and 185 controls. bCTXs, bone alkaline phosphatase (bAL, iPTH were higher and creatinine clearance (Ccr was lower in PD and HD compared with controls (p40 ml/min. bCTXs (p<0.05 in PD and bCTXs and bAL in HD patients were higher than controls, even when iPTH was within normal range (<65 pg/ml. Patients with severe secondary hyperparathyroidism showed higher bone markers than patients with normal or moderately increased iPTH (p<0.001. These results suggest that even when there is no increase in iPTH, bone remodeling increases (possibly due to other factors exhibiting higher bone resorption, and bCTXs would seem to be an adequate non-invasive tool to assess early bone changes in CRF and prevent future fractures. Bone marker measurements in ROD would be useful to identify patients who may require bone biopsy. However, further studies comparing both methods must be performed before replacing bone biopsy with serum b-CTX.

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

50 CFR 622.38 - Landing fish intact.

Science.gov (United States)

2010-10-01

... that is operating under the respective trip limits. Such cut-off fish also may be sold. A maximum of... 50 Wildlife and Fisheries 8 2010-10-01 2010-10-01 false Landing fish intact. 622.38 Section 622.38... Landing fish intact. The operator of a vessel that fishes in the EEZ is responsible for ensuring that fish...

Effects of hydrolysed casein, intact casein and intact whey protein on energy expenditure and appetite regulation

DEFF Research Database (Denmark)

Bendtsen, Line Quist; Lorenzen, Janne Kunchel; Gomes, Sisse

2014-01-01

Casein and whey differ in amino acid composition and in the rate of absorption; however, the absorption rate of casein can be increased to mimic that of whey by exogenous hydrolysis. The objective of the present study was to compare the effects of hydrolysed casein (HC), intact casein (IC......) and intact whey (IW) on energy expenditure (EE) and appetite regulation, and thereby to investigate the influence of amino acid composition and the rate of absorption. In the present randomised cross-over study, twenty-four overweight and moderately obese young men and women consumed three isoenergetic...

Advanced glycation end-products (AGEs accumulation in skin: relations with chronic kidney disease-mineral and bone disorder

Directory of Open Access Journals (Sweden)

Renata de Almeida França

2017-08-01

Full Text Available Abstract Introduction: Chronic kidney disease (CKD is associated with high morbidity and mortality rates, main causes related with cardiovascular disease (CVD and bone mineral disorder (CKD-BMD. Uremic toxins, as advanced glycation end products (AGEs, are non-traditional cardiovascular risk factor and play a role on development of CKD-BMD in CKD. The measurement of skin autofluorescence (sAF is a noninvasive method to assess the level of AGEs in tissue, validated in CKD patients. Objective: The aim of this study is analyze AGEs measured by sAF levels (AGEs-sAF and its relations with CVD and BMD parameters in HD patients. Methods: Twenty prevalent HD patients (HD group and healthy subjects (Control group, n = 24, performed biochemical tests and measurements of anthropometric parameters and AGEs-sAF. In addition, HD group performed measurement of intact parathormone (iPTH, transthoracic echocardiogram and radiographies of pelvis and hands for vascular calcification score. Results: AGEs-sAF levels are elevated both in HD and control subjects ranged according to the age, although higher at HD than control group. Single high-flux HD session does not affect AGEs-sAF levels. AGEs-sAF levels were not related to ventricular mass, interventricular septum or vascular calcification in HD group. AGEs-sAF levels were negatively associated with serum iPTH levels. Conclusion: Our study detected a negative correlation of AGEs-sAF with serum iPTH, suggesting a role of AGEs on the pathophysiology of bone disease in HD prevalent patients. The nature of this relation and the clinical application of this non-invasive methodology for evaluation AGEs deposition must be confirmed and clarified in future studies.

Pharmacokinetics of erythropoietin in intact and anephric dogs

International Nuclear Information System (INIS)

Fu, J.S.; Lertora, J.J.; Brookins, J.; Rice, J.C.; Fisher, J.W.

1988-01-01

The present studies were performed to determine the pharmacokinetic parameters of erythropoietin in intact and anephric dogs by use of unlabeled crude native erythropoietin (nEp) and iodine 125-labeled purified recombinant erythropoietin (rEp) given by intravenous infusion for 15 minutes. Sephadex G-75 gel filtration was used to confirm that the 125I-rEp molecule remained iodinated in dog plasma during the 24-hour period of these studies. The plasma disappearance of erythropoietin conformed to a biexponential equation for both nEp and 125I-rEp, with the central compartment being larger than the peripheral compartment. The mean distribution half-life of 75.3 +/- 21.2 minutes for nEp was significantly (p less than 0.05) longer than that of 125I-rEp (23.7 +/- 5.0 minutes) in intact dogs. The intercompartmental clearance (CIic) for nEp (0.018 +/- 0.006 L/kg/hr) was significantly smaller than that of 125I-rEp (0.068 +/- 0.018 L/kg/hr) in intact dogs (p less than 0.05). There were no significant differences in apparent volume of distribution, elimination half-life, and elimination clearance (CIe) for nEp and rEp in intact dogs. The mean elimination half-life for 125I-rEp in intact dogs (9.0 +/- 0.6 hours) and anephric dogs (13.8 +/- 1.4 hours) was significantly different (p less than 0.05). The CIe for 125I-rEp in anephric dogs (0.008 +/- 0.001 L/kg/hr) was significantly (p less than 0.05) smaller than that of 125I-rEp in intact dogs (0.011 +/- 0.001 L/kg/hr). There were no significant differences in apparent volume of distribution, distribution half-life, and CIic for 125I-rEp in intact and anephric dogs

[Parathyroid cancer in a patient with previous history of hypernephroma: a clinical case].

Science.gov (United States)

Martín Navarro, J; Mendoza, E; Mateos, P; Cereceda, A; Coca, S

2007-01-01

We report the clinical case of a 55 year-old male patient, with a previous history of nephrectomy by hypernephroma sixteen years ago, first presenting hypercalcemia and rising of intact parathyroid hormone (iPTH) levels. A localization study revealed an intrathyroid nodule with cystic appearance. After undergoing a hemi-thyroidectomy, the patient is diagnosed with parathyroid carcinoma. This article analyzes previously published cases presenting parathyroidal pathologies associated with hypernephroma. A broader differential diagnosis--including the screening of parathyroidal pathologies should be considered in patients with hypercalcemia and hypernephroma.

Quantitative Analysis of Human Salivary Gland-Derived Intact Proteome Using Top-Down Mass Spectrometry

Energy Technology Data Exchange (ETDEWEB)

Wu, Si; Brown, Joseph N.; Tolic, Nikola; Meng, Da; Liu, Xiaowen; Zhang, Haizhen; Zhao, Rui; Moore, Ronald J.; Pevzner, Pavel A.; Smith, Richard D.; Pasa-Tolic, Ljiljana

2014-05-31

There are several notable challenges inherent to fully characterizing the entirety of the human saliva proteome using bottom-up approaches, including polymorphic isoforms, post-translational modifications, unique splice variants, deletions, and truncations. To address these challenges, we have developed a top-down based liquid chromatography-mass spectrometry (LC-MS) approach, which cataloged 20 major human salivary proteins with a total of 83 proteoforms, containing a broad range of post-translational modifications. Among these proteins, several previously reported disease biomarker proteins were identified at the intact protein level, such as beta-2 microglobulin (B2M). In addition, intact glycosylated proteoforms of several saliva proteins were also characterized, including intact N-glycosylated protein prolactin inducible protein (PIP) and O-glycosylated acidic protein rich protein (aPRP). These characterized proteoforms constitute an intact saliva proteoform database, which was used for quantitative comparison of intact salivary proteoforms among six healthy individuals. Human parotid (PS) and submandibular/sublingual gland (SMSL) secretion samples (2 μg of protein each) from six healthy individuals were compared using RPLC coupled with the 12T FTICR mass spectrometer. Significantly different protein and PTM patterns were resolved with high reproducibility between PS and SMSL glands. The results from this study provide further insight into the potential mechanisms of PTM pathways in oral glandular secretion, expanding our knowledge of this complex yet easily accessible fluid. Intact protein LC-MS approach presented herein can potentially be applied for rapid and accurate identification of biomarkers from only a few microliters of human glandular saliva.

Isolation of intact elastin fibers devoid of microfibrils.

NARCIS (Netherlands)

Daamen, W.F.; Hafmans, T.G.M.; Veerkamp, J.H.; Kuppevelt, A.H.M.S.M. van

2005-01-01

Purification protocols for elastin generally result in greatly damaged elastin fibers and this likely influences the biological response. We here describe a novel protocol for the isolation of elastin whereby the fibers stay intact, and introduce the term "elastin fiber" for intact elastic fibers

Intact and Degraded Component Criticality Calculations of N Reactor Spent Nuclear Fuel

International Nuclear Information System (INIS)

L. Angers

2001-01-01

The objective of this calculation is to perform intact and degraded mode criticality evaluations of the Department of Energy's (DOE) N Reactor Spent Nuclear Fuel codisposed in a 2-Defense High-Level Waste (2-DHLW)/2-Multi-Canister Overpack (MCO) Waste Package (WP) and emplaced in a monitored geologic repository (MGR) (see Attachment I). The scope of this calculation is limited to the determination of the effective neutron multiplication factor (k eff ) for both intact and degraded mode internal configurations of the codisposal waste package. This calculation will support the analysis that will be performed to demonstrate the technical viability for disposing of U-metal (N Reactor) spent nuclear fuel in the potential MGR

Differential effects of androgens on coronary blood flow regulation and arteriolar diameter in intact and castrated swine

Directory of Open Access Journals (Sweden)

O’Connor Erin K

2012-05-01

Full Text Available Abstract Background Low endogenous testosterone levels have been shown to be a risk factor for the development of cardiovascular disease and cardiovascular benefits associated with testosterone replacement therapy are being advocated; however, the effects of endogenous testosterone levels on acute coronary vasomotor responses to androgen administration are not clear. The objective of this study was to compare the effects of acute androgen administration on in vivo coronary conductance and in vitro coronary microvascular diameter in intact and castrated male swine. Methods Pigs received intracoronary infusions of physiologic levels (1–100 nM of testosterone, the metabolite 5α-dihydrotestosterone, and the epimer epitestosterone while left anterior descending coronary blood flow and mean arterial pressure were continuously monitored. Following sacrifice, coronary arterioles were isolated, cannulated, and exposed to physiologic concentrations (1–100 nM of testosterone, 5α-dihydrotestosterone, and epitestosterone. To evaluate effects of the androgen receptor on acute androgen dilation responses, real-time PCR and immunohistochemistry for androgen receptor were performed on conduit and resistance coronary vessels. Results In vivo, testosterone and 5α-dihydrotestosterone produced greater increases in coronary conductance in the intact compared to the castrated males. In vitro, percent maximal dilation of microvessels was similar between intact and castrated males for testosterone and 5α-dihydrotestosterone. In both studies epitestosterone produced significant increases in conductance and microvessel diameter from baseline in the intact males. Androgen receptor mRNA expression and immunohistochemical staining were similar in intact and castrated males. Conclusions Acute coronary vascular responses to exogenous androgen administration are increased by endogenous testosterone, an effect unrelated to changes in androgen receptor expression.

Effects of Sucroferric Oxyhydroxide Compared to Lanthanum Carbonate and Sevelamer Carbonate on Phosphate Homeostasis and Vascular Calcifications in a Rat Model of Chronic Kidney Failure

Directory of Open Access Journals (Sweden)

Olivier Phan

2015-01-01

Full Text Available Elevated serum phosphorus, calcium, and fibroblast growth factor 23 (FGF23 levels are associated with cardiovascular disease in chronic renal disease. This study evaluated the effects of sucroferric oxyhydroxide (PA21, a new iron-based phosphate binder, versus lanthanum carbonate (La and sevelamer carbonate (Se, on serum FGF23, phosphorus, calcium, and intact parathyroid hormone (iPTH concentrations, and the development of vascular calcification in adenine-induced chronic renal failure (CRF rats. After induction of CRF, renal function was significantly impaired in all groups: uremic rats developed severe hyperphosphatemia, and serum iPTH increased significantly. All uremic rats (except controls then received phosphate binders for 4 weeks. Hyperphosphatemia and increased serum iPTH were controlled to a similar extent in all phosphate binder-treatment groups. Only sucroferric oxyhydroxide was associated with significantly decreased FGF23. Vascular calcifications of the thoracic aorta were decreased by all three phosphate binders. Calcifications were better prevented at the superior part of the thoracic and abdominal aorta in the PA21 treated rats. In adenine-induced CRF rats, sucroferric oxyhydroxide was as effective as La and Se in controlling hyperphosphatemia, secondary hyperparathyroidism, and vascular calcifications. The role of FGF23 in calcification remains to be confirmed.

Plasma intact fibroblast growth factor 23 levels in women with bulimia nervosa: A cross-sectional pilot study

Directory of Open Access Journals (Sweden)

Yoshiuchi Kazuhiro

2011-06-01

Full Text Available Abstract Fibroblast growth factor (FGF 23, a circulating 26-kDa peptide produced by osteogenic cells, is a novel phosphaturic factor. In our previous study, binge-eating/purging type anorexia nervosa (AN-BP patients had elevated plasma intact FGF23 (iFGF23 levels, while restricting type (AN-R patients had plasma iFGF23 levels similar to healthy controls. Although bulimia nervosa (BN patients as well as some patients with AN-BP regularly engage in binge eating, there have been no studies regarding plasma iFGF23 levels in BN patients. Therefore, this study was performed to determine plasma iFGF23 concentrations in BN patients and healthy controls. The study population consisted of 13 female BN patients and 11 healthy female controls. Blood samples were collected from all subjects after overnight fasting. Plasma iFGF23 was measured using an ELISA kit in a cross-sectional manner. The two-tailed Mann-Whitney U-test was used to assess differences between BN patients and healthy controls. In addition, BN patients were divided into two groups based on questionnaire-reported binge eating frequency immediately prior to participation in this study: high frequency of binge eating (once a week or more; HF group; n = 8 and low frequency of binge eating (less than once a week; LF group; n = 5. Two-tailed Mann-Whitney U-test with Bonferroni's correction was performed after the Kruskal-Wallis test to assess differences between HF group, LF group, and healthy controls. Median (quartiles plasma iFGF23 levels were greater in BN patients (35.5 [14.8-65.0] pg/ml than in controls (3.8 [not detected-5.3] pg/ml; p = 0.002. In addition, median (quartiles plasma iFGF23 levels were greater in the HF group (62.3 [44.4-73.4] pg/ml than in controls (p

A phase 3, multicentre, randomized, double-blind, placebo-controlled, parallel-group study to evaluate the efficacy and safety of etelcalcetide (ONO-5163/AMG 416), a novel intravenous calcimimetic, for secondary hyperparathyroidism in Japanese haemodialysis patients.

Science.gov (United States)

Fukagawa, Masafumi; Yokoyama, Keitaro; Shigematsu, Takashi; Akiba, Takashi; Fujii, Akifumi; Kuramoto, Takuto; Odani, Motoi; Akizawa, Tadao

2017-10-01

Secondary hyperparathyroidism (SHPT) is a major complication associated with chronic kidney disease. We evaluated the efficacy and safety of etelcalcetide (ONO-5163/AMG 416), a novel intravenous calcimimetic, in Japanese haemodialysis patients with SHPT. In this phase 3, multicentre, randomized, double-blind, placebo-controlled, parallel-group study, etelcalcetide was administered three times per week at an initial dose of 5 mg, and subsequently adjusted to doses between 2.5 and 15 mg at 4-week intervals for 12 weeks. A total of 155 SHPT patients with serum intact parathyroid hormone (iPTH) levels ≥300 pg/mL were assigned to receive etelcalcetide (n = 78) or placebo (n = 77). The primary endpoint was the proportion of patients with decreased serum iPTH to the target range proposed by the Japanese Society for Dialysis Therapy (60-240 pg/mL). The major secondary endpoint was the proportion of patients with ≥30% reductions in serum iPTH from baseline. The proportion of patients meeting the primary endpoint was significantly higher for etelcalcetide (59.0%) versus placebo (1.3%). Similarly, the proportion of patients meeting the major secondary endpoint was significantly higher for etelcalcetide (76.9%) versus placebo (5.2%). Serum albumin-corrected calcium, phosphorus and intact fibroblast growth factor-23 levels were decreased in the etelcalcetide group. Nausea, vomiting and symptomatic hypocalcaemia were mild with etelcalcetide. Serious adverse events related to etelcalcetide were not observed. This study demonstrated the efficacy and safety of etelcalcetide. As the only available intravenous calcium-sensing receptor agonist, etelcalcetide is likely to provide a new treatment option for SHPT in haemodialysis patients. © The Author 2017. Published by Oxford University Press on behalf of ERA-EDTA.

Urinary calcium to creatinine ratio: a potential marker of secondary hyperparathyroidism in patients with vitamin D-dependent rickets type 1A.

Science.gov (United States)

Miyai, Kentaro; Onishi, Toshikazu; Kashimada, Kenichi; Hasegawa, Yukihiro

2015-01-01

Patients with vitamin D-dependent rickets type 1A (VDDR1A) are usually treated with alfacalcidol, an analog of vitamin D. Around puberty, an increased dose of alfacalcidol is recommended for these patients to avoid hypocalcemia and secondary hyperparathyroidism. However, no indicators of secondary hyperparathyroidism except for PTH are presently known. The aim of this study is to evaluate whether urinary calcium to creatinine ratio (U-Ca/Cr) is useful as a biomarker of secondary hyperparathyroidism in VDDR1A patients in order to determine the proper dose of alfacalcidol. Two brothers with VDDR1A were recruited who had null mutations of CYP27B1 which encodes 1-alpha-hydroxylase of vitamin D. We investigated the relationship between U-Ca/Cr and intact-PTH around puberty when the brothers showed hypocalcemia with secondary hyperparathyroidism. The results were compared to those of five patients with vitamin D deficiency (VDD). As a result, high intact-PTH levels were observed when U-Ca/Cr decreased to less than 0.1 (mg/mg) in both VDDR1A brothers. This relationship was also observed in the VDD patients. However, it is necessary to take into account body calcium status, either in depletion or in excess, to accurately evaluate the relationship between U-Ca/Cr and secondary hyperparathyroidism. First, low U-Ca/Cr was detected in situations with calcium depletion without hyperparathyroidism in the VDDR1A patients. Second, high U-Ca/Cr with hyperparathyroidism could be detected theoretically in a condition of excess calcium supply. In conclusion, a U-Ca/Cr ratio of less than 0.1 (mg/mg) in VDDR1A patients is useful to accurately evaluate calcium depletion and secondary hyperparathyroidism.

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.

Science.gov (United States)

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.

Serum Parathyroid Hormone Is a New Potential Risk Factor in Multiple Myeloma

Directory of Open Access Journals (Sweden)

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.

Anti-parathyroid treatment effectiveness and persistence in incident haemodialysis patients with secondary hyperparathyroidism.

Science.gov (United States)

de Francisco, Angel Luis Martín; Gillespie, Iain Andrew; Gioni, Ioanna; Floege, Jürgen; Kronenberg, Florian; Marcelli, Daniele; Wheeler, David Collins; Froissart, Marc; Drueke, Tilman Bernhard

2016-01-01

Anti-parathyroid treatment initiation and discontinuation are important decisions in chronic haemodialysis (HD) patients, where pill burden is often excessive. The present study aimed to describe secondary hyperparathyroidism (sHPT) drug therapy changes in HD patients. Retrospective observational cohort study of incident European HD patients with sHPT who were prescribed calcitriol or alfacalcidol (alpha calcitriol), paricalcitol or cinacalcet. Treatment-naïve patients prescribed alpha calcitriol (N=2259), paricalcitol (N=1689) and cinacalcet (N=1245) were considered for analysis. Serum intact parathyroid hormone (iPTH) levels decreased post-initiation with all treatment modalities; serum calcium and phosphate levels increased in response to activated vitamin D derivatives but decreased with cinacalcet. Approximately one-third of alpha calcitriol and paricalcitol patients but less than one-quarter of cinacalcet patients discontinued treatment. Although the three groups had comparable serum iPTH control at the time of treatment discontinuation, they differed in terms of calcium and phosphate levels. Following discontinuation, the evolution of laboratory parameters differed by treatment modality: whilst iPTH increased for all three treatment groups, calcium and phosphate decreased in patients who were being treated with alpha calcitriol and paricalcitol at the time of discontinuation, and increased in those who had been treated with cinacalcet. In conditions of daily clinical practice, attaining and maintaining recommended biochemical control of sHPT appears to be more frequently achievable with cinacalcet than with activated vitamin D compounds. Copyright © 2015 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

Global forest loss disproportionately erodes biodiversity in intact landscapes.

Science.gov (United States)

Betts, Matthew G; Wolf, Christopher; Ripple, William J; Phalan, Ben; Millers, Kimberley A; Duarte, Adam; Butchart, Stuart H M; Levi, Taal

2017-07-27

Global biodiversity loss is a critical environmental crisis, yet the lack of spatial data on biodiversity threats has hindered conservation strategies. Theory predicts that abrupt biodiversity declines are most likely to occur when habitat availability is reduced to very low levels in the landscape (10-30%). Alternatively, recent evidence indicates that biodiversity is best conserved by minimizing human intrusion into intact and relatively unfragmented landscapes. Here we use recently available forest loss data to test deforestation effects on International Union for Conservation of Nature Red List categories of extinction risk for 19,432 vertebrate species worldwide. As expected, deforestation substantially increased the odds of a species being listed as threatened, undergoing recent upgrading to a higher threat category and exhibiting declining populations. More importantly, we show that these risks were disproportionately high in relatively intact landscapes; even minimal deforestation has had severe consequences for vertebrate biodiversity. We found little support for the alternative hypothesis that forest loss is most detrimental in already fragmented landscapes. Spatial analysis revealed high-risk hot spots in Borneo, the central Amazon and the Congo Basin. In these regions, our model predicts that 121-219 species will become threatened under current rates of forest loss over the next 30 years. Given that only 17.9% of these high-risk areas are formally protected and only 8.9% have strict protection, new large-scale conservation efforts to protect intact forests are necessary to slow deforestation rates and to avert a new wave of global extinctions.

Effects of Diabetes Mellitus, Age, and Duration of Dialysis on Parathormone in Chronic Hemodialysis Patients

Directory of Open Access Journals (Sweden)

Nasri Hamid

2008-01-01

Full Text Available Secondary hyperparathyroidism (SHPTH can develop early in the course of chronic renal failure and becomes more prominent as kidney function declines. We studied the effect of diabetes, age, and dialysis on parathyroid function in 60 (21 women, 39 males; 44 non-diabetic, 16 diabetic hemodialysis (HD patients. Serum intact PTH (iPTH, calcium, phosphorus, alkaline phosphatase (ALP, and magnesium (Mg were measured. Adequacy of HD was evaluated by calculating the urea reduction rate (URR. There were significantly lower values of serum iPTH, ALP, and dialysis adequacy among diabetic than non-diabetes HD patients. In addition, there were an inverse correlation of age and serum iPTH (r= -0.27, p= 0.034 as well as age and serum phosphorus (r= -0.28, p= 0.031. There was also a positive correlation between serum iPTH with the duration (r= 0.001, p=0.42 and doses of dialysis treatment (r= 0.38, p= 0.002. We conclude that a significant negative correlation between age and serum phosphorus and lower parathyroid activity in diabetic HD patients, which implies more prevalence of bone disease in elderly diabetic HD patients. Further study of bone disease in this group of patients is required to evaluate its effect on outcome and different therapeutic interventions.

Impact of Annexin A 7 Deficiency on FGF23 Plasma Concentrations

Directory of Open Access Journals (Sweden)

Anja T. Umbach

2016-11-01

Full Text Available Background/Aims: The release of fibroblast growth factor FGF23, a powerful regulator of 1,25(OH2D3 formation and mineral metabolism, is stimulated by store-operated Ca2+ entry (SOCE, which is accomplished by the pore forming Ca2+ release activated channel protein Orai1. Regulators of Orai1 and thus FGF23 release include serum & glucocorticoid inducible kinase SGK1, a kinase up-regulated by glucocorticosteroids. Some effects of glucocorticoids require the presence of annexin A7, such as suppression of prostaglandin E2 in gastric glands. The present study thus explored whether annexin A7 impacts on FGF23 plasma levels. Methods: Comparisons were made between gene targeted mice lacking functional annexin A7 (Anx7-/- and their wild type littermates (Anx7+/+. Serum C-terminal-FGF23, intact FGF23, 1,25(OH2D3 and PTH concentrations were measured by ELISA or EIA. The serum and urinary phosphate concentrations were measured by colorimetry, the serum Ca2+ concentration and the urinary Ca2+ concentration by flame photometry. Results: Serum C-terminal FGF23 levels and corticosterone levels were significantly higher and serum 1,25(OH2 D3 and PTH levels were significantly lower in Anx7-/- than in Anx7+/+ mice. Water intake was slightly but significantly higher in Anx7-/- mice than in Anx7+/+ mice. No significant difference was observed between Anx7-/- and Anx7+/+ mice in urinary fluid excretion, plasma Ca2+ concentration, plasma phosphate concentration and urinary Ca2+ output. The urinary phosphate output was significantly lower in Anx7-/- mice than in Anx7+/+ mice. Conclusion: Annexin A7 deficiency upregulates FGF23 plasma levels, an effect paralleled by increased corticosterone plasma levels, as well as decreased 1,25(OH2 D3 and PTH plasma levels.

Visual speech alters the discrimination and identification of non-intact auditory speech in children with hearing loss.

Science.gov (United States)

Jerger, Susan; Damian, Markus F; McAlpine, Rachel P; Abdi, Hervé

2017-03-01

responses for the intact vs. non-intact different pairs (e.g., Baa:/-B/aa) and more intact onset responses for nonword repetition (Baz for/-B/az). Thus visual speech altered both discrimination and identification in the CHL-to a large extent for the/B/onsets but only minimally for the/G/onsets. The CHL identified the stimuli similarly to the CNH but did not discriminate the stimuli similarly. A bias-free measure of the children's discrimination skills (i.e., d' analysis) revealed that the CHL had greater difficulty discriminating intact from non-intact speech in both modes. As the degree of HL worsened, the ability to discriminate the intact vs. non-intact onsets in the auditory mode worsened. Discrimination ability in CHL significantly predicted their identification of the onsets-even after variation due to the other variables was controlled. These results clearly established that visual speech can fill in non-intact auditory speech, and this effect, in turn, made the non-intact onsets more difficult to discriminate from intact speech and more likely to be perceived as intact. Such results 1) demonstrate the value of visual speech at multiple levels of linguistic processing and 2) support intervention programs that view visual speech as a powerful asset for developing spoken language in CHL. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Visual Speech Alters the Discrimination and Identification of Non-Intact Auditory Speech in Children with Hearing Loss

Science.gov (United States)

Jerger, Susan; Damian, Markus F.; McAlpine, Rachel P.; Abdi, Hervé

2017-01-01

Performance in the audiovisual mode showed more same responses for the intact vs. non-intact different pairs (e.g., Baa:/–B/aa) and more intact onset responses for nonword repetition (Baz for/–B/az). Thus visual speech altered both discrimination and identification in the CHL—to a large extent for the /B/ onsets but only minimally for the /G/ onsets. The CHL identified the stimuli similarly to the CNH but did not discriminate the stimuli similarly. A bias-free measure of the children’s discrimination skills (i.e., d’ analysis) revealed that the CHL had greater difficulty discriminating intact from non-intact speech in both modes. As the degree of HL worsened, the ability to discriminate the intact vs. non-intact onsets in the auditory mode worsened. Discrimination ability in CHL significantly predicted their identification of the onsets—even after variation due to the other variables was controlled. Conclusions These results clearly established that visual speech can fill in non-intact auditory speech, and this effect, in turn, made the non-intact onsets more difficult to discriminate from intact speech and more likely to be perceived as intact. Such results 1) demonstrate the value of visual speech at multiple levels of linguistic processing and 2) support intervention programs that view visual speech as a powerful asset for developing spoken language in CHL. PMID:28167003

Hip fracture risk in relation to vitamin D supplementation and serum 25-hydroxyvitamin D levels: a systematic review and meta-analysis of randomised controlled trials and observational studies

Directory of Open Access Journals (Sweden)

Roddam Andrew W

2010-06-01

Full Text Available Abstract Background Vitamin D supplementation for fracture prevention is widespread despite conflicting interpretation of relevant randomised controlled trial (RCT evidence. This study summarises quantitatively the current evidence from RCTs and observational studies regarding vitamin D, parathyroid hormone (PTH and hip fracture risk. Methods We undertook separate meta-analyses of RCTs examining vitamin D supplementation and hip fracture, and observational studies of serum vitamin D status (25-hydroxyvitamin D (25(OHD level, PTH and hip fracture. Results from RCTs were combined using the reported hazard ratios/relative risks (RR. Results from case-control studies were combined using the ratio of 25(OHD and PTH measurements of hip fracture cases compared with controls. Original published studies of vitamin D, PTH and hip fracture were identified through PubMed and Web of Science databases, searches of reference lists and forward citations of key papers. Results The seven eligible RCTs identified showed no significant difference in hip fracture risk in those randomised to cholecalciferol or ergocalciferol supplementation versus placebo/control (RR = 1.13[95%CI 0.98-1.29]; 801 cases, with no significant difference between trials of 21 (heterogeneity = 51.02, p 216 (heterogeneity = 137.9, p 29 (heterogeneity = 149.68, p Conclusions Neither higher nor lower dose vitamin D supplementation prevented hip fracture. Randomised and observational data on vitamin D and hip fracture appear to differ. The reason for this is unclear; one possible explanation is uncontrolled confounding in observational studies. Post-fracture PTH levels are unrelated to hip fracture risk.

Direct suppressive effect of acute metabolic and respiratory alkalosis on parathyroid hormone secretion in the dog.

Science.gov (United States)

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

Long-Term Therapy Outcomes When Treating Chronic Kidney Disease Patients with Paricalcitol in German and Austrian Clinical Practice (TOP Study

Directory of Open Access Journals (Sweden)

Nicholas Obermüller

2017-09-01

Full Text Available Paricalcitol is approved for prevention and therapy of secondary hyperparathyroidism (sHPT in patients with chronic kidney disease (CKD, with only short-term data in clinical routine settings. A 12-month observational study was conducted in Germany and Austria (90 centers, 761 patients from 2008 to 2013. Laboratory values, demographical, and clinical data were documented in 629 dialysis patients and 119 predialysis patients. In predialysis patients, median intact parathormone (iPTH was 180.0 pg/mL (n = 105 at the start of the study, 115.7 pg/mL (n = 105 at last documentation, and 151.8 pg/mL (n = 50 at month 12, with 32.4% of the last documented iPTH values in the KDOQI (Kidney Disease Outcomes Quality Initiative target range. In dialysis patients, median iPTH was 425.5 pg/mL (n = 569 at study start, 262.3 pg/mL (n = 569 at last documentation, and 266.1 pg/mL (n = 318 at month 12, with 36.5% of dialysis patients in the KDOQI target range. Intravenous paricalcitol showed more homogenous iPTH control than oral treatment. Combined analysis of all dialysis patients indicated comparable and stable mean serum calcium and phosphate levels throughout the study. Clinical symptoms, such as itching, bone pain, and fatigue, were improved compared with study entry. The spectrum and frequency of adverse events mirrored the known pattern for patients on dialysis. Paricalcitol is efficacious and has a consistent safety profile in sHPT over 12 months.

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.

Science.gov (United States)

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.

Characterization of the anion sensitive ATPase in intact vacuoles of Kalanchoe diagremontiana

Energy Technology Data Exchange (ETDEWEB)

Kobza, J.; Uribe, E.G.

1986-04-01

A method for the isolation of intact vacuoles from K. daigremontiana was developed which produced high yields of relatively pure vacuoles as determined by marker enzyme contamination. Upon isolation, the vacuoles were stabilized by the inclusion of 5% (w/v) ficoll. Enzyme activity was insensitive to vanadate and azide but was strongly inhibited by DCCD. Enzyme activity was strictly dependent on the inclusion of Mg/sup 2 +/ and was stimulated by anions as depicted by the series, NO/sub 3//sup -/ < Br/sup -/ < SO/sub 4//sup -/ < HCO/sub 3//sup -/ < Cl/sup -/. It was found that in intact vacuoles the ATPase activity was stimulated by phosphate to a level equivalent to that found with the chloride. The enzyme exhibited Michaelis-Menten kinetics with a Km for Mg-ATP complex of 0.51 mM.

A new point mutation in the deoxyribonuclic acid-binding domain of the vitamine D receptor in a kindred with hereditary 1,25-dihydroxyvitamin d-resistant rickets

Energy Technology Data Exchange (ETDEWEB)

Yagi, Hideki; Miyake, Hiroshi; Nagashima, Kanji; Kuroume, Takayoshi (Gunma Univ. School of Medicine (Japan)); Ozone, K.; Pike, J.W. (Baylor College of Medicine, Houston, TX (United States))

1993-02-01

Hereditary 1,25-dihydroxyvitamin D [1,25-(OH)[sub 2]D]-resistant rickets (HVDRR) is a rare disorder characterized by rickets, alopecia, hypocalcemia, secondary hyperparathyroidism, and normal or elevated serum 1,25-dihydroxyvitamin D levels. The authors describe a patient with typical clinical characteristics of HVDRR, except that elevated levels of serum phosphorus were present coincident with increased levels of serum intact PTH. The patient was treated with high dose calcium infusion after an ineffective treatment with 1[alpha]-hydroxyvitamin D[sub 3]; serum calcium and phosphorus as well as intact PTH and alkaline phosphatase levels were normalized. Evaluation of phytohemagglutinin-activated lymphocytes derived from this patient revealed that 1,25-(OH)[sub 2]D[sub 3] was unable to inhibit thymidine incooperation, a result that contrast with the capacity of 1,25-(OH)[sub 2]D[sub 3] to inhibit uptake into normal activated lymphocytes. 1,25-(OH)[sub 2]D[sub 3] did not induce human osteocalcin promoter activity after transfection of this DNA linked to a reporter gene into patient cells. Cointroduction of a human vitamin D receptor (VDR) cDNA expression vector with the reporter plasmid, however, restored the hormone response. Evaluation of extracts from the patient cells for VDR DNA binding revealed a defect in DNA binding. Analysis of genomic DNA from the patient's cells by PCR confirmed the presence of a point mutation in exon 2 of the VDR. This exon directs synthesis of a portion of the DNA-binding domain of the receptor. We conclude that the genetic basis for 1,25-(OH)[sub 2]D[sub 3] resistance in this kindred with VDR-positive HVDRR is due to a single base mutation in the VDR that leads to production of a receptor unable to interact appropriately with DNA. 20 refs., 3 figs., 1 tab.

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....

Establishment of sandwich ELISA for soluble alpha-Klotho measurement: Age-dependent change of soluble alpha-Klotho levels in healthy subjects.

Science.gov (United States)

Yamazaki, Yuji; Imura, Akihiro; Urakawa, Itaru; Shimada, Takashi; Murakami, Junko; Aono, Yukiko; Hasegawa, Hisashi; Yamashita, Takeyoshi; Nakatani, Kimihiko; Saito, Yoshihiko; Okamoto, Nozomi; Kurumatani, Norio; Namba, Noriyuki; Kitaoka, Taichi; Ozono, Keiichi; Sakai, Tomoyuki; Hataya, Hiroshi; Ichikawa, Shoji; Imel, Erik A; Econs, Michael J; Nabeshima, Yo-Ichi

2010-07-30

Alpha-Klotho (alphaKl) regulates mineral metabolism such as calcium ion (Ca(2+)) and inorganic phosphate (Pi) in circulation. Defects in mice result in clinical features resembling disorders found in human aging. Although the importance of transmembrane-type alphaKl has been demonstrated, less is known regarding the physiological importance of soluble-type alphaKl (salphaKl) in circulation. The aims of this study were: (1) to establish a sandwich ELISA system enabling detection of circulating serum salphaKl, and (2) to determine reference values for salphaKl serum levels and relationship to indices of renal function, mineral metabolism, age and sex in healthy subjects. We successively developed an ELISA to measure serum salphaKl in healthy volunteers (n=142, males 66) of ages (61.1+/-18.5year). The levels (mean+/-SD) in these healthy control adults were as follows: total calcium (Ca; 9.46+/-0.41mg/dL), Pi (3.63+/-0.51mg/dL), blood urea nitrogen (BUN; 15.7+/-4.3mg/dL), creatinine (Cre; 0.69+/-0.14mg/dL), 1,25 dihydroxyvitamin D (1,25(OH)(2)D; 54.8+/-17.7pg/mL), intact parathyroid hormone (iPTH; 49.2+/-20.6pg/mL), calcitonin (26.0+/-12.3pg/mL) and intact fibroblast growth factor (FGF23; 43.8+/-17.6pg/mL). Serum levels of salphaKl ranged from 239 to 1266pg/mL (mean+/-SD; 562+/-146pg/mL) in normal adults. Although salphaKl levels were not modified by gender or indices of mineral metabolism, salphaKl levels were inversely related to Cre and age. However, salphaKl levels in normal children (n=39, males 23, mean+/-SD; 7.1+/-4.8years) were significantly higher (mean+/-SD; 952+/-282pg/mL) than those in adults (mean+/-SD; 562+/-146, Plevel was notably lower than those of age-matched controls. We established a detection system to measure human serum salphaKl for the first time. Age, Ca and Pi seem to influence serum salphaKl levels in a normal population. This detection system should be an excellent tool for investigating salphaKl functions in mineral metabolism. Copyright

Screening for secondary hyperparathyroidism in preterm infants.

Science.gov (United States)

Dowa, Yuri; Kawai, Masahiko; Kanazawa, Hoshinori; Iwanaga, Kougoro; Matsukura, Takashi; Heike, Toshio

2016-10-01

The major cause of osteopathy of prematurity is dietary phosphate deficiency, but secondary hyperparathyroidism caused by calcium deficiency or vitamin D deficiency is also important. Because parathyroid hormone (PTH) mobilizes calcium and phosphate from the bone, hyperparathyroidism worsens osteopathy of prematurity. In order to identify useful markers to screen for and diagnose hyperparathyroidism in preterm infants, we measured serum and urinary biochemical markers. Several biomarkers, including serum intact PTH (iPTH), were measured in urine and serum samples obtained from 95 preterm infants, and the relationship between serum iPTH and the other parameters was analyzed. Mean gestation was 33.2 ± 2.9 weeks, and mean birthweight was 1705 ± 402 g. Samples were collected around postnatal day 17.3 ± 7.4. Fourteen infants (14.7%) had iPTH >65 pg/mL. Cut-offs for serum alkaline phosphatase (ALP) and percent tubular reabsorption rate of phosphate (%TRP) were fixed at 1300 IU/L and 93%, respectively using receiver operating characteristic curves with iPTH cut-off of 65 pg/mL. Serum ALP was proven to be a good marker: ALP had a sensitivity of 78.6% and a specificity of 86.4%, while %TRP itself was not: %TRP had a sensitivity of 64.3% and a specificity of 58.0%. Combined measurement of serum ALP (>1300 IU/L) and %TRP (≤93%), however, had a specificity of 93.8% for detecting elevated iPTH. Measurement of serum ALP (>1300 IU/L) is considered as an effective screening method to detect hyperparathyroidism. In addition, combined assessment of ALP(>1300 IU/L) and %TRP(≤93%) is a good indicator of elevated iPTH in preterm infants. © 2016 Japan Pediatric Society.

pGlyco 2.0 enables precision N-glycoproteomics with comprehensive quality control and one-step mass spectrometry for intact glycopeptide identification.

Science.gov (United States)

Liu, Ming-Qi; Zeng, Wen-Feng; Fang, Pan; Cao, Wei-Qian; Liu, Chao; Yan, Guo-Quan; Zhang, Yang; Peng, Chao; Wu, Jian-Qiang; Zhang, Xiao-Jin; Tu, Hui-Jun; Chi, Hao; Sun, Rui-Xiang; Cao, Yong; Dong, Meng-Qiu; Jiang, Bi-Yun; Huang, Jiang-Ming; Shen, Hua-Li; Wong, Catherine C L; He, Si-Min; Yang, Peng-Yuan

2017-09-05

The precise and large-scale identification of intact glycopeptides is a critical step in glycoproteomics. Owing to the complexity of glycosylation, the current overall throughput, data quality and accessibility of intact glycopeptide identification lack behind those in routine proteomic analyses. Here, we propose a workflow for the precise high-throughput identification of intact N-glycopeptides at the proteome scale using stepped-energy fragmentation and a dedicated search engine. pGlyco 2.0 conducts comprehensive quality control including false discovery rate evaluation at all three levels of matches to glycans, peptides and glycopeptides, improving the current level of accuracy of intact glycopeptide identification. The N-glycoproteome of samples metabolically labeled with 15 N/ 13 C were analyzed quantitatively and utilized to validate the glycopeptide identification, which could be used as a novel benchmark pipeline to compare different search engines. Finally, we report a large-scale glycoproteome dataset consisting of 10,009 distinct site-specific N-glycans on 1988 glycosylation sites from 955 glycoproteins in five mouse tissues.Protein glycosylation is a heterogeneous post-translational modification that generates greater proteomic diversity that is difficult to analyze. Here the authors describe pGlyco 2.0, a workflow for the precise one step identification of intact N-glycopeptides at the proteome scale.

Total parathyroidectomy with forearm auto-transplantation improves the quality of life and reduces the recurrence of secondary hyperparathyroidism in chronic kidney disease patients.

Science.gov (United States)

Li, Jia-Gen; Xiao, Zhang-Sheng; Hu, Xian-Jie; Li, Yun; Zhang, Xing; Zhang, Song-Ze; Shan, Ai-Qin

2017-12-01

Our study aims to explore the effect of total parathyroidectomy (PTX) with forearm autotransplantation (FAT) on the quality of life and recurrence of secondary hyperparathyroidism (SHPT) in chronic kidney disease patients. A total of 104 chronic kidney disease patients with SHPT were enrolled and divided into the PTX (n = 62) and PTX + FAT (n = 42) groups. The operation efficacy was evaluated by analyzing preoperative and postoperative values, including levels of intact parathyroid hormone (iPTH), serum phosphorus, serum calcium, alkaline phosphatase (ALP), calcium-phosphorus product, signs and symptoms, and MOS 36-item short-form health survey (SF-36) scores. Moreover, complications and recurrences were followed up for 12 months after the operation. Binary logistic regression was to present the risk factors for the recurrence of chronic kidney disease patients with SHPT. Compared with the preoperative values, the PTX and PTX + FAT groups showed decrease postoperative levels of iPTH, serum phosphorus, serum calcium, calcium-phosphorus product, bone pain, and skin pruritus at all time periods. The PTX and PTX + FAT groups demonstrated decreased ALP, fracture or deformity, and coronary artery calcification at 1 month, decreased short stature at 3 months after the operation but increased SF-36 score after operation. Compared with the PTX group, the level of iPTH decreased and the levels of serum calcium, calcium-phosphorus product increased at 3, 6, and 12 months after the operation in the PTX + FAT group. The levels of ALP, fracture or deformity, short stature, and SF-36 decreased separately at 1 week and 6 and 12 months after the operation, along with the decrease of coronary artery calcification and the recurrence rate, respectively, at 6 and 12 months after the operation in the PTX + FAT group when compared with those in the PTX group. Logistic regression analysis evidenced that the preoperative iPTH level, SF-36 score, and operation

The effects of nocturnal compared with conventional hemodialysis on mineral metabolism: A randomized-controlled trial.

Science.gov (United States)

Walsh, Michael; Manns, Braden J; Klarenbach, Scott; Tonelli, Marcello; Hemmelgarn, Brenda; Culleton, Bruce

2010-04-01

Hyperphosphatemia is common among patients receiving dialysis and is associated with increased mortality. Nocturnal hemodialysis (NHD) is a long, slow dialytic modality that may improve hyperphosphatemia and disorders of mineral metabolism. We performed a randomized-controlled trial of NHD compared with conventional hemodialysis (CvHD); in this paper, we report detailed results of mineral metabolism outcomes. Prevalent patients were randomized to receive NHD 5 to 6 nights per week for 6to 10 hours per night or to continue CvHD thrice weekly for 6 months. Oral phosphate binders and vitamin D analogs were adjusted to maintain phosphate, calcium and parathyroid hormone (PTH) levels within recommended targets. Compared with CvHD patients, patients in the NHD group had a significant decrease in serum phosphate over the course of the study (0.49 mmol/L, 95% confidence interval 0.24-0.74; P=0.002) despite a significant reduction in the use of phosphate binders. Sixty-one percent of patients in the NHD group compared with 20% in the CvHD group had a decline in intact PTH (P=0.003). Nocturnal hemodialysis lowers serum phosphate, calcium-phosphate product and requirement for phosphate binders. The effects of NHD on PTH are variable. The impact of these changes on long-term cardiovascular and bone-related outcomes requires further investigation.

DNA damage in hemodialysis patients with chronic kidney disease; a test of the role of diabetes mellitus; a comet assay investigation.

Science.gov (United States)

Mamur, Sevcan; Unal, Fatma; Altok, Kadriye; Deger, Serpil Muge; Yuzbasioglu, Deniz

2016-04-01

The incidence of chronic kidney disease (CKD) is increasing rapidly. Diabetes mellitus (DM) is the most important cause of CKD. We studied the possible role of DM in CKD patients with respect to DNA damage, as assessed by the comet assay in 60 CKD patients (with or without DM) undergoing hemodialysis and in 26 controls. Effects of other factors, such as age, sex, hypertension, duration of hemodialysis, body mass index (BMI), and levels of hemoglobin (HB), intact parathormone (iPTH), and ferritin (FER), were also examined. Primary DNA damage measured by the comet assay was significantly higher in CKD patients than in controls. Among CKD patients, the following correlations were observed. (1) There was no difference in comet tail length or tail intensity between diabetic and non-diabetic individuals. (2) Age, sex, hemoglobin, hypertension, duration of hemodialysis, and ferritin levels affected neither tail length nor intensity. (3) BMI values above 25kg/m(2) and iPTH levels above 300pg/ml were associated with significantly greater comet tail length. Our results indicate that primary DNA damage is increased in CKD patients undergoing hemodialysis, compared to controls; however, DM had no additional effect. Copyright © 2016. Published by Elsevier B.V.

Severe hyperparathyroidism in a pre-dialysis chronic kidney disease patient treated with a very low protein diet.

Science.gov (United States)

Ohta, Eriko; Akazawa, Masanobu; Noda, Yumi; Mandai, Shintaro; Naito, Shotaro; Ohta, Akihito; Sohara, Eisei; Okado, Tomokazu; Rai, Tatemitsu; Uchida, Shinichi; Sasaki, Sei

2012-03-01

The present report describes a case of a 64-year-old pre-dialysis woman with chronic kidney disease (CKD) stage 5, who developed severe hyperparathyroidism. This patient had been on a very low protein diet (VLPD) to delay the progression of CKD and the need for renal replacement therapy (RRT). Her serum calcium levels were high-normal to slightly high during this time. However, her serum intact parathyroid hormone (PTH) levels increased from 400 to 1160 pg/ml rapidly over a period of 3 months. Serum 1,25-(OH)2D levels were low, and ultrasound of the neck showed three markedly enlarged parathyroid glands exceeding 2 cm. Parathyroidectomy was performed, and all glands showed nodular hyperplasia, which indicated severe secondary hyperparathyroidism leading to tertiary. Severe secondary hyperparathyroidism requiring surgical intervention is usually observed in patients with long-term RRT and is relatively rare in the pre-dialysis patient. In this case, extension of the pre-dialysis period by VLPD may have predisposed this patient to develop severe secondary hyperparathyroidism. Thus, careful monitoring of calcium, phosphorus, and PTH may be necessary in patients treated with VLPD even before renal replacement therapy. Furthermore, initiation of dialysis should not be excessively delayed by strict protein restriction dietary therapy.

Intact collagen and atelocollagen sponges: Characterization and ESEM observation

International Nuclear Information System (INIS)

Ruozi, Barbara; Tosi, Giovanni; Leo, Eliana; Parma, Bruna; Vismara, Susanna; Forni, Flavio; Vandelli, Maria Angela

2007-01-01

In this study we have investigated the chemical-physical and morphological properties of intact and atelocollagen sponges used for tissue engineering. The porous sponges were prepared by lyophilization and their physico-chemical characteristics (water binding capacity, denaturing temperature, amino group content) were investigated. Considering the importance of the 'in vivo' interactions between these sponges and the tissue, our attention was addressed (a) to clarify the relationships between the morphology and the amount of water absorbed and (b) to evaluate the influence of pepsin-alkaline treatment on the reorganization of the atelocollagen fibres. Conventional scanning electron microscopy (SEM) and environmental scanning electron microscopy (ESEM) were employed to study the morphology and wetting behaviour of the intact and atelocollagen sponges. The observations by SEM indicated remarkable differences both in the structure and dimension of the pores between intact and atelocollagen sponges. At the data are related to a different water binding capacity. However, the ESEM observations, achieved by changing the relative humidity in the operative chamber, demonstrated that the water adsorbed can be removed with major difficulty from atelocollagen sponges than from intact ones

Intact proinsulin and beta-cell function in lean and obese subjects with and without type 2 diabetes

DEFF Research Database (Denmark)

Røder, M E; Dinesen, B; Hartling, S G

1999-01-01

, total proinsulin immunoreactivity (PIM), intact insulin, and C-peptide (by radioimmunoassay) by specific enzyme-linked immunosorbent assays in the fasting state and during a 120-min glucagon (1 mg i.v.) stimulation test. Lean (BMI 23.5 +/- 0.3 kg/m2) (LD) and obese (30.1 +/- 0.4 kg/m2) (OD) type 2...... diabetic patients matched for fasting glucose (10.2 +/- 0.6 vs. 10.3 +/- 0.4 mmol/l) were compared with age- and BMI-matched lean (22.4 +/- 0.6 kg/m2) (LC) and obese (30.8 +/- 0.9 kg/m2) (OC) normal control subjects. RESULTS: Diabetic patients (LD vs. LC and OD vs. OC) had elevated fasting levels of intact......, most pronounced in the lean group. The ratio of intact proinsulin to PIM was higher in diabetic patients after stimulation in both LD versus LC: 32 +/- 3 vs. 23 +/- 2%, and OD versus OC: 28 +/- 4 vs. 16 +/- 2%, both P obese normal subjects, intact proinsulin/PIM was lower both in the fasting...

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.

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

Directory of Open Access Journals (Sweden)

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.

Isotope inequilibrium of glucose metabolites in intact cells and particlefree supernatants of Ehrlich ascites tumor

International Nuclear Information System (INIS)

Daehnfeldt, J.L.; Winge, P.

1975-01-01

With an enzyme degradative technique, isotope inequilibrium of glucose metabolites was demonstrated in intact cells and particle-free supernatants of Ehrlich ascites tumor using I- 14 C-glucose as tracer. Inequilibrium was found between glucose and glucose-6-phosphate, glucose and fructose-6-phosphate, glucose and 6-phosphogluconate, while glucose-6-phosphate and fructose-6-phosphate were found to be in near equilibrium within the incubation time investigated. Glucose and lactate were found to be in near equilibrium after 8 min in intact cells. Calculations based on the equilibrium levels found, showed that these inequilibria could not be explained by the effects of the pentose cycle. (U.S.)

Vitamin D status in relation to obesity, bone mineral density, bone turnover markers and vitamin D receptor genotypes in healthy Saudi pre- and postmenopausal women.

Science.gov (United States)

Ardawi, M-S M; Qari, M H; Rouzi, A A; Maimani, A A; Raddadi, R M

2011-02-01

The various factors that may contribute to vitamin D deficiency or insufficiency were examined among healthy Saudi pre- and postmenopausal women. Vitamin D deficiency was highly prevalent among studied Saudi women with obesity, poor sunlight exposure, poor dietary vitamin D supplementation and age as the main risk factors. The various factors that may contribute to vitamin D deficiency or insufficiency in relation to bone health among Saudi women are not known. The main objectives of the present study were to determine the factors influencing vitamin D status in relation to serum 25-hydroxyvitamin D (25(OH)D), intact parathyroid hormone (PTH), bone turnover markers (BTMs), bone mineral density (BMD), and vitamin D receptor genotype (VDR) in healthy Saudi pre- and postmenopausal women. A total number of 1,172 healthy Saudi women living in the Jeddah area were randomly selected and studied. Anthropometric parameters, socioeconomic status, sun exposure index together with serum levels of 25(OH)D, calcitriol, intact PTH, Ca, PO4, Mg, creatinine, albumin, and biochemical BTMs were measured. BMD was measured by a dual energy X-ray absorptiometry and VDR genotypes were also determined. About 80.0% of Saudi women studied exhibited vitamin D deficiency (serum 25(OH)D75 nmol/L). Secondary hyperparathyroidism was evident in 18.5% and 24.6% in pre- and postmenopausal women with 25(OH)Dobesity, poor exposure to sunlight, poor dietary vitamin D supplementation, and age.

Clinical analysis of 15 patients with primary hyperparathyroidism

International Nuclear Information System (INIS)

Yasumatsu, Ryuji; Okura, Kenji; Yamamoto, Tomoya

2007-01-01

A retrospective review was performed on 15 patients with primary hyperparathyroidism who were initially treated at our hospital between 2001 and 2006. The 15 patients (4 men and 11 women) ranged in age from 30 to 83 years. Histological examinations revealed 12 parathyroid adenomas and 3 hyperplasia. Ultrasonography and 99m Tc sestamibi scintigraphy were found to be the most useful modalities for accurately diagnosing the localization of parathyroid gland tumors. A resection of the enlarged gland was performed in 14 patients while the other patient underwent a hemithyroidectomy and parathyroidectomy. No complications, such as recurrent laryngeal nerve palsy or permanent hypocalcemia, were observed after surgery. The serum intact parathyroid hormone (PTH) concentration decreased significantly in all patients and the 13 of 15 patients were normocalcemic, however, the other 2 patients had persistent hypercalcemia after the operation. We speculated that these two patients had multiple parathyroid gland tumors. We conclude that intra-operative intact PTH monitoring is therefore an effective tool for the successful treatment of primary parathyroidism. (author)

Pakistani Immigrant Children and Adults in Denmark Have Severely Low Vitamin D Status

DEFF Research Database (Denmark)

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...

Measurement of diffusive properties of intact rock

Energy Technology Data Exchange (ETDEWEB)

Harvey, K B

1996-12-01

In the Postclosure Assessment of a Reference System for the Disposal of Canada`s Nuclear Fuel Waste (Goodwin et al. 1994) the disposal vault is assumed to be surrounded by a zone of intact rock, referred to as the `exclusion zone.` A sensitivity analysis of the relative effectiveness of the several engineered and natural barriers that contribute to the safety of the reference disposal system has shown that this zone of intact rock is the most effective of these barriers to the movement of radionuclides through the reference system. Peer review of the geosphere model used in the case study for the EIS (Environmental Impact Statement) of the Canadian Nuclear Fuel Waste Management Program has identified the need to quantify the properties of the intact rock surrounding the disposal vault that would control the transport of radionuclides by diffusion. The Postclosure Assessment also identified the need for appropriate values of the free water diffusion coefficient (D{sub o}) for {sup 129}1 and {sup 14}C. The measurement of rock resistivity allows the calculation of the Formation Factor for a rock This review describes the Formation Factor, diffusivity, permeability, and porosity, and how these properties might be measured or inferred for insitu rock under the conditions that apply to the intact rock surrounding a potential disposal vault. The importance of measuring the intrinsic diffusion coefficient (D{sup i}) of diffusing species under solution salinities simulating those of groundwaters is emphasised, and a method of measurement is described that is independent of the diffusing medium, and which would be appropriate for measurements made in chemically complex media such as groundwaters. (author). 95 refs., 4 tabs., 39 figs.

Measurement of diffusive properties of intact rock

International Nuclear Information System (INIS)

Harvey, K.B.

1996-12-01

In the Postclosure Assessment of a Reference System for the Disposal of Canada's Nuclear Fuel Waste (Goodwin et al. 1994) the disposal vault is assumed to be surrounded by a zone of intact rock, referred to as the 'exclusion zone.' A sensitivity analysis of the relative effectiveness of the several engineered and natural barriers that contribute to the safety of the reference disposal system has shown that this zone of intact rock is the most effective of these barriers to the movement of radionuclides through the reference system. Peer review of the geosphere model used in the case study for the EIS (Environmental Impact Statement) of the Canadian Nuclear Fuel Waste Management Program has identified the need to quantify the properties of the intact rock surrounding the disposal vault that would control the transport of radionuclides by diffusion. The Postclosure Assessment also identified the need for appropriate values of the free water diffusion coefficient (D o ) for 129 1 and 14 C. The measurement of rock resistivity allows the calculation of the Formation Factor for a rock This review describes the Formation Factor, diffusivity, permeability, and porosity, and how these properties might be measured or inferred for insitu rock under the conditions that apply to the intact rock surrounding a potential disposal vault. The importance of measuring the intrinsic diffusion coefficient (D i ) of diffusing species under solution salinities simulating those of groundwaters is emphasised, and a method of measurement is described that is independent of the diffusing medium, and which would be appropriate for measurements made in chemically complex media such as groundwaters. (author). 95 refs., 4 tabs., 39 figs

Valine pyrrolidide preserves intact glucose-dependent insulinotropic peptide and improves abnormal glucose tolerance in minipigs with reduced beta-cell mass

DEFF Research Database (Denmark)

Larsen, Marianne Olholm; Rolin, Bidda; Ribel, Ulla

2003-01-01

levels of intact GLP-1 but increased levels of intact GIP (from 4543 +/- 1880 to 9208 +/- 3267 pM x min; P glucose tolerance (area under the curve [AUC] for glucose reduced from 1904 +/- 480 to 1582 +/- 353 mM x min; P =.05). VP did not increase insulin levels during the oral......The incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are important in blood glucose regulation. However, both incretin hormones are rapidly degraded by the enzyme dipeptidyl peptidase IV (DPPIV). The concept of DPPIV inhibition as a treatment...... glucose tolerance test (OGTT) but increased the insulinogenic index in normal animals (from 83 +/- 42 to 192 +/- 108; P

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....

Genistein Stimulates Jejunum Chloride Secretion via an Akt-Mediated Pathway in Intact Female Mice

Directory of Open Access Journals (Sweden)

Lana Leung

2015-02-01

Full Text Available Background/Aims: We have previously shown that daily subcutaneous injections with the naturally occurring phytoestrogen genistein (600 mg genistein/kg body weight/day, 600G results in a significantly increased basal intestinal chloride, Cl-, secretion (Isc, a measure of transepithelial secretion in intact C57BL/6J female mice after 1-week of treatment, compared to controls (DMSO vehicle injected. Removal of endogenous estrogen via ovariectomy (OVX had no effect on the 600G-mediated increase in basal Isc. Methods: Given the estrogen-like characteristics of genistein, we compared the effects of daily estradiol (E2 injections (10 mg E2/kg body weight/day, 10E2 on basal Isc in intact and OVX mice. In intact mice, 10E2 was without effect on basal Isc, however, in OVX mice, 10E2 significantly increased basal Isc (mimicked 600G. The goal of the current study was to characterize the intracellular signaling pathways responsible for mediating 600G- or 10E2-stimulated increases in basal Isc in intact female or OVX mice. Results: We measured total protein expression in isolated segments of jejunum using western blot from the following six groups of mice; intact or OVX with; 600G, 10E2 or control. The proteins of interest were: Akt, p-Akt, p-PDK1, p-PTEN, p-c-Raf, p-GSK-3β, rap-1 and ERK1/2. All blots were normalized to GAPDH levels (n = 6-18/group. Conclusion: These data suggest that the presence of the endogenous sex steroid, estrogen, modifies the intracellular signaling pathway required to mediate Cl- secretion when the intestine is exposed to exogenous 600G or E2. These studies may have relevance for designing pharmacological tools for women with intestinal chloride secretory dysfunctions.

Using Spores for Fusarium spp. Classification by MALDI-Based Intact Cell/Spore Mass Spectrometry

Directory of Open Access Journals (Sweden)

Wolfgang Winkler

2012-01-01

Full Text Available Fusarium is a widespread genus of filamentous fungi and a member of the soil microbial community. Certain subspecies are health threatening because of their mycotoxin production that affects the human and animal food chain. Thus, for early and effective pest control, species identification is of particular interest; however, differentiation on the subspecies level is challenging and time-consuming for this fungus. In the present study, we show the possibilities of intact cell mass spectrometry for spore analysis of 22 different Fusarium strains belonging to six Fusarium subspecies. We found that species differentiation is possible if mass spectrometric analyses are performed under well-defined conditions with fixed parameters. A critical point for analysis is a proper sample preparation of spores, which increases the quality of mass spectra with respect to signal intensity and m/z value variations. It was concluded that data acquistion has to be performed automatically; otherwise, user-specific variations are introduced generating data which cannot fit the existing datasets. Data that show clearly that matrix-assisted laser desorption ionization-based intact cell/intact spore mass spectrometry (IC/ISMS can be applied to differentiate closely related Fusarium spp. are presented. Results show a potential to build a database on Fusarium species for accurate species identification, for fast response in the case of infections in the cornfield. We furthermore demonstrate the high precision of our approach in classification of intact Fusarium species according to the location of their collection.

Study of chronic kidney disease-mineral bone disorders in newly detected advanced renal failure patients: A Hospital-based cross-sectional study

Directory of Open Access Journals (Sweden)

Praveen Kumar Etta

2017-01-01

Full Text Available We aim to evaluate the disturbances in mineral metabolism, abnormalities in bone mineral density (BMD, and extraskeletal calcification in newly detected, untreated predialysis stage 4 and 5 chronic kidney disease (CKD patients at a tertiary care hospital in North India. This is cross-sectional observational study. A total of 95 (68 males, 27 females newly detected patients underwent clinical evaluation, biochemical assessment [serum calcium, phosphorus, alkaline phosphatase (ALP, albumin, creatinine, intact parathyroid hormone (iPTH, 25- hydroxyvitamin D (25(OHD], BMD measurement (at spine, hip, and forearm by dual-energy X-ray absorptiometry (DXA, lateral abdominal radiograph [for abdominal aortic calcification (AAC], skeletal survey (to look for any abnormality including fractures, and echocardiography [for any cardiac valvular calcification (CVC]. Symptoms related to CKD-mineral bone disorder were seen in 33.6% of the study patients. Prevalence of hypocalcemia, hyperphosphatemia, hyperparathyroidism, and hypovitaminosis D was 64.2%, 81.1%, 49.5%, and 89.5%, respectively. CVC was seen in 22.1% of patients on echocardiography, mostly involving the mitral valve. Patients with CVC were more likely to be males and smokers. There was no significant difference in iPTH levels between patients with or without CVC. AAC was seen in 10.5% of patients on lateral abdominal X-ray. Patients with AAC had higher levels of iPTH, phosphorus, and ALP and lower levels of calcium compared to patients without AAC. BMD by DXA showed a low bone mass in 41.05% of our patients and was more prevalent in CKD stage 5. Most of the study patients had hyperparathyroidism and low 25(OHD levels. Our study shows that newly detected, naïve Indian CKD patients have a high prevalence of disturbances of mineral metabolism including hyperparathyroidism, Vitamin D deficiency, abnormal BMD, and valvular and vascular calcification, even before initiating dialysis.

Failure to Diagnose Hyperparathyroidism in 10,432 Patients With Hypercalcemia: Opportunities for System-level Intervention to Increase Surgical Referrals and Cure.

Science.gov (United States)

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.

Synthesis and physicochemical properties of Zr-MCM-41 mesoporous molecular sieves and Pt/H3PW12O40/Zr-MCM-41 catalysts

International Nuclear Information System (INIS)

Chen, L.F.; Wang, J.A.; Norena, L.E.; Aguilar, J.; Navarrete, J.; Salas, P.; Montoya, J.A.; Del Angel, P.

2007-01-01

For the first time, modifications of the surface and framework of Si-MCM-41 by depositing a heteropolyacid on the surface and by introducing foreign Zr 4+ ions into the framework are investigated. The Zr-modified Si-MCM-41 mesoporous materials (hereafter referred as WSZn, n=Si/Zr=25, 15, 8, 4) were synthesized through a surfactant-templated preparation approach, using low-cost fumed silica as the Si precursor. After impregnation with 25 wt% of H 3 PW 12 O 40 , the surface Broensted acidity of the Pt/H 3 PW 12 O 40 /WSZn catalysts was greatly enhanced by 2-10 times relative to the bare WSZn support. Two kinds of supported heteropolyacids were formed: (i) bulk-like heteropolyacid crystals with unchanged Keggin structures, and (ii) highly dispersed heteropolyacid with distorted Keggin units. The formation of various kinds of heteropolyacid structures is closely related to the interaction between the heteropolyanions and the hydroxyl groups in the host support. - Graphical abstract: Modifications of the surface and framework of Si-MCM-41 by depositing a heteropolyacid on the surface and by introducing foreign Zr 4+ ions into the framework are investigated. Broensted acidity of the Pt/H 3 PW 12 O 40 /Zr-MCM-41 catalysts was greatly enhanced by 2-10 times relative to the bare Zr-MCM-41 support

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

International Nuclear Information System (INIS)

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

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.

Bone uptake of Tc-99m MIBI in patients with hyperparathyroidism

International Nuclear Information System (INIS)

Zhao, Yunyun; Wang, Qian

2014-01-01

The study aimed to investigate the incidence of bone uptake of tracer on Tc-99m MIBI imaging and explore its influencing factors and significance for diagnosis of metabolic bone disease (MBD) in patients with hyperparathyroidism (HPT). Seventy-nine consecutive patients with histopathologically confirmed HPT (63 primary and 16 secondary) who had preoperative Tc-99m MIBI imaging were retrospectively evaluated. Serum calcium (Ca), phosphorus (P), and intact parathyroid hormone (iPTH) were measured for all patients, and serum alkaline phosphatase (ALP) was measured for 62 patients. Of the 79 patients, 50 underwent bone mineral density (BMD) examination and 30 underwent bone scintigraphy. The incidence and characteristics of abnormal bone uptake of MIBI were recorded. Mann-Whitney test was performed to determine if serum iPTH, Ca, P, ALP, and BMD were different between the patients with and without MIBI bone uptake. Logistic regression analysis was used to analyze the factors that influence the bone uptake of MIBI. The concordance rate between Tc-99m MIBI imaging and bone scintigraphy in delineating MBD was calculated. Tc-99m MIBI imaging disclosed the abnormal bone uptake of tracer in 22 (27.8%) patients. Of them, 19 showed diffusely increased activity in skeleton, 2 showed focal uptake in brown tumors, and one showed both above patterns. Patients with bone uptake MIBI had higher level of serum iPTH (Z=-4.34, P < 0.001) and ALP (Z=-3.50, P < 0.001) than those without bone uptake. Logistic regression analysis also showed that bone uptake of MIBI was correlated with serum iPTH (OR=4.42, P < 0.001) and ALP (OR=3.21, P=0.002). Among the 30 patients that underwent bone scintigraphy, 76.7% patients showed signs of MBD, and the concordance rate between Tc-99m MIBI imaging and bone scintigraphy was 60% for detecting MBD. Bone uptake of MIBI in patients with HPT is commonly related to a high level of iPTH and ALP; it probably reflects an active stage of MBD, and it should be

High prevalence of secondary hyperparathyroidism in chronic kidney disease patients on dialysis in Argentina.

Science.gov (United States)

Douthat, Walter G; Castellano, Mauro; Berenguer, Leandro; Guzmán, M Alejandra; de Arteaga, Javier; Chiurchiu, Carlos R; Massari, Pablo U; Garay, Gabriela; Capra, Raúl; de La Fuente, Jorge L

2013-01-01

There are few data in Argentina on the prevalence and management of bone and mineral metabolism (BMM) in patients with chronic kidney disease (CKD). A survey was carried out in dialysis units in 2010 to measure the prevalence of and types of treatments for BMM disorders in Argentina. The data obtained was then compared to the published results from other large population studies. We recorded characteristics of dialysis centres and participating patients, the frequency of measurements and individual results for BMM biochemical markers, as well as the type of management used to control hyperphosphataemia and secondary hyperparathyroidism. 1210 patients from 25 dialysis centres in Argentina participated in the study (representing 4.7% of the country’s prevalent dialysis population in 2010). The mean patient age was 55.3±17.6 years, 60.8% were male, 3.3% were on peritoneal dialysis and 29.1% suffered diabetes. In all centres, phosphataemia and calcaemia were measured on a monthly basis, 60% of centres measured intact parathyroid hormone (iPTH) every 6 months, 36% every 3 to 4 months, and 4% annually. As recommended by K/DOQI, 51.6% of patients had adequate levels of calcium (8.4-9.5 mg/dl), 51.6% had adequate phosphorus (3.5-5.5 mg/dl) and 21.1% displayed acceptable iPTH levels (150-300 pg/ml). 24% had iPTH 300 pg/ml. iPTH ≥600 pg/ml was present in 28.3%, and 13.3% had values ≥1000 pg/ml. These figures differed from those published by the DOPPS II study, in which 51.1% of patients had iPTH hyperparathyroidism, oral or intravenous calcitriol was predominantly used (50.5%) with a small percentage of patients receiving paricalcitol or doxercalciferol. The present study shows a high prevalence of secondary hyperparathyroidism, which differs from that published by other large population studies. There was a high proportion of patients with BMM markers outside the ranges suggested by K/DOQI. Mainly phosphate binders based on calcium and calcitriol continue to be used

pth moment exponential stability of stochastic memristor-based bidirectional associative memory (BAM) neural networks with time delays.

Science.gov (United States)

Wang, Fen; Chen, Yuanlong; Liu, Meichun

2018-02-01

Stochastic memristor-based bidirectional associative memory (BAM) neural networks with time delays play an increasingly important role in the design and implementation of neural network systems. Under the framework of Filippov solutions, the issues of the pth moment exponential stability of stochastic memristor-based BAM neural networks are investigated. By using the stochastic stability theory, Itô's differential formula and Young inequality, the criteria are derived. Meanwhile, with Lyapunov approach and Cauchy-Schwarz inequality, we derive some sufficient conditions for the mean square exponential stability of the above systems. The obtained results improve and extend previous works on memristor-based or usual neural networks dynamical systems. Four numerical examples are provided to illustrate the effectiveness of the proposed results. Copyright © 2017 Elsevier Ltd. All rights reserved.

Subsequent influences of feeding intact green seaweed Ulva lactuca to growing lambs on the seminal and testicular characteristics in rams.

Science.gov (United States)

Samara, E M; Okab, A B; Abdoun, K A; El-Waziry, A M; Al-Haidary, A A

2013-12-01

The present experiment was designed to investigate the subsequent influences of supplementing different levels of intact green seaweed Ulva lactuca (0%, 3%, and 5% DM) to growing sexually immature lambs during the growth period (74 d) on the seminal and testicular characteristics of sexually mature rams. Ulva lactuca was manually collected, adequately prepared, and then incorporated into lambs' diets. Eighteen male 3-mo-old lambs of the Awassi breed with a mean BW of 22.57 kg (SD = 1.08) were randomly assigned into treatments. The obtained results indicate that offering Ulva lactuca at the level of 3% or 5% DM to lambs during the growth period had no subsequent impacts (P > 0.05) on liver and kidney functions as well as blood water balance in rams, thereby suggesting that Ulva lactuca can be safely supplemented to lambs during growing. However, our findings point out that feeding a lamb diet supplemented with intact Ulva lactuca failed to demonstrate any subsequent benefit (P > 0.05) on the growth performance, thermoregulatory responses, and plasma oxidative status in rams. Above all, it was clearly evident that supplementing intact Ulva lactuca to lambs had demonstrated subsequent negative influences (P Ulva lactuca during the growth period compared to control rams. The deleterious impacts of feeding intact Ulva lactuca on spermatogenesis and germ cell loss were proven to be attributed to the dysfunction of Sertoli cells. Collectively, these results provide novel insights on the subsequent influences of dietary supplementation of intact Ulva lactuca to lambs. The consistent evidence of profound negative impacts on seminal and testicular characteristics as well as the resulting data of no improvement of subsequent growth, thermoregulation, and plasma oxidative status in rams prompts us to tentatively recommend the avoidance of feeding intact Ulva lactuca to lambs.

Multiple regression technique for Pth degree polynominals with and without linear cross products

Science.gov (United States)

Davis, J. W.

1973-01-01

A multiple regression technique was developed by which the nonlinear behavior of specified independent variables can be related to a given dependent variable. The polynomial expression can be of Pth degree and can incorporate N independent variables. Two cases are treated such that mathematical models can be studied both with and without linear cross products. The resulting surface fits can be used to summarize trends for a given phenomenon and provide a mathematical relationship for subsequent analysis. To implement this technique, separate computer programs were developed for the case without linear cross products and for the case incorporating such cross products which evaluate the various constants in the model regression equation. In addition, the significance of the estimated regression equation is considered and the standard deviation, the F statistic, the maximum absolute percent error, and the average of the absolute values of the percent of error evaluated. The computer programs and their manner of utilization are described. Sample problems are included to illustrate the use and capability of the technique which show the output formats and typical plots comparing computer results to each set of input data.

Primary hyperparathyroidism with classic and severe skeletal involvement.

Science.gov (United States)

Sandoval, Mark Anthony S; Paz-Pacheco, Elizabeth

2010-08-26

A 63-year-old woman has had multiple repeated fractures. A diagnosis of primary hyperparathyroidism (PHPT) was made after she was found to be hypercalcaemic with an elevated level of intact parathyroid hormone (iPTH). Radiographs revealed classic and severe bone findings in PHPT, features which were common in the past but are thought to be rare at this modern age. She also had nephrolithiasis and osteoporosis. An enlarged parathyroid gland was seen on ultrasound and CT scan, and hyperfunction was demonstrated by scintigraphy. Parathyroidectomy was performed. Histopathologic analysis revealed a parathyroid adenoma. She developed the hungry-bone syndrome 7 days postoperatively, which resolved with with administration of calcium and calcitriol.

Liver polyribosome distribution in intact and adrenalectomized rats exposed to. gamma. radiation

Energy Technology Data Exchange (ETDEWEB)

Yatvin, M B; Abdel-Halim, M N [Wisconsin Univ., Madison (USA). Dept. of Radiology; Wisconsin Univ., Madison (USA). Dept. of Human Oncology)

1978-06-01

The mechanism(s) by which gamma radiation influences liver polyribosome distribution was studied in groups of intact and adrenalectomized male rats. A shift from light to heavy aggregates occurred in the polyribosomes of both intact and adrenalectomized rats after they were exposed to gamma rays. In irradiated adrenalectomized rats, however, the shift to heavier aggregates was not as great as that which occurred in irradiated adrenal-intact animals. Subcutaneous injection of cortisone acetate (10 mg/100 g body weight) also altered the liver polyribosome patterns of both intact and adrenalectomized rats within 8 hours of its administration. The shift which occurred following cortisone administration, however, was less striking than that seen after irradiation only. Thus, although adrenal glucocorticoids contribute to the radiation-indu ied shift in liver polyribosomes in adrenal-intact rats, other factors appear to be involved, since the shift is also obtained in adrenalectomized animals.

Prevalence and severity of anemia in pediatric hemodialysis patients, a single center study

Directory of Open Access Journals (Sweden)

Afshin Azhir

2006-12-01

Full Text Available BACKGROUNDS: This study was conducted to determine the prevalence and severity of anemia in children and adolescents on chronic hemodialysis, and to identify independent predictors of anemia in children on hemodialysis. METHODS: This cross-sectional study was performed between September 2005 and January 2006. The study population consisted of 25 patients aged 7−20 years on chronic hemodialysis from pediatric hemodialysis centers in Isfahan. RESULTS: A total of 22 (88% patients had hemoglobin levels of <11 g/dL (anemic and 12 patients (48% had hemoglobin levels of <8 g/dL (severe anemia. The mean age of these patients was 15.5 ± 3.7 years. Mean time on chronic dialysis was 20.44 ± 15.25 months. Anemia was more common and more severe among children who were on dialysis for less than 6 months. There was an inverse relationship between the severity of anemia and duration of hemodialysis (P = 0.019, r = – 0.465. Nearly all patients were treated with erythropoietin, Children with more severe anemia received slightly higher dose of erythropoietin (P = 0.09, r = 0.202. There was a significant difference between serum albumin values in anemic patients and patients without anemia (P = 0.023. There was a correlation between serum albumin and hemoglobin level (r = 0.511, P = 0.01. Intact PTH levels were >200 pg/ml in 16 patients (66% and >400 pg/ml in 9 patients (37. 5%. There was a reverse correlation between intact PTH level >200 pg/ml and hemoglobin level (r = -0.505, P = 0.046. CONCLUSIONS: The prevalence of anemia in hemodialysis children in Isfahan appears to be higher than that reported in the other studies in spite of extensive use of rHuEPO and iron supplementation. We found this to be especially true for patients new on hemodialysis (less than 6 months and in those with low albumin and severe hyperparathyroidism. KEY WORDS: Hemodialysis, anemia, children.

Parathyroid Hormone Measurement in Prediction of Hypocalcaemia following Thyroidectomy

International Nuclear Information System (INIS)

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)

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

Sorption of cesium in intact rock

International Nuclear Information System (INIS)

Puukko, E.

2014-04-01

The mass distribution coefficient K d is used in performance assessment (PA) to describe sorption of a radionuclide on rock. The R d is determined using crushed rock which causes uncertainty in converting the R d values to K d values for intact rock. This work describes a method to determine the equilibrium of sorption on intact rock. The rock types of the planned Olkiluoto waste disposal site were T-series mica gneiss (T-MGN), T-series tonalite granodiorite granite gneiss (T-TGG), P-series tonalite granodiorite granite gneiss (P-TGG) and pegmatitic granite (PGR). These rocks contain different amount of biotite which is the main sorbing mineral. The sorption of cesium on intact rock slices was studied by applying an electrical field to speed up migration of cesium into the rock. Cesium is in the solution as a noncomplex cation Cs + and it is sorbed by ion exchange. The tracer used in the experiments was 134 Cs. The experimental sorption on the intact rock is compared with values calculated using the in house cation exchange sorption model (HYRL model) in PHREEQC program. The observed sorption on T-MGN and T-TGG rocks was close to the calculated values. Two PGR samples were from a depth of 70 m and three samples were from a depth of 150 m. Cesium sorbed more than predicted on the two 70 m PGR samples. The sorption of Cs on the three 150 m PGR samples was small which was consistent with the calculations. The pegmatitic granite PGR has the smallest content of biotite of the four rock types. In the case of P-TGG rock the observed values of sorption were only half of the calculated values. Two kind of slices were cut from P-TGG drill core. The slices were against and to the direction of the foliation of the biotite rims. The sorption of cesium on P-TGG rock was same in both cases. The results indicated that there was no effect of the directions of the electric field and the foliation of biotite in the P-TGG rock. (orig.)

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

Science.gov (United States)

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.

Xenopus egg cytoplasm with intact actin.

Science.gov (United States)

Field, Christine M; Nguyen, Phuong A; Ishihara, Keisuke; Groen, Aaron C; Mitchison, Timothy J

2014-01-01

We report optimized methods for preparing Xenopus egg extracts without cytochalasin D, that we term "actin-intact egg extract." These are undiluted egg cytoplasm that contains abundant organelles, and glycogen which supplies energy, and represents the least perturbed cell-free cytoplasm preparation we know of. We used this system to probe cell cycle regulation of actin and myosin-II dynamics (Field et al., 2011), and to reconstitute the large, interphase asters that organize early Xenopus embryos (Mitchison et al., 2012; Wühr, Tan, Parker, Detrich, & Mitchison, 2010). Actin-intact Xenopus egg extracts are useful for analysis of actin dynamics, and interaction of actin with other cytoplasmic systems, in a cell-free system that closely mimics egg physiology, and more generally for probing the biochemistry and biophysics of the egg, zygote, and early embryo. Detailed protocols are provided along with assays used to check cell cycle state and tips for handling and storing undiluted egg extracts. © 2014 Elsevier Inc. All rights reserved.

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

the healed ribs were stiffer than intact ribs in torsion, compression, and bending simulations, as expected when examining bone callus composed of woven bone. Administration of both hMSCs and PTH worked synergistically in rib fracture healing, suggesting this approach may pave the way to treat multiple rib fractures as well as additional fractures in various anatomical sites.

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.

Persistent hyperparathyroidism is a major risk factor for fractures in the five years after kidney transplantation.

Science.gov (United States)

Perrin, P; Caillard, S; Javier, R M; Braun, L; Heibel, F; Borni-Duval, C; Muller, C; Olagne, J; Moulin, B

2013-10-01

The risk of fractures after kidney transplantation is high. Hyperparathyroidism frequently persists after successful kidney transplantation and contributes to bone loss, but its impact on fracture has not been demonstrated. This longitudinal study was designed to evaluate hyperparathyroidism and its associations with mineral disorders and fractures in the 5 posttransplant years. We retrospectively analyzed 143 consecutive patients who underwent kidney transplantation between August 2004 and April 2006. The biochemical parameters were determined at transplantation and at 3, 12 and 60 months posttransplantation, and fractures were recorded. The median intact parathyroid hormone (PTH) level was 334 ng/L (interquartile 151-642) at the time of transplantation and 123 ng/L (interquartile 75-224) at 3 months. Thirty fractures occurred in 22 patients. The receiver operating characteristic (ROC) curve analysis for PTH at 3 months (area under the ROC curve = 0.711, p = 0.002) showed that a good threshold for predicting fractures was 130 ng/L (sensitivity = 81%, specificity = 57%). In a multivariable analysis, independent risk factors for fracture were PTH >130 ng/L at 3 months (adjusted hazard ratio [AHR] = 7.5, 95% CI 2.18-25.50), and pretransplant osteopenia (AHR = 2.7, 95% CI 1.07-7.26). In summary, this study demonstrates for the first time that persistent hyperparathyroidism is an independent risk factor for fractures after kidney transplantation. © Copyright 2013 The American Society of Transplantation and the American Society of Transplant Surgeons.

A randomized, double-blind, placebo-controlled trial of calcium acetate on serum phosphorus concentrations in patients with advanced non-dialysis-dependent chronic kidney disease

Directory of Open Access Journals (Sweden)

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.

Insulin-like growth factor I is required for the anabolic actions of parathyroid hormone on mouse bone

Science.gov (United States)

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.

Clinical efficacy and safety of pamidronate therapy on bone mass density in early post-renal transplant period: a meta-analysis of randomized controlled trials.

Directory of Open Access Journals (Sweden)

Zijie Wang

Full Text Available INTRODUCTION: The overall effect of pamidronate on bone mass density (BMD in the early renal transplant period varies considerably among studies. The effects of pamidronate on graft function have not been determined. MATERIALS AND METHODS: A comprehensive search was conducted in PubMed, the Cochrane Central Register of Controlled Trials (CENTRAL and Embase independently by two authors. Randomized controlled trials of pamidronate evaluating bone loss in the first year of renal transplantation were included. Methods reported in the "Cochrane Handbook for Systematic Reviews of Interventions 5.0.2" were used to evaluate changes of lumbar spine and femoral neck BMD, and serum creatinine, calcium and intact parathyroid hormone (iPTH levels. Fixed or random effect models were used as appropriate. RESULTS: Six randomized trials evaluating 281 patients were identified. One hundred forty-four were treated with pamidronate and 137 were control patients. Administration of pamidronate was associated with significant reduction of bone loss in the lumbar spine, compared to the control group (standardized mean difference (SMD  = 24.62 [16.25, 32.99]. There was no difference between the pamidronate treated and control femoral neck BMD (SMD  = 3.53 [-1.84, 8.90]. A significant increase in the serum creatinine level of the intervention group was seen, compared to the control group. The serum calcium and iPTH of the pamidronate and control groups were not different after 1 year (serum creatinine: SMD  = -3.101 [-5.33, -0.89]; serum calcium: SMD  = 2.18 [-0.8, 5.16]; serum iPTH: SMD  = 0.06 [-0.19, 0.31]. Heterogeneity was low for serum calcium and iPTH and high for serum creatinine. CONCLUSIONS: This meta-analysis demonstrated the beneficial clinical efficacy of pamidronate on BMD with no association with any alteration in graft function during the first year of renal transplantation. Significant heterogeneity precludes the conclusion of the

The correlation between histologic placentitis and amnionitis and the amnioniotic fluid's inflammatory cytokines in case of spontaneous pre-term labor with intact membrane

Directory of Open Access Journals (Sweden)

Agus Abadi

2001-12-01

Full Text Available Pre-term labor is presumed to result from spreading of lower genital infection to upper part, subsequently to decidual and choioamniotic tissues. Host response to this injury include the expression of protein which is responsible to the inflammatory reactions. The expression of the inflammatory cytokines such as IL-1β, IL-6, IL-8 and TNF-α increase in case of infection.These cytokines may play an essential role in the pathophysiology of spontaneous pretem labor with intact membrane.An observational analytic cohort study was caried out on cases of spontaneous pre-tefln labor with intact membrane. The objectives of this study are to examine the relationship between l the histologic amnionitis and placentitis and the incidence of preterm delivery,2 the expression of amniotic fluid's IL-1β, IL-6, IL-8 and TNF-α and the incidence of preterm delivery, 3 the level of amniotic fluid's IL-1β, IL-6, IL-8 and TNF-α and the grade of histologic amnionitis and placentitis in case of pre-term labor with intact membrane. Cases of spontaneous Pre'teftn labor with intact membrane which underwent transabdominal amniocentesis at admission and managed as standard procedure for pre-term labor with intact membrane. Atl of the cases were observed until the delivery of the baby, eithir preterm or term. The membrane and the placentawere cut postnatally and then the histologic acute inflammation eyaluated based on the criteria of Salafia.The level of amniotic fluid IL-1β, IL-6, IL-8 and TNF-α were analyzed quantitatively by Elisa method. This study showed thet the degree of histologic amnionitis and placentitis, and the level of amniotic fluid's IL-1β, IL-6, IL-8 and TNF-α were significantly higher in pre-term compared to terrn deliveries (p<0.05 and lhere were a positive correlation between the grade of histoLogic inflammation and the level of amniotic fluid's cytokines (Spearmann Rank Conelation test; p<0,05 in cases of preterm labor with intact membrane. The

Novel GALNT3 mutations causing hyperostosis-hyperphosphatemia syndrome result in low intact fibroblast growth factor 23 concentrations.

Science.gov (United States)

Ichikawa, Shoji; Guigonis, Vincent; Imel, Erik A; Courouble, Mélanie; Heissat, Sophie; Henley, John D; Sorenson, Andrea H; Petit, Barbara; Lienhardt, Anne; Econs, Michael J

2007-05-01

Hyperostosis-hyperphosphatemia syndrome (HHS) is a rare metabolic disorder characterized by hyperphosphatemia and localized hyperostosis. HHS is caused by mutations in GALNT3, which encodes UDP-N-acetyl-alpha-D-galactosamine:polypeptide N- acetylgalactosaminyltransferase 3. Familial tumoral calcinosis (TC), characterized by ectopic calcifications and hyperphosphatemia, is caused by mutations in the GALNT3 or fibroblast growth factor 23 (FGF23) genes. Our objective was to identify mutations in FGF23 or GALNT3 and determine serum FGF23 levels in an HHS patient. Mutation detection in FGF23 and GALNT3 was performed by DNA sequencing, and serum FGF23 concentrations were measured by ELISA. A 5-year-old French boy with HHS and his family members participated. The patient presented with painful cortical lesions in his leg. Radiographs of the affected bone showed diaphyseal hyperostosis. The lesional tissue comprised trabeculae of immature, woven bone surrounded by fibrous tissue. Biochemistry revealed elevated phosphate, tubular maximum rate for phosphate reabsorption per deciliter of glomerular filtrate, and 1,25-dihydroxyvitamin D levels. The patient was a compound heterozygote for two novel GALNT3 mutations. His parents and brother were heterozygous for one of the mutations and had no biochemical abnormalities. Intact FGF23 level in the patient was low normal, whereas C-terminal FGF23 was elevated, a pattern similar to TC. The presence of GALNT3 mutations and elevated C-terminal, but low intact serum FGF23, levels in HHS resemble those seen in TC, suggesting that HHS and TC are different manifestations of the same disorder. The absence of biochemical abnormalities in the heterozygous individuals suggests that one normal allele is sufficient for secretion of intact FGF23.

Assessment of geomechanical properties of intact Opalinus Clay - Expert report

International Nuclear Information System (INIS)

Amann, F.; Vogelhuber, M.

2015-11-01

This comprehensive report published by the Swiss Federal Nuclear Safety Inspectorate ENSI presents an expert report published on the assessment of the geomechanical properties of intact Opalinus Clay. This review report addresses the conceptual constitutive framework for repositories in Opalinus Clay. The author addresses the geomechanical fundamentals that are necessary in order to adequately judge experiments on intact Opalinus Clay and the interpretation of the results. The report assesses in detail the various test series on intact Opalinus Clay carried out along with the interpretations made by experts and NAGRA. Further assessments are quoted including those on sample geometries tested, effective strength properties, undrained shear strength properties and elastic properties. The results of work done by other experts are also presented and discussed. The report is completed with a list of relevant literature

Assessment of geomechanical properties of intact Opalinus Clay - Expert report

Energy Technology Data Exchange (ETDEWEB)

Amann, F. [Eidgenössische Technische Hochschule ETHZ, Zürich (Switzerland); Vogelhuber, M. [Dr. von Moos AG, Geotechnisches Büro, Zürich (Switzerland)

2015-11-15

This comprehensive report published by the Swiss Federal Nuclear Safety Inspectorate ENSI presents an expert report published on the assessment of the geomechanical properties of intact Opalinus Clay. This review report addresses the conceptual constitutive framework for repositories in Opalinus Clay. The author addresses the geomechanical fundamentals that are necessary in order to adequately judge experiments on intact Opalinus Clay and the interpretation of the results. The report assesses in detail the various test series on intact Opalinus Clay carried out along with the interpretations made by experts and NAGRA. Further assessments are quoted including those on sample geometries tested, effective strength properties, undrained shear strength properties and elastic properties. The results of work done by other experts are also presented and discussed. The report is completed with a list of relevant literature.

Parathyroid changes after high dose radioactive iodine in patients with thyroid cancer

International Nuclear Information System (INIS)

Guven, A.; Salman, S.; Boztepe, H.; Yarman, S.; Tanakol, R.; Azizlerli, H.; Alagol, F.

2009-01-01

The study aimed to investigate the effect of high dose radioactive iodine (RAI) on parathyroid function in patients with differentiated thyroid cancer. Nineteen patients (8 men/11 women, age 46.5±13.2 years) undergoing RAI for thyroid remnant ablation were enrolled in the study. The biochemical parameters related to parathyroid function [serum calcium (Ca), phosphate (P), creatinine (Cr), alkaline phosphatase (ALP), intact parathyroid hormone (iPTH), urinary Ca, cAMP concentrations and the maximum tubular capacity for phosphate per unit volume of glomerular filtrate (TmP/GFR)] were evaluated at baseline and at the 1st, 3rd, 6th and 12th months of RAI administration. SPSS 15.0 was used for statistical analysis. For all patients, thyroid-stimulating hormone levels were >30 U/ml at baseline and <0.1 U/ml at the following visits. Serum iPTH levels were decreased significantly at the 6th month and reached basal levels at the 12th month (baseline vs. 6th p=0.027, 1st vs. 6th p=0.011, 3rd vs. 6th p=0.047, 3rd vs. 12th p=0.014, 6th vs. 12th p=0.001). At the 6th month, P and TmP/GFR levels were higher (p=0.036, 0.017, respectively), and urinary cAMP measurements were lower (p=0.020) compared to those of the 1st month. No difference was detected concerning the other parameters. Serum Ca levels decreased below 2.1 mmol/l in several patients (n=5 at 1st month, n=4 at 3rd month, n=8 at 6th month and n=3 at 12th month) without clinical symptoms. The study indicated a transient decline in PTH levels at the 6th month following RAI therapy. Although this decrease did not cause symptoms in any of the present cases, this pattern might be important especially in individuals with diminished parathyroid background. (author)

Single molecule approaches for quantifying transcription and degradation rates in intact mammalian tissues.

Science.gov (United States)

Bahar Halpern, Keren; Itzkovitz, Shalev

2016-04-01

A key challenge in mammalian biology is to understand how rates of transcription and mRNA degradation jointly shape cellular gene expression. Powerful techniques have been developed for measuring these rates either genome-wide or at the single-molecule level, however these techniques are not applicable to assessment of cells within their native tissue microenvironment. Here we describe a technique based on single molecule Fluorescence in-situ Hybridization (smFISH) to measure transcription and degradation rates in intact mammalian tissues. The technique is based on dual-color libraries targeting the introns and exons of the genes of interest, enabling visualization and quantification of both nascent and mature mRNA. We present a software, TransQuant, that facilitates quantifying these rates from smFISH images. Our approach enables assessment of both transcription and degradation rates of any gene of interest while controlling for the inherent heterogeneity of intact tissues. Copyright © 2015 Elsevier Inc. All rights reserved.

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.

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

Risk factors for post-tonsillectomy hemorrhage.

Science.gov (United States)

Ikoma, Ryo; Sakane, Sayaka; Niwa, Kazutomo; Kanetaka, Sayaka; Kawano, Toshiro; Oridate, Nobuhiko

2014-08-01

The aim of the present study was to investigate the rate of post-tonsillectomy hemorrhage (PTH) in a single institution and to evaluate the clinical risk factors for PTH. We reviewed the records of 692 patients who underwent tonsillectomy (TE) at Yokohama Minami Kyosai Hospital in Japan. PTH grades were grouped into three categories according to the severity of the hemorrhagic episode: (I) minimal hemorrhage that stopped after noninvasive treatment, (II) hemorrhage requiring treatment with local anesthesia, and (III) hemorrhage requiring reoperation under general anesthesia in the operating room. Clinical risk factors such as sex, age (adults vs. children), TE indication, surgeon's skill level, operative time, ligature type, and duration of antibiotic administration for PTH were investigated. Among the 692 patients, 80 (11.6%) showed PTH, with primary and secondary hemorrhage accounting for 1.6% and 10.0%, respectively. A category III PTH was observed in 18 patients; thus, the overall risk of reoperation was 2.6%. The PTH episode most frequently occurred on postoperative days 5 and 6. The frequency of PTH was significantly higher in male patients and in adults (Pdefinition of PTH. Clinical risk factors for PTH were adult age and male gender. The surgeon's skill level was an additional risk factor for category III PTH. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Research on intact marine ecosystems: a lost era.

Science.gov (United States)

Stachowitsch, Michael

2003-07-01

It is proposed that a new, fifth era should be added to the four historical phases of marine research identified by Rupert Riedl, specifically an era devoted to studying and ameliorating disturbed marine ecosystems. In an age of global environmental deterioration, many marine ecosystems and organisms are high on the list of threatened entities. This poor status prompts research that would otherwise have been unnecessary and hinders research that would normally have been conducted. I argue that research into intact marine ecosystems is becoming increasingly difficult, and that most of our future insights into marine habitats will stem from knowledge gained by examining various disfunctions of those systems rather than their functions. The new era will therefore differ from past research in its underlying aim, the range of topics studied, the selection and funding of those topics, the validity of its conclusions, and in its urgency. Sea turtles and cetaceans are cited as case studies at the organismic level, shallow-water benthic communities, including coral reefs, at the ecosystem level.

Total paratyreoidektomi og autotransplantation af parathyreoideavaev. Vurdering af autotransplantatets funktion 5-10 år efter operationen ved hjoelp af lokal iskoemisk blokade

DEFF Research Database (Denmark)

Knudsen, L; Brandi, L; Daugaard, H

1997-01-01

hyperparathyroidism (HPT) and one patient suffered from hypoparathyroidism. Nine of the patients were available for measurements of the plasma concentrations of intact parathyroid hormone (iPTH) at rest and during a shortlasting ischaemic blockade of the autotransplant. In eight patients, the ischaemic blockade...... alternative to the surgical treatment of secondary HPT and that the ischaemic blockade manoeuvre seems suitable for assessment of the function of parathyroid autotransplants....

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

A Convenient In Vivo Model Using Small Interfering RNA Silencing to Rapidly Assess Skeletal Gene Function.

Directory of Open Access Journals (Sweden)

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

Self-etching adhesive on intact enamel, with and without pre-etching.

Science.gov (United States)

Devarasa, G M; Subba Reddy, V V; Chaitra, N L; Swarna, Y M

2012-05-01

Bond strengths of composite resin to enamel using self-etch adhesive (SEA) Clearfil SE bond system on intact enamel and enamel pre-etched with phosphoric acid were compared. The objective was to determine if the pre-etching would increase the bond strengths of the SEA systems to intact enamel and to evaluate the effect of pre-etching on bond formation of self-etch adhesives on intact enamel. Labial surfaces of 40 caries free permanent upper central and lateral incisors were cleaned, sectioned of their roots. All specimens were mounted on acrylic block and divided randomly into four groups. In two groups the application of self-etch adhesive, Clearfil SE bond was carried as per manufacturer's instructions, composite cylinders were built, whereas in the other two groups, 37% phosphoric acid etching was done before the application of self-etching adhesives. Then the resin tags were analyzed using scanning electron microscope and shear bond strength was measured using Instron universal testing machine. When phosphoric acid was used, there was significant increase in the depth of penetration of resin tags and in the Shear Bond Strength of composite to enamel. The results indicate that out of both treatment groups, pre-etching the intact enamel with 37% phosphoric acid resulted in formation of longer resin tags and higher depth of penetration of resin tags of the Clearfil SE bond, and attaining higher bond strength of the Clearfil SE bond to intact enamel. Copyright © 2011 Wiley Periodicals, Inc.

Transformation of sweet orange [Citrus sinensis (L.) Osbeck] with pthA-nls for acquiring resistance to citrus canker disease.

Science.gov (United States)

Yang, Li; Hu, Chunhua; Li, Na; Zhang, Jiayin; Yan, Jiawen; Deng, Ziniu

2011-01-01

The COOH terminal of pthA encoding three nuclear localizing signals (NLS) was amplified by polymerase chain reaction (PCR) from the plasmid of Xanthomonas axonopodis pv. citri, the pathogen of citrus canker disease. Then the sense and antisense strands of the nls were cloned into pBI121 vector. pthA-nls driven by the CaMV35 s promoter was transferred into sweet orange via Agrobacterium -mediated transformation. Successful integration was confirmed by PCR and Southern blotting, and 12 sense-nls (nls (+)) and 9 antisense-nls (nls (-)) transgenic clones were obtained. The expression of nls fragment was analyzed by RT-PCR, Real time q-PCR and Western blotting, in which the specific NLS protein was detected only in nls (+) transgenic clones. In an in vitro assay, when pin-puncture inoculation was performed with 2.5 × 10(7) cfu/ml of bacterial solution, the nls (+) transgenic clones showed no typical lesion development, while typical symptoms were observed in the wild types and the nls (-) transgenic clones. In vivo assay results indicated that the nls (+) transgenic clones showed less disease incidence, in comparison with the wild types and the nls (-) transgenic clones, when pin-puncture inoculation was performed with 10(4)-10(5) cfu/ml. The minimum disease incidence was 23.3% for 'Sucarri' sweet orange and 33.3% for 'Bingtang' sweet orange. When 10(4)-10(7) cfu/ml of pathogen was spray inoculated, the nls (+) transgenic clones did not show any symptom, and even the concentration raised to 10(9) cfu/ml, the disease incidence was 20-80%, while the wild types and the nls (-) transgenic clones had 100% disease development with whatever concentration of inoculum. Two transgenic clones were confirmed to be resistant to citrus canker disease in the repeated inoculation. The results suggested that the transformation of nls sense strands may offer an effective way to acquire resistance to citrus canker disease.

Neural activation differences in amputees during imitation of intact versus amputee movements

Directory of Open Access Journals (Sweden)

William F Cusack

2012-06-01

Full Text Available The mirror neuron system has been attributed with increased activation in motor-related cortical areas upon viewing of another’s actions. Recent work suggests that limb movements that are similar and dissimilar in appearance to that of the viewer equivalently activate the mirror neuron system. It is unclear if this result can be observed in the action encoding areas in amputees who use prosthetic devices. Intact subjects and upper extremity amputee prosthesis users were recruited to view video demonstrations of tools being used by an intact actor and a prosthetic device user. All subjects were asked to pantomime the movements seen in the video while recording electroencephalography. Intact subjects showed equivalent left parietofrontal activity during imitation after watching the intact or prosthetic arm. Likewise, when prosthesis users imitated prosthesis demonstrations, typical left parietofrontal activation was observed during planning. When prosthesis users imitated intact actors, a new pattern was revealed which showed greater bilateral parietal and occipital activity during movement planning (p<0.001. This change may be required for prosthesis users to imitate movements in which the limb states between the observed and the observer do not match. The finding that prosthesis users imitating other prosthesis users showed typical left parietofrontal activation suggests that these subjects engage normal planning related activity when they are able to imitate a limb matching their own. This result has significant implications on rehabilitation, as standard therapy involves training with an intact occupational therapist, which could necessitate atypical planning mechanisms in amputees when learning to use their prosthesis.

The Multilevel Mixed Intact Group Analysis: A Mixed Method to Seek, Detect, Describe and Explain Differences Between Intact Groups

NARCIS (Netherlands)

Schoonenboom, J.I.

2014-01-01

Educational innovations often involve intact subgroups, such as school classes or university departments. In small-scale educational evaluation research, typically involving 1 to 20 subgroups, differences among these subgroups are often neglected. This article presents a mixed method from a

[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.

Threats to intact tropical peatlands and opportunities for their conservation.

Science.gov (United States)

Roucoux, K H; Lawson, I T; Baker, T R; Del Castillo Torres, D; Draper, F C; Lähteenoja, O; Gilmore, M P; Honorio Coronado, E N; Kelly, T J; Mitchard, E T A; Vriesendorp, C F

2017-12-01

Large, intact areas of tropical peatland are highly threatened at a global scale by the expansion of commercial agriculture and other forms of economic development. Conserving peatlands on a landscape scale, with their hydrology intact, is of international conservation importance to preserve their distinctive biodiversity and ecosystem services and maintain their resilience to future environmental change. We explored threats to and opportunities for conserving remaining intact tropical peatlands; thus, we excluded peatlands of Indonesia and Malaysia, where extensive deforestation, drainage, and conversion to plantations means conservation in this region can protect only small fragments of the original ecosystem. We focused on a case study, the Pastaza-Marañón Foreland Basin (PMFB) in Peru, which is among the largest known intact tropical peatland landscapes in the world and is representative of peatland vulnerability. Maintenance of the hydrological conditions critical for carbon storage and ecosystem function of peatlands is, in the PMFB, primarily threatened by expansion of commercial agriculture linked to new transport infrastructure that is facilitating access to remote areas. There remain opportunities in the PMFB and elsewhere to develop alternative, more sustainable land-use practices. Although some of the peatlands in the PMFB fall within existing legally protected areas, this protection does not include the most carbon-dense (domed pole forest) areas. New carbon-based conservation instruments (e.g., REDD+, Green Climate Fund), developing markets for sustainable peatland products, transferring land title to local communities, and expanding protected areas offer pathways to increased protection for intact tropical peatlands in Amazonia and elsewhere, such as those in New Guinea and Central Africa which remain, for the moment, broadly beyond the frontier of commercial development. © 2017 The Authors. Conservation Biology published by Wiley Periodicals, Inc

The association between body composition, 25(OH)D, and PTH and bone mineral density in black African and Asian Indian population groups.

Science.gov (United States)

George, Jaya A; Micklesfield, L K; Norris, S A; Crowther, N J

2014-06-01

There are few data on the contribution of body composition to bone mineral density (BMD) in non-Caucasian populations. We therefore studied the contribution of body composition, and possible confounding of 25-hydroxyvitamin D and PTH, to BMD at various skeletal sites in black African (BA) and Asian Indian (AI) subjects. This was a cross-sectional study in Johannesburg, South Africa. BMD, body fat, and lean mass were measured using dual x-ray absorptiometry and abdominal fat distribution by ultrasound in 714 healthy subjects, aged 18-65 years. Whole-body (subtotal), hip, femoral neck, and lumbar spine (lumbar) BMD were significantly higher in BA than AI subjects (P < .001 for all). Whole-body lean mass positively associated with BMD at all sites in both ethnic groups (P < .001 for all) and partially explained the higher BMD in BA females compared with AI females. Whole-body fat mass correlated positively with lumbar BMD in BA (P = .001) and inversely with subtotal BMD in AI subjects (P < .0001). Visceral adiposity correlated inversely with subtotal BMD in the BA (P = .037) and with lumbar BMD in the AI group (P = .005). No association was found between serum 25-hydroxyvitamin D and BMD. PTH was inversely associated with hip BMD in the BA group (P = .01) and with subtotal (P = .002), hip (P = .001), and femoral BMD (P < .0001) in the AI group. Significant differences in whole-body and site-specific BMD between the BA and AI groups were observed, with lean mass the major contributor to BMD at all sites in both groups. The contribution of other components of body composition differed by site and ethnic group.

Ultrastructure and Light Microscope Analysis of Intact Skin after a Varying Number of Low Level Laser Irradiations in Mice

Directory of Open Access Journals (Sweden)

Mamie Mizusaki Iyomasa

2014-01-01

Full Text Available Low level laser therapy (LLLT has been used to relieve pain, inflammation, and wound healing processes. Thus, the skin is overexposed to laser and this effect is not completely understood. This study analyzed the effects of the number of laser applications (three, six, and 10 on the intact skin of the masseteric region in mice of strain HRS/J. The animals (n=30 were equally divided into control (0 J/cm2 and irradiated (20 J/cm2, and each of these groups was further equally divided according to the number of laser applications (three, six, and 10 and underwent LLLT on alternate days. Samples were analyzed by light microscopy and transmission electron microscope (TEM. The animals receiving applications exhibited open channels more dilated between the keratinocytes and photobiomodulation effect on endothelial cells and fibroblasts by TEM. Under the light microscope after 10 laser applications, the type I collagen decreased (P<0.05 compared to the three and six applications. Under these experimental conditions, all numbers of applications provided photobiomodulatory effect on the epidermis and dermis, without damage. More studies are needed to standardize the energy density and number of applications recommended for laser therapy to have a better cost-benefit ratio associated with treatment.

Epispadias in boys with an intact prepuce

NARCIS (Netherlands)

Bos, E. M. E.; Kuijper, C. F.; Chrzan, R. J.; Dik, P.; Klijn, A. J.; de Jong, T. P. V. M.

2014-01-01

To present an overview of the clinical presentation and pathological anatomy, and the results of surgical correction of 7 cases of epispadias with intact prepuce; a rare condition that has only occasionally been reported in literature. A retrospective search was performed in the surgical and

HYDROCARBON VAPOR DIFFUSION IN INTACT CORE SLEEVES

Science.gov (United States)

The diffusion of 2,2,4-trimethylpentane (TMP) and 2,2,5-trimethylhexane (TMH) vapors put of residually contaminated sandy soil from the U.S. Environmental Protection Agency (EPA) field research site at Traverse City, Michigan, was measured and modeled. The headspace of an intact ...

Adiposity in relation to vitamin D status and parathyroid hormone levels : a population-based study in older men and women

NARCIS (Netherlands)

Snijder, Marieke B; van Dam, Rob M; Visser, Marjolein; Deeg, Dorly J H; Dekker, Jacqueline M; Bouter, Lex M; Seidell, Jaap C; Lips, Paul

OBJECTIVE: In small case-control studies, obesity was associated with worse vitamin D status. Our aim was to assess the association of adiposity (anthropometric measures as well as dual energy x-ray absorptiometry) with serum 25-hydroxyvitamin D (25-OH-D) and serum PTH levels in a large

Digested BLG can induce tolerance when co-administered with intact BLG in Brown Norway rats

DEFF Research Database (Denmark)

Bøgh, Katrine Lindholm; Barkholt, Vibeke; Madsen, Charlotte Bernhard

the human gastro-duodenal digestion process. Four different fractions of BLG-digest was made, based on sizes of peptides or aggregates hereof. Intact BLG and the four fractions of BLG-digesta were characterized by protein chemical analyses. Brown Norway (BN) rats were immunised i.p. three times without......Background: Milk is a major constituent of small children’s diet. Milk allergy is also one of the most common allergies in small children. Prevention, treatment and general understanding of this allergy are therefore important. Methods: Intact BLG was digested in an in vitro model simulating...... the use of adjuvant with either PBS (control), 200 µg of intact BLG, 30 µg of intact BLG, 200 µg of digested BLG (with 30 µg of intact BLG), 200 µg of digested BLG, 200 µg of a fraction of large complexes or 200 µg of a fraction of small complexes (all three without intact BLG). Sera from BN rats were...

On the pth moment stability of the binary airfoil induced by bounded noise

International Nuclear Information System (INIS)

Wu, Jiancheng; Li, Xuan; Liu, Xianbin

2017-01-01

Highlights: • We obtain finite pth moment Lyapunov exponent for binary airfoil subject to a bounded noise. • Based on perturbation approach and Green's functions method, second differential eigenvalue equation governing moment Lyapunov exponent is established. • The types of singular points are investigated. • The eigenvalue problem is solved analytically and numerically. • The effects of noise and system parameters on the moment Lyapunov exponent and the stochastic stability of the system are discussed. - Abstract: In the paper, the stochastic stability of the binary airfoil subject to the effect of a bounded noise is studied through the determination of moment Lyapunov exponents. The noise excitation here is often used to model a realistic model of noise in many engineering application. The partial differential eigenvalue problem governing the moment Lyapunov exponent is established. Via the Feller boundary classification, the types of singular points are discussed here, and for the system discussed, the singular points only exist in end points. The fundamental methods used are the perturbation approach and the Green's functions method. With these methods, the second-order expansions of the moment Lyapunov exponents are obtained, which are shown to be in good agreement with those obtained using Monte Carlo simulation. The effects of noise and system parameters on the moment Lyapunov exponent and the stochastic stability of the binary airfoil system are discussed.

Prevalence and severity of disordered mineral metabolism in patients with chronic kidney disease: A study from a tertiary care hospital in India

Directory of Open Access Journals (Sweden)

Sanjay Vikrant

2016-01-01

Full Text Available Background: Disordered mineral metabolism is common complications of chronic kidney disease (CKD. However, there are limited data on the pattern of these disturbances in Indian CKD population. Materials and Methods: This was a prospective observational study of CKD-mineral and bone disorder (CKD-MBD over a period of 3 years. The biochemical markers of CKD-MBD, namely, calcium, phosphorus, alkaline phosphatase, intact parathyroid hormone (iPTH, and 25-hydoxyvitamin Vitamin D3 (25OHD, were measured in newly diagnosed CKD Stage 3–5 and prevalent CKD Stage 5D adult patients. Results: A total of 462 patients of CKD Stage 3–5D were studied. The frequency of various biochemical abnormalities was hypocalcemia (23.8%, hypercalcemia (5.4%, hypophosphatemia (2.8%, hyperphosphatemia (55.4%, raised alkaline phosphatase (56.9%, secondary hyperparathyroidism (82.7%, and hypoparathyroidism (1.5%. 25OHD was done in 335 (72.5% patients and 90.4% were found to have Vitamin D deficiency. About 70.6% of the patients had iPTH levels were above kidney disease outcomes quality initiative (KDOQI target range. Nondiabetic CKD as compared to diabetic CKD had a higher alkaline phosphatase (P = 0.016, a higher iPTH (P = 0.001 a higher proportion of patients with iPTH above KDOQI target range (P = 0.09, and an elevated alkaline phosphatase (P = 0.004. The 25OHD levels were suggestive of severe Vitamin D deficiency in 33.7%, Vitamin D deficiency in 45.4%, and Vitamin D insufficiency in 11.3% patients. There was a significant positive correlation between iPTH with alkaline phosphatase (r = 0.572, P = 0.001, creatinine (r = 0.424, P = 0.001, and phosphorus (r = 0.241, P = 0.001 and a significant negative correlation with hemoglobin (r = −0.325, 0.001, age (r = −0.169, P = 0.002, and 25OHD (r = −0.126, P = 0.021. On multivariate logistic regression analysis, an elevated alkaline phosphatase was a significant predictor of hyperparathyroidism (odds ratio 9.7, 95

Intacting Integrity in coping with health issues

DEFF Research Database (Denmark)

Jepsen, Stine Leegaard; Bastrup Jørgensen, Lene; Fridlund, Bengt

2017-01-01

The aim of this study was to develop a formal substantive theory (FST) on the multidimensional behavioral process of coping with health issues. Intacting integrity while coping with health issues emerged as the core category of this FST. People facing health issues strive to safeguard and keep...

Fluorescent-protein stabilization and high-resolution imaging of cleared, intact mouse brains.

Directory of Open Access Journals (Sweden)

Martin K Schwarz

Full Text Available In order to observe and quantify long-range neuronal connections in intact mouse brain by light microscopy, it is first necessary to clear the brain, thus suppressing refractive-index variations. Here we describe a method that clears the brain and preserves the signal from proteinaceous fluorophores using a pH-adjusted non-aqueous index-matching medium. Successful clearing is enabled through the use of either 1-propanol or tert-butanol during dehydration whilst maintaining a basic pH. We show that high-resolution fluorescence imaging of entire, structurally intact juvenile and adult mouse brains is possible at subcellular resolution, even following many months in clearing solution. We also show that axonal long-range projections that are EGFP-labelled by modified Rabies virus can be imaged throughout the brain using a purpose-built light-sheet fluorescence microscope. To demonstrate the viability of the technique, we determined a detailed map of the monosynaptic projections onto a target cell population in the lateral entorhinal cortex. This example demonstrates that our method permits the quantification of whole-brain connectivity patterns at the subcellular level in the uncut brain.

Performance of intact and castrated beef cattle in an intensive croppasture rotation system

Directory of Open Access Journals (Sweden)

Tercilio Turini

2015-07-01

Full Text Available This research had as objective to evaluate the performance of intact or castrated beef cattle in a croppasture rotation system. The experiment was conducted during 2004 and 2005, and carried out at the Cooperativa Agropecuária Mourãoense (COAMO Experimental Farm, in Campo Mourão city, Paraná state. It was used a completely randomized design, with two treatments, intact or castrated. Forty ½Angus+½Nelore crossbred animals, with average age of nine months, were used. Half of the animals were castrated at weaning, and the other half was kept intact. Pasture was composed of two areas. The winter field, established after soybean crop, was composed by a mixture of black oat (Avena strigosa and Italian ryegrass (Lolium multiforum. The summer field was composed by stargrass (Cynodon nlemfuensis and Mombaça grass (Panicum maximum. During the winter time it was used a continues grazing system, with regulator animals (put and take, and during the summer an intensive rotational system, with regulator animals and fixed grazing period. Intact animals presented higher average daily weight gain (0.907 vs 0.698 kg, slaughter weight (490.9 vs 442.2 kg, and hot carcass weight (250.2 vs 232.6 kg. Slaughter age was influenced by sexual condition, being lesser in the intact animals. Carcass dressing percentage was similar for the groups. Castrated animals showed better finishing fat cover and backfat thickness (3.45 vs 2.70 mm compared to intact ones. Therefore, it can be concluded that intact animals presents better performance than castrated ones when finished in an intensive crop-pasture rotation system, however, they may not present the minimum required fat cover, when slaughter at young ages.

Cholesteatoma behind an intact tympanic membrane: histopathologic evidence for a tympanic membrane origin.

Science.gov (United States)

Sudhoff, H; Linthicum, F H

2001-07-01

Several theories have been proposed with respect to the origin and pathogenesis of cholesteatoma behind an intact tympanic membrane. The authors describe a case of cholesteatoma behind an intact tympanic membrane in a 71-year-old man with a history of tympanic membrane retraction fixed to the incus without evidence of a perforation. The membrane eventually became detached, and remnants of keratinizing squamous epithelium were found on the incus. Mechanisms such as metaplasia, ectopic epidermis rests, or ingrowth of meatal epidermis have been proposed to explain the pathogenesis of cholesteatoma behind an intact tympanic membrane. These findings, based on temporal bone histopathology, support the role of an acquired epidermal rest. This case report provides evidence that cholesteatoma behind an intact tympanic membrane can be established from a resolved retraction of the pars tensa of the tympanic membrane.

The Multilevel Mixed Intact Group Analysis: A Mixed Method to Seek, Detect, Describe, and Explain Differences Among Intact Groups

Science.gov (United States)

Schoonenboom, Judith

2016-01-01

Educational innovations often involve intact subgroups, such as school classes or university departments. In small-scale educational evaluation research, typically involving 1 to 20 subgroups, differences among these subgroups are often neglected. This article presents a mixed method from a qualitative perspective, in which differences among…

Structural determination of intact proteins using mass spectrometry

Science.gov (United States)

Kruppa, Gary [San Francisco, CA; Schoeniger, Joseph S [Oakland, CA; Young, Malin M [Livermore, CA

2008-05-06

The present invention relates to novel methods of determining the sequence and structure of proteins. Specifically, the present invention allows for the analysis of intact proteins within a mass spectrometer. Therefore, preparatory separations need not be performed prior to introducing a protein sample into the mass spectrometer. Also disclosed herein are new instrumental developments for enhancing the signal from the desired modified proteins, methods for producing controlled protein fragments in the mass spectrometer, eliminating complex microseparations, and protein preparatory chemical steps necessary for cross-linking based protein structure determination.Additionally, the preferred method of the present invention involves the determination of protein structures utilizing a top-down analysis of protein structures to search for covalent modifications. In the preferred method, intact proteins are ionized and fragmented within the mass spectrometer.

Correlação entre fotoproteção e concentrações de 25 hidroxi-vitamina D e paratormônio Correlation between photoprotection and 25 hydroxyvitamin D and parathyroid hormone levels

Directory of Open Access Journals (Sweden)

Marcus Maia

2007-06-01

Full Text Available FUNDAMENTOS- A preocupação com o risco de câncer da pele levou à difusão da fotoproteção em larga escala, e atualmente se discute se haveria, associado a essa recomendação, risco para o desenvolvimento de hipovitaminose D. OBJETIVOS - Avaliar em pacientes orientados para proteção solar, o estado atual de seu estoque de vitamina D. MÉTODOS - Avaliaram-se as concentrações de 25 hidroxivitamina D (25OHD e do hormônio da paratireóide (PTH em grupos de indivíduos com e sem orientação para fotoproteção, moradores da cidade de São Paulo. RESULTADOS - Encontrou-se diferença significativa entre os níveis de 25OHD, maiores no grupo fotoexposto, 35,4ng/mL [21,86- 72,20], em relação ao fotoprotegido, 29,2ng/mL [23,10-45,80]. Também houve diferença com relação ao PTH, maior no grupo fotoexposto, 29,8pg/mL [18,98-73,94], do que no fotoprotegido, 19,24pg/mL [8,06-66,18]. CONCLUSÕES - Apesar dessas diferenças, não havia indivíduos deficientes de vitamina D nessa amostra, e os níveis de PTH mantiveram- se dentro dos valores de normalidade. A radiação ultravioleta solar do cotidiano foi suficiente para promover uma síntese adequada de 25OHD.BACKGROUND - The great concern about skin cancer risk led to the dissemination of photoprotection in high scale. Nowadays the association of this recommendation and the risk of develop hypovitaminosis D is discussed. OBJECTIVE - To evaluate vitamin D storage in patients submitted to sun protection. METHODS - The levels of 25-hydroxyvitamin D (25OHD and parathyroid hormone (PTH were evaluated in groups of individuals living in the city of São Paulo who received or not orientation about photoprotection. RESULTS - Significant differences in 25OHD levels were found between the groups, being higher in the photoexposed group (35.40 ng/mL [21.86-72.20] as compared to the photoprotected group (29.20 ng/mL [23.10-45.80]. There was also difference in PTH levels, being higher in the photoexposed

How can we conserve intact tropical peatlands?

Science.gov (United States)

Lawson, Ian; Roucoux, Katherine

2017-04-01

The scientific community has, for more than three decades, been expressing increasing alarm about the fate of peatlands in parts of Indonesia and Malaysia, where extensive land-use conversion and drainage for rice and oil palm have greatly compromised peatland hydrology, ecology, biological richness, and carbon storage. The discourse in the literature on these peatlands is now moving on from attempts to preserve the last remaining fragments of peat-swamp forest, towards discussion of how best to restore damaged ecosystems, and whether it is possible to manage plantations more 'sustainably'. It is becoming increasingly clear, however, that peatlands occur quite widely in other parts of the lowland tropics, including parts of Amazonia and the Congo Basin, and many of these peatlands can reasonably be described as 'intact': although few if any parts of the tropics are totally unaffected by human actions, the hydrology and functional ecology of these systems appear to be close to a 'natural' state. The question then arises as to what should be done with the knowledge of their existence. Here we analyse the arguments in favour of protecting intact peatlands, and the potential conflicts with other priorities such as economic development and social justice. We evaluate alternative mechanisms for protecting intact peatlands, focusing on the particular issues raised by peatlands as opposed to other kinds of tropical ecosystem. We identify ways in which natural science agendas can help to inform these arguments, using our own contributions in palaeoecology and carbon mapping as examples. Finally, we argue for a radical reconsideration of research agendas in tropical peatlands, highlighting the potential contribution of methodologies borrowed from the social sciences and humanities.

Bone-remodeling transcript levels are independent of perching in end-of-lay white leghorn chickens.

Science.gov (United States)

Dale, Maurice D; Mortimer, Erin M; Kolli, Santharam; Achramowicz, Erik; Borchert, Glenn; Juliano, Steven A; Halkyard, Scott; Sietz, Nick; Gatto, Craig; Hester, Patricia Y; Rubin, David A

2015-01-23

Osteoporosis is a bone disease that commonly results in a 30% incidence of fracture in hens used to produce eggs for human consumption. One of the causes of osteoporosis is the lack of mechanical strain placed on weight-bearing bones. In conventionally-caged hens, there is inadequate space for chickens to exercise and induce mechanical strain on their bones. One approach is to encourage mechanical stress on bones by the addition of perches to conventional cages. Our study focuses on the molecular mechanism of bone remodeling in end-of-lay hens (71 weeks) with access to perches. We examined bone-specific transcripts that are actively involved during development and remodeling. Using real-time quantitative PCR, we examined seven transcripts (COL2A1 (collagen, type II, alpha 1), RANKL (receptor activator of nuclear factor kappa-B ligand), OPG (osteoprotegerin), PTHLH (PTH-like hormone), PTH1R (PTH/PTHLH type-1 receptor), PTH3R (PTH/PTHLH type-3 receptor), and SOX9 (Sry-related high mobility group box)) in phalange, tibia and femur. Our results indicate that the only significant effect was a difference among bones for COL2A1 (femur > phalange). Therefore, we conclude that access to a perch did not alter transcript expression. Furthermore, because hens have been used as a model for human bone metabolism and osteoporosis, the results indicate that bone remodeling due to mechanical loading in chickens may be a product of different pathways than those involved in the mammalian model.

Association of Secondary Hyperparathyroidism with Coronary Artery Disease in Patients on Regular Hemodialysis

Directory of Open Access Journals (Sweden)

Azar BARADARAN

2011-12-01

Full Text Available Objective: To understand the association of parathormone excess due to secondary hyperparathyroidism and hyperphosphatemia with coronary artery disease, a study was designed on a group of stable hemodialysis (HD patients. Methods: This cross-sectional study was carried out on patients undergoing maintenance HD. Blood samples were collected after overnight fasting for serum calcium, phosphorus, and intact serum parathormone (iPTH. The presence of cardiac chest pain was confirmed through the complaint of heart burn or epigastric pain, retrosternal discomfort and chest compression was confirmed by symmetrical depressed T wave at that time on a 12-lead ECG by means of a 12-channel and also reliving the pain after taking sublingual Trinitroglycerine pearls (TNG. Results: A sample of 36 stable HD patients was investigated. The mean age of patients was 46.5±17 years. The length of the time patients have been on hemodialysis were 32± 36 months (Median = 19 months. About 21% of patients had chest pain. Mean±SD of intact PTH of patients was 434±455 pg/ml (Median = 309 pg/ml. In this study, there was a significant difference of hemodialysis duration (p = 0.009, hemodialysis amount (p = 0.029 and also serum phosphorus (p = 0.013 between patients with and without cardiac chest pain. There was also a significant difference of iPTH (p = 0.026 between male hemodialysis patients with and without cardiac chest pain. Conclusion: Our data supported the importance of better control of serum phosphorus and also treatment of parathormone excess as the responsible factors promoting the coronary artery disease in hemodialysis patients.

Actin-Sorting Nexin 27 (SNX27)-Retromer Complex Mediates Rapid Parathyroid Hormone Receptor Recycling*

Science.gov (United States)

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

THE CARDIOVASCULAR EFFECTS OF CINACALCET IN HEMODIALYSIS PATIENTS WITH SECONDARY HYPERPARATHYROIDISM

Directory of Open Access Journals (Sweden)

Sungjin Chung

2012-06-01

Full Text Available Vascular changes characterized by calcification of either intima or media result in arterial stiffness and cardiac hypertrophy, especially in hemodialyais patients with secondary hyperparathyroidism. The purpose of this study is to evaluate the effects of cinacalcet on arterial compliance and cardiac hypertrophy. We studied 14 patients with ESRD who had high levels of intact PTH (iPTH, >300 pg/mL and of corrected serum calcium (cCa, >9.0 mg/dL with cinacalcet over 20-week period prospectively. After 20 weeks treatment, we performed flow-mediated dialation (FMD, cadio-ankle vascular index (CAVI and echocardiographic analyses. Twenty weeks cinaclacet treatment significantly decreased blood levels of iPTH (628.2±250.8 vs. 251.7±237.4 pg/ml, p<0.01, calcium (9.7±0.7 vs.8.7±0.6 mg/dl, P<0.01, phosphorus (6.8±1.3 vs. 5.0±1.4 mg/dl, P<0.01, calcium x phosphorus product (64.8±15.4 vs. 43.5±14.9, P<0.01 and 25(OH vitamin D (9.9±3.4 vs. 8.2±2.7 ng/mL, P<0.05. There were no significant changes in LV mass, the ejection fraction and fractional shortening. In contrast, cinacalcet significantly improved FMD (8.6±2.9 vs. 14.3±2.8%, P<0.01 and enhanced CAVI (8.8±2.3 vs. 7.6±2.4, P<0.05, respectively. In conclusion, cinacalcet treatment in hemodialysis patients with secondary hyperparathyroidism ameliorates endothelial dysfunction and arterial compliance.

Optimized Planning Target Volume for Intact Cervical Cancer

International Nuclear Information System (INIS)

Khan, Alvin; Jensen, Lindsay G.; Sun Shuai; Song, William Y.; Yashar, Catheryn M.; Mundt, Arno J.; Zhang Fuquan; Jiang, Steve B.; Mell, Loren K.

2012-01-01

Purpose: To model interfraction clinical target volume (CTV) variation in patients with intact cervical cancer and design a planning target volume (PTV) that minimizes normal tissue dose while maximizing CTV coverage. Methods and Materials: We analyzed 50 patients undergoing external-beam radiotherapy for intact cervical cancer using daily online cone-beam computed tomography (CBCT). The CBCTs (n = 972) for each patient were rigidly registered to the planning CT. The CTV was delineated on the planning CT (CTV 0 ) and the set of CBCTs ({CTV 1 –CTV 25 }). Manual (n = 98) and automated (n = 668) landmarks were placed over the surface of CTV 0 with reference to defined anatomic structures. Normal vectors were extended from each landmark, and the minimum length required for a given probability of encompassing CTV 1 –CTV 25 was computed. The resulting expansions were used to generate an optimized PTV. Results: The mean (SD; range) normal vector length to ensure 95% coverage was 4.3 mm (2.7 mm; 1–16 mm). The uniform expansion required to ensure 95% probability of CTV coverage was 13 mm. An anisotropic margin of 20 mm anteriorly and posteriorly and 10 mm superiorly, inferiorly, and laterally also would have ensured a 95% probability of CTV coverage. The volume of the 95% optimized PTV (1470 cm 3 ) was significantly lower than both the anisotropic PTV (2220 cm 3 ) and the uniformly expanded PTV (2110 cm 3 ) (p 0 , 5–10 mm along the interfaces of CTV 0 with the bladder and rectum, and 10–14 mm along the anterior surface of CTV 0 at the level of the uterus. Conclusion: Optimizing PTV definition according to surface landmarking resulted in a high probability of CTV coverage with reduced PTV volumes. Our results provide data justifying planning margins to use in practice and clinical trials.

Selective Vitamin D Receptor Activation as Anti-Inflammatory Target in Chronic Kidney Disease

Directory of Open Access Journals (Sweden)

J. Donate-Correa

2014-01-01

Full Text Available Paricalcitol, a selective vitamin D receptor (VDR activator used for treatment of secondary hyperparathyroidism in chronic kidney disease (CKD, has been associated with survival advantages, suggesting that this drug, beyond its ability to suppress parathyroid hormone, may have additional beneficial actions. In this prospective, nonrandomised, open-label, proof-of-concept study, we evaluated the hypothesis that selective vitamin D receptor activation with paricalcitol is an effective target to modulate inflammation in CKD patients. Eight patients with an estimated glomerular filtration rate between 15 and 44 mL/min/1.73 m2 and an intact parathyroid hormone (PTH level higher than 110 pg/mL received oral paricalcitol (1 μg/48 hours as therapy for secondary hyperparathyroidism. Nine patients matched by age, sex, and stage of CKD, but a PTH level <110 pg/mL, were enrolled as a control group. Our results show that five months of paricalcitol administration were associated with a reduction in serum concentrations of hs-CRP (13.9%, P<0.01, TNF-α (11.9%, P=0.01, and IL-6 (7%, P<0.05, with a nonsignificant increase of IL-10 by 16%. In addition, mRNA expression levels of the TNFα and IL-6 genes in peripheral blood mononuclear cells decreased significantly by 30.8% (P=0.01 and 35.4% (P=0.01, respectively. In conclusion, selective VDR activation is an effective target to modulate inflammation in CKD.

Parathyroid hormone, but not vitamin D, is associated with the metabolic syndrome in morbidly obese women and men: a cross-sectional study

Directory of Open Access Journals (Sweden)

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.

Does human leukocyte elastase degrade intact skin elastin?

DEFF Research Database (Denmark)

Schmelzer, Christian E H; Jung, Michael C; Wohlrab, Johannes

2012-01-01

This study aimed to investigate the susceptibility of intact fibrillar human elastin to human leukocyte elastase and cathepsin G. Elastin is a vital protein of the extracellular matrix of vertebrates, and provides exceptional properties including elasticity and tensile strength to many tissues...... and organs, including the aorta, lung, cartilage, elastic ligaments and skin, and is thus critical for their long-term function. Mature elastin is an insoluble and extremely durable protein that undergoes very little turnover, but sustained exposure to proteases may lead to irreversible and severe damage......, and thus to functional loss of the elastic fiber network. Hence, it is a key issue to understand which enzymes actually initiate elastolysis under certain pathological conditions or during intrinsic aging. In this paper, we provide a complete workflow for isolation of pure and intact elastin from very...

DNA synthesis in periportal and perivenous hepatocytes of intact and hepatectomized young mice.

Science.gov (United States)

Fernández-Blanco, A; Inda, A M; Errecalde, A L

2015-01-01

DNA synthesis of hepatocytes in two areas of Intact and Hepatectomized young mice liver along a circadian period was studied. DNA synthesis was significantly different at all analyzed time points in Intact and Hepatectomized animals. Differences between periportal and perivenous hepatocytes were found in hepatectomized animals at 04/42 and 08/46 hr of day/hour post-hepatectomy. DNAs peak in periportal hepatocytes regenerating liver occurs 4 hr earlier than in perivenous hepatocytes, probably reflecting their shorter G1 phase. Besides, daily mean values of regenerating livers were higher than those observed in Intact animals, as a consequence of surgical removal.

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...

Multi-Axis Prosthetic Knee Resembles Alpine Skiing Movements of an Intact Leg

Science.gov (United States)

Demšar, Ivan; Duhovnik, Jože; Lešnik, Blaž; Supej, Matej

2015-01-01

The purpose of the study was to analyse the flexion angles of the ski boot, ankle and knee joints of an above-knee prosthesis and to compare them with an intact leg and a control group of skiers. One subject with an above-knee amputation of the right leg and eight healthy subjects simulated the movement of a skiing turn by performing two-leg squats in laboratory conditions. By adding additional loads in proportion to body weight (BW; +1/3 BW, +2/3 BW, +3/3 BW), various skiing regimes were simulated. Change of Flexion Angle (CoFA) and Range of Motion (RoM) in the ski boot, ankle and knee joints were calculated and compared. An average RoM in the skiing boot on the side of prosthesis (4.4 ± 1.1°) was significantly lower compared to an intact leg (5.9 ± 1.8°) and the control group (6.5 ± 2.3°). In the ankle joint, the average RoM was determined to be 13.2±2.9° in the prosthesis, 12.7 ± 2.8° in an intact leg and 14.8±3.6 in the control group. However, the RoM of the knee joint in the prosthesis (42.2 ± 4.2°) was significantly larger than that of the intact leg (34.7 ± 4.4°). The average RoM of the knee joint in the control group was 47.8 ± 5.4°. The influences of additional loads on the kinematics of the lower extremities were different on the side of the prosthesis and on the intact leg. In contrast, additional loads did not produce any significant differences in the control group. Although different CoFAs in the ski boot, ankle and knee joints were used, an above-knee prosthesis with a built-in multi-axis prosthetic knee enables comparable leg kinematics in simulated alpine skiing. Key points The RoM in the ski boot on the side of the prosthetic leg was smaller than the RoM of the intact leg and the control group of healthy subjects. The RoM in the ankle joint of prosthetic leg was comparable to that of the intact leg and the control group of healthy subjects. The RoM in the prosthetic knee joint was greater than the RoM in the knee joint of the

The development of structural complexity in the child's concept of family: the effect of cognitive stage, sex, and intactness of family.

Science.gov (United States)

Wedemeyer, N V; Bickhard, M H; Cooper, R G

1989-12-01

Twenty-eight boys and 28 girls at each of the Piagetian preoperational, concrete operational, and formal operational cognitive stages were given an interview focusing on their concepts of family. Half of each group were from intact families, and half were from divorced families. Interviews were scored for two structural aspects of the concept of family: conceptual level, and use of dimensions that structure the concept. The complexity of children's concepts was strongly related to cognitive stage and, to a lesser degree, to sex. Frequency of use of concept dimensions was strongly affected by general developmental level, though not specifically cognitive stage, and by intactness of family, but to a lesser degree by sex. Specific information is provided on the effect of these factors on perceptions of family composition, parental roles, and breadth of family activities.

Antimicrobial activity of a new intact skin antisepsis formulation.

Science.gov (United States)

Russo, Antonello; Viotti, Pier Luigi; Vitali, Matteo; Clementi, Massimo

2003-04-01

Different antiseptic formulations have shown limitations when applied to disinfecting intact skin, notably short-term tolerability and/or efficacy. The purpose of this study was optimizing a new antiseptic formulation specifically targeted at intact skin disinfection and evaluating its in vitro microbicidal activity and in vivo efficacy. The biocidal properties of the antiseptic solution containing 0.5% chloramine-T diluted in 50% isopropyl alcohol (Cloral; Eurospital SpA Trieste, Italy) were measured in vitro versus gram-positive-, gram-negative-, and acid-alcohol-resistant germs and fungi with standard suspension tests in the presence of fetal bovine serum. Virus-inhibiting activity was evaluated in vitro against human cytomegalovirus, herpes simplex virus, poliovirus, hepatitis B virus, and hepatitis C virus. Tests used different methods for the different biologic and in vitro replication capacity of these human viruses. Lastly, Cloral tolerability and skin colonization retardation efficacy after disinfection were studied in vivo. The antiseptic under review showed fast and sustained antimicrobial activity. The efficacy of Cloral against clinically important bacterial and viral pathogens and fungi was highlighted under the experimental conditions described in this article. Finally, microbial regrowth lag and no side effects were documented in vivo after disinfection of 11 volunteers. A stable chloramine-T solution in isopropyl alcohol may be suggested for intact skin antisepsis.

Investigation of Mitochondrial Dysfunction by Sequential Microplate-Based Respiration Measurements from Intact and Permeabilized Neurons

Science.gov (United States)

Clerc, Pascaline; Polster, Brian M.

2012-01-01

Mitochondrial dysfunction is a component of many neurodegenerative conditions. Measurement of oxygen consumption from intact neurons enables evaluation of mitochondrial bioenergetics under conditions that are more physiologically realistic compared to isolated mitochondria. However, mechanistic analysis of mitochondrial function in cells is complicated by changing energy demands and lack of substrate control. Here we describe a technique for sequentially measuring respiration from intact and saponin-permeabilized cortical neurons on single microplates. This technique allows control of substrates to individual electron transport chain complexes following permeabilization, as well as side-by-side comparisons to intact cells. To illustrate the utility of the technique, we demonstrate that inhibition of respiration by the drug KB-R7943 in intact neurons is relieved by delivery of the complex II substrate succinate, but not by complex I substrates, via acute saponin permeabilization. In contrast, methyl succinate, a putative cell permeable complex II substrate, failed to rescue respiration in intact neurons and was a poor complex II substrate in permeabilized cells. Sequential measurements of intact and permeabilized cell respiration should be particularly useful for evaluating indirect mitochondrial toxicity due to drugs or cellular signaling events which cannot be readily studied using isolated mitochondria. PMID:22496810

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

Impulse radar scanning of intact salt at the Avery Island Mine

International Nuclear Information System (INIS)

Cook, C.W.

1980-05-01

A series of experiments was run in the Avery Island Mine to evaluate the capability of an impulse radar to locate anomalies and simulated waste targets in intact dome salt. Voids in salt were difficult to detect. On the positive side, metal targets and simulated waste (glass) were easily located in intact salt. Radar scanning at ranges of greater than 25 meters and short-range resolution of target positions to within a few centimeters were achieved

Bioavailability and in vivo metabolism of intact glucosinolates

DEFF Research Database (Denmark)

Sørensen, Jens Christian; Frandsen, Heidi Blok; Jensen, Søren Krogh

2016-01-01

Health benefits associated with consumption of cruciferous vegetables have received considerable attention with a hitherto focus on the role and bioactivity of glucosinolate degradation products. We investigated the in vivo metabolism of intact glucosinolates by following their fate in digesta an...

Interactions between calcium and phosphorus in the regulation of the production of fibroblast growth factor 23 in vivo

Science.gov (United States)

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

Bone-Remodeling Transcript Levels Are Independent of Perching in End-of-Lay White Leghorn Chickens

Directory of Open Access Journals (Sweden)

Maurice D. Dale

2015-01-01

Full Text Available Osteoporosis is a bone disease that commonly results in a 30% incidence of fracture in hens used to produce eggs for human consumption. One of the causes of osteoporosis is the lack of mechanical strain placed on weight-bearing bones. In conventionally-caged hens, there is inadequate space for chickens to exercise and induce mechanical strain on their bones. One approach is to encourage mechanical stress on bones by the addition of perches to conventional cages. Our study focuses on the molecular mechanism of bone remodeling in end-of-lay hens (71 weeks with access to perches. We examined bone-specific transcripts that are actively involved during development and remodeling. Using real-time quantitative PCR, we examined seven transcripts (COL2A1 (collagen, type II, alpha 1, RANKL (receptor activator of nuclear factor kappa-B ligand, OPG (osteoprotegerin, PTHLH (PTH-like hormone, PTH1R (PTH/PTHLH type-1 receptor, PTH3R (PTH/PTHLH type-3 receptor, and SOX9 (Sry-related high mobility group box in phalange, tibia and femur. Our results indicate that the only significant effect was a difference among bones for COL2A1 (femur > phalange. Therefore, we conclude that access to a perch did not alter transcript expression. Furthermore, because hens have been used as a model for human bone metabolism and osteoporosis, the results indicate that bone remodeling due to mechanical loading in chickens may be a product of different pathways than those involved in the mammalian model.

Isolation of intact sub-dermal secretory cavities from Eucalyptus

Directory of Open Access Journals (Sweden)

Goodger Jason QD

2010-09-01

Full Text Available Abstract Background The biosynthesis of plant natural products in sub-dermal secretory cavities is poorly understood at the molecular level, largely due to the difficulty of physically isolating these structures for study. Our aim was to develop a protocol for isolating live and intact sub-dermal secretory cavities, and to do this, we used leaves from three species of Eucalyptus with cavities that are relatively large and rich in essential oils. Results Leaves were digested using a variety of commercially available enzymes. A pectinase from Aspergillus niger was found to allow isolation of intact cavities after a relatively short incubation (12 h, with no visible artifacts from digestion and no loss of cellular integrity or cavity contents. Several measurements indicated the potential of the isolated cavities for further functional studies. First, the cavities were found to consume oxygen at a rate that is comparable to that estimated from leaf respiratory rates. Second, mRNA was extracted from cavities, and it was used to amplify a cDNA fragment with high similarity to that of a monoterpene synthase. Third, the contents of the cavity lumen were extracted, showing an unexpectedly low abundance of volatile essential oils and a sizeable amount of non-volatile material, which is contrary to the widely accepted role of secretory cavities as predominantly essential oil repositories. Conclusions The protocol described herein is likely to be adaptable to a range of Eucalyptus species with sub-dermal secretory cavities, and should find wide application in studies of the developmental and functional biology of these structures, and the biosynthesis of the plant natural products they contain.

Occurence of translocations between irradiated and intact chromosomes of Drosophila melanogaster

International Nuclear Information System (INIS)

Myasnyankina, E.N.; Abeleva, Eh.A.; Generalova, M.V.

1980-01-01

Two translocations between irradiated father and intact mother autosomes are obtained in Drosophila melanogaster. Five out of 283 regular translocations (between the second and the third chromosomes of an irradiated male) are accompanied by a recombination over the second or the third chromosomes. Nine flies out of twenty considered to be recombinants, could originate due to mutations. The data obtained prove that intact female autosomes can take part in the exchange with homologic (recombinations) and heterologic (translocations) irradiated male autosomes

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

Direct detection of radicals in intact soybean nodules

DEFF Research Database (Denmark)

Mathieu, C; Moreau, S; Frendo, P

1998-01-01

Electron paramagnetic resonance spectroscopy has been employed to examine the nature of the metal ions and radicals present in intact root nodules of soybean plants grown in the absence of nitrate. The spectra obtained from nodules of different ages using this non-invasive technique show dramatic...... differences, suggesting that there are both qualitative and quantitative changes in the metal ion and radical species present. A major component of the spectra obtained from young nodules is assigned to a complex (Lb-NO) of nitric oxide (NO.) with the heme protein leghemoglobin (Lb). This Lb-NO species, which...... has not been previously detected in intact root nodules of plants grown in the absence of nitrate, is thought to be formed by reaction of nitric oxide with iron(II) leghemoglobin. The nitric oxide may be generated from arginine via a nitric oxide synthase-like activity present in the nodules...

Linear response at the 4-component relativistic density-functional level: application to the frequency-dependent dipole polarizability of Hg, AuH and PtH2

International Nuclear Information System (INIS)

Salek, Pawel; Helgaker, Trygve; Saue, Trond

2005-01-01

We report the implementation and application of linear response density-functional theory (DFT) based on the 4-component relativistic Dirac-Coulomb Hamiltonian. The theory is cast in the language of second quantization and is based on the quasienergy formalism (Floquet theory), replacing the initial state dependence of the Runge-Gross theorem by periodic boundary conditions. Contradictions in causality and symmetry of the time arguments are thereby avoided and the exchange-correlation potential and kernel can be expressed as functional derivatives of the quasienergy. We critically review the derivation of the quasienergy analogues of the Hohenberg-Kohn theorem and the Kohn-Sham formalism and discuss the nature of the quasienergy exchange-correlation functional. Structure is imposed on the response equations in terms of Hermiticity and time-reversal symmetry. It is observed that functionals of spin and current densities, corresponding to time-antisymmetric operators, contribute to frequency-dependent and not static electric properties. Physically, this follows from the fact that only a time-dependent electric field creates a magnetic field. It is furthermore observed that hybrid functionals enhance spin polarization since only exact exchange contributes to anti-Hermitian trial vectors. We apply 4-component relativistic linear response DFT to the calculation of the frequency-dependent polarizability of the isoelectronic series Hg, AuH and PtH 2 . Unlike for the molecules, the effect of electron correlation on the polarizability of the mercury atom is very large, about 25%. We observe a remarkable performance of the local-density approximation (LDA) functional in reproducing the experimental frequency-dependent polarizability of this atom, clearly superior to that of the BLYP and B3LYP functionals. This allows us to extract Cauchy moments (S(-4) = 382.82 and S(-6) = 6090.89 a.u.) that we believe are superior to experiment since we go to higher order in the Cauchy

Assessment of renal function following irradiation of the intact spleen for hodgkin disease

International Nuclear Information System (INIS)

Birkhead, B.M.; Dobbs, C.E.; Beard, M.F.; Tyson, J.W.; Fuller, E.A.

1979-01-01

Twenty-three patients with clinical Stage IA to IIIB Hodgkin disease underwent extended-field radiotherapy, including the intact spleen. In 17 of those patients, there was little evidence of renal dysfunction resulting from partial irradiation of the left kidney, which is inherent in such treatment. While isotopic images revealed an anatomic defect in the upper pole of the left kidney in one-third of the patients, dynamic studies showed that this anatomic alteration was not accompanied by any demonstrable dysfunction. Consistently normal serum BUN and creatinine levels in all patients tended to affirm that conclusion

Attachment, conflict and self-esteem in adolescents from intact and divorced families / Apego, conflito e auto-estima em adolescentes de famílias intactas e divorciadas

OpenAIRE

Catarina Pinheiro Mota; Paula Mena Matos

2009-01-01

This study aimed to analyze the differential contribution to adolescent's self-esteem concerning family structure (intact and divorced families), interparental conflict, and attachment to parents and peers. The sample consisted of 403 adolescents, aged from 14 to 19. Univariate ANOVA showed that family structure does not predict self-esteem, but adolescents from intact families with higher levels of interparental conflict presented lower self-esteem. Parental attachment patterns derived from ...

Bone Status Among Patients With Nonsurgical Hypoparathyroidism, Autosomal Dominant Hypocalcaemia, and Pseudohypoparathyroidism: A Cohort Study.

Science.gov (United States)

Underbjerg, Line; Malmstroem, Sofie; Sikjaer, Tanja; Rejnmark, Lars

2018-03-01

Nonsurgical hypoparathyroidism (Ns-HypoPT) and pseudohypoparathyroidism (PHP) are both rare diseases, characterized by hypocalcemia. In Ns-HypoPT, PTH levels are low, whereas patients with PHP often have very high levels due to receptor-insensitivity to PTH (PTH-resistance). Accordingly, we hypothesized that indices of bone turnover and bone mineralization/architecture are similar in Ns-HypoPT and PHP despite marked differences in PTH levels. We studied 62 patients with Ns-HypoPT and 31 with PHP as well as a group of age- and sex-matched healthy controls. We found a significantly higher areal BMD (aBMD) by DXA among patients with Ns-HypoPT, both compared with PHP and the background population. Compared with Ns-HypoPT, PHP patients had significantly lower total and trabecular volumetric BMD (vBMD) assessed by quantitative computed tomography (QCT) scans at the spine and hip. High-resolution peripheral quantitative computed tomography (HRpQCT) scans showed a lower trabecular area and vBMD as well as a lower trabecular number at the tibia in PHP compared to Ns-HypoPT and matched controls. In PHP, PTH levels correlated with levels of markers of bone formation (osteocalcin, bone-specific alkaline phosphatase, P1NP), and bone resorption (CTx). In adult males, levels of bone markers were significantly higher in PHP compared with Ns-HypoPT. Levels of procalcitonin and calcitonin were significantly higher in PHP compared with Ns-HypoPT. In conclusion, indices of bone turnover, density, and microarchitecture differ between patients with Ns-HypoPT and PHP. Our data suggest that patients with PHP do not have a complete skeletal resistance to PTH and that the effects of chronically high PTH levels in PHP are mostly confined to the trabecular tissue. © 2017 American Society for Bone and Mineral Research. © 2017 American Society for Bone and Mineral Research.

Comparison of the Pharmacological Effects of Paricalcitol Versus Calcitriol on Secondary Hyperparathyroidism in the Dialysis Population.

Science.gov (United States)

Večerić-Haler, Željka; Romozi, Karmen; Antonič, Manja; Benedik, Miha; Ponikvar, Jadranka Buturović; Ponikvar, Rafael; Knap, Bojan

2016-06-01

Management of secondary hyperparathyroidism (SHPT) in dialysis population includes the use of active vitamin D forms, among which paricalcitol was shown to be more effective at reducing parathyroid hormone (PTH) concentrations. A prospective randomized study comparing the effectiveness and safety of peroral paricalcitol and calcitriol in suppressing PTH concentrations in 20 hemodialysis patients was performed comparing the influence of agents on PTH suppression, calcium (Ca) and phosphate (P) level and calcium-phosphorus product (C×P). The study was performed in an "intent to treat" manner with primary end point in reduction of PTH level in the target area of 150 > PTH < 300 ng/L after 3 months. At the time point 3 months after therapy induction paricalcitol and calcitriol were equally efficient at correcting PTH levels, with paricalcitol showing significantly less calcemic effect than calcitriol. © 2016 International Society for Apheresis, Japanese Society for Apheresis, and Japanese Society for Dialysis Therapy.

Capillary zone electrophoresis-mass spectromet of intact proteins

NARCIS (Netherlands)

Domínguez-Vega, Elena; Haselberg, Rob; Somsen, Govert W.

2016-01-01

Capillary electrophoresis (CE) coupled with mass spectrometry (MS) has proven to be a powerful analytical tool for the characterization of intact proteins. It combines the high separation efficiency, short analysis time, and versatility of CE with the mass selectivity and sensitivity offered by MS

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...

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

Losing a jewel—Rapid declines in Myanmar’s intact forests from 2002-2014

Science.gov (United States)

Horning, Ned; Khaing, Thiri; Thein, Zaw Min; Aung, Kyaw Moe; Aung, Kyaw Htet; Phyo, Paing; Tun, Ye Lin; Oo, Aung Htat; Neil, Anthony; Thu, Win Myo; Songer, Melissa; Huang, Qiongyu; Connette, Grant; Leimgruber, Peter

2017-01-01

New and rapid political and economic changes in Myanmar are increasing the pressures on the country’s forests. Yet, little is known about the past and current condition of these forests and how fast they are declining. We mapped forest cover in Myanmar through a consortium of international organizations and environmental non-governmental groups, using freely-available public domain data and open source software tools. We used Landsat satellite imagery to assess the condition and spatial distribution of Myanmar’s intact and degraded forests with special focus on changes in intact forest between 2002 and 2014. We found that forests cover 42,365,729 ha or 63% of Myanmar, making it one of the most forested countries in the region. However, severe logging, expanding plantations, and degradation pose increasing threats. Only 38% of the country’s forests can be considered intact with canopy cover >80%. Between 2002 and 2014, intact forests declined at a rate of 0.94% annually, totaling more than 2 million ha forest loss. Losses can be extremely high locally and we identified 9 townships as forest conversion hotspots. We also delineated 13 large (>100,000 ha) and contiguous intact forest landscapes, which are dispersed across Myanmar. The Northern Forest Complex supports four of these landscapes, totaling over 6.1 million ha of intact forest, followed by the Southern Forest Complex with three landscapes, comprising 1.5 million ha. These remaining contiguous forest landscape should have high priority for protection. Our project demonstrates how open source data and software can be used to develop and share critical information on forests when such data are not readily available elsewhere. We provide all data, code, and outputs freely via the internet at (for scripts: https://bitbucket.org/rsbiodiv/; for the data: http://geonode.themimu.info/layers/geonode%3Amyan_lvl2_smoothed_dec2015_resamp) PMID:28520726

Non-intact zona improves development of murine preimplantation ...

African Journals Online (AJOL)

ajl5

2012-09-25

Sep 25, 2012 ... 2College of Animal Science and Technology, Northwest A & F University, Yangling, ... Key words: Mouse, non-intact zona embryos, adenovirus vector with green fluorescent protein (pAd-GFP), .... Based on microscopic examination, the ZP of some ..... permeable structure of ZP that allowed penetration of.

Intact skin and not stripped skin is crucial for the safety and efficacy of peanut epicutaneous immunotherapy (EPIT in mice

Directory of Open Access Journals (Sweden)

Mondoulet Lucie

2012-11-01

Full Text Available Abstract Background Epicutaneous immunotherapy (EPIT on intact skin with an epicutaneous delivery system has already been used in preclinical and clinical studies. In epicutaneous vaccination and immunotherapy, the stripping of skin before application of the allergen is suggested to facilitate the passage of allergen through immune cells. Objectives The aim of this study was to compare the immunological response induced by EPIT performed on intact and stripped skin in a mouse model of peanut allergy. Methods After oral sensitization with peanut and cholera toxin, BALB/c mice were epicutaneously treated using an epicutaneous delivery system (Viaskin® (DBV Technologies, Paris applied either on intact skin or on stripped skin. Following EPIT, mice received an exclusive oral peanut regimen, aimed at triggering esophageal and jejunal lesions. We assessed eosinophil infiltration by histology, mRNA expression in the esophagus, antibody levels and peripheral T-cell response. Results EPIT on intact skin significantly reduced Th2 immunological response (IgE response and splenocyte secretion of Th2 cytokines as well as esophageal eosinophilia (2.7 ± 0.9, compared to Sham 19.9 ± 1.5, p  Conclusions Epicutaneous allergen-specific immunotherapy needs the integrity of superficial layers of the stratum corneum to warranty safety of treatment and to induce a tolerogenic profile of the immune response.

Bioengineered human IAS reconstructs with functional and molecular properties similar to intact IAS

Science.gov (United States)

Singh, Jagmohan

2012-01-01

Because of its critical importance in rectoanal incontinence, we determined the feasibility to reconstruct internal anal sphincter (IAS) from human IAS smooth muscle cells (SMCs) with functional and molecular attributes similar to the intact sphincter. The reconstructs were developed using SMCs from the circular smooth muscle layer of the human IAS, grown in smooth muscle differentiation media under sterile conditions in Sylgard-coated tissue culture plates with central Sylgard posts. The basal tone in the reconstructs and its changes were recorded following 0 Ca2+, KCl, bethanechol, isoproterenol, protein kinase C (PKC) activator phorbol 12,13-dibutyrate, and Rho kinase (ROCK) and PKC inhibitors Y-27632 and Gö-6850, respectively. Western blot (WB), immunofluorescence (IF), and immunocytochemical (IC) analyses were also performed. The reconstructs developed spontaneous tone (0.68 ± 0.26 mN). Bethanechol (a muscarinic agonist) and K+ depolarization produced contraction, whereas isoproterenol (β-adrenoceptor agonist) and Y-27632 produced a concentration-dependent decrease in the tone. Maximal decrease in basal tone with Y-27632 and Gö-6850 (each 10−5 M) was 80.45 ± 3.29 and 17.76 ± 3.50%, respectively. WB data with the IAS constructs′ SMCs revealed higher levels of RhoA/ROCK, protein kinase C-potentiated inhibitor or inhibitory phosphoprotein for myosin phosphatase (CPI-17), phospho-CPI-17, MYPT1, and 20-kDa myosin light chain vs. rectal smooth muscle. WB, IF, and IC studies of original SMCs and redispersed from the reconstructs for the relative distribution of different signal transduction proteins confirmed the feasibility of reconstruction of IAS with functional properties similar to intact IAS and demonstrated the development of myogenic tone with critical dependence on RhoA/ROCK. We conclude that it is feasible to bioengineer IAS constructs using human IAS SMCs that behave like intact IAS. PMID:22790596

Near-infrared reflectance spectroscopy for predicting amino acids content in intact processed animal proteins.

Science.gov (United States)

De la Haba, Maria José; Garrido-Varo, Ana; Guerrero-Ginel, José Emilio; Pérez-Marín, Dolores C

2006-10-04

Near-infrared calibrations were developed for the instantaneous prediction of amino acids composition of processed animal proteins (PAPs). Two sample presentation modes were compared (ground vs intact) for demonstrating the viability of the analysis in the intact form, avoiding the need for milling. Modified partial least-squares (MPLS) equations for the prediction of amino acids in PAPs were developed using the same set of samples (N = 92 PAPs) analyzed in ground and intact form and in three cups differing in the optical window size. The standard error for cross validation (SECV) and the coefficient of determination (1-VR) values yielded with the calibrations developed using the samples analyzed in the intact form showed similar or even better accuracy than those obtained with finely ground samples. The excellent predictive ability (1-VR > 0.90; CV marketing of these important protein feed ingredients, alleviating the costs and time associated with the routine quality controls.

Effectiveness and safety of a 6-month treatment with paricalcitol in patients on hemodialysis with secondary hyperparathyroidism.

Science.gov (United States)

Olaizola, Inés; Caorsi, Hena; Fajardo, Laura; Ferreiro, Alejandro; Campistrus, Nieves; Dolinsky, Deyanira; Petraglia, Alicia; Ambrosoni, Pablo

2016-01-01

The mineral bone disorder, particularly secondary hyperparathyroidism, in chronic kidney disease (CKD) has a systemic impact affecting not only bone metabolism. Therefore its correction is important to prevent cardiovascular, inflammatory and immune diseases. To assess the effectiveness and safety of intravenous paricalcitol administered over a 6 month period for the treatment of secondary hyperparathyroidism (SHPT) in patients undergoing conventional hemodialysis, with close follow-up of treatment response. A phase 4 clinical trial was performed comparing clinical and laboratory data before and after 6 months of treatment. SHPT patients undergoing hemodialysis who were naïve to vitamin D metabolites or had failed to current therapy were included. Clinical and laboratory characteristics were analyzed. Efficacy analyses were based on intact parathyroid hormone (iPTH) levels and were performed using data from patients who completed 6 months of treatment. Nineteen of the 26 patients enrolled completed 6 months of treatment. All patients exhibited reduced baseline iPTH levels (mean reduction, 371.8 pg/mL; 95% CI, 273.3-470.2 pg/mL]; 17 patients (89.5%) had reductions exceeding 30%. Twelve patients (63%) achieved therapeutic success (defined as iPTH serum levels 150-300 pg/mL), with a median time of 2 months from the beginning of treatment. All reported episodes of hypercalcemia (n = 2) and hyperphosphatemia (n = 34) were asymptomatic. No major therapy-related serious AEs were reported. Paricalcitol was safely administered and was associated with significant decreases in iPTH levels over the study period. A doença metabólica óssea, em particular o hiperparatireoidismo secundário, na doença renal crônica (DRC) tem um impacto sistêmico que afeta nem só o metabolismo ósseo. Por tanto, sua correção é importante para prevenir as doenças do sistema imunitário, inflamatório e cardiovascular. Avaliar a eficácia e a segurança do paricalcitol intravenoso

Partial rescue of postnatal growth plate abnormalities in Ihh mutants by expression of a constitutively active PTH/PTHrP receptor.

Science.gov (United States)

Maeda, Yukiko; Schipani, Ernestina; Densmore, Michael J; Lanske, Beate

2010-02-01

Indian hedgehog (Ihh) is essential for chondrocyte proliferation/differentiation and osteoblast differentiation during prenatal endochondral bone formation. Ihh expression in postnatal chondrocytes has a non-redundant role in maintaining a growth plate and sustaining trabecular bone after birth. Loss of Ihh in postnatal chondrocytes results in fusion of the growth plate and a decrease in trabecular bone. In order to normalize this abnormal chondrocyte phenotype and to investigate whether a putative rescue of the growth plate anomalies is sufficient to correct the severe alterations in the bone, we expressed a constitutively active PTH/PTHrP receptor (an Ihh downstream target) in the chondrocytes of Col2 alpha 1-Cre ER; Ihh(dld) mice by mating Col2 alpha 1-Cre ER; Ihh(fl/fl) mice with Col2 alpha 1-constitutively active PTH/PTHrP receptor transgenic mice (Jansen, J). Col2 alpha 1-Cre ER; Ihh(f/f); J mice were then injected with tamoxifen at P0 to generate Col2 alpha 1-Cre ER; Ihh(d/d); J mice. In contrast with the previously reported growth plate phenotype of Col2 alpha 1-Cre ER; Ihh(d/d) mice that displayed ectopic chondrocyte hypertrophy at P7, growth plates of Col2 alpha 1-Cre ER; Ihh(d/d); J double mutants were well organized, and exhibited a gene expression pattern similar to the one of control mice. However, expression of osteoblast markers and Dkk1, a Wnt signaling target, remains decreased in the bone collar of Col2 alpha 1-Cre ER; Ihh(d/d); J mice when compared to control mice despite the rescue of abnormal chondrocyte differentiation. Moreover, proliferation of chondrocytes was still significantly impaired in Col2 alpha 1-Cre ER; Ihh(d/d); J mice, and this eventually led to the fusion of the growth plate at P14. In summary, we have demonstrated that expression of a Jansen receptor in chondrocytes was able to rescue abnormal chondrocyte differentiation but not impaired chondrocyte proliferation and the bone anomalies in mice lacking the Ihh gene in

Detection of parathyroid hormone using an electrochemical impedance biosensor based on PAMAM dendrimers.

Science.gov (United States)

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.

Comparative 25-OH-vitamin D level in institutionalized women older than 65 years from two cities in Spain and Argentina having a similar solar radiation index.

Science.gov (United States)

Portela, María Luz Pita Martin; Mónico, Amália; Barahona, Antonieta; Dupraz, Hernan; Sol Gonzales-Chaves, Macarena Maria; Zeni, Susana Noemi

2010-03-01

The present study evaluated and compared vitamin D nutritional status and calcium-phosphorus metabolism in institutionalized women >65 y from two cities that have a similar sun irradiation index (heliophany). The study was carried out in women living in similar social-status institutions from geographic cities having a similar solar radiation index (Lleida, Spain, n=49, and suburban Buenos Aires, Argentina [BA], n=48) at the end of summer. Fish consumption was higher in the Lleida group, as was red-meat consumption in the BA group. In both groups mean calcium intake was 800 mg/d. The daily intake of vitamin D was higher in the BA group (P100 pg/mL were found in 24% and 20% of women in Lleida and BA, respectively. There was a marked increase in carboxy-terminal telopeptide cross-links of type I collagen levels and a decrease in 25OHD with an increase in PTH levels (Pbone alkaline phosphatase increased significantly only when the PTH concentration duplicated the reference range. Even at the end of summer, vitamin D deficiency/insufficiency was prevalent in the two studied institutionalized elderly women. In the narrow range of the dietary calcium intake (close to 800 mg/d) of both studied groups, secondary hyperparathyroidism was absent when 25OHD levels were >17 ng/dL, indicating changes in the regulation control of serum PTH and consequently the changes in this threshold. As a result, vitamin D deficiency must be reversed to avoid the increment in bone turnover and to ensure the endocrine and paracrine functions of vitamin D for overall health and well-being. Copyright (c) 2010 Elsevier Inc. All rights reserved.

A high-throughput mass spectrometry assay to simultaneously measure intact insulin and C-peptide.

Science.gov (United States)

Taylor, Steven W; Clarke, Nigel J; Chen, Zhaohui; McPhaul, Michael J

2016-04-01

Measurements of fasting levels of insulin and C-peptide are useful in documenting insulin resistance and may help predict development of diabetes mellitus. However, the specific insulin and C-peptide levels associated with specific degrees of insulin resistance have not been defined, owing to marked variability among immunoassays and lack of standardization. Herein, we describe a multiplexed liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay for intact insulin and C-peptide. Insulin and C-peptide were enriched from patient sera using monoclonal antibodies immobilized on magnetic beads and processed on a robotic liquid handler. Eluted peptides were analyzed by LC-MS/MS. Bovine insulin and a stable isotopically-labeled (13C/15N) C-peptide were utilized as internal standards. The assay had an analytical measurement range of 3 to 320 μIU/ml (18 to 1920 pmol/l) for insulin and 0.11 to 27.2 ng/ml (36 to 9006 pmol/l) for C-peptide. Intra- and inter-day assay variation was less than 11% for both peptides. Of the 5 insulin analogs commonly prescribed to treat diabetes, only the recombinant drug insulin lispro caused significant interference for the determination of endogenous insulin. There were no observed interferences for C-peptide. We developed and validated a high-throughput, quantitative, multiplexed LC-MS/MS assay for intact insulin and C-peptide. Copyright © 2016 Elsevier B.V. All rights reserved.

Aboveground Biomass Variability Across Intact and Degraded Forests in the Brazilian Amazon

Science.gov (United States)

Longo, Marcos; Keller, Michael; Dos-Santos, Maiza N.; Leitold, Veronika; Pinage, Ekena R.; Baccini, Alessandro; Saatchi, Sassan; Nogueira, Euler M.; Batistella, Mateus; Morton, Douglas C.

2016-01-01

Deforestation rates have declined in the Brazilian Amazon since 2005, yet degradation from logging, re, and fragmentation has continued in frontier forests. In this study we quantified the aboveground carbon density (ACD) in intact and degraded forests using the largest data set of integrated forest inventory plots (n 359) and airborne lidar data (18,000 ha) assembled to date for the Brazilian Amazon. We developed statistical models relating inventory ACD estimates to lidar metrics that explained70 of the variance across forest types. Airborne lidar-ACD estimates for intact forests ranged between 5.0 +/- 2.5 and 31.9 +/- 10.8 kg C m(exp -2). Degradation carbon losses were large and persistent. Sites that burned multiple times within a decade lost up to 15.0 +/- 0.7 kg C m(-2)(94%) of ACD. Forests that burned nearly15 years ago had between 4.1 +/- 0.5 and 6.8 +/- 0.3 kg C m(exp -2) (22-40%) less ACD than intact forests. Even for low-impact logging disturbances, ACD was between 0.7 +/- 0.3 and 4.4 +/- 0.4 kg C m(exp -2)(4-21%) lower than unlogged forests. Comparing biomass estimates from airborne lidar to existing biomass maps, we found that regional and pan-tropical products consistently overestimated ACD in degraded forests, under-estimated ACD in intact forests, and showed little sensitivity to res and logging. Fine-scale heterogeneity in ACD across intact and degraded forests highlights the benefits of airborne lidar for carbon mapping. Differences between airborne lidar and regional biomass maps underscore the need to improve and update biomass estimates for dynamic land use frontiers, to better characterize deforestation and degradation carbon emissions for regional carbon budgets and Reduce Emissions from Deforestation and forest Degradation(REDD+).

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.

Phosphorylation of intact erythrocytes in human muscular dystrophy

International Nuclear Information System (INIS)

Johnson, R.M.; Nigro, M.

1986-01-01

The uptake of exogenous 32 Pi into the membrane proteins of intact erythrocytes was measured in 8 patients with Duchenne muscular dystrophy. No abnormalities were noted after autoradiographic analysis. This contrasts with earlier results obtained when isolated membranes were phosphorylated with gamma-[ 32 P]ATP, and suggests a possible reinterpretation of those experiments

Sympathetic Nervous Regulation of Calcium and Action Potential Alternans in the Intact Heart.

Science.gov (United States)

Winter, James; Bishop, Martin J; Wilder, Catherine D E; O'Shea, Christopher; Pavlovic, Davor; Shattock, Michael J

2018-01-01

Rationale: Arrhythmogenic cardiac alternans are thought to be an important determinant for the initiation of ventricular fibrillation. There is limited information on the effects of sympathetic nerve stimulation (SNS) on alternans in the intact heart and the conclusions of existing studies, focused on investigating electrical alternans, are conflicted. Meanwhile, several lines of evidence implicate instabilities in Ca handling, not electrical restitution, as the primary mechanism underpinning alternans. Despite this, there have been no studies on Ca alternans and SNS in the intact heart. The present study sought to address this, by application of voltage and Ca optical mapping for the simultaneous study of APD and Ca alternans in the intact guinea pig heart during direct SNS. Objective : To determine the effects of SNS on APD and Ca alternans in the intact guinea pig heart and to examine the mechanism(s) by which the effects of SNS are mediated. Methods and Results : Studies utilized simultaneous voltage and Ca optical mapping in isolated guinea pig hearts with intact innervation. Alternans were induced using a rapid dynamic pacing protocol. SNS was associated with rate-independent shortening of action potential duration (APD) and the suppression of APD and Ca alternans, as indicated by a shift in the alternans threshold to faster pacing rates. Qualitatively similar results were observed with exogenous noradrenaline perfusion. In contrast with previous reports, both SNS and noradrenaline acted to flatten the slope of the electrical restitution curve. Pharmacological block of the slow delayed rectifying potassium current (I Ks ), sufficient to abolish I Ks -mediated APD-adaptation, partially reversed the effects of SNS on pacing-induced alternans. Treatment with cyclopiazonic acid, an inhibitor of the sarco(endo)plasmic reticulum ATPase, had opposite effects to that of SNS, acting to increase susceptibility to alternans, and suggesting that accelerated Ca reuptake

Therapy of Hypoparathyroidism by Replacement with Parathyroid Hormone

Directory of Open Access Journals (Sweden)

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.

Persistent disorders of mineral metabolism after one year of kidney transplantation.

Science.gov (United States)

Gomes, Larissa Kruger; Custódio, Melani Ribeiro; Contieri, Fabiana Loss de Carvalho; Riella, Miguel C; Nascimento, Marcelo Mazza do

2016-01-01

The persistence of mineral metabolism disorders after renal transplant (RT) appears to possess a negative impact over graft and patient's survival. To evaluate the parameters of mineral metabolism and the persistence of hyperparathyroidism (HPT) in transplanted patients for a 12-month period after the procedure. Retrospective analysis of 41 transplants (18 women- 44%, mean age of 39 ± 15 years) performed in a University Hospital, evaluating changes of calcium (Ca), phosphorus (P) and parathyroid hormone (PTH) and the prevalence of persistent HPT. The patients were divided into two groups accordingly to PTH levels prior to Tx: Group 1 with PTH ≤ 300 pg/mL (n = 21) and Group 2 with PTH > 300 pg/mL (n = 20). The persistency of HPT after transplant was defined as PTH ≥ 100 pg/mL. The evolution of biochemical parameters and the persistency of HPT were analyzed in each group after 1 year of transplant. After a one-year of follow up, 5% of the patients presented hypophosphatemia (p 10.2 mg/dL) and 48% persistency of HPT (PTH ≥ 100 pg/mL). There was a positive correlation between the PTH pre and post Tx (r = 0.42/p = 0.006) and a negative correlation between PTH and Ca pre-Tx (r = -0.45/p = 0.002). However, there was no significant difference among groups 1 and 2 regarding PTH levels pre and post Tx. The findings in this article suggest that mineral metabolism alterations and the persistency of HPT may occur after one year of renal Tx, mainly in patients which present high PTH levels prior toTx. A persistência de distúrbios do metabolismo mineral ósseo após o transplante renal (Tx) parece possuir um impacto negativo sobre a sobrevida do enxerto e do paciente. avaliar os parâmetros do metabolismo mineral e a persistência de hiperparatiroidismo (pHPT) 12 meses após o Tx. Análise retrospectiva de 41 transplantes (18 mulheres- 44%, idade de 39 ± 15 anos) realizados em um Hospital Universitário, avaliando cálcio (Ca), fósforo (P), hormônio da paratire

Hyperparathyroidism complicating CYP 24A1 mutations.

Science.gov (United States)

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.

Long-term effect of cinacalcet hydrochloride on abdominal aortic calcification in patients on hemodialysis with secondary hyperparathyroidism

Directory of Open Access Journals (Sweden)

Nakayama K

2013-12-01

Full Text Available Kazunori Nakayama,1,2 Kazushi Nakao,1,2 Yuji Takatori,1,2 Junko Inoue,1 Shoichirou Kojo,1 Shigeru Akagi,1,2 Masaki Fukushima,2 Jun Wada,1 Hirofumi Makino11Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2Shigei Medical Research Hospital, Okayama, JapanBackground: Secondary hyperparathyroidism (SHPT is one of the common complications in dialysis patients, and is associated with increased risk of vascular calcification. The effects of cinacalcet hydrochloride treatment on bone and mineral metabolism have been previously reported, but the benefit of cinacalcet on vascular calcification remains uncertain. The aim of this study was to evaluate the impact of cinacalcet on abdominal aortic calcification in dialysis patients.Subjects and methods: Patients were on maintenance hemodialysis with insufficiently controlled SHPT (intact parathyroid hormone [PTH] >180 pg/mL by conventional therapies. All subjects were initially administered 25 mg cinacalcet daily, with concomitant use of calcitriol analogs. Abdominal aortic calcification was annually evaluated by calculating aortic calcification area index (ACAI using multidetector computed tomography (MDCT, from 12 months before to 36 months after the initiation of cinacalcet therapy.Results: Twenty-three patients were analyzed in this study. The mean age was 59.0±8.7 years, 34.8% were women, and the mean dialysis duration was 163.0±76.0 months. After administration of cinacalcet, serum levels of intact PTH, phosphorus, and calcium significantly decreased, and mean Ca × P values significantly decreased from 67.4±7.9 mg2/dL2 to 52±7.7 mg2/dL2. Although the ACAI value did not decrease during the observation period, the increase in ACAI between 24 months and 36 months after cinacalcet administration was significantly suppressed.Conclusion: Long-term administration of cinacalcet was associated with reduced progression of

The exploration of the changes in bone metabolism in patients with abnormal thyroid function

International Nuclear Information System (INIS)

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

2001-01-01

To explore the changes in bone metabolism with abnormal thyroid function, BGP and PTH in 91 patients with hyperthyroidism, 37 patients with hypothyroidism, 51 controls, were measured by means of IRMA, calcaneus heel bone density (BMD) was measured by means of 241 Am single photon absorptiometry. BGP levels in hyperthyroidism were significantly higher than those in controls (P < 0.001). BGP levels in hypothyroidism were significantly lower than those in controls (P < 0.001). PTH levels in hyperthyroidism were a little lower than those in controls (P < 0.05). PTH levels in hypothyroidism were significantly higher than those in controls (P < 0.001). The measurement of BMD showed that the prevalence rates of osteoporosis (OP) in hyperthyroidism and hypothyroidism were significantly higher than those in controls. In hyperthyroidism and hypothyroidism groups the age of OP tends to be younger. The patients with hyperthyroidism over 55 years of age were all suffered from OP. The changes in BGP and PTH were earlier than BMD, so BGP and PTH can be used as sensitive indicator of the changes in bone metabolism with abnormal thyroid function, especially for curative effect observations

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

Effect of perioperative application of L-asrginine combined with intacted protein compound preparations on postoperative antitumor immunity and tumor load in patients with gastric cancer

Directory of Open Access Journals (Sweden)

Xiu-Lan Jiang

2016-10-01

Full Text Available Objective: To analyze the effect of perioperative application of L-arginine combined with intacted protein compound preparations on postoperative antitumor immunity and tumor load in patients with gastric cancer. Methods: A total of 68 patients with gastric cancer received radical operation, and according to different perioperative nutrition intervention, they were divided into control group (normal glucose saline enteral nutrition and observation group (L-arginine combined with intacted protein compound preparations enteral nutrition by half. Postoperative short-term antitumor immune cell levels and serum levels of illness-related indexes, nutrition and inflammation indexes of two groups were detected, patients were followed up for 3 years and the gastric stump MRI changes were observed. Results: Venous blood CD4+ T lymphocyte level and CD4+ /CD8+ ratio of observation group 3 months after treatment were higher than those of control group while CD8+ T lymphocyte and Treg cell levels were lower than those of control group; serum Pentraxin-3, CYFRA21-1, TTF-1 and HE4 levels were lower than those of control group; ALB, PA and IL-2 levels were higher than those of control group while IL-6 and IL-10 levels were lower than those of control group (P<0.05. Gastric stump MRI images 3 years after operation were significantly different between two groups. Conclusions: Perioperative application of L-arginine combined with intacted protein compound preparations can optimize postoperative immune and nutritional state in patients with gastric cancer, and it also has positive effect on reducing the incidence of long-term gastric stump carcinoma and other aspects.

Effect of TheraCyte-encapsulated parathyroid cells on lumbar fusion in a rat model.

Science.gov (United States)

Chen, Sung-Hsiung; Huang, Shun-Chen; Lui, Chun-Chung; Lin, Tzu-Ping; Chou, Fong-Fu; Ko, Jih-Yang

2012-09-01

Implantation of TheraCyte 4 × 10(6) live parathyroid cells can increase the bone marrow density of the spine of ovariectomized rats. There has been no published study examining the effect of such implantation on spinal fusion outcomes. The purpose of this study was to examine the effect of TheraCyte-encapsulated parathyroid cells on posterolateral lumbar fusions in a rat model. Forty Sprague-Dawley rats underwent single-level, intertransverse process spinal fusions using iliac crest autograft. The rats were randomly assigned to two groups: Group 1 rats received sham operations on their necks (control; N = 20); Group 2 rats were implanted with TheraCyte-encapsulated 4 × 10(6) live parathyroid cells into the subcutis of their necks (TheraCyte; N = 20). Six weeks after surgery the rats were killed. Fusion was assessed by inspection, manual palpation, radiography, and histology. Blood was drawn to measure the serum levels of calcium, phosphorus, and intact parathyroid hormone (iPTH). Based on manual palpation, the control group had a fusion rate of 33 % (6/18) and the TheraCyte group had a fusion rate of 72 % (13/18) (P = 0.044). Histology confirmed the manual palpation results. Serum iPTH levels were significantly higher in the TheraCyte group compared with the control group (P TheraCyte-encapsulated 4 × 10(6) live parathyroid cells than in control rats without significant change in serum calcium or phosphorus concentrations. As with any animal study, the results may not extrapolate to a higher species. Further studies are needed to determine if these effects are clinically significant.

SOLITARY CHEMORECEPTOR CELL SURVIVAL IS INDEPENDENT OF INTACT TRIGEMINAL INNERVATION

Science.gov (United States)

Gulbransen, Brian; Silver, Wayne; Finger, Tom

2008-01-01

Nasal solitary chemoreceptor cells (SCCs) are a population of specialized chemosensory epithelial cells presumed to broaden trigeminal chemoreceptivity in mammals (Finger et al., 2003). SCCs are innervated by peptidergic trigeminal nerve fibers (Finger et al., 2003) but it is currently unknown if intact innervation is necessary for SCC development or survival. We tested the dependence of SCCs on innervation by eliminating trigeminal nerve fibers during development with neurogenin-1 knockout mice, during early postnatal development with capsaicin desensitization, and during adulthood with trigeminal lesioning. Our results demonstrate that elimination of innervation at any of these times does not result in decreased SCC numbers. In conclusion, neither SCC development nor mature cell maintenance is dependent on intact trigeminal innervation. PMID:18300260

Patterns in the Parathyroid Response to Sodium Bicarbonate Infusion Test in Healthy Volunteers

Directory of Open Access Journals (Sweden)

Theodossis S. Papavramidis

2014-01-01

Full Text Available Background. The sodium bicarbonate infusion test evaluates the function of the parathyroid glands. The present study aims to evaluate the range of parathyroid response in healthy individuals and the potential influence of various factors. Methods. Fifty healthy volunteers were subjected to the test. Levels of vitamin D, calcium, albumin, and PTH were measured before infusion. PTH was measured at 3, 5, 10, 30, and 60 minutes after infusion. Results. A curve describing the response of parathyroids to the test was drawn. Twenty percent of the subjects had blunted PTH response. No significant difference was observed between normal and blunted responders concerning age, BMI, baseline PTH, or calcium levels. Nonetheless, there was a significant difference in vitamin D levels (P=0.024. Interpretation. The test is easy to perform and may be used for everyday screening. It has to be clarified whether our observations are, at least partly, produced due to the presence of individuals with a constitutively blunted response or if low levels of vitamin D decrease the ability of the parathyroids to respond. Whichever the case, PTH response of normal individuals to sodium bicarbonate infusion test is more varied than previously thought and vitamin D levels influence it.

Serum Bone Resorption Markers after Parathyroidectomy for Renal Hyperparathyroidism: Correlation Analyses for the Cross-Linked N-telopeptide of Collagen I and Tartrate-Resistant Acid Phosphatase

Directory of Open Access Journals (Sweden)

Kuo-Chin Hung

2012-01-01

Full Text Available Patients on long-term dialysis may develop secondary hyperparathyroidism (SHPT with increased serum concentrations of bone resorption markers such as the cross-linked N-telopeptide of type I collagen (NTX and type-5b tartrate-resistant acid phosphatase (TRAP. When SHPT proves refractory to treatment, parathyroidectomy (PTX may be needed. Renal patients on maintenance HD who received PTX for refractory SHPT (n=23 or who did not develop refractory SHPT (control subjects; n=25 were followed prospectively for 4 weeks. Serum intact parathyroid hormone (iPTH, NTX, TRAP, and bone alkaline phosphatase (BAP concentrations were measured serially and correlation analyses were performed. iPTH values decreased rapidly and dramatically. BAP values increased progressively with peak increases observed at 2 weeks after surgery. NTX and TRAP values decreased concurrently and progressively through 4 weeks following PTX. A significant correlation between TRAP and NTX values was observed before PTX but not at 4 weeks after PTX. Additionally, the fractional changes in serum TRAP were larger than those in serum NTX at all times examined after PTX. Serum iPTH, TRAP, and NTX values declined rapidly following PTX for SHPT. Serum TRAP values declined to greater degrees than serum NTX values throughout the 4-week period following PTX.

Vitamin D and parathyroid hormone are associated with gait instability and poor balance performance in mid-age to older aged women.

Science.gov (United States)

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.

El nivel de la hormona paratiroidea (PTH y no el de fósforo sérico es predictor de la progresión de la enfermedad renal en pacientes mayores con enfermedad renal crónica avanzada

Directory of Open Access Journals (Sweden)

Néstor Gabriel Toapanta Gaibor

2017-03-01

Conclusiones: En nuestro grupo de pacientes de edad avanzada el deterioro de la función renal es muy lento, especialmente en los pacientes en estadio 5. La albuminuria y la PTH al inicio del seguimiento son factores pronósticos en la evolución de su función renal.

/sup 31/P-NMR studies of respiratory regulation in the intact myocardium

Energy Technology Data Exchange (ETDEWEB)

From, A H.L.; Petein, M A; Zimmer, S W; Michurski, S P; Ugurbil, K

1986-10-06

The mechanism by which mitochondrial respiration is coupled to ATP consumption in intact tissues is unclear. The authors determined the relationship between high-energy phosphate levels and oxygen consumption rate in rat hearts operating over a range of workloads and perfused with different substrates. With pyruvate + glucose perfusion, ADP levels were in general very low, and varied with MVO/sub 2/ yielding an apparent K/sub m/ of 25 +- 5 ..mu..M, suggesting regulation of oxidative phosphorylation through availability of ADP. In contrast, with glucose perfusion in the presence or absence of insulin, ADP levels, ADP/ATP ratio or the phosphate potential were relatively constant over the workload range examined and generally not correlated with alterations in MVO/sub 2/; it is suggested that under these conditions, carbon substrate delivery to the mitochondria may control mitochondrial respiration. The common feature of both of the suggested regulatory mechanisms is substrate limitation which, however, is exercised at different metabolic points depending on the carbon substrate available to the myocardium. 19 refs.; 2 figs.; 1 table.

Superolateral Dislocation of Intact Mandibular Condyle: A Case Report and Review of Literature

OpenAIRE

Saikrishna, Degala; Shyam Sundar, S.; Mamata, K. S.

2015-01-01

Anteromedial fracture dislocation of the mandibular condyle is common but a superolateral dislocation of an intact condyle is quite rare. This type of dislocation is often misdiagnosed or completely overlooked and hence inadequately addressed. We report a case of a 41-year-old male patient who experienced superolateral dislocation of the intact condyle with symphysis fracture and panfacial fracture following a road-traffic accident, and review of literature of superolateral dislocations from ...

Prediction of valid acidity in intact apples with Fourier transform near infrared spectroscopy*

OpenAIRE

Liu, Yan-de; Ying, Yi-bin; Fu, Xia-ping

2005-01-01

To develop nondestructive acidity prediction for intact Fuji apples, the potential of Fourier transform near infrared (FT-NIR) method with fiber optics in interactance mode was investigated. Interactance in the 800 nm to 2619 nm region was measured for intact apples, harvested from early to late maturity stages. Spectral data were analyzed by two multivariate calibration techniques including partial least squares (PLS) and principal component regression (PCR) methods. A total of 120 Fuji appl...

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%).

Risk/benefit in prophylaxis and treatment of secondary hyperparathyroidism. A comparison of two low calcium peritoneal dialysis fluids

DEFF Research Database (Denmark)

Bro, S; Brandi, L; Olgaard, K

1996-01-01

levels after 2-6 weeks of treatment. No statistically significant difference was observed between the two groups. In both groups median PTH levels were kept below 2.5 times the upper normal limit for non-uraemic patients; median P concentrations below 1.80 mmol/l and median iCa levels within 1.25-1......OBJECTIVE: A comparison of (i) levels of plasma ionized calcium (Ca), phosphate (P) and iPTH, (ii) risk of hypercalcaemia and (iii) need for Al-containing P binders, in patients on CAPD treated with calcium carbonate as the main P binder and twice weekly oral doses of alfacalcidol for control...... of secondary hyperparathyroidism during a 1 year follow-up after switching from a dialysis fluid with a Ca concentration of 1.75 mmol/l to 1.25 mmol/l (n = 39) or 1.35 mmol/l (n = 37). RESULTS: In both groups, a significant initial increase of iPTH was seen. However, iPTH was again suppressed to baseline...

Multi-Axis Prosthetic Knee Resembles Alpine Skiing Movements of an Intact Leg

Directory of Open Access Journals (Sweden)

Ivan Demšar, Jože Duhovnik, Blaž Lešnik, Matej Supej

2015-12-01

Full Text Available The purpose of the study was to analyse the flexion angles of the ski boot, ankle and knee joints of an above-knee prosthesis and to compare them with an intact leg and a control group of skiers. One subject with an above-knee amputation of the right leg and eight healthy subjects simulated the movement of a skiing turn by performing two-leg squats in laboratory conditions. By adding additional loads in proportion to body weight (BW; +1/3 BW, +2/3 BW, +3/3 BW, various skiing regimes were simulated. Change of Flexion Angle (CoFA and Range of Motion (RoM in the ski boot, ankle and knee joints were calculated and compared. An average RoM in the skiing boot on the side of prosthesis (4.4 ± 1.1° was significantly lower compared to an intact leg (5.9 ± 1.8° and the control group (6.5 ± 2.3°. In the ankle joint, the average RoM was determined to be 13.2±2.9° in the prosthesis, 12.7 ± 2.8° in an intact leg and 14.8±3.6 in the control group. However, the RoM of the knee joint in the prosthesis (42.2 ± 4.2° was significantly larger than that of the intact leg (34.7 ± 4.4°. The average RoM of the knee joint in the control group was 47.8 ± 5.4°. The influences of additional loads on the kinematics of the lower extremities were different on the side of the prosthesis and on the intact leg. In contrast, additional loads did not produce any significant differences in the control group. Although different CoFAs in the ski boot, ankle and knee joints were used, an above-knee prosthesis with a built-in multi-axis prosthetic knee enables comparable leg kinematics in simulated alpine skiing.

Peptide fragments induce a more rapid immune response than intact proteins in earthworms.

Science.gov (United States)

Hanusová, R; Tucková, L; Halada, P; Bezouska, K; Bilej, M

1999-01-01

The effect of in vivo proteolytic processing of protein antigen was studied in Eisenia foetida earthworms. Parenteral administration of the protein antigen induces elevated levels of an antigen-binding protein (ABP) which recognizes the protein used for stimulation. When the protein antigen is administered simultaneously with nontoxic serine proteinase inhibitor, ABP levels remain close to background. On the other hand, the in vivo adaptive response of earthworms to peptide fragments obtained by coelomic fluid digestion of the foreign antigen occurs even in the presence of proteinase inhibitor and, moreover, is significantly faster as compared to the response to intact antigen. These findings confirm the role of proteolytic processing in earthworms. MALDI mass spectrometric analysis of the fragments after coelomic fluid digestion has revealed the presence of the peptide fragments with molecular weights in the mass range 700-1100 Da.

Visual Speech Fills in Both Discrimination and Identification of Non-Intact Auditory Speech in Children

Science.gov (United States)

Jerger, Susan; Damian, Markus F.; McAlpine, Rachel P.; Abdi, Herve

2018-01-01

To communicate, children must discriminate and identify speech sounds. Because visual speech plays an important role in this process, we explored how visual speech influences phoneme discrimination and identification by children. Critical items had intact visual speech (e.g. baez) coupled to non-intact (excised onsets) auditory speech (signified…

Presence of orally administered rice bran oil γ-oryzanol in its intact form in mouse plasma.

Science.gov (United States)

Kobayashi, Eri; Ito, Junya; Kato, Shunji; Sawada, Kazue; Matsuki, Midori; Hashimoto, Hiroyuki; Miyazawa, Teruo; Nakagawa, Kiyotaka

2016-12-07

Although the beneficial effects (e.g., lipid-lowering activity) of γ-oryzanol (OZ), a mixture of ferulic acid esters of plant sterols and triterpene alcohols, have been extensively investigated, few studies have evaluated the absorption and metabolism of OZ. Moreover, it is unclear whether OZ, once ingested, is directly absorbed by the intestine into the bloodstream at a sufficient level to exhibit activity. Here, we prepared OZ concentrate from purified rice bran oil (Rice Oil OZ), determined the concentration of OZ in the preparation (cycloartenyl ferulate equivalent concentration; 52.2%), and then carried out chromatography-mass spectrometry analysis of plasma samples from mice after oral administration of Rice Oil OZ. The OZ concentrations of plasma from the control (vehicle-treated) mice were low (trace levels); however, at 5 h after a single oral administration of the Rice Oil OZ (600 mg per kg body weight), the levels significantly increased, reaching 17.6 ng mL -1 for cycloartenyl ferulate, 28.2 ng mL -1 for 24-methylenecycloartanyl ferulate isomers, 15.6 ng mL -1 for campesteryl ferulate, and 5.1 ng mL -1 for β-sitosteryl ferulate, respectively, expressed in equivalence of cycloartenyl ferulate in plasma. These results provided the first mass spectrometric evidence suggesting that a portion of orally administered OZ is directly absorbed by the intestine and is present in the intact form in plasma. The presence of a significant amount of OZ in its intact form in plasma may explain the beneficial effects of OZ in vivo.

EPIC Trial: education programme impact on serum phosphorous control in CKD 5D patients on hemodialysis

Directory of Open Access Journals (Sweden)

Carmen Tzanno Branco Martins

Full Text Available Abstract Introduction: In stage 5D chronic kidney disease (CKD 5D patients, the encouragement of treatment adherence by health professionals is a significant clinical challenge. Objectives: This study evaluates the impact of a nutritional education programme on hyperphosphatemia, utilizing the transtheoretical model of behavior change (TMBC. Subjects and Methods: A prospective interventional study comprising 179 CKD 5D patients with hypophosphatemia. The 4-month educational programme took place during dialysis sessions. Demographic and laboratory data were evaluated, whilst the TMBC was utilized both pre- and post-intervention. Results: 132 patients showed a positive change and significant reduction in phosphate levels, whilst 47 patients showed a negative change and little reduction in phosphate levels. Positive changes were identified at different levels of literacy. 117/179 participants had ongoing treatment with sevelamer throughout the trial period. 61 patients with intact parathyroid hormone (iPTH 300 pg/ml also showed a decrease in phosphate levels. Conclusions: Nutritional education programmes can achieve excellent results when appropriately applied. An education programme may be effective across different literacy levels.

Differences in School Behavior and Achievement between Children from Intact, Reconstituted, and Single-Parent Families.

Science.gov (United States)

Featherstone, Darin R.; And Others

1992-01-01

Analyzed differences in school behavior and achievement among students (n=530) in grades six through nine from intact, reconstituted, and single-parent families. Students from intact, two-parent families had fewer absences and tardies, higher grade point averages, and fewer negative and more positive teacher behavioral ratings than did those from…

Characterization of intact subcellular bodies in whole bacteria by cryo-electron tomography and spectroscopic imaging.

Science.gov (United States)

Comolli, L R; Kundmann, M; Downing, K H

2006-07-01

We illustrate the combined use of cryo-electron tomography and spectroscopic difference imaging in the study of subcellular structure and subcellular bodies in whole bacteria. We limited our goal and focus to bodies with a distinct elemental composition that was in a sufficiently high concentration to provide the necessary signal-to-noise level at the relatively large sample thicknesses of the intact cell. This combination proved very powerful, as demonstrated by the identification of a phosphorus-rich body in Caulobacter crescentus. We also confirmed the presence of a body rich in carbon, demonstrated that these two types of bodies are readily recognized and distinguished from each other, and provided, for the first time to our knowledge, structural information about them in their intact state. In addition, we also showed the presence of a similar type of phosphorus-rich body in Deinococcus grandis, a member of a completely unrelated bacteria genus. Cryo-electron microscopy and tomography allowed the study of the biogenesis and morphology of these bodies at resolutions better than 10 nm, whereas spectroscopic difference imaging provided a direct identification of their chemical composition.

Mass Spectrometry of Intact Proteins Reveals +98 u Chemical Artifacts Following Precipitation in Acetone.

Science.gov (United States)

Güray, Melda Z; Zheng, Shi; Doucette, Alan A

2017-02-03

Protein precipitation in acetone is frequently employed ahead of mass spectrometry for sample preconcentration and purification. Unfortunately, acetone is not chemically inert; mass artifacts have previously been observed on glycine-containing peptides when exposed to acetone under acidic conditions. We herein report a distinct chemical modification occurring at the level of intact proteins when incubated in acetone. This artifact manifests as one or more satellite peaks in the MS spectrum of intact protein, spaced 98 u above the mass of the unmodified protein. Other artifacts (+84, +112 u) also appear upon incubation of proteins or peptides in acetone. The reaction is pH-sensitive, being suppressed when proteins are exposed to acetone under acidic conditions. The +98 u artifact is speculated to originate through an intermediate product of aldol condensation of acetone to form diacetone alcohol and mesityl oxide. A +98 u product could originate from nucleophilic attack on mesityl oxide or through condensation with diacetone alcohol. Given the extent of modification possible upon exposure of proteins to acetone, particularly following overnight solvent exposure or incubation at room temperature, an awareness of the variables influencing this novel modification is valued by proteomics researchers who employ acetone precipitation for protein purification.

Regrowth of Cirsium arvense from intact roots and root fragments at different soil depths

Directory of Open Access Journals (Sweden)

Thomsen, Mette Goul

2014-02-01

Full Text Available In the present work we measured the shoot rate from intact roots and from root fragments of Cirsium arvense at different digging depths and the number of leaves were used as estimate of minimum regenerative capacity. The experiments were performed on four sites with three or four repetitions of each treatment. On each site plot, the soil was removed down to a given depth within a 1 x 1 m square. All plant parts was excavated from the soil and the soil was either replaced without any root material, or roots of C. arvense was cut into 10 cm long fragments and replaced into the source hole. Shoot number, aboveground biomass and number of leaves were measured. Digging depth and time explained 50% - 60% of the variation in biomass (P<0.001. Replacement of root fragments increased the shoot number in one out of four treatments but did not affect biomass produced compared to production from undisturbed root systems. Number of leaves showed that shoots from all digging depths passed the level of minimum regenerative capacity. We conclude that the intact root system from all depths was able to regenerate within one season and it has a high contribution to the produced biomass compared with root fragments in the upper soil layers.

Effects of power densities, continuous and pulse frequencies, and number of sessions of low-level laser therapy on intact rat brain.

Science.gov (United States)

Ilic, Sanja; Leichliter, Sandra; Streeter, Jackson; Oron, Amir; DeTaboada, Luis; Oron, Uri

2006-08-01

The aim of the present study was to investigate the possible short- and long-term adverse neurological effects of low-level laser therapy (LLLT) given at different power densities, frequencies, and modalities on the intact rat brain. LLLT has been shown to modulate biological processes depending on power density, wavelength, and frequency. To date, few well-controlled safety studies on LLLT are available. One hundred and eighteen rats were used in the study. Diode laser (808 nm, wavelength) was used to deliver power densities of 7.5, 75, and 750 mW/cm2 transcranially to the brain cortex of mature rats, in either continuous wave (CW) or pulse (Pu) modes. Multiple doses of 7.5 mW/cm2 were also applied. Standard neurological examination of the rats was performed during the follow-up periods after laser irradiation. Histology was performed at light and electron microscopy levels. Both the scores from standard neurological tests and the histopathological examination indicated that there was no long-term difference between laser-treated and control groups up to 70 days post-treatment. The only rats showing an adverse neurological effect were those in the 750 mW/cm2 (about 100-fold optimal dose), CW mode group. In Pu mode, there was much less heating, and no tissue damage was noted. Long-term safety tests lasting 30 and 70 days at optimal 10x and 100x doses, as well as at multiple doses at the same power densities, indicate that the tested laser energy doses are safe under this treatment regime. Neurological deficits and histopathological damage to 750 mW/cm2 CW laser irradiation are attributed to thermal damage and not due to tissue-photon interactions.

Binding of radiolabelled luteinizing hormone to intact and ovariectomised rat uterus

International Nuclear Information System (INIS)

Sen, S.; Bhattacharya, S.

1992-01-01

Binding of ovine LH to uterine tissue preparation from intact and ovariectomised rat clearly indicates that uterus possesses specific binding sites for LH. Binding characteristics of LH to uterine tissue preparation from intact rat showed saturability with high affinity and low capacity. Scatchard plot analysis showed dissociation constant of the specific binding site to be 0.12 x 10 -9 mol/l and the number of binding sites was 2.31±0.05 fmol/mg protein. Ovariectomy did not change the binding affinity but effected a decrease in the number of binding sites (1.7 ± 0.08 f mol/mg protein). LH treatment of ovariectomized (ovx) rat had no effect on binding affinity but significantly increased the number of binding sites (3.23 ± 0.1 f mol/mg protein). Reduction of uterine weight due to ovariectomy and marked increase of ovx rat uterine weight by LH administration indicate a source of estrogen in ovx rat. An in vitro uterine tissue slice (from intact and ovx rat) incubation showed depletion of 17 β-estradiol (E 2 ) content in ovx rat which significantly elevated on LH addition. Data suggest the LH binding to rat uterine tissue has biological relevance. (author). 16 refs., 4 figs. 1 tab

Vitamin D status in kidney transplant patients

DEFF Research Database (Denmark)

Ewers, Bettina; Gasbjerg, Ane; Mølgaard, Christian

2008-01-01

BACKGROUND: A high prevalence of vitamin D insufficiency has been found in the general population and in patients with chronic kidney disease. OBJECTIVE: The aim was to examine vitamin D status and determinants and metabolic correlates of serum 25-hydroxyvitamin D in a population of adult Danish...... kidney transplant patients. DESIGN: This was a cross-sectional study of 173 adult kidney transplant patients with a mean (+/-SD) age of 53.4 +/- 11.7 y and a median graft age of 7.4 y (interquartile range: 3.3-12.7 y). Serum concentrations of intact parathyroid hormone (S-PTH), 25-hydroxyvitamin D [S-25....... Low S-25(OH)D concentrations were associated with 1) increased S-PTH concentrations (P = 0.0002), independently of S-1,25(OH)(2)D concentrations, and 2) decreased S-1,25(OH)(2)D concentrations (P = 0.002), independently of graft function. CONCLUSIONS: Hypovitaminosis D is common among Danish kidney...