Parathyroid hormone: radioimmunoassay and clinical interpretation

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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

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

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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.

Serum ionized calcium, intact PTH and novel markers of bone turnover in bedridden elderly patients.

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

1994-12-01

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

Screening for secondary hyperparathyroidism in preterm infants.

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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.

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

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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.

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

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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.

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

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

2017-03-01

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

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

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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.
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Oxidation of PTH: in vivo feature or effect of preanalytical conditions?

NARCIS (Netherlands)

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

2018-01-01

Background: Posttranslational oxidation of parathyroid hormone (PTH) modifies its biological activity. Measurement of non-oxidized PTH (n-oxPTH) could be an improvement in assessing PTH status, as intact PTH may rather reflect oxidative stress. However, it is debated whether oxidation of PTH occurs

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

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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.

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.

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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

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

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

2009-05-01

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

The 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)

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

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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.

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

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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.

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.

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

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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.

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

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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.

The effect of leptin replacement on parathyroid hormone, RANKL-osteoprotegerin axis, and Wnt inhibitors in young women with hypothalamic amenorrhea.

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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.

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 carcinoma in tertiary hyperparathyroidism.

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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.

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

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

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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.

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

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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.

A Case of Primary Hyperparathyroidism due to Intrathyroidal Parathyroid Cyst

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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.

Radioimmunoassay of parathyroid hormone: past and future

International Nuclear Information System (INIS)

Yalow, R.S.

1986-01-01

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

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

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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

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.

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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

Expanding the net: The re-evaluation of the multidimensional nomogram calculating the upper limit of normal PTH (maxPTH) in the setting of secondary hyperparathyroidism and the development of the MultIdimensional Predictive hyperparaTHyroid model (Mi-PTH).

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

2016-01-01

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

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....

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

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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.

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.

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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.

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

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Ho Chiang-Hong

2011-02-01

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

Acute regulation of circulating parathyroid hormone (PTH) molecular forms by calcium: utility of PTH fragments/PTH(1-84) ratios derived from three generations of PTH assays.

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

2006-01-01

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

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.

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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.

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

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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

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

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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

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

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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.

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

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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

Management of chronic kidney disease–mineral and bone disorder: Korean working group recommendations

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Eunah Hwang

2015-03-01

Full Text Available For Korean dialysis patients, chronic kidney disease–mineral bone disorder is a serious burden because of cardiovascular calcification and mortality. However, recent epidemiologic data have demonstrated that many patients undergoing maintenance hemodialysis are out of the target ranges of serum calcium, phosphorus, and intact parathyroid hormone. Thus, we felt the necessity for the development of practical recommendations to treat abnormal serum phosphorus, calcium, and iPTH in dialysis patients. In this paper, we briefly comment on the measurement of serum calcium, phosphorus, iPTH, dialysate calcium concentration, dietary phosphorus restriction, use of phosphate binders, and medical and surgical options to correct secondary hyperparathyroidism. In particular, for the optimal management of secondary hyperparathyroidism, we suggest a simplified medication adjustment according to certain ranges of serum phosphorus and calcium. Large-scale, well-designed clinical studies are required to support our strategies to control chronic kidney disease–mineral bone disorder in this country. Based on such data, our practice guidelines could be established and better long-term outcomes should be anticipated in our dialysis patients.

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

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

2014-06-01

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

Primary hyperparathyroidism with classic and severe skeletal involvement

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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...

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...

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

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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

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

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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.

Use of Extended-Release Calcifediol to Treat Secondary Hyperparathyroidism in Stages 3 and 4 Chronic Kidney Disease.

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Sprague, Stuart M; Crawford, Paul W; Melnick, Joel Z; Strugnell, Stephen A; Ali, Shaukat; Mangoo-Karim, Roberto; Lee, Sungchun; Petkovich, P Martin; Bishop, Charles W

2016-01-01

Vitamin D insufficiency and secondary hyperparathyroidism (SHPT) are associated with increased morbidity and mortality in chronic kidney disease (CKD) and are poorly addressed by current treatments. The present clinical studies evaluated extended-release (ER) calcifediol, a novel vitamin D prohormone repletion therapy designed to gradually correct low serum total 25-hydroxyvitamin D, improve SHPT control and minimize the induction of CYP24A1 and FGF23. Two identical multicenter, randomized, double-blind, placebo-controlled studies enrolled subjects from 89 US sites. A total of 429 subjects, balanced between studies, with stage 3 or 4 CKD, SHPT and vitamin D insufficiency were randomized 2:1 to receive oral ER calcifediol (30 or 60 µg) or placebo once daily at bedtime for 26 weeks. Most subjects (354 or 83%) completed dosing, and 298 (69%) entered a subsequent open-label extension study wherein ER calcifediol was administered without interruption for another 26 weeks. ER calcifediol normalized serum total 25-hydroxyvitamin D concentrations (>30 ng/ml) in >95% of per-protocol subjects and reduced plasma intact parathyroid hormone (iPTH) by at least 10% in 72%. The proportion of subjects receiving ER calcifediol who achieved iPTH reductions of ≥30% increased progressively with treatment duration, reaching 22, 40 and 50% at 12, 26 and 52 weeks, respectively. iPTH lowering with ER calcifediol was independent of CKD stage and significantly greater than with placebo. ER calcifediol had inconsequential impact on serum calcium, phosphorus, FGF23 and adverse events. Oral ER calcifediol is safe and effective in treating SHPT and vitamin D insufficiency in CKD. © 2016 S. Karger AG, Basel.

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

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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.

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

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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.

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

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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.

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

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Yongxin Ren

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

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

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

2011-01-01

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

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

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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.

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

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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.

Metabolism of labeled parathyroid hormone. V. Collected biological studies

Energy Technology Data Exchange (ETDEWEB)

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

1975-01-01

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

Serum intact parathyroid hormone levels in cats with chronic kidney disease

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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.

Age-related changes in bone in the dog: calcium homeostasis

International Nuclear Information System (INIS)

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

1984-01-01

To explore the changes in the relationship between skeletal and Ca 2+ homeostasis with age, a study was made of 50 dogs divided into four age groups. The skeletal uptake of 85 Sr decreased markedly with age, and the immunoreactive parathyroid hormone (iPTH) level increased. There was a significant correlation between iPTH value and the calculated short-term exchange of Ca in bone. Bone formation and bone resorption decreased with age except that in the oldest group of dogs the resorption increased. The authors suggest that in aging dogs the skeletal exchange of Ca falls to a very low level that decreases the immediate effect of PTH and thus leads to a chronic net increase in circulating PTH. Concomitant with this is an increase in osteoclastic bone resorption and, over a long time, loss of skeletal mass

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

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Zhang Qiao

2013-01-01

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

Normal Parathyroid Function with Decreased Bone Mineral Density in Treated Celiac Disease

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Bernard Lemieux

2001-01-01

Full Text Available Decreased bone mineral density (BMD has been reported in patients with celiac disease in association with secondary hyperparathyroidism. The present study investigated whether basal parathyroid hormone (PTH remained elevated and whether abnormalities of parathyroid function were still present in celiac disease patients treated with a gluten-free diet. Basal seric measurements of calcium and phosphate homeostasis and BMD were obtained in 17 biopsy-proven patients under treatment for a mean period of 5.7±3.7 years (range 1.1 to 15.9. In addition, parathyroid function was studied with calcium chloride and sodium citrate infusions in seven patients. Basal measurements of patients were compared with those of 26 normal individuals, while parathyroid function results were compared with those of seven sex- and age-matched controls. Basal results were similar in patients and controls except for intact PTH (I-PTH (3.77±0.88 pmol/L versus 2.28±0.63 pmol/L, P<0.001, which was higher in the former group but still within normal limits. Mean 25-hydroxy vitamin D and 1,25-dihydroxy vitamin D values were normal in patients. Parathyroid function results were also found to be similar in both groups. Compared with a reference population of the same age (Z score, patients had significantly lower BMDs of the hip (-0.60±0.96 SDs, P<0.05 and lumbar spine (-0.76±1.15 SDs, P<0.05. T scores were also decreased for the hip (-1.3±0.9 SDs, P<0.0001 and lumbar spine (-1.4±1.35 SDs, P<0.0001, with two to three patients being osteoporotic (T score less than -2.5 SDs and seven to eight osteopenic (T score less than -1 SDs but greater than or equal to -2.5 SDs in at least one site. Height and weight were the only important determinants of BMD values by multivariate or logistical regression analysis in these patients. The results show higher basal I-PTH values with normal parathyroid function in treated celiac disease. Height and weight values are, but I-PTH values are not

Predictors of hyperparathyroidism in renal transplant recipients

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Houssaini, T.S.; Arrayahani, M.; Rhou, H.; Amar, Y.; Benamar, L.; Ouzeddoun, N.; Bayahia, R.

2008-01-01

The changes in parathyroid hormone secretion after successful renal transplantation remain to be clearly elucidated. Our study was aimed at identifying the predictors of hyperparathyroidism in renal transplant recipients. A retrospective single center study involving 37 renal transplant recipients, with a follow-up of at least one year, was performed. All transplants were performed using kidneys from living related donors. The average age of study patients was 30+-10 years, with a male-female ratio of 1.31. The mean duration on hemodialysis (HD) prior to transplantation was 25+-18 months. All the grafts but one were functional after a mean follow-up of 41+-21 months. We noted a rapid reduction of the mean parathyroid hormone (iPTH) level from 383+-265 pg/ml before transplantation to 125+-67 pg/ml at one year and 108+-66 pg/ml at two years after transplantation (p=0.01). Bivariate analysis revealed that the level of iPTH obtained during follow-up correlated with the duration on HD (p=0.03), the serum creatinine at 24-months (p=0.013), and to the level of iPTH in the first year post transplantation (P=<0.001). Other clinical or laboratory parameters were not predictive of hyperparathyroidism after kidney transplantation. Liner regression showed that only the serum creatinine at 24-months independently correlated with the level of iPTH at last follow-up (p=0.02). Our study suggests that short duration on HD and a functional graft are the main predictors of correction of hyperparathyroidism after renal transplantation. (author)

Experience with radioimmunoassay of serum parathormone

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Vokrouhlicka, O.; Huskova, M.; Erben, J.; Base, J.

1978-01-01

The working procedure is described used for the assessment of immunoreactive parathormone in serum (iPTH) using a Calbiochem kit and a kit produced by Cambridge Nuclear Radiopharmaceuticals Corporation (CNRC). Using the Calbiochem kit usable results were not obtained because the antiserum was of low standard and undefinable, and because of the difficult labelling of antigen (bovine PTH). The CNRC kit which contains antiserum against -COOH terminals is suited for the assessment of chronic hypersecretion of PTH. Using this set, concentrations of iPTH in the serum of 19 patients with urolithiasis (of which 3 patients were with hyperparathyroidism) were assessed as well as of one patient with late rickets and hyperparathyroidism, 23 dialyzed patients with chronic renal failure and 14 healthy subjects. The results can be considered so far from the clinical aspect as preliminary; from the methodological aspect very valuable experience was gained. (author)

The study of calcitriol, cinacalcet combined with nursing intervention effect of SHPT, calcium, phosphorus metabolism and parathyroid hormone on MHD patients

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Le Chen

2017-06-01

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

Response of Vitamin D Concentration to Vitamin D3 Administration in Older Adults without Sun Exposure: A Randomized Double-Blind Trial.

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Schwartz, Janice B; Kane, Lynn; Bikle, Daniel

2016-01-01

To determine the dose-response relationship between 25-hydroxyvitamin D (25(OH)D) and supplemental vitamin D3 in elderly nursing home residents. Randomized double-blind investigation. Nursing home. Of 81 women (n=51) and men (n=30) (mean age 87.4±8) enrolled, 72 completed the study. Sixteen weeks of oral vitamin D3 at 800, 2,000, or 4,000 IU/d or 50,000 IU/wk. The main outcome was 25(OH)D concentrations (tandem mass spectrometry) after 16 weeks. Free 25(OH)D and intact parathyroid hormone (iPTH) were also analyzed. Safety monitoring of calcium and estimated glomerular filtration rate was performed, and adherence and clinical status were measured. 25(OH)D concentrations increased with dose (Pd than 800 or 2,000 IU/d, but 800 IU and 2,000 IU/d did not differ. One subject receiving 800 IU/d had concentrations less than 20 ng/mL. All subjects receiving more than 2000 IU/d had concentrations of 20 ng/mL and greater. Free 25(OH)D concentrations rose with total 25(OH) vitamin D. Total and free 25(OH)D were related to calcium concentrations; only free 25(OH)D was related to iPTH. 25(OH)D increased linearly with 800 to 4,000 IU/d and 50,000 IU/wk of vitamin D3, without a ceiling effect. Data suggest that some elderly adults will require more than 800 IU/d of vitamin D3 to ensure adequate vitamin D levels. Changes in 25(OH)D with vitamin D3 were related to starting concentrations (greatest with the lowest concentrations and unchanged with 800 and 2,000 IU/d if 20-40 ng/mL). Relationships between serum calcium and iPTH and free 25(OH)D suggest the potential for free 25(OH)D in defining optimal 25(OH)D concentrations. © 2016, Copyright the Authors Journal compilation © 2016, The American Geriatrics Society.

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

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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

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

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

1986-02-01

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

Primary hyperparathyroidism with classic and severe skeletal involvement.

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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.

Effects of hemodialysis on serum fetuin-A levels

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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

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

Delayed Surgery for Parathyroid Adenoma Misdiagnosed as a Thyroid Nodule and Treated with Radiofrequency Ablation

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Ho-Su Kim

2013-09-01

Full Text Available Primary hyperparathyroidism occurs as a result of isolated parathyroid adenoma in 80% to 85% of all cases. A 99mtechnetium (99mTc sestamibi scan or neck ultrasonography is used to localize the neoplasm prior to surgical intervention. A 53-year-old female was referred for the exclusion of metabolic bone disease. She presented with low back pain that had persisted for the past 6 months and elevated serum alkaline phosphatase (1,253 IU/L. Four years previously, she had been diagnosed at a local hospital with a 2.3-cm thyroid nodule, which was determined to be pathologically benign. Radiofrequency ablation was performed at the same hospital because the nodule was still growing during the follow-up period 2 years before the visit to our hospital, and the procedure was unsuccessful in reducing the size of the nodule. The results of the laboratory tests in our hospital were as follows: serum calcium, 14.6 mg/dL; phosphorus, 3.5 mg/dL; and intact parathyroid hormone (iPTH, 1,911 pg/mL. Neck ultrasonography and 99mTc sestamibi scan detected a 5-cm parathyroid neoplasm in the left lower lobe of the patient's thyroid; left parathyroidectomy was performed. This case indicated that thyroid ultrasonographers and pathologists need to be experienced enough to differentiate a parathyroid neoplasm from a thyroid nodule; 99mTc sestamibi scan, serum calcium, and iPTH levels can help to establish the diagnosis of parathyroid neoplasm.

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

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Wolf-Georg Forssmann

2016-08-01

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

Rat parathyroid hormone (rPTH) ELISAs specific for regions (2-7), (22-34) and (40-60) of the rat PTH structure: influence of sex and age.

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

2010-09-15

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

Prevalence of 25-hydroxyvitamin D deficiency in healthy personnel from an academic institution of an urban area in Costa Rica

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Gamboa-Gamboa T

2015-10-01

Full Text Available Tatiana Gamboa-Gamboa,1 Gabriel Abarca-Soto,2 José G Jiménez-Montero3,4 1Department of Research and Nutrition, Universidad de Ciencias Médicas, San José, Costa Rica; 2Department of Research, School of Medicine, Universidad de Ciencias Médicas, San José, Costa Rica; 3Department of Postgraduate Studies, Universidad de Ciencias Médicas, San José, Costa Rica; 4Department of Endocrinology, Hospital CIMA, San José, Costa Rica Objective: The aim of this study was to determine 25-hydroxyvitamin D concentrations in healthy employees of the Universidad de Ciencias Médicas, Costa Rica. Methods: Levels of 25-hydroxyvitamin D, calcium, phosphorus, intact parathyroid hormone (iPTH, and creatinine were measured in 80 people. Solar ultraviolet radiation exposure and 25-hydroxyvitamin D intake were estimated using a previously designed questionnaire. Participants were 52 women aged (mean ± standard deviation 35.8±10.0 years old, body mass index of 27.1±5.9 kg/m2, and 26 men aged 36.4±10.8 years old, body mass index of 27.5±5.0 kg/m2. Results: All participants were normocalcemic, eight females were postmenopausal, three were hypertensive; none had renal, gastrointestinal, or thyroid disease. The level of 25-hydroxyvitamin D was 23.9±7.0 ng/dL and iPTH 40.1±17.5 pg/dL. A level of 25-hydroxyvitamin D $30 ng/dL was seen in 17% of the population. The eight participants with iPTH higher than 67 ng/dL, had 25-hydroxyvitamin D of 18.9±4.8 ng/dL. Two participants who received 25-hydroxyvitamin D and calcium supplements were excluded. Conclusion: The 25-hydroxyvitamin D insufficiency and deficiency found in healthy employees from an academic center in Costa Rica may be due to working long hours in-doors and solar ultraviolet radiation exposure. It is unknown whether secondary hyperparathyroidism seen in nearly 10% of this population, may have long-term effects on bone health. Keywords: vitamin D deficiency, osteoporosis, secondary hyperparathyroidism

THE CARDIOVASCULAR EFFECTS OF CINACALCET IN HEMODIALYSIS PATIENTS WITH SECONDARY HYPERPARATHYROIDISM

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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.

Enhanced chondrogenesis and Wnt signaling in PTH-treated fractures.

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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

Cost effectiveness of paricalcitol versus cinacalcet with low-dose vitamin D for management of secondary hyperparathyroidism in haemodialysis patients in the USA.

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Sharma, Amit; Marshall, Thomas S; Khan, Samina S; Johns, Beverly

2014-02-01

The IMPACT SHPT [Improved Management of Intact Parathyroid Hormone (iPTH) with Paricalcitol-Centered Therapy Versus Cinacalcet Therapy with Low-Dose Vitamin D in Hemodialysis Patients with Secondary Hyperparathyroidism] study compared the effectiveness of paricalcitol and cinacalcet in the management of secondary hyperparathyroidism in haemodialysis patients but did not report the costs or cost effectiveness of these treatments. The aim of this study was to compare the cost effectiveness of a paricalcitol-based regimen versus cinacalcet with low-dose vitamin D for management of secondary hyperparathyroidism in haemodialysis patients from a US payer perspective, using a 1-year time horizon. This was a post hoc cost-effectiveness analysis of data collected for US patients enrolled in the IMPACT SHPT study-a 28-week, randomized, open-label, phase 4, multinational study (ClinicalTrials.gov identifier: NCT00977080). Patients eligible for the IMPACT SHPT study were aged≥18 years with stage 5 chronic kidney disease, had been receiving maintenance haemodialysis three times weekly for at least 3 months before screening and were to continue haemodialysis during the study. Only US patients who reached the evaluation period (weeks 21-28) were included in this secondary analysis. US subjects in the IMPACT SHPT study were randomly assigned to receive intravenous paricalcitol, or oral cinacalcet plus fixed-dose intravenous doxercalciferol, for 28 weeks. Patients in the paricalcitol group could also receive supplemental cinacalcet for hypercalcaemia. The primary effectiveness endpoint in the IMPACT SHPT study was the proportion of subjects who achieved a mean intact parathyroid hormone (iPTH) level of 150-300 pg/mL during the evaluation period. In this secondary analysis, we estimated the incremental cost-effectiveness ratio (ICER), comparing paricalcitol-treated patients with cinacalcet-treated patients on the basis of this primary endpoint and several secondary endpoints

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

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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.

Effect of Ramadan fasting in Saudi Arabia on serum bone profile and immunoglobulins.

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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.

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

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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.

Risk factors of post renal transplant hyperparathyroidism

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

2009-01-01

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

Compliance with guidelines and predictors of mortality in hemodialysis. Learning from Serbia patients

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Ljubica Djukanović

2015-05-01

Conclusion: Substantial proportion of patients examined failed to meet KDOQI guidelines targets. The relative risk of time to death was associated with being outside the targets for Kt/V, hemoglobin and iPTH.

The study in the relationship between serum calcium and serum parathyroid hormone (PTH) by employing the various kits of PTH assay

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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)

Intermittent Parathyroid Hormone Enhances Cancellous Osseointegration of a Novel Murine Tibial Implant

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

2015-01-01

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

Overproduction of an amino-terminal form of PTH distinct from human PTH(1-84) in a case of severe primary hyperparathyroidism: influence of medical treatment and surgery.

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

2005-06-01

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

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

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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.

Paricalcitol Versus Calcifediol for Treating Hyperparathyroidism in Kidney Transplant Recipients

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Josep M. Cruzado

2018-01-01

Conclusion: Both PAR and CAL reduced iPTH, but PAR was associated with a higher proportion of patients with iPTH <70 pg/ml. These results do not support the use of PAR to treat posttransplantation hyperparathyroidism.

Use of cinacalcet for the management of hyperparathyroidism in patients with different degrees of renal failure

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José M. Orellana

2016-03-01

Conclusions: Cinacalcet at low doses is effective in the management of SHPT in CKD patients who are not on dialysis. Its use reduces iPTH and calcaemia, without causing serious side effects or significant changes in renal function.

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

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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)

Acute and chronic regulation of circulating PTH: significance in health and in disease.

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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.

Clinical Characteristics of Patients with Diabetic Nephropathy on Maintenance Hemodialysis: A Multicenter Cross-sectional Survey in Anhui Province, Eastern China

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Hu Chen

2016-01-01

Conclusions: DN patients on MHD in Anhui province exhibited different clinical characteristics compared to non-DN hemodialysis patients. They presented higher percentage in TCC use and cardiovascular complication, lower serum albumin and iPTH levels than those in non-DN patients.

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

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Pinheiro Pedro LC

2012-07-01

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

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

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

2008-05-01

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

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

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Skwara Adrian

2010-04-01

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

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

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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)

Aluminum toxicity in dialysis patients: Radiographic findings and establishment of biopsy-sparing criteria

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Kriegshauser, J.S.; Swee, R.G.; McCarthy, J.T.; Hauser, M.F.

1986-01-01

Aluminum toxicity in dialysis patients currently requires bone biopsy for diagnosis. The authors retrospectively reviewed the findings in 63 dialysis patients who had undergone bone biopsies. In 30 patients biopsies were negative for aluminum toxicity and in 33 patients biopsies were positive. In 17 of the 30 biopsy-negative patients, absence of aluminum toxicity could be predicted by a high parathyroid hormone (iPTH) level (>200 μEq/ml) and fewer than three fractures, or by the presence of osteosclerosis on radiographs. No biopsy-positive patients met these criteria (P < .001). In 16 of 33 biopsy-positive patients aluminum toxicity could be predicted by a low iPTH level (<500 μEq/ml) and more than three fractures. No biopsy-negative patient met these criteria (P < .001). Thus, based on the criteria we have identified, 52.4% of the patients could have been spared biopsy

Effects of continuous and pulsatile PTH treatments on rat bone marrow stromal cells

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

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Jose Gilberto H. Vieira

2012-01-01

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

PTH treatment activates intracortical bone remodeling in patients with hypoparathyroidism

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

2017-01-01

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

Deletion of PTH rescues skeletal abnormalities and high osteopontin levels in Klotho-/- mice.

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Quan Yuan

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

The role of leptin and other hormones related to bone metabolism and appetite-regulation as determinants of gain in body fat and fat-free mass in 8-11 year old children

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

2015-01-01

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

PTH Gene Polymorphism and Breast Cancer Risk in Kazakhstan

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Nurgul Sikhayeva

2014-12-01

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

Biochemical and Clinical Variables of Normal Parathyroid and Hyperparathyroid Diabetic Chronic Kidney Disease Patients

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Syed Abdul Kader

2016-09-01

Full Text Available Background: In chronic kidney disease (CKD intact parathyroid hormone (iPTH level is often increased before clinical hyperphosphatemia occurs. Despite its importance very few studies evaluated parathyroid status in CKD. Objective: The study was undertaken to estimate level of parathormone in diabetic CKD patients at a tertiary level hospital and assessing its relationship with different parameters like hemoglobin, calcium etc. and comparing biochemical and clinical variables between normal parathyroid and hyperparathyroid groups. Materials and Methods: It was a hospital based cross-sectional study involving purposively selected chronic kidney disease patients attending nephrology and endocrinology outdoor and indoor services of BIRDEM hospital, Dhaka, Bangladesh. Study was conducted during the period of April to October 2010. All the subjects were divided into two groups based on serum parathormone level and different parameters were compared between groups. Results: The mean duration of chronic kidney disease was significantly higher in hyperparathyroid group than that in the normal group (<0.001. Retinopathy and hypertension were more common in hyperparathyroid group than that in patients with normal serum parathormone (p<0.001 and p=0.012. Neuropathy was solely present in hyperparathyroid group (p<0.001. Mean fasting blood glucose, serum creatinine and serum phosphate were significantly higher in the hyperparathyroid group compared to normal group (p<0.001 in all cases while the mean serum calcium and haemoglobin were lower in hyperparathyroid group than those in the normal group (p<0.001 in both cases. Serum creatinine and serum parathormone bears a significantly linear relationship (r=0.986, p<0.001, while serum parathormone and serum calcium bears a significantly negative relationship (r=−0.892 and p<0.001. Conclusion: Earlier intervention on the basis of iPTH in addition to other biochemical parameters of chronic kidney disease is

The role of leptin and other hormones related to bone metabolism and appetite regulation as determinants of gain in body fat and fat-free mass in 8-11-year-old children.

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

2015-03-01

Regulation of body composition during childhood is complex. Numerous hormones are potentially involved. Leptin has been proposed to restrain weight gain, but results are inconsistent. We examined whether baseline fasting levels of ghrelin, adiponectin, leptin, insulin, IGF-I, osteocalcin, and intact parathyroid hormone (iPTH) were associated with body composition cross sectionally and longitudinally in 633 8-11-year-olds. Data on hormones and body composition by dual-energy x-ray absorptiometry from the OPUS School Meal Study were used. We looked at baseline hormones as predictors of baseline fat mass index (FMI) or fat-free mass index (FFMI), and also subsequent changes (3 and 6 months) in FMI or FFMI using models with hormones individually or combined. Cross-sectionally, baseline leptin was positively associated with FMI in girls (0.211 kg/m(2) pr. μg/mL; 97.5% confidence interval [CI],0.186-0.236; P < .001) and boys (0.231 kg/m(2) pr. μg/mL; 97.5% CI, 0.200-0.261; P < .001). IGF-I in both sexes and iPTH in boys were positively associated with FMI. An inverse association between adiponectin and FFMI in boys and a positive association between IGF-I and FFMI were found in girls. In longitudinal models, baseline leptin was inversely associated with subsequent changes in FMI (-0.018 kg/m(2) pr. μg/mL; 97.5% CI, -0.034 - -0.002; P = .028) and FFMI (-0.014 kg/m(2) pr. μg/mL; 97.5% CI, -0.024 - -0.003; P = .006) in girls. Cross-sectional findings support that leptin is produced in proportion to body fat mass, but the longitudinal observations support that leptin inhibits gains in FMI and FFMI in girls, a finding that may reflect preserved leptin sensitivity in this predominantly normal weight population.

Discrepancies in Clinic and Ambulatory Blood Pressure in Korean Chronic Kidney Disease Patients

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2017-01-01

Blood pressure (BP) control is considered the most important treatment for preventing chronic kidney disease (CKD) progression and associated cardiovascular complications. However, clinic BP is insufficient to diagnose hypertension (HT) and to monitor overall BP control because it does not correlate well with ambulatory blood pressure monitoring (ABPM). We enrolled 387 hypertensive CKD patients (stages G1–G4, 58.4% male with median age 61 years) from 3 hospitals in Korea. HT of clinic BP and ABPM was classified as ≥ 140/90 and ≥ 130/80 mmHg, respectively. Clinic BP control rate was 60.2%. The median 24-hour systolic blood pressures (SBPs) of CKD G3b and CKD G4 were significantly higher than those of CKD G1–2 and CKD G3a. However, the median 24-hour SBPs were not different between CKD G1–2 and CKD G3a or between CKD G3b and CKD G4. Of all patients, 5.7%, 38.0%. 42.3%, and 14.0% were extreme-dippers, dippers, non-dippers, and reverse-dippers, respectively. Non-/reverse-dippers independently correlated with higher Ca × P product, higher intact parathyroid hormone (iPTH), and lower albumin. Normal BP was 33.3%, and sustained, masked, and white-coat HT were 29.7%, 26.9%, and 10.1%, respectively. White-coat HT independently correlated with age ≥ 61 years and masked HT independently correlated with CKD G3b/G4. In conclusion, ABPM revealed a high prevalence of non-/reverse-dippers and sustained/masked HT in Korean CKD patients. Clinicians should try to obtain a CKD patient's ABPM, especially among those who are older or who have advanced CKD as well as those with abnormal Ca × P product, iPTH, and albumin. PMID:28378550

Evaluation of Bone Mineral Density in Children with Thalassemia Major

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Betül Bakan

2012-12-01

Full Text Available Aim: Fragile bones develop due to various factors in thalassemic patients. Even with optimum management, osteoporosis occurs, contributing to morbidity in majority of patients with thalassemia major (TM. Our aim was to evaluate bone health of thalassemic children using biochemical parameters and bone mineral density (BMD, and to emphasize the precautionary measures and early diagnosis of osteoporosis. Material and Methods: Thirteen children (5 females, 8 males, age <18 years with TM were included in the study. Age, duration, weight, height, transfusion frequency, medication use were recorded. Following laboratory analysis were obtained: Whole blood count, fasting blood glucose, ferritin, alanine aminotransferase, aspartate aminotransferase, calcium, phosphorus, alkaline phosphatase, thyroid stimulating hormone, free thyroxin, and intact parathyroid hormone (iPTH. BMD was determined using dual energy X-ray absorptiometry (DXA from femur and lumbar vertebrae. Patients with DXA Z-score <-2 was defined as osteoporotic. Results: The mean age was 7.85±3.17 years and body mass index (BMI was 14.68±1.93 kg/m2. The rest of the results were as follows: Lumbar BMD 0.464±0.108 g/cm2; total femur BMD 0.581± 0.114 g/cm2; lumbar DEXA Z-score 2.44±1.60; total femur DEXA -0.93±1.19. Osteoporosis ratio was determined as 69% in the lumbar vertebrae and 10% in the femur. A significant positive correlation was found between lumbar-femoral BMD and BMI, and a significant negative correlation was observed between femoral BMD and iPTH. Conclusion: BMD is low in thalassemic children. Despite regular transfusions and chelation therapy, osteoporosis starts early in life. (Turkish Journal of Osteoporosis 2012;18: 72-7

Management of secondary hyperparathyroidism: practice patterns and outcomes of cinacalcet treatment with or without active vitamin D in Austria and Switzerland - the observational TRANSIT Study.

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Pronai, Wolfgang; Rosenkranz, Alexander R; Bock, Andreas; Klauser-Braun, Renate; Jäger, Christine; Pendl, Gunther; Hemetsberger, Margit; Lhotta, Karl

2017-05-01

Secondary hyperparathyroidism is a complex disorder requiring an individualized multicomponent treatment approach. This study was conducted to identify treatment combinations used in clinical practice in Austria and Switzerland and the potential to control this disorder. A total of 333 adult hemodialysis and peritoneal dialysis patients were analyzed. All patients received conventional care prior to initiation of a cinacalcet-based regimen. During the study, treatment components, e.g. cinacalcet, active vitamin D analogues and phosphate binders, were adapted to individual patient requirements and treatment dynamics were documented. Overall, the mean intact parathyroid hormone (iPTH) increased from 64.2 pmol/l to 79.6 pmol/l under conventional therapy and decreased after cinacalcet initiation to 44.0 pmol/l after 12 months (mean decrease between baseline and 12 months -45%). Calcium remained within the normal range throughout the study and phosphorus ranged around the upper limit of normal. The Kidney Disease: Improving Global Outcomes (KDIGO) target achievement for iPTH increased from 44.5% of patients at baseline to 65.7% at 12 months, corrected calcium from 58.9% to 51.9% and phosphorus from 18.4% to 24.4%. On average, approximately 30% of patients adapted their regimen from one observation period to the next. The reasons for changing a given regimen were to attain or maintain any of the bone mineral markers within recommended targets and to avoid developments to extreme values. Some regional differences in practice patterns were identified. No new safety signals emerged. In conclusion, cinacalcet appears to be a necessary treatment component to achieve recommended targets. The detailed composition of the treatment mix should be adapted to patient requirements and reassessed on a regular basis.

Gene structure, transcripts and calciotropic effects of the PTH family of peptides in Xenopus and chicken

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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.

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Jose Candelario

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

Subtotal parathyroidectomy for secondary renal hyperparathyroidism: a 20-year surgical outcome study.

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Konturek, Aleksander; Barczyński, Marcin; Stopa, Małgorzata; Nowak, Wojciech

2016-11-01

The aim of this study was to evaluate the outcomes of surgery for patients with secondary renal hyperparathyroidism (rHPT). This is a retrospective cohort study. Our institutional database was searched for eligible patients treated in 1995-2014. The inclusion criterion was initial parathyroidectomy for rHPT. Clinical and follow-up data were analyzed to estimate the cure rate (primary outcome), and morbidity (secondary outcome). The study group comprised 297 patients (154 females, age 44.5 ± 13.7 years, follow-up 24.6 ± 10.5 months), including 268 (90.2 %) patients who had underwent subtotal parathyroidectomy, and 29 (9.8 %) who had had incomplete parathyroidectomy. Intraoperative iPTH assay was utilized in 207 (69.7 %) explorations. Persistent rHPT occurred in 12/268 (4.5 %) patients after subtotal parathyroidectomy and 5/29 (17.2 %) subjects after incomplete parathyroidectomy (p = 0.005). The patients operated on with intraoperative iPTH assay had a higher cure rate than non-monitored individuals, 201/207 (97.1 %) vs. 79/90 (87.8 %), respectively (p = 0.001). In-hospital mortality occurred in 1/297 (0.3 %) patient. The hungry bone syndrome occurred in 84/268 (31.3 %) patients after subtotal parathyroidectomy and 2/29 (6.9 %) subjects after incomplete parathyroidectomy (p = 0.006). Transient recurrent laryngeal nerve paresis occurred in 14/594 (2.4 %) and permanent in 5/594 (0.8 %) nerves at risk. Subtotal parathyroidectomy is a safe and efficacious treatment for patients with rHPT. Utilization of intraoperative iPTH assay can guide surgical exploration and improve the cure rate.

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

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

2005-11-01

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

Establishment of reference values in a healthy population and interpretation of serum PTH concentrations in hemodialyzed patients according to the KDIGO Guidelines using the Lumipulse® G whole PTH (3rd generation) assay.

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

2018-04-01

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

The role of oral sodium bicarbonate supplementation in maintaining acid-base balance and its influence on the cardiovascular system in chronic hemodialysis patients - results of a prospective study.

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Voiculeț, C; Zară, O; Bogeanu, C; Văcăroiu, I; Aron, G

2016-01-01

calcifications (p = 0.036) between the study and the control group. The average dose of phosphate binders was significantly higher in the study group (p = 0.01). At the end of the study, the serum iPTH average levels were decreased in the study group (p < 0.001) and significantly increased in the control group (p < 0.001). Conclusions: Avoiding large variations in serum bicarbonate levels is an important step in hemodialysis patients' management because wide acidosis-alkalosis variation can increase cardiovascular risks in terms of altering the vessel walls elasticity and favoring their calcifications. Abbreviations : GFR = glomerular filtration rate,PWV = pulse wave velocity, iPTH = intact parathyroid hormone,AR = alkaline reserve, BP = blood pressure,mEq = milliequivalents,L = liter.

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

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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

Structure of non-(1-84) PTH fragments secreted by parathyroid glands in primary and secondary hyperparathyroidism.

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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...

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

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Mary C. Hames

2013-11-01

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

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

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

1999-12-01

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

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

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)

Neurological, psychological, and cognitive disorders in patients with chronic kidney disease on conservative and replacement therapy.

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Lai, Silvia; Mecarelli, Oriano; Pulitano, Patrizia; Romanello, Roberto; Davi, Leonardo; Zarabla, Alessia; Mariotti, Amalia; Carta, Maria; Tasso, Giorgia; Poli, Luca; Mitterhofer, Anna Paola; Testorio, Massimo; Frassetti, Nicla; Aceto, Paola; Galani, Alessandro; Lai, Carlo

2016-11-01

Chronic kidney disease (CKD) is a highly prevalent condition in the world. Neurological, psychological, and cognitive disorders, related to CKD, could contribute to the morbidity, mortality, and poor quality of life of these patients. The aim of this study was to assess the neurological, psychological, and cognitive imbalance in patients with CKD on conservative and replacement therapy.Seventy-four clinically stable patients affected by CKD on conservative therapy, replacement therapy (hemodialysis (HD), peritoneal dialysis (PD)), or with kidney transplantation (KT) and 25 healthy controls (HC), matched for age and sex were enrolled. Clinical, laboratory, and instrumental examinations, as renal function, inflammation and mineral metabolism indexes, electroencephalogram (EEG), psychological (MMPI-2, Sat P), and cognitive tests (neuropsychological tests, NPZ5) were carried out.The results showed a significant differences in the absolute and relative power of delta band and relative power of theta band of EEG (P = 0.008, P therapy, and Grade 2-3 in KT patients. The scales of MMPI-2 hysteria and paranoia, are significantly correlated with creatinine, eGFR, serum nitrogen, CRP, 1,25-(OH)2D3, intact parathyroid hormone (iPTH), phosphorus, and cynical and hysterical personality, are correlated with higher relative power of delta (P = 0.016) and theta band (P = 0.016). Moreover, all NPZ5 scores showed a significant difference between the means of nephropathic patients and the means of the HC, and a positive correlation with eGFR, serum nitrogen, CRP, iPTH, and vitamin D.In CKD patients, simple and noninvasive instruments, as EEG, and cognitive-psychological tests, should be performed and careful and constant monitoring of renal risk factors, probably involved in neuropsychological complications (inflammation, disorders of mineral metabolism, electrolyte disorders, etc.), should be carried out. Early identification and adequate therapy of neuropsychological

Factors associated with low bone mass in the hemodialysis patients – a cross-sectional correlation study

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Huang Guey-Shiun

2009-06-01

Full Text Available Abstract Background Low bone mass is common in end-stage renal disease patients, especially those undergoing hemodialysis. It can lead to serious bone health problems such as fragility fractures. The purpose of this study is to investigate the risk factors of low bone mass in the hemodialysis patients. Methods Sixty-three subjects on hemodialysis for at least 6 months were recruited from a single center for this cross-sectional study. We collected data by questionnaire survey and medical records review. All subjects underwent a bone mineral density (BMD assay with dual-energy x-ray absorptiometry at the lumbar spine and right hip. Data were statistically analyzed by means of descriptive analysis, independent t test and one way analysis of variance for continuous variables, Pearson product-moment correlation to explore the correlated factors of BMD, and stepwise multiple linear regression to identify the predictors of low bone mass. Results Using WHO criteria as a cutoff point, fifty-one subjects (81% had a T-score lower than -1, of them 8 subjects (13% had osteoporosis with the femoral neck most commonly affected. Regarding risk factors, age, serum alkaline phosphatase (ALP level, and intact parathyroid hormone (iPTH level had significant negative correlations with the femoral neck and lumbar spine BMD. On the other hand, serum albumin level, effective exercise time, and body weight (BW had significant positive correlations with the femoral neck and lumbar spine BMD. Age, effective exercise time, and serum albumin level significantly predicted the femoral neck BMD (R2 × 0.25, whereas BW and the ALP level significantly predicted the lumbar spine BMD (R2 × 0.20. Conclusion This study showed that advanced age, low BW, low serum albumin level, and high ALP and iPTH levels were associated with a low bone mass in the hemodialysis patients. We suggest that regular monitoring of the femoral neck BMD, maintaining an adequate serum albumin level and BW

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

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

2017-05-01

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

Effects of PTH and Ca2+ on renal adenyl cyclase

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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

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

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

2013-08-01

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

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

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

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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

99mTc-HMDP Bone Uptake Quantification and Plasma Osteocalcin, PTH Levels in Hemodialysis Patients

International Nuclear Information System (INIS)

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

1996-01-01

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

Maximizing PTH Anabolic Osteoporosis Therapy

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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

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

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

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

2014-12-15

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

Calcitonin impairs the anabolic effect of PTH in young rats and stimulates expression of sclerostin by osteocytes.

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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

The treatment of secondary hyperparathyroidism in haemodialysis patients' refractory to alfacalcidol

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L V Egshatyan

2012-06-01

Full Text Available Background. Secondary hyperparathyroidism (sHPT is one of the serious complications in chronic kidney disease and is associated with progressive bone disease and vascular calcification.The objective of the study was to determine the impact of Mimpara (Cinacalcet HCl on mineral disorder, bone turnover and bone mineral density (BMD versus parathyroidectomy (PTx in haemodialysis patients’ refractory to alfacalcidol. Materials and methods. 62 haemodialysis patients with sHPT were enrolled in this 6=months prospective study. All of them had surgical indications for PTx. Surgical indications was established according to clinical or biological assessment. 40 patients underwent Mimpara treatment. Dose of Mimpara was titrated every 4 weeks. Sequential doses included 30–180 (mean 59.1 ± 34.2 mg/day. 22 patients underwent PTx. The surgical technique was depended on quantity of hyperplastic parathyroid glands.Results. In 6 months mean iPTH, Ca, Са×Р, CTx and OC levels significantly decreased by 55.7%, 13.8%,34.3%, 21.4 and 1.4% in the Mimpara group vs. 90.7%, 14%, 55.5%, 58.7% and 26.9% in the PTx group. Median serum iPTH level decreased by 30% after initiation of Mimpara in 94.3% patients, from them by 50%in 74.3%. Achieved the KDOQI treatment targets for PTH in 28.6% patients.In 6 months after PTx median serum iPTH level was <100 pg/ml in 50% patients, achieved the KDOQI treatment targets in 27.3%, <300 pg/ml in 18.2%. Median serum 25(ОНD after PTx significantly increase by 127.3% vs 6.72% in the Mimpara group. In 6 months active restoration of BMD was found in the PTx patients, and patients treated with Cinacalcet showed stabilization of BMD.Mimpara therapy led to a reduction in glandular volume during the course of the study: in both glands with a baseline volume <500 mm3 and with a baseline volume ≥500 mm3. Conclusions. PTx and Cinacalcet therapy improves phosphorus=calcium homeostasis, bone turnover, but bone resorption and formation

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

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

2007-05-01

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

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

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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.

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...

Role of acidosis-induced increases in calcium on PTH secretion in acute metabolic and respiratory acidosis in the dog.

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

2004-05-01

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

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

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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

Nuclear medicine diagnostic experience for 25 patients with parathyroid disease accompanied elevated serum PTH level

International Nuclear Information System (INIS)

Su Li; Huang Chenggang; Niu Wenqiang; Wu Liwen

2010-01-01

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

Are PTH levels related to oxidative stress and inflammation in chronic kidney disease patients on hemodialysis?

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Marcel Jaqueto

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

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

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Jodi A. Carlson Scholz

2012-12-01

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

Long-term effects of intermittent equine parathyroid hormone fragment (ePTH-1-37) administration on bone metabolism in healthy horses.

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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.

La proteína PthB de Xanthomonas axonopodis pv. manihotis es autoactiva en ensayos de doble hibrido

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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.

Failed Switching off in the MIBI-Parathyroid Scintigraphy in a Dialyzed Patient with Secondary Hyperparathyroidism Responsive to Cinacalcet Therapy

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Piergiorgio Bolasco

2010-01-01

Full Text Available The aims of your case report is to show the predictivity of Tc99m-sestamibi (MIBI scintigraphy and doppler ultrasound imaging on secondary hyperparathyroidism (SHPT in a patient responsive to calcimimetic treatment. Moreover, it has been reported that calcimimetic has great potential in reducing the volume of the parathyroid gland. On the other hand, the MIBI scintigraphy is considered a crucial diagnostic procedure to monitor the response to therapy in terms of turnover and cellular metabolism; whereas, ultrasound to monitor the volume variation in response to treatment. It is described the case of a 73-year-old man on hemodialysis from 1995 for ESRD. Within 2 years the patient gradually developed SHPT with progressively increased iPTH up to 1,000 ρg/ml. The ultrasound, highlighted the presence of two parathyroid hyperplasia, confirmed by scintigraphy, showing focal increase uptake of sestamibi in the same anatomical areas. As a result of the patient's refusal to perform a parathyroidectomy, cinacalcet, was administered (65 mg overage daily dose. After a year of treatment, there was a striking decrease of iPTH (from 1300 to 57 ρg/ml, −95%; but, on the contrary to expectations, this positive metabolic outcome, was not followed by parathyroid changes in ultrasound and scintigraphic findings.

PTH/PTHrP Receptor Mediates Cachexia in Models of Kidney Failure and Cancer.

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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.

Increased bone radiotracer uptake in renal osteodystrophy

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de Graaf, P.; Schicht, I.M.; de Graeff, J.; te Velde, J.; Kleiverda, K.; Pauwels, E.K.J.

1982-04-01

Bone radiotracer uptake in renal osteodystrophy was investigated in 35 dialysis patients by correlating the results of quantitative bone scintigraphy with those of biochemical and bone morphometric studies. There were highly significant correlations (P < 0.001) between the total skeletal activity and the biochemical (iPTH and alkaline phosphatase), and histologic parameters of hyperparathyroidism. These clinical results strongly suggest that increased bone turnover i.e. hyperparathyroidism, rather than osteomalacia is the major cause of increased skeletal uptake in renal osteodystrophy.

Anabolic action of parathyroid hormone (PTH) does not compromise bone matrix mineral composition or maturation.

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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

Identification of six novel PTH1R mutations in families with a history of primary failure of tooth eruption.

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

2013-01-01

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

Identification of six novel PTH1R mutations in families with a history of primary failure of tooth eruption.

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Lotte Risom

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

Blood-pressure-independent wall thickening of intramyocardial arterioles in experimental uraemia: evidence for a permissive action of PTH.

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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).

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

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Yu-mi Lee

2015-01-01

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

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...

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

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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.

Targeting sphingosine-1-phosphate lyase as an anabolic therapy for bone loss.

Science.gov (United States)

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

2018-05-01

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

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

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

Vitamin D status and association to bone health in 781 healthy 8–11 years old Danish school children: preliminary results from the Opus school meal study

DEFF Research Database (Denmark)

Petersen, R. A.; Damsgaard, C. T.; Dalskov, S.

2013-01-01

for bone area (BA), age, height, weight, gender, pubertal stage, ethnicity and physical activity. Likewise, no associations were found between serum 25(OH)D and BA or BMD. Conclusion: A substantial number of Danish children did not reach the recommended level of 25(OH)D (>50 nmol/l) during autumn. Despite...... conducted and anthropometry, puberty stage, intake of dietary supplements and physical activity was measured. Whole body DXA scans were performed and total body less head (TBLH) DXA values were used in data analyses. Results: Serum 25(OH)D ranged from 15.2 to 132 nmol/l, with mean of 60.7±18.7 nmol......PTH (P=0.012) concentrations than boys. Serum 25(OH)D was inversely associated with iPTH without, and with, adjustment for age, gender, pubertal stage, month and ethnicity (P

CaPTHUS scoring model in primary hyperparathyroidism: can it eliminate the need for ioPTH testing?

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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.

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

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

2018-01-15

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

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

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

2015-11-01

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

Alteração do teor de cálcio no banho de DP para 2,5 mEq/L é eficaz no reestabelecimento dos valores preconizados por diretrizes atuais em pacientes com PTH < 150 pg/dL Low-calcium peritoneal dialysis solution is effective in bringing PTH levels to the range recommended by current guidelines in patients with PTH levels < 150 pg/dL

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Thyago Proença de Moraes

2010-09-01

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

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.

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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.

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

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

2006-05-01

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

Influence of Secondary Hyperparathyroidism Induced by Low Dietary Calcium, Vitamin D Deficiency, and Renal Failure on Circulating Rat PTH Molecular Forms.

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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.

In vivo PTH provokes apical NHE3 and NaPi2 redistribution and Na-K-ATPase inhibition

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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....

Long-term suppression of secondary hyperparathyroidism by intravenous 1 alpha-hydroxyvitamin D3 in patients on chronic hemodialysis

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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...

Long-term treatment with calcium-alpha-ketoglutarate corrects secondary hyperparathyroidism.

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Zimmermann, E; Wassmer, S; Steudle, V

1996-01-01

Calcium-alpha-ketoglutarate (Ca-ket) is known as a highly effective phosphate (P) binder in hemodialysis (HD) patients. In addition, alpha-ketoglutarate has been shown to improve metabolic alterations. We investigated the effect of long-term P-binding therapy with Ca-ket to determine whether P accumulation is the main reason of secondary hyperparathyroidism (HPT) in HD patients or not. Ca-ket was prescribed to 14 HD patients as a soluble preparation in a mean dosage of 4.5 g/day (0.975 g elemental Ca) for a period of 36 months. Serum P continuously dropped from prestudy 2.6 +/- 0.1 (mean +/- SEM) to 1.9 +/- 0.07 mmol/l (p < 0.001), whereas serum Ca increased from 2.2 +/- 0.1 to 2.47 +/- 0.08 mmol/l (p < 0.05). Thus, Ca/P ratio in serum converted significantly from 0.91 +/- 0.02 (prestudy) to 1.28 +/- 0.01 (p < 0.001). Intact parathyroid hormone (iPTH) continuously normalized in all patients from 29 +/- 5 to 8 +/- 2 pmol/l (p < 0.001). The present data show that long-term treatment with Ca-ket normalizes secondary HPT by simultaneously P binding and correcting Ca/P ratio in serum without vitamin D treatment.

Coexistence of parathyroid adenoma and papillary thyroid carcinoma: Experience of a single center

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Ebubekir Gündeş

2013-01-01

Full Text Available Objective: The aim of this study was to describe experienceswith concurrent parathyroid adenoma and papillarythyroid carcinoma.Methods: Eight patients with concurrent parathyroid adenomaand papillary thyroid carcinoma were identifiedbetween 2005 and 2012, and their medical records werereviewed retrospectively.Results: Of the eight patients identified, two were maleand six were female; their mean age was 53.6 years.The mean serum calcium concentration was 11.7 mg/dL.Intact parathyroid hormone (iPTH concentrations werehigh in all patients, with a mean concentration of 338 pg/mL. The most frequently used surgical technique was totalthyroidectomy plus parathyroid adenoma excision (n=6.The mean size of the thyroid carcinoma was 1.2 cm, andone case showed metastatic lymph nodes in the centralcompartment. The mean parathyroid adenoma size wasfound to be 2.1(0.6- 3.5 cm, according to the longest sizeof the adenom. Six patients (75% developed postoperativecomplications, including temporary symptomatic hypocalcemiain 4 patients (50%, hematoma developmentin 1 patient (12.5% and temporary vocal cord paralysis inone patient (12.5%.Conclusion: Thyroid carcinoma and parathyroid adenomaare rarely concomitant. Rarely hyperparathyroidismmay be accompanied with thyroid carcinomas so preoperativelythyroid gland should be properly examined. Thyroidwith parathyroid surgery are risk factors of recurrentlaryngeal nerve injury and hypoparathyroidism.Key words: Papillary thyroid cancer; parathyroid adenoma;thyroidectomy

Long-term mortality after parathyroidectomy among chronic kidney disease patients with secondary hyperparathyroidism: a systematic review and meta-analysis.

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Chen, Lin; Wang, Kongbo; Yu, Shanlan; Lai, Liping; Zhang, Xiaoping; Yuan, Jingjing; Duan, Weifeng

2016-08-01

Parathyroidectomy (PTx) and medical treatments are both recommended for reducing serum intact parathyroid hormone (iPTH) and curing secondary hyperparathyroidism (sHPT) in patients with chronic kidney disease (CKD), but their therapeutic effects on long-term mortality are not well-known. Thus, we aim to assess such therapeutic effect of PTx. Electronic literatures published on Pubmed, Embase, and Cochrane Central Register of Controlled Trials in any language until 27 November 2015 were systematically searched. All literatures that compared outcomes (survival rate or mortality rate) between PTx-treated and medically-treated CKD patients with sHPT were included. Finally, 13 cohort studies involving 22053 patients were included. Data were extracted from all included literatures in a standard form. The outcomes of all-cause and cardiovascular mortalities were assessed using DerSimonian and Laird's random effects model. We find PTx-treated versus medically-treated patients had a 28% reduction in all-cause mortality and a 37% reduction in cardiovascular mortality. Thus, PTx versus medical treatments might reduce the risks of all-cause and cardiovascular mortalities in CKD patients with sHPT. Further studies with prospective and large-sample clinical trials are needed to find out the real effect of PTx and to assess whether mortality rates differ among patterns of PTx.

Effects of add on PTH(1-84) substitution therapy in hypoparathyroidism: results from a double-blind randomised controlled study

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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...

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

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

2017-01-01

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

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

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Kohei Nishitani

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

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.

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

2016-02-01

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

On the pth moment estimates of solutions to stochastic functional differential equations in the G-framework.

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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.

Changes in bone geometry and microarchitecture caused by intermittent administration of PTH. Comparison with those by exercise load

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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

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Oliveira Juliana Helena Abreu de

2003-01-01

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

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...

Effect of vitamin D, calcium and multiple micronutrients supplementation on lipid profile in pre-menopausal Bangladeshi garment factory workers with hypovitaminosis D.

Science.gov (United States)

Islam, Md Zahirul; Shamim, Abu Ahmed; Akhtaruzzaman, Mohammad; Kärkkäinen, Merja; Lamberg-Allardt, Christel

2014-12-01

Elevated total cholesterol and low-density lipoprotein cholesterol in sera are both well-known risk factors of coronary heart disease. Adequate vitamin D status is important for optimal function of many organs and tissues of our body. There is continuing controversy about the effect of adequate vitamin D consumption on serum lipids and lipoproteins. The present study assessed the effect of vitamin D, calcium and multiple micronutrients supplementation on the lipid profile in Bangladeshi young female garment factory workers who have hypovitaminosis D. This placebo-controlled intervention trial conducted over a period of one year randomly assigned a total of 200 apparently healthy subjects aged 16-36 years to 4 groups. The subjects received daily supplements of 400 IU of vitamin D (VD group) or 400 IU of vitamin D+600 mg of calcium lactate (VD-Ca group), or multiple micronutrients with 400 IU of vitamin-D+600 mg of calcium lactate (MMN-VD-Ca group), or the group consuming placebo (PL group). Serum concentrations of lipid and lipoprotein, 25-hydroxyvitamin D (25OHD) and intact parathyroid hormone (iPTH) were measured at baseline and after one year of follow-up. No significant changes in the serum levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), LDL-C/HDL-C ratio were observed in the supplemented groups compared to the placebo group. Supplementation had a positive effect (pS-iPTH had the greatest increase in HDL-C. The results suggest that consumption of adequate vitamin D with calcium or MMN for one-year may have no impact on serum lipid profile in the subjects studied. Longer-term clinical trials with different doses of supplemental vitamin D are warranted in evaluating the effect of intervention.

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)

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...

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.

Malnutrition and its association with inflammation and vascular disease in children on maintenance dialysis.

Science.gov (United States)

Canpolat, Nur; Caliskan, Salim; Sever, Lale; Tasdemir, Mehmet; Ekmekci, Ozlem Balcı; Pehlivan, Gulseren; Shroff, Rukshana

2013-11-01

Malnutrition is associated with both inflammation and atherosclerotic cardiovascular disease in adults with chronic kidney disease. We studied the prevalence of malnutrition and its possible associations with inflammation and vascular disease in children on chronic dialysis. Thirty-three patients on maintenance dialysis (18 peritoneal dialysis, 15 hemodialysis) and 19 age- and gender- matched healthy controls were studied. Nutritional status was assessed by anthropometric measurements including body mass index (BMI), upper arm measurements, multifrequency bioimpedance analysis (BIA) and serum levels of albumin, prealbumin, and cholesterol. Inflammation was assessed by serum levels of C-reactive protein (CRP), interleukin (IL)-6, and tumor necrosis factor (TNF)-alpha. The carotid artery intima thickness (cIMT) was measured to assess vascular disease. Compared with healthy children, patients had lower anthropometric measurements (P Malnutrition was present in 8 (24%) and lower BIA-based fat mass was independently associated with higher IL-6 levels (P = 0.035). An increased cIMT was present in 16 (48.5%); however, there was no difference in cIMT-SDS between patients with and without malnutrition. Carotid IMT did not show any association with nutritional indices; but positively correlated with serum IL-6 (P = 0.037), CRP (P = 0.012), and iPTH (P = 0.009), and independently associated with only iPTH (P = 0.018). Children on dialysis are at an increased risk of malnutrition, inflammation, and vascular disease. Although each of these three conditions exists, there is no interaction among them all. We postulate that the malnutrition-inflammation-atherosclerosis (MIA) complex might not exist in pediatric dialysis patients.

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

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)

Spontaneous Resolution of Primary Hyperparathyroidism in Parathyroid Adenoma

Directory of Open Access Journals (Sweden)

Sara J. Micale

2012-01-01

Full Text Available A 71 yo woman with primary hyperparathyroidism awaiting surgery because of significant hypercalcemia and hypercalciuria presented to the local emergency department with the chief complaints of discomfort in her neck, sore throat, and difficulty swallowing. She was found to be hypocalcemic with a calcium level of 8.1 mg/dL. She was seen by her endocrinologist three days later at which time serum calcium, iPTH, and serum phosphate levels were all within normal limits. Based on history and a series of ultrasounds the patient was diagnosed with spontaneous infarction of her parathyroid adenoma, which resulted in resolution of her primary hyperparathyroidism.

Treatment of osteoporosis with TheraCyte-encapsulated parathyroid cells: a study in a rat model.

Science.gov (United States)

Chou, F-F; Huang, S-C; Chen, S-S; Wang, P-W; Huang, P-H; Lu, K-Y

2006-01-01

The purpose of this study was to evaluate parathyroid function at monthly intervals following the implantation of TheraCyte-encapsulated live human parathyroid cells into ovariectomized rats and to determine the effect on bone mineral density (BMD) 4 months after ovariectomy ( 3 months after implantation). Parathyroid tissues were obtained from patients undergoing surgery for secondary hyperparathyroidism. In total, 21 Sprague-Dawley rats divided randomly into three groups were subjected to one of three treatments: (1) implanted with TheraCyte A-encapsulated 4x10(6) live parathyroid cells; (2) implanted with TheraCyte B-encapsulated 4x10(5) live parathyroid cells; (3) a sham operation; the control group. Rats were ovariectomized 1 month prior to the implantation of the TheraCyte. Blood was drawn at the time of implantation and at monthly intervals thereafter for 3 months to check the levels of calcium, phosphorus and intact parathyroid hormone (iPTH). The BMD of the lumbar spine (L1-L5) and of the left femoral bone was measured with dual-energy-X-ray absorptiometry (DEXA) 1 month after ovariectomy and 3 months after implantation of the TheraCyte (4 months after ovariectomy). We found that the viability ratio of cryopreserved tissues was between 55 and 79% after thawing. In the control group, the BMD of the lumbar spine (L1-L5) had not decreased significantly (p=0.237) nor had the BMD of the left femoral bone increased significantly (p=0.063) 3 months after implantation. In the TheraCyte A group, the BMD of both the lumbar spine (p=0.018) and left femoral bone (p=0.018) had increased significantly 3 months after implantation. In the TheraCyte B group, the BMD of both the lumbar spine (p=0.017) and the left femoral bone (p=0.025) had also increased significantly 3 months after implantation. Serum iPTH levels were higher in the TheraCyte A group than in the TheraCyte B group (p=0.006), and higher in the TheraCyte B group than in the control group (p=0.040). Serum

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.

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.

Bone metabolism dynamics in the early post-transplant period following kidney and liver transplantation.

Science.gov (United States)

Schreiber, Peter W; Bischoff-Ferrari, Heike A; Boggian, Katia; Bonani, Marco; van Delden, Christian; Enriquez, Natalia; Fehr, Thomas; Garzoni, Christian; Hirsch, Hans H; Hirzel, Cédric; Manuel, Oriol; Meylan, Pascal; Saleh, Lanja; Weisser, Maja; Mueller, Nicolas J

2018-01-01

Bone disease contributes to relevant morbidity after solid organ transplantation. Vitamin D has a crucial role for bone metabolism. Activation of vitamin D depends on the endocrine function of both, liver and kidney. Our study assessed key markers of bone metabolism at time of transplantation and 6 months after transplantation among 70 kidney and 70 liver recipients. In 70 kidney recipients 25-OH vitamin D levels did not differ significantly between peri-transplant (median 32.5nmol/l) and 6 months post-transplant (median 41.9nmol/l; P = 0.272). Six months post-transplant median 1, 25-(OH)2 vitamin D levels increased by >300% (from 9.1 to 36.5ng/l; Ptransplantation and of intact parathyroid hormone 6 months post-transplant. Among 70 liver recipients, 25-OH vitamin D, 1, 25-(OH)2 vitamin D and intact parathyroid hormone levels were not significantly altered between peri-transplant and 6 months post-transplant. Contrary to kidney recipients, median CTx increased by 60.0% (from 0.45 to 0.72 ng/ml; P = 0.002) and P1NP by 49.3% (from 84.0 to 125.4ng/ml; P = 0.001) in the longitudinal course. Assessed biomarkers didn't differ between liver recipients with and without fractures. To conclude, the assessed panel of biomarkers proved highly dynamic after liver as well as kidney transplantation in the early post-transplant period. After kidney transplantation a significant gain in 1, 25-(OH)2 vitamin D combined with a decline in iPTH, CTx and P1NP, whereas after liver transplantation an increase in CTx and P1NP were characteristic.

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.

Effect of alendronate on early bone loss of renal transplant recipients.

Science.gov (United States)

Abediazar, S; Nakhjavani, M R

2011-03-01

Renal transplant recipients (RTRs) are at risk of developing osteoporosis and osteopenia due to underlying renal osteodystrophy, hypophosphatemia, and immunosuppression. This process occurs more frequently in the first year after renal transplantation (RTX), resulting in eventual bone loss and fractures. The purpose of this study was to evaluate the effect of low-dose alendronate to prevent early bone loss after RTX. We prospectively studied 43 successful RTR including 22 men and 21-women with a mean overall age of 39.16±11.73 years, mean body mass index of 23.6±3.73, and mean dialysis duration of 25.73±17.67 months. We matched them based on age and sex: the alendronate-treated group received vitamin D (Vit D) during the study plus 30 mg alendronate weekly from 1 month after RTX. The control group only received Vit D. We measured serum calcium, phosphate, alkaline phosphatase, blood urea, creatinine, and intact parathyroid hormone (iPTH) at the pretransplant baseline and monthly thereafter as well as BMD of the lumbar spine, femur, and radius pretransplant baseline versus 3 and 6 months after RTX. At 6 month after RTX, the lumbar BMD in the alendronate group increased significantly from 0.819±0.11 to 0.863±0.14 (Pbone loss and increase BMD immediately after RTX. Copyright © 2011. Published by Elsevier Inc.

Survival after parathyroidectomy in chronic hemodialysis patients with severe secondary hyperparathyroidism.

Science.gov (United States)

Moldovan, Diana; Racasan, Simona; Kacso, Ina Maria; Rusu, Crina; Potra, Alina; Bondor, Cosmina; Patiu, Ioan Mihai; Gherman-Căprioară, Mirela

2015-11-01

The life for end-stage renal disease patients has remarkably improved in the last years. Although mineral and bone disorders remain as unsolved complication, in severe secondary hyperparathyroidism (sHPT), the ultimate treatment is parathyroidectomy (PTX). It is an old treatment, but there are still insufficient data regarding survival after PTX. The study goals were to compare 2-year mortality and morbidity after PTX in surgically versus medically treated sHPT and to compare the efficacy and safety in subtotal versus total PTX in a cohort of patients receiving hemodialysis (HD). This prospective, longitudinal study was carried out on a cohort of chronic HD patients with severe sHPT (iPTH over 700 pg/ml). Among the overall HD population, 26 patients underwent PTX. This group was compared to a control group treated with specific drugs. Laboratory parameters, specific symptoms and mortality were registered after 24 months of follow-up for each group. The subgroups of subtotal and total PTX patients were also compared. All average values of mineral markers were significantly reduced after PTX, as a proof that surgical treatment was effective. The reduction in mineral markers and the improvement in symptoms and mortality rates were similar after total and subtotal PTX. Bone pain was significantly lower in patients after PTX than in those drug treated (p = 0.0005), but not muscle weakness and itching. Survival at 2 years was better in patients surgically treated (PTX) despite significantly higher mean baseline values of iPTH, Ca and ALP compared to patients medically treated (p = 0.03). We compared clinical and laboratory outcomes in HD patients with severe sHPT. Mortality, bone pain and mineral markers were improved by PTX. Total and subtotal PTX had similar clinical outcomes.

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.

Role of bone photonic densitometry in uremic osteodystrophy

International Nuclear Information System (INIS)

Specchi Bighi, E.; Baldelli, S.; Argalia, G.

1987-01-01

The aim of this investigation is to evaluate the role of bone photonic densitometry in uremic osteodystrophy. Bone mineral contenent (BMC) and bone density (BD) have been measured in 80 hemodialyzed patients by double photonic emission densitometry. Photonic densitometry shows an higher sensibility to quantitative changes in bone mineral contenent than metacarpal index (IM). Photonic densitometry is unable to differentiate osteoporosis from osteomalacia; this differential diagnosis can be obtained by radiological analysis: low BD and low IM means osteoporosis, low BD and resorptive changes in cortical bone means osteomalacia and/or hyperparathyroidism. Photonic densitometry is particulary suitable for uremic osteodystrophy follow-up because of its easy ripetibility and innocuousness and for its close correlation with iPTH variations

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

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

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...

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

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)

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)

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.

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...

Effect of high flux hemodialysis on plasma toxin molecule contents and body’s microinflammatory state in patients with uremia

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Zheng-Nan We

2016-03-01

Full Text Available Objective: To analyze the effect of high flux hemodialysis on plasma toxin molecule contents and body’s microinflammatory state in patients with uremia. Methods: A total of 96 cases of patients with uremia receiving inpatient dialysis in our hospital from June 2011 to March 2015 were selected as research subjects and randomly divided into observation group and control group, each group with 48 cases. Control group received low flux hemodialysis (LF-HD, observation group received high flux hemodialysis (HF-HD, and then levels of plasma renal function-related toxins, oxidative stress-related toxins, leptin, intact parathyroid hormone and asymmetric dimethylarginine as well as levels of microinflammatory state-related factors of two groups were compared. Results: Plasma BUN, Scr, UA and β2-MG levels of observation group after dialysis were significantly lower than those of control group; plasma MDA and Cor levels of observation group after dialysis were lower than those of control group, and levels of GSH and SOD were higher than those of control group; plasma Leptin, iPTH and ADMA levels of observation group after 1 time and 5 times of dialysis were significantly lower than those of control group; plasma hs-CRP, IL-6, TNF-α and ASAA levels of observation group after dialysis were significantly lower than those of control group. Conclusion: High flux hemodialysis for patients with uremia can effectively eliminate related toxins in the body and reduce systemic microinflammatory state, and it has active clinical significance.

Vitamin D supplementation does not improve human skeletal muscle contractile properties in insufficient young males.

Science.gov (United States)

Owens, Daniel J; Webber, Daniel; Impey, Samuel G; Tang, Jonathan; Donovan, Timothy F; Fraser, William D; Morton, James P; Close, Graeme L

2014-06-01

Vitamin D may be a regulator of skeletal muscle function, although human trials investigating this hypothesis are limited to predominantly elderly populations. We aimed to assess the effect of oral vitamin D3 in healthy young males upon skeletal muscle function. Participants (n = 29) received an oral dose of 10,000 IU day(-1) vitamin D3 (VITD) or a visually identical placebo (PLB) for 3 months. Serum 25[OH]D and intact parathyroid hormone (iPTH) were measured at baseline and at week 4, 8 and 12. Muscle function was assessed in n = 22 participants by isokinetic dynamometry and percutaneous isometric electromyostimulation at baseline and at week 6 and 12. Baseline mean total serum 25[OH]D was 40 ± 17 and 41 ± 20 nmol L(-1) for PLB and VITD, respectively. VITD showed a significant improvement in total 25[OH]D at week 4 (150 ± 31 nmol L(-1)) that remained elevated throughout the trial (P L(-1)) compared with baseline. Despite marked increases in total serum 25[OH]D in VITD and a decrease in PLB, there were no significant changes in any of the muscle function outcome measures at week 6 or 12 for either group (P > 0.05). Elevating total serum 25[OH]D to concentrations > 120 nmol L(-1) has no effect on skeletal muscle function. We postulate that skeletal muscle function is only perturbed in conditions of severe deficiency (L(-1)).

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...

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

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

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

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.

Increased rate of osteoporosis, low lean mass, and fragility fractures in COPD patients: association with disease severity.

Science.gov (United States)

Graumam, R Q; Pinheiro, M M; Nery, L E; Castro, C H M

2018-03-21

A very high rate of osteoporosis, fractures, and low lean mass was observed in patients with chronic obstructive pulmonary disease (COPD). Disease severity was associated with bone and muscle adverse outcomes, while age ≥ 63.5 years old, low lean mass, higher iPTH, and a T-score below - 2.5 were all associated with higher risk of fracture. Osteoporosis is frequently neglected in patients with COPD. We aimed at evaluating the rate of osteoporosis, fractures, and low lean mass in patients with COPD. Ninety-nine patients with COPD (53 women, 64.5 ± 9.6 years old, and 46 men, 65.9 ± 8.0 years old) underwent bone densitometry (DXA) with body composition analyses. Healthy individuals (N = 57) not exposed to tobacco matched by sex, age, and body mass index (BMI) were used as controls. Spirometry, routine laboratory workout, and conventional thoracolumbar radiography surveying for vertebral deformities were performed in all patients. Osteoporosis was found in 40.4% of the COPD patients against only 13.0% of the healthy controls (p = 0.001). Vertebral fractures were seen in 24.4% of the men and 22.0% of the women with COPD. Disease severity (GOLD 3 and 4) was significantly associated with higher risk of vitamin D deficiency (p = 0.032), lower BMD (both men and women at all sites), higher frequency of osteoporosis (in women at all sites), lower skeletal mass index, and higher rate of low lean mass (in both men and women) than healthy controls and COPD patients with milder disease (GOLD 1 and 2). Age was a main predictor of vertebral fractures (OR = 1.164 (1.078-9.297); p lean mass were associated with FEV 1% lean mass, high iPTH, and low bone mass were all significantly associated with fractures in COPD patients.

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.

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.

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

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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.

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

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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.

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

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.

Pituitary Gigantism: A Case Report

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Rana Bhattacharjee

2012-01-01

Full Text Available Objective: To present a rare case of gigantism. Case Report: A 25-year-old lady presented with increased statural growth and enlarged body parts noticed since the age of 14 years, primary amenorrhea, and frontal headache for the last 2 years.She has also been suffering from non-inflammatory low back pain with progressive kyphosis and pain in the knees, ankles, and elbows for the last 5 years. There was no history of visual disturbance, vomiting, galactorrhoea, cold intolerance. She had no siblings. Family history was non-contributory.Blood pressure was normal. Height 221 cm, weight 138 kg,body mass index (BMI28. There was coarsening of facial features along with frontal bossing and prognathism, large hands and feet, and small goitre. Patient had severe kyphosis and osteoarthritis of knees. Confrontation perimetry suggested bitemporal hemianopia. Breast and pubic hair were of Tanner stage 1. Serum insulin like growth factor-1 (IGF1 was 703 ng/ml with all glucose suppressedgrowth hormone (GHvalues of >40 ng/ml. Prolactin was 174 ng/ml. Basal serum Lutenising Hormone (LH, follicle stimulating Hormone (FSH was low. Oral glucose tolerance test (OGTT, liver and renal function tests, basal cortisol and thyroid profile, Calcium, phosphorus and Intact Parathyroid hormone (iPTH were normal.Computed tomographyscan of brain showed large pituitary macroadenoma. Automated perimetry confirmed bitemporal hemianopia. A diagnosis of gigantism due to GH secreting pituitary macroadenoma with hypogonadotrophichypogonadism was made. Debulking pituitary surgery followed by somatostatin analogue therapy with gonadal steroid replacement had been planned, but the patient refused further treatment.

Pituitary gigantism: a case report.

Science.gov (United States)

Bhattacharjee, Rana; Roy, Ajitesh; Goswami, Soumik; Selvan, Chitra; Chakraborty, Partha P; Ghosh, Sujoy; Biswas, Dibakar; Dasgupta, Ranen; Mukhopadhyay, Satinath; Chowdhury, Subhankar

2012-12-01

To present a rare case of gigantism. A 25-year-old lady presented with increased statural growth and enlarged body parts noticed since the age of 14 years, primary amenorrhea, and frontal headache for the last 2 years. She has also been suffering from non-inflammatory low back pain with progressive kyphosis and pain in the knees, ankles, and elbows for the last 5 years. There was no history of visual disturbance, vomiting, galactorrhoea, cold intolerance. She had no siblings. Family history was non-contributory. Blood pressure was normal. Height 221 cm, weight 138 kg, body mass index (BMI)28. There was coarsening of facial features along with frontal bossing and prognathism, large hands and feet, and small goitre. Patient had severe kyphosis and osteoarthritis of knees. Confrontation perimetry suggested bitemporal hemianopia. Breast and pubic hair were of Tanner stage 1. Serum insulin like growth factor-1 (IGF1) was 703 ng/ml with all glucose suppressedgrowth hormone (GH)values of >40 ng/ml. Prolactin was 174 ng/ml. Basal serum Lutenising Hormone (LH), follicle stimulating Hormone (FSH) was low. Oral glucose tolerance test (OGTT), liver and renal function tests, basal cortisol and thyroid profile, Calcium, phosphorus and Intact Parathyroid hormone (iPTH) were normal. Computed tomographyscan of brain showed large pituitary macroadenoma. Automated perimetry confirmed bitemporal hemianopia. A diagnosis of gigantism due to GH secreting pituitary macroadenoma with hypogonadotrophichypogonadism was made. Debulking pituitary surgery followed by somatostatin analogue therapy with gonadal steroid replacement had been planned, but the patient refused further treatment.

Low parathyroid hormone levels in bedridden geriatric patients with vitamin D deficiency.

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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.

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

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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 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...

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...

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

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

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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.

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.

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

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Randon R.B.

2005-01-01

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

Effects and safety of calcimimetics in end stage renal disease patients with secondary hyperparathyroidism: a meta-analysis.

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Qian Zhang

Full Text Available PURPOSE: Secondary hyperparathyroidism (SHPT is one of the most common abnormalities of mineral metabolism in patients with chronic kidney disease. We performed a meta-analysis to determine the effect and safety of cinacalcet in SHPT patients receiving dialysis. METHODS: The meta-analysis was performed to determine the effect and safety of cinacalcet in SHPT patients receiving dialysis by using the search terms 'cinacalcet' or 'mimpara' or 'sensipar' or 'calcimimetic' or 'R586' on MEDLINE and EMBASE (January 1990 to February 2012. RESULTS: Fifteen trials were included, all of which were performed between 2000 and 2011 enrolling a total of 3387 dialysis patients. Our study showed that calcimimetic agents effectively ameliorated iPTH levels(WMD, -294.36 pg/mL; 95% CI, -322.76 to -265.95, P<0.001 in SHPT patients and reduced serum calcium (WMD, -0.81 mg/dL; 95% CI, -0.89 to -0.72, P<0.001 and phosphorus disturbances(WMD, -0.29 mg/dL; 95% CI, -0.41 to -0.17, P<0.001. The percentage of patients in whom there was a 30% decrease in serum iPTH levels by the end of the dosing was higher in cinacalcet group than that in control group(OR = 10.75, 95% CI: 6.65-17.37, P<0.001. However, no significant difference was found in all-cause mortality and all adverse events between calcimimetics and control groups(OR = 0.86, 95% CI: 0.46-1.60, P = 0.630; OR = 1.30, 95% CI: 0.78-2.18, P = 0.320, respectively. Compared with the control therapy, there was a significant increase in the episodes of hypocalcemia (OR = 2.46, 95% CI: 1.58-3.82, P<0.001, nausea (OR = 2.45, 95% CI: 1.29-4.66, P = 0.006, vomiting(OR = 2.78, 95% CI: 2.14-3.62, P<0.001, diarrhea(OR = 1.51, 95% CI: 1.04-2.20, P = 0.030 and upper respiratory tract infection (OR = 1.79, 95% CI: 1.20-2.66, P = 0.004in calcimimetics group. CONCLUSIONS: Calcimimetic treatment effectively improved biochemical parameters of SHPT patients receiving dialysis without increasing all-cause mortality and all adverse events.

Vitamin D-binding protein, vitamin D status and serum bioavailable 25(OH)D of young Asian Indian males working in outdoor and indoor environments.

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Goswami, Ravinder; Saha, Soma; Sreenivas, Vishnubhatla; Singh, Namrata; Lakshmy, Ramakrishnan

2017-03-01

Urban Asian Indians generally have low serum 25(OH)D. Information on serum bioavailable 25(OH)D and the effect of prolonged sun-exposure in them is not known. We assessed serum 25(OH)D and bioavailable 25(OH)D in males with varying durations of sun-exposure in Delhi during August-September. Serum 25(OH)D, vitamin D-binding protein (DBP), bioavailable 25(OH)D, free 25(OH)D index, iPTH, ionized calcium and sun-index were assessed in outdoor, mixed outdoor-indoor and indoor workers (n = 88, 32 and 74, respectively). The mean sun-index (12.0 ± 6.25, 4.3 ± 2.20 and 0.7 ± 0.62, respectively; P < 0.001) was highest outdoors and lowest indoors. Serum 25(OH)D (29.0 ± 8.61, 19.1 ± 5.73 and 10.9 ± 4.19 ng/ml, respectively; P < 0.001), bioavailable 25(OH)D and free 25(OH)D index were maximum in outdoor workers followed by mixed-exposure and indoor workers. Their mean serum DBP levels (241.2 ± 88.77, 239.3 ± 83.40 and 216.6 ± 63.93 µg/ml, respectively; P = 0.12) were comparable. Mean serum iPTH was significantly lower in outdoor than indoor workers and showed inverse correlations with serum 25(OH)D, bioavailable 25(OH)D and free 25(OH)D index (r = -0.401, -0.269 and -0.236, respectively; P < 0.001 in all). Daily dietary-calorie intake was higher and calcium lower in outdoor than indoor workers. On regression analysis, sun-exposure was the only significant variable, increasing serum 25(OH)D by 2.03 ng/ml per hour of sun-exposure (95 % confidence interval 1.77-2.28; P < 0.001). Outdoor workers with prolonged sun-exposure were vitamin D-sufficient, with higher serum bioavailable 25(OH)D than the indoor workers during summer. Use of serum DBP levels did not affect the interpretation of their vitamin D status.

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...

A novel complex model of hemodialysis adequacy: Predictive value and relationship with malnutrition inflammation score

Directory of Open Access Journals (Sweden)

Vlatković Vlastimir

2017-01-01

Full Text Available Target dialysis dose to ensure the best patient outcome is still a matter of debate. Traditional models have a number of limitations and do not comprehensively reflect all factors involved. In this study we present a new complex model of dialysis adequacy, the hemodialysis adequacy score (HAS, and evaluate its prognostic value, as well as its relationship with the malnutrition-inflammation score (MIS. The components of HAS included paradigms of the 6 major factors known to influence the outcome of hemodialysis (HD patients: the modified Karnofsky index (KI, the Charlson comorbidity index (CCI, Kt/V and URR measures of dialysis dose, body mass index (BMI and serum albumin level, serum levels of hemoglobin and ferritin, intact parathyroid hormone (iPTH and calciumphosphorus solubility product. The score was evaluated in a 24-month prospective study on 147 HD patients. Odds ratio analysis showed that hospitalized patients had twice the chance to have HAS >13 compared to those who were not hospitalized during the study period (OR=2.152, CI 95% (1.0024- 4.619. Mortality rate was significantly higher in patients with a HAS >13 at the 12-month follow-up (χ2=16.416, p 13 had significantly higher probability of death (log-rank Cox- Mantel=17.920, df=1, p <0.00023. The HAS directly and significantly correlated with the MIS at all measurements (p <0.0001. Results confirmed that the HAS is a useful tool to assess dialysis adequacy with a good prognostic value. The cutoff level for the HAS at 13 points was associated with an unfavorable outcome.

The impact of calcineurin inhibitors on neutrophil gelatinase-associated lipocalin and fibroblast growth factor 23 in long-term kidney transplant patients.

Science.gov (United States)

Bleskestad, Inger Hjørdis; Thorsen, Inga Strand; Jonsson, Grete; Skadberg, Øyvind; Gøransson, Lasse Gunnar

2017-08-01

Neutrophil gelatinase-associated lipocalin (NGAL), a protein with bacteriostatic functions rapidly excreted from stimulated or damaged epithelial cells, is elevated in acute and chronic kidney disease. A calcineurin dependent signaling pathway for fibroblast growth factor 23 (FGF23) has been revealed, but the effect of calcineurin inhibitors (CNIs) on the levels of NGAL and markers of mineral metabolism in long-term kidney transplant patients has not been explored. In a cross-sectional study, 39 patients who received a first kidney transplant more than 10 years ago were split into two groups based on whether (n=28) or not (n=11) they used CNIs. Only patients with well-functioning grafts defined as an estimated glomerular filtration rate ≥45 mL/min per 1.73 m 2 were included. The median levels of NGAL, intact parathyroid hormone (iPTH), and iFGF23 were significantly higher in CNI users vs CNI nonusers, 167.0 (134.0-235.0) ng/mL vs 105.0 (91.3-117.0) ng/mL, P<.001, 13.8 (10.0-17.3) pmol/L vs 8.4 (6.4-9.9) pmol/L, P=.003, and 81.6 (56.4-116.5) pg/mL vs 61.8 (43.3-72.1) pg/mL, P=.04 respectively. The median levels of iFGF23 were higher in CNI users compared to CNI nonusers giving support to the notion of a CNI induced FGF23 resistance in the parathyroid. The net result of CNIs side effects needs to be further explored. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

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...

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.

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.

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...

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

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

Assessing the effect of dietary calcium intake and 25 OHD status on bone turnover in women in Pakistan.

Science.gov (United States)

Khan, Aysha Habib; Naureen, Ghazala; Iqbal, Romaina; Dar, Farhan Javed

2013-01-01

Bone health assessed in three towns of Karachi, Pakistan in females showed poor calcium intake, vitamin D deficiency, secondary hyperparathyroidism, and high bone turnover. Correlates of high bone turnover included females residing in Saddar Town, underweight females less than 30 years of age from low socio-economic status, and secondary hyperparathyroidism. To assess bone health and association of dietary calcium and 25 hydroxy vitamin D with bone turnover in the community-dwelling females of Karachi. Bone health was assessed in three randomly selected towns of Karachi, Pakistan. One premenopausal female fulfilling the inclusion criteria from each household was included in the study. Dietary calcium was assessed through a food frequency questionnaire and biochemical markers including calcium, phosphates, albumin, magnesium, creatinine, and SGPT, intact parathyroid hormone, 25 hydroxy vitamin D, and N-telopeptide of type I collagen were measured to assess the bone health. Three hundred and five females were included from three towns. Overall, 90.5% of females had vitamin D deficiency with 42.6 and 23.3% having secondary hyperparathyroidism and high bone turn over respectively. Prevalence of vitamin D deficiency, secondary hyperparathyroidism, and high bone turnover was significantly different among towns. Mean vitamin D levels were significantly low and iPTH levels significantly high in females with high bone turnover. Calcium intake was not significantly different among females with normal, high, and low bone turnover. Correlates of high bone turnover included females residing in Saddar Town, underweight females less than 30 years of age belonging to low socio-economic status, and secondary hyperparathyroidism. Compromised bone health is seen in community-dwelling females of Karachi. There is a need to perform large-scale community-based studies in all age groups to understand the interplay of markers in our population to understand the impact of these variables

Icodextrine and insulin resistance in continuous ambulatory peritoneal dialysis patients.

Science.gov (United States)

Canbakan, Mustafa; Sahin, Gülizar Manga

2007-01-01

Insulin resistance is commonly observed in uremic patients. Glucose-based peritoneal dialysis solutions have long-term metabolic complications like hyperinsulinemia, hyperlipidemia, and obesity. The purpose of this study was to examine the insulin resistance in patients undergoing continuous ambulatory peritoneal dialysis (CAPD) with standard glucose and icodextrin containing solutions. The entire non diabetic CAPD patients of our center were studied: forty-four patients in all who were on CAPD treatment for 36.2 +/- 23.7 months. Twenty-seven of them (11 male and 16 female) with a mean age of 46 +/- 16 years were treated with standard glucose solutions (glucose group). The other 17 patients (10 male and 7 female) with a mean age of 49 +/- 16 years were treated with standard glucose solutions during the day and icodextrin dwell during the night, for a median of 12 +/- 6.3 months (icodextrin group). Morning fasting serum insulin levels were 20.59 +/- 17.86 in the glucose group and 10.15 +/- 6.87 in the icodextrin group (p = 0.0001). Homeostasis Model Assessment Method scores of the glucose group were significantly higher (4.8+/-4.1 vs 2.3+/- 1.7; p = 0.025) than the icodextrin group. A significant positive correlation of HOMA score with insulin, fasting plasma glucose, and triglyceride levels were found in HOMA (IR+) patients. Twenty patients of the icodextrin group (74%) and 15 patients of the glucose group (88%) were hypertensive, but there was no statistically significant difference between the two groups (p = 0.13). The groups showed no significant differences for body mass index and serum levels of glucose, total cholesterol, LDL cholesterol, VLDL cholesterol, HDL cholesterol, triglyceride, intact parathyroid hormone (iPTH), and fibrinogen. In conclusion, the use of icodextrin in the long nighttime dwell can reduce serum insulin levels and increase insulin sensitivity in CAPD patients.

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 ...

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.

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

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

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.

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

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....

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

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

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

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.

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.

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.

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

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.

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.)

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

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.

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.

Vascular calcification in diabetic foot and its association with calcium homeostasis

Directory of Open Access Journals (Sweden)

Jayshree Swain

2012-01-01

Full Text Available Introduction: Vascular calcification (VC, long thought to result from passive degeneration, involves a complex process of biomineralization resembling osteogenesis, frequently observed in diabetes and is an indicator of diabetic peripheral vascular disease with variable implications. Aim and Objective : To study the association between vascular calcification and calcium homeostasis in diabetic patients with foot ulcers without stage 4, 5 chronic kidney disease. Materials and Methods : A total of 74 patients with diabetic foot ulcer were enrolled, and VC was detected by X-ray and Doppler methods. Serum calcium, phosphate, alkaline phosphatase (ALKP, fasting and post-prandial glucose levels, and glycosylated hemoglobin (HbA1C were recorded. Serum iPTH and 25 (OH vitamin D were estimated by immune radiometric assay and radioimmunoassay, respectively. Data was analyzed by SPSS 16.0. Results: Vascular calcification was present in 42% of patients. Significant difference in the mean (±SD of vitamin D, HbA1C, and eGFR was observed in VC +ve compared to VC -ve. There was no significant association of age, duration, BMI, PTH, Ca, PO4, ALKP with that of VC incidence. Severe vitamin D deficiency was more common in VC +ve (51.6% compared to in VC -ve (18.6%. Sub-group analysis showed that the risk of VC was significantly higher (RR = 2.4, P < 0.05, 95% C.I. = 0.058-2.88 in patients with vitamin D < 10 ng/ml compared to others. Conclusion: Vitamin D deficiency could be a risk for vascular calcification, which possibly act through receptors on vascular smooth muscle cells or modulates osteoprotegerin/RANKL system like other factors responsible for VC in diabetic foot patients.

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

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.

Effect of short-term intravenous ascorbic acid on reducing ferritin in hemodialysis patients.

Science.gov (United States)

Jalalzadeh, M; Shekari, E; Mirzamohammadi, F; Ghadiani, M H

2012-05-01

Resistance to recombinant erythropoietin (rEPO) in hemodialysis patients may be due to inadequate iron recruitment and defect in iron use. In this cross over randomized clinical trial, 30 hemodialysis patients with serum ferritin levels of ≥500 ng/ml, hemoglobin ≤11.0 g/dl, and transferrin saturation (TSAT) of 20% or less were administrated intravenous iron (50-100 mg/wk) and rEPO (120-360 U/kg/wk) for 6 months. Patients were excluded if there was a clear explanation for rEPO hyporesponsiveness. Patients were divided into two groups. Group1 received standard care and 500 mg of intravenous ascorbic acid (IVAA) with each dialysis session in the first week of each month for a total of 3 months. Group 2 received standard care only. After 2 month washout period, groups were crossed over. Each month hemoglobin (Hb) was assessed. Iron, TIBC (transferrin iron binding capacity), TSAT, iPTH (intact parathyroid hormone), liver enzymes, albumin and cholesterol levels were measured every 3 months. After 3 months of intervention, Hb significantly increased from 10.11 to 12.19 g/dl (P <0 0.001; 95% confidence interval [CI] 2.7-1.4) and TSAT increased from 18.9 to 28.1% (P = 0.008; 95% CI 0.09-3), while ferritin and serum iron declined significantly from 1391 to 938 ng/ml (P = 0.001; 95% CI 216-689), 97.2 to 64.6 (P = 0.001; 95% CI 14.8-50.4) in the study group. Change of Hb over time in IVAA group was significant (P < 0.0005). There were significant differences between two groups in change of Hb level over time (P < 0.0005) and treatment effect (P = 0.002). Baseline laboratory tests were similar in the two groups and there was no carry over effect at phase 2. We showed that low amount of IVAA could reduce ferritin level and enhance Hb and TSAT, suggesting improved iron utilization.

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 ...

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.

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...

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

Understanding spoken language is an audiovisual event that depends critically on the ability to discriminate and identify phonemes yet we have little evidence about the role of early auditory experience and visual speech on the development of these fundamental perceptual skills. Objectives of this research were to determine 1) how visual speech influences phoneme discrimination and identification; 2) whether visual speech influences these two processes in a like manner, such that discrimination predicts identification; and 3) how the degree of hearing loss affects this relationship. Such evidence is crucial for developing effective intervention strategies to mitigate the effects of hearing loss on language development. Participants were 58 children with early-onset sensorineural hearing loss (CHL, 53% girls, M = 9;4 yrs) and 58 children with normal hearing (CNH, 53% girls, M = 9;4 yrs). Test items were consonant-vowel (CV) syllables and nonwords with intact visual speech coupled to non-intact auditory speech (excised onsets) as, for example, an intact consonant/rhyme in the visual track (Baa or Baz) coupled to non-intact onset/rhyme in the auditory track (/-B/aa or/-B/az). The items started with an easy-to-speechread/B/or difficult-to-speechread/G/onset and were presented in the auditory (static face) vs. audiovisual (dynamic face) modes. We assessed discrimination for intact vs. non-intact different pairs (e.g., Baa:/-B/aa). We predicted that visual speech would cause the non-intact onset to be perceived as intact and would therefore generate more same-as opposed to different-responses in the audiovisual than auditory mode. We assessed identification by repetition of nonwords with non-intact onsets (e.g.,/-B/az). We predicted that visual speech would cause the non-intact onset to be perceived as intact and would therefore generate more Baz-as opposed to az- responses in the audiovisual than auditory mode. Performance in the audiovisual mode showed more same

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

Objectives Understanding spoken language is an audiovisual event that depends critically on the ability to discriminate and identify phonemes yet we have little evidence about the role of early auditory experience and visual speech on the development of these fundamental perceptual skills. Objectives of this research were to determine 1) how visual speech influences phoneme discrimination and identification; 2) whether visual speech influences these two processes in a like manner, such that discrimination predicts identification; and 3) how the degree of hearing loss affects this relationship. Such evidence is crucial for developing effective intervention strategies to mitigate the effects of hearing loss on language development. Methods Participants were 58 children with early-onset sensorineural hearing loss (CHL, 53% girls, M = 9;4 yrs) and 58 children with normal hearing (CNH, 53% girls, M = 9;4 yrs). Test items were consonant-vowel (CV) syllables and nonwords with intact visual speech coupled to non-intact auditory speech (excised onsets) as, for example, an intact consonant/rhyme in the visual track (Baa or Baz) coupled to non-intact onset/rhyme in the auditory track (/–B/aa or /–B/az). The items started with an easy-to-speechread /B/ or difficult-to-speechread /G/ onset and were presented in the auditory (static face) vs. audiovisual (dynamic face) modes. We assessed discrimination for intact vs. non-intact different pairs (e.g., Baa:/–B/aa). We predicted that visual speech would cause the non-intact onset to be perceived as intact and would therefore generate more same—as opposed to different—responses in the audiovisual than auditory mode. We assessed identification by repetition of nonwords with non-intact onsets (e.g., /–B/az). We predicted that visual speech would cause the non-intact onset to be perceived as intact and would therefore generate more Baz—as opposed to az— responses in the audiovisual than auditory mode. Results

Pakistanis living in Oslo have lower serum 1,25-dihydroxyvitamin D levels but higher serum ionized calcium levels compared with ethnic Norwegians. The Oslo Health Study

Science.gov (United States)

Holvik, Kristin; Meyer, Haakon E; Søgaard, Anne Johanne; Haug, Egil; Falch, Jan A

2007-01-01

Background Persons of Pakistani origin living in Oslo have a much higher prevalence of vitamin D deficiency and secondary hyperparathyroidism but similar bone mineral density compared with ethnic Norwegians. Our objective was to investigate whether Pakistani immigrants living in Oslo have an altered vitamin D metabolism by means of compensatory higher serum levels of 1,25-dihydroxyvitamin D (s-1,25(OH)2D) compared with ethnic Norwegians; and whether serum levels of ionized calcium (s-Ca2+) differ between Pakistanis and Norwegians. Methods In a cross-sectional, population-based study venous serum samples were drawn from 94 Pakistani men and 67 Pakistani women aged 30–60 years, and 290 Norwegian men and 270 Norwegian women aged 45–60 years; in total 721 subjects. Results Pakistanis had lower s-1,25(OH)2D compared with Norwegians (p Oslo with low vitamin D status and secondary hyperparathyroidism have lower s-1,25(OH)2D compared with ethnic Norwegians. However, the Pakistanis have higher s-Ca2+. The cause of the higher s-Ca2+ in Pakistanis in spite of their higher iPTH remains unclear. PMID:17945003

Primary hyperparathyroidism at nishi kobe medical center

International Nuclear Information System (INIS)

Omori, Koichi; Yamashita, Masaru; Kishimoto, Masanao; Tsuji, Tomoko

2002-01-01

Since 1994, there have been 10 cases (1 male, 9 females, 37-72 years old) of primary hyperparathyroidism at our hospital. CT, ultrasonography (US), and MIBI scintigraphy (MIBI) were undertaken for preoperative imaging of the parathyroid tumor. In 9 adenoma cases, accurate localization was obtained in 6 of 9 cases for US, in 8 of 8 cases for CT, and in 9 of 9 cases for MIBI. After the surgery, laboratory data of Ca and i-PTH were in the normal range. Histopathological diagnosis showed 9 adenoma cases and 1 hyperplasia case. Three cases were associated with thyroid diseases. This paper presents two cases with rare clinical symptoms. The chief complaint of the first case was hoarseness. Transient recurrent nerve palsy was observed two times in 2 years. During the surgery, the tumor existed just behind the right recurrent nerve. By histological examination, the tumor was diagnosed as parathyroid adenoma. There has been no recurrent nerve palsy since the surgery. The second case had been treated after diagnosis of deglusion for 3 years in a psychiatry clinic. CT and MIBI showed parathyroid tumor just below the right lobe of the thyroid. After surgery, psychological symptoms were dramatically improved. (author)

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.

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.

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

(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.

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.

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

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.

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)

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

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

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...

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.

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

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...

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

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.

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.

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.

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.

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

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+).

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

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...

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

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’

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.

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.

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

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.

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.

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.

Calcium and Vitamin D Metabolism in Pediatric Nephrotic Syndrome; An Update on the Existing Literature

Directory of Open Access Journals (Sweden)

Mohammad Esmaeeili

2015-03-01

Full Text Available  Minimal Change Disease (MCD is the leading cause of childhood Nephrotic Syndrome (NS. Therefore in pediatrics nephrotic syndrome, most children beyond the first year of life will be treated with corticosteroids without an initial biopsy. Children with NS often display a number of calcium homeostasis disturbances causing abnormal bone histology, including hypocalcemia, reduced serum vitamin D metabolites, impaired intestinal absorption of calcium, and elevated levels of immunoreactive parathyroid hormone (iPTH. These are mainly attributed to the loss of a variety of plasma proteins and minerals in the urine as well as steroid therapy. Early diagnosis and management of these abnormalities, could prevent the growth retardation and renal osteodystrophy that affects children with nephrotic syndrome. Here we reviewed the literature for changes of calcium and vitamin D metabolism in nephrotic syndrome and its consequences on bones, also the effect of corticosteroid and possible preventive strategies that could be done to avoid long term outcomes in children. Although the exact biochemical basis for Changes in levels of calcium and vitamin D metabolites in patients with NS remains speculative; Because of the potential adverse effects of these changes among growing children, widespread screening for vitamin D deficiency or routine vitamin D supplementation should be considered.

Relationship between arterial hypertension and renal damage in chronic kidney disease: insights from ABPM.

Science.gov (United States)

Paoletti, Ernesto; Bellino, Diego; Amidone, Marco; Rolla, Davide; Cannella, Giuseppe

2006-01-01

To date, few studies have used ambulatory pressure monitoring (ABPM) in patients with chronic kidney disease (CKD) before the start of dialysis treatment. The aim of this study was therefore to ascertain the correlates of arterial hypertension assessed by ABPM in CKD patients at their first referral to a nephrologist. We studied 244 (164 men; mean age 63 years) nondiabetic patients with CKD. Each patient had blood pres-sure (BP) measured by 24-hour ABPM, creatinine clearance (CrCl) estimated according to the Cockcroft-Gault formula, and Hgb concentration, serum lipids, iPTH, daily urinary protein (Uprot) and sodium (UNa) excretion assessed using routine methods. According to ABPM data analysis, 81 patients were normotensives, 78 were stable hypertensives, 26 had day-time hypertension and 59 had nocturnal hypertension. ANOVA showed both lower CrCl (p=0.0033), and higher Uprot (p nighttime SBP > 24-hour PP > daytime PP > daytime SBP > 24-hour SBP. In CKD patients, proteinuria is the strongest correlate of arterial hypertension and particularly of increased nocturnal PP, possibly as an expression of vascular damage. On the basis of these results, ABPM appears to be the most reliable tool for detecting the associations between raised BP (particularly nighttime hypertension) and renal damage in CKD patients not yet on renal replacement therapy (RRT).

Renal and cardiovascular morbidities associated with APOL1 among African American and Non-African American children with focal segmental glomerulosclerosis.

Directory of Open Access Journals (Sweden)

Robert P Woroniecki

2016-11-01

Full Text Available Background and objectives: African American (AA children with focal segmental glomerulosclerosis (FSGS have later onset disease that progresses more rapidly than in non-AA children. It is unclear how APOL1 genotypes contribute to kidney disease risk, progression and cardiovascular morbidity in children. Design, setting, participants, & measurements: We examined the prevalence of APOL1 genotypes and associated cardiovascular phenotypes among children with FSGS in the Chronic Kidney Disease in Children (CKiD study; an ongoing multicenter prospective cohort study of children aged 1-16 years with mild to moderate kidney disease.Results: A total of 140 AA children in the CKiD study were genotyped. HR APOL1 genotypes were present in 24% of AA children (33/140 and were associated with FSGS, p 3 mg/L (33% vs. 15%, p=0.12 and obesity (48% vs. 19%, p=0.01. There were no differences in glomerular filtration rate, hemoglobin, iPTH, or calcium-phosphate product. Conclusions: AA children with HR APOL1 genotype and FSGS have increase prevalence of obesity and LVH despite a later age of FSGS onset, while adjusting for socioeconomic status. Treatment of obesity may be an important component of CKD and LVH management in this population.

Cinacalcet versus Parathyroidectomy in the Treatment of Secondary Hyperparathyroidism Post Renal Transplantation.

Science.gov (United States)

Soliman, Amin R; Maamoun, Hoda A; Soliman, Mahmoud A; Darwish, Hatem; Elbanna, Esam

2016-09-01

Persistent hyperparathyroidism (HPT) with hypercalcemia is prevalent after transplant and is considered a risk factor for progressive bone loss and fractures and vascular calcification, as well as the development of tubulointerstitial calcifications of renal allografts and graft dysfunction. The subtotal parathyroidectomy is the standard treatment, although currently it has been replaced by the calcimimetic cinacalcet. The hypothesis of this study is that subtotal parathyroidectomy is superior to cinacalcet for treatment of persistent secondary parathyroidectomy post renal transplant, with minimal morbidity and significantly it reduces the cost of treatment after transplantation. We report our long-term clinical experience with either cinacalcet or parathyroidectomy in 59 kidney transplant recipients with hyperparathyroidism. Group one included medical treatment with cinacalcet and had 45 patients while parathyroidectomy patients (group 2) were 16 patients with two of them excluded because of surgical failure. No difference was found between groups for any parameter. A greater short-term change of calcium and phosphorus homeostasis obtained by surgery than by cinacalcet, and in long term change, no significant difference between the two groups. The main findings of this study are that correction of severe hyperparathyroidism was similar in both surgical and cinacalcet groups with the absence of a difference of long-term serum iPTH 1-84 levels between the two groups.

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...

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.

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…

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.

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…

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...

Risks for Conduct Disorder Symptoms Associated with Parental Alcoholism in Stepfather Families versus Intact Families from a Community Sample

Science.gov (United States)

Foley, Debra L.; Pickles, Andrew; Rutter, Michael; Gardner, Charles O.; Maes, Hermine H.; Silberg, Judy L.; Eaves, Lindon J.

2004-01-01

Background: It is not known if the prevalence of parental psychiatric disorders is higher in stepfather than intact families, or if parental alcoholism is differentially associated with risk for conduct disorder (CD) symptoms in stepfather families versus intact families. Method: The sample comprised 839 girls and 741 boys from 792 intact families…

Behavior Management Style of Single Parents and Intact Families.

Science.gov (United States)

Smith, Douglas K.; And Others

Studies examining the behavior management styles of parents as a function of family intactness and parent employment status are lacking. To assess parental style of behavior management, the Parental Management Questionnaire (PMQ) was completed by 1,957 parents of elementary school children (50% response rate). The PMQ is based on Aronfreed's…

Quantitative proteomic analysis of intact plastids.

Science.gov (United States)

Shiraya, Takeshi; Kaneko, Kentaro; Mitsui, Toshiaki

2014-01-01

Plastids are specialized cell organelles in plant cells that are differentiated into various forms including chloroplasts, chromoplasts, and amyloplasts, and fulfill important functions in maintaining the overall cell metabolism and sensing environmental factors such as sunlight. It is therefore important to grasp the mechanisms of differentiation and functional changes of plastids in order to enhance the understanding of vegetality. In this chapter, details of a method for the extraction of intact plastids that makes analysis possible while maintaining the plastid functions are provided; in addition, a quantitative shotgun method for analyzing the composition and changes in the content of proteins in plastids as a result of environmental impacts is described.

Comparison of allergenicity and immunogenicity of an intact allergen vaccine and commercially available allergoid products for birch pollen immunotherapy.

Science.gov (United States)

Lund, L; Henmar, H; Würtzen, P A; Lund, G; Hjortskov, N; Larsen, J N

2007-04-01

Specific immunotherapy with intact allergen vaccine is a well-documented treatment for allergic diseases. Different vaccine formulations are currently commercially available, the active ingredient either being intact allergens or chemically modified allergoids. The rationale behind allergoids is to decrease allergenicity while maintaining immunogenicity. However, data from the German health authorities based on reporting of adverse events over a 10-year period did not indicate increased safety of allergoids over intact allergens. The objective of this study was to investigate the effect of chemical modification on allergenicity and immunogenicity comparing four commercial allergoid products for birch pollen immunotherapy with an intact allergen vaccine. Solid-phase IgE inhibition and histamine release assays were selected as model systems for allergenicity, and a combination of human T cell proliferation and IgG titres following mouse immunizations were used to address the immunogenicity of the intact allergen vaccine and the four allergoids. In all assays, the products were normalized with respect to the manufacturer's recommended maintenance dose. IgE inhibition experiments showed a change in epitope composition comparing intact allergen vaccine with allergoid. One allergoid product induced enhanced histamine release compared to the intact allergens, while the other three allergoids showed reduced release. Standard T cell stimulation assays using lines from allergic patients showed a reduced response for all allergoids compared with the intact allergen vaccine regardless of the cell type used for antigen presentation. All allergoids showed reduced capacity to induce allergen-specific IgG responses in mice. While some allergoids were associated with reduced allergenicity, a clear reduction in immunogenicity was observed for all allergoid products compared with the intact allergen vaccine, and the commercial allergoids tested therefore do not fulfil the allergoid

Raman spectroscopy of normal oral buccal mucosa tissues: study on intact and incised biopsies

Science.gov (United States)

Deshmukh, Atul; Singh, S. P.; Chaturvedi, Pankaj; Krishna, C. Murali

2011-12-01

Oral squamous cell carcinoma is one of among the top 10 malignancies. Optical spectroscopy, including Raman, is being actively pursued as alternative/adjunct for cancer diagnosis. Earlier studies have demonstrated the feasibility of classifying normal, premalignant, and malignant oral ex vivo tissues. Spectral features showed predominance of lipids and proteins in normal and cancer conditions, respectively, which were attributed to membrane lipids and surface proteins. In view of recent developments in deep tissue Raman spectroscopy, we have recorded Raman spectra from superior and inferior surfaces of 10 normal oral tissues on intact, as well as incised, biopsies after separation of epithelium from connective tissue. Spectral variations and similarities among different groups were explored by unsupervised (principal component analysis) and supervised (linear discriminant analysis, factorial discriminant analysis) methodologies. Clusters of spectra from superior and inferior surfaces of intact tissues show a high overlap; whereas spectra from separated epithelium and connective tissue sections yielded clear clusters, though they also overlap on clusters of intact tissues. Spectra of all four groups of normal tissues gave exclusive clusters when tested against malignant spectra. Thus, this study demonstrates that spectra recorded from the superior surface of an intact tissue may have contributions from deeper layers but has no bearing from the classification of a malignant tissues point of view.

Secretion of intact proteins and peptide fragments by lysosomal pathways of protein degradation

International Nuclear Information System (INIS)

Isenman, L.D.; Dice, J.F.

1989-01-01

We report that degradation of proteins microinjected into human fibroblasts is accompanied by release into the culture medium of peptide fragments and intact proteins as well as single amino acids. For the nine proteins and polypeptides microinjected, acid-precipitable radioactivity, i.e. peptide fragments and/or intact proteins, ranged from 10 to 67% of the total released radioactivity. Peptide fragments and/or intact protein accounted for 60% of the radioactivity released into the medium by cells microinjected with ribonuclease A. Two major radiolabeled peptide fragments were found, and one was of an appropriate size to function as an antigen in antigen-presenting cells. The peptides released from microinjected ribonuclease A were derived from lysosomal pathways of proteolysis based on several lines of evidence. Previous studies have shown that microinjected ribonuclease A is degraded to single amino acids entirely within lysosomes. We show that release of free amino acids and peptide fragments and/or intact protein was equivalently stimulated by serum deprivation and equivalently inhibited by NH4Cl. We also show that lysosomal degradation of endocytosed [3H]ribonuclease A was accompanied by the release of two peptide fragments similar in size and charge to those from microinjected [ 3 H]ribonuclease A. These findings demonstrate that degradation within lysosomes occurs in a manner that spares specific peptides; they also suggest a previously unsuspected pathway by which cells can secrete cytosol-derived polypeptides

Potential effects of omega-3 fatty acids on anemia and inflammatory markers in maintenance hemodialysis patients.

Science.gov (United States)

Gharekhani, Afshin; Khatami, Mohammad-Reza; Dashti-Khavidaki, Simin; Razeghi, Effat; Abdollahi, Alireza; Hashemi-Nazari, Seyed-Saeed; Mansournia, Mohammad-Ali

2014-01-07

Anemia is a common complication among hemodialysis (HD) patients. Although intravenous iron and erythropoiesis-stimulating agents revolutionized anemia treatment, about 10% of HD patients show suboptimal response to these agents. Systemic inflammation and increased serum hepcidin level may contribute to this hyporesponsiveness. Considering the anti-inflammatory properties of omega-3 fatty acids, this study aimed to evaluate potential role of these fatty acids in improving anemia and inflammation of chronic HD patients. In this randomized, placebo-controlled trial, 54 adult patients with HD duration of at least 3 months were randomized to ingest 1800 mg of either omega-3 fatty acids or matching placebo per day for 4 months. Anemia parameters including blood hemoglobin, serum iron, transferrin saturation (TSAT), erythropoietin resistance index, and required dose of intravenous iron and erythropoietin, and serum concentrations of inflammatory/anti-inflammatory markers including interleukin (IL)-6, tumor necrosis factor (TNF)-α, IL-10, C-reactive protein (CRP), hepcidin, ferritin, intact parathyroid hormone (iPTH), and ratios of IL-10 to IL-6 and IL-10 to TNF-α were measured at baseline and after 4 months of the intervention. 45 subjects (25 in the omega-3 and 20 in the placebo group) completed the study. No significant changes were observed in blood hemoglobin, serum iron, TSAT, and required dose of intravenous iron in either within or between group comparisons. Additionally, erythropoietin resistance index as well as required dose of intravenous erythropoietin showed no significant change in the omega-3 group compared to the placebo group. Although a relative alleviation in inflammatory state appeared in the omega-3 group, the mean differences of inflammatory and anti-inflammatory markers between the two groups did not reach statistically significant level except for IL-10-to-IL-6 ratio and serum ferritin level which showed significant changes in favor of omega-3

40 CFR 261.40 - Conditional Exclusion for Used, Intact Cathode Ray Tubes (CRTs) Exported for Recycling.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 25 2010-07-01 2010-07-01 false Conditional Exclusion for Used, Intact Cathode Ray Tubes (CRTs) Exported for Recycling. 261.40 Section 261.40 Protection of Environment...) Exported for Recycling. Used, intact CRTs exported for recycling are not solid wastes if they meet the...

Radioimmunolocalization and selective delivery of radiation in a rat model system: comparison of intact and fragmented antibody

International Nuclear Information System (INIS)

Walker, K.Z.; Seymour-Munn, K.; Axiak, S.M.; Raison, R.L.; Basten, A.; Towson, J.E.; Bautovitch, G.J.; Morris, J.

1988-01-01

Monoclonal antibody (MoAb) fragments are known to have advantages over intact immunoglobulins for radioimmunoscintigraphy. It is less clear whether they are as effective in the delivery of radioimmunotherapy. The imaging and dosimetric properties of an intact MoAb, K-1-21, reactive against human kappa light chains (LC) were compared with that of its F(ab') 2 and Fab fragments using a normal rat model system. Two days after injection of 131 I-K-1-21 into rats bearing antigen-sepharose implants, gamma camera images showed specific localization of the MoAb to the target (kappa LC) but not to the control (lambda LC) implant. Better images were obtained with K-1-21 F(ab') 2 than with Fab or intact antibody. Mean kappa implant: blood ratios were 8.6 ± 3.9 for Fab, 7.9 ± 1.8 for F(ab') 2 and 2.0 ± 0.3 for intact K-1-21. The improvement associated with the use of 131 I-K-1-21 fragments was, however, achieved at the expense of lower absolute values of activity at the target site. Thus the absorbed dose delivered to the implant by the intact K-1-21 was double that delivered with F(ab') 2 and six times that delivered with Fab. As intact K-1-21 also delivered a greater radiation dose to normal tissues, F(ab') 2 fragments may have the greatest overall advantages for therapy with radionuclide MoAb conjugates. (author)

Oxidation of molecular tritium by intact soils

International Nuclear Information System (INIS)

Sweet, C.W.; Murphy, C.E. Jr.

1980-01-01

The effects of environmental factors on the rate of oxidation of molecular tritium (T 2 ) to tritiated water (HTO) were determined for intact soils during field exposures. Maximum deposition velocities of approximately 0.03 cm/sec were measured for T 2 at low wind speeds for a variety of soils over a wide range of conditions. Deposition velocities were slightly inhibited in wet soils and at 0 0 C. In dry soils, oxidation of T 2 to HTO occurred deeper in the soil profile, but deposition velocities were unaffected

Decomposition of intact chicken feathers by a thermophile in combination with an acidulocomposting garbage-treatment process.

Science.gov (United States)

Shigeri, Yasushi; Matsui, Tatsunobu; Watanabe, Kunihiko

2009-11-01

In order to develop a practical method for the decomposition of intact chicken feathers, a moderate thermophile strain, Meiothermus ruber H328, having strong keratinolytic activity, was used in a bio-type garbage-treatment machine working with an acidulocomposting process. The addition of strain H328 cells (15 g) combined with acidulocomposting in the garbage machine resulted in 70% degradation of intact chicken feathers (30 g) within 14 d. This degradation efficiency is comparable to a previous result employing the strain as a single bacterium in flask culture, and it indicates that strain H328 can promote intact feather degradation activity in a garbage machine currently on the market.

Prevalence of depressive symptoms in older nursing home residents with intact cognitive function in Taiwan.

Science.gov (United States)

Hu, Sophia H; Chuang, Yeu-Hui; Ting, Yeh-Feng; Lin, Kuan-Yu; Hsieh, Chia-Jung

2018-03-25

The investigators aimed to explore the prevalence of depressive symptoms and associated factors among older residents with intact cognitive function in nursing homes in Taiwan. A cross-sectional descriptive and correlational research design was used. A convenience sample of 178 older residents without cognitive impairment was recruited from 36 nursing homes in Southern Taiwan. The questionnaires included demographic data; the Barthel Index, which assesses the ability to perform activities of daily living; and the Geriatric Depression Scale Short Form. Among older residents in nursing homes with intact cognitive function, 39.3% had depressive symptoms. Age, religion, previous living status, previous working status, being totally dependent in physical function, and being severely dependent in physical function were significant predictors of depressive symptoms among cognitively intact older residents. The findings highlight the critical mental healthcare issues among older residents with intact cognitive function in nursing homes. Practical strategies for preventing the occurrence of depressive symptoms and caring for those who have depressive symptoms should be developed, especially for younger or dependent older residents or residents who have never been employed, have no religious beliefs, or have lived alone before they moved into an institution. © 2018 Wiley Periodicals, Inc.

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.

46 CFR 173.025 - Additional intact stability standards: Counterballasted vessels.

Science.gov (United States)

2010-10-01

...) SUBDIVISION AND STABILITY SPECIAL RULES PERTAINING TO VESSEL USE Lifting § 173.025 Additional intact stability standards: Counterballasted vessels. (a) Each vessel equipped to counterballast while lifting must be shown... loading and operation and at each combination of hook load and crane radius. (b) When doing the...

In vitro permeation of palladium powders through intact and damaged human skin.

Science.gov (United States)

Crosera, Matteo; Mauro, Marcella; Bovenzi, Massimo; Adami, Gianpiero; Baracchini, Elena; Maina, Giovanni; Larese Filon, Francesca

2018-05-01

The use of palladium (Pd) has grown in the last decades, commonly used in automotive catalytic converters, jewellery and dental restorations sectors. Both general and working population can be exposed to this metal, which may act as skin sensitizer. This study investigated in vitro palladium powders permeation through excised intact and damaged human skin using the Franz diffusion cell method and the effect of rapid skin decontamination using sodium laureth-sulphate. 1 mL of a 10 min sonicated suspension made of 2.5 g of Pd powder in 50 mL synthetic sweat at pH 4.5 and room temperature was applied to the outer surface of the skin membranes for 24 h. Pd permeation, assessed by ICP-MS, was higher when damaged skin was used (p = 0.03). Final flux permeation values and lag times were 0.02 ± 0.01 μg cm -2  h -1 and 6.00 ± 3.95 h for intact, and 0.10 ± 0.02 μg cm -2  h -1 and 2.05 ± 1.49 h for damaged skin samples, respectively. Damaged skin protocol enhances Pd skin penetration inside dermal layer (p = 0.04), thus making the metal available for systemic uptake. Pd penetration (p = 0.02) and permeation (p = 0.012) through intact skin decreased significantly when a cleaning procedure was applied. This study demonstrates that after skin exposure to Pd powders a small permeation of the metal happen both through intact and damaged skin and that an early decontamination with a common cleanser can significantly decrease the final amount of metal available forsystemic uptake. Copyright © 2018 Elsevier B.V. All rights reserved.

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.

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.

IgE epitopes of intact and digested Ara h 1

DEFF Research Database (Denmark)

Bøgh, Katrine Lindholm; Nielsen, H.; Madsen, Charlotte Bernhard

2012-01-01

epitopes have been suggested to be of great importance. ObjectiveThe aim of this study was to identify IgE specific epitopes of intact and digested Ara h 1, and to compare epitope patterns between humans and rats. MethodsSera from five peanut allergic patients and five Brown Norway rats were used...... to identify intact and digested Ara h 1-specific IgE epitopes by competitive immunoscreening of a phage-displayed random hepta-mer peptide library using polyclonal IgE from the individual sera. The resulting peptide sequences were mapped on the surface of a three-dimensional structure of the Ara h 1 molecule...... to mimic epitopes using a computer-based algorithm. ResultsPatients as well as rats were shown to have individual IgE epitope patterns. All epitope mimics were conformational and found to cluster into three different areas of the Ara h 1 molecule. Five epitope motifs were identified by patient IgE, which...

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.

Discrimination between intact and decayed pulp regions in carious teeth by ADC mapping.

Science.gov (United States)

Cankar, Ksenija; Nemeth, Lidija; Bajd, Franci; Vidmar, Jernej; Serša, Igor

2014-01-01

The aim of this study was to evaluate an advanced magnetic resonance imaging (MRI) method, apparent diffusion coefficient (ADC) mapping, in the functional assessment of carious teeth. 38 extracted human teeth with scores of 0, 3 and 6 according to International Caries Detection and Assessment System (ICDAS) criteria were screened and subsequently analyzed by MRI at 2.35 T. Histology sectioning of teeth was used for the gold standard by analyzing two extreme cases (intact and severely decayed). ADC maps of the same teeth were calculated from corresponding diffusion-weighted images and used to obtain ADC distributions along dental pulp as functions of the relative pulp length measured from the occlusal pulp side. The measured distributions were analyzed for the best fit by a four-parameter three-segment linear regression model for ADC distribution along the pulp. MRI results were in good agreement with findings in histological sections of identical teeth. The best fit model parameters, relative decayed region depth, relative transition region width and ADC values of intact and decayed pulp tissue, showed statistically significant differences between the ADC values of intact and decayed pulp tissue (1.0 × 10(-9) m(2)/s vs. 0.74-0.89 × 10(-9) m(2)/s) and the relative decayed region depth progressing with ICDAS score (3 vs. 46% with ICDAS 3 vs. ICDAS 6). The results of this feasibility study confirmed relevance of ADC mapping for the discrimination and localization of intact and decayed regions in dental pulps of carious teeth. © 2014 S. Karger AG, Basel.

Blood epididymal barrier to [3H]-inulin in intact and vasectomized hamsters

International Nuclear Information System (INIS)

Turner, T.T.; D'Addario, D.A.; Howards, S.S.

1981-01-01

The net transport of [ 3 H]-inulin into the fluids of the hamster seminiferous and caput, corpus, and cauda epididymal tubules was examined in both intact animals and those vasectomized 10 months previously. Mean isotope concentrations in reproductive tract tubule fluids did not exceeded 10 per cent of blood plasma isotope concentrations during the experiment. There were no significant differences in net transport of [ 3 H]-inulin into any of the tubule fluids sampled. Ten months after vasectomy, the seminiferous tubule, and all regions of the epididymal tubule retain the capacity to exclude [ 3 H]-insulin. Thus in the hamster 10 months after vasectomy, the blood testis and blood epididymal barriers to inulin are intact

Effects of ignoring baseline on modeling transitions from intact cognition to dementia.

Science.gov (United States)

Yu, Lei; Tyas, Suzanne L; Snowdon, David A; Kryscio, Richard J

2009-07-01

This paper evaluates the effect of ignoring baseline when modeling transitions from intact cognition to dementia with mild cognitive impairment (MCI) and global impairment (GI) as intervening cognitive states. Transitions among states are modeled by a discrete-time Markov chain having three transient (intact cognition, MCI, and GI) and two competing absorbing states (death and dementia). Transition probabilities depend on two covariates, age and the presence/absence of an apolipoprotein E-epsilon4 allele, through a multinomial logistic model with shared random effects. Results are illustrated with an application to the Nun Study, a cohort of 678 participants 75+ years of age at baseline and followed longitudinally with up to ten cognitive assessments per nun.

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

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)

Radiation-induced adaptive response in the intact mouse

International Nuclear Information System (INIS)

Yonezawa, Morio

2009-01-01

The author and coworkers have revealed that radiation adaptive response (AR) is seen also in the bone marrow of the intact mouse, of which details are described here. First, SPF ICR mice were pre-irradiated (PI) with 0-0.1 Gy of X-ray and after 2 months, subsequently irradiated (SI) with 7.75 Gy. Survival rates at 30 days after SI were about 14% in mice with PI 0-0.025 Gy whereas 40% or more in animals with PI 0.05-0.1 Gy: bone marrow death was found significantly suppressed in this effective PI dose range. The death 2 weeks after SI was found also inhibited at PI 0.3-0.5 Gy. Second, PI doses and interval between PI and SI for acquiring the radio-resistance (RR) were studied and third, the PI 0.3-0.5 Gy with SI 8.0 Gy at 9-17 days later revealed that regional PI of the head (central nervous system) was found unnecessary for RR and of abdomen (systems of hemopoiesis, immunity and digestion), essential. Fourth, strain difference of RR was shown by the fact that RR was observed only in C57BL mouse as well, but neither in BALB/c nor C3H strain. Next, at 12 days after SI 4.25-6.75 Gy (PI 0.5 Gy at 14 days before), mouse spleen cells were subjected to colony formation analysis by counting the endogenous hemopoietic stem cells, which revealed that those cells were increased to about 5 times by PI. Suppression of SI-induced hemorrhage was found in mice with PI by the decreased fecal hemoglobin content. Finally, AR was similarly studied in p53 +/+ and its knockout C57BL mice and was not found in the latter animal, indicating the participation of p53 in AR of the intact mouse. Elucidation of AR mechanisms in the intact animal seems to require somewhat different aspect from that in cells. The results were controvertible to the general concept that radiation risk is proportional to cumulative dose, suggesting that low dose radiation differs from high dose one in biological effect. (K.T.)

Transfer Comparison Study Nitrogen on the Intact and Decapitated Legumes by Using the 15N Labeling Technique

International Nuclear Information System (INIS)

Widjayanto, Didik W.

1998-01-01

The experiment was done in order to evaluate the N transfer from the intact and decapitated legumes by using the 15 N labeling technique. Seven days after final labeling the above ground biomass from labeled legume species was removed and the remaining stalks capped to prevent regrowth. Twenty days after final labeling (fourteen days after capping) the all treatments were sample and analyzed. The decapitated legumes appeared to transfer more percentage N than the intact legumes. Although both decapitated and intact legumes transferred, the transfer of N did not incur a dry matter and N yield benefit

Comparison of efficacy of the phosphate binders nicotinic acid and sevelamer hydrochloride in hemodialysis patients

Directory of Open Access Journals (Sweden)

Farrokhlagha Ahmadi

2012-01-01

Full Text Available Hyperphosphatemia is a significant risk factor for the development of ectopic calcification and coronary artery diseases in patients on hemodialysis (HD, and must be controlled with the use of phosphate binders. Studies comparing the effects of sevelamer and nicotinic acid, both similar non-calcium and non-aluminum phosphate binders, are not available. In this study, 40 patients on HD with a serum phosphorus level of more than 6 mg/dL were enrolled. After a two week washout period without phosphate binders, the patients were randomly divided into two equal groups (n = 20 and were started on nicotinic acid or sevelamer for a period of four weeks. The dose of nicotinic acid used was 500 mg and that of sevelamer was 1600 mg daily. Blood samples were drawn for the measurement of the total calcium (Ca, phosphorus (P, alkaline phosphatase (ALP, triglyceride (TG, total cholesterol (Chol, high-density lipoprotein (HDL, low-density lipoprotein (LDL, uric acid and parathyroid hormone (PTH. Patients receiving sevelamer showed a significant reduction in serum P level (2.2 ± 0.69 mg/dL; P <0.0001 in comparison with the nicotinic acid group (1.7 ± 1.06 mg/dL; P = 0.004. Reduction in the Ca-P product was significantly different in the two groups; in the sevelamer group, it was 21 ± 7; (P <0.0001 while in the nicotinic acid group, it was 16 ± 11 (P = 0.007. Also, patients on sevelamer showed greater reduction in the mean TG level (38.9 ± 92 mg/dL; P = 0.005. No significant changes were observed in the mean serum Ca, total Chol, HDL, LDL, ALP and iPTH levels in the two study groups. Our short-term study suggests that although nicotinic acid reduced hyperphosphatemia, sevelamer showed higher efficacy in controlling hyperphosphatemia as well as the Ca-P product.

Bone growth during rapamycin therapy in young rats

Directory of Open Access Journals (Sweden)

He Yu-Zhu

2009-01-01

Full Text Available Abstract Background Rapamycin is an effective immunosuppressant widely used to maintain the renal allograft in pediatric patients. Linear growth may be adversely affected in young children since rapamycin has potent anti-proliferative and anti-angiogenic properties. Methods Weanling three week old rats were given rapamycin at 2.5 mg/kg daily by gavage for 2 or 4 weeks and compared to a Control group given equivalent amount of saline. Morphometric measurements and biochemical determinations for serum calcium, phosphate, iPTH, urea nitrogen, creatinine and insulin-growth factor I (IGF-I were obtained. Histomorphometric analysis of the growth plate cartilage, in-situ hybridization experiments and immunohistochemical studies for various proteins were performed to evaluate for chondrocyte proliferation, chondrocyte differentiation and chondro/osteoclastic resorption. Results At the end of the 2 weeks, body and tibia length measurements were shorter after rapamycin therapy associated with an enlargement of the hypertrophic zone in the growth plate cartilage. There was a decrease in chondrocyte proliferation assessed by histone-4 and mammalian target of rapamycin (mTOR expression. A reduction in parathyroid hormone/parathyroid hormone related peptide (PTH/PTHrP and an increase in Indian hedgehog (Ihh expression may explain in part, the increase number of hypertrophic chondrocytes. The number of TRAP positive multinucleated chondro/osteoclasts declined in the chondro-osseous junction with a decrease in the receptor activator of nuclear factor kappa β ligand (RANKL and vascular endothelial growth factor (VEGF expression. Although body and tibial length remained short after 4 weeks of rapamycin, changes in the expression of chondrocyte proliferation, chondrocyte differentiation and chondro/osteoclastic resorption which were significant after 2 weeks of rapamycin improved at the end of 4 weeks. Conclusion When given to young rats, 2 weeks of rapamycin

In vitro evaluation of percutaneous diffusion of uranyl nitrate through intact or excoriated skin of rat and pig

International Nuclear Information System (INIS)

Petitot, F.; Moreels, A.M.; Paquet, F.

2004-01-01

At the present time, the International Commission on Radiological Protection (ICRP) has not published any model concerning internal radioactive contamination by uptake from wounds. The aims of our work were to determine the time available to treat contamination of intact or wounded skin before a significant uptake of uranium occurred and to evaluate the consequences of incomplete decontamination on uranium uptake. The kinetics of percutaneous diffusion of uranium through intact or excoriated skin and its distribution in skin layers were evaluated using an in vitro technique. Our data demonstrated a dramatic increase of uranium percutaneous diffusion through excoriated skin compared with intact skin. Significant uptake of uranium through excoriated skin occurred in only 30 min, indicating that there is only a short interval available to treat a contaminated wound effectively. Moreover, in the case of an incompletely decontaminated superficial wound, viable epidermis behaved as a reservoir for uranium that remained bioavailable. At the present time, potential uptake of uranium and perhaps other radionuclides through intact or wounded skin is not adequately taken into account by radiological protection agencies. Our results emphasize the need for further study and modeling of uptake of radionuclides through intact or wounded skin. (author)

Influence of fluoride varnish on shear bond strength of a universal adhesive on intact and demineralized enamel.

Science.gov (United States)

Ortiz-Ruiz, Antonio José; Muñoz-Gómez, Iban Jesús; Pérez-Pardo, Ana; Germán-Cecilia, Concepción; Martínez-Beneyto, Yolanda; Vicente, Ascensión

2018-04-27

The aim was to evaluate the effect of fluoride varnish on the shear bond strength (SBS) on polished and non-polished intact and demineralized enamel. Bovine incisors (half demineralized) were used. Bifluorid 12™ was applied. Bonding was made with Futurabond ® M + and GrandioSO, 24 h and 7 days after varnishing. In some groups, varnish was removed by polishing before bonding. SBS was measured. Fracture type was determined by stereomicroscopy and scanning electron microscope (SEM) observations of the enamel surface were made. Between-group differences were determined by one-way ANOVA and the Tukey test. Associations between study factors and fracture modes were analysed using contingency tables and Pearson's chi-squared test. For intact enamel, SBS on varnished enamel at 24 h was significantly less than in the other groups. SBS recovered 7 days after varnishing. Varnish elimination after 24 h significantly increased the SBS. However, removal at 7 days did not modify SBS. SBS on demineralized enamel groups was significantly less than in intact enamel, except for demineralized enamel varnished and removed at 7 days. Demineralized enamel was associated with cohesive enamel fractures and intact enamel with cohesive fractures of the composite and adhesive fractures. SEM of varnish surfaces showed a homogenous layer scattered with amorphous precipitate. In conclusion, on intact enamel fluoride varnish had a negative effect on SBS at 24 h, which disappeared after 7 days. On demineralized enamel, varnish did not reduce SBS at either time. Polishing the varnished enamel surface showed a similar SBS to intact enamel after 7 days.

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.

The effect of self-transcendence on depression in cognitively intact nursing home patients.

Science.gov (United States)

Haugan, Gørill; Innstrand, Siw Tone

2012-01-01

Aims. This study's aim was to test the effects of self-transcendence on depression among cognitively intact nursing home patients. Background. Depression is considered the most frequent mental disorder among the elderly population. Specifically, the depression rate among nursing home patients is three to four times higher than that among community-dwelling elderly. Therefore, finding new and alternative ways to prevent and decrease depression is of great importance for nursing home patients' well-being. Self-transcendence is related to spiritual as well as nonspiritual factors, and it is described as a correlate and resource for well-being among vulnerable populations and at the end of life. Methods. A two-factor construct of the self-transcendence scale (interpersonal and intrapersonal) and the hospital anxiety and depression scale (HADS) was applied. A sample of 202 cognitively intact nursing home patients in central Norway was selected to respond to the questionnaires in 2008/2009. Results. A hypothesized SEM model demonstrated significant direct relationships and total effects of self-transcendence on depression. Conclusion and Implication for Practice. Facilitating patients' self-transcendence, both interpersonally and intrapersonally, might decrease depression among cognitively intact nursing home patients.

Construction of disturbed and intact soil blocks to develop percolating soil based treatment systems for dirty water from dairy farms.

Science.gov (United States)

Brookman, S K E; Chadwick, D R; Headon, D M

2002-03-01

Intact soil blocks with a surface area of 1.8 x 1.6 m, 1.0 m deep, were excavated in a coarse sandy loam. The sides of the soil blocks were supported with plywood before using hydraulic rams to force a steel cutting plate beneath them. Disturbed soil blocks of the same depth as the intact blocks were also established. Experiments were conducted to determine purification efficiencies for biological oxygen demand (BOD), molybdate reactive phosphorus (MRP), nitrate and ammonium-N after the application of dirty water. A preliminary experiment is described where a low application of dirty water was applied to the soil blocks, 2 mm day(-1). In addition, a chloride tracer was conducted for the duration of the experiment. Disturbed soil had a purification efficiency for BOD of 99% compared to 96% from intact soil (Pammonium-N were 100 and 99%, respectively, for the intact and disturbed soils. Nitrate-N concentration increased in leachate from both treatments reaching maximum concentrations of 15 and 8 mg l(-1) from disturbed and intact soils, respectively. Chloride traces for each soil block followed similar patterns with 47 and 51% loss from disturbed and intact soils, respectively.

Feasible pickup from intact ossicular chain with floating piezoelectric microphone.

Science.gov (United States)

Kang, Hou-Yong; Na, Gao; Chi, Fang-Lu; Jin, Kai; Pan, Tie-Zheng; Gao, Zhen

2012-02-22

Many microphones have been developed to meet with the implantable requirement of totally implantable cochlear implant (TICI). However, a biocompatible one without destroying the intactness of the ossicular chain still remains under investigation. Such an implantable floating piezoelectric microphone (FPM) has been manufactured and shows an efficient electroacoustic performance in vitro test at our lab. We examined whether it pick up sensitively from the intact ossicular chain and postulated whether it be an optimal implantable one. Animal controlled experiment: five adult cats (eight ears) were sacrificed as the model to test the electroacoustic performance of the FPM. Three groups were studied: (1) the experiment group (on malleus): the FPM glued onto the handle of the malleus of the intact ossicular chains; (2) negative control group (in vivo): the FPM only hung into the tympanic cavity; (3) positive control group (Hy-M30): a HiFi commercial microphone placed close to the site of the experiment ear. The testing speaker played pure tones orderly ranged from 0.25 to 8.0 kHz. The FPM inside the ear and the HiFi microphone simultaneously picked up acoustic vibration which recorded as .wav files to analyze. The FPM transformed acoustic vibration sensitively and flatly as did the in vitro test across the frequencies above 2.0 kHz, whereas inefficiently below 1.0 kHz for its overloading mass. Although the HiFi microphone presented more efficiently than the FPM did, there was no significant difference at 3.0 kHz and 8.0 kHz. It is feasible to develop such an implantable FPM for future TICIs and TIHAs system on condition that the improvement of Micro Electromechanical System and piezoelectric ceramic material technology would be applied to reduce its weight and minimize its size.

Feasible pickup from intact ossicular chain with floating piezoelectric microphone

Directory of Open Access Journals (Sweden)

Kang Hou-Yong

2012-02-01

Full Text Available Abstract Objectives Many microphones have been developed to meet with the implantable requirement of totally implantable cochlear implant (TICI. However, a biocompatible one without destroying the intactness of the ossicular chain still remains under investigation. Such an implantable floating piezoelectric microphone (FPM has been manufactured and shows an efficient electroacoustic performance in vitro test at our lab. We examined whether it pick up sensitively from the intact ossicular chain and postulated whether it be an optimal implantable one. Methods Animal controlled experiment: five adult cats (eight ears were sacrificed as the model to test the electroacoustic performance of the FPM. Three groups were studied: (1 the experiment group (on malleus: the FPM glued onto the handle of the malleus of the intact ossicular chains; (2 negative control group (in vivo: the FPM only hung into the tympanic cavity; (3 positive control group (Hy-M30: a HiFi commercial microphone placed close to the site of the experiment ear. The testing speaker played pure tones orderly ranged from 0.25 to 8.0 kHz. The FPM inside the ear and the HiFi microphone simultaneously picked up acoustic vibration which recorded as .wav files to analyze. Results The FPM transformed acoustic vibration sensitively and flatly as did the in vitro test across the frequencies above 2.0 kHz, whereas inefficiently below 1.0 kHz for its overloading mass. Although the HiFi microphone presented more efficiently than the FPM did, there was no significant difference at 3.0 kHz and 8.0 kHz. Conclusions It is feasible to develop such an implantable FPM for future TICIs and TIHAs system on condition that the improvement of Micro Electromechanical System and piezoelectric ceramic material technology would be applied to reduce its weight and minimize its size.

The uptake of radioactive iodine in rat intact Graafian follicles

International Nuclear Information System (INIS)

Lieberman, L.M.; Lieberman, G.L.; Lieberman, M.E.

1984-01-01

The concentration of iodine-131 in the ovaries of mammals has important implications in the use of I-131 for the diagnosis and treatment of thyroid disease in women. The authors studied the I-131 uptake in whole ovaries and in isolated Graafian follicles of sexually mature rats. Adult female Sprague-Dawley rats, in groups of 5-6 animals, were injected IP with 10-50 μCi of I-131, at 3, 12, and 24 hrs prior to the day of proestrus and killed on the day of proestrus. The thyroid gland and ovaries were removed intact and these organs, as well as eight other tissue specimens, were weighed. The large preovulatory follicles (6-9/ovary) were then isolated under a dissecting microscope and the remaining ovary weighed. All samples were counted in a gamma well counter and the % dose/g estimated. The thyroid gland showed 23.7% dose/organ at 24 hrs. Blood decreased from 1.6% dose/g at 3 hrs to 0.5% dose/g at 24 hrs with the uterus showing 1.1% dose/g and 0.4% dose/g at the same times. Ovarian tissue was 0.5, 0.1, and 0.1% dose/g at 3,12, and 24 hrs respectively, while the intact Graafian follicles had from one-tenth to one-third the concentration of the ovary at the same times. (0.05, 0.03, and 0.03% dose/g). The authors found that the intact Graafian follicle concentrates approximately one-thirtieth to one-sixteenth of the I-131 in the blood and one-tenth to one-third of the I-131 in the ovary. This suggests that there is no active uptake of I-131 in the follicle or follicular fluid

Calculation of ion currents across the inner membrane of functionally intact mitochondria

Science.gov (United States)

Kane, Daniel A; Pavlov, Evgeny V

2013-01-01

Mitochondrial ion transport systems play a central role in cell physiology. Rates of Ca2+ and K+ transport across the inner mitochondrial membrane have been derived from the measurement of ion accumulation over time within functional isolated mitochondria or mitochondria of cultured cells. Alternatively, the electrical currents generated by ionic flux have been directly measured in purified and swollen mitochondrial samples (mitoplasts) or reconstituted channels, and typically range from 1 pA to several 100s pA. However, the direct electrophysiological approach necessarily requires extensive processing of the mitochondria prior to measurement, which can only be performed on isolated mitoplasts. To compare rates of mitochondrial ion transport measured in electrophysiological experiments to those measured in intact mitochondria and cells, we converted published rates of mitochondrial ion uptake into units of ionic current. We estimate that for monovalent ions, uptake by intact mitochondria at the rate of 1 nmol ∙ mg−1 protein ∙ min−1 is equivalent to 0.2 fA of current per whole single mitochondrion (0.4 fA for divalent ions). In intact mitochondria, estimated rates of electrogenic cation uptake are limited to 1–100 fA of integral current per single mitochondrion. These estimates are orders of magnitude lower than the currents through mitochondrial channels directly measured via patch-clamp or artificial lipid bilayer approaches. PMID:24037064

Transport of beta-aminopropionitrile through intact skin or scar tissue

International Nuclear Information System (INIS)

Gibeault, J.D.; Cravens, R.B. Jr.; Chvapil, M.

1989-01-01

A lathyrogen, [ 14 C]aminopropionitrile (beta APN), was administered to 34 rats either in K-Y jelly or saline vehicles onto intact shaven skin or onto a healed splinted deep excision wound. The dynamics of beta APN transport and content in the skin or repair tissue was observed after 2, 5, 8, and 24 hr of topical administration. The repair tissue quickly absorbed the lathyrogen and reached maximum at the 2-hr sampling. The content of beta APN in the repair tissue was twice as high as that in K-Y jelly vehicle and remained high and stable for at least 24 hr only when beta APN was administered through a saline vehicle. The transport of beta APN through intact skin, irrespective of the vehicle tested, was slow and continuously increased. The study showed that almost 20% of the beta APN administered onto the wounded skin area was transported into the repair tissue within 2 hr. We suggest that, due to the absence of epidermal stratum corneum from the repair tissue, drugs, such as beta APN, penetrate quickly into the wound

Enzymatic methylation of band 3 anion transporter in intact human erythrocytes

International Nuclear Information System (INIS)

Lou, L.L.; Clarke, S.

1987-01-01

Band 3, the anion transport protein of erythrocyte membranes, is a major methyl-accepting substrate of the intracellular erythrocyte protein carboxyl methyltransferase (S-adenosyl-L-methionine: protein-D-aspartate O-methyltransferase; EC 2.1.1.77). The localization of methylation sites in intact cells by analysis of proteolytic fragments indicated that sites were present in the cytoplasmic N-terminal domain as well as the membranous C-terminal portion of the polypeptide. The amino acid residues that serve as carboxyl methylation sites of the erythrocyte anion transporter were also investigated. 3 H-Methylated band 3 was purified from intact erythrocytes incubated with L-[methyl- 3 H]methionine and from trypsinized and lysed erythrocytes incubated with S-adenosyl-L-[methyl- 3 H]methionine. After proteolytic digestion with carboxypeptidase Y, D-aspartic acid beta-[ 3 H]methyl ester was isolated in low yields (9% and 1%, respectively) from each preparation. The bulk of the radioactivity was recovered as [ 3 H]methanol, and the amino acid residue(s) originally associated with these methyl groups could not be determined. No L-aspartic acid beta-[ 3 H]methyl ester or glutamyl gamma-[ 3 H]methyl ester was detected. The formation of D-aspartic acid beta-[ 3 H]methyl esters in this protein in intact cells resulted from protein carboxyl methyltransferase activity since it was inhibited by adenosine and homocysteine thiolactone, which increases the intracellular concentration of the potent product inhibitor S-adenosylhomocysteine, and cycloleucine, which prevents the formation of the substrate S-adenosyl-L-[methyl- 3 H]methionine

Proceedings of the international workshop on mechanistic understanding of radionuclide migration in compacted/intact systems

International Nuclear Information System (INIS)

Tachi, Yukio; Yui, Mikazu

2010-03-01

The international workshop on mechanistic understanding of radionuclide migration in compacted / intact systems was held at ENTRY, JAEA, Tokai on 21st - 23rd January, 2009. This workshop was hosted by Japan Atomic Energy Agency (JAEA) as part of the project on the mechanistic model/database development for radionuclide sorption and diffusion behavior in compacted / intact systems. The overall goal of the project is to develop the mechanistic model / database for a consistent understanding and prediction of migration parameters and its uncertainties for performance assessment of geological disposal of radioactive waste. The objective of the workshop is to integrate the state-of-the-art of mechanistic sorption and diffusion model in compacted / intact systems, especially in bentonite / clay systems, and discuss the JAEA's mechanistic approaches and future challenges, especially the following discussions points; 1) What's the status and difficulties for mechanistic model/database development? 2) What's the status and difficulties for applicability of mechanistic model to the compacted/intact system? 3) What's the status and difficulties for obtaining evidences for mechanistic model? 4) What's the status and difficulties for standardization of experimental methodology for batch sorption and diffusion? 5) What's the uncertainties of transport parameters in radionuclides migration analysis due to a lack of understanding/experimental methodologies, and how do we derive them? This report includes workshop program, overview and materials of each presentation, summary of discussions. (author)

Forest Loss in Protected Areas and Intact Forest Landscapes: A Global Analysis.

Science.gov (United States)

Heino, Matias; Kummu, Matti; Makkonen, Marika; Mulligan, Mark; Verburg, Peter H; Jalava, Mika; Räsänen, Timo A

2015-01-01

In spite of the high importance of forests, global forest loss has remained alarmingly high during the last decades. Forest loss at a global scale has been unveiled with increasingly finer spatial resolution, but the forest extent and loss in protected areas (PAs) and in large intact forest landscapes (IFLs) have not so far been systematically assessed. Moreover, the impact of protection on preserving the IFLs is not well understood. In this study we conducted a consistent assessment of the global forest loss in PAs and IFLs over the period 2000-2012. We used recently published global remote sensing based spatial forest cover change data, being a uniform and consistent dataset over space and time, together with global datasets on PAs' and IFLs' locations. Our analyses revealed that on a global scale 3% of the protected forest, 2.5% of the intact forest, and 1.5% of the protected intact forest were lost during the study period. These forest loss rates are relatively high compared to global total forest loss of 5% for the same time period. The variation in forest losses and in protection effect was large among geographical regions and countries. In some regions the loss in protected forests exceeded 5% (e.g. in Australia and Oceania, and North America) and the relative forest loss was higher inside protected areas than outside those areas (e.g. in Mongolia and parts of Africa, Central Asia, and Europe). At the same time, protection was found to prevent forest loss in several countries (e.g. in South America and Southeast Asia). Globally, high area-weighted forest loss rates of protected and intact forests were associated with high gross domestic product and in the case of protected forests also with high proportions of agricultural land. Our findings reinforce the need for improved understanding of the reasons for the high forest losses in PAs and IFLs and strategies to prevent further losses.

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...

Protein methylation reactions in intact pea chloroplasts

International Nuclear Information System (INIS)

Niemi, K.J.

1989-01-01

Post-translational protein methylation was investigated in Pisum sativum chloroplasts. Intact pea chloroplasts were incubated with ( 3 H-methyl)-S-adenosylmethionine under various conditions. The chloroplasts were then separated into stromal and thylakoid fractions and analyzed for radioactivity transferred to protein. Light enhanced the magnitude of labeling in both fractions. One thylakoid polypeptide with an apparent molecular mass of 43 kDa was labeled only in the light. Several other thylakoid and stromal proteins were labeled in both light and dark-labeling conditions. Both base-labile methylation, carboxy-methylesters and base-stable groups, N-methylations were found. Further characterization of the methyl-transfer reactions will be presented

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.

Microseismic Analysis of Fracture of an Intact Rock Asperity Traversing a Sawcut Fault

Science.gov (United States)

Mclaskey, G.; Lockner, D. A.

2017-12-01

Microseismic events carry information related to stress state, fault geometry, and other subsurface properties, but their relationship to large and potentially damaging earthquakes is not well defined. We conducted laboratory rock mechanics experiments that highlight the interaction between a sawcut fault and an asperity composed of an intact rock "pin". The sample is a 76 mm diameter cylinder of Westerly granite with a 21 mm diameter cylinder (the pin) of intact Westerly granite that crosses the sawcut fault. Upon loading to 80 MPa in a triaxial machine, we first observed a slip event that ruptured the sawcut fault, slipped about 35 mm, but was halted by the rock pin. With continued loading, the rock pin failed in a swarm of thousands of M -7 seismic events similar to the localized microcracking that occurs during the final fracture nucleation phase in an intact rock sample. Once the pin was fractured to a critical point, it permitted complete rupture events on the sawcut fault (stick-slip instabilities). No seismicity was detected on the sawcut fault plane until the pin was sheared. Subsequent slip events were preceded by 10s of foreshocks, all located on the fault plane. We also identified an aseismic zone on the fault plane surrounding the fractured rock pin. A post-mortem analysis of the sample showed a thick gouge layer where the pin intersected the fault, suggesting that this gouge propped open the fault and prevented microseismic events in its vicinity. This experiment is an excellent case study in microseismicity since the events separate neatly into three categories: slip on the sawcut fault, fracture of the intact rock pin, and off-fault seismicity associated with pin-related rock joints. The distinct locations, timing, and focal mechanisms of the different categories of microseismic events allow us to study how their occurrence is related to the mechanics of the deforming rock.

Length of time domestic dogs (Canis familiaris) spend smelling urine of gonadectomised and intact conspecifics.

Science.gov (United States)

Riach, Anna C; Asquith, Rachel; Fallon, Melissa L D

2017-09-01

Domestic dogs (Canis familiaris) use urine to communicate among themselves, however, it is unknown whether the gonadectomy (neutering or spaying) of a dog affects this communication in anyway. Urine samples from 10 intact and 10 gonadectomised, unfamiliar dogs were presented to 12 tester dogs to sniff under controlled conditions in a pilot study. The amount of time the tester dogs spent sniffing each sample was recorded. Overall, tester dogs were recorded smelling the urine of gonadectomised individuals for a longer time. In addition to the type of urine sample, the result is likely to have been influenced by the sex and status (gonadectomised or intact) of the tester dogs. The observed increase in the length of time spent sniffing urine from gonadectomised individuals could be explained by the tester dogs experiencing more difficulty in gaining information from the urine or facing more confusion while analysing the urine compared to the intact urine they have evolved to smell. Copyright © 2017 Elsevier B.V. All rights reserved.

Effect of lowering dietary calcium intake on fractional whole body calcium retention

International Nuclear Information System (INIS)

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

1988-01-01

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

Isolation and Properties of Intact Chromoplasts from Tomato Fruits

OpenAIRE

Norio, Iwatsuki; Ryuichi, Moriyama; Tadashi, Asahi; Laboratory of Biochemistry, Faculty of Agriculture, Nagoya University; Laboratory of Biochemistry, Faculty of Agriculture, Nagoya University; Laboratory of Biochemistry, Faculty of Agriculture, Nagoya University

1984-01-01

Intact chromoplasts were isolated from tomato fruits at different ripening stages by Percoll density gradient centrifugation. The isolated chromoplast fractions were contaminated very little by other organelles, although the fraction from fully ripened fruits contained some mitochondria and microbodies. As the transformation of chloroplasts to chromoplasts proceeded, the density of the plastids decreased from 1.096 to 1.075g・cm^ and the decrease was related to a decrease in chlorophyll and an...

Conductive hearing loss with an intact tympanic membrane due to non-inflammatory causes.

Science.gov (United States)

Choi, Jin Hyuk; Lee, Min Young; Park, Ji Hye; Lee, Kyu-Yup; Lee, Sang Heun; Jang, Jeong Hun

2016-04-01

We analyzed audiologic and surgical findings in patients with conductive hearing loss (CHL) with an intact tympanic membrane (TM) that was of a non-inflammatory origin. We reviewed data from patients who underwent exploratory tympanotomy for CHL with intact TM from January 1995 to November 2012. Patients with diseases of non-inflammatory origin were enrolled (69 patients; 79 ears). Patients were categorized into two groups: non-trauma (50 ears) and trauma (29 ears). Demographic data, intraoperative findings, and audiologic results were obtained and analyzed. Overall, the second decade was the most common age of diagnosis in both the non-trauma and trauma groups. Operative findings showed that ossicular dislocation was more prevalent than ossicular fixation; all trauma group subjects had ossicular dislocation. Short columellization or partial ossicular replacement was the most frequently adopted surgical procedures in both groups. Overall, audiologically, air-conduction thresholds (ACs) and air-bone gaps were significantly improved over the short- and long-term period in both groups. However, the non-trauma group had significantly higher preoperative ACs than the trauma group, especially at low frequencies. This study provides clinicians with useful information regarding the clinical characteristics of CHL with intact TM of non-inflammatory origin. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Insight into the Supramolecular Architecture of Intact Diatom Biosilica from DNP-Supported Solid-State NMR Spectroscopy.

Science.gov (United States)

Jantschke, Anne; Koers, Eline; Mance, Deni; Weingarth, Markus; Brunner, Eike; Baldus, Marc

2015-12-07

Diatom biosilica is an inorganic/organic hybrid with interesting properties. The molecular architecture of the organic material at the atomic and nanometer scale has so far remained unknown, in particular for intact biosilica. A DNP-supported ssNMR approach assisted by microscopy, MS, and MD simulations was applied to study the structural organization of intact biosilica. For the first time, the secondary structure elements of tightly biosilica-associated native proteins in diatom biosilica were characterized in situ. Our data suggest that these proteins are rich in a limited set of amino acids and adopt a mixture of random-coil and β-strand conformations. Furthermore, biosilica-associated long-chain polyamines and carbohydrates were characterized, thereby leading to a model for the supramolecular organization of intact biosilica. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Prototypic and Arkypallidal Neurons in the Dopamine-Intact External Globus Pallidus

Science.gov (United States)

Abdi, Azzedine; Mallet, Nicolas; Mohamed, Foad Y.; Sharott, Andrew; Dodson, Paul D.; Nakamura, Kouichi C.; Suri, Sana; Avery, Sophie V.; Larvin, Joseph T.; Garas, Farid N.; Garas, Shady N.; Vinciati, Federica; Morin, Stéphanie; Bezard, Erwan

2015-01-01

Studies in dopamine-depleted rats indicate that the external globus pallidus (GPe) contains two main types of GABAergic projection cell; so-called “prototypic” and “arkypallidal” neurons. Here, we used correlative anatomical and electrophysiological approaches in rats to determine whether and how this dichotomous organization applies to the dopamine-intact GPe. Prototypic neurons coexpressed the transcription factors Nkx2-1 and Lhx6, comprised approximately two-thirds of all GPe neurons, and were the major GPe cell type innervating the subthalamic nucleus (STN). In contrast, arkypallidal neurons expressed the transcription factor FoxP2, constituted just over one-fourth of GPe neurons, and innervated the striatum but not STN. In anesthetized dopamine-intact rats, molecularly identified prototypic neurons fired at relatively high rates and with high regularity, regardless of brain state (slow-wave activity or spontaneous activation). On average, arkypallidal neurons fired at lower rates and regularities than prototypic neurons, and the two cell types could be further distinguished by the temporal coupling of their firing to ongoing cortical oscillations. Complementing the activity differences observed in vivo, the autonomous firing of identified arkypallidal neurons in vitro was slower and more variable than that of prototypic neurons, which tallied with arkypallidal neurons displaying lower amplitudes of a “persistent” sodium current important for such pacemaking. Arkypallidal neurons also exhibited weaker driven and rebound firing compared with prototypic neurons. In conclusion, our data support the concept that a dichotomous functional organization, as actioned by arkypallidal and prototypic neurons with specialized molecular, structural, and physiological properties, is fundamental to the operations of the dopamine-intact GPe. PMID:25926446

Ingested soluble CD14 from milk is transferred intact into the blood of newborn rats.

Science.gov (United States)

Ward, Tonya L; Spencer, William J; Davis, Laura D R; Harrold, Joann; Mack, David R; Altosaar, Illimar

2014-02-01

Milk acts as an edible immune system that is transferred from mother to newborn. Soluble Cluster of Differentiation 14 (sCD14) is a protein found in significant quantities in human milk (~8-29 µg/ml). At a 10-fold lower concentration in the blood (~3 µg/ml), the most notable role of sCD14 is to sequester lipopolysaccharides of Gram-negative bacteria from immune cells. To explore the pharmacodynamics of this milk protein and its biological fate, the biodistribution of radiolabeled sCD14 ((14)C, (125)I) was monitored in 10-d-old rat pups. Up to 3.4 ± 2.2% of the radiolabeled sCD14 administered was observed, intact, in the pup blood for up to 8 h post-ingestion. Additionally, 30.3 ± 13.0% of the radiolabeled sCD14 administered was observed degraded in the stomach at 8 h post-ingestion. A reservoir of intact, administered sCD14 (3.2 ± 0.3%), however, remained in the stomach at 8 h post-ingestion. Intact sCD14 was observed in the small intestine at 5.5 ± 1.6% of the dose fed at 8 h post-ingestion. The presence of intact sCD14 in the blood and the gastrointestinal tract of newborns post-ingestion has implications in the development of allergies, obesity, and other inflammation-related pathogeneses later in life.

A method to detect transfected chloramphenicol acetyltransferase gene expression in intact animals

International Nuclear Information System (INIS)

Narayanan, R.; Jastreboff, M.M.; Chiu, Chang Fang; Ito, Etsuro; Bertino, J.R.

1988-01-01

A rapid procedure is described for assaying chloramphenicol acetyltransferase enzyme activity in intact animals following transfection of the RSV CAT plasmid into mouse bone marrow cells by electroporation. The reconstituted mice were injected with [ 14 C]chloramphenicol and ethyl acetate extracts of 24-h urine samples were analyzed by TLC autoradiography for the excretion of 14 C-labeled metabolites. CAT expression in vivo can be detected by the presence of acetylated 14 C-labeled metabolites in the urine within 1 week after bone marrow transplantation and, under the conditions described, these metabolites can be detected for at least 3 months. CAT expression in intact mice as monitored by the urine assay correlates with the CAT expression in the hematopoietic tissues assayed in vitro. This method offers a quick mode of screening for introduced CAT gene expression in vivo without sacrificing the mice

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.

Beta Adrenergic Regulation of Intrapulmonary Arteriovenous Anastomoses in Intact Rat and Isolated Rat Lungs

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Melissa L. Bates

2017-04-01

Full Text Available Intrapulmonary arteriovenous anastomoses (IPAVA allow large diameter particles of venous origin to bypass the pulmonary capillary bed and embolize the systemic arterial circulation. IPAVA have been routinely observed in healthy humans with exercise, hypoxia, and catecholamine infusion, but the mechanism by which they are recruited is not well-defined. We hypothesized that beta-adrenergic receptor stimulation recruits IPAVA and that receptor blockade would limit hypoxia-induced IPAVA recruitment. To test our hypothesis, we evaluated the transpulmonary passage of microspheres in intact rats and isolated rats lung infused with the beta-adrenergic receptor agonist isoproterenol. We also evaluated IPAVA recruitment in intact rats with hypoxia and the beta-adrenergic receptor blocker propranolol. We found that IPAVA are recruited in the intact rat by isoproterenol and their recruitment by hypoxia can be minimized by propranolol, suggesting a role for the adrenergic system in the recruitment of IPAVA by hypoxia. IPAVA recruitment is completely abolished by ventilation with 100% oxygen. Isoproterenol also recruits IPAVA in isolated rat lungs. The fact that isoproterenol can recruit IPAVA in isolated lungs, without increased pulmonary flow, suggests that elevated cardiac output is not required for IPAVA recruitment.

Perineal hernia repair using an autologous tunica vaginalis communis in nine intact male dogs.

Science.gov (United States)

Pratummintra, Kittiya; Chuthatep, Suwicha; Banlunara, Wijit; Kalpravidh, Marissak

2013-01-01

Perineal hernia in dogs is very problematic and mostly requires surgical reconstruction of the weak pelvic diaphragm. Tissue or synthetic grafts have been used for the correction after failure of the conventional herniorrhaphy. Aim of this clinical trial was to assess the possible use of the autologous tunica vaginalis communis as a free graft for perineal hernia repair in intact male dogs. Seven unilateral and 2 bilateral perineal hernias in nine intact male dogs free from testicular and scrotal neoplasms were included in this study. The median surgical time for unilateral herniorrhaphy was 75 min. The median follow-up time was 13 months. The success of the autografting, based on no recurrence and comfort of the animals during urination and defecation, was found in ten of 11 hernias; giving a success rate of 90.91%. One hernia (9.09%) recurred 10 days after surgery. Histopathological examination of the apposing area between the graft and the adjacent tissue, taken during the repair of the recurred case at day 20, revealed neovascularization and connective tissue ingrowth. In conclusion, the tunica vaginalis autograft can be used for perineal herniorrhaphy in intact male dogs.

Metabolism of inhaled ethane and pentane by the intact rat

International Nuclear Information System (INIS)

Daugherty, M.S.; Luddent, T.M.; Burk, R.F.

1986-01-01

Measurement of exhaled ethane or pentane is a noninvasive technique for studying in vivo lipid peroxidation. Many past studies have assumed that pentane and ethane are not metabolized. Radiolabeled ( 14 C) ethane and pentane were used to study the disposition of these compounds in intact rats. Rats were placed for 8 h in a closed plexiglass chamber fitted with a system for replenishing chamber atmospheric O 2 . Evolved CO 2 was trapped by recirculating chamber air through 3 N NaOH contained in a vessel external to the chamber. Radiolabeled ethane or pentane was injected into the chamber at the start of each experiment. The percent of 14 C-activity added to the chamber recovered in the CO 2 trap, urine, and chamber air at the end of the experiment (8 h) in the [ 14 C]-ethane (n=5) and [ 14 C]-pentane (n=4) studies are presented. Results indicate that both ethane and pentane are metabolized to CO 2 in the intact rat. Possible changes in ethane and pentane metabolism must be considered if the exhalation rates of these hydrocarbons are to be used as indices of in vivo lipid peroxidation

Allergenicity, immunogenicity and dose-relationship of three intact allergen vaccines and four allergoid vaccines for subcutaneous grass pollen immunotherapy.

Science.gov (United States)

Henmar, H; Lund, G; Lund, L; Petersen, A; Würtzen, P A

2008-09-01

Different vaccines containing intact allergens or chemically modified allergoids as active ingredients are commercially available for specific immunotherapy. Allergoids are claimed to have decreased allergenicity without loss of immunogenicity and this is stated to allow administration of high allergoid doses. We compared the allergenicity and immunogenicity of four commercially available chemically modified grass pollen allergoid products with three commercially available intact grass pollen allergen vaccines. The allergenicity was investigated with immunoglobulin (Ig)E-inhibition and basophil activation assays. Human T cell proliferation and specific IgG-titres following mouse immunizations were used to address immunogenicity. Furthermore, intact allergen vaccines with different contents of active ingredients were selected to study the influence of the allergen dose. In general, a lower allergenicity for allergen vaccines was clearly linked to a reduced immunogenicity. Compared with the vaccine with the highest amount of intact allergen, the allergoids caused reduced basophil activation as well as diminished immunogenicity demonstrated by reduced T cell activation and/or reduced induction of murine grass-specific IgG antibodies. Interestingly, intact allergen vaccines with lower content of active ingredient exhibited similarly reduced allergenicity, while immunogenicity was still higher or equal to that of allergoids. The low allergenicity observed for some allergoids was inherently linked to a significantly lower immunogenic response questioning the rationale behind the chemical modification into allergoids. In addition, the linkage between allergenicity, immunogenicity and dose found for intact allergen vaccines and the immunogen as well as allergenic immune responses observed for allergoids suggest that the modified allergen vaccines do not contain high doses of immunologically active ingredients.

Operative findings of conductive hearing loss with intact tympanic membrane and normal temporal bone computed tomography.

Science.gov (United States)

Kim, Se-Hyung; Cho, Yang-Sun; Kim, Hye Jeong; Kim, Hyung-Jin

2014-06-01

Despite recent technological advances in diagnostic methods including imaging technology, it is often difficult to establish a preoperative diagnosis of conductive hearing loss (CHL) in patients with an intact tympanic membrane (TM). Especially, in patients with a normal temporal bone computed tomography (TBCT), preoperative diagnosis is more difficult. We investigated middle ear disorders encountered in patients with CHL involving an intact TM and normal TBCT. We also analyzed the surgical results with special reference to the pathology. We reviewed the medical records of 365 patients with intact TM, who underwent exploratory tympanotomy for CHL. Fifty nine patients (67 ears, eight bilateral surgeries) had a normal preoperative TBCT findings reported by neuro-radiologists. Demographic data, otologic history, TM findings, preoperative imaging findings, intraoperative findings, and pre- and postoperative audiologic data were obtained and analyzed. Exploration was performed most frequently in the second and fifth decades. The most common postoperative diagnosis was stapedial fixation with non-progressive hearing loss. The most commonly performed hearing-restoring procedure was stapedotomy with piston wire prosthesis insertion. Various types of hearing-restoring procedures during exploration resulted in effective hearing improvement, especially with better outcome in the ossicular chain fixation group. In patients with CHL who have intact TM and normal TBCT, we should consider an exploratory tympanotomy for exact diagnosis and hearing improvement. Information of the common operative findings from this study may help in preoperative counseling.

Human skin penetration of silver nanoparticles through intact and damaged skin

International Nuclear Information System (INIS)

Larese, Francesca Filon; D'Agostin, Flavia; Crosera, Matteo; Adami, Gianpiero; Renzi, Nadia; Bovenzi, Massimo; Maina, Giovanni

2009-01-01

There is a growing interest on nanoparticle safety for topical use. The benefits of nanoparticles have been shown in several scientific fields, but little is known about their potential to penetrate the skin. This study aims at evaluating in vitro skin penetration of silver nanoparticles. Experiments were performed using the Franz diffusion cell method with intact and damaged human skin. Physiological solution was used as receiving phase and 70 μg/cm 2 of silver nanoparticles coated with polyvinylpirrolidone dispersed in synthetic sweat were applied as donor phase to the outer surface of the skin for 24 h. The receptor fluid measurements were performed by electro thermal atomic absorption spectroscopy (ETAAS). Human skin penetration was also determined by using transmission electron microscope (TEM) to verify the location of silver nanoparticles in exposed membranes. Median silver concentrations of 0.46 ng cm -2 (range -2 (range 0.43-11.6) were found in the receiving solutions of cells where the nanoparticles solution was applied on intact skin (eight cells) and on damaged skin (eight cells), respectively. Twenty-four hours silver flux permeation in damaged skin was 0.62 ± 0.2 ng cm -2 with a lag time <1 h. Our experimental data showed that silver nanoparticles absorption through intact and damaged skin was very low but detectable, and that in case of damaged skin it was possible an increasing permeation of silver applied as nanoparticles. Moreover, silver nanoparticles could be detected in the stratum corneum and the outermost surface of the epidermis by electron microscopy. We demonstrated for the first time that silver applied as nanoparticles coated with polyvinylpirrolidone is able to permeate the damaged skin in an in vitro diffusion cell system

Spatially Rearranged Object Parts Can Facilitate Perception of Intact Whole Objects

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Laura eCacciamani

2014-05-01

Full Text Available The familiarity of an object depends on the spatial arrangement of its parts; when the parts are spatially rearranged, they form a novel, unrecognizable configuration. Yet the same collection of parts comprises both the familiar and novel configuration. Is it possible that the collection of familiar parts activates a representation of the intact familiar configuration even when they are spatially rearranged? We presented novel configurations as primes before test displays that assayed effects on figure-ground perception from memories of intact familiar objects. In our test displays, two equal-area regions shared a central border; one region depicted a portion of a familiar object. Previous research with such displays has shown that participants are more likely to perceive the region depicting a familiar object as the figure and the abutting region as its ground when the familiar object is depicted in its upright orientation rather than upside down. The novel primes comprised either the same or a different collection of parts as the familiar object in the test display (part-rearranged and control primes, respectively. We found that participants were more likely to perceive the familiar region as figure in upright vs. inverted displays following part-rearranged primes but not control primes. Thus, priming with a novel configuration comprising the same familiar parts as the upcoming figure-ground display facilitated orientation-dependent effects of object memories on figure assignment. Similar results were obtained when the spatially rearranged collection of parts was suggested on the groundside of the prime’s border, suggesting that familiar parts in novel configurations access the representation of their corresponding intact whole object before figure assignment. These data demonstrate that familiar parts access memories of familiar objects even when they are arranged in a novel configuration.

Spatially rearranged object parts can facilitate perception of intact whole objects.

Science.gov (United States)

Cacciamani, Laura; Ayars, Alisabeth A; Peterson, Mary A

2014-01-01

The familiarity of an object depends on the spatial arrangement of its parts; when the parts are spatially rearranged, they form a novel, unrecognizable configuration. Yet the same collection of parts comprises both the familiar and novel configuration. Is it possible that the collection of familiar parts activates a representation of the intact familiar configuration even when they are spatially rearranged? We presented novel configurations as primes before test displays that assayed effects on figure-ground perception from memories of intact familiar objects. In our test displays, two equal-area regions shared a central border; one region depicted a portion of a familiar object. Previous research with such displays has shown that participants are more likely to perceive the region depicting a familiar object as the figure and the abutting region as its ground when the familiar object is depicted in its upright orientation rather than upside down. The novel primes comprised either the same or a different collection of parts as the familiar object in the test display (part-rearranged and control primes, respectively). We found that participants were more likely to perceive the familiar region as figure in upright vs. inverted displays following part-rearranged primes but not control primes. Thus, priming with a novel configuration comprising the same familiar parts as the upcoming figure-ground display facilitated orientation-dependent effects of object memories on figure assignment. Similar results were obtained when the spatially rearranged collection of parts was suggested on the groundside of the prime's border, suggesting that familiar parts in novel configurations access the representation of their corresponding intact whole object before figure assignment. These data demonstrate that familiar parts access memories of familiar objects even when they are arranged in a novel configuration.

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.

The relationships between self-transcendence and spiritual well-being in cognitively intact nursing home patients.

Science.gov (United States)

Haugan, Gørill; Rannestad, Toril; Hammervold, Randi; Garåsen, Helge; Espnes, Geir A

2014-03-01

Self-transcendence is considered a developmental process of personal maturity and a vital resource of well-being in later adulthood. Measurement of the associations between self-transcendence and spiritual well-being in cognitively intact nursing home patients has not been previously published. The aim of this study was to identify the relationships between self-transcendence and spiritual well-being in cognitively intact nursing home patients. A cross-sectional design using the self-transcendence scale and the FACIT-Sp spiritual well-being questionnaire was adopted. A sample of 202 cognitively intact nursing home patients in mid-Norway was selected to respond to the questionnaires in 2008 and 2009. Statistical analyses were conducted using lisrel 8.8 (Scientific Software International, Chicago, IL, USA) and structural equation modelling. A hypothesised structural equation model comprising a two-factor construct of self-transcendence and a three-factor construct of spiritual well-being demonstrated significant direct relationships between self-transcendence and spiritual well-being and total effects of self-transcendence on spiritual well-being. Facilitating patients' self-transcendence, both interpersonally and intrapersonally, might increase spiritual well-being among cognitively intact nursing home patients, which is seen to be of great importance to nursing home patients' overall satisfaction and satisfaction with staff. The two-factor construct of self-transcendence and the three-factor construct of FACIT-Sp allow a more complex examination of the associations between the constructs and prove more specific guidelines for nursing interventions promoting well-being in nursing home patients. © 2013 Blackwell Publishing Ltd.

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.

The effect of hepatoprotective preparations thioctacid and flavobion on histones in intact and regenerating lever in irradiated rats

International Nuclear Information System (INIS)

Kozhurkova, M.; Kropachova, E.; Mishurova, R.; Reksa, R.

1992-01-01

The changes in concentration, total content of histones and relative proportion of individual histone fractions in intact and regenerating liver were followed in rats after administration of hepatoprotective agents flavobion and thioctacid and after whole-body gamma irradiation with a dose 5.7 Gy. Thioctacid alone caused an increase in histone concentration in intact liver whereas flavobion alone did not produce significant quantitative changes. Irradiation alone decreased markedly the concentration and total content of histones in intact as well as regenerating liver of unprotected rats. Administration of thioctacid or flavobion protected from these quantitative histone changes or alleviated them consideradly. In relative proportion of individual histone fractions, the most profound changes were found in H1 histone after flavobion application

Effects of intraoperative electron irradiation in the dog on cell turnover in intact and surgically-anastomosed aorta and intestine

International Nuclear Information System (INIS)

Sindelar, W.F.; Morrow, B.M.; Travis, E.L.; Tepper, J.; Merkel, A.B.; Kranda, K.; Terrill, R.

1983-01-01

Adults dogs were subjected to laparotomy and intraoperative electron irradiation after division and reanastomosis of aorta or after construction of a blind loop of small intestine having a transverse suture line and an end-to-side anastomosis. Dogs received intraoperative irradiation of both intact and anastomosed aorta or intestine in doses of 0, 2000, 3000, or 4500 rad. Animals were sacrificed at seven days or three months following treatment. At 24 hours prior to sacrifice, dogs received 5 mCi tritiated thymidine intravenously. Irradiated and non-irradiated segments of aorta and small intestine, including intact and anastomotic regions, were analyzed for tritiated thymidine incorporation and were subjected to autoradiography. Incorporation studies showed diminution in tritiated thymidine uptake by irradiated portions of aorta and small intestine, in both intact and anastomotic regions. Autoradiograms revealed that irradiated areas of intact or anastomotic aorta or intestine had diminished labeling of stromal cells, suggesting a lowered cell proliferative capacity of irradiated tissue compared to non-irradiated portions. Inflammatory cells showed similar labeling indices in irradiated and non-irradiated tissues, both intact and surgically-manipulated, suggesting that irradiation does not significantly affect a subsequent local inflammatory response. Radiation-induced decreases in tritiated thymidine incoporation in irradiated aorta and small intestine were generally more marked at seven days than at three months following irradiation, suggesting that radiation-induced depression of cell turnover rates decreases with time

The Fate of Dissolved Creosote Compounds in an Intact Fratured Clay Column

DEFF Research Database (Denmark)

Broholm, Kim; Arvin, Erik; Hansen, Asger

1995-01-01

The fate of 16 different organics typical for creosote was studied under aerobic conditions in a large intact fractured clay column experiment. Some of the organics (benzene, toluene, o-xylene, phenol, and o-cresol) were transported at the same rate as bromide through the fractured clay, whereas ...

Tolerance of a standard intact protein formula versus a partially hydrolyzed formula in healthy, term infants

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Marunycz John D

2009-06-01

Full Text Available Abstract Background Parents who perceive common infant behaviors as formula intolerance-related often switch formulas without consulting a health professional. Up to one-half of formula-fed infants experience a formula change during the first six months of life. Methods The objective of this study was to assess discontinuance due to study physician-assessed formula intolerance in healthy, term infants. Infants (335 were randomized to receive either a standard intact cow milk protein formula (INTACT or a partially hydrolyzed cow milk protein formula (PH in a 60 day non-inferiority trial. Discontinuance due to study physician-assessed formula intolerance was the primary outcome. Secondary outcomes included number of infants who discontinued for any reason, including parent-assessed. Results Formula intolerance between groups (INTACT, 12.3% vs. PH, 13.7% was similar for infants who completed the study or discontinued due to study physician-assessed formula intolerance. Overall study discontinuance based on parent- vs. study physician-assessed intolerance for all infants (14.4 vs.11.1% was significantly different (P = 0.001. Conclusion This study demonstrated no difference in infant tolerance of intact vs. partially hydrolyzed cow milk protein formulas for healthy, term infants over a 60-day feeding trial, suggesting nonstandard partially hydrolyzed formulas are not necessary as a first-choice for healthy infants. Parents frequently perceived infant behavior as formula intolerance, paralleling previous reports of unnecessary formula changes. Trial Registration clinicaltrials.gov: NCT00666120

Clonal expansion of genome-intact HIV-1 in functionally polarized Th1 CD4+ T cells.

Science.gov (United States)

Lee, Guinevere Q; Orlova-Fink, Nina; Einkauf, Kevin; Chowdhury, Fatema Z; Sun, Xiaoming; Harrington, Sean; Kuo, Hsiao-Hsuan; Hua, Stephane; Chen, Hsiao-Rong; Ouyang, Zhengyu; Reddy, Kavidha; Dong, Krista; Ndung'u, Thumbi; Walker, Bruce D; Rosenberg, Eric S; Yu, Xu G; Lichterfeld, Mathias

2017-06-30

HIV-1 causes a chronic, incurable disease due to its persistence in CD4+ T cells that contain replication-competent provirus, but exhibit little or no active viral gene expression and effectively resist combination antiretroviral therapy (cART). These latently infected T cells represent an extremely small proportion of all circulating CD4+ T cells but possess a remarkable long-term stability and typically persist throughout life, for reasons that are not fully understood. Here we performed massive single-genome, near-full-length next-generation sequencing of HIV-1 DNA derived from unfractionated peripheral blood mononuclear cells, ex vivo-isolated CD4+ T cells, and subsets of functionally polarized memory CD4+ T cells. This approach identified multiple sets of independent, near-full-length proviral sequences from cART-treated individuals that were completely identical, consistent with clonal expansion of CD4+ T cells harboring intact HIV-1. Intact, near-full-genome HIV-1 DNA sequences that were derived from such clonally expanded CD4+ T cells constituted 62% of all analyzed genome-intact sequences in memory CD4 T cells, were preferentially observed in Th1-polarized cells, were longitudinally detected over a duration of up to 5 years, and were fully replication- and infection-competent. Together, these data suggest that clonal proliferation of Th1-polarized CD4+ T cells encoding for intact HIV-1 represents a driving force for stabilizing the pool of latently infected CD4+ T cells.

Uptake and clearance of plutonium-238 from intact liver and liver cells transplanted into fat pads of F344/N rats

International Nuclear Information System (INIS)

Brooks, A.L.; Guilmette, R.A.; Hahn, F.F.; Jirtle, R.L.

1985-01-01

An understanding of the role of liver cells and the intact liver in plutonium biokinetics is needed. Liver cells were isolated from rats, injected into fat pads of recipient rats, and allowed 21 days to form cell colonies. Rats then received a single intraperitoneal injection of 1 μCi 238 Pu-citrate and were serially sacrificed. Uptake, retention, and distribution of Pu in intact liver and in liver cells growing in fat pads were determined. Intact liver cells took up about twice as much 238 Pu as liver cells transplanted into fat pads. However, the retention kinetics of Pu were similar for both the liver cells in the fat pads and the intact liver cells when the retention was expressed as activity per cell. 4 references, 1 figure, 1 table

Radionuclide sorption on crushed and intact granitic rock

International Nuclear Information System (INIS)

Eriksen, Tryggve E.; Locklund, Birgitta

1989-05-01

The specific surface areas and distribution ratios for sorption of 85 Sr, 137 Cs and 152 Eu were measured for crushed and intact granite rock. The experimental data can be accommodated by a sorption model encompassing sorption on outer and inner surface. It is clearly demonstrated that the time required to obtain reliable Kd-values for the sorption of strongly sorbing radionuclides like 152 Eu is very long due to solution depletion and slow diffusion into the rock. A combination of surface area measurements and batch sorption with small particles may therefore be preferable when studying strongly sorbing nuclides. (authors) (17 figs., 6 tabs.)

Sediment carbon and nutrient fluxes from cleared and intact temperate mangrove ecosystems and adjacent sandflats.

Science.gov (United States)

Bulmer, Richard H; Schwendenmann, Luitgard; Lohrer, Andrew M; Lundquist, Carolyn J

2017-12-01

The loss of mangrove ecosystems is associated with numerous impacts on coastal and estuarine function, including sediment carbon and nutrient cycling. In this study we compared in situ fluxes of carbon dioxide (CO 2 ) from the sediment to the atmosphere, and fluxes of dissolved inorganic nutrients and oxygen across the sediment-water interface, in intact and cleared mangrove and sandflat ecosystems in a temperate estuary. Measurements were made 20 and 25months after mangrove clearance, in summer and winter, respectively. Sediment CO 2 efflux was over two-fold higher from cleared than intact mangrove ecosystems at 20 and 25months after mangrove clearance. The higher CO 2 efflux from the cleared site was explained by an increase in respiration of dead root material along with sediment disturbance following mangrove clearance. In contrast, sediment CO 2 efflux from the sandflat site was negligible (≤9.13±1.18mmolm -2 d -1 ), associated with lower sediment organic matter content. The fluxes of inorganic nutrients (NH 4 + , NO x and PO 4 3- ) from intact and cleared mangrove sediments were low (≤20.37±18.66μmolm -2 h - 1 ). The highest NH 4 + fluxes were measured at the sandflat site (69.21±13.49μmolm -2 h - 1 ). Lower inorganic nutrient fluxes within the cleared and intact mangrove sites compared to the sandflat site were associated with lower abundance of larger burrowing macrofauna. Further, a higher fraction of organic matter, silt and clay content in mangrove sediments may have limited nutrient exchange. Copyright © 2017 Elsevier B.V. All rights reserved.

Collagen fibril size and crimp morphology in ruptured and intact Achilles tendons

DEFF Research Database (Denmark)

Magnusson, S P; Qvortrup, K; Larsen, Jytte Overgaard

2002-01-01

tendons. Crimp angle did not display any region-specific differences, or any difference between the rupture and intact tendons. In conclusion, these data suggest that although crimp morphology is unchanged there appears to be a site-specific loss of larger fibrils in the core and periphery of the Achilles...

46 CFR 173.020 - Intact stability standards: Counterballasted and non-counterballasted vessels.

Science.gov (United States)

2010-10-01

...) SUBDIVISION AND STABILITY SPECIAL RULES PERTAINING TO VESSEL USE Lifting § 173.020 Intact stability standards... vessel that is not equipped to counter-ballast while lifting must be shown by design calculations to... and crane radius. (b) Each vessel must have a righting arm curve with the following characteristics...

Forest loss in protected areas and intact forest landscapes : A global analysis

NARCIS (Netherlands)

Heino, Matias; Kummu, Matti; Makkonen, Marika; Mulligan, Mark; Verburg, Peter H.; Jalava, Mika; Räsänen, Timo A.

2015-01-01

In spite of the high importance of forests, global forest loss has remained alarmingly high during the last decades. Forest loss at a global scale has been unveiled with increasingly finer spatial resolution, but the forest extent and loss in protected areas (PAs) and in large intact forest

Cutaneous mast cell maturation does not depend on an intact bone marrow microenvironment

International Nuclear Information System (INIS)

Charley, M.R.; Mikhael, A.; Sontheimer, R.D.; Gilliam, J.N.; Bennett, M.

1984-01-01

A study was made to determine whether the maturation of murine cutaneous mast cells from stem cells depends on an intact bone marrow microenvironment. Normal bone marrow cells (+/+) were infused into 2 groups of mast cell-deficient mice: WBB6F1-W/Wv mice and 89 Sr-pretreated W/Wv mice. 89 Sr is a long-lived bone-seeking radioisotope which provides continuous irradiation of the marrow and thereby ablates the marrow microenvironment. Skin biopsies revealed that the 89 Sr-pretreated mice and the controls had repopulated their skin with mast cells equally well. Natural killer cell function was significantly depressed in the 89 Sr-treated mice, confirming that the marrow microenvironment had been functionally altered. It appears that, although the precursors for cutaneous mast cells are marrow derived, they do not need an intact marrow microenvironment for maturation

Carboxyl-terminal parathyroid hormone fragments: role in parathyroid hormone physiopathology.

Science.gov (United States)

D'Amour, Pierre; Brossard, Jean-Hugues

2005-07-01

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

Palladium nanoparticles exposure: Evaluation of permeation through damaged and intact human skin.

Science.gov (United States)

Larese Filon, Francesca; Crosera, Matteo; Mauro, Marcella; Baracchini, Elena; Bovenzi, Massimo; Montini, Tiziano; Fornasiero, Paolo; Adami, Gianpiero

2016-07-01

The intensified use of palladium nanoparticles (PdNPs) in many chemical reactions, jewellery, electronic devices, in car catalytic converters and in biomedical applications lead to a significant increase in palladium exposure. Pd can cause allergic contact dermatitis when in contact with the skin. However, there is still a lack of toxicological data related to nano-structured palladium and information on human cutaneous absorption. In fact, PdNPs, can be absorbed through the skin in higher amounts than bulk Pd because NPs can release more ions. In our study, we evaluated the absorption of PdNPs, with a size of 10.7 ± 2.8 nm, using intact and damaged human skin in Franz cells. 0.60 mg cm(-2) of PdNPs were applied on skin surface for 24 h. Pd concentrations in the receiving solutions at the end of experiments were 0.098 ± 0.067 μg cm(-2) and 1.06 ± 0.44 μg cm(-2) in intact skin and damaged skin, respectively. Pd flux permeation after 24 h was 0.005 ± 0.003 μg cm(-2) h(-1) and 0.057 ± 0.030 μg cm(-2) h(-1) and lag time 4.8 ± 1.7 and 4.2 ± 3.6 h, for intact and damaged skin respectively. This study indicates that Pd can penetrate human skin. Copyright © 2016 Elsevier Ltd. All rights reserved.

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.)

Boron-11 MRI and MRS of intact animals infused with a boron neutron capture agent

International Nuclear Information System (INIS)

Kabalka, G.W.; Davis, M.; Bendel, P.

1988-01-01

Boron neutron capture therapy (BNCT) depends on the delivery of boron-containing drugs to a targeted lesion. Currently, the verification and quantification of in vivo boron content is a difficult problem. Boron-11 spectroscopy was utilized to confirm the presence of a dimeric sulfhydryl dodecaborane BNCT agent contained in an intact animal. Spectroscopy experiments revealed that the decay time of transverse magnetization of the boron-11 spins was less than 1 ms which precluded the use of a 2DFT imaging protocol. A back-projection protocol was developed and utilized to generate the first boron-11 image of a BNCT agent in the liver of an intact Fisher 344 rat

The action of cobra venom phospholipase A2 isoenzymes towards intact human erythrocytes

NARCIS (Netherlands)

Roelofsen, B.; Sibenius Trip, M.; Verheij, H.M.; Zevenbergen, J.L.

1980-01-01

1. 1. Cobra venom phospholipase A2 from three different sources has been fractionated into different isoenzymes by DEAE ion-exchange chromatography. 2. 2. Treatment of intact human erythrocytes with the various isoenzymes revealed significant differences in the degree of phosphatidylcholine

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.

Family relationships and the psychosocial adjustment of school-aged children in intact families

NARCIS (Netherlands)

Hakvoort, E.M.; Bos, H.M.W.; van Balen, F.; Hermanns, J.M.A.

2010-01-01

The authors investigated whether the quality of three family relationships (i.e., marital, parent-child, sibling) in intact families are associated with each other and with children's psychosocial adjustment. Data were collected by means of maternal and child reports (N = 88) using standardized

Intrahippocampal administration of an androgen receptor antagonist, flutamide, can increase anxiety-like behavior in intact and DHT-replaced male rats.

Science.gov (United States)

Edinger, Kassandra L; Frye, Cheryl A

2006-08-01

Testosterone (T) and its 5alpha-reduced metabolite, dihydrotestosterone (DHT), can decrease anxiety-like behavior; however, the mechanisms underlying these effects have not been established. First, we hypothesized that if T reduces anxiety-like behavior through actions of its 5alpha-reduced metabolite, DHT, then gonadectomy (GDX) would increase anxiety-like behavior, an effect which would be reversed by systemic administration of DHT. Second, we hypothesized that if T and DHT reduce anxiety-like behavior in part through actions at intracellular androgen receptors in the hippocampus, then administration of an androgen receptor antagonist, flutamide, directly to the hippocampus should increase anxiety-like behavior of intact and DHT-replaced, but not GDX, male rats. Inserts that were empty or contained flutamide were applied directly to the dorsal hippocampus of intact, GDX, or GDX and DHT-replaced rats 2 h prior to testing in the open field, elevated plus maze, or defensive freezing tasks. GDX rats exhibited significantly more anxiety-like behaviors than intact or DHT-replaced rats. Intact and DHT-replaced rats administered flutamide to the hippocampus showed significantly more anxiety-like behavior than did intact and DHT-replaced controls. However, flutamide alone did not increase anxiety-like behavior of GDX rats. Together, these findings suggest that androgens can decrease anxiety-like behavior of male rats in part through DHT's actions at androgen receptors in the hippocampus.

Intact Four-atom Organic Tetracation Stabilized by Charge Localization in the Gas Phase.

Science.gov (United States)

Yatsuhashi, Tomoyuki; Toyota, Kazuo; Mitsubayashi, Naoya; Kozaki, Masatoshi; Okada, Keiji; Nakashima, Nobuaki

2016-10-05

Several features distinguish intact multiply charged molecular cations (MMCs) from other species such as monocations and polycations: high potential energy, high electron affinity, a high density of electronic states with various spin multiplicities, and charge-dependent reactions. However, repulsive Coulombic interactions make MMCs quite unstable, and hence small organic MMCs are currently not readily available. Herein, we report that the isolated four-atom molecule diiodoacetylene survives after the removal of four electrons via tunneling. We show that the tetracation remains metastable towards dissociation because of the localization (91-95 %) of the positive charges on the terminal iodine atoms, ensuring minimum Coulomb repulsion between adjacent atoms as well as maximum charge-induced attractive dipole interactions between iodine and carbon. Our approach making use of iodines as the positively charged sites enables small organic MMCs to remain intact. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Does intact pleura during internal mammary artery harvesting decreases pleuropulmonary complications

International Nuclear Information System (INIS)

Paracha, V.I.; Iqbal, M.A.; Rashid, A.

2011-01-01

Objective: To evaluate the effects on postoperative pulmonary function of pleural integrity versus opened pleura, in patients who receive a left internal mammary artery graft. Study Design: Randomized control trial. Place and Duration of study: Armed Forces Institute of Cardiology and National Institute of Heart Diseases, Rawalpindi from June 2009 to Feb 2010. Patients and Methods: The study was conducted on 62 patients who underwent elective coronary artery bypass grafting. The patients were divided into 2 groups: Group A consisted of patients who underwent internal mammary artery harvesting with opened pleura (n=31) while Group B consisted of patients having internal mammary artery harvested with intact pleura (n=31). To monitor pleuro-pulmonary complications, chest radiography was performed routinely 1 day before operation and on the second, fourth and sixth postoperative days. The preoperative, after extubation, and first postoperative day values of partial oxygen pressure (PaO/sub 2/), partial carbon dioxide pressure (PaCO/sub 2/), oxygen (O/sub 2/) saturation and haematocrit were recorded for comparison. The effect of intact pleura on IMA traction was also recorded by serial cardiac enzymes measurement and electrocardiography in the immediate postoperative period. Results: Pleural effusion occurred more often in patients of Group A (35.5% versus 12.9%) which was statistically significant (P 0.038). However, no significant differences were recorded in postoperative respiratory complications. Reoperation for postoperative bleeding and tamponade was done in 6.5% and 3.2% of cases in Group B respectively but none Group A; however it was not statistically significant (P 0.076). The mean postoperative hospital stay was 7.84 days for Group A and 7.58 days for Group B. Conclusion: Pleural integrity during IMA harvesting decreases pleural effusion. Although, no significant differences were recorded in postoperative lung complications, intact pleural technique of IMA

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.

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…

Detection of intact megadalton protein assemblies of vanillyl-alcohol oxidase by mass spectrometry

NARCIS (Netherlands)

Berkel, van W.J.H.; Heuvel, van den R.H.H.; Versluis, C.; Heck, A.

2000-01-01

Well-resolved ion signals of intact large protein assemblies, with molecular masses extending above one million Dalton, have been detected and mass analyzed using electrospray ionization mass spectrometry, with an uncertainty in mass of <0.2&Eth;The mass spectral data seem to reflect known

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.

A new infusion pathway intactness monitoring system.

Science.gov (United States)

Ogawa, Hidekuni; Yonezawa, Yoshiharu; Maki, Hiromichi; Ninomiya, Ishio; Sata, Koji; Hamada, Shingo; Caldwell, W Morton

2006-01-01

A new infusion pathway monitoring system has been developed for hospital and home use. The system consists of linear integrated circuits and a low-power 8-bit single chip microcomputer which constantly monitors the infusion pathway intactness. An AC (alternating current) voltage is induced on the patient's body by electrostatic coupling from the normal 100 volt, 60 Hz AC power line wiring field in the patient's room. The induced AC voltage can be recorded by a main electrode wrapped around the infusion polyvinyl chloride tube. A reference electrode is wrapped on the electrode to monitor the AC voltage around the main electrode. If the injection needle or infusion tube becomes detached, then the system detects changes in the induced AC voltages and alerts the nursing station, via the nurse call system or PHS (personal handy phone system).

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.

Differential isotope dansylation labeling combined with liquid chromatography mass spectrometry for quantification of intact and N-terminal truncated proteins

International Nuclear Information System (INIS)

Tang, Yanan; Li, Liang

2013-01-01

Graphical abstract: -- Highlights: •LC–MS was developed for quantifying protein mixtures containing both intact and N-terminal truncated proteins. • 12 C 2 -Dansylation of the N-terminal amino acid of proteins was done first, followed by microwave-assisted acid hydrolysis. •The released 12 C 2 -dansyl labeled N-terminal amino acid was quantified using 13 C 2 -dansyl labeled amino acid standards. •The method provided accurate and precise results for quantifying intact and N-terminal truncated proteins within 8 h. -- Abstract: The N-terminal amino acids of proteins are important structure units for maintaining the biological function, localization, and interaction networks of proteins. Under different biological conditions, one or several N-terminal amino acids could be cleaved from an intact protein due to processes, such as proteolysis, resulting in the change of protein properties. Thus, the ability to quantify the N-terminal truncated forms of proteins is of great importance, particularly in the area of development and production of protein-based drugs where the relative quantity of the intact protein and its truncated form needs to be monitored. In this work, we describe a rapid method for absolute quantification of protein mixtures containing intact and N-terminal truncated proteins. This method is based on dansylation labeling of the N-terminal amino acids of proteins, followed by microwave-assisted acid hydrolysis of the proteins into amino acids. It is shown that dansyl labeled amino acids are stable in acidic conditions and can be quantified by liquid chromatography mass spectrometry (LC–MS) with the use of isotope analog standards

Aboveground biomass variability across intact and degraded forests in the Brazilian Amazon

Science.gov (United States)

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

2016-01-01

Deforestation rates have declined in the Brazilian Amazon since 2005, yet degradation from logging, fire, 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)...

2-Methoxyestradiol Reduces Angiotensin II-Induced Hypertension and Renal Dysfunction in Ovariectomized Female and Intact Male Mice.

Science.gov (United States)

Pingili, Ajeeth K; Davidge, Karen N; Thirunavukkarasu, Shyamala; Khan, Nayaab S; Katsurada, Akemi; Majid, Dewan S A; Gonzalez, Frank J; Navar, L Gabriel; Malik, Kafait U

2017-06-01

Cytochrome P450 1B1 protects against angiotensin II (Ang II)-induced hypertension and associated cardiovascular changes in female mice, most likely via production of 2-methoxyestradiol. This study was conducted to determine whether 2-methoxyestradiol ameliorates Ang II-induced hypertension, renal dysfunction, and end-organ damage in intact Cyp1b1 -/- , ovariectomized female, and Cyp1b1 +/+ male mice. Ang II or vehicle was infused for 2 weeks and administered concurrently with 2-methoxyestradiol. Mice were placed in metabolic cages on day 12 of Ang II infusion for urine collection for 24 hours. 2-Methoxyestradiol reduced Ang II-induced increases in systolic blood pressure, water consumption, urine output, and proteinuria in intact female Cyp1b1 -/- and ovariectomized mice. 2-Methoxyestradiol also reduced Ang II-induced increase in blood pressure, water intake, urine output, and proteinuria in Cyp1b1 +/+ male mice. Treatment with 2-methoxyestradiol attenuated Ang II-induced end-organ damage in intact Cyp1b1 -/- and ovariectomized Cyp1b1 +/+ and Cyp1b1 -/- female mice and Cyp1b1 +/+ male mice. 2-Methoxyestradiol mitigated Ang II-induced increase in urinary excretion of angiotensinogen in intact Cyp1b1 -/- and ovariectomized Cyp1b1 +/+ and Cyp1b1 -/- female mice but not in Cyp1b1 +/+ male mice. The G protein-coupled estrogen receptor 1 antagonist G-15 failed to alter Ang II-induced increases in blood pressure and renal function in Cyp1b1 +/+ female mice. These data suggest that 2-methoxyestradiol reduces Ang II-induced hypertension and associated end-organ damage in intact Cyp1b1 -/- , ovariectomized Cyp1b1 +/+ and Cyp1b1 -/- female mice, and Cyp1b1 +/+ male mice independent of G protein-coupled estrogen receptor 1. Therefore, 2-methoxyestradiol could serve as a therapeutic agent for treating hypertension and associated pathogenesis in postmenopausal females, and in males. © 2017 American Heart Association, Inc.

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.

Potential clinical usefulness of new glandular and circulating parathyroid peptides illuminated by sequence specific radioimmunoassay

International Nuclear Information System (INIS)

Lindall, A.W.; Cecchettin, M.

1981-01-01

It is now well known that human PTH peptides constitute a heterogeneous population of fragments of the eighty-four amino acid molecules. Over the years, considerable confusion has resulted from measurements made in both clinical and experimental settings with radioimmunoassays of either undefined or partially-defined specificity for a particular region of the intact molecule. The approach of the authors has been to make use of modern technology to synthesize peptide fragments that mimic portions of native molecules, and to use these fragments in RIA. A more detailed description of a portion of this work will appear in the Journal of Clinical Endocrinology and Metabolism. (Auth.)

Double Outlet Right Ventricle With Intact Ventricular Septum: Avulsion or Exclusion.

Science.gov (United States)

Menon, Sabarinath; Kumar, C J Ashok; Mathew, Thomas; Venkateshwarn, S; Jayakumar, K; Dharan, Baiju S

2016-03-01

Double outlet right ventricle (DORV) is almost always associated with a ventricular septal defect. The variant of DORV with intact ventricular septum is very uncommon and may be associated with fetal demise or death immediately after birth. Reports of successful palliation of these patients to the stage of superior cavopulmonary anastomosis (bidirectional Glenn shunt) are rare. We describe the case of a child with DORV with intact ventricular septum who underwent successful palliation. This condition often provides a diagnostic, interventional, and surgical challenge. Patients generally require either balloon atrial septostomy or surgical atrial septectomy for survival, with the addition of a Blalock-Tausig shunt or pulmonary artery band depending on the pulmonary blood flow. Very few patients survive to a Glenn procedure. For those who do survive, a decision must be made regarding the management of the hypertensive and hypoplastic left ventricle (LV) and associated mitral regurgitation. The LV can be excluded by either mitral valve avulsion or closure (exclusion) of the mitral valve with a patch. The choice of the technique should be carefully made and depends in part on the size of the LV. In our patient, who was successfully palliated by bidirectional Glenn shunt, the LV was managed by means of mitral valve avulsion. © The Author(s) 2015.

Assessment of characteristic failure envelopes for intact rock using results from triaxial tests

OpenAIRE

Muralha, J.; Lamas, L.

2014-01-01

The paper presents contributions to the statistical study of the parameters of the Mohr-Coulomb and Hoek-Brown strength criteria, in order to assess the characteristic failure envelopes for intact rock, based on the results of several sets of triaxial tests performed by LNEC. 10p DBB/NMMR

Importance of an intact dura in management of compound elevated fractures; a short series and literature review.

Science.gov (United States)

Mohindra, Sandeep; Singh, Harnarayan; Savardekar, Amey

2012-01-01

To describe compound elevated fractures (CEFs) of the skull vault, with radiological pictures, management problems and prognosticative factors. The authors describe three cases of CEFs of the cranium, their mode of injury, clinical findings, radiological images and management problems. The authors have reviewed the existing literature regarding epidemiological data, neurological status, dural breech, methods of management and final outcome, in respect of CEFs. The first case had no dural breech, the second case had completely shattered dura, with extruding brain matter from the wound, while the third case had an elevated bone flap in consequence to large extradural haematoma. The patients with intact dura had relatively favourable outcome, when compared to patients with shattered dura. Three cases are added to the existing 10 such cases described in English literature. The major cause of unfavourable outcome remains sepsis and the presence of intact dura places these cases in the relatively safe category, regarding infective complications. The authors attempt at highlighting the importance of intact dura with such an injury. The review of literature supports favourable outcomes in patients having no dural breech.

Transport of indoleacetic acid in intact corn coleoptiles

International Nuclear Information System (INIS)

Parker, K.E.; Briggs, W.R.

1990-01-01

We have characterized the transport of [ 3 H]indoleacetic acid (IAA) in intact corn (Zea mays L.) coleoptiles. We have used a wide range of concentrations of added IAA (28 femtomoles to 100 picomoles taken up over 60 minutes). The shape of the transport curve varies with the concentration of added IAA, although the rate of movement of the observed front of tracer is invariant with concentration. At the lowest concentration of tracer used, the labeled IAA in the transport stream is not detectably metabolized or immobilized, curvature does not develop as a result of tracer application, and normal phototropic and gravitropic responsiveness are not affected. Therefore we believe we are observing the transport of true tracer quantities of labeled auxin at this lowest concentration

Effects of reactive Mn(III)-oxalate complexes on structurally intact plant cell walls

Science.gov (United States)

Summering, J. A.; Keiluweit, M.; Goni, M. A.; Nico, P. S.; Kleber, M.

2011-12-01

Lignin components in the in plant litter are commonly assumed to have longer residence times in soil than many other compounds, which are supposedly, more easily degradable. The supposed resistance of lignin compounds to decomposition is generally attributed to the complex chain of biochemical steps required to create footholds in the non-porous structure of ligno-cellulose in cell walls. Interestingly, Mn(III) complexes have shown the ability to degrade ligno-cellulose. Mn(III) chelated by ligands such as oxalate are soluble oxidizers with a high affinity for lignin structures. Here we determined (i) the formation and decay kinetics of the Mn(III)-oxalate complexes in aqueous solution and (ii) the effects that these complexes have on intact ligno-cellulose. UV/vis spectroscopy and iodometric titrations confirmed the transient nature of Mn(III)-oxalate complexes with decay rates being in the order of hours. Zinnia elegans tracheary elements - a model ligno-cellulose substrate - were treated with Mn(III)-oxalate complexes in a newly developed flow-through reactor. Soluble decomposition products released during the treatment were analyzed by GC/MS and the degree of cell integrity was measured by cell counts, pre- and post-treatment counts indicate a decrease in intact Zinnia elegans as a result of Mn(III)-treatment. GC/MS results showed the release of a multitude of solubilized lignin breakdown products from plant cell walls. We conclude that Mn(III)-oxalate complexes have the ability to lyse intact plant cells and solubilize lignin. Lignin decomposition may thus be seen as resource dependent, with Mn(III) a powerful resource that should be abundant in terrestrial characterized by frequent redox fluctuations.

Effect of metabolic control on parathyroid hormone secretion in diabetic patients

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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.

Differential isotope dansylation labeling combined with liquid chromatography mass spectrometry for quantification of intact and N-terminal truncated proteins

Energy Technology Data Exchange (ETDEWEB)

Tang, Yanan; Li, Liang, E-mail: Liang.Li@ualberta.ca

2013-08-20

Graphical abstract: -- Highlights: •LC–MS was developed for quantifying protein mixtures containing both intact and N-terminal truncated proteins. •{sup 12}C{sub 2}-Dansylation of the N-terminal amino acid of proteins was done first, followed by microwave-assisted acid hydrolysis. •The released {sup 12}C{sub 2}-dansyl labeled N-terminal amino acid was quantified using {sup 13}C{sub 2}-dansyl labeled amino acid standards. •The method provided accurate and precise results for quantifying intact and N-terminal truncated proteins within 8 h. -- Abstract: The N-terminal amino acids of proteins are important structure units for maintaining the biological function, localization, and interaction networks of proteins. Under different biological conditions, one or several N-terminal amino acids could be cleaved from an intact protein due to processes, such as proteolysis, resulting in the change of protein properties. Thus, the ability to quantify the N-terminal truncated forms of proteins is of great importance, particularly in the area of development and production of protein-based drugs where the relative quantity of the intact protein and its truncated form needs to be monitored. In this work, we describe a rapid method for absolute quantification of protein mixtures containing intact and N-terminal truncated proteins. This method is based on dansylation labeling of the N-terminal amino acids of proteins, followed by microwave-assisted acid hydrolysis of the proteins into amino acids. It is shown that dansyl labeled amino acids are stable in acidic conditions and can be quantified by liquid chromatography mass spectrometry (LC–MS) with the use of isotope analog standards.

Reconciling certification and intact forest landscape conservation.

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Kleinschroth, Fritz; Garcia, Claude; Ghazoul, Jaboury

2018-05-29

In 2014, the Forest Stewardship Council (FSC) added a new criterion to its principles that requires protection of intact forest landscapes (IFLs). An IFL is an extensive area of forest that lacks roads and other signs of human activity as detected through remote sensing. In the Congo basin, our analysis of road networks in formally approved concessionary logging areas revealed greater loss of IFL in certified than in noncertified concessions. In areas of informal (i.e., nonregulated) extraction, road networks are known to be less detectable by remote sensing. Under the current definition of IFL, companies certified under FSC standards are likely to be penalized relative to the noncertified as well as the informal logging sector on account of their planned road networks, despite an otherwise better standard of forest management. This could ultimately undermine certification and its wider adoption, with implications for the future of sustainable forest management.

Plastic Change along the Intact Crossed Pathway in Acute Phase of Cerebral Ischemia Revealed by Optical Intrinsic Signal Imaging

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Xiaoli Guo

2016-01-01

Full Text Available The intact crossed pathway via which the contralesional hemisphere responds to the ipsilesional somatosensory input has shown to be affected by unilateral stroke. The aim of this study was to investigate the plasticity of the intact crossed pathway in response to different intensities of stimulation in a rodent photothrombotic stroke model. Using optical intrinsic signal imaging, an overall increase of the contralesional cortical response was observed in the acute phase (≤48 hours after stroke. In particular, the contralesional hyperactivation is more prominent under weak stimulations, while a strong stimulation would even elicit a depressed response. The results suggest a distinct stimulation-response pattern along the intact crossed pathway after stroke. We speculate that the contralesional hyperactivation under weak stimulations was due to the reorganization for compensatory response to the weak ipsilateral somatosensory input.

Isolation of intact sub-dermal secretory cavities from Eucalyptus

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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.

Surface plasmon resonance sensing: from purified biomolecules to intact cells.

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Su, Yu-Wen; Wang, Wei

2018-04-12

Surface plasmon resonance (SPR) has become a well-recognized label-free technique for measuring the binding kinetics between biomolecules since the invention of the first SPR-based immunosensor in 1980s. The most popular and traditional format for SPR analysis is to monitor the real-time optical signals when a solution containing ligand molecules is flowing over a sensor substrate functionalized with purified receptor molecules. In recent years, rapid development of several kinds of SPR imaging techniques have allowed for mapping the dynamic distribution of local mass density within single living cells with high spatial and temporal resolutions and reliable sensitivity. Such capability immediately enabled one to investigate the interaction between important biomolecules and intact cells in a label-free, quantitative, and single cell manner, leading to an exciting new trend of cell-based SPR bioanalysis. In this Trend Article, we first describe the principle and technical features of two types of SPR imaging techniques based on prism and objective, respectively. Then we survey the intact cell-based applications in both fundamental cell biology and drug discovery. We conclude the article with comments and perspectives on the future developments. Graphical abstract Recent developments in surface plasmon resonance (SPR) imaging techniques allow for label-free mapping the mass-distribution within single living cells, leading to great expansions in biomolecular interactions studies from homogeneous substrates functionalized with purified biomolecules to heterogeneous substrates containing individual living cells.

Family Relationships and the Psychosocial Adjustment of School-Aged Children in Intact Families

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Hakvoort, Esther M.; Bos, Henny M. W.; Van Balen, Frank; Hermanns, Jo M. A.

2010-01-01

The authors investigated whether the quality of three family relationships (i.e., marital, parent-child, sibling) in intact families are associated with each other and with children's psychosocial adjustment. Data were collected by means of maternal and child reports (N = 88) using standardized instruments (i.e., Marital Satisfaction Scale,…

Estimating Carbon Dynamics in an Intact Lowland Mixed Dipterocarp Forest Using a Forest Carbon Model

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Jongyeol Lee

2017-04-01

Full Text Available Intact dipterocarp forests in Asia act as crucial carbon (C reservoirs, and it is therefore important to investigate the C dynamics in these forests. We estimated C dynamics, together with net ecosystem production (NEP, in an intact tropical dipterocarp forest of Brunei Darussalam. Fifty-four simulation units (plots; 20 m × 20 m were established and initial C stocks were determined via direct field measurement. The C dynamics were annually simulated with a regression model and the Forest Biomass and Dead organic matter Carbon (FBDC model. The initial C stock (Mg C·ha−1 of biomass, litter, dead wood and mineral soil were 213.1 ± 104.8, 2.0 ± 0.8, 31.3 ± 38.8, and 80.7 ± 15.5, respectively. Their annual changes (Mg C·ha−1·year−1 were 3.2 ± 1.1, 0.2 ± 0.2, −3.7 ± 6.1, and −0.3 ± 1.1, respectively. NEP was −0.6 ± 6.1 Mg C·ha−1·year−1, showing large heterogeneity among the plots. The initial C stocks of biomass and dead wood, biomass turnover rates and dead wood decay rates were elucidated as dominant factors determining NEP in a sensitivity analysis. Accordingly, investigation on those input data can constrain an uncertainty in determining NEP in the intact tropical forests.

Radioiodination of an outer membrane protein in intact Rickettsia prowazekii

International Nuclear Information System (INIS)

Smith, D.K.; Winkler, H.H.

1980-01-01

Intact Rickettsia prowazekii was radiolabeled with the glucose oxidase-lactoperoxidase method of iodination. Separation of the rickettsial extract into cytoplasmic, outer and inner membrane fractions demonstrated that the outer membrane was preferentially labeled. Analysis of the polypeptides of these fractions on high-resolution slab polyacrylamide gels showed that most of the 125 I was in polypeptide T49, an outer membrane constituent. Additional outer membrane polypeptides were iodinated in broken envelope preparations, demonstrating that T49 is uniquely accessible to the external environment and the asymmetric polypeptide organization of the outer membrane

Effects of radiation quality on the opening of stomata in intact Phaseolus vulgaris leaves

International Nuclear Information System (INIS)

Sikorska, K.; Kozłowska, B.; Ciereszko, I.; Maleszewski, S.

1997-01-01

In intact French bean (Phaseolus vulgaris L.) leaves blue radiation enhanced opening of stomata both when it was used individually and when it was used as preirradiation before ''white light'' irradiation. Effects of red radiation were just the contrary

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

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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.

Intact skull chronic windows for mesoscopic wide-field imaging in awake mice

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Silasi, Gergely; Xiao, Dongsheng; Vanni, Matthieu P.; Chen, Andrew C. N.; Murphy, Timothy H.

2016-01-01

Background Craniotomy-based window implants are commonly used for microscopic imaging, in head-fixed rodents, however their field of view is typically small and incompatible with mesoscopic functional mapping of cortex. New Method We describe a reproducible and simple procedure for chronic through-bone wide-field imaging in awake head-fixed mice providing stable optical access for chronic imaging over large areas of the cortex for months. Results The preparation is produced by applying clear-drying dental cement to the intact mouse skull, followed by a glass coverslip to create a partially transparent imaging surface. Surgery time takes about 30 minutes. A single set-screw provides a stable means of attachment for mesoscale assessment without obscuring the cortical field of view. Comparison with Existing Methods We demonstrate the utility of this method by showing seed-pixel functional connectivity maps generated from spontaneous cortical activity of GCAMP6 signals in both awake and anesthetized mice. Conclusions We propose that the intact skull preparation described here may be used for most longitudinal studies that do not require micron scale resolution and where cortical neural or vascular signals are recorded with intrinsic sensors. PMID:27102043

Determination of the intracellular pH of intact erythrocytes by 1H NMR spectroscopy

International Nuclear Information System (INIS)

Rabenstein, D.L.; Isab, A.A.

1982-01-01

A method is described for determining the intracellular pH of intact erythrocytes by 1 H NMR. The determination is based on the pH dependence of the chemical shifts of resonances for carbon-bounded protons of an indicator molecule (imidazole) in intact cells. The imidazole is introduced into the erythrocytes by incubation in an isotonic saline solution of the indicator. The pH dependence of the chemical shifts of the imidazole resonances is calibrated from 1 H NMR spectra of the imidazole-containing red cell lysates whose pH is varied by the addition of acid or base and measured directly with a pH electrode. To reduce in intensity or eliminate the much more intense envelope of resonances from the hemoglobin, the 1 H NMR measurements are made by either the spin-echo Fourier transform technique or by the transfer-or-saturation by cross-relaxation method

Supracapsular glued intraocular lens in progressive subluxated cataracts: Technique to retain an intact vitreous face.

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Jacob, Soosan; Narasimhan, Smita; Agarwal, Amar; Mazzotta, Cosimo; Rechichi, Miguel; Agarwal, Athiya

2017-03-01

We describe a technique to prevent late intraocular lens (IOL) subluxation and dislocation that can be associated with progressive zonulopathy. Supracapsular glued IOL fixation is done to retain an intact anterior hyaloid face and avoid vitreous disturbance while providing stable long-term IOL fixation. Phacoemulsification is followed by glued IOL implantation above intact anterior and posterior capsules. Sclerotomies are created ab interno in a supracapsular plane under diametrically opposite lamellar scleral flaps without entering the vitreous cavity. Haptics are externalized in the supracapsular plane and tucked into intrascleral tunnels. Intraoperative or postoperative posterior capsulorhexis or capsulotomy and anterior capsule relaxing cuts can prevent capsule phimosis. Copyright © 2017 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.

Association of Bystander Interventions With Neurologically Intact Survival Among Patients With Bystander-Witnessed Out-of-Hospital Cardiac Arrest in Japan.

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Nakahara, Shinji; Tomio, Jun; Ichikawa, Masao; Nakamura, Fumiaki; Nishida, Masamichi; Takahashi, Hideto; Morimura, Naoto; Sakamoto, Tetsuya

2015-07-21

Neurologically intact survival after out-of-hospital cardiac arrest (OHCA) has been increasing in Japan. However, associations between increased prehospital care, including bystander interventions and increases in survival, have not been well estimated. To estimate the associations between bystander interventions and changes in neurologically intact survival among patients with OHCA in Japan. Retrospective descriptive study using data from Japan's nationwide OHCA registry, which started in January 2005. The registry includes all patients with OHCA transported to the hospital by emergency medical services (EMS) and recorded patients' characteristics, prehospital interventions, and outcomes. Participants were 167,912 patients with bystander-witnessed OHCA of presumed cardiac origin in the registry between January 2005 and December 2012. Prehospital interventions by bystander, including defibrillation using public-access automated external defibrillators and chest compression. Neurologically intact survival was defined as Glasgow-Pittsburgh cerebral performance category score 1 or 2 and overall performance category scores 1 or 2 at 1 month or at discharge. The association between the interventions and neurologically intact survival was evaluated. From 2005 to 2012, the number of bystander-witnessed OHCAs of presumed cardiac origin increased from 17,882 (14.0 per 100,000 persons [95% CI, 13.8-14.2]) to 23,797 (18.7 per 100,000 persons [95% CI, 18.4-18.9]), and neurologically intact survival increased from 587 cases (age-adjusted proportion, 3.3% [95% CI, 3.0%-3.5%]) to 1710 cases (8.2% [95% CI, 7.8%-8.6%]). The rates of bystander chest compression increased from 38.6% to 50.9%, bystander-only defibrillation increased from 0.1% to 2.3%, bystander defibrillation combined with EMS defibrillation increased from 0.1% to 1.4%, and EMS-only defibrillation decreased from 26.6% to 23.5%. Performance of bystander chest compression, compared with no bystander chest compression

Phonological abilities in literacy-impaired children: Brain potentials reveal deficient phoneme discrimination, but intact prosodic processing

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Claudia Männel

2017-02-01

Full Text Available Intact phonological processing is crucial for successful literacy acquisition. While individuals with difficulties in reading and spelling (i.e., developmental dyslexia are known to experience deficient phoneme discrimination (i.e., segmental phonology, findings concerning their prosodic processing (i.e., suprasegmental phonology are controversial. Because there are no behavior-independent studies on the underlying neural correlates of prosodic processing in dyslexia, these controversial findings might be explained by different task demands. To provide an objective behavior-independent picture of segmental and suprasegmental phonological processing in impaired literacy acquisition, we investigated event-related brain potentials during passive listening in typically and poor-spelling German school children. For segmental phonology, we analyzed the Mismatch Negativity (MMN during vowel length discrimination, capturing automatic auditory deviancy detection in repetitive contexts. For suprasegmental phonology, we analyzed the Closure Positive Shift (CPS that automatically occurs in response to prosodic boundaries. Our results revealed spelling group differences for the MMN, but not for the CPS, indicating deficient segmental, but intact suprasegmental phonological processing in poor spellers. The present findings point towards a differential role of segmental and suprasegmental phonology in literacy disorders and call for interventions that invigorate impaired literacy by utilizing intact prosody in addition to training deficient phonemic awareness.

In Vivo Real-Time Imaging of Exogenous HGF-Triggered Cell Migration in Rat Intact Soleus Muscles

International Nuclear Information System (INIS)

Ishido, Minenori; Kasuga, Norikatsu

2012-01-01

The transplantation of myogenic cells is a potentially effective therapy for muscular dystrophy. However, this therapy has achieved little success because the diffusion of transplanted myogenic cells is limited. Hepatocyte growth factor (HGF) is one of the primary triggers to induce myogenic cell migration in vitro. However, to our knowledge, whether exogenous HGF can trigger the migration of myogenic cells (i.e. satellite cells) in intact skeletal muscles in vivo has not been reported. We previously reported a novel in vivo real-time imaging method in rat skeletal muscles. Therefore, the present study examined the relationship between exogenous HGF treatment and cell migration in rat intact soleus muscles using this imaging method. As a result, it was indicated that the cell migration velocity was enhanced in response to increasing exogenous HGF concentration in skeletal muscles. Furthermore, the expression of MyoD was induced in satellite cells in response to HGF treatment. We first demonstrated in vivo real-time imaging of cell migration triggered by exogenous HGF in intact soleus muscles. The experimental method used in the present study will be a useful tool to understand further the regulatory mechanism of HGF-induced satellite cell migration in skeletal muscles in vivo

Dissolution of intact UO2 pellet in batch and rotary dissolver conditions

International Nuclear Information System (INIS)

Jayendra Kumar Gelatar; Bijendra Kumar; Sampath, M.; Shekhar Kumar; Kamachi Mudali, U.; Natarajan, R.

2015-01-01

Comparative dissolution of intact un-irradiated UO 2 pellet of PHWR fuel dimensions was performed in batch and dynamic rotary dissolver conditions in aqueous nitric acid solutions at elevated temperatures. The extent of dissolution was estimated by determining the uranium concentration of the resulting aqueous solution. It was observed that rate of dissolution was much faster in dynamic conditions as compared to static batch conditions. (author)

Preparation of intact mitochondria using free-flow isoelectric focusing with post-pH gradient sample injection for morphological, functional and proteomics studies

International Nuclear Information System (INIS)

He, Yu-Chen; Kong, Fan-Zhi; Fan, Liu-Yin; Wu, Jane Y.; Liu, Xiao-Ping; Li, Jun; Sun, Yan; Zhang, Qiang; Yang, Ying; Wu, Xue-Jing; Xiao, Hua; Cao, Cheng-Xi

2017-01-01

Mitochondria play essential roles in both energy metabolism and cell signaling, which are critical for cell survival. Although significant efforts have been invested in understanding mitochondrial biology, methods for intact mitochondria preparation are technically challenging and remain to be improved. New methods for heterogeneous mitochondria purification will therefore boost our understanding on their physiological and biophysical properties. Herein, we developed a novel recycling free-flow isoelectric focusing (RFFIEF) with post-pH gradient sample injection (post-PGSI) for preparative separation of mitochondria. Crude mitochondria of rabbit liver obtained from differential centrifugation were purified by the developed method according to their pI values as six fractions. Transmission electron microscope images revealed that intact mitochondria existed in two fractions of pH 6.24 and 6.61, degenerative mitochondria were in two fractions of pH 5.46 and 5.72, and inner membrane vesicles (IMVs) appeared in the fractions of pH 4.70 and 5.04. Membrane potential measurement proved a dramatic difference between intact mitochondria and IMVs, which reflected the bioactivity of obtained populations. Particularly, proteomics analyses revealed that more number of proteins were identified in the intact fractions than that of IMVs or crude mitochondria, which demonstrated that RFFIEF could be powerful tool for the preparation of intact organelle as well as their proteomic and in-depth biological analysis. - Highlights: • Mitochondrial subpopulation was successfully separated according to their pIs via the developed RFFIEF method. • The post-PGSI method was introduced for the first time to achieve higher recovery of intact mitochondria. • Quick preparation of mitochondria subpopulation via the developed RFFIEF for both pI determination and downstream research.

Pathophysiology of preterm labor with intact membranes.

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Talati, Asha N; Hackney, David N; Mesiano, Sam

2017-11-01

Preterm labor with intact membranes is a major cause of spontaneous preterm birth (sPTB). To prevent sPTB a clear understanding is needed of the hormonal interactions that initiate labor. The steroid hormone progesterone acting via its nuclear progesterone receptors (PRs) in uterine cells is essential for the establishment and maintenance of pregnancy and disruption of PR signaling (i.e., functional progesterone/PR withdrawal) is key trigger for labor. The process of parturition is also associated with inflammation within the uterine tissues and it is now generally accepted that inflammatory stimuli from multiple extrinsic and intrinsic sources induce labor. Recent studies suggest inflammatory stimuli induce labor by affecting PR transcriptional activity in uterine cells to cause functional progesterone/PR withdrawal. Advances in understanding the functional interaction of inflammatory load on the pregnancy uterus and progesterone/PR signaling is opening novel areas of research and may lead to rational therapeutic strategies to effectively prevent sPTB. Copyright © 2017 Elsevier Inc. All rights reserved.

Single guard cell recordings in intact plants : light-induced hyperpolarization of the plasma membrane

NARCIS (Netherlands)

Roelfsema, MRG; Steinmeyer, R; Staal, M; Hedrich, R