pTH (2-34) (human)

In 8 adolescents with end-stage renal disease (ESRD), basal PTH concentrations measured with a novel immunoradiometric assay (IRMA) (Scantibodies Laboratory, Inc.; S-IRMA) were invariably lower than those estimated with an established assay (Nichols Institute; N-IRMA) (263 +/- 228 versus 645 +/- 442 pg/ml, respectively; p<0.00001). During in vivo dynamic testing, set points for calcium-regulated PTH release were indistinguishable for both IRMAs (1.21 +/- 0.05 versus 1.22 +/- 0.06). However, maximal PTH concentrations were significantly lower when measured by S-IRMA then by N-IRMA (557 +/- 448 and 1114 +/- 606 pg/ml, respectively); minimum PTH concentrations were 41 +/- 65 pg/ml (5.0 +/- 4.2% of maximum) and 189 +/- 137 pg/ml (13.6 +/- 7.2% of maximum), respectively. Correlation between PTH and blood ionized calcium indicated that PTH measured by S-IRMA decreased more readily than the concentrations determined by N-IRMA. The N-IRMA showed indistinguishable cross-reactivity with hPTH(1-84) and hPTH(7-84), while the S-IRMA detected only the full-length peptide. Furthermore, the radiolabeled detection antibody of the N-IRMA interacted equivalently with hPTH(1-34) and hPTH(2-34), while the S-IRMA showed crossreactivity only with hPTH(1-34). These differences in assay specificity could explain the observed differences in ESRD, and suggest that PTH concentrations estimated by the S-IRMA reflect more accurately the amount of biologically active PTH in the circulation. Since low concentrations of PTH are frequently associated with adynamic bone disease, our findings may have significant implications for the treatment of renal osteodystrophy with calcium and/or biologically active vitamin D analogs.

We previously demonstrated that the [Ca2+]i response to PTH is heterogeneous in single UMR-106-01 osteogenic sarcoma cells. To verify whether response heterogeneity is a universal feature of PTH signal transduction, cAMP production was monitored in monolayer cultures of UMR-106-01 cells and human trabecular bone osteoblasts (HOB) using the cAMP-sensitive fluorescent indicator FlCRhR. FlCRhR was microinjected into single cells, and the 500-530/> 560 nm fluorescence ratio was monitored by confocal laserscanning video imaging as a measure of cAMP concentration ([cAMP]). Virtually all UMR-106-01 cells exposed to bovine PTH(1-34) (10(-7) M) exhibited an increase in intracellular [cAMP], with an average fluorescence ratio change of 145 +/- 17% of baseline (n = 15), corresponding to nearly maximal dissociation of protein kinase A. In the continued presence of the hormone (10(-7) M), [cAMP] remained elevated for at least 30 minutes. This effect was accompanied by a slow translocation of the fluorescein-labeled catalytic subunit of protein kinase A from the cytoplasm to the nucleus. In contrast, PTH(1-34) caused no detectable increase in [cAMP] in HOB cells, although PGE2 (3 x 10(-6) M) stimulation was able to increase the FlCRhR ratio (154 +/- 27%, n = 10). The truncated fragment PTH(2-34) was only 67% as potent at PTH(1-34), but deletion of the first two amino acids at the N terminus abolished the hormone's ability to stimulate cAMP production in UMR-106-01 cells. Brief exposure to 10(-7) M of either PTH(3-34) or PTH(7-34) did not affect the amplitude of the fluorescence ratio change induced by equimolar doses of PTH(1-34). Thus, in osteoblast-like cells stimulated with PTH, the [cAMP] response is much more homogeneous from cell to cell than the [Ca2+]i response.

Background: The reference intervals of biochemical markers were significantly affected by age and gender, especially in minors. In recent years, many provinces and regions in China had established reference intervals for children's hematological indicators. Without considering the instruments and reagents, the reference interval will also be affected by the region, economic development, eating habits, and other factors. Therefore, the reference interval of any hematological indicators is not necessarily a fixed range, it changes with certain factors. In our study, we analyzed the changes of biochemical markers in different serum total Ca and 25-OH-D concentrations, and established the reference intervals of biochemical markers in 3-year-old children, explored the change trend of biochemical markers with different serum total Ca and 25-OH-D concentration. Methods: Data was collected from 226 cases of 3-year-old children for biochemical markers, in the Chinese PLA General Hospital in August 2015. The data were divided into a high-level group (serum total Ca > 2.63 mmol/L and 25-OH-D > 40.81 ng/mL) and a low-level group (serum total Ca < 2.54 mmol/L and 25-OH-D < 32.64 ng/mL) according to serum total Ca and 25-OH-D levels for comparison. The change trend of biochemical markers was compared according to serum total Ca and 25-OH-D level. Results: The Glu levels in boys were significantly higher than that in girls, but CHO and LDL-C in girls were significantly higher than that in boys. The reference intervals of ATL (5.6 - 22.1 U/L), ALB (44.8 - 55.2 g/L), TP (62.7 - 83.1 g/L), ALP (154.4 - 379.7 U/L), GGT (7.2 - 15.9 U/L), Glu (boys: 4.08 - 5.91 mmol/L; girls: 4.05 - 5.37 mmol/L), UREA (2.7 - 6.3 mmol/L), CREA (26.4 - 46.8 µmol/L), UA (182.4 - 400.2 µmol/L), TG (0.43 - 1.67 mmol/L), CHO (boys: 3.19 - 5.96 mmol/L; girls: 3.03 - 6.51 mmol/L), HDL-C (0.98 - 2.24 mmol/L), LDL-C (boys: 1.30 - 3.64 mmol/L; girls: 1.24 - 4.27 mmol/L), total Ca (2.34 - 2.85 mmol/L), PHOS (1.38 - 2.06 mmol/L), Mg (0.83 - 1.06 mmol/L), osteocalcin (41.64 - 91.92 ng/mL), PTH (12.08 - 43.06 pg/mL), 25-OH-D (19.66 - 56.37 ng/mL), β-CrossLaps (0.82 - 1.88 ng/mL), TP1NP (357.9 - 1025.7 μg/L) were established. ALT, TP, ALB, GGT, Glu, CHO, HDL-C, LDL-C, UREA, CREA, PHOS, Mg, and ALP in high level group were significantly higher than those in low level group. There was no significant difference in TG, UA, TP1NP, osteocalcin, PTH and β-CrossLaps between high level group and low-level group. With the increase of serum total Ca and 25-OH-D levels, most of the biochemical markers had a gradually increasing trend. However, biochemical markers of bone (TP1NP, osteocalcin, PTH, β-CrossLaps) showed different trends. Conclusions: This study established the reference intervals of biochemical markers of 3-year-old children. The changes of serum total Ca and 25-OH-D levels in children reflected the changes of glucose and lipid metabolism, liver and kidney function markers, and indirectly reflected the growth and development of children and various organ functions. Maintaining high levels of serum total Ca and 25-OH-D can promote the growth and development of children.