We report PTH-independent roles of the CaSR in modulating the response to exogenous 1,25(OH) 2D3 in mice with targeted disruption of both the CaSR and PTH genes (C-P-) compared with that in mice with disruption of the PTH gene alone (C-P-) or wild-type

mice (C-P-). After intraperitoneal injection of 0.5 ng/g body wt 1,25(OH)(2)D-3, peak calcemic responses were observed at 24 h in all three genotypes in association with 1) a greater increase in serum Ca2+ in C-P- mice than in the other LCL161 molecular weight genotypes on a Ca2+ replete diet that was attenuated by a Ca2+-deficient diet and pamidronate, 2) increased urinary Ca2+-to-creatinine ratios (UCa/Cr) in the C-P- and C-P- mice but a lowered ratio in the C-P- mice on a Ca2+-replete diet, and 3) no increase in calcitonin (CT) secretion in the C-P- and C-P- mice and a small increase in the C-P- mice. PTH deficiency had the anticipated effects on the expression of key genes involved in Ca2+ transport at baseline in the duodenum and Compound C nmr kidney, and injection of 1,25(OH) 2D3 increased gene expression 8 h later. However, the changes in the genes evaluated did not fully explain the differences in serum Ca2+ seen among the genotypes. In conclusion, mice lacking the full-length CaSR have increased sensitivity to the calcemic action of 1,25(OH) 2D3 in the setting of PTH deficiency. This is principally from enhanced

1,25(OH)(2)D-3-mediated gut Ca2+ absorption and decreased renal Ca2+ excretion, without any differences in

bone-related release of Ca2+ or CT secretion among the three genotypes that could explain the differences in their calcemic responses.”
“Background Elevated blood concentrations selleck compound of troponin proteins or brain natriuretic peptide (BNP) worsen the prognosis of patients with pulmonary embolism (PE). Novel biomarkers that reflect mechanisms of right ventricle (RV) damage from PE may provide additional prognostic value. We compare the prognostic use of BNP, troponin 1, D-dimer, monocyte chemoattractant protein-1, matrix metalloproteinase, myeloperoxidase, C-reactive protein, and caspase 3 as biomarkers of RV damage and adverse outcomes in submassive PE.\n\nMethods This article used a prospective cohort study of normotensive (systolic blood pressure always > 100 mm Hg) patients with computed tomographic angiography-diagnosed PE. All patients underwent echocardiography and phlebotomy at diagnosis, and survivors had another echocardiography 6 months later. We tested each biomarker for prognostic significance, requiring a lower limit 95% CI > 0.50 for the area under the receiver operating characteristic curve (AUROC) with a reference standard positive of RV hypokinesis on either echocardiogram. Biomarkers with prognostic significance were dichotomized at the concentration that yielded highest likelihood ratio positive and mortality rates compared (Fisher exact test).\n\nResults We enrolled 152 patients with complete data.