Inhibition of the Progesterone Nuclear Receptor during the Bone Linear Growth Phase Increases Peak Bone Mass in Female Mice

Augmentation of the peak bone mass (PBM) may be one of the most effective interventions to reduce the risk of developing osteoporosis later in life; however treatments to augment PBM are currently limited. Our study evaluated whether a greater PBM could be achieved either in the progesterone nuclear receptor knockout mice (PRKO) or by using a nuclear progesterone receptor (nPR) antagonist, RU486 in mice. Compared to their wild type (WT) littermates the female PRKO mice developed significantly higher cancellous and cortical mass in the distal femurs, and this was associated with increased bone formation. The high bone mass phenotype was partially reproduced by administering RU486 in female WT mice from 1–3 months of age. Our results suggest that the inhibition of the nPR during the rapid bone growth period (1–3 months) increases osteogenesis, which results in acquisition of higher bone mass. Our findings suggest a crucial role for progesterone signaling in bone acquisition and inhibition of the nPR as a novel approach to augment bone mass, which may have the potential to reduce the burden of osteoporosis

Alexander Scordelis Memorial Session: Thin Shell Concrete Structures

IASS-IACM 2008 Session: Alexander Scordelis Memorial Session: Thin Shell Concrete Structures -- Note: Video is available for the Keynote Lectures by Billington, Meyer and Willam -- Session Organizers: Maria GARLOCK (Princeton University), John ABEL (Cornell Univ.) -- Keynote Lecture and Video: "Alexander Scordelis: Friend, colleague and mentor" by David P. BILLINGTON (Princeton University) -- Keynote Lecture and Video: "Alexander C. Scordelis and concrete shells" by Christian MEYER (Columbia University) -- Keynote Lecture and Video: "Alexander C. Scordelis: Legacy in finite element analysis of reinforced concrete" by Kaspar J. WILLAM (University of Colorado) -- Keynote Lecture: "Alex C. Scordelis? great achievements in bridge engineering ? From computer programs to the Golden Gate Bridge retrofit" by Ekkehard RAMM (Stuttgart University) -- "3-D pushover analysis of a collapsed reinforced concrete chimney" by Wei HUANG (KPFF Consulting Engineers), Phillip L. GOULD (Washington University) -- "Structural optimization of concrete hyperbolic paraboloid umbrella shells" by Powell DRAPER, Maria E. Moreyra GARLOCK, David P. BILLINGTON (Princeton University) -- "Delamination in a two-layer thin-shell concrete dome with unanticipated construction openings" by Sinead C. MAC NAMARA (Syracuse University) -- "Testing, modeling and constructing wood-plastic composite Catalan vaults" by Edmond SALIKLIS, Kyle WHITE (Cal Poly) -- "Concrete vaulting in Imperial Rome: A structural analysis of the Great Hall of Trajan's Markets" by Renato PERUCCHIO, Philip BRUNE (University of Rochester) -- "Numerical study of steel corrosion in concrete shell members" by O. Burkan ISGOR, Mohammad POUR-GHAZ, Pouria GHODS (Carleton University

The spectrum of renal involvement in patients with inflammatory myopathies

International audienceData regarding the incidence and outcome of renal involvement in patients with inflammatory myopathies (IM) remain scarce. We assessed the incidence and causes of acute kidney injury (AKI) and chronic kidney disease (CKD) in 150 patients with dermatomyositis, polymyositis, and antisynthetase syndrome followed in 3 French referral centers. Renal involvement occurred in 35 (23.3%) patients: AKI in 16 (10.7%), and CKD in 31 (20.7%) patients. The main cause of AKI was drug or myoglobinuria-induced acute tubular necrosis. Male sex, cardiovascular risk factors, cardiac involvement, and initial proteinuria \textgreater0.3 g/d were associated with the occurrence of AKI. The outcome of patients with AKI was poor: 13 (81%) progressed to CKD and 2 (12.5%) reached end-stage renal disease. In multivariate survival analysis, age at IM onset, male sex, a history of cardiovascular events, and a previous episode of AKI were associated with the risk of CKD. We also identified 14 IM patients who underwent a kidney biopsy in 10 nephrology centers. Renal pathology disclosed a wide range of renal disorders, mainly immune-complex glomerulonephritis. We identified in 5 patients a peculiar pattern of severe acute renal vascular damage consisting mainly of edematous thickening of the intima of arterioles. We found that AKI and CKD are frequent in patients with IM. Prevention of AKI is crucial in these patients, as AKI is a major contributor to their relatively high risk of CKD. A peculiar pattern of acute vascular damage is part of the spectrum of renal diseases associated with IM