A selective inhibitor of the osteoclastic V-H(+)-ATPase prevents bone loss in both thyroparathyroidectomized and ovariectomized rats

A potent and selective inhibitor of the osteoclastic V-H(+)-ATPase, (2Z,4E)-5-(5,6-dichloro-2-indolyl)-2-methoxy-N-(1,2,2,6,6-pentamethylpiperidin-4-yl) -2,4-pentadienamide (SB 242784), was evaluated in two animal models of bone resorption. SB 242784 completely prevented retinoid-induced hypercalcemia in thyroparathyroidectomized (TPTX) rats when administered orally at 10 mg/kg. SB 242784 was highly efficacious in the prevention of ovariectomy-induced bone loss in the rat when administered orally for 6 months at 10 mg/kg/d and was partially effective at 5 mg/kg/d. Its activity was demonstrated by measurement of bone mineral density (BMD), biochemical markers of bone resorption, and histomorphometry. SB 242784 was at least as effective in preventing bone loss as an optimal dose of estrogen. There were no adverse effects of compound administration and no effects on kidney function or urinary acidity. Selectivity of the inhibitor was further studied using an in situ cytochemical assay for bafilomycin-sensitive V-H(+)-ATPase using sections of osteoclastoma and numerous other tissues. SB 242784 inhibited the osteoclast enzyme at 1,000-fold lower concentrations than enzymes in any of the other tissues evaluated. SB 242784 demonstrates the utility of selective inhibition of the osteoclast V-H(+)-ATPase as a novel approach to the prevention of bone loss in humans

Biometric conversion factors as a unifying platform for comparative assessment of invasive freshwater bivalves

Invasive bivalves continue to spread and negatively impact freshwater ecosystems worldwide. As different metrics for body size and biomass are frequently used within the literature to standardise bivalve related ecological impacts (e.g. respiration and filtration rates), the lack of broadly applicable conversion equations currently hinders reliable comparison across bivalve populations. To facilitate improved comparative assessment amongst studies originating from disparate geographic locations, we report body size and biomass conversion equations for six invasive freshwater bivalves (or species complex members) worldwide: Corbicula fluminea, C. largillierti, Dreissena bugensis, D. polymorpha, Limnoperna fortunei and Sinanodonta woodiana, and tested the reliability (i.e. precision and accuracy) of these equations. Body size (length, width, height) and biomass metrics of living-weight (LW), wet-weight (WW), dry-weight (DW), dry shell-weight (SW), shell free dry-weight (SFDW) and ash-free dry-weight (AFDW) were collected from a total of 44 bivalve populations located in Asia, the Americas and Europe. Relationships between body size and individual biomass metrics, as well as proportional weight-to-weight conversion factors, were determined. For most species, although inherent variation existed between sampled populations, body size directional measurements were found to be good predictors of all biomass metrics (e.g. length to LW, WW, SW or DW: R2 = 0.82–0.96), with moderate to high accuracy for mean absolute error (MAE): ±9.14–24.19%. Similarly, narrow 95%–confidence limits and low MAE were observed for most proportional biomass relationships, indicating high reliability for the calculated conversion factors (e.g. LW to AFDW; CI range: 0.7–2.0, MAE: ±0.7–2.0%). Synthesis and applications. Our derived biomass prediction equations can be used to rapidly estimate the biologically active biomass of the assessed species, based on simpler biomass or body size measurements for a wide range of situations globally. This allows for the calculation of approximate average indicators that, when combined with density data, can be used to estimate biomass per geographic unit-area and contribute to quantification of population-level effects. These general equations will support meta-analyses, and allow for comparative assessment of historic and contemporary data. Overall, these equations will enable conservation managers to better understand and predict ecological impacts of these bivalves