Effect of cinacalcet on urine calcium excretion and supersaturation in genetic hypercalciuric stone-forming rats

Idiopathic hypercalciuria is the most common metabolic abnormality in patients with nephrolithiasis. Through successive inbreeding, we have developed a strain of rats whose urine calcium (UCa) excretion is ∼8–10-fold greater than that of control rats and who spontaneously form kidney stones. We have termed these rats genetic hypercalciuric stone-forming (GHS) rats. The physiology of the hypercalciuria in the GHS rats closely parallels that of man. We have recently shown that the GHS rat kidneys have an increased number of receptors for calcium (CaR) compared to Sprague–Dawley rats, the strain of rats originally bred to develop the GHS rats. Calcimimetics, such as cinacalcet (Cin), increase the sensitivity of the CaR to Ca. The effects of Cin on UCa are complex and difficult to predict. We tested the hypothesis that Cin would alter urinary (U) Ca and supersaturation with respect to calcium hydrogen phosphate (CaHPO4) and calcium oxalate (CaOx). GHS or control rats were fed a normal Ca diet (0.6% Ca) for 28 days with Cin (30 mg/kg/24 h) added to the diet of half of each group for the last 14 days. The protocol was then repeated while the rats were fed a low Ca (0.02% Ca) diet. We found that Cin led to a marked reduction in circulating parathyroid hormone and a modest reduction in serum Ca. Cin did not alter UCa when the GHS rats were fed the normal Ca diet but lowered UCa when they were fed the low Ca diet. However, Cin did not alter U supersaturation with respect to either CaOx or CaHPO4 on either diet. If these findings in GHS rats can be confirmed in man, it suggests that Cin would not be an effective agent in the treatment of human idiopathic hypercalciuria and resultant stone formation

Global Journalist: The Unsettled Clash Between Palestine and Israel

On this March 28, 2002 program, journalists discuss how a bombing in Netanya, Israel is connected the growing concerns of religious extremism in the Middle East

Global Journalist: Unrest in Israel

In this October 28, 2004 program, host Stuart Loory discusses the implications of the Israeli Knesset's approval of a plan to withdraw from the Gaza Strip, and the reportedly serious illness of Palestinian leader Yasser Arafat on peace talks in the region

Nutrient Controls on Export Production in the Southern Ocean

We use observations from novel biogeochemical profiling floats deployed by the Southern Ocean Carbon and Climate Observations and Modeling program to estimate annual net community production (ANCP; associated with carbon export) from the seasonal drawdown of mesopelagic oxygen and surface nitrate in the Southern Ocean. Our estimates agree with previous observations in showing an increase in ANCP in the vicinity of the polar front (∼3 mol C m−2 y−1), compared to lower rates in the subtropical zone (≤ 1 mol C m−2 y−1) and the seasonal ice zone (<2 mol C m−2 y−1). Paradoxically, the increase in ANCP south of the subtropical front is associated with elevated surface nitrate and silicate concentrations, but decreasing surface iron. We hypothesize that iron limitation promotes silicification in diatoms, which is evidenced by the low silicate to nitrate ratio of surface waters around the Antarctic polar front. High diatom silicification increases the ballasting effect of particulate organic carbon and overall ANCP in this region. A model-based assessment of our methods shows a good agreement between ANCP estimates based on oxygen and nitrate drawdown and the modeled downward organic carbon flux at 100 m. This agreement supports the presumption that net biological consumption is the dominant process affecting the drawdown of these chemical tracers and that, given sufficient data, ANCP can be inferred from observations of oxygen and/or nitrate drawdown in the Southern Ocean

Global Journalist: Iraq War and the Israeli-Palestinian Conflict

In this Sepember 26, 2002 episode of Global Journalist, host Stuart Loory and four journalists discuss the Israeli-Palestinian conflict and the upcoming war against Iraq. Guests from the US, Palestine, Israel and France discuss how the invasion of Iraq would bring impact to the Arab world and Israel, as the US is making its effort to gain support from European allies to its cause in Iraq

The Ultraviolet Radiation Environment Around M dwarf Exoplanet Host Stars

The spectral and temporal behavior of exoplanet host stars is a critical input to models of the chemistry and evolution of planetary atmospheres. At present, little observational or theoretical basis exists for understanding the ultraviolet spectra of M dwarfs, despite their critical importance to predicting and interpreting the spectra of potentially habitable planets as they are obtained in the coming decades. Using observations from the Hubble Space Telescope, we present a study of the UV radiation fields around nearby M dwarf planet hosts that covers both FUV and NUV wavelengths. The combined FUV+NUV spectra are publically available in machine-readable format. We find that all six exoplanet host stars in our sample (GJ 581, GJ 876, GJ 436, GJ 832, GJ 667C, and GJ 1214) exhibit some level of chromospheric and transition region UV emission. No "UV quiet" M dwarfs are observed. The bright stellar Ly-alpha emission lines are reconstructed, and we find that the Ly-alpha line fluxes comprise ~37-75% of the total 1150-3100A flux from most M dwarfs; > 10^{3} times the solar value. The F(FUV)/F(NUV) flux ratio, a driver for abiotic production of the suggested biomarkers O2 and O3, is shown to be ~0.5-3 for all M dwarfs in our sample, > 10^{3} times the solar ratio. For the four stars with moderate signal-to-noise COS time-resolved spectra, we find UV emission line variability with amplitudes of 50-500% on 10^{2} - 10^{3} s timescales. Finally, we observe relatively bright H2 fluorescent emission from four of the M dwarf exoplanetary systems (GJ 581, GJ 876, GJ 436, and GJ 832). Additional modeling work is needed to differentiate between a stellar photospheric or possible exoplanetary origin for the hot (T(H2) \approx 2000-4000 K) molecular gas observed in these objects.Comment: ApJ, accepted. 16 pages, 10 figures. On-line data at: http://cos.colorado.edu/~kevinf/muscles.htm