In vivo and in vitro assessment of mirtazapine pharmacokinetics in cats with liver disease.

BackgroundLiver disease (LD) prolongs mirtazapine half-life in humans, but it is unknown if this occurs in cats with LD and healthy cats.Hypothesis/objectivesTo determine pharmacokinetics of administered orally mirtazapine in vivo and in vitro (liver microsomes) in cats with LD and healthy cats.AnimalsEleven LD and 11 age-matched control cats.MethodsCase-control study. Serum was obtained 1 and 4 hours (22 cats) and 24 hours (14 cats) after oral administration of 1.88 mg mirtazapine. Mirtazapine concentrations were measured by liquid chromatography with tandem mass spectrometry. Drug exposure and half-life were predicted using limited sampling modeling and estimated using noncompartmental methods. in vitro mirtazapine pharmacokinetics were assessed using liver microsomes from 3 LD cats and 4 cats without LD.ResultsThere was a significant difference in time to maximum serum concentration between LD cats and control cats (median [range]: 4 [1-4] hours versus 1 [1-4] hours; P = .03). The calculated half-life of LD cats was significantly prolonged compared to controls (median [range]: 13.8 [7.9-61.4] hours versus 7.4 [6.7-9.1] hours; P < .002). Mirtazapine half-life was correlated with ALT (P = .002; r = .76), ALP (P < .0001; r = .89), and total bilirubin (P = .0008; r = .81). The rate of loss of mirtazapine was significantly different between microsomes of LD cats (-0.0022 min-1 , CI: -0.0050 to 0.00054 min-1 ) and cats without LD (0.01849 min-1 , CI: -0.025 to -0.012 min-1 ; P = .002).Conclusions and clinical importanceCats with LD might require less frequent administration of mirtazapine than normal cats

SN 2010jl in UGC 5189: Yet another luminous type IIn supernova in a metal-poor galaxy

We present ASAS data starting 25 days before the discovery of the recent type IIn SN 2010jl, and we compare its light curve to other luminous IIn SNe, showing that it is a luminous (M_I ~ -20.5) event. Its host galaxy, UGC 5189, has a low gas-phase oxygen abundance (12 + log(O/H) = 8.2), which reinforces the emerging trend that over-luminous core-collapse supernovae are found in the low-metallicity tail of the galaxy distribution, similar to the known trend for the hosts of long GRBs. We compile oxygen abundances from the literature and from our own observations of UGC 5189, and we present an unpublished spectrum of the luminous type Ic SN 2010gx that we use to estimate its host metallicity. We discuss these in the context of host metallicity trends for different classes of core-collapse objects. The earliest generations of stars are known to be enhanced in [O/Fe] relative to the Solar mixture; it is therefore likely that the stellar progenitors of these overluminous supernovae are even more iron-poor than they are oxygen-poor. A number of mechanisms and massive star progenitor systems have been proposed to explain the most luminous core-collapse supernovae; any successful theory will need to include the emerging trend that points towards low-metallicity for the massive progenitor stars. This trend for very luminous supernovae to strongly prefer low-metallicity galaxies should be taken into account when considering various aspects of the evolution of the metal-poor early universe. (abridged)Comment: 27 pages, 7 figures, 2 tables. Accepted for publication in Ap

Safety and efficacy of intravenous infusion of allogeneic cryopreserved mesenchymal stem cells for treatment of chronic kidney disease in cats: results of three sequential pilot studies

INTRODUCTION: Administration of mesenchymal stem cells (MSCs) has been shown to improve renal function in rodent models of chronic kidney disease (CKD), in part by reducing intrarenal inflammation and suppressing fibrosis. CKD in cats is characterized by tubulointerstitial inflammation and fibrosis, and thus treatment with MSCs might improve renal function and urinary markers of inflammation in this disease. Therefore, a series of pilot studies was conducted to assess the safety and efficacy of intravenous administration of allogeneic adipose-derived MSCs (aMSCs) in cats with naturally occurring CKD. METHODS: Cats enrolled in these studies received an intravenous infusion of allogeneic aMSCs every 2 weeks collected from healthy, young, specific pathogen-free cats. Cats in pilot study 1 (six cats) received 2 × 10(6) cryopreserved aMSCs per infusion, cats in pilot study 2 (five cats) received 4 × 10(6) cryopreserved aMSCs per infusion, and cats in pilot study 3 (five cats) received 4 × 10(6) aMSCs cultured from cryopreserved adipose. Serum biochemistry, complete blood count, urinalysis, urine protein, glomerular filtration rate, and urinary cytokine concentrations were monitored during the treatment period. Changes in clinical parameters were compared statistically by means of repeated measures analysis of variance (ANOVA) followed by Bonferroni’s correction. RESULTS: Cats in pilot study 1 had few adverse effects from the aMSC infusions and there was a statistically significant decrease in serum creatinine concentrations during the study period, however the degree of decrease seems unlikely to be clinically relevant. Adverse effects of the aMSC infusion in cats in pilot study 2 included vomiting (2/5 cats) during infusion and increased respiratory rate and effort (4/5 cats). Cats in pilot study 3 did not experience any adverse side effects. Serum creatinine concentrations and glomerular filtration rates did not change significantly in cats in pilot studies 2 and 3. CONCLUSIONS: Administration of cryopreserved aMSCs was associated with significant adverse effects and no discernible clinically relevant improvement in renal functional parameters. Administration of aMSCs cultured from cryopreserved adipose was not associated with adverse effects, but was also not associated with improvement in renal functional parameters

SN2012ab: A Peculiar Type IIn Supernova with Aspherical Circumstellar Material

We present photometry, spectra, and spectropolarimetry of supernova (SN) 2012ab, mostly obtained over the course of $\sim 300$ days after discovery. SN 2012ab was a Type IIn (SN IIn) event discovered near the nucleus of spiral galaxy 2MASXJ12224762+0536247. While its light curve resembles that of SN 1998S, its spectral evolution does not. We see indications of CSM interaction in the strong intermediate-width emission features, the high luminosity (peak at absolute magnitude $M=-19.5$), and the lack of broad absorption features in the spectrum. The H$\alpha$ emission undergoes a peculiar transition. At early times it shows a broad blue emission wing out to $-14{,}000$ km $\mathrm{s^{-1}}$ and a truncated red wing. Then at late times ($>$ 100$\,$days) it shows a truncated blue wing and a very broad red emission wing out to roughly $+20{,}000$ km $\mathrm{s^{-1}}$. This late-time broad red wing probably arises in the reverse shock. Spectra also show an asymmetric intermediate-width H$\alpha$ component with stronger emission on the red side at late times. The evolution of the asymmetric profiles requires a density structure in the distant CSM that is highly aspherical. Our spectropolarimetric data also suggest asphericity with a strong continuum polarization of $\sim 1-3$% and depolarization in the H$\alpha$ line, indicating asphericity in the CSM at a level comparable to that in other SNe IIn. We estimate a mass-loss rate of $\dot{M} = 0.050\, {\rm M}_{\odot}\,\mathrm{yr^{-1}}$ for $v_{\rm pre} = 100$$\,$km$\,$$\mathrm{s^{-1}}$ extending back at least 75$\,$yr prior to the SN. The strong departure from axisymmetry in the CSM of SN 2012ab may suggest that the progenitor was an eccentric binary system undergoing eruptive mass loss.Comment: 18 pages, 12 figure

Hydrogen-poor superluminous stellar explosions

Supernovae (SNe) are stellar explosions driven by gravitational or thermonuclear energy, observed as electromagnetic radiation emitted over weeks or more. In all known SNe, this radiation comes from internal energy deposited in the outflowing ejecta by either radioactive decay of freshly-synthesized elements (typically 56Ni), stored heat deposited by the explosion shock in the envelope of a supergiant star, or interaction between the SN debris and slowly-moving, hydrogen-rich circumstellar material. Here we report on a new class of luminous SNe whose observed properties cannot be explained by any of these known processes. These include four new SNe we have discovered, and two previously unexplained events (SN 2005ap; SCP 06F6) that we can now identify as members. These SNe are all ~10 times brighter than SNe Ia, do not show any trace of hydrogen, emit significant ultra-violet (UV) flux for extended periods of time, and have late-time decay rates which are inconsistent with radioactivity. Our data require that the observed radiation is emitted by hydrogen-free material distributed over a large radius (~10^15 cm) and expanding at high velocities (>10^4 km s^-1). These long-lived, UV-luminous events can be observed out to redshifts z>4 and offer an excellent opportunity to study star formation in, and the interstellar medium of, primitive distant galaxies.Comment: Accepted to Nature. Press embargoed until 2011 June 8, 18:00 U

The Palomar Transient Factory photometric catalog 1.0

We construct a photometrically calibrated catalog of non-variable sources from the Palomar Transient Factory (PTF) observations. The first version of this catalog presented here, the PTF photometric catalog 1.0, contains calibrated R_PTF-filter magnitudes for about 21 million sources brighter than magnitude 19, over an area of about 11233 deg^2. The magnitudes are provided in the PTF photometric system, and the color of a source is required in order to convert these magnitudes into other magnitude systems. We estimate that the magnitudes in this catalog have typical accuracy of about 0.02 mag with respect to magnitudes from the Sloan Digital Sky Survey. The median repeatability of our catalog's magnitudes for stars between 15 and 16 mag, is about 0.01 mag, and it is better than 0.03 mag for 95% of the sources in this magnitude range. The main goal of this catalog is to provide reference magnitudes for photometric calibration of visible light observations. Subsequent versions of this catalog, which will be published incrementally online, will be extended to a larger sky area and will also include g_PTF-filter magnitudes, as well as variability and proper motion information.Comment: 6 pages, 6 figures, PASP in pres

Slow-Speed Supernovae from the Palomar Transient Factory: Two Channels

Since the discovery of the unusual prototype SN 2002cx, the eponymous class of low-velocity, hydrogen-poor supernovae has grown to include at most another two dozen members identified from several heterogeneous surveys, in some cases ambiguously. Here we present the results of a systematic study of 1077 hydrogen-poor supernovae discovered by the Palomar Transient Factory, leading to nine new members of this peculiar class. Moreover we find there are two distinct subclasses based on their spectroscopic, photometric, and host galaxy properties: The "SN 2002cx-like" supernovae tend to be in later-type or more irregular hosts, have more varied and generally dimmer luminosities, have longer rise times, and lack a Ti II trough when compared to the "SN 2002es-like" supernovae. None of our objects show helium, and we counter a previous claim of two such events. We also find that these transients comprise 5.6+17-3.7% (90% confidence) of all SNe Ia, lower compared to earlier estimates. Combining our objects with the literature sample, we propose that these subclasses have two distinct physical origins.Comment: 49 pages, 36 figures, submitted to Ap