Role of plasma arginine vasopressin in the impaired water diuresis of isolated glucocorticoid deficiency in the rat

Role of plasma arginine vasopressin in the impaired water diuresis of isolated glucocorticoid deficiency in the rat. The role of antidiuretic hormone in the impaired water excretion of isolated glucocorticoid deficiency was investigated in the thyroxin-re-placed, anterior hypophysectomized rat. Hypophysectomized rats demonstrated marked impairment in the excretion of an oral water load (32 ± 4% vs. 94 ± 4%), plasma hypoosmolality (281 ± 2 vs. 289 ± 2 mOsm/kg), and hyponatremia (129 ± 1 vs. 140 ± 1 mEq/liter) compared to controls (all P < 0.001). These defects were associated with increased levels of plasma arginine vasopressin (3.05 ± 0.45 vs. 1.38 ± 0.11 pg/ml; P < 0.001). Following physiologic corticosterone replacement in hypophysectomized rats, the percentage of the water load excreted, free water clearance, plasma sodium, plasma osmolality, and circulating levels of plasma arginine vasopressin were all restored to control values. This correction of water diuresis occurred in the absence of changes in GFR or solute excretion. The defect in water excretion and the elevation of plasma arginine vasopressin could not be corrected by chronic extracellular volume expansion in the absence of glucocorticoid replacement. It is concluded that (a) increased secretion of vasopressin plays an important role in the impaired water diuresis of isolated glucorticoid deficiency; (b) physiologic corticosterone replacement corrects both the impaired water excretion and the increased secretion of vasopressin associated with glucocorticoid deficiency; and (c) a volume-independent nonosmotic stimulus to vasopressin secretion may be activated by the chronic absence of glucocorticoid hormones.Rôle de l'rginine vasopressine du plasma dans l'ncapacite de diluer l'urine au cours du déficit isolé en glucocorticoïdes chez le rat. Le rôle de l'hormone antidiurétique dans l'incapacité à diluer l'urine au cours du déficit isolé en glucocorticoïdes a été étudié chez des rats ayant subi une hypophysectomie antérieure et compensés par de la thyroxine. Les rats hypohysectomisés ont un déficit important de l'excrétion d'une charge en eau (32 ± 4% contre 94 ± 4%), une hypoosmolalité plasmatique (281 ± 2 contre 289 ± 2 mOsm/kg), et une hyponatrémie (129 ± 1 contre 140 ± 1 mEq/liter), par comparaison aux contrôles (P < 0,001). Ces modifications sont associées à des concentrations plasmatiques élevées d'arginine vasopressine (3,05 ± 0,45 contre 1,38 ± 0,11 pg/ml; P < 0,001). L'administration de corticostérone aux rats hypophysectomisés ramène aux valeurs contrôles le pourcentage de la charge d'eau excrétée, la clearance de l'eau libre, la natrémie, l'osmolalité plasmatique et la concentration circulante d'arginine vasopressine. Cette restauration de la diurèse aqueuse est observée en l'absence de modifications du débit de filtration glomérulaire ou du débit urinaire de substances dissoutes. Le déficit d'excrétion de l'eau et l'augmentation de l'arginine vasopressine du plasma ne peuvent pas être corrigés par une expansion chronique du volume extra-cellulaire en l'absence de traitement substitutif par les glucocorticoïdes. I1 est conclu que: (a) l'augmentation de la sécrétion de vasopressine joue un rôle important dans l'incapacité de diluer les urines observée au cours du déficit en glucocorticoïdes; (b) un traitement substitutif par des doses physiologiques de corticostérone corrige à la fois le déficit d'excrétion de l'eau et la sécrétion excessive de vasopressine associés au déficit en glucocorticoïdes; et (c) un stimulus, non osmotique et indépendant du volume extracellulaire, de la sécrétion de vasopressine peut être activé par l'absence chronique d'hormones glucocorticoïdes

The Comparative Toxicogenomics Database (CTD).

The Mount Desert Island Biological Laboratory in Salsbury Cove, Maine, USA, is developing the Comparative Toxicogenomics Database (CTD), a community-supported genomic resource devoted to genes and proteins of human toxicologic significance. CTD will be the first publicly available database to a) provide annotated associations among genes, proteins, references, and toxic agents, with a focus on annotating data from aquatic and mammalian organisms; b) include nucleotide and protein sequences from diverse species; c) offer a range of analysis tools for customized comparative studies; and d) provide information to investigators on available molecular reagents. This combination of features will facilitate cross-species comparisons of toxicologically significant genes and proteins. These comparisons will promote understanding of molecular evolution, the significance of conserved sequences, the genetic basis of variable sensitivity to environmental agents, and the complex interactions between the environment and human health. CTD is currently under development, and the planned scope and functions of the database are described herein. The intent of this report is to invite community participation in the development of CTD to ensure that it will be a valuable resource for environmental health, molecular biology, and toxicology research

Combinatorial pharmacodynamics of polymyxin B and tigecycline against heteroresistant Acinetobacter baumannii

The prevalence of heteroresistant Acinetobacter baumannii is increasing. Infections due to these resistant pathogens pose a global treatment challenge. Here, the pharmacodynamic activities of polymyxin B (PMB) (2–20 mg/L) and tigecycline (0.15–4 mg/L) were evaluated as monotherapy and in combination using a 4 × 4 concentration array against two carbapenem-resistant and polymyxin-heteroresistant A. baumannii isolates. Time Kill Experiments was employed at starting inocula of 106 and 108 CFU/mL over 48 h. Clinically relevant combinations of PMB (2 mg/L) and tigecycline (0.90 mg/L) resulted in greater reductions in the bacterial population compared with polymyxin alone by 8 h (ATCC 19606, −6.38 vs. −3.43 log10 CFU/mL; FADDI AB115, −1.38 vs. 2.08 log10 CFU/mL). At 10× the clinically achievable concentration (PMB 20 mg/L in combination with tigecycline 0.90 mg/L), there was bactericidal activity against FADDI AB115 by 4 h that was sustained until 32 h, and against ATCC 19606 that was sustained for 48 h. These studies show that aggressive polymyxin-based dosing in combination with clinically achievable tigecycline concentrations results in early synergistic activity that is not sustained beyond 8 h, whereas combinations with higher tigecycline concentrations result in sustained bactericidal activity against both isolates at both inocula. These results indicate a need for optimised front-loaded polymyxin-based combination regimens that utilise high polymyxin doses at the onset of treatment to achieve good pharmacodynamic activity whilst minimising adverse events

Natural history of HFE simple heterozygosity for C282Y and H63D: A prospective 12-year study

Background and Aim - The risk of hemochromatosis-related morbidity for HFE simple heterozygosity for either the C282Y or H63D substitutions in the HFE protein was assessed using a prospective community-based cohort study. Methods - HFE genotypes were measured for 31 192 persons of northern European descent, aged between 40 and 69 years when recruited to the Melbourne Collaborative Cohort Study, and subjects were followed for an average of 12 years. For a random sample of 1438 participants stratified according to HFE genotype, two sets of biochemical iron indices performed 12 years apart and, at follow-up only, the presence/absence of six disease features associated with hereditary hemochromatosis were obtained. Summary data for 257 (139 female) C282Y simple heterozygotes and 123 (74 female) H63D simple heterozygotes were compared with 330 (181 female) controls with neither HFE mutation. Results - At baseline, mean transferrin saturation (TS) (95% confidence interval) and prevalence of TS > 55% were 35.14% (33.25, 37.04) and 3/112 (3%), 33.03% (29.9, 36.15) and 0/39 (0%), and 29.67% (27.93, 31.4) and 3/135 (2%) for C282Y, H63D and wild-type male participants, respectively. At follow-up, mean TS levels remained similar to baseline levels for both men and women irrespective of simple heterozygosity for either mutation. No HFE C282Y or H63D simple heterozygotes had documented iron overload (based on hepatic iron measures or serum ferritin greater than 1000 mg/L at baseline with documented therapeutic venesection). Conclusion - No documented iron overload was observed for HFE simple heterozygotes for either C282Y or H63D, and morbidity for both HFE simple heterozygote groups was similar to that of HFE wild-type participants

Effect of COVID-19 on presentations of decompensated liver disease in Scotland

BACKGROUND AND AIMS: SARS-CoV-2 and consequent pandemic has presented unique challenges. Beyond the direct COVID-related mortality in those with liver disease, we sought to determine the effect of lockdown on people with liver disease in Scotland. The effect of lockdown on those with alcohol-related disease is of interest; and whether there were associated implications for a change in alcohol intake and consequent presentations with decompensated disease. METHODS: We performed a retrospective analysis of patients admitted to seven Scottish hospitals with a history of liver disease between 1 April and 30 April 2020 and compared across the same time in 2017, 2018 and 2019. We also repeated an intermediate assessment based on a single centre to examine for delayed effects between 1 April and 31 July 2020. RESULTS: We found that results and outcomes for patients admitted in 2020 were similar to those in previous years in terms of morbidity, mortality, and length of stay. In the Scotland-wide cohort: admission MELD (Model for End-stage Liver Disease) (16 (12–22) vs 15 (12–19); p=0.141), inpatient mortality ((10.9% vs 8.6%); p=0.499) and length of stay (8 days (4–15) vs 7 days (4–13); p=0.140). In the Edinburgh cohort: admission MELD (17 (12–23) vs 17 (13–21); p=0.805), inpatient mortality ((13.7% vs 10.1%; p=0.373) and length of stay (7 days (4–14) vs 7 days (3.5–14); p=0.525)). CONCLUSION: This assessment of immediate and medium-term lockdown impacts on those with chronic liver disease suggested a minimal effect on the presentation of decompensated liver disease to secondary care

Development of a Benchmark Eddy Flux Evapotranspiration Dataset for Evaluation of Satellite-Driven Evapotranspiration Models Over the CONUS

A large sample of ground-based evapotranspiration (ET) measurements made in the United States, primarily from eddy covariance systems, were post-processed to produce a benchmark ET dataset. The dataset was produced primarily to support the intercomparison and evaluation of the OpenET satellite-based remote sensing ET (RSET) models and could also be used to evaluate ET data from other models and approaches. OpenET is a web-based service that makes field-delineated and pixel-level ET estimates from well-established RSET models readily available to water managers, agricultural producers, and the public. The benchmark dataset is composed of flux and meteorological data from a variety of providers covering native vegetation and agricultural settings. Flux footprint predictions were developed for each station and included static flux footprints developed based on average wind direction and speed, as well as dynamic hourly footprints that were generated with a physically based model of upwind source area. The two footprint prediction methods were rigorously compared to evaluate their relative spatial coverage. Data from all sources were post-processed in a consistent and reproducible manner including data handling, gap-filling, temporal aggregation, and energy balance closure correction. The resulting dataset included 243,048 daily and 5,284 monthly ET values from 194 stations, with all data falling between 1995 and 2021. We assessed average daily energy imbalance using 172 flux sites with a total of 193,021 days of data, finding that overall turbulent fluxes were understated by about 12% on average relative to available energy. Multiple linear regression analyses indicated that daily average latent energy flux may be typically understated slightly more than sensible heat flux. This dataset was developed to provide a consistent reference to support evaluation of RSET data being developed for a wide range of applications related to water accounting and water resources management at field to watershed scales

Discovery and Rossiter-McLaughlin Effect of Exoplanet Kepler-8b

We report the discovery and the Rossiter-McLaughlin effect of Kepler-8b, a transiting planet identified by the NASA Kepler Mission. Kepler photometry and Keck-HIRES radial velocities yield the radius and mass of the planet around this F8IV subgiant host star. The planet has a radius RP = 1.419 RJ and a mass, MP = 0.60 MJ, yielding a density of 0.26 g cm^-3, among the lowest density planets known. The orbital period is P = 3.523 days and orbital semima jor axis is 0.0483+0.0006/-0.0012 AU. The star has a large rotational v sin i of 10.5 +/- 0.7 km s^-1 and is relatively faint (V = 13.89 mag), both properties deleterious to precise Doppler measurements. The velocities are indeed noisy, with scatter of 30 m s^-1, but exhibit a period and phase consistent with the planet implied by the photometry. We securely detect the Rossiter-McLaughlin effect, confirming the planet's existence and establishing its orbit as prograde. We measure an inclination between the projected planetary orbital axis and the projected stellar rotation axis of lambda = -26.9 +/- 4.6 deg, indicating a moderate inclination of the planetary orbit. Rossiter-McLaughlin measurements of a large sample of transiting planets from Kepler will provide a statistically robust measure of the true distribution of spin-orbit orientations for hot jupiters in general.Comment: 26 pages, 8 figures, 2 tables; In preparation for submission to the Astrophysical Journa

Planetary Candidates Observed by Kepler VI: Planet Sample from Q1-Q16 (47 Months)

\We present the sixth catalog of Kepler candidate planets based on nearly 4 years of high precision photometry. This catalog builds on the legacy of previous catalogs released by the Kepler project and includes 1493 new Kepler Objects of Interest (KOIs) of which 554 are planet candidates, and 131 of these candidates have best fit radii <1.5 R_earth. This brings the total number of KOIs and planet candidates to 7305 and 4173 respectively. We suspect that many of these new candidates at the low signal-to-noise limit may be false alarms created by instrumental noise, and discuss our efforts to identify such objects. We re-evaluate all previously published KOIs with orbital periods of >50 days to provide a consistently vetted sample that can be used to improve planet occurrence rate calculations. We discuss the performance of our planet detection algorithms, and the consistency of our vetting products. The full catalog is publicly available at the NASA Exoplanet Archive.Comment: 18 pages, to be published in the Astrophysical Journal Supplement Serie

The Infrared Array Camera (IRAC) for the Spitzer Space Telescope

The Infrared Array Camera (IRAC) is one of three focal plane instruments in the Spitzer Space Telescope. IRAC is a four-channel camera that obtains simultaneous broad-band images at 3.6, 4.5, 5.8, and 8.0 microns. Two nearly adjacent 5.2x5.2 arcmin fields of view in the focal plane are viewed by the four channels in pairs (3.6 and 5.8 microns; 4.5 and 8 microns). All four detector arrays in the camera are 256x256 pixels in size, with the two shorter wavelength channels using InSb and the two longer wavelength channels using Si:As IBC detectors. IRAC is a powerful survey instrument because of its high sensitivity, large field of view, and four-color imaging. This paper summarizes the in-flight scientific, technical, and operational performance of IRAC.Comment: 7 pages, 3 figures. Accepted for publication in the ApJS. A higher resolution version is at http://cfa-www.harvard.edu/irac/publication