Simplified Iohexol-Based Method for Measurement of Glomerular Filtration Rate in Goats and Pigs

SIMPLE SUMMARY: To improve the treatment of patients with kidney disease, new therapies are being developed. Before being used on humans, such therapies need to be tested on animals with kidney disease because reduced kidney function may influence the safety and efficacy of the treatment. Using large animals for this purpose is important because they tolerate frequent blood sampling, which allows for repeated monitoring. Goats seem particularly suitable for the evaluation of novel hemodialysis therapies since they are docile, have easily accessible neck veins to obtain blood access and body weights comparable with humans. Currently, no simple method is available to measure kidney function in goats (with or without impaired kidney function). Therefore, we developed a simple method to measure the kidney function in goats and pigs, which is based on a single injection of iohexol and requires three blood samples. Subsequently, kidney function can be calculated using a formula derived from pharmacokinetic modelling. The measurement of kidney function using our simplified method is relatively easy to perform, reduces total blood sampling and eliminates the need for an indwelling bladder catheter as compared to existing methods that require continuous infusion of a substance and timed urine collection. ABSTRACT: The preclinical evaluation of novel therapies for chronic kidney disease requires a simple method for the assessment of kidney function in a uremic large animal model. An intravenous bolus of iohexol was administered to goats (13 measurements in n = 3 goats) and pigs (23 measurements in n = 5 pigs) before and after induction of kidney failure, followed by frequent blood sampling up to 1440 min. Plasma clearance (CL) was estimated by a nonlinear mixed-effects model (CL(NLME)) and by a one-compartmental pharmacokinetic disposition model using iohexol plasma concentrations during the terminal elimination phase (CL(1CMT)). A simple method (CL(SM)) for the calculation of plasma clearance was developed based on the most appropriate relationship between CL(NLME) and CL(1CMT). CL(SM) and CL(NLME) showed good agreement (CL(NLME)/CL(SM) ratio: 1.00 ± 0.07; bias: 0.03 ± 1.64 mL/min; precision CL(SM) and CL(NLME): 80.9% and 80.7%, respectively; the percentage of CL(SM) estimates falling within ±30% (P30) or ±10% (P10) of CL(NLME): 53% and 12%, respectively). For mGFR(NLME) vs. mGFR(SM), bias was −0.25 ± 2.24 and precision was 49.2% and 53.6%, respectively, P30 and P10 for mGFR based on CL(SM) were 71% and 24%, respectively. A simple method for measurement of GFR in healthy and uremic goats and pigs was successfully developed, which eliminates the need for continuous infusion of an exogenous marker, urine collection and frequent blood sampling

English in product advertisements in non-english speaking countries in western europe: Product image and comprehension of the text

Although English has been shown to be the most frequently used foreign language in product advertisements in countries where it is not the native language, little is known about its effects. This article examines the response to advertisements in English compared to the response to the same ad in the local language in Western Europe on members of the target group for which the ad was intended: 715 young, highly educated female consumers. The use of English in a product ad does not appear to have any impact on image and price of the product, but it does affect text comprehension: the meaning of almost 40% of the English phrases was not understood. These results were the same for all countries involved in the study, irrespective of whether the respondents\u27 (self-) reported proficiency in English is high or low. © Taylor & Francis Group, LLC

The Extraordinary `Superthin' Spiral Galaxy UGC7321. I. Disk Color Gradients and Global Properties from Multiwavelength Observations

We present B- and R-band imaging and photometry, H-alpha narrow-band imaging, NIR H-band imaging, and HI 21-cm spectroscopy of the nearby Sd spiral galaxy UGC7321. UGC7321 exhibits a remarkably thin stellar disk with no bulge component. The galaxy has a very diffuse, low surface brightness disk, which appears to suffer little internal extinction in spite of its edge-on geometry. The UGC7321 disk shows significant B-R color gradients in both the radial and vertical directions. These color gradients cannot be explained solely by dust and are indicative of changes in the mix of stellar ages and/or metallicity as a function of both radius and height above the galaxy plane. The outer regions of the UGC7321 disk are too blue to be explained by low metallicity alone (B-R<0.6), and must be relatively young. However, the galaxy also contains stellar populations with B-R>1.1, indicating it is not a young or recently-formed galaxy. The disk of UGC7321 is not a simple exponential, but exhibits a light excess at small radii, as well as distinct surface brightness zones. Together the properties of UGC7321 imply that it is an under-evolved galaxy in both a dynamical and in a star-formation sense. (Abridged)Comment: Accepted to the Astronomical Journal; 28 pages, 1 table and 21 figures (GIF and postscript

Star Formation from Galaxies to Globules

The empirical laws of star formation suggest that galactic-scale gravity is involved, but they do not identify the actual triggering mechanisms for clusters in the final stages. Many other triggering processes satisfy the empirical laws too, including turbulence compression and expanding shell collapse. The self-similar nature of the gas and associated young stars suggests that turbulence is more directly involved, but the small scale morphology of gas around most embedded clusters does not look like a random turbulent flow. Most clusters look triggered by other nearby stars. Such a prominent local influence makes it difficult to understand the universality of the Kennicutt and Schmidt laws on galactic scales. A unified view of multi-scale star formation avoids most of these problems. Ambient self-gravity produces spiral arms and drives much of the turbulence that leads to self-similar structures, while localized energy input from existing clusters and field supernovae triggers new clusters in pre-existing clouds. The hierarchical structure in the gas made by turbulence ensures that the triggering time scales with size, giving the Schmidt law over a wide range of scales and the size-duration correlation for young star fields. The efficiency of star formation is determined by the fraction of the gas above a critical density of around 10^5 m(H2)/cc. Star formation is saturated to its largest possible value given the fractal nature of the interstellar medium.Comment: accepted for ApJ, 42 pages, Dannie Heineman prize lecture, January 200

The Metamorphosis of Tidally Stirred Dwarf Galaxies

We present results from high-resolution N-Body/SPH simulations of rotationally supported dwarf irregular galaxies moving on bound orbits in the massive dark matter halo of the Milky Way.The dwarf models span a range in disk surface density and the masses and sizes of their dark halos are consistent with the predictions of cold dark matter cosmogonies. We show that the strong tidal field of the Milky Way determines severe mass loss in their halos and disks and induces bar and bending instabilities that transform low surface brightness dwarfs (LSBs) into dwarf spheroidals (dSphs) and high surface brightness dwarfs (HSBs) into dwarf ellipticals (dEs) in less than 10 Gyr. The final central velocity dispersions of the remnants are in the range 8-30 km/s and their final $v/\sigma$ falls to values $< 0.5$, matching well the kinematics of early-type dwarfs. The transformation requires the orbital time of the dwarf to be \simlt 3-4 Gyr, which implies a halo as massive and extended as predicted by hierarchical models of galaxy formation to explain the origin of even the farthest dSph satellites of the Milky Way, Leo I and Leo II. Only dwarfs with central dark matter densities as high as those of Draco and Ursa Minor can survive for 10 Gyr in the proximity of the Milky Way: this is naturally achieved within hierarchical models, where the densest objects should have small orbital times due to their early formation epochs. Part of the gas is stripped and part is funneled to the center due to the bar, generating one strong burst of star formation in HSBs and smaller, multiple bursts in LSBs. Extended low-surface brightness stellar and gaseous streams originate from LSBs and, when projected along the line of sight, can lead to overestimate the mass-to-light ratio of the bound remnant by a factor \simlt 2,Comment: 29 pages, 34 figures, submitted to ApJ. Figures 5,11 and 32 are given as separate GIF files. Other figures and the movies of the simulations can be found at http://pcblu.mib.infn.it/~lucio/LG/LG.htm

Can the PROPER intervention reduce psychotropic drug prescription in nursing home residents with dementia?:Results of a cluster-randomized controlled trial

Objectives:To evaluate the effect of the PROPER intervention in nursing home residents with dementia on the prevalence of psychotropic drug use and neuropsychiatric symptoms.Design:A cluster-randomized controlled design with two parallel groups (intervention versus usual care) and assessments at 0, 6, 12, and 18 months.Setting:Thirty-one dementia special care units within 13 long-term care organizations in the Netherlands.Participants:Three hundred eighty nursing home residents with dementiaIntervention:The PROPER intervention consisted of a structured and repeated multidisciplinary medication review, supported by education and continuous evaluation.Measurements:Prescriptions of antipsychotics, antidepressants, anxiolytics, and hypnotics, and occurrence of neuropsychiatric symptoms.Results:The prescription of any type of psychotropic drugs increased in the intervention group, and decreased in the control group, with an estimated difference of 3.9 percentage points per 6 months (p = 0.01). Effects for the individual drug groups were minor (differences of 1.6 percentage points and below per 6 months) and not statistically significant. The occurrence of neuropsychiatric symptoms remained stable in both the intervention and control groups during the follow-up of 18 months.Conclusions:The PROPER intervention failed to demonstrate effectiveness in reducing the prevalence of psychotropic drugs. It may be interesting to enrich the intervention with components that address personal attitudes and communication between nursing home professionals, not only with respect to the prescription of psychotropic drugs, but also to neuropsychiatric symptoms

Search for the evidence of endocrine disruption in the aquatic environment; Lessons to be learned from joint biological and chemical monitoring in the European project COMPREHEND

Between January 1999 and December 2001, the European Community project COMPREHEND was performed. The overall aim of COMPREHEND was to assess endocrine disruption in the aquatic environment in Europe, consequent to effluent discharge, with emphasis on estrogenic activity. COMPREHEND demonstrated the widespread occurrence of estrogenic effluents across Europe and presented evidence of impacts on a range of wild fish species. Using a variety of bioassays in combination with chemical analytical methods, estrogenic steroids of human origin from domestic wastewater effluents were identified as the most pervasive problem, although alkylphenols may be important estrogenic components of some industrial effluents. New tools have been developed for the identification of estrogenic effluents, and recommendations are made for the improvement of existing techniques. We have shown that individual fish within natural populations may be feminized to varying degrees, but it has not been possible to show, using traditional fish population parameters, that the survival of fish populations is threatened. However, laboratory-based fish life-cycle studies demonstrate the sensitivity of fish to estrogen (and androgen) exposure and how this might lead to complex (and potentially damaging) genetic changes at the population level. New approaches to this problem, utilizing recent advances made in the field of molecular and population genetics, are recommended. Finally, a study of estrogenic and androgenic activity of waste waters during the treatment process has shown that some of the existing wastewater treatment technologies have the potential to eliminate or minimize the hormonal activity of the final effluen

Abundance Gradients and the Formation of the Milky Way

In this paper we adopt a chemical evolution model, which is an improved version of the Chiappini, Matteucci and Gratton (1997) model, assuming two main accretion episodes for the formation of the Galaxy. The present model takes into account in more detail than previously the halo density distribution and explores the effects of a threshold density in the star formation process, during both the halo and disk phases. In the comparison between model predictions and available data, we have focused our attention on abundance gradients as well as gas, stellar and star formation rate distributions along the disk. We suggest that the mechanism for the formation of the halo leaves detectable imprints on the chemical properties of the outer regions of the disk, whereas the evolution of the halo and the inner disk are almost completely disentangled. This is due to the fact that the halo and disk densities are comparable at large Galactocentric distances and therefore the gas lost from the halo can substantially contribute to building up the outer disk. We also show that the existence of a threshold density for the star formation rate, both in the halo and disk phase, is necessary to reproduce the majority of observational data in the solar vicinity and in the whole disk. Moreover, we predict that the abundance gradients along the Galactic disk must have increased with time and that the average [alpha/Fe] ratio in stars (halo plus disk) slightly decrease going from 4 to 10 Kpcs from the Galactic center. We also show that the same ratios increase substantially towards the outermost disk regions and the expected scatter in the stellar ages decreases, because the outermost regions are dominated by halo stars.Comment: 41 pages (including the figures), To be published in Ap

Gas Mass Fractions and the Evolution of LSB Dwarf Galaxies

The optical and HI properties for a sample of low surface brightness (LSB) dwarf galaxies, cataloged from the Second Palomar Sky Survey, is presented. Gas mass fractions for LSB dwarfs reach the highest levels of any know galaxy type (f_g=95%) confirming that their low stellar densities are due to inefficient conversion of gas mass into stellar mass. Comparison with star formation models indicates that the blue optical colors of LSB dwarfs is not due to low metallicity or recent star formation and can only be explained by a dominant stellar population that is less than 5 Gyrs in mean age. If star formation occurs in OB complexes, similar to normal galaxies, then LSB dwarfs must undergo weak bursts traveling over the extent of the galaxy to maintain their LSB nature, which contributes to their irregular morphological appearance.Comment: 23 pages AAS LaTeX, 7 figures, accepted for publication in A

Development of a Multiphoton Fluorescence Lifetime Imaging Microscopy (FLIM) system using a Streak Camera

We report the development and detailed calibration of a multiphoton fluorescence lifetime imaging system (FLIM) using a streak camera. The present system is versatile with high spatial (0.2 micron) and temporal (50 psec) resolution and allows rapid data acquisition and reliable and reproducible lifetime determinations. The system was calibrated with standard fluorescent dyes and the lifetime values obtained were in very good agreement with values reported in literature for these dyes. We also demonstrate the applicability of the system to FLIM studies in cellular specimens including stained pollen grains and fibroblast cells expressing green fluorescent protein. The lifetime values obtained matched well with those reported earlier by other groups for these same specimens. Potential applications of the present system include the measurement of intracellular physiology and Fluorescence Resonance Energy Transfer (FRET) imaging which are discussed in the context of live cell imaging