Hemodynamic and inotropic effects of endothelin-1 in vivo

Endothelin-1 (ET-1) is known to have strong vasoactive properties. Contradictory results have been reported with regard to its inotropic effects. This study examined the dose-dependent (500, 1000, 2500, 5000 and 10,000 ng ET-1/kg vs. NaCl controls) hemodynamic and inotropic effects of ET-1 in 53 open-chest rats during and after a 7-min infusion. Besides measurements in the intact circulation the myocardial function was examined by isovolumic registrations independent of peripheral vascular effects. A transient ET-1 induced (500, 1000, 2500, 5000 ng ET-1/kg) decrease of the left ventricular systolic pressure (LVSP) and the mean aortic pressure (AoPmean) was followed by a dose-related rise of these pressures (LVSP: -1%, -1%, +8%, +16% vs. preinfusion values; AoPmean: -11%, +9%, +39%, +52%). Heart rate (HR) was not influenced by ET-1. Due to the dose-dependent decrease of the stroke volume (SV) the cardiac output (CO) was reduced (CO: -8%, -23%, -40%, -50%). After an initial vasodilatation ET-1 elevates the total peripheral resistance (TPR: -1%, +49%, +139%, +215%) dose-dependently. 10,000 ng ET-1/kg was a lethal dose resulting in cardiac failure within minutes (low output). Since the maximum of the isovolumic LVSP (peak LVSP) and the corresponding dP/dtmax (peak dP/dtmax) were unchanged under ET-1, the isovolumic measurements do not indicate a positive inotropic effect of ET-1 in vivo in contrast to published results of in vitro experiments. It may be possible that a direct positive inotropic effect of ET-1 observed in in vitro studies is counterbalanced in vivo by an indirect negative inotropic effect due to the coronary-constrictive effect of ET-1

Enzyme-linked immunosorbent assay for urinary albumin at low concentrations

We describe an enzyme-linked immunosorbent assay (ELISA) for urinary albumin. It requires only commercially available reagents, can detect as little as 16 micrograms of albumin per liter, and analytical recovery ranges from 92 to 116%. The assay is simple, rapid, and inexpensive. Albumin excretion was 6.2 (SD 4.1) mg/24 h in healthy subjects (n = 40), 14.7 (SD 7.2) mg/24 h in albumin-test-strip-negative Type I diabetics (n = 11), and 19.7 (SD 16.2) mg/24 h in patients with essential hypertension (n = 12)

Magnetotransport of lanthanum doped RuSr2GdCu2O8 - the role of gadolinium

Strongly underdoped RuSr_1.9La_0.1GdCu_2O_8 has been comprehensively studied by dc magnetization, microwave measurements, magnetoresistivity and Hall resistivity in fields up to 9 T and temperatures down to 1.75 K. Electron doping by La reduces the hole concentration in the CuO2 planes and completely suppresses superconductivity. Microwave absorption, dc resistivity and ordinary Hall effect data indicate that the carrier concentration is reduced and a semiconductor-like temperature dependence is observed. Two magnetic ordering transitions are observed. The ruthenium sublattice orders antiferromagnetically at 155 K for low applied magnetic field and the gadolinium sublattice antiferromagnetically orders at 2.8 K. The magnetoresistivity exhibits a complicated temperature dependence due to the combination of the two magnetic orderings and spin fluctuations. It is shown that the ruthenium magnetism influences the conductivity in the RuO2 layers while the gadolinium magnetism influences the conductivity in the CuO2 layers. The magnetoresistivity is isotropic above 4 K, but it becomes anisotropic when gadolinium orders antiferromagnetically.Comment: 7 pages, 9 figures, submitted to European Physical Journal

First Results of the PixelGEM Central Tracking System for COMPASS

For its physics program with a high-intensity hadron beam of up to 2e7 particles/s, the COMPASS experiment at CERN requires tracking of charged particles scattered by very small angles with respect to the incident beam direction. While good resolution in time and space is mandatory, the challenge is imposed by the high beam intensity, requiring radiation-hard detectors which add very little material to the beam path in order to minimize secondary interactions. To this end, a set of triple-GEM detectors with a hybrid readout structure consisting of pixels in the beam region and 2-D strips in the periphery was designed and built. Successful prototype tests proved the performance of this new detector type, showing both extraordinary high rate capability and detection efficiency. The amplitude information allowed to achieve spatial resolutions about a factor of 10 smaller than the pitch and a time resolution close to the theoretical limit imposed by the layout. The PixelGEM central tracking system consisting of five detectors, slightly improved with respect to the prototype, was completely installed in the COMPASS spectrometer in spring 2008

Cyclosporine A attenuates the natriuretic action of loop diuretics by inhibition of renal COX-2 expression

Cyclosporine A attenuates the natriuretic action of loop diuretics by inhibition of renal COX-2 expression.BackgroundIt is known that inhibition of cyclooxygenase (COX) impairs the renal actions of loop diuretics. Recently, we found that cyclosporine A (CsA) inhibits renal COX-2 expression. Therefore, we examined the interferences of CsA with the renal actions of loop diuretics.MethodWe investigated the renal effects of furosemide administration (12mg/day subcutaneously) in male Sprague-Dawley rats receiving in addition vehicle, CsA (15mg/kg × day), rofecoxib (10mg/kg × day), or a combination of both.ResultsCsA, rofecoxib, and their combination lowered the furosemide-induced increase of prostaglandin E2 (PGE2) and of 6-keto prostaglandin F1α (6-keto PGF1α) excretion by 55% and by 70%. They also lowered furosemide stimulated renal excretion of sodium and water by about 65% and 60%. Basal as well as furosemide-induced stimulation of plasma renin activity (PRA) and of renal renin mRNA was further enhanced by CsA. In contrast, rofecoxib attenuated the furosemide-induced rise of PRA and of renin mRNA, both in the absence and in the presence of CsA. In addition, the increase in plasma 6-keto PGF1α levels by furosemide was further enhanced by CsA and was attenuated by rofecoxib.ConclusionTaken together, our data suggest that CsA acts as an antinatriuretic, likely by the inhibition of COX-2–mediated renal prostanoid formation. Since the furosemide-induced stimulation of the renin system is not attenuated by CsA but by COX-2 inhibition, we speculate that extrarenal COX-2–derived prostanoids may be involved in the stimulation of the renin system by CsA and by loop diuretics

Gene expression of adenosine receptors along the nephron

Gene expression of adenosine receptors along the nephron.BackgroundIn view of the multiple effects of adenosine on kidney function, this study aimed to determine the expression of adenosine receptors (AR) along the rat and mouse nephron.MethodsFor this purpose, we semiquantified mRNA abundance for adenosine A1-, A2A-, A2B-, and A3 receptors by RNAse protection and by reverse transcription-polymerase chain reaction (RT-PCR) in the kidney zones and in the different nephron segments of mice and rats.ResultsWe found very similar expression patterns for rat and mice. For the kidney zones A1-AR mRNA and A2A-AR mRNA abundance displayed a marked difference, with an increase from cortex to the inner medulla. This was not seen for A2B receptors, which showed in general a rather weak expression. Along the nephron, A1-AR was strongly expressed in the thin limbs of Henle and in the collecting duct system and to a lesser extent in the medullary thick ascending limb. A2A-AR mRNA was clearly detected in glomeruli but not in other nephron segments. A2B-AR mRNA was strongly expressed in the cortical thick ascending limb of Henle and in the distal convoluted tubule. A3-AR mRNA was not found in any nephron segment.ConclusionOur data demonstrate a distinct mutual expression of the AR subtypes along the nephron. A1 receptors are expressed in medullary tubular structures, while A2B receptors are predominant in cortical tubular structures. A2A receptor expression in the kidney appears to be restricted to vascular cells

Neural representation of calling songs and their behavioral relevance in the grasshopper auditory system

Acoustic communication plays a key role for mate attraction in grasshoppers. Males use songs to advertise themselves to females. Females evaluate the song pattern, a repetitive structure of sound syllables separated by short pauses, to recognize a conspecific male and as proxy to its fitness. In their natural habitat females often receive songs with degraded temporal structure. Perturbations may, for example, result from the overlap with other songs. We studied the response behavior of females to songs that show different signal degradations. A perturbation of an otherwise attractive song at later positions in the syllable diminished the behavioral response, whereas the same perturbation at the onset of a syllable did not affect song attractiveness. We applied naïve Bayes classifiers to the spike trains of identified neurons in the auditory pathway to explore how sensory evidence about the acoustic stimulus and its attractiveness is represented in the neuronal responses. We find that populations of three or more neurons were sufficient to reliably decode the acoustic stimulus and to predict its behavioral relevance from the single-trial integrated firing rate. A simple model of decision making simulates the female response behavior. It computes for each syllable the likelihood for the presence of an attractive song pattern as evidenced by the population firing rate. Integration across syllables allows the likelihood to reach a decision threshold and to elicit the behavioral response. The close match between model performance and animal behavior shows that a spike rate code is sufficient to enable song pattern recognition.Peer Reviewe

Heterobimetallic Gold/Ruthenium Complexes Synthesized via Post‐functionalization and Applied in Dual Photoredox Gold Catalysis

The synthesis of heterobimetallic AuI/RuII complexes of the general formula syn- and anti-[{AuCl}(L1∩L2){Ru(bpy)$_{2}$}][PF$_{6}$]$_{2}$ is reported. The ditopic bridging ligand L1∩L2 refers to a P,N hybrid ligand composed of phosphine and bipyridine substructures, which was obtained via a post-functionalization strategy based on Diels-Alder reaction between a phosphole and a maleimide moiety. It was found that the stereochemistry at the phosphorus atom of the resulting 7-phosphanorbornene backbone can be controlled by executing the metal coordination and the cycloaddition reaction in a different order. All precursors, as well as the mono- and multimetallic complexes, were isolated and fully characterized by various spectroscopic methods such as NMR, IR, and UV-vis spectroscopy as well as cyclic voltammetry. Photophysical measurements show efficient phosphorescence for the investigated monometallic complex anti-[(L1∩L2){Ru(bpy)$_{2}$}][PF$_{6}$]$_{2}$ and the bimetallic analogue syn-[{AuCl}(L1∩L2){Ru(bpy)$_{2}$}][PF$_{6}$]$_{2}$, thus indicating a small influence of the {AuCl} fragment on the photoluminescence properties. The heterobimetallic Au$^{I}$/Ru$^{II}$ complexes syn- and anti-[{AuCl}(L1∩L2){Ru(bpy)$_{2}$}][PF$_{6}$]$_{2}$ are both active catalysts in the P-arylation of aryldiazonium salts promoted by visible light with H-phosphonate affording arylphosphonates in yields of up to 91 %. Both dinuclear complexes outperform their monometallic counterparts

Toll-like receptor 4 in experimental kidney transplantation: early mediator of endogenous danger signals

The role of toll-like receptors (TLRs) has been described in the pathogenesis of renal ischemia/reperfusion injury, but data on the expression and function of TLR4 during renal allograft damage are still scarce. We analyzed the expression of TLR4 in an experimental rat model 6 and 28 days after allogeneic kidney transplantation in comparison to control rats and rats after syngeneic transplantation. On day 6, a significant induction in TLR4 expression - restricted to the glomerular compartment - was found in acute rejecting allografts only. TLR4 expression strongly correlated with renal function, and TLR4 induction was accompanied by a significant increase in CC chemokine expression within the graft as well as in urinary CC chemokine excretion. TLR4 induction may be caused by an influx of macrophages as well as TLR4-expressing intrinsic renal cells. Fibrinogen deposition in renal allografts correlated with renal TLR4 expression and may act as a potent stimulator of chemokine release via TLR4 activation. This study provides, for the first time, data about the precise intrarenal localization and TLR4 induction after experimental kidney transplantation. It supports the hypothesis that local TLR4 activation by endogenous ligands may be one pathological link from unspecific primary allograft damage to subsequent chemokine release, infiltration and activation of immune cells leading to deterioration of renal function and induction of renal fibrosis. Copyright (c) 2012 S. Karger AG, Base

Multistimuli‐Responsive [3]Dioxaphosphaferrocenophanes with Orthogonal Switches

Novel multistimuli-responsive phosphine ligands comprising a redox-active [3]dioxaphosphaferrocenophane backbone and a P-bound imidazolin-2-ylidenamino entity that allows switching by protonation are reported. Investigation of the corresponding metal complexes and their redox behaviour are reported and show the sensitivity of the system towards protonation and metal coordination. The experimental findings are supported by DFT calculations. Protonation and oxidation events are applied in Rh-catalysed hydrosilylations and demonstrate a remarkable influence on reactivity and/or selectivity