Cisplatin-induced emesis: systematic review and meta-analysis of the ferret model and the effects of 5-HT3 receptor antagonists

PURPOSE: The ferret cisplatin emesis model has been used for ~30 years and enabled identification of clinically used anti-emetics. We provide an objective assessment of this model including efficacy of 5-HT(3) receptor antagonists to assess its translational validity. METHODS: A systematic review identified available evidence and was used to perform meta-analyses. RESULTS: Of 182 potentially relevant publications, 115 reported cisplatin-induced emesis in ferrets and 68 were included in the analysis. The majority (n = 53) used a 10 mg kg(−1) dose to induce acute emesis, which peaked after 2 h. More recent studies (n = 11) also used 5 mg kg(−1), which induced a biphasic response peaking at 12 h and 48 h. Overall, 5-HT(3) receptor antagonists reduced cisplatin (5 mg kg(−1)) emesis by 68% (45–91%) during the acute phase (day 1) and by 67% (48–86%) and 53% (38–68%, all P < 0.001), during the delayed phase (days 2, 3). In an analysis focused on the acute phase, the efficacy of ondansetron was dependent on the dosage and observation period but not on the dose of cisplatin. CONCLUSION: Our analysis enabled novel findings to be extracted from the literature including factors which may impact on the applicability of preclinical results to humans. It reveals that the efficacy of ondansetron is similar against low and high doses of cisplatin. Additionally, we showed that 5-HT(3) receptor antagonists have a similar efficacy during acute and delayed emesis, which provides a novel insight into the pharmacology of delayed emesis in the ferret

A review of elliptical and disc galaxy structure, and modern scaling laws

A century ago, in 1911 and 1913, Plummer and then Reynolds introduced their models to describe the radial distribution of stars in `nebulae'. This article reviews the progress since then, providing both an historical perspective and a contemporary review of the stellar structure of bulges, discs and elliptical galaxies. The quantification of galaxy nuclei, such as central mass deficits and excess nuclear light, plus the structure of dark matter halos and cD galaxy envelopes, are discussed. Issues pertaining to spiral galaxies including dust, bulge-to-disc ratios, bulgeless galaxies, bars and the identification of pseudobulges are also reviewed. An array of modern scaling relations involving sizes, luminosities, surface brightnesses and stellar concentrations are presented, many of which are shown to be curved. These 'redshift zero' relations not only quantify the behavior and nature of galaxies in the Universe today, but are the modern benchmark for evolutionary studies of galaxies, whether based on observations, N-body-simulations or semi-analytical modelling. For example, it is shown that some of the recently discovered compact elliptical galaxies at 1.5 < z < 2.5 may be the bulges of modern disc galaxies.Comment: Condensed version (due to Contract) of an invited review article to appear in "Planets, Stars and Stellar Systems"(www.springer.com/astronomy/book/978-90-481-8818-5). 500+ references incl. many somewhat forgotten, pioneer papers. Original submission to Springer: 07-June-201

Characterization of nociceptin/orphanin FQ binding sites in dog brain membranes

Nociceptin/orphanin FQ (N/OFQ) is the endogenous ligand for the N/OFQ receptor (NOP), whose characteristics in the dog are unknown. We therefore compared [3H]N/OFQ binding in dog and rat brain membranes. Radioligand saturation/competition studies with these membranes and leucyl-[3H]N/OFQ(1– 17)OH or the novel radioligand [3H]N/OFQ(1–13)NH2 were performed to determine receptor density and ligand affinity. The density of classic opioid receptors was determined by using [3H]diprenorphine. Leucyl- [3H]N/OFQ(1–17)OH binding was concentration dependent and saturable in dog (maximum binding capacity [Bmax], 28.7 2.8 fmol/mg of protein; equilibrium dissociation constant as negative log [pKd], 10.27 0.11) and rat (Bmax, 137.0 12.9 fmol/mg of protein; pKd, 10.410.05). In comparison, the Bmax and pKd of [3H]diprenorphine were, respectively, 77.75.3 fmol/mg of protein and 9.74 0.09 in dog and 79.1 18.2 fmol/mg of protein and 9.51 0.04 in rat. In dog, [3H]N/OFQ(1–13)NH2 binding to NOP receptors was also saturable (Bmax, 23.7 2.0 fmol/mg of protein; pKd, 10.16 0.12). In both species, leucyl-[3H]N/ OFQ(1–17)OH was displaced by various NOP ligands. Dynorphin A, N/OFQ(1–5)NH2, and nocistatin were essentially inactive. There was a significant positive correlation (r2 0.95; P 0.0001) between pKi values (an estimate of affinity) obtained in displacement studies in rat and dog. We have demonstrated a low density of NOP receptors, measured with two radioligands, in dog, and these receptors display a high degree of pharmacological similarity with those natively expressed in the rat

Unpaired electrons in the heavy-fermion superconductor CeCoIn5.

Thermal conductivity and specific heat were measured in the superconducting state of the heavy-fermion material Ce(1-x)La(x)CoIn5. With increasing impurity concentration x, the suppression of T(c) is accompanied by the increase in residual electronic specific heat expected of a d-wave superconductor, but it occurs in parallel with a decrease in residual electronic thermal conductivity. This contrasting behavior reveals the presence of uncondensed electrons coexisting with nodal quasiparticles. An extreme multiband scenario is proposed, with a d-wave superconducting gap on the heavy-electron sheets of the Fermi surface and a negligible gap on the light, three-dimensional pockets

Absence of 3a0 charge density wave order in the infinite-layer nickelate NdNiO2

A hallmark of many unconventional superconductors is the presence of many-body interactions that give rise to broken-symmetry states intertwined with superconductivity. Recent resonant soft X-ray scattering experiments report commensurate 3a0 charge density wave order in infinite-layer nickelates, which has important implications regarding the universal interplay between charge order and superconductivity in both cuprates and nickelates. Here we present X-ray scattering and spectroscopy measurements on a series of NdNiO2+x samples, which reveal that the signatures of charge density wave order are absent in fully reduced, single-phase NdNiO2. The 3a0 superlattice peak instead originates from a partially reduced impurity phase where excess apical oxygens form ordered rows with three-unit-cell periodicity. The absence of any observable charge density wave order in NdNiO2 highlights a crucial difference between the phase diagrams of cuprate and nickelate superconductors

Orbital symmetries of charge density wave order in YBa 2 Cu 3 O 6+ x

Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). Charge density wave (CDW) order has been shown to compete and coexist with superconductivity in underdoped cuprates. Theoretical proposals for the CDW order include an unconventional d-symmetry form factor CDW, evidence for which has emerged from measurements, including resonant soft x-ray scattering (RSXS) in YBa2Cu3O6+x (YBCO). Here, we revisit RSXS measurements of the CDW symmetry in YBCO, using a variation in the measurement geometry to provide enhanced sensitivity to orbital symmetry. We show that the (0 0.31 L) CDW peak measured at the Cu L edge is dominated by an s form factor rather than a d form factor as was reported previously. In addition, by measuring both (0.31 0 L) and (0 0.31 L) peaks, we identify a pronounced difference in the orbital symmetry of the CDW order along the a and b axes, with the CDW along the a axis exhibiting orbital order in addition to charge order