Inhibition of α9α10 nicotinic acetylcholine receptors prevents chemotherapy-induced neuropathic pain

Opioids are first-line drugs for moderate to severe acute pain and cancer pain. However, these medications are associated with severe side effects, and whether they are efficacious in treatment of chronic nonmalignant pain remains controversial. Medications that act through alternative molecular mechanisms are critically needed. Antagonists of α9α10 nicotinic acetylcholine receptors (nAChRs) have been proposed as an important nonopioid mechanism based on studies demonstrating prevention of neuropathology after trauma-induced nerve injury. However, the key α9α10 ligands characterized to date are at least two orders of magnitude less potent on human vs. rodent nAChRs, limiting their translational application. Furthermore, an alternative proposal that these ligands achieve their beneficial effects by acting as agonists of GABA(B) receptors has caused confusion over whether blockade of α9α10 nAChRs is the fundamental underlying mechanism. To address these issues definitively, we developed RgIA4, a peptide that exhibits high potency for both human and rodent α9α10 nAChRs, and was at least 1,000-fold more selective for α9α10 nAChRs vs. all other molecular targets tested, including opioid and GABA(B) receptors. A daily s.c. dose of RgIA4 prevented chemotherapy-induced neuropathic pain in rats. In wild-type mice, oxaliplatin treatment produced cold allodynia that could be prevented by RgIA4. Additionally, in α9 KO mice, chemotherapy-induced development of cold allodynia was attenuated and the milder, temporary cold allodynia was not relieved by RgIA4. These findings establish blockade of α9-containing nAChRs as the basis for the efficacy of RgIA4, and that α9-containing nAChRs are a critical target for prevention of chronic cancer chemotherapy-induced neuropathic pain

Multimodality Treatment with Conventional Transcatheter Arterial Chemoembolization and Radiofrequency Ablation for Unresectable Hepatocellular Carcinoma

Background/Aims: To evaluate the efficacy of multimodality treatment consisting of conventional transcatheter arterial chemoembolization (TACE) and radiofrequency ablation (RFA) in patients with non-resectable and non-ablatable hepatocellular carcinoma (HCC). Methods: In this retrospective study, 85 consecutive patients with HCC (59 solitary, 29 multifocal HCC) received TACE followed by RFA between 2001 and 2010. The mean number of tumors per patient was 1.6 +/- 0.7 with a mean size of 3.0 +/- 0.9 cm. Both local efficacy and patient survival were evaluated. Results: Of 120 treated HCCs, 99 (82.5%) showed a complete response (CR), while in 21 HCCs (17.5%) a partial response was depicted. Patients with solitary HCC revealed CR in 91% (51/56); in patients with multifocal HCC (n = 29) CR was achieved in 75% (48 of 64 HCCs). The median survival for all patients was 25.5 months. The 1-, 2-, 3- and 5-year survival rates were 84.6, 58.7, 37.6 and 14.6%, respectively. Statistical analysis revealed a significant difference in survival between Barcelona Clinic Liver Cancer (BCLC) A (73.4 months) and B (50.3 months) patients, while analyses failed to show a difference for Child-Pugh score, Cancer of Liver Italian Program (CLIP) score and tumor distribution pattern. Conclusion: TACE combined with RFA provides an effective treatment approach with high local tumor control rates and promising survival data, especially for BCLC A patients. Randomized trials are needed to compare this multimodality approach with a single modality approach for early-stage HCC. Copyright (C) 2011 S. Karger AG, Base

Strong fragmentation of low-energy electromagnetic excitation strength in 117^{117}Sn

Results of nuclear resonance fluorescence experiments on $^{117}$Sn are reported. More than 50 $\gamma$ transitions with $E_{\gamma} < 4$ MeV were detected indicating a strong fragmentation of the electromagnetic excitation strength. For the first time microscopic calculations making use of a complete configuration space for low-lying states are performed in heavy odd-mass spherical nuclei. The theoretical predictions are in good agreement with the data. It is concluded that although the E1 transitions are the strongest ones also M1 and E2 decays contribute substantially to the observed spectra. In contrast to the neighboring even $^{116-124}$Sn, in $^{117}$Sn the $1^-$ component of the two-phonon $[2^+_1 \otimes 3^-_1]$ quintuplet built on top of the 1/2$^+$ ground state is proved to be strongly fragmented.Comment: 4 pages, 3 figure

Production of η′\eta\prime Mesons in the pp→ppη′pp \to pp\eta\prime Reaction at 3.67 GeV/c

The ratio of the total exclusive production cross sections for $\eta\prime$ and $\eta$ mesons has been measured in the $pp$ reaction at $p_{beam}=3.67$ GeV/c. The observed $\eta\prime/\eta$ ratio is $(0.83\pm{0.11}^{+0.23}_{-0.18})\times 10^{-2}$ from which the exclusive $\eta\prime$ meson production cross section is determined to be $(1.12\pm{0.15}^{+0.42}_{-0.31})\mu b$. Differential cross section distributions have been measured. Their shape is consistent with isotropic $\eta\prime$ meson production.Comment: 14 pages, 5 figures, accepted by Phys.Lett.

Pathway to the Square Kilometre Array - The German White Paper -

The Square Kilometre Array (SKA) is the most ambitious radio telescope ever planned. With a collecting area of about a square kilometre, the SKA will be far superior in sensitivity and observing speed to all current radio facilities. The scientific capability promised by the SKA and its technological challenges provide an ideal base for interdisciplinary research, technology transfer, and collaboration between universities, research centres and industry. The SKA in the radio regime and the European Extreme Large Telescope (E-ELT) in the optical band are on the roadmap of the European Strategy Forum for Research Infrastructures (ESFRI) and have been recognised as the essential facilities for European research in astronomy. This "White Paper" outlines the German science and R&D interests in the SKA project and will provide the basis for future funding applications to secure German involvement in the Square Kilometre Array.Comment: Editors: H. R. Kl\"ockner, M. Kramer, H. Falcke, D.J. Schwarz, A. Eckart, G. Kauffmann, A. Zensus; 150 pages (low resolution- and colour-scale images), published in July 2012, language English (including a foreword and an executive summary in German), the original file is available via the MPIfR homepag

Influence of drying process and particle size of persimmon fibre on its physicochemical, antioxidant, hydration and emulsifying properties

[EN] Persimmon, given its current surplus production, could be an alternative source for the extraction of certain interesting ingredients for the food industry and human health, such as fibre. Thus, the aim of this study was to analyse the influence of hot air and freeze-drying, as well as the particle size of fibre extracted from persimmon peels or pulp on their physicochemical, antioxidant, hydration and emulsifying properties, compared to commercial fibres (from peach, lemon, orange and apple). The results showed that both freeze-dried persimmon pulp and freeze-dried peel had better hydration properties and oil holding capacity than other fibres analysed, although the swelling capacity was higher for lemon fibre. Freeze-dried persimmon peel fibre showed higher values of emulsion stability than commercial fibres. Finally, the antioxidant activity of the smallest sized persimmon peel fibre obtained by freeze-drying was higher than that for lemon, orange and peach fibre.The authors acknowledge the support of the Universtitat Politecnica de Valencia and certify that there is no conflict of interest with any financial organization regarding the material discussed in the manuscript.Martínez-Las Heras, R.; Landines, E.; Heredia Gutiérrez, AB.; Castelló Gómez, ML.; Andrés Grau, AM. (2017). Influence of drying process and particle size of persimmon fibre on its physicochemical, antioxidant, hydration and emulsifying properties. Journal of Food Science and Technology. 54(9):1-11. doi:10.1007/s13197-017-2728-zS111549Abdul-Hamid A, Luan YS (2000) Functional properties of dietary fibre prepared from defatted rice bran. Food Chem 68:15–19Adams MR, Moss MO (1997) Microbiología de los alimentos. 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A Comparative Computer Simulation of Dendritic Morphology

Computational modeling of neuronal morphology is a powerful tool for understanding developmental processes and structure-function relationships. We present a multifaceted approach based on stochastic sampling of morphological measures from digital reconstructions of real cells. We examined how dendritic elongation, branching, and taper are controlled by three morphometric determinants: Branch Order, Radius, and Path Distance from the soma. Virtual dendrites were simulated starting from 3,715 neuronal trees reconstructed in 16 different laboratories, including morphological classes as diverse as spinal motoneurons and dentate granule cells. Several emergent morphometrics were used to compare real and virtual trees. Relating model parameters to Branch Order best constrained the number of terminations for most morphological classes, except pyramidal cell apical trees, which were better described by a dependence on Path Distance. In contrast, bifurcation asymmetry was best constrained by Radius for apical, but Path Distance for basal trees. All determinants showed similar performance in capturing total surface area, while surface area asymmetry was best determined by Path Distance. Grouping by other characteristics, such as size, asymmetry, arborizations, or animal species, showed smaller differences than observed between apical and basal, pointing to the biological importance of this separation. Hybrid models using combinations of the determinants confirmed these trends and allowed a detailed characterization of morphological relations. The differential findings between morphological groups suggest different underlying developmental mechanisms. By comparing the effects of several morphometric determinants on the simulation of different neuronal classes, this approach sheds light on possible growth mechanism variations responsible for the observed neuronal diversity

Environmental occurrence, analysis, and toxicology of toxaphene compounds.

Toxaphene production, in quantities similar to those of polychlorinated biphenyls, has resulted in high toxaphene levels in fish from the Great Lakes and in Arctic marine mammals (up to 10 and 16 microg g-1 lipid). Because of the large variabiliity in total toxaphene data, few reliable conclusions can be drawn about trends or geographic differences in toxaphene concentrations. New developments in mass spectrometric detection using either negative chemical ionization or electron impact modes as well as in multidimensional gas chromatography recently have led researchers to suggest congener-specific approaches. Recently, several nomenclature systems have been developed for toxaphene compounds. Although all systems have specific advantages and limitations, it is suggested that an international body such as the International Union of Pure and Applied Chemistry make an attempt to obtain uniformity in the literature. Toxicologic information on individual chlorobornanes is scarce, but some reports have recently appeared. Neurotoxic effects of toxaphene exposure such as those on behavior and learning have been reported. Technical toxaphene and some individual congeners were found to be weakly estrogenic in in vitro test systems; no evidence for endocrine effects in vivo has been reported. In vitro studies show technical toxaphene and toxaphene congeners to be mutagenic. However, in vivo studies have not shown genotoxicity; therefore, a nongenotoxic mechanism is proposed. Nevertheless, toxaphene is believed to present a potential carcinogenic risk to humans. Until now, only Germany has established a legal tolerance level for toxaphene--0.1 mg kg-1 wet weight for fish