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https://www.readbyqxmd.com/read/27824928/carbenoxolone-disodium-treatment-for-canine-pituitary-dependent-hyperadrenocorticism
#1
Takahiro Teshima, Hirotaka Matsumoto, Tomoko Okusa, Rion Uchiyama, Hidekazu Koyama
Pituitary-dependent hyperadrenocorticism (PDH) is mainly caused by pituitary corticotroph tumors in dogs. A characteristic feature of corticotroph tumors is their resistance to negative feedback by glucocorticoids. In some animal species, including dogs, the aberrant expression of 11β-hydroxysteroid dehydrogenase (11HSD), a cortisol metabolic enzyme, is observed in corticotroph tumors. We previously reported that carbenoxolone (CBX), an inhibitor of 11HSD, suppressed ACTH secretion from the pituitary gland, and decreased cortisol concentrations in healthy dogs...
2016: PloS One
https://www.readbyqxmd.com/read/27792814/glycyrrhizin-reduces-hmgb1-and-bacterial-load-in-pseudomonas-aeruginosa-keratitis
#2
Sandamali A Ekanayaka, Sharon A McClellan, Ronald P Barrett, Shikhil Kharotia, Linda D Hazlett
Purpose: High mobility group box 1 (HMGB1) contributes to poor disease outcome in Pseudomonas aeruginosa keratitis. This study tests the prophylactic effect of treatment with HMGB1 inhibitors, glycyrrhizin (GLY) and its derivative, carbenoxolone (CBX), for Pseudomonas keratitis. Methods: We treated C57BL/6 (B6) mice subconjunctivally with GLY or CBX, infected with a noncytotoxic clinical isolate (KEI 1025) or a cytotoxic strain (ATCC 19660) of P. aeruginosa, and injected intraperitoneally with either agent...
October 1, 2016: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/27776252/the-role-of-spinal-interleukin-1%C3%AE-and-astrocyte-connexin-43-in-the-development-of-mirror-image-pain-in-an-inflammatory-pain-model
#3
Hoon-Seong Choi, Dae-Hyun Roh, Seo-Yeon Yoon, Soon-Gu Kwon, Sheu-Ran Choi, Suk-Yun Kang, Ji-Young Moon, Ho-Jae Han, Hyun-Woo Kim, Alvin J Beitz, Jang-Hern Lee
Although we have recently demonstrated that carrageenan-induced inflammation upregulates the expression of spinal interleukin (IL)-1β, which inhibits spinal astrocyte activation and results in the delayed development of Mirror-Image Pain (MIP), little is known regarding the mechanisms that underlie how spinal IL-1β inhibits the astrocyte activation. In this study, we examined the effect of spinal IL-1β on astrocyte gap junctions (GJ) and the development of MIP. Following unilateral carrageenan (CA) injection, mechanical allodynia (MA) was evaluated at various time points...
October 20, 2016: Experimental Neurology
https://www.readbyqxmd.com/read/27773720/the-role-of-spinal-interleukin-1%C3%AE-and-astrocyte-connexin-43-in-the-development-of-mirror-image-pain-in-an-inflammatory-pain-model
#4
Hoon-Seong Choi, Dae-Hyun Roh, Seo-Yeon Yoon, Soon-Gu Kwon, Sheu-Ran Choi, Suk-Yun Kang, Ji-Young Moon, Ho-Jae Han, Hyun-Woo Kim, Alvin J Beitz, Jang-Hern Lee
Although we have recently demonstrated that carrageenan-induced inflammation upregulates the expression of spinal interleukin (IL)-1β, which inhibits spinal astrocyte activation and results in the delayed development of Mirror-Image Pain (MIP), little is known regarding the mechanisms that underlie how spinal IL-1β inhibits the astrocyte activation. In this study, we examined the effect of spinal IL-1β on astrocyte gap junctions (GJ) and the development of MIP. Following unilateral carrageenan (CA) injection, mechanical allodynia (MA) was evaluated at various time points...
October 20, 2016: Experimental Neurology
https://www.readbyqxmd.com/read/27720686/role-of-pannexin-1-in-clostridium-perfringens-beta-toxin-caused-cell-death
#5
Soshi Seike, Masaya Takehara, Keiko Kobayashi, Masahiro Nagahama
BACKGROUND: Beta-toxin produced by Clostridium perfringens is a key virulence factor of fatal hemorrhagic enterocolitis and enterotoxemia. This toxin belongs to a family of β-pore-forming toxins (PFTs). We reported recently that the ATP-gated P2X7 receptor interacts with beta-toxin. The ATP-release channel pannexin 1 (Panx1) is an important contributor to P2X7 receptor signaling. Hence, we investigated the involvement of Panx1 in beta-toxin-caused cell death. METHODS: We examined the effect of Panx1 in beta-toxin-induced cell death utilizing selective antagonists, knockdown of Panx1, and binding using dot-blot analysis...
December 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27705766/investigation-of-lrrc8-mediated-volume-regulated-anion-currents-in-xenopus-oocytes
#6
Héctor Gaitán-Peñas, Antonella Gradogna, Lara Laparra-Cuervo, Carles Solsona, Victor Fernández-Dueñas, Alejandro Barrallo-Gimeno, Francisco Ciruela, Melike Lakadamyali, Michael Pusch, Raúl Estévez
Volume-regulated anion channels (VRACs) play an important role in controlling cell volume by opening upon cell swelling. Recent work has shown that heteromers of LRRC8A with other LRRC8 members (B, C, D, and E) form the VRAC. Here, we used Xenopus oocytes as a simple system to study LRRC8 proteins. We discovered that adding fluorescent proteins to the C-terminus resulted in constitutive anion channel activity. Using these constructs, we reproduced previous findings indicating that LRRC8 heteromers mediate anion and osmolyte flux with subunit-dependent kinetics and selectivity...
October 4, 2016: Biophysical Journal
https://www.readbyqxmd.com/read/27693814/retinal-gap-junctions-are-involved-in-rhythmogenesis-of-neuronal-activity-at-remote-locations-study-on-infra-slow-oscillations-in-the-rat-olivary-pretectal-nucleus
#7
Patrycja Orlowska-Feuer, Jagoda S Jeczmien-Lazur, Hanna J Szkudlarek, Marian H Lewandowski
A subpopulation of olivary pretectal nucleus (OPN) neurons fire action potentials in a rhythmic manner with an eruption of activity occurring approximately every two minutes. These infra-slow oscillations depend critically on functional retinal input and are subject to modulation by light. Interestingly, the activity of photoreceptors is necessary for the emergence of the rhythm and while classic photoreceptors (rods and cones) are necessary in darkness and dim light, melanopsin photoreceptors are indispensable in bright light...
December 17, 2016: Neuroscience
https://www.readbyqxmd.com/read/27693517/carbenoxolone-exposure-during-late-gestation-in-rats-alters-placental-expressions-of-p53-and-estrogen-receptors
#8
Maie D Al-Bader, Sara A Jasem, Narayana Kilarkaje
Gestational carbenoxolone exposure inhibits placental 11β-hydroxysteroid dehydrogenase (11β-HSD), the physiological barrier for glucocorticoids, which increases fetal exposure to glucocorticoids and induces intrauterine growth restriction (IUGR). We hypothesized that carbenoxolone exposure influences the expression of placental estrogen receptors-α and β (ERα & ERβ) and p53 leading to inhibited fetal and placental growth. Pregnant Sprague-Dawley rats were injected twice daily with either carbenoxolone (10mg/kg; s...
September 28, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27677339/extracellular-atp-is-involved-in-dsrna-induced-muc5ac-production-via-p2y2r-in-human-airway-epithelium
#9
Yutaka Shishikura, Akira Koarai, Hiroyuki Aizawa, Mutsuo Yamaya, Hisatoshi Sugiura, Mika Watanabe, Yuichiro Hashimoto, Tadahisa Numakura, Tomonori Makiguti, Kyoko Abe, Mituhiro Yamada, Toshiaki Kikuchi, Yasushi Hoshikawa, Yoshinori Okada, Masakazu Ichinose
BACKGROUND: In response to tissue damage or inflammation, adenosine-5'-triphosphate (ATP) is released into the extracellular compartment and has been demonstrated to augment inflammation via purinergic P2 receptors (P2Rs). Recently, ATP has been shown to be increased in the airways of COPD patients. In the present study, we examined the possible involvement of extracellular ATP in airway mucus hypersecretion during viral-induced COPD exacerbations. METHODS: The involvement of extracellular ATP in the release of a major airway mucin, MUC5AC, and its signal pathway was examined after stimulation with polyinosine-polycytidylic acid [poly(I:C)], a synthetic analog of dsRNA to mimic viral infection, and rhinovirus (RV) infection in NCI-H292 cells and differentiated airway epithelial cells from COPD patients...
September 27, 2016: Respiratory Research
https://www.readbyqxmd.com/read/27677209/mechanical-antihypersensitivity-effect-induced-by-repeated-spinal-administrations-of-a-trpa1-antagonist-or-a-gap-junction-decoupler-in-peripheral-neuropathy
#10
Hong Wei, Hai-Yun Wu, Zuyue Chen, Ai-Niu Ma, Xiao-Fang Mao, Teng-Fei Li, Xin-Yan Li, Yong-Xiang Wang, Antti Pertovaara
Spinal transient receptor potential ankyrin 1 (TRPA1) channel is associated with various pain hypersensitivity conditions. Spinally, TRPA1 is expressed by central terminals of nociceptive nerve fibers and astrocytes. Among potential endogenous agonists of TRPA1 is H2O2 generated by d-amino acid oxidase (DAAO) in astrocytes. Here we studied whether prolonged block of the spinal TRPA1 or astrocytes starting at time of injury attenuates development and/or maintenance of neuropathic hypersensitivity. Additionally, TRPA1 and DAAO mRNA were determined in the dorsal root ganglion (DRG) and spinal dorsal horn (SDH)...
September 24, 2016: Pharmacology, Biochemistry, and Behavior
https://www.readbyqxmd.com/read/27661112/transfer-of-functional-micrornas-between-glioblastoma-and-microvascular-endothelial-cells-through-gap-junctions
#11
Dominique Thuringer, Jonathan Boucher, Gaetan Jego, Nicolas Pernet, Laurent Cronier, Arlette Hammann, Eric Solary, Carmen Garrido
Extensive invasion and angiogenesis are hallmark features of malignant glioblastomas. Here, we co-cultured U87 human glioblastoma cells and human microvascular endothelial cells (HMEC) to demonstrate the exchange of microRNAs that initially involve the formation of gap junction communications between the two cell types. The functional inhibition of gap junctions by carbenoxolone blocks the transfer of the anti-tumor miR-145-5p from HMEC to U87, and the transfer of the pro-invasive miR-5096 from U87 to HMEC...
September 20, 2016: Oncotarget
https://www.readbyqxmd.com/read/27618417/histamine-induced-dilation-of-isolated-porcine-retinal-arterioles-role-of-endothelium-derived-hyperpolarizing-factor
#12
Shinichi Otani, Taiji Nagaoka, Tsuneaki Omae, Ichiro Tanano, Takayuki Kamiya, Shinji Ono, Travis W Hein, Lih Kuo, Akitoshi Yoshida
PURPOSE: Although endothelium-dependent nitric oxide (NO)-mediated dilation of retinal arterioles has been well described, the role of endothelium-derived hyperpolarizing factor (EDHF) in the retinal arteriolar response remains unclear. In the current study, we examined the contribution of EDHF to the retinal arteriolar dilation to the inflammatory agent histamine and investigated the signaling mechanisms underlying this vasomotor activity. METHODS: Porcine retinal arterioles were isolated, cannulated, and pressurized without flow for functional study by using video microscopic techniques...
September 1, 2016: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/27575957/interventions-for-men-and-women-with-their-first-episode-of-genital-herpes
#13
REVIEW
Rachel Heslop, Helen Roberts, Deralie Flower, Vanessa Jordan
BACKGROUND: Genital herpes is incurable, and is caused by the herpes simplex virus (HSV). First-episode genital herpes is the first clinical presentation of herpes that a person experiences. Current treatment is based around viral suppression in order to decrease the length and severity of the episode. OBJECTIVES: To determine the effectiveness and safety of the different existing treatments for first-episode genital herpes on the duration of symptoms and time to recurrence...
2016: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/27567941/astrocyte-sigma-1-receptors-modulate-connexin-43-expression-leading-to-the-induction-of-below-level-mechanical-allodynia-in-spinal-cord-injured-mice
#14
Sheu-Ran Choi, Dae-Hyun Roh, Seo-Yeon Yoon, Soon-Gu Kwon, Hoon-Seong Choi, Ho-Jae Han, Alvin J Beitz, Jang-Hern Lee
We have previously shown using a spinal cord injury (SCI) model that gap junctions contribute to the early spread of astrocyte activation in the lumbar spinal cord and that this astrocyte communication plays critical role in the induction of central neuropathic pain. Sigma-1 receptors (Sig-1Rs) have been implicated in spinal astrocyte activation and the development of peripheral neuropathic pain, yet their contribution to central neuropathic pain remains unknown. Thus, we investigated whether SCI upregulates spinal Sig-1Rs, which in turn increase the expression of the astrocytic gap junction protein, connexin 43 (Cx43) leading to the induction of central neuropathic pain...
December 2016: Neuropharmacology
https://www.readbyqxmd.com/read/27484379/self-assembly-modes-of-glycyrrhetinic-acid-esters-in-view-of-the-crystal-packing-of-related-triterpene-molecules
#15
Dominik Langer, Barbara Wicher, Wojciech Szczołko, Maria Gdaniec, Ewa Tykarska
The crystal structures of three ester derivatives of glycyrrhetinic acid (GE) are reported. X-ray crystallography revealed that despite differences in the size of the ester substituents (ethyl, isopropyl and 2-morpholinoethyl) the scheme of molecular self-assembly is similar in all three cases but differs significantly from that observed in other known GE esters. According to our analysis, the two basic patterns of self-assembly of GE esters observed in their unsolvated crystals correspond to two distinct orientations of the ester groups relative to the triterpene backbone...
August 1, 2016: Acta Crystallographica Section B, Structural Science, Crystal Engineering and Materials
https://www.readbyqxmd.com/read/27421240/is-electrical-coupling-involved-in-the-generation-of-posterior-hypothalamic-theta-rhythm
#16
Renata Bocian, Bartosz Caban, Paulina Kłos-Wojtczak, Jan Konopacki, Tomasz Kowalczyk
Data obtained in in vitro experiments and urethane anaesthetized animals have revealed that the mechanisms responsible for the generation of hippocampal cholinergic theta rhythm are specifically affected by the administration of broad spectrum gap junctions (GJs) blocker - carbenoxolone (CBX). The aim of this study was to examine the effect of GJs modulation on the production of posterior hypothalamic theta. Specifically, we were interested in evaluating whether CBX could attenuate the theta rhythm recorded from the supramammillary nucleus and posterior hypothalamic nuclei, in both in vitro and in vivo preparations...
September 2016: European Journal of Neuroscience
https://www.readbyqxmd.com/read/27406134/characterization-of-intercellular-communication-and-mitochondrial-donation-by-mesenchymal-stromal-cells-derived-from-the-human-lung
#17
Kenneth Andrew Sinclair, Stephanie Terase Yerkovich, Peter Mark-Anthony Hopkins, Daniel Charles Chambers
BACKGROUND: Bone marrow-derived mesenchymal stromal cells (BM-MSCs) are capable of repairing wounded lung epithelial cells by donating cytoplasmic material and mitochondria. Recently, we characterized two populations of human lung-derived mesenchymal stromal cells isolated from digested parenchymal lung tissue (LT-MSCs) from healthy individuals or from lung transplant recipients' bronchoalveolar lavage fluid (BAL-MSCs). The aim of this study was to determine whether LT-MSCs and BAL-MSCs are also capable of donating cytoplasmic content and mitochondria to lung epithelial cells...
July 12, 2016: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/27371687/a-gap-junction-inhibitor-carbenoxolone-induces-spatiotemporal-dispersion-of-renal-cortical-perfusion-and-impairs-autoregulation
#18
Nicholas Mitrou, Branko Braam, William A Cupples
Renal autoregulation dynamics originating from the myogenic response (MR) and tubuloglomerular feedback (TGF) can synchronize over large regions of the kidney surface, likely through gap junction-mediated electrotonic conduction and reflecting distributed operation of autoregulation. We tested the hypotheses that inhibition of gap junctions reduces spatial synchronization of autoregulation dynamics, abrogates spatial and temporal smoothing of renal perfusion, and impairs renal autoregulation. In male Long-Evans rats, we infused the gap junction inhibitor carbenoxolone (CBX) or the related glycyrrhizic acid (GZA) that does not block gap junctions into the renal artery and monitored renal blood flow (RBF) and surface perfusion by laser speckle contrast imaging...
September 1, 2016: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/27358056/altered-urothelial-atp-signalling-in-major-subset-of-human-overactive-bladder-patients-with-pyuria
#19
Alberto Contreras-Sanz, Louise Krska, Aswini A Balachandran, Natasha L Curtiss, Rajvinder Khasriya, Stephen Kelley, Matthew Strutt, Hardyal S Gill, Kevin M Taylor, Kylie J Mansfield, Changhao Wu, Claire M Peppiatt-Wildman, James Malone-Lee, Jonathan Duckett, Scott S Wildman
RATIONALE: Overactive Bladder (OAB) is an idiopathic condition, characterized by urgency, urinary frequency and urgency incontinence, in the absence of routinely traceable urinary infection. We have described microscopic pyuria (≥10 wbc μl-1) in patients suffering from the worst symptoms. It is established that inflammation is associated with increased ATP release from epithelial cells, and extracellular ATP originating from the urothelium following increased hydrostatic pressure, is a mediator of bladder sensation...
June 29, 2016: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/27355484/dynamic-regulation-of-cell-volume-and-extracellular-atp-of-human-erythrocytes
#20
M Florencia Leal Denis, H Ariel Alvarez, Natalia Lauri, Cora L Alvarez, Osvaldo Chara, Pablo J Schwarzbaum
INTRODUCTION: The peptide mastoparan 7 (MST7) triggered in human erythrocytes (rbcs) the release of ATP and swelling. Since swelling is a well-known inducer of ATP release, and extracellular (ATPe), interacting with P (purinergic) receptors, can affect cell volume (Vr), we explored the dynamic regulation between Vr and ATPe. METHODS AND TREATMENTS: We made a quantitative assessment of MST7-dependent kinetics of Vr and of [ATPe], both in the absence and presence of blockers of ATP efflux, swelling and P receptors...
2016: PloS One
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