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https://www.readbyqxmd.com/read/28729624/taxanes-and-platinum-derivatives-impair-schwann-cells-via-distinct-mechanisms
#1
Satoshi Imai, Madoka Koyanagi, Ziauddin Azimi, Yui Nakazato, Mayuna Matsumoto, Takashi Ogihara, Atsushi Yonezawa, Tomohiro Omura, Shunsaku Nakagawa, Shuji Wakatsuki, Toshiyuki Araki, Shuji Kaneko, Takayuki Nakagawa, Kazuo Matsubara
Impairment of peripheral neurons by anti-cancer agents, including taxanes and platinum derivatives, has been considered to be a major cause of chemotherapy-induced peripheral neuropathy (CIPN), however, the precise underlying mechanisms are not fully understood. Here, we examined the direct effects of anti-cancer agents on Schwann cells. Exposure of primary cultured rat Schwann cells to paclitaxel (0.01 μM), cisplatin (1 μM), or oxaliplatin (3 μM) for 48 h induced cytotoxicity and reduced myelin basic protein expression at concentrations lower than those required to induce neurotoxicity in cultured rat dorsal root ganglion (DRG) neurons...
July 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28729062/pharmacological-activation-of-ampk-inhibits-incision-evoked-mechanical-hypersensitivity-and-the-development-of-hyperalgesic-priming-in-mice
#2
Michael D Burton, Dipti V Tillu, Khadijah Mazhar, Galo L Mejia, Marina N Asiedu, Kufreobong Inyang, Travis Hughes, Bo Lian, Gregory Dussor, Theodore J Price
New therapeutics to manage post-surgical pain are needed to mitigate the liabilities of opioid and other analgesics. Our previous work shows that key modulators of excitability in peripheral nociceptors, such as extracellular signal-regulated kinases (ERK) are inhibited by activation of adenosine monophosphate activated protein kinase (AMPK). We hypothesized that AMPK activation would attenuate acute incision-evoked mechanical hypersensitivity and the development of hyperalgesic priming caused by surgery in mice...
July 17, 2017: Neuroscience
https://www.readbyqxmd.com/read/28727705/activation-of-the-rage-stat3-pathway-in-the-dorsal-root-ganglion-contributes-to-the-persistent-pain-hypersensitivity-induced-by-lumbar-disc-herniation
#3
Xin-Sheng Zhang, Xiao Li, Hai-Jie Luo, Zhu-Xi Huang, Cui-Cui Liu, Qing Wan, Shu-Wei Xu, Shao-Ling Wu, Song-Jian Ke, Chao Ma
BACKGROUND: Clinically, chronic low back pain and sciatica associated with lumbar disc herniation (LDH) is a common musculoskeletal disorder. Due to the unawareness of detailed mechanisms, it is difficult to get an effective therapy. OBJECTIVE: The aim of the present study was to identify the role of the RAGE/STAT3 pathway in the dorsal root ganglion (DRG) on the formation and development of persistent pain hypersensitivity induced by LDH. STUDY DESIGN: Controlled animal study...
July 2017: Pain Physician
https://www.readbyqxmd.com/read/28723879/suppression-of-sympathetic-nerve-sprouting-by-local-administration-of-an-%C3%AE-antagonist-around-the-dorsal-root-ganglion-in-a-lumbar-radiculopathy-model
#4
Izaya Ogon, Tsuneo Takebayashi, Tsuyoshi Miyakawa, Takehito Iwase, Katsumasa Tanimoto, Yoshinori Terashima, Syunsuke Jimbo, Takeshi Kobayashi, Noritsugu Tohse, Toshihiko Yamashita
STUDY DESIGN: Animal experimental study with intervention OBJECTIVE.: The purpose of this study was to elucidate whether local administration of an α-antagonist around the dorsal root ganglion (DRG) suppressed sympathetic nerve sprouting, from the acute to the chronic pain development phase, in a lumbar radiculopathy model using immunohistochemical methods. SUMMARY OF BACKGROUND DATA: The abnormal sympathetic-somatosensory interaction may underlie some forms of neuropathic pain...
July 18, 2017: Spine
https://www.readbyqxmd.com/read/28722693/ikk-nf-%C3%AE%C2%BAb-dependent-satellite-glia-activation-induces-spinal-cord-microglia-activation-and-neuropathic-pain-after-nerve-injury
#5
Hyoungsub Lim, Hyunkyoung Lee, Kyungchul Noh, Sung Joong Lee
Increasing evidence indicates that both microglia and satellite glial cell (SGC) activation play causal roles in neuropathic pain development after peripheral nerve injury; however, the activation mechanisms and their contribution to neuropathic pain remain elusive. To address this issue, we generated Ikkβ conditional knockout mice (Cnp-Cre/Ikkβ; cIkkβ) in which IKK/NF-κB-dependent proinflammatory SGC activation was abrogated. In these mice, nerve injury-induced spinal cord microglia activation and pain hypersensitivity were significantly attenuated compared to those in control mice...
May 30, 2017: Pain
https://www.readbyqxmd.com/read/28722281/collagen-organization-regulates-stretch-initiated-pain-related-neuronal-signals-in-vitro-implications-for-structure-function-relationships-in-innervated-ligaments
#6
Sijia Zhang, Sagar Singh, Beth A Winkelstein
Injury to the spinal facet capsule, an innervated ligament with heterogeneous collagen organization, produces pain. Although mechanical facet joint trauma activates embedded afferents, it is unclear if, and how, the varied extracellular microstructure of its ligament affects sensory transduction for pain from mechanical inputs. To investigate the effects of macroscopic deformations on afferents in collagen matrices with different organizations, an in vitro neuron-collagen construct (NCC) model was used. NCCs with either randomly organized or parallel aligned collagen fibers were used to mimic the varied microstructure in the facet capsular ligament...
July 19, 2017: Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society
https://www.readbyqxmd.com/read/28721080/a-cost-analysis-of-a-broad-spectrum-antibiotic-therapy-in-the-empirical-treatment-of-health-care-associated-infections-in-cirrhotic-patients
#7
Cristina Lucidi, Vincenza Di Gregorio, Giancarlo Ceccarelli, Mario Venditti, Oliviero Riggio, Manuela Merli
BACKGROUND: Early diagnosis and appropriate treatment of infections in cirrhosis are crucial. As new guidelines in this context, particularly for health care-associated (HCA) infections, would be needed, we performed a trial documenting whether an empirical broad-spectrum antibiotic therapy is more effective than the standard one for these infections. Because of the higher daily cost of broad-spectrum than standard antibiotics, we performed a cost analysis to compare: 1) total drug costs, 2) profitability of hospital admissions...
2017: ClinicoEconomics and Outcomes Research: CEOR
https://www.readbyqxmd.com/read/28720830/effect-of-cxcl12-cxcr4-signaling-on-neuropathic-pain-after-chronic-compression-of-dorsal-root-ganglion
#8
Yang Yu, Xini Huang, Yuwei Di, Lintao Qu, Ni Fan
Neuropathic pain is a complex, chronic pain state that often accompanies tissue damage, inflammation or injury of the nervous system. However the underlying molecular mechanisms still remain unclear. Here, we showed that CXCL12 and CXCR4 were upregulated in the dorsal root ganglion (DRG) after chronic compression of DRG (CCD), and some CXCR4 immunopositive neurons were also immunopositive for the nociceptive neuronal markers IB4, TRPV1, CGRP, and substance P. The incidence and amplitude of CXCL12-induced Ca(2+) response in primary sensory neurons from CCD mice was significantly increased compared to those from control animals...
July 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28718822/a-bacterial-toxin-with-analgesic-properties-hyperpolarization-of-drg-neurons-by-mycolactone
#9
Ok-Ryul Song, Han-Byul Kim, Samuel Jouny, Isabelle Ricard, Alexandre Vandeputte, Nathalie Deboosere, Estelle Marion, Christophe J Queval, Pierre Lesport, Emmanuel Bourinet, Daniel Henrion, Seog Bae Oh, Guillaume Lebon, Guillaume Sandoz, Edouard Yeramian, Laurent Marsollier, Priscille Brodin
Mycolactone, a polyketide molecule produced by Mycobacterium ulcerans, is the etiological agent of Buruli ulcer. This lipid toxin is endowed with pleiotropic effects, presents cytotoxic effects at high doses, and notably plays a pivotal role in host response upon colonization by the bacillus. Most remarkably, mycolactone displays intriguing analgesic capabilities: the toxin suppresses or alleviates the pain of the skin lesions it inflicts. We demonstrated that the analgesic capability of mycolactone was not attributable to nerve damage, but instead resulted from the triggering of a cellular pathway targeting AT₂ receptors (angiotensin II type 2 receptors; AT₂R), and leading to potassium-dependent hyperpolarization...
July 18, 2017: Toxins
https://www.readbyqxmd.com/read/28712484/relevance-of-dna-damage-repair-in-the-management-of-prostate-cancer
#10
Patricia Banks, Wen Xu, Declan Murphy, Paul James, Shahneen Sandhu
Recent insights into the genomic aberrations that underlie and drive prostate cancer have redoubled efforts to molecularly stratify treatments based on predictive markers. Approximately 23% of patients with metastatic castration-resistant prostate cancer exhibit somatic or germline aberrations in genes implicated in DNA repair, such as BRCA2, BRCA1, ATM, CHEK2, and PALB2, as well as mismatch repair genes. At least 10% of men with advanced disease have germline mutations in DNA-repair genes (DRG). The enrichment of DRG defects in metastatic disease compared with localized, primary tumors suggests a possible role in carcinogenesis, disease progression, and potentially accounts for a more aggressive phenotype...
June 27, 2017: Current Problems in Cancer
https://www.readbyqxmd.com/read/28708759/long-noncoding-rna-mrak009713-is-a-novel-regulator-of-neuropathic-pain-in-rats
#11
Guilin Li, Huaide Jiang, Chaoran Zheng, Gaochun Zhu, Yurong Xu, Xuan Sheng, Bing Wu, Jingjing Guo, Shuanghua Zhu, Yuting Zhan, Weijian Lin, Rui Ding, Chunping Zhang, Shuangmei Liu, Lifang Zou, Zhihua Yi, Shangdong Liang
Long noncoding RNAs (lncRNAs) have been implicated in neuropathy. Here we identify and validate an lncRNA, MRAK009713, as a primary regulator of neuropathic pain in chronic constriction injury (CCI) rats. MRAK009713 expression was markedly increased in CCI rats associated with enhanced pain behaviors and small interfering RNA (siRNA) against MRAK009713 significantly reduced both mechanical and thermal hyperalgesia in the CCI rats. MRAK009713 is predicted to interact with the nociceptive P2X3 receptor by CatRAPID, a bioinformatics technology...
July 11, 2017: Pain
https://www.readbyqxmd.com/read/28707151/-acceptance-of-medical-apps-and-e%C3%A2-books-among-german-radiologists
#12
S Schleder, L M Dendl, C Niessen, C Stroszczynski, A G Schreyer
PURPOSE: Smartphones, tablet PCs, mobile applications (apps) and electronic book files (e-books) affect our lives in private and job-related settings. The aim of this study was to analyze the behavior of radiologists on smartphones, tablet PCs and e‑books and to investigate its effect on their daily work. MATERIALS AND METHODS: An online survey containing of 23 questions was conducted using Survey Monkey© ( www.surveymonkey.com ). The invitation to the survey was done using the newsletter of the German Radiological Society (DRG)...
July 13, 2017: Der Radiologe
https://www.readbyqxmd.com/read/28707043/leadless-pacing-current-state-and-future-direction
#13
REVIEW
Matthias Merkel, Philipp Grotherr, Andrea Radzewitz, Claus Schmitt
Leadless pacing is now an established alternative to conventional pacing with subcutaneous pocket and transvenous lead for patients with class I or II single-chamber pacing indication. Available 12-month follow-up data shows a 48% fewer major complication rate in patients with Micra™ compared to a historical control group in a nonrandomized study [1]. There is one system with Food and Drug Administration (FDA) approval and two with the Communauté Européenne (CE) mark. The OPS code for the implantation is 8-83d...
July 13, 2017: Cardiology and Therapy
https://www.readbyqxmd.com/read/28702476/regulatable-transgene-expression-for-prevention-of-chemotherapy-induced-peripheral-neuropathy
#14
Daisuke Kawata, Zetang Wu
Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating complication associated with drug treatment of cancer for which there are no effective strategies of prevention or treatment. In this study, we examined the effect of intermittent expression of neurotophin-3 (NT-3) or interleukin-10 (IL-10) from replication-defective herpes simplex virus (HSV)-based regulatable vectors delivered by subcutaneous inoculation to the dorsal root ganglion (DRG) on the development of paclitaxel-induced peripheral neuropathy...
September 15, 2017: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/28701920/tlx3-function-in-the-dorsal-root-ganglion-is-pivotal-to-itch-and-pain-sensations
#15
Chengcheng Huang, Fumin Lu, Ping Li, Cheng Cao, Zijing Liu
Itch, a sensation eliciting a desire to scratch, is distinct from but not completely independent of pain. Inspiring achievements have been made in the characterization of itch-related receptors and neurotransmitters, but the molecular mechanisms controlling the development of pruriceptors remain poorly understood. Here, our RNAseq and in situ hybridization data show that the transcription factor Tlx3 is required for the expression of a majority of itch-related molecules in the dorsal root ganglion (DRG). As a result, Tlx3(F/F);Nav1...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28701796/camk-ii-%C3%AE-down-regulation-protects-dorsal-root-ganglion-neurons-from-ropivacaine-hydrochloride-neurotoxicity
#16
Xian-Jie Wen, Xiao-Hong Li, Heng Li, Hua Liang, Chen-Xiang Yang, Han-Bing Wang
T-type calcium channels are intimately involved in the local anesthetics neurotoxicity. Does CaMKIIγ regulate T-type calcium currents in local anesthetics neurotoxicity? This study generated pAd-CaMKIIγ and pAd-shRNA adenovirus vectors to up- and down-regulate CaMKIIγ mRNA expression in dorsal root ganglion neurons (DRG). Normal DRG (Normal group), empty vector DRG (Empty vector group), pAd-CaMKIIγ DRG (pAd-CaMKIIγ group) and pAd-shRNA DRG (pAd-shRNA group) were treated or untreated with 3 mM ropivacaine hydrochloride for 4 h...
July 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28701025/epidemiology-of-hepatic-encephalopathy-in-german-hospitals-the-ephe-study
#17
Christian Labenz, Marcus-Alexander Wörns, Jörn M Schattenberg, Yvonne Huber, Peter Robert Galle, Joachim Labenz
Background Hepatic encephalopathy (HE) is a serious complication of liver cirrhosis. The proportion of patients with liver cirrhosis attending German hospitals suffering from HE is unknown. Methods In the first part of the study, data of 14 community hospitals and 5 university hospitals covering the years 2010 and 2011 were analyzed retrospectively for the DRG codes of liver cirrhosis and hepatic encephalopathy. In the second prospective part of the multicenter observational study, all patients with liver cirrhosis attending the departments of gastroenterology of 16 participating community hospitals within a study period of 3 months were included and screened for HE clinically according to the West Haven criteria (grades 1 - 4)...
July 12, 2017: Zeitschrift Für Gastroenterologie
https://www.readbyqxmd.com/read/28700339/trypsin-protease-activated-receptor-2-signaling-contributes-to-pancreatic-cancer-pain
#18
Jiao Zhu, Xue-Rong Miao, Kun-Ming Tao, Hai Zhu, Zhi-Yun Liu, Da-Wei Yu, Qian-Bo Chen, Hai-Bo Qiu, Zhi-Jie Lu
Pain treatment is a critical aspect of pancreatic cancer patient clinical care. This study investigated the role of trypsin-protease activated receptor-2 (PAR-2) in pancreatic cancer pain. Pancreatic tissue samples were collected from pancreatic cancer (n=22) and control patients (n=22). Immunofluorescence analyses confirmed colocalization of PAR-2 and neuronal markers in pancreatic cancer tissues. Trypsin levels and protease activities were higher in pancreatic cancer tissue specimens than in the controls...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28700081/spinal-nociceptive-circuit-analysis-with-recombinant-adeno-associated-viruses-the-impact-of-serotypes-and-promoters
#19
Karen Haenraets, Edmund Foster, Helge Johannssen, Vinnie Kandra, Noemie Frezel, Timothy Steffen, Valeria Jaramillo, Jean-Charles Paterna, Hanns Ulrich Zeilhofer, Hendrik Wildner
Recombinant adeno-associated virus (rAAV) vector-mediated gene transfer into genetically defined neuron subtypes has become a powerful tool to study the neuroanatomy of neuronal circuits in the brain and to unravel their functions. More recently this methodology has also become popular for the analysis of spinal cord circuits. To date a variety of naturally occurring AAV serotypes and genetically modified capsid variants are available but transduction efficiency in spinal neurons, target selectivity and the ability for retrograde tracing are only incompletely characterized...
July 12, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28698219/the-transcription-factor-c-ebp%C3%AE-in-the-dorsal-root-ganglion-contributes-to-peripheral-nerve-trauma-induced-nociceptive-hypersensitivity
#20
Zhisong Li, Yuanyuan Mao, Lingli Liang, Shaogen Wu, Jingjing Yuan, Kai Mo, Weihua Cai, Qingxiang Mao, Jing Cao, Alex Bekker, Wei Zhang, Yuan-Xiang Tao
Changes in gene transcription in the dorsal root ganglion (DRG) after nerve trauma contribute to the genesis of neuropathic pain. We report that peripheral nerve trauma caused by chronic constriction injury (CCI) increased the abundance of the transcription factor C/EBPβ (CCAAT/enhancer binding protein β) in the DRG. Blocking this increase mitigated the development and maintenance of CCI-induced mechanical, thermal, and cold pain hypersensitivities without affecting basal responses to acute pain and locomotor activity...
July 11, 2017: Science Signaling
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