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Britt I Drögemöller, Jose G Monzon, Amit P Bhavsar, Adrienne E Borrie, Beth Brooks, Galen E B Wright, Geoffrey Liu, Daniel J Renouf, Christian K Kollmannsberger, Philippe L Bedard, Folefac Aminkeng, Ursula Amstutz, Claudette A Hildebrand, Erandika P Gunaretnam, Carol Critchley, Zhuo Chen, Liam R Brunham, Michael R Hayden, Colin J D Ross, Karen A Gelmon, Bruce C Carleton
Importance: Cisplatin-induced ototoxic effects are an important complication that affects testicular cancer survivors as a consequence of treatment. The identification of genetic variants associated with this adverse drug reaction will further our mechanistic understanding of its development and potentially lead to strategies to prevent ototoxic effects. Objective: To identify the genetic variants associated with cisplatin-induced ototoxic effects in adult testicular cancer patients...
April 27, 2017: JAMA Oncology
Qingzhu Wang, Hongchun Zhao, Tihua Zheng, Wenjun Wang, Xiaolin Zhang, Andi Wang, Bo Li, Yanfei Wang, Qingyin Zheng
As it displays progressive hair-cell loss and degeneration of spiral ganglion neurons (SGNs) characterized by early-onset progressive hearing loss (ePHL), DBA/2J is an inbred mouse strain widely used in hearing research. Mouse nerve growth factor (mNGF), as a common exogenous nerve growth factor (NGF), has been studied extensively for its ability to promote neuronal survival and growth. To determine whether mNGF can ameliorate progressive hearing loss (PHL) in DBA/2J mice, saline or mNGF was given to DBA/2J mice of either sex by daily intramuscular injection from the 1st to the 9th week after birth...
March 27, 2017: Journal of Neuroscience Research
Lixiang Gao, Ruli Ge, Gang Xie, Dandan Yao, Ping Li, Oumei Wang, Xiufang Ma, Fengchan Han
Objectives: To investigate the otoprotective effects of mouse nerve growth factor (mNGF) in A/J mice. Methods: The mice at postnatal day 7 (P7) were randomly separated into a mNGF treated group (mNGF group) and a distilled water (for injection) treated group (control group). The mNGF dissolved in distilled water or distilled water alone was given to the mice once every other day from P7 by intramuscular injection in the hips. The otoprotective effects of mNGF in A/J mice were observed in a time course manner...
March 8, 2017: Clinical and Experimental Otorhinolaryngology
Xiaoyu Yu, Wenwen Liu, Zhaomin Fan, Fuping Qian, Daogong Zhang, Yuechen Han, Lei Xu, Gaoying Sun, Jieyu Qi, Shasha Zhang, Mingliang Tang, Jianfeng Li, Renjie Chai, Haibo Wang
c-Myb is a transcription factor that plays a key role in cell proliferation, differentiation, and apoptosis. It has been reported that c-Myb is expressed within the chicken otic placode, but whether c-Myb exists in the mammalian cochlea, and how it exerts its effects, has not been explored yet. Here, we investigated the expression of c-Myb in the postnatal mouse cochlea and HEI-OC1 cells and found that c-Myb was expressed in the hair cells (HCs) of mouse cochlea as well as in cultured HEI-OC1 cells. Next, we demonstrated that c-Myb expression was decreased in response to neomycin treatment in both cochlear HCs and HEI-OC1 cells, suggesting an otoprotective role for c-Myb...
January 23, 2017: Scientific Reports
Jing Zhang, Yong-Li Song, Ke-Yong Tian, Jian-Hua Qiu
Noise-induced hearing loss (NIHL) is a serious health concern and prevention of hair cell death or therapeutic intervention at the early stage of NIHL is critical to preserve hearing. Minocycline is a semi-synthetic derivative of tetracycline and has been shown to have otoprotective effects in ototoxic drug-induced hearing impairment, however, whether minocycline can protect against NIHL has not been investigated. The present study demonstrated elevated ABR (auditory brainstem response) thresholds and outer hair cell loss following traumatic noise exposure, which was mitigated by intraperitoneal administration of minocycline (45mg/kg/d) for 5 consecutive days...
February 3, 2017: Neuroscience Letters
David R Freyer, Lu Chen, Mark D Krailo, Kristin Knight, Doojduen Villaluna, Bonnie Bliss, Brad H Pollock, Jagadeesh Ramdas, Beverly Lange, David Van Hoff, Michele L VanSoelen, John Wiernikowski, Edward A Neuwelt, Lillian Sung
BACKGROUND: Sodium thiosulfate is an antioxidant shown in preclinical studies in animals to prevent cisplatin-induced hearing loss with timed administration after cisplatin without compromising the antitumour efficacy of cisplatin. The primary aim of this study was to assess sodium thiosulfate for prevention of cisplatin-induced hearing loss in children and adolescents. METHODS: ACCL0431 was a multicentre, randomised, open-label, phase 3 trial that enrolled participants at 38 participating Children's Oncology Group hospitals in the USA and Canada...
January 2017: Lancet Oncology
M Müller, M Tisch, H Maier, H Löwenheim
BACKGROUND: High-intensity noise exposure from impulse and blast noise events often leads to acute hearing loss and may cause irreversible permanent hearing loss as a long-term consequence. Here, a treatment regime was developed to limit permanent damage based on a preclinical animal model of acute noise trauma. AIM: To develop clinical trials for the treatment of acute noise traumas using approved drugs. The otoprotective potential of glucocorticoids applied locally to the inner ear was examined...
November 23, 2016: HNO
M Müller, M Tisch, H Maier, H Löwenheim
BACKGROUND: High-intensity noise exposure from impulse and blast noise events often leads to acute hearing loss and may cause irreversible permanent hearing loss as a long-term consequence. Here, a treatment regime was developed to limit permanent damage based on a preclinical animal model of acute noise trauma. AIM: To develop clinical trials for the treatment of acute noise traumas using approved drugs. The otoprotective potential of glucocorticoids applied locally to the inner ear was examined...
November 2016: HNO
Jorrit W van As, Henk van den Berg, Elvira C van Dalen
BACKGROUND: Platinum-based therapy, including cisplatin, carboplatin, oxaliplatin or a combination of these, is used to treat a variety of paediatric malignancies. One of the most important adverse effects is the occurrence of hearing loss or ototoxicity. In an effort to prevent this ototoxicity, different otoprotective medical interventions have been studied. This review is the second update of a previously published Cochrane review. OBJECTIVES: To assess the efficacy of medical interventions to prevent hearing loss and to determine possible effects of these interventions on anti-tumour efficacy, toxicities other than hearing loss and quality of life in children with cancer treated with platinum-based therapy...
September 27, 2016: Cochrane Database of Systematic Reviews
Anthony J Garcia-Prats, H Simon Schaaf, Anneke C Hesseling
A growing number of children globally are being treated for multidrug-resistant tuberculosis (MDR-TB). The second-line injectable antituberculosis medications amikacin, kanamycin and capreomycin, traditionally a mainstay of MDR-TB treatment, cause important adverse effects including permanent sensorineural hearing loss, nephrotoxicity, electrolyte abnormalities, injection pain and local injection site complications. Areas covered: To characterize the safety and tolerability of the second-line injectables in children treated for MDR-TB, we reviewed data on the mechanism of injectable associated adverse effects, risk factors for their development, and the incidence of injectable-associated adverse effects in adults and children treated for MDR-TB...
November 2016: Expert Opinion on Drug Safety
Dawn Konrad-Martin, Gayla L Poling, Laura E Dreisbach, Kelly M Reavis, Garnett P McMillan, Judi A Lapsley Miller, Lynne Marshall
The purpose of this report is to provide guidance on the use of otoacoustic emissions (OAEs) as a clinical trial outcome measure for pharmaceutical interventions developed to prevent acquired hearing loss secondary to cochlear insult. OAEs are a rapid, noninvasive measure that can be used to monitor cochlear outer hair cell function. Serial monitoring of OAEs is most clearly established for use in hearing conservation and ototoxicity monitoring programs in which they exhibit more frequent and earlier changes compared with pure-tone audiometry...
September 2016: Otology & Neurotology
Kathleen Campbell, Tanisha Hammill, Michael Hoffer, Jonathan Kil, Colleen Le Prell
The purpose of this article is to provide guidelines for determining a Significant Noise-Induced Threshold Shift in clinical trials involving human populations. The article reviews recommendations for the standards to be referenced for human subjects, equipment, test environment, and personnel. Additional guidelines for military populations are provided. Guidelines for the calibration of audiometers, sound booth noise levels, and immitance equipment are provided. In addition the guidance provides specific suggestions for the subjects history before study onset, and otoscopy...
September 2016: Otology & Neurotology
Yüksel Olgun, Günay Kırkım, Zekiye Altun, Safiye Aktaş, Efsun Kolatan, Müge Kiray, Alper Bağrıyanık, Aybüke Olgun, Deniz Çakır Kızmazoğlu, Candan Özoğul, Hülya Ellidokuz, Pınar Erçetin, Bülent Şerbetçioğlu, Osman Yılmaz, Enis Alpin Güneri
OBJECTIVE: The aim of our study was to investigate the effects Korean Red Ginseng (KRG) on cisplatin (CDDP) ototoxicity in vivo and in vitro. MATERIALS AND METHODS: The first part of the study was conducted on the House Ear Institute-Organ of Corti 1 (HEI-OC1) cell line. Cells were treated with CDDP, KRG, and their combination for 24 h. Cell viability, apoptosis, and the expression of 84 apoptosis-related genes were analyzed. In the second part of the study, 30 Wistar albino rats were divided into five groups...
August 2016: Journal of International Advanced Otology
Michael Perny, Marta Roccio, Denis Grandgirard, Magdalena Solyga, Pascal Senn, Stephen L Leib
UNLABELLED: Hearing loss is an important sequela of pneumococcal meningitis (PM), occurring in up to 30% of survivors. The role of the severity of infection on hearing function and pathomorphological consequences in the cochlea secondary to PM have not been investigated to date. Using a well-established model of PM, we systematically investigated the functional hearing outcome and the long-term fate of neurosensory cells in the cochlea, i.e., hair cells and spiral ganglion neurons (SGNs), with a focus on their tonotopic distribution...
July 20, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Mirela Alves Dias, André Luiz Lopes Sampaio, Alessandra Ramos Venosa, Elienai de Alencar Meneses, Carlos Augusto Costa Pires Oliveira
OBJECTIVE: The purpose of this study was to evaluate, by using distortion product otoacoustic emission test, the action of Ginkgo biloba extract 761, which has a known antioxidant property, as a possible otoprotective against cisplatin induced hearing loss. This prospective and double blinded study was conducted on individuals that were to begin cisplatin treatment in a tertiary university center. They were randomized and allocated in two groups: control group (CG) (n = 07) receiving placebo and cisplatin and study group (SG) (n = 08) receiving Ginkgo biloba extract 761 (240 mg/day) and cisplatin...
2015: International Tinnitus Journal
Lukas D Landegger, Clemens Honeder, Chengjing Zhu, Hanna Schöpper, Elisabeth Engleder, Franz Gabor, Wolfgang Gstoettner, Christoph Arnoldner
BACKGROUND: Selective glucocorticoid receptor modulators (SEGRMs) comprise a novel class of drugs promising both reduced side effects and similar pharmacological potency relative to glucocorticoids, which presently serve as the only clinical treatment for many otologic disorders. In the first otologic SEGRM experiment in an animal model of noise trauma, we compare the effects of Compound A (a SEGRM) and dexamethasone (potent glucocorticoid). METHODS: Forty adult guinea pigs received experimental treatment once daily for ten days...
May 11, 2016: Journal of Negative Results in Biomedicine
Deron R Herr, Marie J Y Reolo, Yee Xin Peh, Wei Wang, Chang-Wook Lee, Rich Rivera, Ian C Paterson, Jerold Chun
Ototoxic drugs, such as platinum-based chemotherapeutics, often lead to permanent hearing loss through apoptosis of neuroepithelial hair cells and afferent neurons of the cochlea. There is no approved therapy for preventing or reversing this process. Our previous studies identified a G protein-coupled receptor (GPCR), S1P2, as a potential mediator of otoprotection. We therefore sought to identify a pharmacological approach to prevent cochlear degeneration via activation of S1P2. The cochleae of S1pr2(-/-) knockout mice were evaluated for accumulation of reactive oxygen species (ROS) with a nitro blue tetrazolium (NBT) assay...
April 15, 2016: Scientific Reports
Matthew Kruger, Robert Boney, Alexander J Ordoobadi, Thomas F Sommers, Josef G Trapani, Allison B Coffin
Moderate to severe hearing loss affects 360 million people worldwide and most often results from damage to sensory hair cells. Hair cell damage can result from aging, genetic mutations, excess noise exposure, and certain medications including aminoglycoside antibiotics. Aminoglycosides are effective at treating infections associated with cystic fibrosis and other life-threatening conditions such as sepsis, but cause hearing loss in 20-30% of patients. It is therefore imperative to develop new therapies to combat hearing loss and allow safe use of these potent antibiotics...
2016: Frontiers in Cellular Neuroscience
Tejbeer Kaur, Vikrant Borse, Sandeep Sheth, Kelly Sheehan, Sumana Ghosh, Srinivasan Tupal, Sarvesh Jajoo, Debashree Mukherjea, Leonard P Rybak, Vickram Ramkumar
UNLABELLED: Cisplatin is a commonly used antineoplastic agent that produces ototoxicity that is mediated in part by increasing levels of reactive oxygen species (ROS) via the NOX3 NADPH oxidase pathway in the cochlea. Recent studies implicate ROS generation in mediating inflammatory and apoptotic processes and hearing loss by activating signal transducer and activator of transcription (STAT1). In this study, we show that the adenosine A1 receptor (A1AR) protects against cisplatin ototoxicity by suppressing an inflammatory response initiated by ROS generation via NOX3 NADPH oxidase, leading to inhibition of STAT1...
April 6, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Katharina Leitmeyer, Andrea Glutz, Cristian Setz, Leonie Wieland, Sulamith Egloff, Daniel Bodmer, Yves Brand
Statins are inhibitors of the 3-hydroxy-3-methylglutaryl-coenzyme A reductase, an enzyme necessary for the production of mevalonate. They are widely used as cholesterol-lowering drugs. However, conflicting data about the effect of statins on neuronal cells has been published. To explore the effect of simvastatin on spiral ganglion neurons (SGNs), SG explants of 5-day-old rats were treated with increasing concentrations of simvastatin. In addition, SG explants were treated with mevalonate and with the combination of simvastatin and mevalonate...
2016: BioMed Research International
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