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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...
October 14, 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
INTRODUCTION: 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...
August 22, 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...
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...
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
Jiwon Chang, June Choi, Yoon Chan Rah, Myung Hoon Yoo, Kyoung Ho Oh, Gi Jung Im, Seung Hoon Lee, Soon Young Kwon, Hae-Chul Park, Sung Won Chae, Hak Hyun Jung
Sodium selenite is a trace element essential for many physiological functions in the body. It is involved in various biological processes; it acts as a cofactor for antioxidant enzymes that protect against free radicals and is reported to limit metal-mediated oxidative DNA damage. In the present study, we investigated the effect of sodium selenite on neomycin ototoxicity in wild-type and transgenic zebrafish (Brn3C: EGFP). Five or six days post-fertilization, zebrafish larvae were co-exposed to 125 μM neomycin and various concentrations (10 μM, 100 μM, 250 μM, and 500 μM) of sodium selenite for 1 h...
2016: PloS One
Kathleen C M Campbell, Seth M Martin, Robert P Meech, Tim L Hargrove, Steven J Verhulst, Daniel J Fox
OBJECTIVE: Test D-methionine (D-met) as an otoprotectant from kanamycin-induced ototoxicity and determine the lowest maximally protective D-met dose. DESIGN: Auditory brainstem responses (ABR) were measured at 4, 8, 14, and 20 kHz at baseline and two, four, and six weeks after kanamycin and D-met administration initiation. ABR threshold shifts assessed auditory function. Following six-week ABR testing, animals were decapitated and cochleae collected for outer hair cell (OHC) quantification...
2016: International Journal of Audiology
Esperanza Bas, Jorge Bohorquez, Stefania Goncalves, Enrique Perez, Christine T Dinh, Carolyn Garnham, Roland Hessler, Adrien A Eshraghi, Thomas R Van De Water
We evaluated the effects of dexamethasone base (DXMb) containing electrode arrays in a guinea pig model of cochlear implantation to determine if eluted DXMb could protect the cochlea against electrode insertion trauma (EIT)-induced: 1) loss of hair cells; 2) disruption of neural elements; 3) increases in hearing thresholds; 4) increased electrical impedance and 5) fibrosis. A guinea pig model of EIT-induced hearing and hair cell losses was used to test silicone electrode arrays that contained either 10%, 1%, 0...
July 2016: Hearing Research
Wendy Landier
Ototoxicity is a well-established toxicity associated with a subgroup of antineoplastic therapies that includes platinum chemotherapy, radiation or surgery involving the ear and auditory nerve, and supportive care agents such as aminoglycoside antibiotics and loop diuretics. The reported prevalence of ototoxicity in patients who have received potentially ototoxic therapy ranges from 4% to 90% depending on factors such as age of the patient population, agent(s) used, cumulative dose, and administration techniques...
June 1, 2016: Cancer
Adrien A Eshraghi, Jonathan Roell, Noah Shaikh, Fred F Telischi, Blake Bauer, Mateo Guardiola, Esperanza Bas, Thomas Van De Water, Ileana Rivera, Jeenu Mittal
UNLABELLED: Conclusions A cocktail combining NAC, Mannitol, and Dexamethasone may be used to prevent loss of residual hearing post-implantation. There is a window of opportunity to treat the cochlea before the onset of cell death in HCs. Objective Inner ear trauma caused by cochlear implant electrode insertion trauma (EIT) initiates multiple molecular mechanisms in hair cells (HCs) or support cells (SCs), resulting in initiation of programmed cell death within the damaged tissues of the cochlea, which leads to loss of residual hearing...
2016: Acta Oto-laryngologica
Rayne Fernandez, Anne Harrop-Jones, Xiaobo Wang, Luis Dellamary, Carl LeBel, Fabrice Piu
The otoprotective effects of OTO-104 were investigated following both acute and chronic administration of cisplatin. The acute administration of cisplatin to guinea pigs resulted in profound hearing loss (70-80 dB SPL) across all frequencies tested. A single intratympanic injection of 6% OTO-104, but not of lower doses, almost completely protected against cisplatin ototoxicity. In contrast, a dexamethasone solution administered under the same experimental conditions offered no otoprotection. OTO-104 was also very effective in protecting against the progressive hearing loss observed with the chronic administration of cisplatin (3 injections at a weekly interval)...
2016: Audiology & Neuro-otology
J Hu, M Xu, J Yuan, B Li, S Entenman, H Yu, Q Y Zheng
Sensorineural hearing loss has long been the subject of experimental and clinical research for many years. The recently identified novel mutation of the Cadherin23 (Cdh23) gene, Cdh23(erl/erl), was proven to be a mouse model of human autosomal recessive nonsyndromic deafness (DFNB12). Tauroursodeoxycholic acid (TUDCA), a taurine-conjugated bile acid, has been used in experimental research and clinical applications related to liver disease, diabetes, neurodegenerative diseases, and other diseases associated with apoptosis...
March 1, 2016: Neuroscience
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