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Ototoxicity

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https://www.readbyqxmd.com/read/28814279/musashi-1-is-the-candidate-of-the-regulator-of-hair-cell-progenitors-during-inner-ear-regeneration
#1
Takahiro Wakasaki, Hiroaki Niiro, Siamak Jabbarzadeh-Tabrizi, Mitsuru Ohashi, Takashi Kimitsuki, Takashi Nakagawa, Shizuo Komune, Koichi Akashi
BACKGROUND: Hair cell loss in the cochlea is caused by ototoxic drugs, aging, and environmental stresses and could potentially lead to devastating pathophysiological effects. In adult mammals, hair cell loss is irreversible and may result in hearing and balance deficits. In contrast, nonmammalian vertebrates, including birds, can regenerate hair cells through differentiation of supporting cells and restore inner ear function, suggesting that hair cell progenitors are present in the population of supporting cells...
August 16, 2017: BMC Neuroscience
https://www.readbyqxmd.com/read/28803710/intrathecal-2-hydroxypropyl-%C3%AE-cyclodextrin-decreases-neurological-disease-progression-in-niemann-pick-disease-type-c1-a-non-randomised-open-label-phase-1-2-trial
#2
Daniel S Ory, Elizabeth A Ottinger, Nicole Yanjanin Farhat, Kelly A King, Xuntian Jiang, Lisa Weissfeld, Elizabeth Berry-Kravis, Cristin D Davidson, Simona Bianconi, Lee Ann Keener, Ravichandran Rao, Ariane Soldatos, Rohini Sidhu, Kimberly A Walters, Xin Xu, Audrey Thurm, Beth Solomon, William J Pavan, Bernardus N Machielse, Mark Kao, Steven A Silber, John C McKew, Carmen C Brewer, Charles H Vite, Steven U Walkley, Christopher P Austin, Forbes D Porter
BACKGROUND: Niemann-Pick disease, type C1 (NPC1) is a lysosomal storage disorder characterised by progressive neurodegeneration. In preclinical testing, 2-hydroxypropyl-β-cyclodextrins (HPβCD) significantly delayed cerebellar Purkinje cell loss, slowed progression of neurological manifestations, and increased lifespan in mouse and cat models of NPC1. The aim of this study was to assess the safety and efficacy of lumbar intrathecal HPβCD. METHODS: In this open-label, dose-escalation phase 1-2a study, we gave monthly intrathecal HPβCD to participants with NPC1 with neurological manifestation at the National Institutes of Health (NIH), Bethesda, MD, USA...
August 10, 2017: Lancet
https://www.readbyqxmd.com/read/28802382/evaluation-of-the-possible-protective-role-of-naringenin-on-gentamicin-induced-ototoxicity-a-preliminary-study
#3
I Koçak, S Sarac, E Aydogan, E Şentürk, D Akakın, K Koroglu, Ö F Özer
OBJECTIVES: The purpose of this study is to evaluate the possible protective role of naringenin in gentamicin-induced ototoxicity through an audiological, biochemical and histopathological evaluation. METHODS: This study was conducted on 32 adult male rats that were randomized into 4 groups(control, gentamicin, naringenin + gentamicin, and naringenin). Naringenin was given to the rats via oral gavage in a dose of 50 mg/kg/day during the 14 day study period. Gentamicin was given by the intraperitoneal route in a dose of 120 mg/kg/day...
September 2017: International Journal of Pediatric Otorhinolaryngology
https://www.readbyqxmd.com/read/28802357/evaluation-of-ototoxicity-of-intratympanic-administration-of-methotrexate-in-rats
#4
Sabri Baki Eren, Remzi Dogan, Alper Yenigun, Bayram Veyseller, Selahattin Tugrul, Orhan Ozturan, Mehmet Serif Aydin
OBJECTIVE: Methotrexate is a dihydrofolate reductase enzyme inhibitor with very high selectivity, and it is an antiproliferative folic acid antagonist used for the treatment of autoimmune diseases. In this study, our objective was to evaluate the effect of intratympanic Methotrexate application in the inner ear. METHODS: This study was planned as an animal study. This study performed in a tertiary referral center. 24 healthy female rats were used in our study. They were separated into three groups...
September 2017: International Journal of Pediatric Otorhinolaryngology
https://www.readbyqxmd.com/read/28796092/oral-administration-of-clinical-stage-drug-candidate-sens-401-effectively-reduces-cisplatin-induced-hearing-loss-in-rats
#5
Mathieu Petremann, Christophe Tran Van Ba, Audrey Broussy, Charlotte Romanet, Jonas Dyhrfjeld-Johnsen
HYPOTHESIS: SENS-401, an oral clinical-stage drug, may reduce cisplatin-induced hearing loss and cochlear damage in an in vivo model. BACKGROUND: Cisplatin is commonly associated with hearing loss, causing significant learning and behavioral difficulties in the pediatric cancer population, and for which there are currently no clinical solutions. SENS-401 has previously been shown to improve acoustic trauma-induced hearing loss in vivo. METHODS: The effect of SENS-401 (R-azasetron besylate) on cisplatin IC50 values was evaluated in a panel of cisplatin-sensitive cell lines (NIH:OVCAR-3, SK-N-AS, NCI-H460, FaDu)...
August 8, 2017: Otology & Neurotology
https://www.readbyqxmd.com/read/28791351/altered-gene-expression-profile-in-a-rat-model-of-gentamicin-induced-ototoxicity-and-nephrotoxicity-and-the-potential-role-of-upregulated-ifi44-expression
#6
Jun-Gen Hu, Yu Fu, Jian-Ju Xu, Xian-Ping Ding, Hui-Qi Xie, Jesse Li-Ling
As demonstrated by Alport syndrome, the co‑occurrence of auditory and urinary system malformations, and gentamicin-induced ototoxicity and nephrotoxicity, the ears and kidneys potentially share certain molecular pathways. In the present study, microarray chips were used to analyze the changes in the gene expression profile using a rat model of gentamicin‑induced ototoxicity and nephrotoxicity, using rat liver tissue as a control. A number of genes were identified to exhibit similar expression changes in the rat ears and kidney tissues, among which microtubule‑associated protein 44 (Ifi44), was selected for further analysis to validate its expression changes and confirm potential involvement in the inflammation process in the disease model...
August 2, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28771738/macrolide-associated-sensorineural-hearing-loss-a-systemic-review
#7
REVIEW
Allison K Ikeda, Anthony A Prince, Jenny X Chen, Judith E C Lieu, Jennifer J Shin
OBJECTIVES: To investigate the potential association of macrolide antibiotics with sensorineural hearing loss (SNHL) and which agents and dosage may be related. To evaluate whether an optimal treatment exists for reversing SNHL that occurs after macrolide therapy. STUDY DESIGN: Systematic review of the literature. METHODS: Computerized (PubMed, EMBASE, Cochrane Library) and manual searches were performed to identify human studies of all ages (patients) who received macrolides (intervention, with or without control) and documented SNHL (outcome)...
August 3, 2017: Laryngoscope
https://www.readbyqxmd.com/read/28760048/protective-effect-of-alpha-linolenic-acid-on-gentamicin-induced-ototoxicity-in-mice
#8
Halil Mahir Kaplan, Ergin Şingirik, Kıvılcım Eren Erdoğan, Figen Doran
Alpha-linolenic acid is one of the fatty acids known as omega 3. Previous studies have shown the antioxidant and anti-inflammatory effects of alpha-linolenic acid, which prevented cell damage by inhibiting apoptotic pathway. Also, it is known that gentamicin activates apoptotic mediators and causes necrosis in the kidney. Due to this reason, we planned a study to evaluate the protective effects of alpha-linolenic acid on gentamicin induced ototoxicity by evaluating inflammation and apoptotic mediators. For this purpose, 100 mg/kg gentamicin (i...
July 31, 2017: Somatosensory & Motor Research
https://www.readbyqxmd.com/read/28758056/single-cell-transcriptome-analysis-of-developing-and-regenerating-spiral-ganglion-neurons
#9
Kelvin Y Kwan
The spiral ganglion neurons (SGNs) of the cochlea are essential for our ability to hear. SGN loss after exposure to ototoxic drugs or loud noise results in hearing loss. Pluripotent stem cell-derived and endogenous progenitor cell types have the potential to become SGNs and are cellular foundations for replacement therapies. Repurposing transcriptional regulatory networks to promote SGN differentiation from progenitor cells is a strategy for regeneration. Advances in the Fludigm C1 workflow or Drop-seq allow sequencing of single cell transcriptomes to reveal variability between cells...
October 2016: Current Pharmacology Reports
https://www.readbyqxmd.com/read/28757873/absence-of-relationship-between-mitochondrial-dna-haplogroups-and-cisplatin-induced-hearing-loss
#10
D Graterol, C Mir, C Garcia-Vaquero, I Braña, A N Pardo, M I Rochera-Villach, A Lyakhovich, M E LLeonart, J Lorente
BACKGROUND: Many drugs used for cancer chemotherapy produce reactive oxygen species, thus leading to various complications including nephrotoxicity, cardiotoxicity, and ototoxicity. OBJECTIVE: We have provided a haplogroup analysis of a cohort of cancer patients treated with chemotherapy and compared factors associated with associated hearing loss. STUDY DESIGN AND METHODS: This observational cohort study includes a pure-tone audiometry of the patients who underwent chemotherapeutic treatment...
2017: International Journal of Otolaryngology
https://www.readbyqxmd.com/read/28738532/genipin-attenuates-cisplatin-induced-nephrotoxicity-by-counteracting-oxidative-stress-inflammation-and-apoptosis
#11
Eglal Mahgoub, Shanmugam Muthu Kumaraswamy, Kamal Hassan Kader, Balaji Venkataraman, Shreesh Ojha, Ernest Adeghate, Mohanraj Rajesh
Cisplatin (CP) is a potent and widely used chemotherapeutic agent. However, the clinical benefits of CP are compromised because it elicits nephrotoxicity and ototoxicity. In this study, we investigated the nephroprotective effects of the phytochemical genipin (GP) isolated from the gardenia (Gardenia jasminoides) fruit, using a murine model of CP-induced nephropathy. GP pretreatment attenuated the CP-induced renal tissue injury by diminishing the serum blood urea nitrogen, creatinine, and cystatin C levels, as well as those of kidney injury molecule-1...
September 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28737283/prevalence-of-hearing-and-vestibular-loss-in-cystic-fibrosis-patients-exposed-to-aminoglycosides
#12
Jaynee A Handelsman, Samya Z Nasr, Crystal Pitts, William M King
AIM: Cystic Fibrosis (CF) patients frequently use aminoglycosides (AGS) to treat CF exacerbation due to colonization with Pseudomonas aeruginosa. Although AGS can cause vestibular and auditory sensory losses that can negatively impact quality of life, little is known about the prevalence of vestibular loss in this population. The aim of this study was to determine the prevalence of hearing loss and/or vestibular dysfunction in CF patients treated with AGS. METHODS: The relationship between hearing status and vestibular status was also investigated...
September 2017: Pediatric Pulmonology
https://www.readbyqxmd.com/read/28737048/ototoxicity-monitoring-in-children-treated-with-platinum-chemotherapy
#13
Beth Brooks, Kristin Knight
OBJECTIVE: To review the prevalence, mechanisms, clinical presentation, risk factors and implications of platinum-induced ototoxicity in paediatric cancer patients based on published evidence, discuss options for monitoring hearing in young children during treatment and review long-term follow-up guidelines. DESIGN: Narrative literature review. RESULTS: Children treated with cisplatin are at high risk of hearing loss and early, accurate identification of ototoxicity is important for medical decision making and hearing rehabilitation...
July 24, 2017: International Journal of Audiology
https://www.readbyqxmd.com/read/28736517/resolution-of-cochlear-inflammation-novel-target-for-preventing-or-ameliorating-drug-noise-and-age-related-hearing-loss
#14
REVIEW
Gilda M Kalinec, Gwen Lomberk, Raul A Urrutia, Federico Kalinec
A significant number of studies support the idea that inflammatory responses are intimately associated with drug-, noise- and age-related hearing loss (DRHL, NRHL and ARHL). Consequently, several clinical strategies aimed at reducing auditory dysfunction by preventing inflammation are currently under intense scrutiny. Inflammation, however, is a normal adaptive response aimed at restoring tissue functionality and homeostasis after infection, tissue injury and even stress under sterile conditions, and suppressing it could have unintended negative consequences...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28730299/prophylactic-etanercept-treatment-in-cisplatin-ototoxicity
#15
Sinem Dasli, Murat Topdag, Ahmet Mutlu, Ahmet Kara, Murat Ozturk
The aim of our study was to evaluate the audiological protective effects of etanercept using distortion product otoacoustic emission (DPOAE) in rats with hearing loss due to cisplatin ototoxicity. The study began with 36 healthy female albino rats; 31 rats had good measurements in DPOAE and were included in the study. On day 0, a single dose of etanercept was given by intraperitoneal administration to 15 rats (etanercept group). No medication was given to the control group. After 24 h, 16 mg/kg cisplatin was given to all rats...
July 20, 2017: European Archives of Oto-rhino-laryngology
https://www.readbyqxmd.com/read/28718886/brainstem-auditory-evoked-responses-in-37-dogs-with-otitis-media-before-and-after-topical-therapy
#16
S Paterson
OBJECTIVES: The objective of this study was to determine whether intra-aural administration of aqueous solutions of marbofloxacin, gentamicin, tobramycin and ticarcillin (used off-licence) was associated with changes in hearing as measured by brainstem auditory evoked responses. MATERIALS AND METHODS: Dogs diagnosed with otitis media (n=37) underwent brainstem auditory evoked response testing and then were treated for their ear disease. First, the external ear canal and middle ear were flushed with sterile saline followed by EDTA tris with 0·15% chlorhexidine...
July 18, 2017: Journal of Small Animal Practice
https://www.readbyqxmd.com/read/28712672/noise-induced-cochlear-synaptopathy-in-rhesus-monkeys-macaca-mulatta
#17
M D Valero, J A Burton, S N Hauser, T A Hackett, R Ramachandran, M C Liberman
Cochlear synaptopathy can result from various insults, including acoustic trauma, aging, ototoxicity, or chronic conductive hearing loss. For example, moderate noise exposure in mice can destroy up to ∼50% of synapses between auditory nerve fibers (ANFs) and inner hair cells (IHCs) without affecting outer hair cells (OHCs) or thresholds, because the synaptopathy occurs first in high-threshold ANFs. However, the fiber loss likely impairs temporal processing and hearing-in-noise, a classic complaint of those with sensorineural hearing loss...
July 8, 2017: Hearing Research
https://www.readbyqxmd.com/read/28708814/chirp-evoked-otoacoustic-emissions-and-middle-ear-absorbance-for-monitoring-ototoxicity-in-cystic-fibrosis-patients
#18
Angela C Garinis, Douglas H Keefe, Lisa L Hunter, Denis F Fitzpatrick, Daniel B Putterman, Garnett P McMillan, Jeffrey A Gold, M Patrick Feeney
OBJECTIVES: The goal of this study was to investigate the use of transient-evoked otoacoustic emissions (TEOAEs) and middle ear absorbance measurements to monitor auditory function in patients with cystic fibrosis (CF) receiving ototoxic medications. TEOAEs were elicited with a chirp stimulus using an extended bandwidth (0.71 to 8 kHz) to measure cochlear function at higher frequencies than traditional TEOAEs. Absorbance over a wide bandwidth (0.25 to 8 kHz) provides information on middle ear function...
July 13, 2017: Ear and Hearing
https://www.readbyqxmd.com/read/28705091/molecular-approaches-to-potentiate-cisplatin-responsiveness-in-carcinoma-therapeutics
#19
REVIEW
Aayushi Jain, Devashree Jahagirdar, Pritish Nilendu, Nilesh Kumar Sharma
Cisplatin has been considered as the crucial regimen of widely prescribed chemotherapy treatment for cancer. The advancing treatment of cancers has reached the border line, where tumors show resistance to cisplatin and may thwart its use. Other than issues of drug resistance, cisplatin has been reported to evince side effects such as nephrotoxicity and ototoxicity. Therefore, there is a compelling need to untangle the problems associated with cisplatin treatment in carcinoma. Areas covered: In this review, we summarize the current status of combinatorial options to bring about better pre-clinical and clinical cisplatin drug responses in carcinoma...
September 2017: Expert Review of Anticancer Therapy
https://www.readbyqxmd.com/read/28703809/epigallocatechin-3-gallate-a-prototypic-chemopreventative-agent-for-protection-against-cisplatin-based-ototoxicity
#20
Vikrant Borse, Raheem F H Al Aameri, Kelly Sheehan, Sandeep Sheth, Tejbeer Kaur, Debashree Mukherjea, Srinivasan Tupal, Michelle Lowy, Sumana Ghosh, Asmita Dhukhwa, Puspanjali Bhatta, Leonard P Rybak, Vickram Ramkumar
Cisplatin-induced ototoxicity is one of the major factors limiting cisplatin chemotherapy. Ototoxicity results from damage to outer hair cells (OHCs) and other regions of the cochlea. At the cellular level, cisplatin increases reactive oxygen species (ROS) leading to cochlear inflammation and apoptosis. Thus, ideal otoprotective drugs should target oxidative stress and inflammatory mechanisms without interfering with cisplatin's chemotherapeutic efficacy. In this study, we show that epigallocatechin-3-gallate (EGCG) is a prototypic agent exhibiting these properties of an effect otoprotective agent...
July 13, 2017: Cell Death & Disease
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