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The design and screening of drugs to prevent acquired sensorineural hearing loss.

ABSTRACT: Sensorineural hearing loss affects a high percentage of the population. Ototoxicity is a serious and pervasive problem in patients treated with cisplatin. Strategies to ameliorate ototoxicity without compromising on antitumor activity of treatments are urgently needed. Similar problems occur with aminoglycoside antibiotic therapy for infections. Noise-induced hearing loss affects a large number of people. The use of ear protection is not always possible or effective. The prevention of hearing loss with drug therapy would have a huge impact in reducing the number of people with hearing loss from these major causes.This review discusses significant research findings dealing with the use of protective agents against hearing loss caused by cisplatin, aminoglycoside antibiotics and noise trauma. The efficacy in animal studies and the application of these protective agents in clinical trials that are ongoing are presented.The reader will gain new insights into current and projected future strategies to prevent sensorineural hearing loss from cisplatin chemotherapy, aminoglycoside antibiotic therapy and noise exposure. The future appears to offer numerous agents to prevent hearing loss caused by cisplatin, aminoglycoside antibiotics and noise. Novel delivery systems will provide ways to guide these protective agents to the desired target areas in the inner ear and circumvent problems with therapeutic interference of antitumor and antibiotics agents as well as minimize undesired side effects.

SUBMITTER: Mukherjea D

PROVIDER: S-EPMC3395201 | biostudies-literature | 2011 May

REPOSITORIES: biostudies-literature

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The design and screening of drugs to prevent acquired sensorineural hearing loss.

Mukherjea Debashree D Rybak Leonard P LP Sheehan Kelly E KE Kaur Tejbeer T Ramkumar Vickram V Jajoo Sarvesh S Sheth Sandeep S

Expert opinion on drug discovery 20110315 5

<h4>Introduction</h4>Sensorineural hearing loss affects a high percentage of the population. Ototoxicity is a serious and pervasive problem in patients treated with cisplatin. Strategies to ameliorate ototoxicity without compromising on antitumor activity of treatments are urgently needed. Similar problems occur with aminoglycoside antibiotic therapy for infections. Noise-induced hearing loss affects a large number of people. The use of ear protection is not always possible or effective. The pre ...[more]

PMID: 22646075

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Project description:Introduction: Sensorineural hearing loss (SNHL) is a prevalent sensory deficit presenting commonly as age-related hearing loss. Other forms of SNHL include noise-induced and sudden SNHL. Recent evidence has pointed to oxidative stress as a common pathogenic pathway in most subtypes of acquired SNHL. MicroRNAs (miRNAs) are small non-coding RNA sequences that suppress target mRNA expression and affect downstream processes. Many studies have shown that miRNAs are integral biomolecules in hypoxia-adaptive responses. They also promote apoptosis in response to oxidative stress resulting in SNHL. Our hypothesis is that miRNAs are involved in the pathophysiological responses to hypoxia and oxidative stress that result in SNHL. This study reviews the evidence for hypoxia-adaptive miRNAs (hypoxamiRs) in different types of acquired SNHL and focuses on miRNAs involved in hypoxia driven SNHL. Methods: Electronic bibliographic databases PubMed, Ovid MEDLINE, Ovid EMBASE, and Web of Science Core Collection were searched independently by two investigators for articles published in English from the inception of individual databases to the end of July 2020. The text word or medical subject heading searches of all fields, titles, abstracts, or subject headings depending on the database were undertaken with combinations of the words "microRNAs", "hypoxia", "hypoxamiRs", "oxidative stress", "ischemia" and "hearing loss". The reference lists of studies meeting the inclusion criteria were searched to identify additional relevant studies. The inclusion criteria included relevant clinical studies with human subjects, animals, and in vitro experiments. The risk of bias was assessed using the Cochrane risk of bias assessment tool for human studies and the Systematic Review Center for Laboratory animal Experimentation (SYRCLE) a risk of bias assessment tool for animal model and in vitro studies. Results: A total of 15 primary articles were selected for full text screening after excluding duplicates, reviews, retracted articles, and articles not published in English. All nine articles meeting the study inclusion criteria were from animal or in vitro model studies and were assessed to be at low risk of bias. miRNAs miR-34a and miR-29b were reported to be involved in SNHL in inner ear cell models exposed to oxidative stress. Signaling pathways Sirtuin 1/peroxisome proliferator-activated receptor gamma coactivator-1-alpha (SIRT1/PGC-1α), SIRT1/p53, and SIRT1/hypoxia-inducible factor 1-alpha (HIF-1α) were identified as underlying pathways involved in acquired SNHL. Conclusion: There is evidence that miR-34a and -29b are involved in hypoxia-driven and other causes of oxidative stress-related acquired SNHL. Further studies are required to determine if these findings are clinically applicable.

Project description:IntroductionTo compare inpatient treated patients with idiopathic (ISSNHL) and non-idiopathic sudden sensorineural hearing loss (NISSNHL) regarding frequency, hearing loss, treatment and outcome.MethodsAll 574 inpatient patients (51% male, median age: 60 years) with ISSNHL and NISSNHL, who were treated in federal state Thuringia in 2011 and 2012, were included retrospectively. Univariate and multivariate statistical analyses were performed.ResultsISSNHL was diagnosed in 490 patients (85%), NISSNHL in 84 patients (15%). 49% of these cases had hearing loss due to acute otitis media, 37% through varicella-zoster infection or Lyme disease, 10% through Menière disease and 7% due to other reasons. Patients with ISSNHL and NISSNHL showed no difference between age, gender, side of hearing loss, presence of tinnitus or vertigo and their comorbidities. 45% of patients with ISSNHL and 62% with NISSNHL had an outpatient treatment prior to inpatient treatment (p < 0.001). The mean interval between onset of hearing loss to inpatient treatment was shorter in ISSNHL (7.7 days) than in NISSNHL (8.9 days; p = 0.02). The initial hearing loss of the three most affected frequencies in pure-tone average (3PTAmax) scaled 72.9 dBHL ± 31.3 dBHL in ISSNHL and 67.4 dBHL ± 30.5 dBHL in NISSNHL. In the case of acute otitis media, 3PTAmax (59.7 dBHL ± 24.6 dBHL) was lower than in the case of varicella-zoster infection or Lyme disease (80.11 dBHL ± 34.19 dBHL; p = 0.015). Mean absolute hearing gain (Δ3PTAmaxabs) was 8.1 dB ± 18.8 dB in patients with ISSNHL, and not different in NISSNHL patients with 10.2 dB ± 17.6 dB. A Δ3PTAmaxabs ≥ 10 dB was reached in 34.3% of the patients with ISSNHL and to a significantly higher rate of 48.8% in NISSNHL patients (p = 0.011).ConclusionsISSNHL and NISSNHL show no relevant baseline differences. ISSNHL tends to have a higher initial hearing loss. NISSHNL shows a better outcome than ISSNHL.

Project description:BackgroundSudden sensorineural hearing loss (SSNHL) is an otologic emergency that warrants urgent management. Pure-tone audiometry remains the gold standard for definitively diagnosing SSNHL. However, in clinical settings such as primary care practices and urgent care facilities, conventional pure-tone audiometry is often unavailable.ObjectiveThis study aimed to determine the correlation between hearing outcomes measured by conventional pure-tone audiometry and those measured by the proposed smartphone-based Ear Scale app and determine the diagnostic validity of the hearing scale differences between the two ears as obtained by the Ear Scale app for SSNHL.MethodsThis cross-sectional study included a cohort of 88 participants with possible SSNHL who were referred to an otolaryngology clinic or emergency department at a tertiary medical center in Taipei, Taiwan, between January 2018 and June 2019. All participants underwent hearing assessments with conventional pure-tone audiometry and the proposed smartphone-based Ear Scale app consecutively. The gold standard for diagnosing SSNHL was defined as the pure-tone average (PTA) difference between the two ears being ≥30 dB HL. The hearing results measured by the Ear Scale app were presented as 20 stratified hearing scales. The hearing scale difference between the two ears was estimated to detect SSNHL.ResultsThe study sample comprised 88 adults with a mean age of 46 years, and 50% (44/88) were females. PTA measured by conventional pure-tone audiometry was strongly correlated with the hearing scale assessed by the Ear Scale app, with a Pearson correlation coefficient of .88 (95% CI .82-.92). The sensitivity of the 5-hearing scale difference (25 dB HL difference) between the impaired ear and the contralateral ear in diagnosing SSNHL was 95.5% (95% CI 87.5%-99.1%), with a specificity of 66.7% (95% CI 43.0%-85.4%).ConclusionsOur findings suggest that the proposed smartphone-based Ear Scale app can be useful in the evaluation of SSNHL in clinical settings where conventional pure-tone audiometry is not available.

Dataset Information

The design and screening of drugs to prevent acquired sensorineural hearing loss.

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The design and screening of drugs to prevent acquired sensorineural hearing loss.

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