Upload
melanie-mcqueen
View
11
Download
0
Embed Size (px)
Citation preview
Therapeutic Prevention of Acquired Hearing LossMelanie McQueen, B.S. and Annelise Gerardi, B.H.S.The University of Texas at AustinSchool of Communication Sciences of Disorders
Overview● Introduction to Oxidative Stress● Role of Oxidative Stress in Acquired
Hearing Loss● Antioxidant Prevention of
Noise-Induced Hearing Loss
Acquired Hearing Loss● Oxidative Stress (free radical
formation)● Types of hearing loss driven by
oxidative stress: ○ Noise-Induced Hearing Loss (NIHL) ○ Drug-Induced Hearing Loss○ Age-Induced Hearing Loss
● NIHL is the most responsive to therapeutic treatment
What Causes NIHL?● Mechanical damage● Ischemia● Oxidative stress
○ Free radical formation in Organ of Corti = death of hair cells
Strategies for Reducing NIHL● Reduce the sound level at the source● Reduce time of exposure to the source● Design better hearing protection
devices● Decrease oxidative stress that induces
cell death in the inner ear through drugs or dietary supplements
Article One: Post-exposure treatment attenuates noise-induced hearing lossNeuroscience (2005)D. Yamashita, H.Y. Jiang, C. Le Prell, J. Schacht, and J. Miller
Background● Free radical formation can occur up to
10 days after noise exposure● Can antioxidant intervention during this
period reduce NIHL?● Can antioxidant intervention during this
period reduce NIHL?
Subjects● 42 male guinea pigs● Divided into 7 groups:Group 1 Group 2 Group 3 Group 4 Group 5 Group 6 Group 7
Control Saline injected on Day 1 (3 days before noise exposure)
Salicylate + trolox injected Days 1 to 14
Salicylate + trolox injected 1 hour after noise exposure until Day 14
Salicylate + trolox injected 1 day after noise exposure until Day 14
Salicylate + trolox injected 3 days after noise exposure until Day 14
Salicylate + trolox injected 5 days after noise exposure until Day 14
*Trolox = 50mg/kg, twice daily*Salicylate = 75 mg/kg, twice daily
Method● Animals in all groups were subjected to
noise on Day 4.● Stimulus = One-octave band noise
centered at 4 kHz @ 120 dB SPL for 5 hours
Outcome Measures● ABR Thresholds:
○ ABR thresholds at 4, 8, and 16 kHz were measured 7 days before treatment and 10 days after noise exposure
● Histological Examinations:○ Left ears processed for histological
hair cell counts○ Right ears processed for
immunohistochemical staining
Results● Reduction in NIHL threshold shift was
directly related to onset of preventative drug treatment
● Effectiveness of treatment decreased with time after noise exposure
Discussion● NIHL and sensory cell death can be
attenuated up to 3 days after noise exposure using a combination of antioxidants (salicylate + trolox)
● Pretreatment was most effective● In general, free radical formation was
reduced in cochlear cells by antioxidant therapy.
Implications● NIHL is a major cause of acquired
hearing loss in the world● Complete elimination of mechanical
cochlear damage and avoidance of acute accidental noise is impractical
● Therefore, could antioxidant treatment within a time window of noise exposure reduce NIHL in humans?
Article Two: Increased vitamin plasma levels in Swedish military personnel treated with nutrients prior to automatic weapon training Noise Health (2011)C. Le Prell, C. Johnson, A. Lindblad, A ̊. Skjo ̈nsberg, M. Ulfendahl, K. Guire, G. Green, M. Campbell, and J Miller
Background● The previous study demonstrated the
effectiveness of combined antioxidants in the prevention of NIHL in guinea pigs
● Can antioxidant treatment translate to the prevention of NIHL in humans?
Subjects● 31 subjects:
○ 10 Swedish military officers○ 21 Swedish military academy trainees
● Advertisements posted on base to encourage people to participate
● Exclusion factors: ○ Gastrointenstinal disturbances, neurological
disturbances, hematological disorders, and auditory/vestibular issues
● Requirements: ○ Symmetrical normal hearing, Type A tymps,
ipsilateral reflexes, and threshold asymmetry at </ 15 dB at all frequencies
Treatment● Micronutrient treatment combination
of beta carotene, vitamin C, vitamin E, and magnesium in the form of a pill
● Dosage was 6 pills a day (3 at a time, twice daily)
Study Design ● Double blind study● Randomized - Subjects
received nutrient or placebo condition for “Arm 1”
○ Each “arm” consisted of a single weapons training class
○ For “Arm 2,” there was a washout period before switching to other pill
Outcome Measures● Questionnaire
○ Self-reporting Hearing and Tinnitus survey
● Otoscopy● Tympanometry● Reflex Testing at 1 kHz @ 100 dB HL● Pure Tone Audiometry● DPOAE’s
Outcome Measures● Noise Exposure levels:
○ 40 shots fired from automatic machine gun in a bunker for over 1 minute while standard hearing protection was worn
● Blood Sampling and Analysis: ○ Collected from 9/10 of the officers○ Levels for vitamin C, vitamin E, beta
carotene and magnesium were measured
○ Taken one day before testing and 2 hours after exposure
Results:● Adverse effects:
○ One subject reported queziness within one day of study. 2 reported feeling ill during or after treatment
● Plasma levels: ○ Post treatment, levels increased for all except
magnesium
○ No reliable change in plasma levels when placebo was consumed first
● Pre 1 Test Outcomes: ○ Minimal differences seen between soldiers and
officers relating to age or effect
● Pre 2 Test Outcomes: ○ No effects on baseline measures
Results● Audiometry:
○ No effect on baseline thresholds thus no opportunity to measure protection against TTS as a function of treatment
● Tinnitus: ○ Reported sporadically, but not
significant
● Treatment group showed a 4-12 dB smaller TTS than placebo group for within subject comparisons
Measured Antioxidant Levels Before and 2 Hours Post Exposure for Placebo and Non Placebo Groups
Black = Pre Gray = Post
Discussion● No consistency in results
● No reliable noise-induced threshold shift was measured for either the placebo or non-placebo group
○ Does not support use of a preventative drug for human hearing protection
● However, elevated plasma levels were found in the blood of participants, which could be helpful for future studies
Discussion● Ear protection was good for avoiding
NIHL in humans...○ However, it created a lack of noise
induced changes, so it could not be determined if nutrients have beneficial effects in relation to hearing loss
● Need to design better studies in order to obtain successful human trials
Sources:Yamashita D; Jiang HY; Le Prell CG; Schacht J; Miller
JM, Neuroscience [Neuroscience], ISSN: 0306-4522, 2005; Vol. 134 (2), pp. 633-42; Publisher: Elsevier Science; PMID: 15961244, Database: MEDLINE
Le Prell CG; Johnson AC; Lindblad AC; Skjönsberg A; Ulfendahl M; Guire K; Green GE; Campbell KC; Miller JM, Noise & Health [Noise Health], ISSN: 1463-1741, 2011 Nov-Dec; Vol. 13 (55), pp. 432-43; Publisher: Medknow Publications Pvt. Ltd; PMID: 22122960, Database: MEDLINE