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Overexpression of copper/zinc-superoxide dismutase protects from kanamycin-induced hearing loss.

The participation of reactive oxygen species in aminoglycoside-induced ototoxicity has been deduced from observations that aminoglycoside-iron complexes catalyze the formation of superoxide radicals in vitro and that antioxidants attenuate ototoxicity in vivo. We therefore hypothesized that overexpression of Cu/Zn-superoxide dismutase (h-SOD1) should protect transgenic mice from ototoxicity. Immunocytochemistry confirmed expression of h-SOD1 in inner ear tissues of transgenic C57BL/6-TgN[SOD1]3Cje mice. Transgenic and nontransgenic littermates received kanamycin (400 mg/kg body weight/day) for 10 days beginning on day 10 after birth. Auditory thresholds were tested by evoked auditory brain stem responses at 1 month after birth. In nontransgenic animals, the threshold in the kanamycin-treated group was 45-50 dB higher than in saline-injected controls. In the transgenic group, kanamycin increased the threshold by only 15 dB over the respective controls. The effects were similar at 12 and 24 kHz. The protection by overexpression of superoxide dismutase supports the hypothesis that oxidant stress plays a significant role in aminoglycoside-induced ototoxicity. The results also suggest transgenic animals as suitable models to investigate the underlying mechanisms and possible strategies for prevention.

Animals↗

Effects of intake and rejection tasks on auditory fatigue.

The effects of sensory intake and rejection tasks on auditory fatigue were examined in 14 male subjects. Auditory thresholds, psychophysical tuning curves and physiological measures of cardiovascular function were obtained before, during, and following a 7 min 110 dB SPL white noise exposure. Acceleration of heart rate was observed under the sensory rejection (mental arithmetic) condition, and poorer post-exposure auditory thresholds and larger Q10 tip values (measured during late post-exposure intervals) were seen when the task required counting of interruptions in the noise. However, Q10 tip values obtained 1 to 2 min post-exposure, when cochlear effects are maximal, failed to confirm a significant difference as a function of task.

Adult↗

When instructions fail. The effects of stimulus control training on brain injury survivors' attending and reporting during hearing screenings.

Bedside hearing screenings are routinely conducted by speech and language pathologists for brain injury survivors during rehabilitation. Cognitive deficits resulting from brain injury, however, may interfere with obtaining estimates of auditory thresholds. Poor comprehension or attention deficits often compromise patient abilities to follow procedural instructions. This article describes the effects of jointly applying behavioral methods and psychophysical methods to improve two severely brain-injured survivors' attending and reporting on auditory test stimuli presentation. Treatment consisted of stimulus control training that involved differentially reinforcing responding in the presence and absence of an auditory test tone. Subsequent hearing screenings were conducted with novel auditory test tones and a common titration procedure. Results showed that prior stimulus control training improved attending and reporting such that hearing screenings were conducted and estimates of auditory thresholds were obtained.

Aged↗

[Vestibular neurotomy versus chemical labyrinthectomy for disabling Menière disease].

OBJECTIVE: To evaluate the efficiency on the vertigos and the impact on the audition of the vestibular neurotomy (VN) and the chemical labyrinthectomy (CL) in patients with severe Menière's disease, in order to determine the precise place for each technique in treatment algorithm. METHOD: Retrospective study of 71 VN (performed between 1986 and 2003) and 35 CL (performed between 1997 and 2003). These two treatments both aim at obtaining a vestibular deafferentation in order to free definitely the patient of vertigo manifestations. Vestibular results have been assessed by caloric tests performed before and 6 months after treatment. Subjective success was evaluated by searching for recurrent attacks of vertigo and by the AAO-HNS (American Academy of Otolaryngology-Head and Neck Society) scale of subjective evaluation of vertigos (follow-up of 6.4 years after VN and 2.4 years after CL). Pure tone audiometry before treatment and then 6 months later was performed. Complications of two types of treatment were recorded and evaluated. RESULTS: In 90% of the cases after VN and 86% of the cases after CL, caloric tests indicated a strong vestibular hyporeflexy (hypovalence > 90%). Attacks of vertigo reoccurred in 5.6% of the cases when the hyporeflexy was strong and 85.7% of the cases when it was weak. The quality of the vestibular results on vertigo depends on the degree of hypovalence after treatment. An improvement of the AAO-HNS scale have been obtained in 93% of the cases in the NV group and in 81% of the cases in the LC group. Attacks of vertigo were recurrent in 7% of the patients operated on by VN and 11.4% of the patients treated by CL. Mean pure tone auditory thresholds changed from 50.24 dB HL to 55.64 dB HL (p=0.003) in the VN group and from 69.11 dB HL to 74.51 dB HL (p=0.41) in the CL group. Comparison of the variations of the mean pure tone auditory thresholds before treatment and 6 months after the end of the treatment doesn't show any significant difference between the 2 groups (p > 0.05). Impairment of the audition superior to 20 dB HL was observed in 8.5% of the patients of each group. The auditive results are similar in the 2 groups. CONCLUSION: These two methods of treatment can not be strictly compared due to several bias in this study. Indeed more patients were treated by VN with a longer follow-up and only the patients with a class C or D audition according to the criteria of the AAO-HNS could be treated by CL. The VN provides a better control of the vertigos than the CL which is an efficient method of treatment in invalidating Meniere's disease. In all the cases, the quality of the results on vertigos depends on the degree of hypovalence after treatment. The auditive results are similar. Since the results of the two treatments are similar, the simplicity of CL encourages us to broaden the indications and to modify the place of the VN in the therapeutic algorithm of Menière's disease.

Adult↗

Gentamicin-induced chronotoxicity: use of body temperature as a circadian marker rhythm.

Aminoglycoside antibiotics produce varying degrees of ototoxicity, dependent on dosage time, in animals synchronized for rhythm study. Herein, we illustrate the use of an economical and reliable system to telemeter body temperature of laboratory animals as an endogenous marker rhythm for gentamicin-induced ototoxicity. Two groups of 3 male Sprague-Dawley rats (250-400 gm) were housed in separate cages in a temperature-controlled room programmed with a 12:12 LD schedule and monitored for hearing thresholds at the frequencies of 8kHz, 16 kHz, 24 kHz and 32 kHz at 2-week intervals. Each rat was dosed with 100 mg/kg/day gentamicin subcutaneously for a duration of 28 days. The animals from one group were dosed at their daily temperature maximum, while the animals of the other group were dosed at their daily temperature minimum. Both after 14 and 28 days of gentamicin treatment there was no important changes in auditory thresholds from baseline values when treatment was timed daily to the circadian peak of body temperature. Animals dosed daily at the trough of the circadian temperature rhythm evidenced an auditory threshold shift of between 5 and 25 dB after 14 days of treatment and a total hearing loss (80-90 dB) after 28 days of such treatment. These results document a dramatically greater level of hearing loss induced in those animals dosed with gentamicin at the body temperature trough (diurnal rest span) as compared to those dosed at the acrophase (nocturnal activity span). The findings indicate that the peak and trough of the circadian pattern of body temperature serve as meaningful markers of the resistance and susceptibility, respectively, of gentamicin-induced ototoxicity in rodent models.

Animals↗

The pattern and stability of postmeningitic hearing loss in children.

Following meningitis, 280 children (168 boys, 112 girls) had audiological assessment, and 87 (31%) were initially found to have a sensorineural hearing loss in one or both ears. Twenty-three children were followed elsewhere. Of 64 children followed for an average of 3.46 years, 55 (86%) exhibited stable auditory thresholds over time, most commonly (24) bilateral, profound/anacusic losses. One moderate and four severe losses were identified, but no bilateral, mild losses. Nineteen children had asymmetric losses with varied audiometric configurations. Seven children presented with a unilateral hearing loss, again with a range of configurations. Auditory thresholds changed over time in nine children, either improving, declining, or fluctuating, over a variable interval ranging from 1 month to 12 years.

Audiometry↗

[The study of biocompatibility of titanium in middle ear cave of guinea-pig].

In order to supply full objective basis about tympanoplasty with titanium, 30 middle ear caves of guinea-pigs were implanted titanium ring in accordance with different time groups. Both before and after titanium ring were implanted, the guinea-pigs were detected in biochemical criterion of blood, titanium content of the hair, the changing of auditory threshold, tissue structural of middle ear and inner ear by energy spectrometry, electro-physiology, microscopy and scanning electron microscopy. The results showed that function of hepatorenal and titanium content of hair haven't significant change between pre- and postimplantation of titanium ring. Only 10 days group, it appeared the rising of auditory threshold and inverting of cilia by ABR and scanning electron microscopy. In 10 days and 1 month groups, there were blood stain and inflammatory cells under mucosa. The results suggested that titanium is good biocompatibility and no toxic for organism and mucosa.

Animals↗

Ototoxicity in rats exposed to ethylbenzene and to two technical xylene vapours for 13 weeks.

Male Sprague-Dawley rats were exposed to ethylbenzene (200, 400, 600 and 800 ppm) and to two mixed xylenes (250, 500, 1,000 and 2,000 ppm total compounds) by inhalation, 6 h/day, 6 days/week for 13 weeks and sacrificed for morphological investigation 8 weeks after the end of exposure. Brainstem auditory-evoked responses were used to determine auditory thresholds at different frequencies. Ethylbenzene produced moderate to severe ototoxicity in rats exposed to the four concentrations studied. Increased thresholds were observed at 2, 4, 8 and 16 kHz in rats exposed to 400, 600 and 800 ppm ethylbenzene. Moderate to severe losses of outer hair cells of the organ of Corti occurred in animals exposed to the four concentrations studied. Exposure to both mixed xylenes produced ototoxicity characterized by increased auditory thresholds and losses of outer hair cells. Ototoxicity potentiation caused by ethylbenzene was observed. Depending on the mixed xylene studied and the area of the concentration-response curves taken into account, the concentrations of ethylbenzene in mixed xylenes necessary to cause a given ototoxicity were 1.7-2.8 times less than those of pure ethylbenzene. Given the high ototoxicity of ethylbenzene, the safety margin of less or equal to two (LOAEL/TWA) might be too small to protect workers from the potential risk of ototoxicity. Moreover, the enhanced ototoxicity of ethylbenzene and para-xylene observed in mixed xylenes should encourage the production of mixed xylenes with the lowest possible concentrations of ethylbenzene and para-xylene.

Air Pollutants, Occupational↗

Relationship of visual two-flash and absolute auditory perceptual sensitivity.

The relationship of two-flash and absolute auditory threshold measures was studied in a sample of 65 male college students. The two-flash threshold showed sensitivity essentially unrelated to absolute auditory sensitivity (r = .03). This result was contrasted with that reported by Hanback and Revelle who found a weak but significantly positive correlation for the sensitivity values for the two tasks.

Adolescent↗

Transtympanic and surface recordings in the diagnosis of retrocochlear disorders.

A series of patients presenting with subsequently surgically confirmed central tumour involving the auditory pathways were investigated using both transtympanic electrocochleography (TT ECochG) and surface recordings of brainstem evoked responses (BER). While ECochG allows a detailed study of peripheral function, BER allow the investigation of neural conduction up to the level of the inferior colliculus. Valuable information can be obtained from: (1) comparison of the amplitudes of the sensory and neural components of the ECochG; (2) comparison of ECochG, BER and auditory thresholds; (3) time interval measurements between the auditory nerve response (N1 on the ECochG) and the inferior colliculus (wave P4-5 on BER); (4) contralateral comparisons. Similar measurements performed in pure cochlear pathologies, mainly in Meniere's disease, yielded very significant differences.

Audiometry↗

Auditory role of lateral trunk channels in cobitid fishes.

In cobitid fishes the anterior part of the swimbladder is encapsulated by bone to varying extent. This might diminish the auditory sensitivity of these otophysine fishes by reducing the vibrations of the swimbladder wall in the sound field. However, according to prior studies the auditory thresholds of the cobitid Botia modesta is similar to that of other otophysine fishes. According to anatomical investigation B. modesta has a cranial encapsulation of the anterior part of the swimbladder (camera aerea Weberiana) as expected and in addition special channels stretching laterally from the swimbladder to the outer body wall. These lateral trunk channels are filled with fat and lymph. They form a muscle-free acoustic window beneath the skin, which could be demonstrated by measuring the auditory brainstem response at 400 Hz, 800 Hz, 1500 Hz, and 3000 Hz. Filling the lateral trunk channels with wettex (cotton/rayon staple) resulted in an increase of the auditory thresholds by 13.6-17.6 dB, indicating mechanical damping of the swimbladder. Our experiments demonstrate that the intact lateral trunk channels enhance the hearing sensitivity of cobitid fishes.

Air Sacs↗

Enhanced neurotoxicity of 3,3'-iminodipropionitrile following carbon tetrachloride pretreatment in the rat.

The consequences of 3,3'-iminodipropionitrile (IDPN) exposure in animals merits attention both because of its unique neurotoxic effects and as a potential model compound of human dyskinetic disorders. An important question that remains to be determined is whether IDPN itself or a putative active metabolite is responsible for the neurotoxic actions of the chemical in vivo. The present work tested the hypothesis that IDPN must be metabolized by the liver to an active metabolite to become neurotoxic. Thus a reduction in IDPN neurotoxicity would be expected when liver function is compromised. Male Long-Evans rats were given ip injections of saline, 100 (IDPN1) or 200 (IDPN2) mg/kg of IDPN for three days. Half of the animals in each IDPN dose group received corn oil po and the other half 1 g/kg of the hepatotoxicant carbon tetrachloride (CCl4) for three days, starting one day before IDPN administration. Body weights were obtained regularly after exposure. Horizontal and vertical motor activity, and acoustic startle response were monitored prior to, and 1,3,9 and 16 weeks after IDPN exposure. An observational rating score was obtained at 1, 3 and 9 weeks. Auditory thresholds for 5- and 40-kHz tones were estimated by reflex modification procedures at 10 weeks. Animals receiving IDPN2 alone displayed the overt behavioral signs characteristic of IDPN intoxication (postural disturbances, head dyskinesias, backward walking, circling, increased motor activity, and decreased startle response). They also showed weight loss, hyperactivity, a transient rearing deficit, decreased startle amplitudes and elevated auditory thresholds for low- and high-frequency tones. None of these symptoms were observed in the animals treated with CCl4 alone, and only a mild transient effect on the observational rating score was shown by the IDPN1 alone animals. In contrast, IDPN1/CCl4 resulted in the same or higher toxicity than the IDPN2 treatment. IDPN2/CCl4 resulted in severe toxicity (38% mortality over a two-week period) and enhanced body weight and behavioral effects compared to IDPN2 alone group. Impairment of xenobiotic biotransformation was confirmed by elevated pentobarbital sleeping time in animals under the same CCl4 dosing regimen. In conclusion, pretreatment with hepatotoxic dosages of CCl4 leads to increased toxicity of IDPN. This suggests that hepatic transformation of the chemical is not required for the manifestation of IDPN-induced neurotoxicity, but instead may be involved in the detoxification of this compound.

Analysis of Variance↗

[Long-term therapy of Ménière's disease. Comparison of the effects of betahistine dihydrochloride and hydrochlorothiazide].

During the last few years betahistine-dihydrochloride has been used extensively in the conservative treatment of M. Ménière. The question has arisen as to whether betahistine-dihydrochloride is more effective than diuretics. The effect of betahistine-dihydrochloride was compared to that of hydrochlorothiazide on 32 M. Ménière-patients. The patients were initially kept under observation for 3 months without medication apart from symptomatic anti-vertigo agents. The patients were then assigned to 2 groups each of 16 subjects and received either 3 X 8 mg betahistine-dihydrochloride or 3 X 25 mg hydrochlorothiazide for 6 months under double-blind conditions. Before and during treatment subjective symptoms such as vertigo, attacks of dizziness, tinnitus, sensation of blockage in the ear and general well-being were assessed at 4-weekly intervals. Apart from this the objective symptoms as measured by pure tone audiograms, Frenzel-test and electronystagmography were recorded. At the moment betahistine-dihydrochloride seems to be the drug of choice for Ménière-patients with a fluctuating auditory threshold. During the 6 months treatment period an impressive reduction in the frequency, severity and duration of the attacks of vertigo as well as an improvement in the general condition was found in all patients. In contrast the diuretic hydrochlorothiazide seemed to show a distinct therapeutic effect on vertigo and general well-being principally during the first few months of treatment in patients with a constant auditory threshold.

Audiometry, Pure-Tone↗

Dietary vitamin E protects the fathead minnow, Pimephales promelas, against noise exposure.

The fathead minnow (Pimephales promelas) was employed to examine if dietary vitamin E supplementation could protect the inner ear from the deleterious effects of noise. Fish were fed one of the three experimental diets containing either: (1) low vitamin E content (14.5 mg/kg diet as alpha-tocopheryl acetate), (2) an adequate amount of vitamin E (50 mg/kg), or (3) high vitamin E content (450 mg/kg). After 4 weeks on the diet, fish were exposed to either 2 or 24 h of intense white noise (142 dB re: 1 microPa, bandwidth 0.3-4.0 kHz). Auditory thresholds were measured, using the auditory brainstem response (ABR) technique, within 0.5 days following noise exposure or within a recovery period of 1.5 days. Additionally, liver samples were analyzed for vitamin E content. Increased vitamin E supplementation was dose-dependently associated with a reduction in statistically significant threshold shifts after noise exposure and an enhancement of recovery (i.e., more complete recovery over a shorter period) for fish exposed to either 2 or 24 h of noise. The results obtained suggest that dietary vitamin E affords protection against noise exposure in a cyprinid fish.

Acoustic Stimulation↗

Effects of underwater noise on auditory sensitivity of a cyprinid fish.

The ability of a fish to interpret acoustic information in its environment is crucial for its survival. Thus, it is important to understand how underwater noise affects fish hearing. In this study, the fathead minnow (Pimephales promelas) was used to examine: (1) the immediate effects of white noise exposure (0.3-4.0 kHz, 142 dB re: 1 microPa) on auditory thresholds and (2) recovery after exposure. Audiograms were measured using the auditory brainstem response protocol and compared to baseline audiograms of fathead minnows not exposed to noise. Immediately after exposure to 24 h of white noise, five out of the eight frequencies tested showed a significantly higher threshold compared to the baseline fish. Recovery was found to depend on both duration of noise exposure and auditory frequency. These results support the hypothesis that the auditory threshold of the fathead minnow can be altered by white noise, especially in its most sensitive hearing range (0.8-2.0 kHz), and provide evidence that these effects can be long term (>14 days).

Animals↗

The effects of 2,4-dithiobiuret on sensory and motor function.

2,4-Dithiobiuret (DTB) exposure causes a delayed onset muscle weakness in rats that has been attributed to depressed neuromuscular transmission. The present study compares the effects of DTB on both sensory and motor function in rats. Adult male Long-Evans hooded rats were exposed to saline, 0.25, 0.5, or 1.0 mg/kg/day DTB, ip, for 5 consecutive days (Days 1-5). Body weights were monitored throughout the experiment. Motor activity was measured for 1 hr in figure-eight mazes on Days 0, 6, 13, and 27. Forelimb and hindlimb grip strength were assessed on Days 6, 13, and 27. Auditory thresholds were determined for 5- and 40-kHz tones using reflex modification of the startle response on Days 0, 7, 14, and 28. Visual function was examined on Day 6 in animals exposed at 0.5 mg/kg/day using flash- and pattern-elicited visual evoked potentials (FEPs and PEPs, respectively). Thermal sensitivity was measured using the hot plate procedure. All motor endpoints were decreased in a dosage- and time-dependent manner; the higher the dosage the longer the effects lasted. There were no effects on any measure of sensory function with the exception of peak N2 of the FEP. Both the amplitude and latency of FEP N2 were altered by DTB exposure. Decreases in body weight were maximal on Day 9 at 1.0 mg/kg/day (20% from control), but recovered by Day 22. Motor activity was suppressed on Day 6 only, whereas grip strength measures were decreased on both Days 6 and 13. Auditory thresholds were not significantly altered; however, baseline startle amplitude was decreased at the highest dosage on Days 7 and 14, but recovered by Day 28. Hot plate latencies were not altered by DTB treatment. These data demonstrate that DTB produces a reversible impairment of motor function, without altering auditory, thermal, or pattern visual function. FEP N2, which is thought to arise from activity generated in the superficial layers of visual cortex, was diminished by DTB treatment, indicating that DTB can alter the function of the CNS, although effects on the motor system are more pronounced.

Animals↗

[Applying distortion product otoacoustic emission in testing human sensory hearing loss].

OBJECTIVE: To probe into the application of distortion product otoacoustic emission (DPOAE) test in human sensory hearing loss (SHL) research using lower stimulus parameter L1 = 65 dB, L2 = 50 dB. METHODS: Elicitation rate, size of DPOAE and correlation between DPOAE and pure tone auditory threshold were analyzed, and then the sensitivity and specificity were calculated. RESULTS: DPOAE was elicited in all of the hearing normal controls (25 subjects, 50 ears). In SHL cases (40 patients, 53 ears), DPOAE was elicited in 51 ears at 4 kHz and 6 kHz, and in 53 ears at 1 kHz and 2 kHz. The DPOAE size at each frequency in the normal group was higher than that in the SHL group (P < 0.05). A negative correlation between DPOAE size and pure tone auditory threshold was revealed by means of Spearman rank sum test. The sensitivity and specificity of DPOAE for testing SHL were better than those in literature reports. CONCLUSION: The DPOAE elicited by lower stimulus parameter mainly reflects the function of outer hair cells of inner ear, and thus it may provide some guidance or information for clinical diagnosis and treatment of SHL.

Adult↗

Hearing loss of a central type secondary to anoxic anoxia.

The effect of anoxic anoxia on the threshold sensitivity and amplitude of the responses from the auditory cortex, inferior colliculus and cochlea to acoustic stimuli in guinea pigs was studied. Decay of the amplitude of the responses from the auditory cortex and the inferior colliculus occurs faster and is more severe than that of the cochlea. Recovery of the amplitude of the responses is slower at the auditory cortex and the inferior colliculus than at the cochlea. Loss of auditory threshold sensitivity in anoxic anoxia is most prominent at the auditory cortex. The loss of sensitivity at the inferior colliculus is the next most severe. The loss of sensitivity at the cochlea is negligible. The relative vulnerability of the central auditory pathway to anoxic anoxia as compared to the end organ is demonstrated.

Animals↗