Effect over time of allopurinol on noise-induced hearing loss in guinea pigs.

Temporary threshold shift (TTS) and permanent threshold shift (PTS) may follow prolonged noise exposure. Several reports suggest that noise-induced damage to the cochlea may be related to the activity of reactive oxygen species (ROS). Drugs that scavenge or block ROS formation also protect the cochlea. Guinea pigs, treated with allopurinol, were exposed to white noise (120 dB SPL) or impulse noise (114 dB SPL) for 2 and 5 h. The protective effect of allopurinol was confirmed, but, at these levels of sound, it was present only after noise exposure up to 2 h. This study also offers evidence suggesting that allopurinol does not influence the establishment of PTS

Down-regulation of otospiralin mRNA in response to acoustic stress in guinea pig

Noise over-stimulation will induce or influence molecular pathways in the cochlea; one approach to the identification of the components of these pathways in the cochlea is to examine genes and proteins that change following different types and levels of stress. Quantitative reverse transcription polymerase chain reaction provides a method to look at differential expression of genes in the acoustic stress response. By using this technique we have revealed a down-regulation of the level of otospiralin mRNA in the cochlea of guinea pigs after white noise over-stimulation for 2 h at 108 dB SPL. Otospiralin represents an inner ear specific protein found in fibrocytes of spiral limbus and spiral ligament in the cochlea, and some regions of the vestibule as the stroma underlying the utricle and crista sensory epithelia and the subepithelial layer of the walls of semicircular canals and maculae. It has been recently reported that transient down-regulation of otospiralin in guinea pigs causes vestibular syndrome and deafness. Our results suggest a possible role of this gene in response to acoustical stress, although the exact mechanism remains to be resolved

Audiometric evaluation of carriers of the connexin 26 mutation 35delG

Mutation in a gap junction protein gene (GJB2 also named connexin 26) is a major cause of autosomal recessive congenital deafness, which is responsible for about 80% of the cases in Mediterranean families, but actually little is known about the influence of GJB2 mutations on the hearing of obligate carriers. We examined GJB2 35delG mutation carrier individuals to test the possible presence and incidence of audiometric abnormalities among carriers of 35delG mutations. Tonal audiometric analysis was performed on a 35delG mutation carrier group (H) and on a non-carrier control group (N). Audiometric evaluations in the control group showed the presence of thresholds within normal limits at all frequencies, while carriers of 35delG mutations presented a decrease of hearing principally at 6,000 and 8,000 Hz. The difference at 6,000 and 8,000 Hz between groups H and N is statistically significan

Paraoxonase and superoxide dismutase gene polymorphisms and noise-induced hearing loss.

BACKGROUND: Noise-induced cochlear epithelium damage can cause hearing loss in industrial workers. In experimental systems, noise induces the release of free radicals and may damage the cochlear sensorial epithelium. Therefore, genes involved in regulating the reactive oxygen species manganese-superoxide dismutase (SOD2) and the antioxidant paraoxonase (PON) could influence cochlea vulnerability to noise. We evaluated whether susceptibility to noise-induced hearing loss (NIHL) is associated with SOD2, PON1, and PON2 polymorphisms in workers exposed to prolonged loud noise. METHODS: We enrolled 94 male workers from an aircraft factory in the study. The SOD2 gene was screened by denaturing reversed-phase HPLC, and the PON1 (Q192R and M55L) and PON2 (S311C) polymorphisms were analyzed by PCR amplification followed by digestion with restriction endonucleases. RESULTS: Three known (A16V, IVS3-23T/G, and IVS3-60T/G) and two new SOD2 polymorphisms (IVS1+ 8A/G and IVS3+107T/A) were identified. Regression analysis showed that PON2 (SC+CC) [odds ratio (OR) = 5.01; 95% confidence interval (CI), 1.11-22.54], SOD2 IVS3-23T/G and IVS3-60T/G (OR = 5.09; 95% CI, 1.27-20.47), age (OR = 1.22; 95% CI, 1.09-1.36), and smoking (OR = 49.49; 95% CI, 5.09-480.66) were associated with NIHL. No association was detected for PON1 (QQ+RR) and PON1 (LL) genotypes. CONCLUSIONS: Our data suggest that SOD2 and PON2 polymorphisms, by exerting variable local tissue antioxidant roles, could predispose to NIHL. However, caution should be exercised in interpreting these data given the small sample size and the difficulty in matching cases to controls regarding the overwhelming risk factor, i.e., smoking at least 10 cigarettes/day

Functional fields in human auditory cortex revealed by time-resolved fMRI without interference of EPI noise

The gradient switching during fast echoplanar functional magnetic resonance imaging (EPI-fMRI) produces loud noises that may interact with the functional activation of the central auditory system induced by experimental acoustic stimuli. This interaction is unpredictable and is likely to confound the interpretation of functional maps of the auditory cortex. In the present study we used an experimental design which does not require the presentation of stimuli during EPI acquisitions and allows for mapping of the auditory cortex without the interference of scanner noise. The design relies on the physiological delays between the onset, or the end, of stimulation and the corresponding hemodynamic response. Owing to these delays and through a time-resolved acquisition protocol it is possible to analyze the decay of the stimulus-specific signal changes after the cessation of the stimulus itself and before the onset of the EPI-acoustic noise related activation (decay-sampling technique). This experimental design, which might permit a more detailed insight in the auditory cortex, has been applied to the study of the cortical responses to pulsed 1000 Hz sine tones. Distinct activation clusters were detected in the Heschl's gyri and the planum temporale, with an increased extension compared to a conventional block-design paradigm. Furthermore, the comparison of the hemodynamic response of the most anterior and the posterior clusters of activation highlighted differential response patterns to the sound stimulation and to the EPI-noise. These differences, attributable to reciprocal saturation effects unevenly distributed over the superior temporal cortex, provided evidence for functionally distinct auditory fields