Cochlear hair cells are the sensory receptors of the auditory system. It is well established that antibiotic drugs such as gentamicin can damage hair cells and cause hearing loss. Rescuing hair cells after ototoxic injury is an important issue in hearing recovery. Although many studies have indicated a positive effect of low-level laser therapy (LLLT) on neural cell survival, there has been no study on the effects of LLLT on cochlear hair cells. Therefore, the aim of this study was to elucidate the effects of LLLT on hair cell survival following gentamicin exposure in organotypic cultures of the cochlea of rats. The cochlea cultures were then divided into a control group (n = 8), a laser-only group (n = 8), a gentamicin-only group (n = 8) and a gentamicin plus laser group (n = 7). The control cultures were allowed to grow continuously for 11 days. The laser-only cultures were irradiated with a laser with a wavelength of 810 nm at 8 mW/cm(2) for 60 min per day (0.48 J/cm(2)) for 6 days. The gentamicin groups were exposed to 1 mM gentamicin for 48 h and allowed to recover (gentamicin-only group) or allowed to recover with daily irradiation (gentamicin plus laser group). The hair cells in all groups were stained with FM1-43 and counted every 3 days. The number of hair cells was significantly larger in the gentamicin plus laser group than in the gentamicin-only group. The number of hair cells was larger in the laser-only group than in the control group, but the difference did not reach statistical significance. These results suggest that LLLT may promote hair cell survival following gentamicin damage in the cochlea. This is the first study in the literature that has demonstrated the beneficial effect of LLLT on the recovery of cochlear hair cells.
Objectives: To evaluate the efficacy and safety of low-level light therapy (LLLT) using new irradiation parameters for chronic unilateral tinnitus with cochlear dysfunction. Design: A single-blind, randomized clinical trial Setting: Tertiary-care hospital center Participants: Participants who had a history of chronic unilateral tinnitus (≥ 3 months) and pure-tone thresholds greater than 15dB (averaged for 3k, 4k, and 6k Hz). Main outcome measures: Numerical rating scales (NRS) measuring loudness, duration, and annoyance, the tinnitus handicap inventory (THI), and psychoacoustical matches of tinnitus loudness and minimum masking levels (MML). Results: Thirty-eight participants were received either a 100-mW diode laser at 830-nm (TINI group; n=19) or placebo (sham group; n=19) irradiation through the tympanic membrane. No adverse events were reported during 2 weeks of 10-interventions (20 minutes/day, five days/week). The NRS measuring duration of tinnitus and psychoacoustical matches of tinnitus loudness significantly decreased over times in the TINI group (p<0.05). However, post-hoc analysis revealed that there was no significant decrease of tinnitus among different time points (baseline, during LLLT, immediately after LLLT, and two weeks after LLLT). There was no placebo effect in the Sham group. Participants who improved the duration by at least one point or improved the loudness matches by more than 5 dB SL two weeks after LLLT tended to have worse pure-tone thresholds. It may suggest that further study is needed in patients with worse pure-tone thresholds to evaluate the therapeutic efficacy of LLLT. Conclusion: Although this preliminary result is insufficient to support the therapeutic efficacy of new laser device for chronic tinnitus, further study is needed in a large number of selected patients.
Photobiomodulation (PBM) has been suggested to have a therapeutic effect on irreversible hearing loss induced by aminoglycosides, including gentamicin (GM). However, its intracellular mechanism(s) in GM-induced ototoxicity remain poorly understood. In the present study, we investigated the effect of PBM in GM-induced ototoxicity in auditory cells. We tried to characterize the downstream process by PBM, and the process that triggered the increased cell viability of auditory cells. As a result, the effects of PBM against GM-induced ototoxicity by increasing ATP levels and mitochondrial membrane potential was confirmed. These results suggest a theory to explain the therapeutic effects and support the use of PBM for aminoglycoside-induced hearing loss.
ObjectivesThe purpose of this study was to evaluate the therapeutic effect of three different types of sounds on tinnitus patients undergoing tinnitus retraining therapy (TRT).MethodsThis is a single-institution retrospective study, performed in one tertiary otological referral center. Thirty-eight adults with subjective idiopathic tinnitus who were followed for at least 9 weeks were enrolled. Sound therapy was delivered in 3 different ways: narrowband noise TRT (nTRT); mixed band noise TRT (mTRT); broadband noise TRT (bTRT). Treatment response was measured through validated psychometric questionnaires: Tinnitus Handicap Inventory (THI), visual analog scale (VAS) on annoyance, and numerical description of hours of tinnitus perception (awareness hours).ResultsA total of 38 patients were followed for at least 9 weeks. In nTRT group, all outcome measures including THI, VAS, and the awareness hours, decreased over 9 weeks with no statistical significance. In mTRT group, all outcome measures except for awareness hours significantly improved 9 weeks after the beginning of the treatment. In bTRT group, all outcome measures decreased significantly in 9 weeks. When therapeutic success is defined as improvement in THI 7 or more, bTRT group (77.8%) showed a higher success rate than other groups for 38 patients with the minimum follow-up of 9 weeks.ConclusionAll three sounds can provide relief in patients with annoying tinnitus after TRT. However, there is difference in the therapeutic effect according to sound types. Broadband sound seems to be better than narrowband sound or mixed sound in relieving the patients from tinnitus. Therefore, sound therapy with broadband noise may be more appropriate during TRT, but further evidence is needed for precise conclusion.
Survivin is an apoptotic and mitotic regulator that is overexpressed in melanoma and a poor prognostic marker in patients with metastatic disease. We recently showed that Survivin enhances melanoma cell motility through Akt-dependent upregulation of α5 integrin. However, the functional role of Survivin in melanoma metastasis is not clearly understood. We found that overexpression of Survivin in LOX and YUSAC2 human melanoma cells increased colony formation in soft agar, and this effect was abrogated by knockdown of α5 integrin by RNA interference. We employed melanoma cell xenografts to determine the in vivo effect of Survivin overexpression on melanoma metastasis. Although Survivin overexpression did not affect primary tumor growth of YUSAC2 or LOX subcutaneous tumors, or indices of proliferation or apoptosis, it significantly increased expression of α5 integrin in the primary tumors and formation of metastatic colonies in the lungs. Additionally, Survivin overexpression resulted in enhanced lung colony formation following intravenous (i.v.) injection of tumor cells in vivo and increased adherence to fibronectin-coated plastic in vitro. Importantly, in vivo inhibition of α5 integrin via intraperitoneal injection of an α5β1 integrin-blocking antibody significantly slowed tumor growth and reduced Survivin-enhanced pulmonary metastasis. Knockdown of α5 integrin in cells prior to i.v. injection also blocked Survivin-enhanced lung colony formation. These findings support a direct role for Survivin in melanoma metastasis, which requires α5 integrin and suggest that inhibitors of α5 integrin may be useful in combating this process.
Noise-induced hearing loss is a common type of hearing loss. The effects of laser therapy have been investigated from various perspectives, including in wound healing, inflammation reduction, and nerve regeneration, as well as in hearing research. A promising feature of the laser is its capability to penetrate soft tissue; depending on the wavelength, laser energy can penetrate into the deepest part of the body without damaging non-target soft tissues. Based on this idea, we developed bilateral transtympanic laser therapy, which uses simultaneous laser irradiation in both ears, and evaluated the effects of bilateral laser therapy on cochlear damage caused by noise overexposure. Thus, the purpose of this research was to assess the benefits of simultaneous bilateral laser therapy compared with unilateral laser therapy and a control. Eighteen Sprague-Dawley rats were exposed to narrow-band noise at 115 dB SPL for 6 h. Multiple auditory brainstem responses were measured after each laser irradiation, and cochlear hair cells were counted after the 15th such irradiation. The penetration depth of the 808 nm laser was also measured after sacrifice. Approximately 5% of the laser energy reached the contralateral cochlea. Both bilateral and unilateral laser therapy decreased the hearing threshold after noise overstimulation in the rat model. The bilateral laser therapy group showed faster functional recovery at all tested frequencies compared with the unilateral laser therapy group. However, there was no difference in the endpoint ABR results or final hair cell survival, which was analyzed histologically.
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