• Molecular & Cellular Toxicology
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• v.5 no.2
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• pp.133-140
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• 2009

Caveolin may be a molecular target for modulation of aging process in cochlear hair cells and have association with oxotoxicity. First we investigated the basal expression of caveolin-1, caveolin-2, caveolin-3, nitric oxide synthase, and superoxide dismutase in UB/OC-1 cochlear hair cell line. By using a RNA interference technique, we investigated whether down-regulation of caveolin influenced telomerase activity and reactive oxygen species (ROS) production in cochlear hair cells. In addition, cisplatin and gentamycin, known ototoxic drugs, were administered to the cochlear cells to determine their impact on caveolin expression. Further attempts at elucidating cellular aging mechanism with caveolin and ototoxic drugs were carried out. The main discoveries were the presence of caveolin-1 in UB/OC-1 cells and that down-regulation of caveolin-1 reduced protein kinase A activity. Telomerase was activated by caveolin down-regulation and caveolin down-regulation inhibited oxidative stress at the mitochondrial level. When cisplatin and gentamycin were administered to the cochlear hair cells during a caveolin expression state, a decrease in telomerase activity and increase ROS activity was observed. Caveolin-1 may modulate the senescent mechanisms in cochlear cells. An increase in caveolin-1 levels can lead to ROS production in the mitochondria which may cause ototoxicity.

• Journal of Biomedical Engineering Research
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• v.28 no.2
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• pp.205-211
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• 2007

A novel envelope extraction algorithm for speech processor of cochlear implants, called adaptation algorithm, was developed which is based on a adaptation effect of the inner hair cell(IHC)/auditory nerve(AN) synapse. We achieved acoustic simulation and hearing experiments with 12 normal hearing persons to compare this adaptation algorithm with existent standard envelope extraction method. The results shows that speech processing strategy using adaptation algorithm showed significant improvements in speech recognition rate under most channel/noise condition, compared to conventional strategy We verified that the proposed adaptation algorithm may yield better speech perception under considerable amount of noise, compared to the conventional speech processing strategy.

• Proceedings of the KOR-BRONCHOESO Conference
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• 1978.06a
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• pp.9.1-10
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• 1978

Recently the authors have observed various wave-forms by insertion of induction coil into the scala tympani as well as attached outer device in the outside of the body in damaged hair cells of the cats. In the cochlear nerve. action potential indicated different polarities induced by examination of the bundle of the cochlear nerve fibers. Impulse wave-form as a result of excitation of cohlear nerve fibers showed bipolar wave-form such as negative 1 and positive 1. Therefore action potential showed also bipolar wave-form as above mentioned. We can obtained suitable response with above mentioned outer and inner device as an exact oscillogram.

• Journal of Biomedical Engineering Research
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• v.14 no.2
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• pp.125-136
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• 1993

The study of Cochlear biomechanics is to clearly define three biomechanical principles of the Cochlea : Activity, Nonlinearity and Feedback. In this article, the Cochlea is linearly and actively modelled in one dimensional time domain. The sharp tunning of the Basilar Membrane displacement is shown when the amplifying activity of hair cells is added to the model. The amplified energy of the travelling displacement wave is emitted throughout the Cochlear fluid, so that the model becomes unstable. A new technique is introduced to reduce strong echos fro the Helicotrema. It makes the model less unstable. Both pure and click tones are used as input stimuli onto the ear durm. When the model is normal, the click response of the model shows that the backward emission of the amplified fluid pressure has mainly the echos from the Helicotrema. However, when the linear and active model is assumed to be abnormal, that is, some of hair cells are damaged not to produce the active process, the effect of the hair cell damage is resulted in the Oto-acoustic emission. The frequency response of the abnormally emitted sound pressure shows that the Oto-acoustic emission has the information about the characteristic frequency of the damaged hair cell. The main aim of this paper is to demonstrate the active biomechanics of the Chchlea in the time domain.

• Journal of Life Science
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• v.18 no.4
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• pp.542-549
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• 2008

Cisplatin (cis-diamminedichloroplatinum II : CDDP) is the most widely used anticancer drug against a variety of human neoplasms. However, its clinical use is limited by the onset of severe side effects, including ototoxicity and nephrotoxicity. Even though a number of evidences in cytotoxic mechanism of cisplatin have been suggested, the role of pro-inflammatory cytokines in cisplatin cytotoxicity of auditory cells has not yet been demonstrated. Herein our data clearly demonstrated that cisplatin decreased the viability of HEI-OC1 auditory cells, which was inhibited by the addition of neutralizing $anti-TNF-{\alpha}$, $anti-IL-1{\beta}$ and anti-IL-6 antibodies. Consistently, Neutralization with antibodies against pro-inflammatory cytokines ameliorated the cell death and disarrangement of cochlea hair cell layers in the rat primary cochlear explants which were treated with cisplatin. Furthermore, exogeneous supplementation with free radical scavengers, including GSH and NAC, significantly prevented the cytotoxicity of cisplatin in the rat primary cochlea explants. We also observed that $TNF-{\alpha}$ was predominantly expressed in Deiters and Hensen's cells located in hair cell zone of cisplatin-treated cochlear explants. These findings suggest that pro-inflammatory cytokines, including $TNF-{\alpha}$, $IL-1{\beta}$ and IL-6, may play a pivotal role in the pathophysiology of hair cell damages caused by ototoxic drug cisplatin.

• Journal of Biomedical Engineering Research
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• v.28 no.5
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• pp.694-702
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• 2007

The adaptation effect originating from the chemical synapse between auditory nerve and inner hair cell gives advantage in accurate representation of temporal cues of incoming speech such as speech onset. Thus it is expected that the modification of conventional speech processing strategies of cochlear implant(CI) by incorporating the adaptation effect will result in considerable improvement of speech perception performance such as consonant perception score. Our purpose in this paper was to evaluate our new CI speech processing strategy incorporating the adaptation effect by the observation of auditory nerve responses. By classifying the presence or absence of speech from the auditory nerve responses, i. e. spike trains, we could quantitatively compare speech onset detection performances of conventional and improved strategies. We could verify the effectiveness of the adaptation effect in improving the speech onset representation characteristics.

• Transactions of the Korean Society of Mechanical Engineers A
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• v.31 no.11
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• pp.1077-1082
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• 2007

We present a micromechanical active amplifier, inspired from the principle of the outer hair cells in cochlea, amplifying both displacement and force. The present micromechanical active amplifier modulates the resonant carrier motion using the variable stiffness spring whose stiffness changes proportionally to the input motion. We design, fabricate, and characterize two types of the amplifiers A and B, each having the variable stiffness spring fur the maximum displacement gain and force gain, respectively. In the experimental study, the amplifier A shows the displacement gain of 5.62, which is 2.15 times larger than that of the amplifier 3. The amplifier B shows the force gain of 10.0, resulting in 1.26 times larger value compared to that of the amplifier A. We experimentally verify that the haircell-inspired micromechanical amplifiers are capable to amplify both displacement and force.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.18 no.1
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• pp.221-233
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• 2005

Background and Objectives : Despite of high prevalence, Tinnitus remains obscure because the cause and mechanism is poorly understood. In the absence of a suitable animal model, past investigations tool place in humans. Recently, the animal model with sodium salicylate ototoxicity is broadly used because of its reversibility. Balyangtongum-Tang had been used clinically to treat tinnitus and other hearing problems. We investigated the effects of Balyangtongum-Tang on cochlear morphologic change induced by sodium salicylate ototoxicity and were to find out its therapeutic effects on ototoxicity in rat model. Materials and Methods : Healthy ten Sprague-Dawley rats were divided into normal(2), control(4) and sample(4) groups. The sample group was given extract of Balyangtongum - Tang(1cc/100g) once a day for 4 days. After 3 hours when last medication were given, the sample and control groups were injected intraperitoneally with sodium salicylate(500mg/kg). We observed the cochlear morphologic changes of rats every 1, 2, 3 and 5 hours after injection. Results : The electron microscopic finding of outer hair cell shows some changes in the curticular plate and cytoplasm. Some vacuoles were found in the control and sample groups. Vacuolization in the curticular plate and cytoplasm of the sample group after 3, 5 hours were similar to the control group. But the curticular plate of the sample group after 1, 2 hours did not from vacuole. On the other hand the control group after 1, 2 hours formed vacuoles in the curticular plate. Light microscopic findings of cochlear duct in control and sample groups didn't find any difference. Conclusion : The results suggest that extract of Balyangtongum-Tang reduces the morphologic changes induced by sodium salicylate ototoxicity and the effects are remarkable in frist 2 hours. However the effective times are different with previous studies, it seems to due to the difference of tolerance and sensitivity of laboratory animals.

• The Korean Journal of Physiology and Pharmacology
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• v.21 no.2
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• pp.251-257
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• 2017

Inhibition of $K^+$ outward currents by linopirdine in the outer hair cells (OHCs) of circling mice (homozygous (cir/cir) mice), an animal model for human deafness (DFNB6 type), was investigated using a whole cell patch clamp technique. Littermate heterozygous (+/cir) and ICR mice of the same age (postnatal day (P) 0 -P6) were used as controls. Voltage steps from -100 mV to 40 mV elicited small inward currents (-100 mV~-70 mV) and slow rising $K^+$ outward currents (-60 mV~40 mV) which activated near -50 mV in all OHCs tested. Linopirdine, a known blocker of $K^+$ currents activated at negative potentials ($I_{K,n}$), did cause inhibition at varying degree (severe, moderate, mild) in $K^+$ outward currents of heterozygous (+/cir) or homozygous (cir/cir) mice OHCs in the concentration range between 1 and $100{\mu}m$, while it was apparent only in one ICR mice OHC out of nine OHCs at $100{\mu}m$. Although the half inhibition concentrations in heterozygous (+/cir) or homozygous (cir/cir) mice OHCs were close to those reported in $I_{K,n}$, biophysical and pharmacological properties of $K^+$ outward currents, such as the activation close to -50 mV, small inward currents evoked by hyperpolarizing steps and TEA sensitivity, were not in line with $I_{K,n}$ reported in other tissues. Our results show that the delayed rectifier type $K^+$ outward currents, which are not similar to $I_{K,n}$ with respect to biophysical and pharmacological properties, are inhibited by linopirdine in the developing (P0~P6) homozygous (cir/cir) or heterozygous (+/cir) mice OHCs.

• The Korean Journal of Physiology and Pharmacology
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• v.19 no.4
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• pp.383-388
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• 2015

$K^+$ outward currents in the outer hair cells (OHCs) of circling mice (homozygous (cir/cir) mice), an animal model for human deafness (DFNB6 type), were investigated using a whole cell patch clamp technique. Littermate heterozygous (+/cir) mice of the same age (postnatal day (P) 0-P6) were used as controls. Similar slow rising $K^+$ currents were observed in both genotypes, but their biophysical and pharmacological properties were quite different. The values of Vhalf for activation were significantly different in the heterozygous (+/cir) and homozygous (cir/cir) mice ($-8.1{\pm}2.2mV$, heterozygous (+/cir) mice (n=7) and $-17.2{\pm}4.2mV$, homozygous (cir/cir) mice (n=5)). The inactivation curve was expressed by a single first order Boltzmann equation in the homozygous (cir/cir) mice, while it was expressed by a sum of two first order Boltzmann equations in the heterozygous (+/cir) mice. The $K^+$ current of homozygous (cir/cir) mice was more sensitive to TEA in the 1 to 10 mM range, while the 4-AP sensitivities were not different between the two genotypes. Removal of external $Ca^{2+}$ did not affect the $K^+$ currents in either genotype, indicating that the higher sensitivity of $K^+$ current to TEA in the homozygous (cir/cir) mice was not due to an early expression of $Ca^{2+}$ activated $K^+$ channels. Our results suggest that the $K^+$ outward current of developing homozygous (cir/cir) mice OHCs is different in both biophysical and pharmacological aspects than that of heterozygous (+/cir) mice.