June Choi

Protective effect of Korean red ginseng extract on cisplatin ototoxicity in HEI-OC1 auditory cells.

Ginseng extract is known to have many beneficial effects, including the reversal of pathological and physiological changes induced by ischemia, stress, and aging. Cisplatin, an effective antineoplastic drug, can cause irreversible sensorineural hearing loss and serious tinnitus in humans; thus cisplatin‐induced ototoxicity is a useful experimental model for ototoxicity. This study investigated the protective effects of Korean red ginseng extract on cisplatin‐induced ototoxicity in auditory cells. Pretreatment with 2.5 mg/mL of ginseng extract prior to application of 20 μm of cisplatin significantly increased cell viability after 48 h of incubation in auditory cells. Pretreatment with ginseng extract significantly attenuated the cisplatin‐induced increase in reactive oxygen species (ROS). Ginseng extract also inhibited the expression of caspase‐3 and poly‐ADP‐ribose polymerase related to cisplatin‐induced apoptosis because a major mechanism of cisplatin‐induced toxicity involves ROS production. Thus, Korean red ginseng extract can play both an anti‐apoptotic and anti‐oxidative role on cisplatin‐induced ototoxicity in an auditory cell line. Copyright

Validation study of portable device for the diagnosis of obstructive sleep apnea according to the new AASM scoring criteria: Watch-PAT 100

Abstract Conclusion: Watch-PAT may provide an accurate and clinically effective portable monitoring method for the diagnosis of obstructive sleep apnea (OSA). Objective: This study was designed to assess the accuracy and clinical efficacy of a wrist-worn portable device (Watch-PAT 100) to diagnose OSA. Methods: Twenty-seven participants with suspected OSA underwent full polysomnography (PSG). Finally, 25 subjects successfully underwent portable monitoring using Watch-PAT after full PSG. The study population consisted of 21 males and 4 females, mean age 40.9 ± 11.2 years (range 21–59). Mean body mass index (BMI) was 26.2 ± 2.6 kg/m2 (range 21.2–32.3). All PSG were manually scored according to the new scoring manual of the American Academy of Sleep Medicine (2007) and the Watch-PAT data were analyzed by the automatic algorithm. Results: There was a high correlation of apnea-hypopnea index (AHI) (r = 0.94, p < 0.001) and lowest oxygen saturation (LSAT) (r = 0.90, p < 0.001) between the PSG and the Watch-PAT. A good agreement was also found between PSG AHI, PSG LSAT and PAT AHI, PAT LSAT, respectively. There was a significantly high concordance of the severity of AHI (Kendall tau-b = 0.897, p < 0.001) between the PSG and the Watch-PAT.

Obstructive sleep apnea syndrome: A child is not just a small adult

Objectives Pediatric obstructive sleep apnea syndrome (OSAS), like adult OSAS, is characterized by intermittent upper airway collapse during sleep and is associated with anatomic and neuromuscular factors. However, the clinical manifestations, diagnostic criteria, and Polysomnographic findings of OSAS in children are likely to be different from those in adults. The purpose of this study was to identify the characteristics that distinguish the clinical manifestations and Polysomnographic findings of OSAS in children from those in adults. Methods The study population consisted of 34 children (mean age, 7.6 years; range, 4 to 16 years) with OSAS and 33 adults (mean age, 40.1 years; range, 18 to 58 years) with OSAS. We compared various clinical manifestations, such as body mass index, tonsil size, severity of symptoms and signs, and Polysomnographic data, between these groups. Results Obesity was more common among the adults, whereas tonsillar hypertrophy was more common among the children. There were significant differences between the groups in the severity of symptoms and signs, including witnessed apnea, daytime sleepiness, morning headache, memory reduction, and daytime fatigue. In the children with OSAS, slow-wave sleep was relatively well preserved, and respiratory events such as apnea and hypopnea occurred mainly during rapid eye movement sleep. Conclusions The clinical manifestations and Polysomnographic findings in children with OSAS differ from those in adults with OSAS.

Protective effects of apocynin on cisplatin‐induced ototoxicity in an auditory cell line and in zebrafish

Cisplatin is a very effective anticancer drug and generates reactive oxygen species (ROS) such as superoxide anions that can deplete antioxidant protective molecules in the cochlea. These processes result in the death of cochlear hair cells by induction of apoptosis. Apocynin, which is used as a specific nicotinamide adenine dinucleotide phosphate oxidase inhibitor, has a preventive effect for intracellular ROS generation. In this study, the effect of apocynin was investigated in a cochlear organ of Corti‐derived cell line, HEI‐OC1 cells, and in transgenic zebrafish (Brn3C: EGFP). To investigate the protective effects of apocynin, HEI‐OC1 cells were treated with various concentrations of apocynin and a 20 µm concentration of cisplatin, simultaneously. An in vivo study of transgenic zebrafish (Brn3C: EGFP) was used to investigate the protective effects of apocynin on cisplatin‐induced hair cell death. In an in vitro study, apocynin appeared to protect against cisplatin‐induced apoptotic features on Hoechst 33258 staining in the HEI‐OC1 cells. Treatment of the HEI‐OC1 cells with 100 µm of apocynin, significantly decreased caspase‐3 activity. Treatment of the cells with a 100 µm concentration of apocynin and a 20 µm concentration of cisplatin significantly decreased the intracellular ROS production. In the in vivo study, apocynin significantly decreased the TUNEL reaction and prevented cisplatin‐induced hair cell loss of the neuromasts in the transgenic zebrafish at low concentrations (125 and 250 µm). These findings suggest that apocynin has antioxidative effects and prevents cisplatin‐induced apoptotic cell death in HEI‐OC1 cells as well as in zebrafish. Copyright

Generation of demyelination models by targeted ablation of oligodendrocytes in the zebrafish CNS.

Demyelination is the pathological process by which myelin sheaths are lost from around axons, and is usually caused by a direct insult targeted at the oligodendrocytes in the vertebrate central nervous system (CNS). A demyelinated CNS is usually remyelinated by a population of oligodendrocyte progenitor cells, which are widely distributed throughout the adult CNS. However, myelin disruption and remyelination failure affect the normal function of the nervous system, causing human diseases such as multiple sclerosis. In spite of numerous studies aimed at understanding the remyelination process, many questions still remain unanswered. Therefore, to study remyelination mechanisms in vivo, a demyelination animal model was generated using a transgenic zebrafish system in which oligodendrocytes are conditionally ablated in the larval and adult CNS. In this transgenic system, bacterial nitroreductase enzyme (NTR), which converts the prodrug metronidazole (Mtz) into a cytotoxic DNA cross-linking agent, is expressed in oligodendrocyte lineage cells under the control of the mbp and sox10 promoter. Exposure of transgenic zebrafish to Mtz-containing media resulted in rapid ablation of oligodendrocytes and CNS demyelination within 48 h, but removal of Mtz medium led to efficient remyelination of the demyelinated CNS within 7 days. In addition, the demyelination and remyelination processes could be easily observed in living transgenic zebrafish by detecting the fluorescent protein, mCherry, indicating that this transgenic system can be used as a valuable animal model to study the remyelination process in vivo, and to conduct high-throughput primary screens for new drugs that facilitate remyelination.

A new patch material for tympanic membrane perforation by trauma: the membrane of a hen egg shell

Abstract Conclusion: The egg shell membrane (ESM) patch may promote tympanic membrane (TM) healing in acute traumatic TM perforation. Objective: To evaluate the use of ESM for treating acute traumatic TM perforation. Methods: We reviewed charts of patients with traumatic TM injury from 2008 to 2011. Treatments were an ESM patch or a perforation edge approximation. We divided patients into two groups according to the treatment used. Each patient was matched by treatment onset and perforation size. We compared healing ratio, healing time, and frequency of otorrhea between the perforation edge approximation group and the ESM patch group. Matched t tests were used for analysis. Results: The healing ratio of the TM showed no significant difference between the two groups, but the time to heal was significantly shorter in the ESM patch group than in the perforation edge approximation group.

Analysis of frequency loss as a prognostic factor in idiopathic sensorineural hearing loss

Abstract Conclusion: The combination of systemic steroids with intratympanic dexamethasone injection (ITDI) did not result in significantly different outcomes from steroid treatment only and did not have any additional beneficial effects. Objective: To evaluate hearing recovery in idiopathic sudden sensorineural hearing loss (ISSNHL) according to frequency and to compare treatment responses between patients treated with systemic steroids and systemic steroids with ITDI. Methods: Ninety-nine patients with ISSNHL were selected to participate in the study by a retrospective medical chart review. Patients were divided into two groups, systemic steroid treatment only and systemic steroid with adjunctive ITDI. Hearing recovery was evaluated by pure tone audiometry (PTA). All patients underwent PTA examination before treatment and after 3 months. Thresholds were analyzed by frequency along with other factors. Results: Low frequency hearing loss responded better than high frequency loss to PTA. When we analyzed pure tone audiogram patterns, all patterns except for the descending type showed better improvement in patients with lower frequency hearing loss than in patients with higher frequency hearing loss.

Protective effects of edaravone against cisplatin-induced hair cell damage in zebrafish

OBJECTIVE Edaravone is known to have a potent free radical scavenging effect. The objective of the present study was to evaluate the effects of edaravone on cisplatin-induced ototoxicity in transgenic zebrafish (Brn3C: EGFP). METHODS Five day post-fertilization zebrafish larvae were exposed to 1000 μM cisplatin and 50 μM, 100 μM, 250 μM, 500 μM, 750 μM, and 1000 μM concentrations of edaravone for 4h. Hair cells within neuromasts of the supraorbital (SO1 and SO2), otic (O1), and occipital (OC1) lateral lines were analyzed by fluorescence microscopy and confocal microscopy (n=10). Hair cell survival was calculated as a percentage of the hair cells in the control group that were not exposed to cisplatin. Ultrastructural changes were evaluated using scanning electron microscopy and transmission electron microscopy. RESULTS Edaravone protected cisplatin-induced hair cell loss of neuromasts (edaravone 750 μM: 8.7 ± 1.5 cells, cisplatin 1000 μM only: 3.7 ± 0.9 cells; n=10, p<0.0001) and decreased the Terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end labeling (TUNEL) reaction. Structures of mitochondria and hair cell within neuromasts in ultrastructural analysis were preserved in zebrafish exposed to 1000 μM cisplatin and 750 μM edaravone for 4h. CONCLUSIONS Edaravone attenuated cisplatin-induced hair cell damage in zebrafish. The results of the current study suggest that cisplatin induces apoptosis, and the apoptotic cell death can be prevented by treatment with edaravone in zebrafish.

Protective effects of caffeic acid phenethyl ester (CAPE) against neomycin-induced hair cell damage in zebrafish

OBJECTIVE Caffeic acid phenethyl ester (CAPE) is known to reduce the generation of oxygen-derived free radicals, which is a major mechanism of aminoglycoside-induced ototoxicity. The objective of the present study was to evaluate the effects of CAPE on neomycin-induced ototoxicity in zebrafish (Brn3c: EGFP). METHODS Five-day post-fertilization zebrafish larvae (n=10) were exposed to 125 μM neomycin and one of the following CAPE concentrations for 1h: 50, 100, 250, 500, or 1000 μM. Ultrastructural changes were evaluated using scanning electron microscopy (SEM). The terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick-end labeling (TUNEL) assay and 2-[4-(dimethylamino)styryl]-N-ethylpyridiniumiodide (DASPEI) assay were performed for evaluation of apoptosis and mitochondrial damage. RESULTS CAPE decreased neomycin-induced hair cell loss in the neuromasts (500 μM CAPE: 12.7 ± 1.1 cells, 125 μM neomycin only: 6.3 ± 1.1 cells; n = 10, P < 0.05). In the ultrastructural analysis, structures of mitochondria and hair cells were preserved when exposed to 125 μM neomycin and 500 μM CAPE. CAPE decreased apoptosis and mitochondrial damage. CONCLUSION In the present study, CAPE attenuated neomycin-induced hair cell damage in zebrafish. The results of the current study suggest that neomycin induces apoptosis, and the apoptotic cell death can be prevented by treatment with CAPE in zebrafish.

Nasopharynx as a microbiologic reservoir in chronic suppurative otitis media: preliminary study.

Objectives The present study was designed to identify the correlations of bacterial strains of the middle ear and the nasopharynx in chronic suppurative otitis media (CSOM) patients who were scheduled for operations. Methods Sixty-three patients with CSOM were enrolled in the study. Culture specimens were collected from the middle ear and nasopharynx of patients who were admitted for operation. Samples collections were performed 3 times; from the middle ear and nasophaynx at the admission day, from the middle ear during the operation, and from the external auditory canal post-operatively. Bacteria were identified by gram staining and biochemical tests. The correspondence rate of organisms which simultaneously exist in the middle ear and the nasopharynx was measured. Results Sixty-eight organisms were isolated from the middle ear and 57 organisms from the nasopharynx among 63 patients. Of 68 bacteria identified in middle ear, 26.52% (18 bacteria) corresponded with those of nasopharynx. MRSA had the high correspondence rate, and of 18 methicillin-resistant Staphylococcus aureus (MRSA) isolated from middle ear, 33.3% (6 bacteria) corresponded with nasophaynx. Meanwhile, 3 organisms of MRSA were detected from the external auditory canal post-operatively, although they were only found in nasopharynx pre-operatively. Conclusion The current trend of middle ear swab alone for bacterial detection would be insufficient to identify the potent MRSA and impede early antibiotic intervention for the effective middle ear surgery. Therefore, it is necessary to perform nasopharynx cultures together with conventional middle ear culture to control potent risk for infection pre-operatively.