Yang Wei-yan

Lower Dose of Aminoglycoside Ototoxic Exposure Causes Presynaptic Alterations Assoicated with Hearing Loss

Abstract Objective To study presynaptic alternations of cochlear ribbons arising from aminoglycoside ototoxic stimuli in C57BL/6J mice. Methods Animals were injected with low dose gentamicin (100 mg/kg/day) for 14 days, From the 14th to 28th days, the mice were maintained free of gentamicin treatment. Immunohistochemistry labeling was employed to trace RIBEYE, a major presynaptic componment of ribbon synapses. RIBEYE/CtBP2 expression levels were assessed and compared with hearing threshold shifts. Auditory function was assessed by auditory brainstem responses. The stereocilia of outer hair cells (OHCs) and IHCs was examined by scanning electron microscopy (SEM). Results Hearing thresholds were elevated with peak hearing loss observed on the 7th day after gentamicin exposure, followed by improvement after the 7th day. RIBEYE/CtBP2 expression directly correlated with observed hearing threshold shifts. Strikingly, we did not see any obvious changes in stereocilia in both OHCs and IHCs until the 28th day. Mild changes in stereocilia were only observed in OHCs on the 28th day. Conclusions These findings indicate that presynapse cochlear ribbons, rather than stereocilia, may be sensitive to aminoglycoside ototoxic exposure in mice cochleae. A pattern of RIBEYE/CtBP2 expression changes seems to parallel hearing threshold shifts and suggests presynaptic response properties to lower dosage of aminoglycoside ototoxic stimuli.

The Cochlear Ribbon Synaptic Response to Aminogiycoside Ototoxicity in C57BL/6J Mice

Abstract Objective To investigate the early change of cochlear ribbon synapses on inner hair cells in response to aminoglycoside ototoxicity. Methods C57BL/6J mice received intraperitoneal injection of gentamicin (100 mg/kg/day), and the apical coil organ of Corti was examined on the 4th, 7th and 10th day (n=10). Littermates without gentamicin treatment served as controls (n=10). RIBEYE on the presynaptic membrane and AMPA receptors on the postsynaptic membrane were labeled with CtBP2 or GluR2/3 respectively. Three dimension reconstruction was conducted using the 3DS MAX 8.0 software. Results There were no disruptions of outer or inner hair cells in all groups. However, the number of ribbon synapses on cochlear inner hair cells increased significantly within 7 days after gentamicin exposure (P Conclusion During the early stage of aminoglycoside ototoxicity, increased population of cochlear ribbon synapses may indicate a significant down-regulation of synaptic function.

Subjective Tinnitus as First Presentation in a Patient with Metastatic Lung Cancer in Temporal Bone - A Case Report

Abstract Metastasis of lung cancer to the temporal bone is a very rare disease and subjective tinnitus as the presenting symptom in these patients is even rarer. Here we report a case in which a 42-year-old male presented with subjective tinnitus of three months, with no pulmonary disease symptoms. Pure tone audiometry indicated moderate conductive deafness in left ear with an air-bone gap of 21.3 dB. HRCT temporal bone scanning indicated high-density shadows in the left epitympanic cavity, sinus tympani and mastoid cavity. Chronic otitis media with cholesteatoma was suspected and surgical treatment recommended. However, preoperative chest x-ray revealed high-density millet lesions scattered widely in both lungs. HRCT lung scanning confirmed the lungs lesions and indicated lung cancer. In order to determine correlations between the temporal bone and pulmonary lesions, a CT-guided trans-mastoid aspiration biopsy and immunohistochemical study were conducted, which confirmed that the temporal bone lesion was metastatic from the lungs. The patient was given a series of chemotherapy immediately and his tinnitus significantly improved after three months of treatment, with full recovery of his hearing and complete resolution of shadows in the mastoid cavity. Unfortunately, he subsequently developed multiple bone metastases in the 9th month and cerebral metastasis in the 18th month. Multiple organ failure resulted in death in 2.5 years.

Endoscope-Assisted Cerebellopontine Angle Surgery

Abstract Objective To report experiences with use of otoendoscopy in cerebellopontine angle (CPA) surgeries. Methods Twenty five cases of CPA surgeries performed between November 2002 and December 2008 in which microscope enabled otoendoscopy was used were reviewed.The 25 cases included 19 cases of acoustic neuroma, 3 cases of CPA facial nerve tumors, 1 case of trigeminal neurinoma, a case of glossopharyngeal neuralgia and 1 case of hemifacial spasm. Endoscopy was used in all cases together with monitoring of brainstem auditory responses and facial electromyography. Postoperative hearing and facial nerve function were evaluated and compared to pre-operative levels. Results Endoscopy provided improved visualization of local anatomy, revealed hidden lesions and reduced unnecessary anatomical distortions. Total resection was achieved in 18 of the 19 acoustic neuroma cases, Facial nerve anatomical integrity was preserved in all 19 cases. One week postoperative House-Brackmann grading was I in 3 cases, II in 10 cases and III in 6 cases. Facial nerve function continued to improve in some cases at 3 months. Total tumor resection was achieved in all 3 patients with facial neurinoma. The facial nerve was sacrificed in 2 of the 3 cases with primary faciohypoglossal nerve anastomosis. Facial nerve function was Grade II and Grade III one year after surgery, respectively. In the case with anatomically preserved facial nerve, postoperative facial nerve function was initially Grade III and improved to II at 3 months. The tumor was completely resected in the trigeminal neurinoma patient with a Grade III postoperative facial nerve function which improved Grade II three months later. Seventeen of the 19 patients with acoustic neuroma retained hearing postoperatively, of these 12 maintained preoperative levels of hearing. Preoperative hearing capacity was preserved in 2 of the 3 patients with facial nerve tumors, but lost in patients with other tumor types. Glossopharyngeal neurotomy (n=1) and microvascular decompression (n=1) resulted in satisfactory symptom relief and no recurrence at 5- and 3-year follow up, respectively Conclusions Otoendos aope-aided technique greatly helps surgical management of CPA and internal auditory canal lesions and other disorders. This minimally invasive technique overcomes many shortcomings inherent to the traditional retrosigmoid approach.

Nuclear Factor kappa B p65 Expression in Mouse Cochlea

Abstract Nuclear factor kappa B(NF-κB) is one of the best-characterized transcription factors playing important roles in many cellular responses to a large variety of stimuli, including inflammatory cytokines, phorbol esters, growth factors, and bacterial and viral products. The aim of this study is to demonstrate NF-κB expression in the mouse cochlea and its enhancement in response to lipopolysaccharides(LPS) and kanamycin(KA) treatment. Methods KA treatment consisted of subcutaneous KA injections at 700 mg/kg twice a day with an eight-hour interval between the two injections for 3 or 7 days. For animals in the LPS treatment group, a single dose of 0.3 mg LPS dissolved in 0.2 ml sterile saline were injected into both bullae through the tympanic membrane and kept there for 3 hours. Animals in the control group received subcutaneous saline injection for 7 days. Following immmunohistochemichal processing with rabbit polyclonal anti-NF-κB p65 antibodies, cryosections of the cochlea were examined for expression of NF-κB p65 in various structures in the cochlea. Results NF-κB p65 expression, identified by presence of brown reaction products characteristic of DAB immunohistochemistry, was visible in the spiral ligament, spiral prominence, tectorial membrane(TM), spiral ganglion and nerve fibers. Relatively weak NF-κB p65 expression was also visualized in the organ of Corti. Within the organ of Corti, the inner hair cells (IHC), outer hair cells (OHC), inner pillar cells (IP), outer pillar cells (OP), Deiter’s cells(DC), and Boettcher’s cells exhibited stronger staining than the inner sulcus cells, Hensen’s cells(HC) and Claudius’cells. No NF-κB p65 expression was seen in the nucleus of the IHC and OHC. NF-κB p65 expression was increased in animals exposed to LPS or KA, demonstrating significant differences in the staining between control animals and LPS/KA-treated animals. NF-κB p65 expression was not significantly different between LPS treated and KA treated animals or between 3 and 7 days in KA-treated animals. Conclusion LPS and KA exposure increases expression of NF-κB p65 in the mouse cochlea.

Mitochondrial DNA A1555G mutation screening using a testing kit method and its significance in preventing aminoglycoside-related hearing loss

Abstract To report a new screening method for mitochondrial DNA 1555A→G mutation and the results of genotype analysis in 19 maternal inherited deafness pedigrees. Method Five hundred and forty-six non-syndromic neuro-sensory hearing loss patients were tested for 1555A→G mutation using a new compact testing kit, which allows clear distinction between wild type and 1555 A→G mutated mtDNAs. Results Nineteen subjects among the 546 patients (3.48%) were found to carry mtDNAA1555G mutation. The results were confirmed by sequencing in an ABI 3100 Avant sequencer. Conclusions Maternal inherited deafness families are a frequently seen in outpatient group. The detection of mtDNA 1555 A→G mutation with a low cost, ready to use detection kit is needed and suitable in China for large scale screening and preventive testing before usage of aminoglycoside antibiotics.