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PURPOSE: Injuries of the nasal vestibular skin caused by the rotating burr shafts can represent a tedious complication following endonasal drilling and is experienced sooner or later by every rhino-surgeon. MATERIAL AND METHODS: To protect the nasal entrance from laceration by the free rotating drill shaft we position an otology speculum in the nasal entrance. The speculum is held in place by the scrub nurse during the critical phase of bone drilling. RESULTS: Following the introduction of the ear speculum protection, we successfully treated our dacryocystostamia procedures (n = 27) and median maxillectomia procedures (n = 6) without any further soft tissue erosions. DISCUSSION: Preventive measures for injuries by endonasal drilling procedures are not reported extensively in literature. This stands in contrast to the fact that these injuries are prone to cause significant suffering as amply described in the case of nostril laceration due to nasogastric intubation or nasogastric feeding tubes. CONCLUSION: The use of a readily available, reusable ear speculum in endonasal drill application eliminated the complication of nasal entrance lacerations throughout our institution, hitherto.
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Lacerações , Humanos , Lacerações/prevenção & controle , Lacerações/etiologia , Instrumentos Cirúrgicos , Nariz/lesões , Nariz/cirurgia , Desenho de Equipamento , Masculino , FemininoRESUMO
Gentamicin is a potent broad-spectrum aminoglycoside antibiotic whose use is hampered by ototoxic side-effects. Hospital gentamicin is a mixture of five gentamicin C-subtypes and several impurities of various ranges of nonexact concentrations. We developed a purification strategy enabling assaying of individual C-subtypes and impurities for ototoxicity and antimicrobial activity. We found that C-subtypes displayed broad and potent in vitro antimicrobial activities comparable to the hospital gentamicin mixture. In contrast, they showed different degrees of ototoxicity in cochlear explants, with gentamicin C2b being the least and gentamicin C2 the most ototoxic. Structure-activity relationships identified sites in the C4'-C6' region on ring I that reduced ototoxicity while preserving antimicrobial activity, thus identifying targets for future drug design and mechanisms for hair cell toxicity. Structure-activity relationship data suggested and electrophysiological data showed that the C-subtypes both bind and permeate the hair cell mechanotransducer channel, with the stronger the binding the less ototoxic the compound. Finally, both individual and reformulated mixtures of C-subtypes demonstrated decreased ototoxicity while maintaining antimicrobial activity, thereby serving as a proof-of-concept of drug reformulation to minimizing ototoxicity of gentamicin in patients.
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Antibacterianos/farmacologia , Cóclea/efeitos dos fármacos , Gentamicinas/efeitos adversos , Gentamicinas/química , Gentamicinas/farmacologia , Animais , Antibacterianos/efeitos adversos , Antibacterianos/química , Antibacterianos/isolamento & purificação , Cóclea/citologia , Contaminação de Medicamentos , Gentamicinas/isolamento & purificação , Células Ciliadas Auditivas/efeitos dos fármacos , Hospitais , Canais Iônicos/metabolismo , Mecanotransdução Celular/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Ratos Sprague-Dawley , Sisomicina/farmacologia , Relação Estrutura-AtividadeRESUMO
PURPOSE: In individuals with severe hearing loss, mobile phone communication is limited despite treatment with a cochlear implant (CI). The goal of this study is to identify the best communication practice for CI users by comparing speech comprehension of conventional mobile phone (GSM) calls, Voice over Internet Protocol (VoIP) calls, and the application of a wireless phone clip (WPC) accessory. METHODS: This study included 13 individuals (mean age 47.1 ± 17.3 years) with at least one CI. Frequency response and objective voice quality were tested for each device, transmission mode and the WPC. We measured speech comprehension using a smartphone for a GSM call with and without WPC as well as VoIP-calls with and without WPC at different levels of white background noise. RESULTS: Frequency responses of the WPC were limited (< 4 kHz); however, speech comprehension in a noisy environment was significantly improved compared to GSM. Speech comprehension was improved by 9-27% utilizing VoIP or WPC compared to GSM. WPC was superior in noisy environments (80 dB SPL broadband noise) compared to GSM. At lower background noise levels (50, 60, 70 dB SPL broadband noise), VoIP resulted in improved speech comprehension with and without WPC. Speech comprehension scores did not correlate with objective voice quality measurements. CONCLUSION: Speech comprehension was best with VoIP alone; however, accessories such as a WPC provide additional improvement in the presence of background noise. Mobile phone calls utilizing VoIP technology, with or without a WPC accessory, result in superior speech comprehension compared to GSM.
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Telefone Celular , Implante Coclear , Implantes Cocleares , Percepção da Fala , Humanos , Adulto , Pessoa de Meia-Idade , Fala , Compreensão , Implante Coclear/métodos , InternetRESUMO
Delivering cochlear implants through a minimally invasive tunnel (1.8 mm in diameter) from the mastoid surface to the inner ear is referred to as direct cochlear access (DCA). Based on cone beam as well as micro-computed tomography imaging, this in vitro study evaluates the feasibility and efficacy of manual cochlear electrode array insertions via DCA. Free-fitting electrode arrays were inserted in 8 temporal bone specimens with previously drilled DCA tunnels. The insertion depth angle, procedural time, tunnel alignment as well as the inserted scala and intracochlear trauma were assessed. Seven of the 8 insertions were full insertions, with insertion depth angles higher than 520°. Three cases of atraumatic scala tympani insertion, 3 cases of probable basilar membrane rupture and 1 case of dislocation into the scala vestibuli were observed (1 specimen was damaged during extraction). Manual electrode array insertion following a DCA procedure seems to be feasible and safe and is a further step toward clinical application of image-guided otological microsurgery.
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Implante Coclear/métodos , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Osso Temporal/cirurgia , Tomografia Computadorizada de Feixe Cônico , Humanos , Processo Mastoide/diagnóstico por imagem , Processo Mastoide/cirurgia , Osso Temporal/diagnóstico por imagem , Microtomografia por Raio-XRESUMO
OBJECTIVES: Sensorineural hearing loss from sound overexposure has a considerable prevalence. Identification of sound hazards is crucial, as prevention, due to a lack of definitive therapies, is the sole alternative to hearing aids. One subjectively loud, yet little studied, potential sound hazard is movie theaters. This study uses smart phones to evaluate their applicability as a widely available, validated sound pressure level (SPL) meter. Therefore, this study measures sound levels in movie theaters to determine whether sound levels exceed safe occupational noise exposure limits and whether sound levels in movie theaters differ as a function of movie, movie theater, presentation time, and seat location within the theater. DESIGN: Six smart phones with an SPL meter software application were calibrated with a precision SPL meter and validated as an SPL meter. Additionally, three different smart phone generations were measured in comparison to an integrating SPL meter. Two different movies, an action movie and a children's movie, were measured six times each in 10 different venues (n = 117). To maximize representativeness, movies were selected focusing on large release productions with probable high attendance. Movie theaters were selected in the San Francisco, CA, area based on whether they screened both chosen movies and to represent the largest variety of theater proprietors. Measurements were analyzed in regard to differences between theaters, location within the theater, movie, as well as presentation time and day as indirect indicator of film attendance. RESULTS: The smart phone measurements demonstrated high accuracy and reliability. Overall, sound levels in movie theaters do not exceed safe exposure limits by occupational standards. Sound levels vary significantly across theaters and demonstrated statistically significant higher sound levels and exposures in the action movie compared to the children's movie. Sound levels decrease with distance from the screen. However, no influence on time of day or day of the week as indirect indicator of film attendance could be found. CONCLUSIONS: Calibrated smart phones with an appropriate software application as used in this study can be utilized as a validated SPL meter. Because of the wide availability, smart phones in combination with the software application can provide high quantity recreational sound exposure measurements, which can facilitate the identification of potential noise hazards. Sound levels in movie theaters decrease with distance to the screen, but do not exceed safe occupational noise exposure limits. Additionally, there are significant differences in sound levels across movie theaters and movies, but not in presentation time.
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Acústica , Telefone Celular , Exposição Ambiental , Perda Auditiva Provocada por Ruído/prevenção & controle , Aplicativos Móveis , Filmes Cinematográficos , Som , Humanos , Ruído , Reprodutibilidade dos TestesRESUMO
BACKGROUND: Electroencephalography (EEG) studies indicate possible associations between tinnitus and changes in the neural activity. However, inconsistent results require further investigation to better understand such heterogeneity and inform the interpretation of previous findings. OBJECTIVE: This study aims to investigate the feasibility of EEG measurements as an objective indicator for the identification of tinnitus-associated neural activities. METHODS: To reduce heterogeneity, participants served as their own control using residual inhibition (RI) to modulate the tinnitus perception in a within-subject EEG study design with a tinnitus group. In addition, comparison with a nontinnitus control group allowed for a between-subjects comparison. We will apply RI stimulation to generate tinnitus and nontinnitus conditions in the same subject. Furthermore, high-frequency audiometry (up to 13 kHz) and tinnitometry will be performed. RESULTS: This work was funded by the Infrastructure Grant of the University of Bern, Bern, Switzerland and Bernafon AG, Bern, Switzerland. Enrollment for the study described in this protocol commenced in February 2018. Data analysis is currently under way and the first results are expected to be submitted for publication in 2019. CONCLUSIONS: This study design helps in comparing the neural activity between conditions in the same individual, thereby addressing a notable limitation of previous EEG tinnitus studies. In addition, the high-frequency assessment will help to analyze and classify tinnitus symptoms beyond the conventional clinical standard. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR1-10.2196/12270.
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To demonstrate the feasibility of robotic middle ear access in a clinical setting, nine adult patients with severe-to-profound hearing loss indicated for cochlear implantation were included in this clinical trial. A keyhole access tunnel to the tympanic cavity and targeting the round window was planned based on preoperatively acquired computed tomography image data and robotically drilled to the level of the facial recess. Intraoperative imaging was performed to confirm sufficient distance of the drilling trajectory to relevant anatomy. Robotic drilling continued toward the round window. The cochlear access was manually created by the surgeon. Electrode arrays were inserted through the keyhole tunnel under microscopic supervision via a tympanomeatal flap. All patients were successfully implanted with a cochlear implant. In 9 of 9 patients the robotic drilling was planned and performed to the level of the facial recess. In 3 patients, the procedure was reverted to a conventional approach for safety reasons. No change in facial nerve function compared to baseline measurements was observed. Robotic keyhole access for cochlear implantation is feasible. Further improvements to workflow complexity, duration of surgery, and usability including safety assessments are required to enable wider adoption of the procedure.
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Cóclea/cirurgia , Implante Coclear/métodos , Implantes Cocleares , Perda Auditiva/cirurgia , Procedimentos Cirúrgicos Robóticos/métodos , Adulto , Idoso , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
Facial nerve damage has a detrimental effect on a patient's life, therefore safety mechanisms to ensure its preservation are essential during lateral skull base surgery. During robotic cochlear implantation a trajectory passing the facial nerve at <0.5 mm is needed. Recently a stimulation probe and nerve monitoring approach were developed and introduced clinically, however for patient safety no trajectory was drilled closer than 0.4 mm. Here we assess the performance of the nerve monitoring system at closer distances. In a sheep model eight trajectories were drilled to test the setup followed by 12 trajectories during which the ENT surgeon relied solely on the nerve monitoring system and aborted the robotic drilling process if intraoperative nerve monitoring alerted of a distance <0.1 mm. Microcomputed tomography images and histopathology showed prospective use of the technology prevented facial nerve damage. Facial nerve monitoring integrated in a robotic system supports the surgeon's ability to proactively avoid damage to the facial nerve during robotic drilling in the mastoid.
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CONCLUSION: A system for robotic cochlear implantation (rCI) has been developed and a corresponding surgical workflow has been described. The clinical feasibility was demonstrated through the conduction of a safe and effective rCI procedure. OBJECTIVES: To define a clinical workflow for rCI and demonstrate its feasibility, safety, and effectiveness within a clinical setting. METHOD: A clinical workflow for use of a previously described image guided surgical robot system for rCI was developed. Based on pre-operative images, a safe drilling tunnel targeting the round window was planned and drilled by the robotic system. Intra-operatively the drill path was assessed using imaging and sensor-based data to confirm the proximity of the facial nerve. Electrode array insertion was manually achieved under microscope visualization. Electrode array placement, structure preservation, and the accuracy of the drilling and of the safety mechanisms were assessed on post-operative CT images. RESULTS: Robotic drilling was conducted with an accuracy of 0.2 mm and safety mechanisms predicted proximity of the nerves to within 0.1 mm. The approach resulted in a minimal mastoidectomy and minimal incisions. Manual electrode array insertion was successfully performed through the robotically drilled tunnel. The procedure was performed without complications, and all surrounding structures were preserved.
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Implante Coclear/métodos , Robótica , Estudos de Viabilidade , Humanos , Tomografia Computadorizada por Raios X , Fluxo de TrabalhoRESUMO
OBJECTIVE: The preservation of residual hearing in cochlear implantation opens the door for optimal functional results. This atraumatic surgical technique requires training; however, the traditional human cadaveric temporal bones have become less available or unattainable in some institutions. This study investigates the suitability of an alternative model, using cadaveric lamb temporal bone, for surgical training of atraumatic round window electrode insertion. INTERVENTION: A total of 14 lamb temporal bones were dissected for cochlear implantation by four surgeons. After mastoidectomy, visualization, and drilling of the round window niche, an atraumatic round window insertion of a Medel Flex24 electrode was performed. Electrode insertion depth and position were verified by computed tomography scans. MAIN OUTCOME MEASURE: All cochleas were successfully implanted using the atraumatic round window approach; however, surgical access through the mastoid was substantially different when compared human anatomy. The mean number of intracochlear electrode contacts was 6.5 (range, 4-11) and the mean insertion depth 10.4 mm (range, 4-20 mm), which corresponds to a mean angular perimodiolar insertion depth of 229 degrees (range 67-540°). Full insertion of the electrode was not possible because of the smaller size of the lamb cochlea in comparison to that of the human. CONCLUSION: The lamb temporal bone model is well suited as a training model for atraumatic cochlear implantation at the level of the round window. The minimally pneumatized mastoid as well as the smaller cochlea can help prepare a surgeon for difficult cochlear implantations. Because of substantial differences to human anatomy, it is not an adequate training model for other surgical techniques such as mastoidectomy and posterior tympanotomy as well as full electrode insertion.
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Implante Coclear/métodos , Procedimentos Cirúrgicos Otológicos/educação , Janela da Cóclea/anatomia & histologia , Janela da Cóclea/cirurgia , Osso Temporal/anatomia & histologia , Osso Temporal/cirurgia , Animais , Competência Clínica , Eletrodos , Humanos , Processo Mastoide/anatomia & histologia , Processo Mastoide/cirurgia , Modelos Anatômicos , OvinosRESUMO
A 39-year-old white man presented with a swollen left upper eyelid secondary to progressive acute bacterial rhinosinusitis (ABRS). Physical examination found a 40% reduction in vision in the left eye and right-sided erythematous temporal swelling with tenderness to palpation. Computed tomography revealed the presence of an inflammatory lesion in the left orbit. Duplex ultrasonography demonstrated a thrombotic occlusion in the right superficial temporal vein (STV). For treatment of the complicated ARBS, the patient received intravenous antibiotics and underwent surgery. The STV thrombophlebitis was treated with low-molecular-weight heparin. Postoperatively, the patient recovered completely and his vision normalized; 10 days later, duplex ultrasonography showed a patent STV. The development of contralateral STV thrombophlebitis is conceivably facilitated by venous anastomoses of the scalp in the front of the head. As a result, embolic spread would be a possible complication of infectious ABRS foci communicating with intraorbital and pericranial veins. To the best of our knowledge, this is the first reported case of such a complication of ARBS in the literature.
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Infecções Bacterianas/complicações , Rinite/complicações , Sinusite/complicações , Lobo Temporal/irrigação sanguínea , Tromboflebite/etiologia , Abscesso/etiologia , Abscesso/terapia , Doença Aguda , Adulto , Humanos , Masculino , Doenças Orbitárias/etiologia , Doenças Orbitárias/terapia , Tromboflebite/terapia , Tomografia Computadorizada por Raios X , VeiasRESUMO
This study investigated the development of the microbial community during a long-term (337 days) anaerobic digestion of maize and sugar beet silage, two feedstocks that significantly differ in their chemical composition. For the characterization of the microbial dynamics, the community profiling method terminal restriction fragment length polymorphism (TRFLP) in combination with a cloning-sequencing approach was applied. Our results revealed a specific adaptation of the microbial community to the supplied feedstocks. Based on the high amount of complex compounds, the anaerobic conversion rate of maize silage was slightly lower compared with the sugar beet silage. It was demonstrated that members from the phylum Bacteroidetes are mainly involved in the degradation of low molecular weight substances such as sugar, ethanol and acetate, the main compounds of the sugar beet silage. It was further shown that species of the genus Methanosaeta are highly sensitive against sudden stress situations such as a strong decrease in the ammonium nitrogen (NH4(+)-N) concentration or a drop of the pH value. In both cases, a functional compensation by members of the genera Methanoculleus and/or Methanosarcina was detected. However, the overall biomass conversion of both feedstocks proceeded efficiently as a steady state between acid production and consumption was recorded, which further resulted in an equal biogas yield.
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Archaea/classificação , Bactérias/classificação , Beta vulgaris/metabolismo , Biota , Silagem/microbiologia , Zea mays/metabolismo , Acetatos/metabolismo , Compostos de Amônio/metabolismo , Anaerobiose , Archaea/genética , Archaea/metabolismo , Bactérias/genética , Bactérias/metabolismo , Metabolismo dos Carboidratos , Etanol/metabolismo , Fermentação , Concentração de Íons de Hidrogênio , Dados de Sequência Molecular , Polimorfismo de Fragmento de Restrição , Análise de Sequência de DNARESUMO
OBJECTIVES: Creation of an atraumatic, hearing-preservation cochleostomy is integral to the future of minimally invasive inner ear surgery. The goal of this study was to develop and characterize a novel chemical approach to cochleostomy. STUDY DESIGN: Prospective animal study. SETTING: Laboratory. METHODS: Experimental animal study in which phosphoric acid gel (PAG) was used to decalcify the otic capsule in 25 Hartley guinea pigs. Five animals in each of 5 surgical groups were studied: (1) mechanically opening the auditory bulla alone, (2) PAG thinning of the basal turn otic capsule, leaving endosteum covered by a layer of bone, (3) micro-pick manual cochleostomy, (4) PAG chemical cochleostomy, exposing the endosteum, and (5) combined PAG/micro-pick cochleostomy, with initial chemical thinning and subsequent manual removal of the last osseous layer. Preoperative and postoperative auditory brainstem responses and otoacoustic emissions were obtained at 2, 6, 10, and 16 kHz. Hematoxylin and eosin-stained paraffin sections were compared. RESULTS: Surgical and histologic findings confirmed that application of PAG provided reproducible local bone removal, and cochlear access was enabled. Statistically significant auditory threshold shifts were observed at 10 kHz (P = .048) and 16 kHz (P = .0013) following cochleostomy using PAG alone (group 4) and at 16 kHz using manual cochleostomy (group 3) (P = .028). No statistically significant, postoperative auditory threshold shifts were observed in the other groups, including PAG thinning with manual completion cochleostomy (group 5). CONCLUSION: Hearing preservation cochleostomy can be performed in an animal model using a novel technique of thinning cochlear bone with PAG and manually completing cochleostomy.
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Cóclea/cirurgia , Modelos Animais de Doenças , Procedimentos Cirúrgicos Otológicos/métodos , Ácidos Fosfóricos/efeitos adversos , Ácidos Fosfóricos/farmacologia , Animais , Limiar Auditivo/efeitos dos fármacos , Limiar Auditivo/fisiologia , Cóclea/fisiopatologia , Potenciais Evocados Auditivos do Tronco Encefálico/efeitos dos fármacos , Potenciais Evocados Auditivos do Tronco Encefálico/fisiologia , Feminino , Cobaias , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Distribuição Aleatória , Sensibilidade e EspecificidadeRESUMO
Bacterial infections represent a rapidly growing challenge to human health. Aminoglycosides are widely used broad-spectrum antibiotics, but they inflict permanent hearing loss in up to ~50% of patients by causing selective sensory hair cell loss. Here, we hypothesized that reducing aminoglycoside entry into hair cells via mechanotransducer channels would reduce ototoxicity, and therefore we synthesized 9 aminoglycosides with modifications based on biophysical properties of the hair cell mechanotransducer channel and interactions between aminoglycosides and the bacterial ribosome. Compared with the parent aminoglycoside sisomicin, all 9 derivatives displayed no or reduced ototoxicity, with the lead compound N1MS 17 times less ototoxic and with reduced penetration of hair cell mechanotransducer channels in rat cochlear cultures. Both N1MS and sisomicin suppressed growth of E. coli and K. pneumoniae, with N1MS exhibiting superior activity against extended spectrum ß lactamase producers, despite diminished activity against P. aeruginosa and S. aureus. Moreover, systemic sisomicin treatment of mice resulted in 75% to 85% hair cell loss and profound hearing loss, whereas N1MS treatment preserved both hair cells and hearing. Finally, in mice with E. coli-infected bladders, systemic N1MS treatment eliminated bacteria from urinary tract tissues and serially collected urine samples, without compromising auditory and kidney functions. Together, our findings establish N1MS as a nonototoxic aminoglycoside and support targeted modification as a promising approach to generating nonototoxic antibiotics.
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Aminoglicosídeos , Antibacterianos , Infecções Bacterianas/tratamento farmacológico , Desenho de Fármacos , Células Ciliadas Auditivas/metabolismo , Perda Auditiva Neurossensorial , Aminoglicosídeos/efeitos adversos , Aminoglicosídeos/síntese química , Aminoglicosídeos/química , Aminoglicosídeos/farmacologia , Animais , Antibacterianos/efeitos adversos , Antibacterianos/síntese química , Antibacterianos/química , Antibacterianos/farmacologia , Bactérias/crescimento & desenvolvimento , Infecções Bacterianas/metabolismo , Infecções Bacterianas/patologia , Avaliação Pré-Clínica de Medicamentos , Células Ciliadas Auditivas/patologia , Perda Auditiva Neurossensorial/induzido quimicamente , Perda Auditiva Neurossensorial/metabolismo , Perda Auditiva Neurossensorial/patologia , Perda Auditiva Neurossensorial/prevenção & controle , Humanos , Camundongos , Ratos , Ratos Sprague-DawleyRESUMO
Sound perception requires functional hair cell mechanotransduction (MET) machinery, including the MET channels and tip-link proteins. Prior work showed that uptake of ototoxic aminoglycosides (AG) into hair cells requires functional MET channels. In this study, we examined whether tip-link proteins, including Cadherin 23 (Cdh23), regulate AG entry into hair cells. Using time-lapse microscopy on cochlear explants, we found rapid uptake of gentamicin-conjugated Texas Red (GTTR) into hair cells from three-day-old Cdh23(+/+) and Cdh23(v2J/+) mice, but failed to detect GTTR uptake in Cdh23(v2J/v2J) hair cells. Pre-treatment of wildtype cochleae with the calcium chelator 1,2-bis(o-aminophenoxy) ethane-N,N,N',N'-tetraacetic acid (BAPTA) to disrupt tip-links also effectively reduced GTTR uptake into hair cells. Both Cdh23(v2J/v2J) and BAPTA-treated hair cells were protected from degeneration caused by gentamicin. Six hours after BAPTA treatment, GTTR uptake remained reduced in comparison to controls; by 24 hours, drug uptake was comparable between untreated and BAPTA-treated hair cells, which again became susceptible to cell death induced by gentamicin. Together, these results provide genetic and pharmacologic evidence that tip-links are required for AG uptake and toxicity in hair cells. Because tip-links can spontaneously regenerate, their temporary breakage offers a limited time window when hair cells are protected from AG toxicity.
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Aminoglicosídeos/metabolismo , Mecanotransdução Celular , Animais , Caderinas/genética , Caderinas/fisiologia , Cálcio/metabolismo , Morte Celular , Quelantes/metabolismo , Ácido Egtázico/análogos & derivados , Células Ciliadas Auditivas/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , MutaçãoRESUMO
Aminoglycosides (AG) are commonly prescribed antibiotics with potent bactericidal activities. One main side effect is permanent sensorineural hearing loss, induced by selective inner ear sensory hair cell death. Much work has focused on AG's initiating cell death processes, however, fewer studies exist defining mechanisms of AG uptake by hair cells. The current study investigated two proposed mechanisms of AG transport in mammalian hair cells: mechanotransducer (MET) channels and endocytosis. To study these two mechanisms, rat cochlear explants were cultured as whole organs in gentamicin-containing media. Two-photon imaging of Texas Red conjugated gentamicin (GTTR) uptake into live hair cells was rapid and selective. Hypocalcemia, which increases the open probability of MET channels, increased AG entry into hair cells. Three blockers of MET channels (curare, quinine, and amiloride) significantly reduced GTTR uptake, whereas the endocytosis inhibitor concanavalin A did not. Dynosore quenched the fluorescence of GTTR and could not be tested. Pharmacologic blockade of MET channels with curare or quinine, but not concanavalin A or dynosore, prevented hair cell loss when challenged with gentamicin for up to 96 hours. Taken together, data indicate that the patency of MET channels mediated AG entry into hair cells and its toxicity. Results suggest that limiting permeation of AGs through MET channel or preventing their entry into endolymph are potential therapeutic targets for preventing hair cell death and hearing loss.
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Aminoglicosídeos/toxicidade , Células Ciliadas Auditivas/metabolismo , Células Ciliadas Auditivas/patologia , Canais Iônicos/metabolismo , Mecanotransdução Celular/efeitos dos fármacos , Animais , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Citoproteção/efeitos dos fármacos , Endocitose/efeitos dos fármacos , Gentamicinas/toxicidade , Células Ciliadas Auditivas/efeitos dos fármacos , Imageamento Tridimensional , Técnicas In Vitro , Ativação do Canal Iônico/efeitos dos fármacos , Cinética , Camundongos , Fótons , Ratos , Ratos Sprague-Dawley , Fatores de Tempo , Xantenos/metabolismoRESUMO
Initial presentation of a white female newborn delivered after normal pregnancy demonstrated a white mass obstructing the left nare. Primary biopsy revealed a focus of fibrotic nasal mucosa that included squamous and respiratory epithelium. After endoscopic resection of the mass, histopathologic examination resulted in the diagnosis of a teratoma. According to our literature review, this is the first case of a teratoma arising from the nasal septum in a white. Worldwide, 3 additional cases have been reported, but none included endoscopic management. This case illustrates our protocol for an endoscopic approach to an obstructive nasal mass in a neonate and our experience in the management of this rare disease.