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1.
Article in English | WPRIM | ID: wpr-878327

ABSTRACT

Objective@#The aim of this study was to explore the ototoxicity of toluene in the early development of zebrafish embryos/larvae.@*Methods@#Zebrafish were utilized to explore the ototoxicity of toluene. Locomotion analysis, immunofluorescence, and qPCR were used to understand the phenotypes and molecular mechanisms of toluene ototoxicity.@*Results@#The results demonstrated that at 2 mmol/L, toluene induced zebrafish larvae death at 120 hours post fertilization (hpf) at a rate of 25.79% and inhibited the rate of hatching at 72 hpf. Furthermore, toluene exposure inhibited the distance travelled and average swimming velocity of zebrafish larvae while increasing the frequency of movements. As shown by fluorescence staining of hair cells, toluene inhibited the formation of lateral line neuromasts and middle line 1 (Ml @*Conclusion@#This study indicated that toluene may affect the development of both the inner ear and lateral line systems in zebrafish, while the lateral line system may be more sensitive to toluene than the inner ear.


Subject(s)
Animals , Ear, Inner/growth & development , Embryo, Nonmammalian/drug effects , Gene Expression Regulation, Developmental/drug effects , Hair Cells, Auditory/metabolism , Lateral Line System/growth & development , Locomotion/drug effects , Ototoxicity/physiopathology , Toluene/toxicity , Zebrafish
2.
Braz. j. med. biol. res ; 54(7): e10579, 2021. tab, graf
Article in English | LILACS | ID: biblio-1249313

ABSTRACT

NOTCH pathway proteins, including the transcriptional factor HES1, play crucial roles in the development of the inner ear by means of the lateral inhibition mechanism, in which supporting cells have their phenotype preserved while they are prevented from becoming hair cells. Genetic manipulation of this pathway has been demonstrated to increase hair cell number. The present study aimed to investigate gene expression effects in hair cells and supporting cells after Hes1-shRNA lentivirus transduction in organotypic cultures of the organ of Corti from postnatal-day-3 mice. Forty-eight hours after in vitro knockdown, Hes1 gene expression was reduced at both mRNA and protein levels. Myo7a (hair cell marker) and Sox2 (progenitor cell marker) mRNA levels also significantly increased. The modulation of gene expression in the organ of Corti upon Hes1 knockdown is consistent with cell phenotypes related to lateral inhibition mechanism interference in the inner ear. The lentivirus-based expression of Hes1-shRNA is a valuable strategy for genetic interference in the organ of Corti and for future evaluation of its efficacy in protocols aiming at the regeneration of hair cells in vivo.


Subject(s)
Animals , Rats , Cochlea , Basic Helix-Loop-Helix Transcription Factors/genetics , Organ of Corti , Cell Differentiation , Receptors, Notch , Transcription Factor HES-1/genetics , Hair Cells, Auditory
3.
Braz. j. otorhinolaryngol. (Impr.) ; 86(2): 222-227, March-Apr. 2020. graf
Article in English | LILACS | ID: biblio-1132576

ABSTRACT

Abstract Introduction: The use of electron microscopy in the study of the inner ear has allowed us to observe minute details of the hair cells, especially in ototoxicity studies; however, the preparation of this material is a difficult and delicate task. In an attempt to simplify the handling of these materials, two agents, toluidine blue and ethylenediamine tetra-acetic acid were tested, in addition to the elimination of osmium tetroxide during the preparation of albino guinea pig cochleae. We also tested the applicability of these methodologies in an ototoxicity protocol. Objective: To verify the quality of the images obtained with and without the use of ethylenediamine tetra-acetic acid, toluidine blue and osmium tetroxide in the preparation of cochleae of albino guinea pigs for the scanning electron microscopy. Methods: Three groups of cochleae were used. In Group 1, 10 cochleae were prepared with the usual methodology, dissecting the optical capsule without decalcification and using osmium tetroxide as a post-fixative agent. In Group 2, we prepared 10 cochleae decalcified with ethylenediamine tetra-acetic acid, injecting toluidine blue in the endolymphatic space to facilitate the identification of the organ of Corti. In Group 3, we used 4 cochleae of guinea pigs that received 3 doses of cisplatin (7.5 mg/kg, D1-D5-D6), two prepared according to the methodology used in Group 1 and two with that used in Group 2. Scanning electron microscopy images were obtained from the organ of Corti region of the basal turn of each cochlea. Results: The organ of Corti was more easily identified with the use of toluidine blue. The dissection of the cochlea was more accurate in the decalcified cochleae. The quality of the images and the preservation of the organ of Corti obtained with the two methodologies were similar. Conclusion: The proposed modifications resulted in images of similar quality as those observed using the traditional methodology.


Resumo Introdução: O emprego da microscopia eletrônica no estudo da orelha interna permitiu observar detalhes minuciosos das células ciliadas especialmente em estudos de ototoxicidade. Entretanto, o preparo desse material é trabalhoso e delicado. Para simplificar a manipulação desses materiais, testou-se o uso de dois agentes, azul de toluidina e ácido etilenodiamino tetra-acético, além da retirada do tetróxido de ósmio na preparação de cócleas de cobaias albinas. Testamos também a aplicabilidade dessas metodologias em um protocolo de ototoxicidade. Objetivo: Verificar a qualidade das imagens obtidas com e sem o uso de ácido etilenodiamino tetra-acético, azul de toluidina e tetróxido de ósmio na preparação de cócleas de cobaias albinas para a microscopia eletrônica de varredura. Método: Foram utilizados três grupos de cócleas. No Grupo 1 preparou-se 10 cócleas com a metodologia usual, dissecando a cápsula ótica sem descalcificac¸ão e utilizando tetróxido de ósmio como pós-fixador. No Grupo 2 preparamos 10 cócleas descalcificadas com ácido etilenodiamino tetra-acético, injetando azul de toluidina no espac¸o endolinfático para facilitar a identificação do órgão de Corti. No Grupo 3 utilizamos 4 cócleas de cobaias que receberam 3 doses de cisplatina (7,5 mg/kg, D1-D5-D6), duas preparadas com a metodologia do Grupo 1 e duas com a do Grupo 2. Foram obtidas imagens da microscopia eletrônica de varredura da região do órgão de Corti do giro basal de cada cóclea. Resultados: O órgão de Corti foi mais facilmente identificado com o azul de touidina. A dissecção da cóclea foi mais precisa nas cócleas descalcificadas A qualidade das imagens e a preservac¸ão do órgão de Corti obtidas com as duas metodologias foi similar. Conclusão: As modificações propostas resultaram em imagens de qualidade similar as observadas com o uso da metodologia tradicional.


Subject(s)
Animals , Female , Cisplatin/toxicity , Cochlea/drug effects , Cochlea/ultrastructure , Organ of Corti/drug effects , Organ of Corti/ultrastructure , Osmium Tetroxide/administration & dosage , Tolonium Chloride/administration & dosage , Microscopy, Electron, Scanning , Edetic Acid/administration & dosage , Guinea Pigs , Hair Cells, Auditory/drug effects , Hair Cells, Auditory/ultrastructure
4.
Int. arch. otorhinolaryngol. (Impr.) ; 23(3): 267-275, July-Sept. 2019. tab, graf
Article in English | LILACS | ID: biblio-1040018

ABSTRACT

Abstract Introduction Riluzole (2-amino-6-trifluoromethoxy benzothiazole) is known as a neuroprotective, antioxidant, antiapoptotic agent. It may have beneficial effects on neuronal cell death due to cisplatin-induced ototoxicity. Objective To evaluate the effect of riluzole on cisplatin-induced ototoxicity in guinea pigs. Methods Twenty-four guinea pigs, studied in three groups, underwent auditory brainstem response evaluation using click and 8 kHz tone burst stimuli. Subsequently, 5 mg/kg of cisplatin were administered to all animals for 3 days intraperitoneally (i.p.) to induce ototoxicity. Half an hour prior to cisplatin, groups 1, 2 and 3 received 2 ml of saline i.p., 6 mg/kg of riluzole hydrochloride i.p., and 8 mg/kg of riluzole hydrochloride i.p., respectively, for 3 days. The auditory brainstem responses were repeated 24 hours after the last drug administration. The cochleae were analyzed by transmission electron microscopy (TEM). Results After drug administiration, for 8,000 Hz stimulus, group 1 had significantly higher threshold shifts when compared with groups 2 (p < 0.05) and 3 (p < 0.05), and there was no significant difference in threshold shifts between groups 2 and 3 (p > 0.05). Transmission electron microscopy findings demonstrated the protective effect of riluzole on the hair cells and the stria vascularis, especially in the group treated with 8 mg/kg of riluzole hydrochloride. Conclusion We can say that riluzolemay have a protective effect on cisplatin- induced ototoxicity. However, additional studies are needed to confirm these results and the mechanisms of action of riluzole.


Subject(s)
Animals , Male , Evoked Potentials, Auditory, Brain Stem/drug effects , Cisplatin/adverse effects , Riluzole/pharmacology , Hearing Loss, Sensorineural/chemically induced , Auditory Threshold/drug effects , Stria Vascularis/drug effects , Stria Vascularis/pathology , Cochlear Nerve/drug effects , Cochlear Nerve/pathology , Riluzole/therapeutic use , Models, Animal , Microscopy, Electron, Transmission , Guinea Pigs , Hair Cells, Auditory/drug effects , Hair Cells, Auditory/pathology , Nerve Degeneration/chemically induced
5.
Braz. j. otorhinolaryngol. (Impr.) ; 85(4): 520-529, July-Aug. 2019. tab, graf
Article in English | LILACS | ID: biblio-1019587

ABSTRACT

Abstract Introduction: Mammalian hair cells and auditory neurons do not show regenerative capacity. Hence, damage to these cell types is permanent and leads to hearing loss. However, there is no treatment that re-establishes auditory function. Regenerative therapies using stem cells represent a promising alternative. Objective: This article aims to review the current literature about the main types of stem cells with potential for application in cell therapy for sensorineural hearing loss, the most relevant experiments already performed in animals, as well as the advances that have been recently made in the field. Methods: Research included the databases PubMed/MEDLINE, Web of Science, Science Direct and SciELO, as well as gray literature. Search strategy included the following main terms: "stem cells", "hair cells" and "auditory neurons". Additionally, the main terms were combined with the following secondary terms: "mesenchymal", "iPS", "inner ear", "auditory". The research was conducted independently by three researchers. Results: Differentiation of stem cells into hair cells and auditory neurons has a high success rate, reaching up to 82% for the first and 100% for the latter. Remarkably, these differentiated cells are able to interact with hair cells and auditory neurons of cochlear explants through formation of new synapses. When transplanted into the cochlea of animals with hearing loss, auditory restoration has been documented to date only in deafferented animals. Conclusion: Advances have been more prominent in cases of auditory neuropathy, since partial improvement of auditory nerve conditions through cell-based therapy may increase the number of patients who can successfully receive cochlear implants.


Resumo Introdução: Nos mamíferos, as células ciliadas e os neurônios auditivos não apresentam capacidade regenerativa. Assim, os danos a esses tipos celulares são permanentes e levam à perda auditiva. Contudo, como não há tratamento que restabeleça a função auditiva, as terapias regenerativas utilizando células-tronco representam uma alternativa promissora. Objetivo: Este artigo tem como objetivo revisar a literatura atual sobre os principais tipos de células-tronco com potencial para aplicação em terapia celular para perda auditiva sensorioneural, os experimentos mais relevantes já realizados em animais, bem como os avanços obtidos recentemente nessa área. Método: As pesquisas incluíram as bases de dados PubMed/MEDLINE, Web of Science, Science Direct e SciELO, além da literatura cinza. A estratégia de busca incluiu os seguintes termos principais: "stem cells", "hair cells" e "auditory neurons". Além disso, os termos principais foram combinados com os seguintes termos secundários: "mesenchymal", "iPS", "inner ear" e "auditory". A pesquisa foi realizada de forma independente por três pesquisadores. Resultados: A diferenciação de células-tronco em células ciliadas e neurônios auditivos têm alta taxa de sucesso, chegando a 82% para o primeiro caso e 100% para o segundo. Notavelmente, essas células diferenciadas são capazes de interagir com células ciliadas e neurônios auditivos de explantes cocleares através da formação de novas sinapses. Quando transplantadas para a cóclea de animais com perda auditiva, a restauração da função auditiva foi observada, até o momento, apenas em animais com ablação do VIII nervo craniano. Conclusão: Os avanços têm sido mais proeminentes em casos de neuropatia auditiva. A melhora parcial das condições do nervo auditivo por meio de terapia baseada em células-tronco pode aumentar o número de pacientes candidatos a receber implantes cocleares com sucesso.


Subject(s)
Humans , Animals , Stem Cell Transplantation , Hearing Loss, Sensorineural/therapy , Cell Differentiation , Cochlear Nerve/cytology , Hair Cells, Auditory
6.
Braz. j. otorhinolaryngol. (Impr.) ; 84(4): 441-447, July-Aug. 2018. graf
Article in English | LILACS | ID: biblio-951855

ABSTRACT

Abstract Introduction Methicillin-resistant staphylococcus aureus is an emerging problem for the treatment of chronic suppurative otitis media, and also for pediatric tympanostomy tube otorrhea. To date, there are no effective topical antibiotic drugs to treat methicillin-resistant staphylococcus aureus otorrhea. Objective In this study, we evaluated the ototoxicity of topical KR-12-a2 solution on the cochlea when it is applied topically in the middle ear of guinea pigs. Methods The antimicrobial activity of KR-12-a2 against methicillin-resistant staphylococcus aureus strains was examined by using the inhibition zone test. Topical application of KR-12-a2 solution, gentamicin and phosphate buffered saline were applied in the middle ear of the guinea pigs after inserting ventilation tubes. Ototoxicity was assessed by auditory brainstem evoked response and scanning electron microscope examination. Results KR-12-a2 produced an inhibition zone against methicillin-resistant staphylococcus aureus from 6.25 µg. Hearing threshold in the KR-12-a2 and PBS groups were similar to that before ventilation tube insertion. However, the gentamicin group showed elevation of the hearing threshold and there were statistically significant differences compared to the phosphate buffered saline or the KR-12-a2 group. In the scanning electron microscope findings, the KR-12-a2 group showed intact outer hair cells. However, the gentamicin group showed total loss of outer hair cells. In our experiment, topically applied KR-12-a2 solution did not cause hearing loss or cochlear damage in guinea pigs. Conclusion In our experiment, topically applied KR-12-a2 solution did not cause hearing loss or cochlear damage in guinea pigs. The KR-12-a2 solution can be used as ototopical drops for treating methicillin-resistant staphylococcus aureus otorrhea; however, further evaluations, such as the definition of optimal concentration and combination, are necessary.


Resumo Introdução O staphylococcus aureus resistente à meticilina é um problema emergente não só para a otite média supurativa crônica, mas também para casos de otorreia crônica em crianças com tubo de ventilação. Até o momento, não há antibióticos tópicos efetivos para a otorreia causada por staphylococcus aureus resistente à meticilina. Objetivo Nesse estudo, avaliamos a ototoxicidade da solução tópica de KR-12-a2 na cóclea quando aplicada topicamente na orelha média de cobaias. Método A atividade antimicrobiana de KR-12-a2 contra cepas de staphylococcus aureus resistente à meticilina foi avaliada utilizando-se o teste de zona de inibição de crescimento. Foram aplicados na orelhas médias de 3 grupos de cobaias, ou solução tópica de KR-12-a2, ou gentamicina ou solução salina tamponada com fosfato após timpanostomia. A ototoxicidade foi avaliada através do exame auditivo de potencial evocado auditivo de tronco encefálico e por microscopia eletrônica de varredura. Resultados O KR-12-a2 produziu uma zona de inibição contra o staphylococcus aureus resistente à meticilina a partir de 6,25 µg. Alterações do limiar de audição no grupo KR-12-a2 e no grupo com solução salina foram semelhantes aos observados antes da inserção do tubo de ventilação. No entanto, o grupo gentamicina apresentou um limiar auditivo mais elevado, estatisticamente significativo em comparação ao grupo solução salina ou ao grupo KR-12-a2. Nos achados da microscopia eletrônica, o grupo KR-12-a2 apresentou células ciliadas externas intactas. No entanto, o grupo gentamicina apresentou perda total das células ciliadas externas. Em nosso experimento, a solução de KR-12-a2 aplicada topicamente não causou perda auditiva ou dano coclear em cobaias. Conclusão Em nosso experimento, a solução de KR-12-a2 aplicada topicamente não causou perda auditiva ou dano coclear em cobaias. A solução de KR-12-a2 pode ser utilizada como gotas otológicas para o tratamento da otorreia causada por staphylococcus aureus resistente à meticilina; no entanto, são necessárias outras avaliações, para a definição da concentração e das associações ideais.


Subject(s)
Animals , Male , Peptide Fragments/toxicity , Cochlea/drug effects , Cathelicidins/toxicity , Methicillin-Resistant Staphylococcus aureus/drug effects , Anti-Bacterial Agents/toxicity , Otitis Media, Suppurative/microbiology , Peptide Fragments/administration & dosage , Auditory Threshold , Staphylococcal Infections/drug therapy , Microscopy, Electron, Scanning , Microbial Sensitivity Tests , Reproducibility of Results , Administration, Topical , Evoked Potentials, Auditory, Brain Stem , Treatment Outcome , Cochlea/physiopathology , Disease Models, Animal , Cathelicidins/administration & dosage , Guinea Pigs , Hair Cells, Auditory/drug effects , Anti-Bacterial Agents/administration & dosage
7.
Audiol., Commun. res ; 23: e2007, 2018. tab, graf
Article in Portuguese | LILACS | ID: biblio-983902

ABSTRACT

RESUMO Objetivo Fazer um levantamento dos medicamentos ototóxicos utilizados no tratamento do câncer pediátrico, apontar os danos das drogas para o sistema auditivo e os métodos utilizados na identificação destes danos nessa população. Estratégia de pesquisa: Foram utilizados periódicos nacionais e internacionais pertinentes ao assunto, acessados eletronicamente em bases de dados da Biblioteca Virtual em Saúde - MS, PubMed, Biblioteca Digital Brasileira de Teses e Dissertações, que envolvessem a população pediátrica com histórico de tratamento oncológico, publicados entre 2007 e 2016, e no Banco de Teses e Dissertações da Coordenação de Aperfeiçoamento de Pessoal de Nível Superior. Critérios de seleção Foram selecionados estudos que contemplassem os seguintes critérios: estudos observacionais nas línguas portuguesa, inglesa ou espanhola e resumos disponíveis que informassem o método de avaliação do dano auditivo. Resultados A amostra final resultou em 12 artigos. Destes, a audiometria tonal limiar foi o método de avaliação auditiva mais utilizado, estando presente em 10 (84,61%) dos estudos, seguido das emissões otoacústicas (46,15%). Todos os estudos foram desenvolvidos com pacientes que fizeram uso de cisplatina ou derivados da platina e, quanto ao dano auditivo, apenas 1 dos estudos incluídos não relatou presença de alteração na população estudada. Conclusão Os derivados da platina expressam papel importante no tratamento do câncer em diversos níveis e são os agentes ototóxicos mais citados em pesquisas. A cóclea é o local mais afetado, mais especificamente as células ciliadas externas. Os métodos de investigação da alteração auditiva mais utilizados são a audiometria tonal limiar e as emissões otoacústicas.


ABSTRACT Objective The aim of the present study was to perform a literature review on ototoxic medications used for the treatment of childhood cancer and determine the harm caused by such drugs to the auditory system as well as the methods used to identify this harm. Search strategy The electronic databases of the Virtual Health Library (Brazilian Health Ministry), PubMed, Brazilian Digital Library of Theses and Dissertations, and Databank of Theses and Dissertations of the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES [Brazilian Coordination for the Advancement of Higher Education Personnel]) were searched for relevant national and international papers involving the pediatric population with a history of treatment for cancer published between 2007 and 2016. Selection criteria Observational studies published in Portuguese, English or Spanish with abstracts available and that informed the method for assessing hearing damage. Results The final sample consisted of 12 articles. Pure-tone threshold audiometry was the used in ten (84.61%) of the studies and otoacoustic emissions were investigated in 46.15%. All studies involved patients who made use of cisplatin or platinum derivatives. Only one of the studies included in the present review reported no changes in hearing in the population studied. Conclusion Platinum derivatives play an important role in the treatment of cancer and are the most widely cited ototoxic agents in studies. The cochlea is the most affected site, specifically the outer hair cells. The most widely used methods for assessing altered hearing are pure-tone threshold audiometry and otoacoustic emissions.


Subject(s)
Humans , Child , Drug-Related Side Effects and Adverse Reactions , Hair Cells, Auditory/drug effects , Hearing Loss , Neoplasms/drug therapy , Audiometry , Carboplatin/adverse effects , Cisplatin/adverse effects , Aminoglycosides/adverse effects , Head and Neck Neoplasms
8.
Yonsei Medical Journal ; : 141-147, 2018.
Article in English | WPRIM | ID: wpr-742492

ABSTRACT

PURPOSE: microRNAs (miRNAs) are non-coding RNAs composed of 20 to 22 nucleotides that regulate development and differentiation in various organs by silencing specific RNAs and regulating gene expression. In the present study, we show that the microRNA (miR)-183 cluster is upregulated during hair cell regeneration and that its inhibition reduces hair cell regeneration following neomycin-induced ototoxicity in zebrafish. MATERIALS AND METHODS: miRNA expression patterns after neomycin exposure were analyzed using microarray chips. Quantitative polymerase chain reaction was performed to validate miR-183 cluster expression patterns following neomycin exposure (500 µM for 2 h). After injection of an antisense morpholino (MO) to miR-183 (MO-183) immediately after fertilization, hair cell regeneration after neomycin exposure in neuromast cells was evaluated by fluorescent staining (YO-PRO1). The MO-183 effect also was assessed in transgenic zebrafish larvae expressing green fluorescent protein (GFP) in inner ear hair cells. RESULTS: Microarray analysis clearly showed that the miR-183 cluster (miR-96, miR-182, and miR-183) was upregulated after neomycin treatment. We also confirmed upregulated expression of the miR-183 cluster during hair cell regeneration after neomycin-induced ototoxicity. miR-183 inhibition using MO-183 reduced hair cell regeneration in both wild-type and GFP transgenic zebrafish larvae. CONCLUSION: Our work demonstrates that the miR-183 cluster is essential for the regeneration of hair cells following ototoxic injury in zebrafish larvae. Therefore, regulation of the miR-183 cluster can be a novel target for stimulation of hair cell regeneration.


Subject(s)
Animals , Animals, Genetically Modified , Cell Count , Gene Expression Profiling , Gene Expression Regulation/drug effects , Gene Knockdown Techniques , Green Fluorescent Proteins/metabolism , Hair Cells, Auditory/drug effects , Hair Cells, Auditory/physiology , Larva/drug effects , Larva/genetics , MicroRNAs/genetics , MicroRNAs/metabolism , Morpholinos/pharmacology , Neomycin/toxicity , Regeneration/drug effects , Regeneration/genetics , Zebrafish/genetics
9.
Chonnam Medical Journal ; : 37-46, 2017.
Article in English | WPRIM | ID: wpr-788362

ABSTRACT

Cochlear sensory hair cells (HCs) are crucial for hearing as mechanoreceptors of the auditory systems. Clarification of transcriptional regulation for the cochlear sensory HC development is crucial for the improvement of cell replacement therapies for hearing loss. Transcription factor Atoh1 is the key player during HC development and regeneration. In this review, we will focus on Atoh1 and its related signaling pathways (Notch, fibroblast growth factor, and Wnt/β-catenin signaling) involved in the development of cochlear sensory HCs. We will also discuss the potential applicability of these signals for the induction of HC regeneration.


Subject(s)
Cochlea , Fibroblast Growth Factors , Hair Cells, Auditory , Hair , Hearing , Hearing Loss , Mechanoreceptors , Regeneration , Transcription Factors
10.
Article in English | WPRIM | ID: wpr-25545

ABSTRACT

Circling mouse (C57BL/6J-cir/cir) deleted the transmembrane inner ear (Tmie) gene is an animal model for human non-syndromic recessive deafness, DFNB6. In circling mouse, hair cells in the cochlea have degenerated and hair bundles have become irregularity as time goes on. Tmie protein carries out a function of the mechanoelectrical transduction channel in cochlear hair cells. Myosin7a (MYO7A) protein has key roles in development of the cochlear hair bundles as well as in the function of cochlear hair cells. To find whether Tmie protein interacts with MYO7A proteins in the cochlea postnatal developmental stage, we investigated expression of the MYO7A proteins in the cochlear hair cells of circling mice by western blot analysis and whole mount immunofluorescence at postnatal day 5 (P5). The expression of MYO7A showed statistically significant increase in the cochlea of C57BL/6J-+/cir and C57BL/6J-cir/cir mice than that of C57BL/6J-+/+ mice. The MYO7A intensity of the cochlear hair cells also increased in C57BL/6J-+/cir and C57BL/6J-cir/cir mice compared with those of C57BL/6J-+/+ mice. Taken together, the results indicate that Tmie protein may have an important role with MYO7A protein in the development and maintenance of the stereociliary bundles during postnatal developmental stage of the cochlea.


Subject(s)
Animals , Blotting, Western , Cochlea , Deafness , Ear, Inner , Fluorescent Antibody Technique , Hair , Hair Cells, Auditory , Humans , Mice , Models, Animal
11.
Chonnam Medical Journal ; : 37-46, 2017.
Article in English | WPRIM | ID: wpr-67656

ABSTRACT

Cochlear sensory hair cells (HCs) are crucial for hearing as mechanoreceptors of the auditory systems. Clarification of transcriptional regulation for the cochlear sensory HC development is crucial for the improvement of cell replacement therapies for hearing loss. Transcription factor Atoh1 is the key player during HC development and regeneration. In this review, we will focus on Atoh1 and its related signaling pathways (Notch, fibroblast growth factor, and Wnt/β-catenin signaling) involved in the development of cochlear sensory HCs. We will also discuss the potential applicability of these signals for the induction of HC regeneration.


Subject(s)
Cochlea , Fibroblast Growth Factors , Hair Cells, Auditory , Hair , Hearing , Hearing Loss , Mechanoreceptors , Regeneration , Transcription Factors
12.
CoDAS ; 28(2): 93-98, mar.-abr. 2016. tab, graf
Article in Portuguese | LILACS | ID: lil-782141

ABSTRACT

RESUMO Introdução Atualmente, somente a hipóxia neonatal grave (evidenciada pelo valor do Apgar) é considerada risco para a deficiência auditiva. A hipóxia é uma das causas mais comuns de lesão e morte celular. Nos casos de hipóxia leve ou moderada, embora menor, a privação da oxigenação está presente e, dessa forma, algum dano ao sistema auditivo pode ocorrer. Objetivo Investigar as amplitudes das emissões otoacústicas em recém-nascidos a termo sem risco para deficiência auditiva que apresentaram hipóxia leve ou moderada. Métodos Foram selecionados 37 recém-nascidos de ambos os sexos, divididos em dois grupos: 25 do grupo controle, formado por recém-nascidos sem hipóxia, e 12 do grupo estudo, formado por recém-nascidos com hipóxia leve ou moderada. Resultados Foram pesquisadas as EOAT e EOAPD em ambos os grupos e comparados os seus resultados. Nas EOAPD foram encontradas diferenças estatísticas entre as amplitudes nas frequências 1.000, 2.800, 4.000 e 6.000 Hz. Nas EOAT foram encontradas diferenças estatísticas nas bandas de frequência de 1.000, 1.400, 2.000, 2.800 e 4.000 Hz, sendo as EOA do grupo estudo menores que as do grupo controle. Conclusão Embora a ocorrência de hipóxia neonatal leve e moderada não seja considerada risco para perda auditiva, a mínima privação do oxigênio durante o momento de hipóxia neonatal parece interferir no funcionamento das células ciliadas externas e, consequentemente, no nível de respostas das emissões otoacústicas. Dessa forma, faz-se necessário o acompanhamento longitudinal desses lactentes, a fim de identificar o possível impacto desses resultados na aquisição de linguagem e, futuramente, no desempenho escolar.


ABSTRACT Introduction Severe neonatal hypoxia (as evidenced by the Apgar value) is currently considered the only risk for hearing loss. Hypoxia is one of the most common causes of injury and cell death. The deprivation of oxygen in mild or moderate cases of hypoxia, although smaller, occurs and could cause damage to the auditory system. Objective To investigate the amplitude of otoacoustic emissions in neonates at term with mild to moderate hypoxia and no risk for hearing loss. Methods We evaluated 37 newborns, divided into two groups: a control group of 25 newborns without hypoxia and a study group of 12 newborns with mild to moderate hypoxia. TEOAE and DPOAE were investigated in both groups. Results The differences between groups were statistically significant in the amplitude of DPOAE at the frequencies of 1000, 2800, 4000 and 6000 Hz. In TEOAE, statistically significant differences were found in all tested frequency bands. OAE of the study group were lower than those in the control group. Conclusion Although the occurrence of mild and moderate neonatal hypoxia is not considered a risk factor for hearing loss, deprivation of minimum oxygen during neonatal hypoxia seems to interfere in the functioning of the outer hair cells and, consequently, alter the response level of otoacoustic emissions. Thus, hese children need longitudinal follow-up in order to identify the possible impact of these results on language acquisition and future academic performance.


Subject(s)
Humans , Male , Female , Infant, Newborn , Otoacoustic Emissions, Spontaneous/physiology , Hearing Loss, Sensorineural/etiology , Hypoxia/complications , Hypoxia/physiopathology , Apgar Score , Reference Values , Time Factors , Severity of Illness Index , Case-Control Studies , Risk Factors , Analysis of Variance , Evoked Potentials, Auditory/physiology , Hair Cells, Auditory/physiology
13.
Int. arch. otorhinolaryngol. (Impr.) ; 19(1): 93-95, Jan-Mar/2015. graf
Article in English | LILACS | ID: lil-741535

ABSTRACT

Introduction Schwannoma of the olfactory groove is an extremely rare tumor that can share a differential diagnosis with meningioma or neuroblastoma. Objectives The authors present a case of giant schwannoma involving the anterior cranial fossa and ethmoid sinuses. Case Report The patient presented with a 30-month history of left nasal obstruction, anosmia, and sporadic ipsilateral bleeding. Computed tomography of the paranasal sinuses revealed expansive lesion on the left nasal cavity extending to nasopharynx up to ethmoid and sphenoid sinuses bilaterally with intraorbital and parasellar extension to the skull base. Magnetic resonance imaging scan confirmed the expansive tumor without dural penetration. Biopsy revealed no evidence of malignancy and probable neural cell. Bifrontal craniotomy was performed combined with lateral rhinotomy (Weber-Ferguson approach), and the lesion was totally removed. The tumor measured 8.0 4.3 3.7 cm and microscopically appeared as a schwannoma composed of interwoven bundles of elongated cells (Antoni A regions)mixed with less cellular regions (Antoni B). Immunohistochemical study stained intensively for vimentin and S-100. Conclusion Schwannomas of the olfactory groove are extremely rare, and the findings of origin of this tumor is still uncertain but recent studies point most probably to the meningeal branches of trigeminal nerve or anterior ethmoidal nerves. .


Subject(s)
Animals , Female , Male , Mice , Cell Membrane Permeability/physiology , Hair Cells, Auditory/physiology , Ion Channels/physiology , Mechanotransduction, Cellular/physiology , Animals, Newborn , Cadherins/genetics , Cell Membrane Permeability/genetics , Chelating Agents/pharmacology , Dihydrostreptomycin Sulfate/pharmacology , Embryo, Mammalian , Egtazic Acid/analogs & derivatives , Egtazic Acid/pharmacology , Hair Cells, Auditory/cytology , Hair Cells, Auditory/drug effects , In Vitro Techniques , Ion Channels/drug effects , Mice, Transgenic , Mechanotransduction, Cellular/drug effects , Mechanotransduction, Cellular/genetics , Membrane Potentials/drug effects , Membrane Potentials/genetics , Myosins/genetics , Organ of Corti/cytology , Protein Precursors/genetics
14.
Ciênc. saúde coletiva ; 20(2): 433-440, 02/2015.
Article in Portuguese | LILACS, BDS | ID: lil-742216

ABSTRACT

A medicina regenerativa implica em uma mudança de paradigma, a regeneração do organismo ao nível celular ou tecidual – um assunto contemporâneo controverso e de difícil estandardização. O artigo apresenta um resumo das tendências científicas, econômicas, sociais e de regulamentação global nessa área, analisadas em relação a dilemas teóricos relevantes em antropologia médica e sociologia da ciência e da saúde. Em especial, aqueles que tratam da construção de um ‘aparato coletivo de sentido’ para as novas entidades biológicas e ontológicas, a formação da cidadania biológica e a governança pela incerteza. Apresentam-se, também, evidências empíricas sobre um fenômeno chave para a governança e a regulamentação, qual seja a instalação de uma nova demanda transnacional em pesquisa e saúde através de mercados paralelos de óvulos e de terapias celulares em experimentação. Utilizam-se dados qualitativos coletados para uma pesquisa mais abrangente, resenhas jornalísticas e entrevistas com lideranças internacionais. Conclui-se com uma reflexão sobre a importância da governança internacional em ensaios clínicos e dos caminhos a serem explorados, visando uma harmonização da diversidade de práticas normativas.


Regenerative medicine involves a paradigm change due to organism regeneration at cellular and tissue level – a controversial contemporary issue and difficult to regulate. This article presents a summary of the main scientific, economic, social and regulatory global trends, analyzed according to relevant theoretical dilemmas in medical anthropology and in the sociology of science and health. This is especially true of the construction of a ‘collective frame of reference’ on the new biological and ontological entities, the shaping of biological citizenship, and governance through uncertainty. Empirical evidence is also presented on a key aspect in regulation and governance, namely the emergence of a new transnational demand in health research through the establishment of parallel markets for ova and experimental cellular therapies. Qualitative data collected for a broader research paper is analyzed, as well as journal reviews and information gathered during interviews with international leaders. The paper concludes with a discussion on the importance on international governance of clinical trials and on further exploration, towards a multilevel harmonization of a diversity of normative practices.


Subject(s)
Humans , Animals , Male , Female , Adult , Mice , Adherens Junctions/metabolism , Cadherins/metabolism , Hair Cells, Auditory/metabolism , Postural Balance/physiology , Saccule and Utricle/metabolism , Adherens Junctions/ultrastructure , Animals, Newborn , Cell Count , Cells, Cultured , Hair Cells, Auditory/cytology , Hair Cells, Auditory/ultrastructure , Hair Cells, Vestibular/cytology , Hair Cells, Vestibular/metabolism , Hair Cells, Vestibular/ultrastructure , Mice, Transgenic , Saccule and Utricle/embryology , Saccule and Utricle/ultrastructure
15.
Acta otorrinolaringol. cir. cabeza cuello ; 43(3): 187-210, 20150000. Ilus
Article in Spanish | LILACS | ID: biblio-966440

ABSTRACT

El interés por la fisiología y patología del sistema auditivo ha crecido en los últimos años, y no sin razón, en Estados Unidos grados variables de hipoacusia afectan al doble de la población afectada por ceguera. El sistema auditivo presenta algunas características fascinantes en su funcionamiento, la cóclea de los mamíferos, por ejemplo, es capaz de responder a vibraciones de tan solo ±0,3nm, el diámetro de un átomo y de detectar estímulos en humanos de hasta 20 KHz. El propósito del órgano de la audición es transformar la energía sonora en un impulso eléctrico que se transmite por el nervio coclear hacia el Sistema Nervioso Central. Esta revisión describe la fisiología coclear haciendo énfasis en la correlación morfofisiológica subyacente, tanto a nivel celular como molecular, intentando seguir la secuencia temporal de eventos mediante la cual un estímulo acústico se traduce en una respuesta neural.


Interest in the physiology and pathology of the auditory system has grown in recent years, not unreasonably, in the United States, variable degrees of hearing loss affect twice the population affected by blindness. The auditory system has some fascinating characteristics in their function, the cochlea of mammals, for example, is able to, answer to vibrations of ± 0,3nm, the diameter of an atom and to detect stimulations in humans up to 20 KHz. The purpose of the hearing organ is to convert sound energy into an electrical impulse that is transmitted by the cochlear nerve to the central nervous system. This review describes the cochlear physiology, making emphasis on the underlying morphophysiological correlation, in a cellular and molecular level, trying to follow the temporal sequence of events, through which, an acoustic stimulus resulting in a neural response.


Subject(s)
Cochlea , Auditory Perception , Hair Cells, Auditory
16.
Article in Chinese | WPRIM | ID: wpr-243831

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the location and distribution of plasma membrane Ca²⁺ -ATPase isoform 2(PMCA2) in the cochleas of C57BL/6J mice at various ages (4w, 14w, 22w, 45w), and to reveal the relationship of PMCA2 and age-related hearing loss (AHL).</p><p><b>METHODS</b>The distribution of PMCA2 in the cochleas of C57BL/6J mice was detected by immunohistochemistry at various ages (4w, 14w, 22w, 45w). Real-time polymerase chain reaction (Rt-PCR) was used to detect the level of PMCA2 mRNA in the cochleas of C57BL/6J mice at the ages of 4, 14, 22 and 45 weeks old respectively. Using SPSS17.0 software for statistical analysis.</p><p><b>RESULTS</b>PMCA2 was mainly located in the hear cells, stria vascularis, and spiral ganglion cells. Faint labeling of PMCA2 was also observed in spiral ligament. Hair cells missed and the number of spiral ganglion cells reduced with age. Expression of PMCA2 in the cochleas of C57BL/6J mice also showed age-related decreasing. The results of Rt-PCR demonstrated the expression of mRNA of gene (Atp2b2) at 14 weeks age was significantly less than 4 week-old mice cochlears (P<0.05). The expression of mRNA of gene (Atp2b2) at 22 weeks age was significantly less than 14 week-old mice cochlears (P<0.05). The expression of mRNA of gene (Atp2b2) at 45 weeks age was significantly less than 14 week-old mice cochlears (P<0.01).</p><p><b>CONCLUSIONS</b>PMCA2 is mainly located in the hear cells, stria vascularis, and spiral ganglion cells. Faint labeling of PMCA2 is also observed in spiral ligament. The expression of PMCA2 demonstrates an age-related decrease with age. The mRNA expression level of PMCA2 gene(Atp2b2) in the cochleas of C57BL/6J mice displayed an age-related decrease. PMCA2 transporters may play a critical role in maintaining the normal morphology of the inner ear and it may be related to AHL.</p>


Subject(s)
Aging , Animals , Cochlea , Hair Cells, Auditory , Metabolism , Isoenzymes , Metabolism , Mice , Mice, Inbred C57BL , Plasma Membrane Calcium-Transporting ATPases , Metabolism , RNA, Messenger , Metabolism , Real-Time Polymerase Chain Reaction , Spiral Ganglion , Cell Biology , Metabolism , Stria Vascularis , Cell Biology , Metabolism
17.
Article in English | WPRIM | ID: wpr-51196

ABSTRACT

In mammals, the auditory system, which includes the cochlea, has a very complex structure harboring many types of cells performing different functions. Among these cells are the auditory hair cells (HCs), which are terminally and well differentiated unique cells which have lost their regenerative potential after development. The auditory HCs are easily damaged by aging as well as during episodes of ototoxicity and acoustic trauma. HCs damages typically occur in the early stage of injury and can result a permanent hearing loss. Recently, there have been tremendous developments from stem cells (SCs) research involving sensorineural hearing loss, but several limitations and obstacles persist in allowing these developments from continuing onto clinical applications. This review discusses the recent advances in SC research in sensorineural hearing loss with the subsequent sections discussing the possible hurdles and limitations that currently preclude their clinical application.


Subject(s)
Aging , Cochlea , Hair Cells, Auditory , Hearing Loss , Hearing Loss, Noise-Induced , Hearing Loss, Sensorineural , Mammals , Stem Cells
18.
Article in Chinese | WPRIM | ID: wpr-748808

ABSTRACT

OBJECTIVE@#To investigate the expression of adaptin-2(AP-2) in mice cochlea and to discuss the probable role in the endocytosis of hair cells.@*METHOD@#Laser scanning confocal microscopy and immune-fluroscence histochemistry were performed in this study.@*RESULT@#In mature mice cochlea, the immunoreactivity for AP-2 was found in the inner hair cells cytoplasm. This protein mainly expressed in the hair cells basal part and nearby the ribbon synapse.@*CONCLUSION@#AP-2 protein mainly expressed in the hair cells synaptic activity zone , which suggested that AP-2 could play an important role in the synaptic vesicle endocytosis. This finding built the foundation for the further research involved in the physiological and pathological role of AP-2.


Subject(s)
Adaptor Protein Complex alpha Subunits , Metabolism , Animals , Cochlea , Hair Cells, Auditory , Hair Cells, Auditory, Inner , Metabolism , Mice , Microscopy, Confocal , Synapses
19.
Article in Chinese | WPRIM | ID: wpr-747743

ABSTRACT

OBJECTIVE@#To investigate the expression of Myosin VI and Disabled-2 (Dab2) in the cochlea of mice at different ages.@*METHOD@#Forty KM mice were divided into four groups according to age, named as postnatal 2 week (P2w), P5w, P9w, P16month. The localization of protein in the basilar membrane of mice cochlea was detected by immunofluorescence staining and laser scanning confocal microscope (LSCM). The mRNA expression level of protein in cochlear at different ages was evaluated by real-time fluorescent quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). Statistical analysis was performed by the SPSS18.0 software.@*RESULT@#Myosin VI and Disabled-2 protein mainly expressed at the apical cytoplasm of hair cells. As for the inner hair cell, Dab2 labeling was abundant especially at the cuticular plate and nearby. Comparing four immunofluorescence staining images of Myosin VI, we found the fluorescence intensity of P2w and P16m were weaker than that of P5w and P9w. After setting P9w as the control group, qRT-PCR revealed that the mRNA expression of MyosinVI and Dab2 in P2w was less than that in the control group (P 0.05).@*CONCLUSION@#Myosin VI and Dab2, two proteins which regulated the clathrin-mediated endocytosis, expressed at hair cells of mice cochlea. In the inner hair cell, this process of endocytosis may be more efficient at the cuticular plate and nearby. The expression level of protein may change in different ages, and this probably leads to a difference of CME, it also may cause a defect of inner hair cells function.


Subject(s)
Adaptor Proteins, Vesicular Transport , Metabolism , Aging , Animals , Cochlea , Metabolism , Endocytosis , Hair Cells, Auditory , Metabolism , Hair Cells, Auditory, Inner , Metabolism , Mice , Microscopy, Confocal , Myosin Heavy Chains , Metabolism
20.
Hanyang Medical Reviews ; : 84-91, 2015.
Article in Korean | WPRIM | ID: wpr-171248

ABSTRACT

Noise-induced hearing loss (NIHL) is the second most common cause of permanent hearing impairment after age-related hearing loss. NIHL is influenced by environmental and genetic factors and the effects of noise can be exacerbated by the administration of ototoxic drugs or exposure to chemicals. The pathophysiology of NIHL is classified as either mechanical injury or metabolic (or biochemical) injury. Exposure of cochleae to intense sounds has been found to disrupt the stereocilia on the hair cells by separating the tip links and to depolymerize actin filaments, resulting in a disturbance in signal transduction. Major mechanisms of metabolic injuries include accumulation of reactive oxygen species enhanced by oxidative stress, cochlear ischemia followed by reperfusion injury, and excitotoxicity to auditory neuron induced by excessive release of the cochlear afferent neurotransmitter, glutamate. Many studies involving therapeutic or preventive trial with antioxidants, JNK inhibitors, and NMDA antagonists have shown partial effectiveness. However, protection from noise before cochlear injury occurs is very important because damaged hair cells and auditory neurons in the mammalian cochleae are unable to regenerate.


Subject(s)
Actin Cytoskeleton , Antioxidants , Apoptosis , Cochlea , Glutamic Acid , Hair , Hair Cells, Auditory , Hearing Loss , Hearing Loss, Noise-Induced , Ischemia , N-Methylaspartate , Neurons , Neurotransmitter Agents , Noise , Oxidative Stress , Reactive Oxygen Species , Reperfusion Injury , Signal Transduction , Stereocilia
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