Os animais com sensibilidade audiogênica, Wistar Audiogenic Rats (WAR) são modelos experimentais utilizados em pesquisas sobre audição, integração sensório-motora e epilepsias, entre elas as crises audiogênicas. O modelo de estimulação sonora repetida conhecido como kindling ou abrasamento audiogênico mimetiza um tipo de epilepsia parcial com envolvimento de estruturas límbicas. É também um modelo genético de grande importância para o estudo das epilepsias porque retrata crises em animais com seleção genética controlada. O objetivo desse estudo foi investigar as alterações morfológicas e funcionais em células ciliadas internas e externas da orelha interna em animais da cepa WAR submetidos ao abrasamento audiogênico comparando-os com animais controle. Foram utilizados 40 animais com idade de 80 a 120 dias. Os animais selecionados foram divididos em quatro grupos de estudo. Foram utilizados os animais que apresentaram função coclear normal, avaliada através do reflexo de Preyer, emissões otoacústicas por produtos de distorção (EOAPD) e limiar eletrofisiológico medido pelos potenciais evocados auditivos de tronco encefálico (PEATE). A avaliação funcional foi realizada antes do primeiro estímulo acústico e imediatamente após o último estímulo acústico. Em seguida foi realizada perfusão intracardíaca, os animais tiveram suas bulas removidas e as cócleas processadas para microscopia eletrônica de varredura. Em relação às EOAPD, os animais do grupo WAR-kindling apresentaram diferença significativa na relação sinal-ruído, sendo que animais WAR pré-kindling possuem valores significativamente superiores aos do pós-kindling. Em relação ao PEATE houve uma diferença significativa, o grupo WAR-kindling apresentou limiares com valores significativamente superiores aos do grupo Wistar kindling. Por microscopia eletrônica de varredura nos animais da cepa WAR observou-se uma estrutura irregular nos feixes de estereocílios das células ciliadas internas (CCI) e células ciliadas externas (CCE). Os exames para avaliação auditiva funcional (EOAPD), eletrofisiológica (PEATE) associados à microscopia eletrônica de varredura permitiram caracterizar as alterações morfológicas e funcionais em CCI e CCE da orelha interna em animais com sensibilidade audiogênica da cepa WAR como potenciais sequelas do abrasamento audiogênico. Os presentes dados confirmam a hipótese de que o abrasamento audiogênico na cepa WAR provoca impacto funcional e morfológico da orelha interna. / Animals of the Wistar Audiogenic Rat (WAR) strain are used as experimental models in research of auditory function, sensorimotor integration and epilepsy studies, including audiogenic seizures. The model of repeated acoustic stimulation mimics temporal lobe partial epilepsy with involvement of limbic structures and is of great importance to the study of epilepsy because it portrays a genetically selected strain. The objective of this study was to investigate the morphological and functional changes in inner and outer hair cells of the inner ear in the WAR strain after exposure to repeated acoustic stimulation and compared to control animals. 40 animals from 80 to 120 days old were included. The animals were divided into four groups of study. The animals used were those with normal cochlear function, evaluated through the Preyer Reflex, otoacoustic emissions by distortion product (DPOAE) and electrophysiological threshold measured by brainstem auditory evoked potentials (ABR). The functional assessment was performed before the first acoustic stimulus and immediately after the last acoustic stimulus. Then was performed intracardiac perfusion, the animals had their bullae removed and cochleas were processed for scanning electron microscopy. In relation to the DPOAE, the animals of the group WAR-kindling showed a significant difference in the signal-to-noise ratio, with WAR pre-kindling animals having values significantly higher than those of the post-kindling group. In relation to ABR there was a significant difference, the WAR-kindling group presented values significantly higher than those in the Wistar kindling group. By scanning electron microscopy in WAR they were observed irregular structural bundles of stereocilia of Outer Hair Cells (OHC) and Inner Hair Cells (IHC). The tests for assessing auditory function by means of DPOAE and electrophysiology (ABR) associated with the scanning electron microscopy allowed to characterize the morphological and functional changes in internal and external hair cells of the inner ear in animals with acoustic stimulation in WAR after audiogenic kindling. The present data confirm the hypothesis that kindling in WAR causes functional impact and morphological alterations in the inner ear.

Submitted by Fabíola Silva (fabiola.silva@famerp.br) on 2016-05-31T15:59:39Z No. of bitstreams: 1 magaliaparecidaoratemenezesdasilva_dissert.pdf: 1848544 bytes, checksum: bf5d6434181a9f1108fd8f5a3dc4fcf0 (MD5) / Made available in DSpace on 2016-05-31T15:59:39Z (GMT). No. of bitstreams: 1 magaliaparecidaoratemenezesdasilva_dissert.pdf: 1848544 bytes, checksum: bf5d6434181a9f1108fd8f5a3dc4fcf0 (MD5) Previous issue date: 2015-07-02 / Introduction: Mutations in the otoferlin gene (OTOF) can account for Auditory Neuropathy. Objective: To investigate the prevalence of mutations in OTOF gene in patients with and without Auditory Neuropathy. Casuistic and Methods: This original cross-sectional study evaluated 16 index cases with auditory neuropathy; 13 patients with sensorineural hearing loss and 20 normal-hearing subjects. DNA was extracted from peripheral blood leukocytes, and the OTOF gene sites were amplified by PCR-RFLP. Results: Out of the 16 index cases, 9 (56%) are female and 7 (44%) are male. Out of the 13 deaf patients, 7 (54%) are male and 6 (46%) female. Among the 20 listeners, 13 (65%) are male and 7 (35%) female. Thirteen (81%) index cases had wild-type genotype (AA) and 3 (19%), had the heterozygous AG genotype for IVS8-2A-G (intron 8) mutation. The 5473C-G (exon 44) mutation was found in a heterozygous state (CG) in 7 (44%) index cases and 9 (56%) had the wild-type allele (CC). Of these mutants, two (25%) are compound heterozygote for the mutations found in intron 8 and exon 44. All patients (100%) with hearing loss and listeners do not have mutations. Conclusion: Differences at the molecular level are found in patients with and without Auditory Neuropathy. / Introdução: Mutações no gene da otoferlina (OTOF) são responsáveis pela Neuropatia Auditiva. Objetivo: Investigar a prevalência de mutações no gene OTOF em pacientes com e sem Neuropatia Auditiva. Casuística e Método: Estudo original em corte transversal no qual foram avaliados 16 casos índice com Neuropatia Auditiva, 13 pacientes com deficiência auditiva sensorioneural (DASN) e 20 indivíduos ouvintes. DNA foi extraído de leucócitos do sangue periférico e regiões do gene OTOF foram analisadas pela técnica PCR-RFLP. Resultados: Dos 16 casos índice, 9 (56%) são do gênero feminino e 7 (44%) do masculino. Dos 13 pacientes com DASN, 7 (54%) são masculinos e 6 (46%) femininos. Dos 20 ouvintes, 13 (65%) são masculinos e 7 (35%) femininos. Treze (81%) casos índice apresentam o genótipo selvagem (AA) e 3 (19%), o genótipo heterozigoto AG para a mutação IVS8-2A-G (intron 8). A mutação 5473C-G (exon 44) foi encontrada em heterozigose (CG) em 7 (44%) dos casos índice e 9 (56%) apresentam o genótipo selvagem (CC). Destes mutantes, dois (25%) são heterozigotos compostos para as mutações encontradas no intron 8 e exon 44. Os pacientes com DASN e os ouvintes não apresentam mutações (100%). Conclusão: Existem diferenças, ao nível molecular, em pacientes com e sem Neuropatia Auditiva.

INTRODUÇÃO: Dentre as medidas da função coclear, a curva de crescimento das Emissões Otoacústicas por produto de distorção (CCEOA PD) permite o registro da amplitude da emissão em função do crescimento sistemático nos níveis de tons primários. A CCEOA PD fornece parâmetros específicos sobre o limiar e o comportamento não-linear das EOA PD, porém a variabilidade das respostas inter e intrasujeitos reduz a confiabilidade dessa medida na avaliação da robustez das respostas cocleares e a relação dessa robustez com os limiares auditivos. OBJETIVOS: Esta pesquisa estudou as interações entre as medidas timpanométricas da orelha média e as medidas de função coclear em adultos jovens sem queixas auditivas, de acordo com as variáveis: antecedentes de alterações de orelha média, sexo e orelha direita / esquerda. MÉTODOS: Participaram 69 indivíduos com audição normal e idades entre 18 e 34 anos, sendo 21 homens e 48 mulheres. A caracterização das condições de orelha média foi obtida pela anamnese, com a informação dos antecedentes de alterações de orelha média e pela timpanometria com sondas de admitância de 226 e 1000 Hz. A audiometria foi realizada com resolução de 01 dB NA, o que possibilitou comparações mais refinadas entre o limiar psicoacústico da audiometria tonal, a amplitude do DP-Gram e os limiares das CCEOA PD. Além dessas variáveis, a interferência dos fatores sexo e orelha foram testadas em todas as análises. RESULTADOS/DISCUSSÃO: Os resultados apontaram que as curvas de crescimento sofreram influência significativa das variáveis sexo, antecedentes de alterações de orelha média e orelha direita \\ esquerda, porém, apenas a interferência dos antecedentes foi constante e causou um padrão de modificação, ou seja, o grupo com antecedentes apresentou respostas aquém das respostas do grupo sem antecedentes. Os limiares audiométricos também apresentaram alta correlação com as amplitudes das EOA PD e com os limiares das CCEOA PD, quando identificadas as variáveis que interferiram nos resultados. Considerando que o ruído de fundo foi controlado nessa pesquisa, durante a avaliação das EOA PD e CCEOA PD, os resultados confirmaram a importância da consideração dessas variáveis na composição de grupos com audição normal em pesquisas com medidas de emissões otoacústicas. Ainda sobre os resultados, foi possível, por meio da medida da curva de crescimento (slope e limiar), demonstrar que o padrão de crescimento das CCEOA PD é diferente nos casos de modificação nas condições de orelha média e isso foi verificado tanto pelos antecedentes de alterações de orelha média quanto pelas medidas timpanométricas com sonda de admitância de 1000 Hz. CONCLUSÃO: O limiar das CCEOA - PD estudado nessa pesquisa apresentou correlação positiva com valores audiométricos e negativa com o DP-Gram. A inclinação da curva de crescimento (slope) também apresentou alta correlação com os antecedentes de alterações de orelha média, apontando o potencial valor desta medida no estudo da função coclear saudável e alterada e, conseqüentemente, sua possível utilização nas medidas prescritivas de amplificação / INTRODUCTION: The Distortion Product Otoacoustic Emissions Input/Output function (DPOAE I/O function) is a subdivision of DPOAE, where the response amplitude is recorded such as a systematic growth function in the primary tones. The DPOAE I/O function provides specific parameters about the DPOAEs threshold and non-linearity. However, the response variability reduces the measure reliability to evaluate the cochlear robustness and the relationship between robustness and hearing thresholds. OBJECTIVE: This research studied the interaction between the tympanometric measures and cochlear functions measures in young adults without hearing complaints, considering the variables: middle-ear alteration antecedents, gender and right / left ear. METHODS: 69 normal hearing subjects, aged from 18 to 34 years participated of the study. From the total, 21 were men and 48 women. To reach the proposed objectives, the middle ear conditions were assessed by anamneses and 226 and 1000 Hz admittance probe-tone tympanometry. The audiometric thresholds were searched with 01 dBHL resolution to enable refined comparisons among pure-tone audiometry and DP-Gram amplitude and DPOAE I/O function thresholds. The gender and ear interference were also evaluated in all analyses. RESULTS/DISCUSSION: The results showed that the variables gender, antecedents and ear affected the I/O functions responses, but only the middle-ear alterations antecedents presented a constant modification pattern. In other words, the group with antecedents presented mainly reduced responses in comparison with no antecedents group. The audiometric thresholds also presented high correlation with DPOAE amplitudes and DPOAE I/O functions thresholds, after the detection of the variables affecting the results. As the background noise was controlled during this study, the results confirmed the importance of monitoring these variables in the normal hearing group compositions to perform researches with DPOAE. Regarding the DPOAE I/O functions (slope and threshold), the growth pattern was modified according the middle ear conditions, verified by the antecedents of middle ear alterations and 1000 Hz admittance probe-tone tympanometry. CONCLUSION: The DPOAE I/O function threshold studied presented positive correlation with audiometric thresholds and negative correlation with DP-Gram. The DPOAE I/O functions slope also showed high correlation with antecedents of middle ear alterations, denoting the potential value of this measure in the study of the healthy and damaged cochlear function and, hence, it possible application in amplification prescriptive measures

The cochlea is an organ which extracts frequency information from the input sound wave. It also produces nerve signals, which are further analysed by the brain and ultimately lead to perception of the sound. An existing model of the cochlea by Fragni`ere is first analysed by simulation. This passive model is found to have the properties that the living cochlea does in terms of the frequency response. An analog VLSI circuit implementation of this cochlear model in CMOS weak inversion is proposed, using log-domain filters in current domain. It is fabricated on a chip and a measurement of a basilar membrane section is performed. The measurement shows a reasonable agreement to the model. However, the circuit is found to have a problem related to transistor mismatch, causing different behaviour in identical circuit blocks. An active cochlear model is proposed to overcome this problem. The model incorporates the effect of the outer hair cells in the living cochlea, which controls the quality factor of the basilar membrane filters. The outer hair cells are incorporated as an extra voltage source in series with the basilar membrane resonator. Its value saturates as the input signal becomes larger, making the behaviour rather closer to that of a passive model. The simulation results show this nonlinear phenomenon, which is also seen in the living cochlea. The contribution of this thesis is summarised as follows: a) the first CMOS weak inversion current domain basilar membrane resonator is designed and fabricated, and b) the first active two-dimensional cochlear model for analog VLSI implementation is developed.

The exquisite frequency selectivity and amplification characteristics of mammalian hearing intimately depend on the fast electromechanical motion of the outer hair cells in the cochlea. This membrane based process, termed electromotility, is driven by the protein prestin which is uniquely present in the OHC lateral wall. Voltage dependent motility, in OHCs and mammalian cells expressing prestin, is accompanied by intramembranous charge movement which is widely considered a signature of electromotility and prestin function. How prestin converts changes in membrane potential into axial length changes of OHCs is currently not understood at the molecular level. Many electromotility models predict that prestin conformational changes are the underlying mechanism connecting charge movement and motility. Currently, however, only indirect evidence for a prestin conformational change is available. Various experiments have indicated that the oligomeric states of prestin may be an important determinant of function. Numerous reports have provided varying estimates of prestin oligomeric state. However, estimates have been based on measurements performed outside the membrane making, firm biophysical conclusions difficult. Biophysical studies of prestin function have demonstrated its dependence on membrane properties. Alterations of membrane cholesterol affect voltage dependence of charge movement and motility. In addition cholesterol manipulations cause spatial redistribution of prestin and possibly change prestin oligomeric state. However, the underlying cause for prestin sensitivity to cholesterol and its relation to membrane distribution is unknown. We have applied single molecule fluorescence (SMF) imaging, single particle tracking (SPT), and Förster resonance energy transfer (FRET) to investigate prestin interactions at the molecular level. The results of our SMF experiments have suggested that prestin forms mainly tetramers and dimers in the cell membrane. Using SPT to map the trajectories of prestin in the membrane, we have found that prestin undergoes diffusion in and hops between membrane confinements of varying size. In addition, we have found that cholesterol affects the size and confinement strength of the compartments but does not affect the diffusivity within the compartments. Finally, using a combination of electrophysiology and FRET we have demonstrated that prestin undergoes voltage dependent structural changes. In total, our results refine our molecular understanding of prestin function.

Although deafness is a universal problem, effective treatments have remained elusive. In order to develop potential treatments, an overall understanding of the cellular process of auditory hair cell regeneration, which occurs in fish but not mammals, must be established. A previous microarray analysis and qRT-PCR validation of noise-exposed zebrafish showed that growth hormone (GH) was significantly upregulated during the process of auditory hair cell regeneration. Thus, GH may play an important role during hair cell regeneration. However, cellular effects of exogenous GH in the zebrafish auditory hair cell regeneration have not been examined after noise exposure. To understand the effect of GH in hair cell regeneration, adult zebrafish were exposed to a 150 Hz pure tone at a source level of 179 dB re 1 μPa RMS for 36 hours. Afterward the fish were immediately injected intraperitoneally with carp recombinant GH (20 μg/gram of body mass) or buffer (0.1 M, pH 7.4 phosphate buffer) and then placed in a recovery tank. The effect of GH on apoptosis in fish inner ear end organs were examined using TUNEL-labeling. Cell proliferation was measured by BrdU incorporation assay. Hair cell regeneration was determined by phalloidin-labeling to allow visualization of hair cell stereociliary bundles. After GH injection, the numbers of TUNEL-labeled cells showed a significant decrease in all three inner ear end organs (saccule, lagena, utricle), suggesting GH may suppress hair cell death induced by acoustic trauma. Higher levels of cell proliferation were also observed in the ears of GH-injected fish, indicating that GH is capable of activating cell mitosis in the zebrafish auditory system. Following sound exposure, the GH-injected group exhibited greater numbers of saccular hair cell bundles compared to the buffer-injected group. These results indicate that GH promotes hair cell regeneration following acoustic damage. Future studies are needed to examine the potential therapeutic benefits of GH in the mammalian ear.

The cochlea is an organ which extracts frequency information from the input sound wave. It also produces nerve signals, which are further analysed by the brain and ultimately lead to perception of the sound. An existing model of the cochlea by Fragni`ere is first analysed by simulation. This passive model is found to have the properties that the living cochlea does in terms of the frequency response. An analog VLSI circuit implementation of this cochlear model in CMOS weak inversion is proposed, using log-domain filters in current domain. It is fabricated on a chip and a measurement of a basilar membrane section is performed. The measurement shows a reasonable agreement to the model. However, the circuit is found to have a problem related to transistor mismatch, causing different behaviour in identical circuit blocks. An active cochlear model is proposed to overcome this problem. The model incorporates the effect of the outer hair cells in the living cochlea, which controls the quality factor of the basilar membrane filters. The outer hair cells are incorporated as an extra voltage source in series with the basilar membrane resonator. Its value saturates as the input signal becomes larger, making the behaviour rather closer to that of a passive model. The simulation results show this nonlinear phenomenon, which is also seen in the living cochlea. The contribution of this thesis is summarised as follows: a) the first CMOS weak inversion current domain basilar membrane resonator is designed and fabricated, and b) the first active two-dimensional cochlear model for analog VLSI implementation is developed.

Thesis (Ph. D.)--University of Washington, 1999. / Vita. Includes bibliographical references (leaves 114-122).

Introdução: O zumbido pode ser definido como a percepção consciente de um som, sem a participação de uma fonte sonora externa. A presença isolada do zumbido, sem a perda auditiva associada sugere que o mesmo pode ser o primeiro sintoma de alterações cocleares que somente serão percebidas depois do aparecimento da perda. Considerando que o zumbido está frequentemente relacionado a disfunções cocleares e mais especificamente a alterações nas células ciliadas, e que nesse caso as funções desempenhadas por elas podem estar comprometidas em algum grau, é possível que alterações nos mecanismos cocleares em pacientes com limiares auditivos ditos normais e queixa de zumbido sejam encontradas. Objetivo: O objetivo do presente estudo foi verificar as diferenças entre as respostas cocleares em mensurações eletroacústicas e psicoacústicas em indivíduos sem perda auditiva, com e sem queixa de zumbido. Método: Participaram do estudo 57 indivíduos com limiares audiométricos dentro dos padrões de normalidade, divididos em dois grupos: grupo-controle composto por 41 sujeitos (81 orelhas) sem queixa de zumbido, e grupo-zumbido composto por 16 sujeitos (31 orelhas) com queixa de zumbido. Os sujeitos foram submetidos à pesquisa das Curvas de Crescimento das Emissões Otoacústicas Produto de Distorção, pesquisa das Curvas Psicofísicas de Sintonia e aplicação do teste TEN. Resultados: Para as CC-EOAPD somente foi observada diferença estatística nas curvas de 3000 e 6000 Hz, para L2=45 dBNPS e L2=55 dBNPS, respectivamente. Para as curvas psicofísicas de sintonia, foram observadas diferenças estatísticas localizadas nas extremidades das curvas, isto é, para a CPS de 2000 Hz com ruído de 6000 e 8000, para a CPS de 3000 Hz, para 8000 Hz, para a CPS de 4000 Hz para o ruído de 2000 e 8000 Hz e para as CPS de 6000 e 8000 Hz para os ruídos de 3000 e 2000 Hz. Para o teste TEN, não foi encontrada presença de zonas mortas da cóclea, entretanto foi observado padrão diferente entre os grupos, caracterizado pelo limiar na presença de ruído ipsilateral estatisticamente mais elevado no grupo-zumbido do que no grupo-controle. Conclusão: Foi observado que apesar de audiologicamente normais, os grupos apresentam desempenhos estatisticamente distintos nos testes aplicados, principalmente nas Curvas Psicofísicas de Sintonia e no teste TEN, evidenciando funcionamentos cocleares diferentes que, possivelmente, comprometem em algum grau os mecanismos cocleares, principalmente a seletividade de frequência / Introduction: Tinnitus can be defined as the conscious perception of a sound without the participation of an external sound source. The association between tinnitus and hearing loss has been well described. The isolated presence of tinnitus, without hearing loss, suggests that it may be the first symptom of cochlear dysfunctions that will be noticed only after the emergence of the hearing loss. Whereas tinnitus is often related to cochlear dysfunction, specifically in hair cells, their mechanisms could be impaired to some degree. Thus, patients with normal hearing and tinnitus, could show some dysfunctions in cochlear mechanisms. Objective: The aim of this study was to investigate the differences between the cochlear responses in electroacoustic and psychoacoustic measurements in subjects with normal hearing, with and without tinnitus. Method: The study included 57 subjects with audiometric thresholds within normal limits, divided into two groups: control group consisted of 41 subjects (81 ears) without tinnitus and tinnitus group consisted of 16 subjects (31 ears) with tinnitus. The subjects were tested for DPOAE-I/O functions, Psychophysical Tuning Curves (PTC) and TEN test. Results: For DPOAE-I/O only statistical difference was observed in the curves of 3000 and 6000 Hz, for L2 = 45 dBSPL and L2 = 55 dBSPL respectively. For the psychophysical tuning curves, statistical differences were observed at the ends of the curves, i.e. for the PTC 2000 Hz with noise 6000 and 8000 to 3000 PTC Hz to 8000 Hz to 4000 Hz PTC for noise 2000 and 8000 Hz and the PTC 6000 and 8000 Hz for the noise of 3000 Hz and 2000 TEN For the TEN test, there were no presence of \"dead regions in the cochlea,\" however different pattern was observed among groups, characterized by the presence of noise threshold ipsilateral statistically higher in the tinnitus group than the control group. Conclusion: We found that despite normal hearing, the groups have statistically different performances in the test applied, especially in psychophysical tuning curves and the TEN test, showing that different runs cochlear possibly commit to some degree the cochlear mechanisms, mainly the frequency selectivity

INTRODUÇÃO: Dentre as medidas da função coclear, a curva de crescimento das Emissões Otoacústicas por produto de distorção (CCEOA PD) permite o registro da amplitude da emissão em função do crescimento sistemático nos níveis de tons primários. A CCEOA PD fornece parâmetros específicos sobre o limiar e o comportamento não-linear das EOA PD, porém a variabilidade das respostas inter e intrasujeitos reduz a confiabilidade dessa medida na avaliação da robustez das respostas cocleares e a relação dessa robustez com os limiares auditivos. OBJETIVOS: Esta pesquisa estudou as interações entre as medidas timpanométricas da orelha média e as medidas de função coclear em adultos jovens sem queixas auditivas, de acordo com as variáveis: antecedentes de alterações de orelha média, sexo e orelha direita / esquerda. MÉTODOS: Participaram 69 indivíduos com audição normal e idades entre 18 e 34 anos, sendo 21 homens e 48 mulheres. A caracterização das condições de orelha média foi obtida pela anamnese, com a informação dos antecedentes de alterações de orelha média e pela timpanometria com sondas de admitância de 226 e 1000 Hz. A audiometria foi realizada com resolução de 01 dB NA, o que possibilitou comparações mais refinadas entre o limiar psicoacústico da audiometria tonal, a amplitude do DP-Gram e os limiares das CCEOA PD. Além dessas variáveis, a interferência dos fatores sexo e orelha foram testadas em todas as análises. RESULTADOS/DISCUSSÃO: Os resultados apontaram que as curvas de crescimento sofreram influência significativa das variáveis sexo, antecedentes de alterações de orelha média e orelha direita \\ esquerda, porém, apenas a interferência dos antecedentes foi constante e causou um padrão de modificação, ou seja, o grupo com antecedentes apresentou respostas aquém das respostas do grupo sem antecedentes. Os limiares audiométricos também apresentaram alta correlação com as amplitudes das EOA PD e com os limiares das CCEOA PD, quando identificadas as variáveis que interferiram nos resultados. Considerando que o ruído de fundo foi controlado nessa pesquisa, durante a avaliação das EOA PD e CCEOA PD, os resultados confirmaram a importância da consideração dessas variáveis na composição de grupos com audição normal em pesquisas com medidas de emissões otoacústicas. Ainda sobre os resultados, foi possível, por meio da medida da curva de crescimento (slope e limiar), demonstrar que o padrão de crescimento das CCEOA PD é diferente nos casos de modificação nas condições de orelha média e isso foi verificado tanto pelos antecedentes de alterações de orelha média quanto pelas medidas timpanométricas com sonda de admitância de 1000 Hz. CONCLUSÃO: O limiar das CCEOA - PD estudado nessa pesquisa apresentou correlação positiva com valores audiométricos e negativa com o DP-Gram. A inclinação da curva de crescimento (slope) também apresentou alta correlação com os antecedentes de alterações de orelha média, apontando o potencial valor desta medida no estudo da função coclear saudável e alterada e, conseqüentemente, sua possível utilização nas medidas prescritivas de amplificação / INTRODUCTION: The Distortion Product Otoacoustic Emissions Input/Output function (DPOAE I/O function) is a subdivision of DPOAE, where the response amplitude is recorded such as a systematic growth function in the primary tones. The DPOAE I/O function provides specific parameters about the DPOAEs threshold and non-linearity. However, the response variability reduces the measure reliability to evaluate the cochlear robustness and the relationship between robustness and hearing thresholds. OBJECTIVE: This research studied the interaction between the tympanometric measures and cochlear functions measures in young adults without hearing complaints, considering the variables: middle-ear alteration antecedents, gender and right / left ear. METHODS: 69 normal hearing subjects, aged from 18 to 34 years participated of the study. From the total, 21 were men and 48 women. To reach the proposed objectives, the middle ear conditions were assessed by anamneses and 226 and 1000 Hz admittance probe-tone tympanometry. The audiometric thresholds were searched with 01 dBHL resolution to enable refined comparisons among pure-tone audiometry and DP-Gram amplitude and DPOAE I/O function thresholds. The gender and ear interference were also evaluated in all analyses. RESULTS/DISCUSSION: The results showed that the variables gender, antecedents and ear affected the I/O functions responses, but only the middle-ear alterations antecedents presented a constant modification pattern. In other words, the group with antecedents presented mainly reduced responses in comparison with no antecedents group. The audiometric thresholds also presented high correlation with DPOAE amplitudes and DPOAE I/O functions thresholds, after the detection of the variables affecting the results. As the background noise was controlled during this study, the results confirmed the importance of monitoring these variables in the normal hearing group compositions to perform researches with DPOAE. Regarding the DPOAE I/O functions (slope and threshold), the growth pattern was modified according the middle ear conditions, verified by the antecedents of middle ear alterations and 1000 Hz admittance probe-tone tympanometry. CONCLUSION: The DPOAE I/O function threshold studied presented positive correlation with audiometric thresholds and negative correlation with DP-Gram. The DPOAE I/O functions slope also showed high correlation with antecedents of middle ear alterations, denoting the potential value of this measure in the study of the healthy and damaged cochlear function and, hence, it possible application in amplification prescriptive measures