Tympanic membranes (TM) that have healed spontaneously after perforation present abnormalities in their structural and mechanical properties; i.e., they are thickened and abnormally dense. These changes result in a deterioration of middle ear (ME) sound transmission, which is clinically presented as a conductive hearing loss (CHL). To fully understand the ME sound transmission under TM pathological conditions, we created a gerbil model with a controlled 50% pars tensa perforation, which was left to heal spontaneously for up to 4 weeks (TM perforations had fully sealed after 2 weeks). After the recovery period, the ME sound transmission, both in the forward and reverse directions, was directly measured with two-tone stimulation. Measurements were performed at the input, the ossicular chain, and output of the ME system, i.e., at the TM, umbo, and scala vestibuli (SV) next to the stapes. We found that variations in ME transmission in forward and reverse directions were not symmetric. In the forward direction, the ME pressure gain decreased in a frequency-dependent manner, with smaller loss (within 10 dB) at low frequencies and more dramatic loss at high frequency regions. The loss pattern was mainly from the less efficient acoustical to mechanical coupling between the TM and umbo, with little changes along the ossicular chain. In the reverse direction, the variations in these ears are relatively smaller. Our results provide detailed functional observations that explain CHL seen in clinical patients with abnormal TM, e.g., caused by otitis media, that have healed spontaneously after perforation or post-tympanoplasty, especially at high frequencies. In addition, our data demonstrate that changes in distortion product otoacoustic emissions (DPOAEs) result from altered ME transmission in both the forward and reverse direction by a reduction of the effective stimulus levels and less efficient transfer of DPs from the ME into the ear canal. This confirms that DPOAEs can be used to assess both the health of the cochlea and the middle ear. 相似文献
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Perfluoroalkyl substances (PFAS) are highly persistent organic pollutants that have been detected in a wide array of environmental matrices and, in turn, diverse biota including humans and wildlife wherein they have been associated with a multitude of toxic, and otherwise adverse effects, including ecosystem impacts. In the present study, we developed a toxicity assay for embryonic stages of mahi-mahi (Coryphaena hippurus), as an environmentally relevant pelagic fish species, and applied this assay to the evaluation of the toxicity of “legacy” and “next-generation” PFAS including, respectively, perfluorooctanoic acid (PFOA) and several perfluoroethercarboxylic acids (PFECA). Acute embryotoxicity, in the form of lethality, was measured for all five PFAS toward mahi-mahi embryos with median lethal concentrations (LC50) in the micromolar range. Consistent with studies in other similar model systems, and specifically the zebrafish, embryotoxicity in mahi-mahi generally (1) correlated with fluoroalkyl/fluoroether chain length and hydrophobicity, i.e., log P, of PFAS, and thus, aligned with a role of uptake in the relative toxicity; and (2) increased with continuous exposure, suggesting a possible role of development stage specifically including a contribution of hatching (and loss of protective chorion) and/or differentiation of target systems (e.g., liver). Compared to prior studies in the zebrafish embryo model, mahi-mahi was significantly more sensitive to PFAS which may be related to differences in either exposure conditions (e.g., salinity) and uptake, or possibly differential susceptibility of relevant targets, for the two species. Moreover, when considered in the context of the previously reported concentration of PFAS within upper sea surface layers, and co-localization of buoyant eggs (i.e., embryos) and other early development stages (i.e., larvae, juveniles) of pelagic fish species to the sea surface, the observed toxicity potentially aligns with environmentally relevant concentrations in these marine systems. Thus, impacts on ecosystems including, in particular, population recruitment are a possibility. The present study is the first to demonstrate embryotoxicity of PFAS in a pelagic marine fish species, and suggests that mahi-mahi represents a potentially informative, and moreover, environmentally relevant, ecotoxicological model for PFAS in marine systems.