The hydrops ex vacuo mechanism relating Eustachian (ET) dysfunction to otitis media with effusion (OME) descried by Politzer has been more completely developed by investigators at our Center. This mechanism includes four casually related, temporally sequential events: 1) the unabated absorption of middle ear (ME) gases (ET dysfunction); 2) a resultant ME under-pressure ; 3) an increased permeability of the mucosal vasculature, and 4) a transduction of fluid into the ME space. The mechanism is supported by studies of the behavior of other biological gas pockets and is consistent with the predictions of mathematical mod4ls of ME pressure regulation. Recent studies conducted by us showed that hydrops ex vacuo is a valid explanation for the development and persistence of OME under appropriate conditions. However, the mechanism responsible for transducing the biological signal(s) associated with the under-pressure and initiating ME mucosal inflammation is not known, and has not been studied. While osmotic and hydrostatic effects have been implicated as co-factors, biochemical assays document the presence within the provoked effusion of both pro-inflammatory cytokines and other chemicals that may have a transducing function as was demonstrated for OME of other etiologies. Because transduction of this signal initiates the inflammatory process, it represents a potential target for other etiologies. Because transduction of this signal initiates the inflammatory process, it represents a potential target for therapies designed to present mucosal inflammation and OME. Therefore, the primary goal of this project is to define the mechanism for signal transduction including: the nature of the signal (e.g. under-pressure, altered gas composition), the sensory components for signal identification (e.g. osmotic, chemoreceptive, baroreceptive), the early cellular response to the signal (e.g. synthesis of cytokines gap juncture disruption), the role of inflammatory chemicals as secondary signals (e.g. lipid based inflammatory mediators, cytokines) and the physiological response of the mucosa to the primary and secondary signals (e.g. gap juncture formation, altered transmucosal potentials, fluid transduction, inflammatory cell influx). The experiments will involve in vitro (cell culture) and in vivo model systems, and will include histopathological, biochemical (proteins, mRNA, lipids) and physiological outcomes. As in past studies, pharmacological probes will be used to identify the role of specific inflammatory mediators in this process. The biochemical changes that promote healing of the mucosa or cause the purported ME complications of tympanostomy tubes are not yet known, and will be investigated using the above techniques and methods.
| Doyle, William J; Swarts, J Douglas (2010) Eustachian tube-Tensor veli palatini muscle-cranial base relationships in children and adults: an osteological study. Int J Pediatr Otorhinolaryngol 74:986-90 |
| Doyle, William J; Yuksel, Sancak; Banks, Juliane et al. (2007) Directional asymmetry in the measured nitrous oxide time constant for middle ear transmucosal gas exchange. Ann Otol Rhinol Laryngol 116:69-75 |
| Doyle, William J (2007) The mastoid as a functional rate-limiter of middle ear pressure change. Int J Pediatr Otorhinolaryngol 71:393-402 |
| Li-Korotky, Ha-Sheng; Kelly, Lori A; Piltcher, Otavio et al. (2007) Evaluation of microbial RNA extractions from Streptococcus pneumoniae. J Microbiol Methods 68:342-8 |
| Chad Kanick, S; Kasi, Sundeep; Douglas Swarts, J et al. (2006) Accuracy of CO2 conductance predicted using a morphometric model of the middle ear mucosa. Acta Otolaryngol 126:1252-9 |
| Kanick, Stephen Chad; Doyle, William J; Ghadiali, Samir N et al. (2005) On morphometric measurement of oxygen diffusing capacity in middle ear gas exchange. J Appl Physiol 98:114-9 |
| Chen, Anton; Li, Ha-Sheng; Hebda, Patricia A et al. (2005) Gene expression profiles of early pneumococcal otitis media in the rat. Int J Pediatr Otorhinolaryngol 69:1383-93 |
| Yuksel, Sancak; Doyle, William J; Banks, Juliane et al. (2005) Nasal prostaglandin challenge increases N2O exchange from blood to middle ear. Auris Nasus Larynx 32:29-32 |
| Casselbrant, Margaretha L; Mandel, Ellen M; Rockette, Howard E et al. (2004) The genetic component of middle ear disease in the first 5 years of life. Arch Otolaryngol Head Neck Surg 130:273-8 |
| Li-Korotky, Ha-Sheng; Swarts, J Douglas; Hebda, Patricia A et al. (2004) Cathepsin gene expression profile in rat acute pneumococcal otitis media. Laryngoscope 114:1032-6 |
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