Inhibitor of γ-secretase alleviates middle ear inflammation by regulating Th2 response in OVA-mediated allergic OME in vivo.

Otitis media with effusion (OME) often occurs in infants and young children, which is related to allergic reactions. Notch signaling pathway plays an important role in allergic responses. In this study, we aimed to investigate the role of Notch signaling pathway in the ovalbumin (OVA)-mediated allergic OME in vivo. OVA-induced OME rats were treated with a control vehicle or a γ-secretase inhibitor, N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester (DAPT) suppressing the Notch signaling. We studied the effect of Notch signaling pathway in OME model, including histopathological assessment, the expression of Th1 cytokines (IFN-γ), Th2 cytokines (IL-4, IL-5), key transcription factors (T-bet, GATA-3) by quantitative real-time polymerase chain reaction (qRT-PCR). In addition, the level of Notch ligand (Jagged1) and the downstream target gene Hes1 were also evaluated by qRT-PCR and immunofluorescent staining. We observed that the production of Th2 cytokines was increased, the level of Th1 cytokines was decreased in OME experimental model. Likewise, Th2-cytokine(IL-4)level was reduced, but the level of Th1 cytokines(IFN-γ) was no changes. Additionally, administration of DAPT induced a decrease in the expression of GATA-3 mRNA, however, no influence on T-bet mRNA production. These results suggest that there is an imbalance with Th1/Th2 in OVA-mediated allergic OME. DAPT treatment can block the Notch signaling pathway and relieve the middle ear inflammation through modulating the level of Th2 responses in OVA-induced allergic OME.

Audiological effectiveness of Bonebridge implantation for bilateral congenital malformation of the external and middle ear.

PURPOSE: To evaluate the audiological effectiveness of Bonebridge implantation in patients with bilateral congenital malformation of the external and middle ear. METHODS: Twenty-eight cases [17 boys and 11 girls; median age, 12 years (range 8-36 years)] had unilateral Bonebridge implantation. Audiological tests were performed preoperatively and postoperatively, and included the pure-tone audiometry test, speech discrimination score (SDS), and evaluation of the unaided and aided hearing thresholds in sound fields. For the group of patients aged > 12 years, Mandarin Speech Test Materials were used to determine the SDS. For the other cases, the Mandarin Lexical Neighborhood Test was used. The daily life efficacy was assessed using the Abbreviated Profile of Hearing Aid Benefit (APHAB) questionnaire postoperatively. The t and t' tests were used in the statistical analyses. RESULTS: The hearing threshold with the Bonebridge improved by 25-35 dB HL, compared to that of the unaided condition. The SDS of patients aged > 12 years improved by about 50%; the SDS also improved by 10-20% in the three patients aged < 12 years. According to the APHAB, the mean Bonebridge scores of ease of communication, background noise, and reverberation decreased by 60.3 ± 15.7, 50.2 ± 11.1, and 59.4 ± 7.8, respectively, compared to the preoperative scores, and the Bonebridge score of aversiveness was higher (69.8 ± 10.8) than the unaided score. CONCLUSIONS: The audiological effectiveness of the Bonebridge was significant and noticeable in bilateral congenital malformation of the external and middle ear. The Bonebridge can be an alternative and effective solution for those patients to improve hearing.