Leupeptin, a calpain inhibitor, protects inner ear hair cells from aminoglycoside ototoxicity.

Inner ear hair cells play a major role in the auditory pathway that converts sound stimulation into electrical signals, and then into a neural code. However this function is often lost by aminoglycoside ototoxicity. The injury of inner ear hair cells from aminoglycoside treatment is considered apoptosis, and caspase is an important participant in the apoptosis pathway in many organs. It has been reported that calpain, a calcium-dependent protease, is essential for mediation and promotion of cell death. The purpose of the present study was to investigate effects of caspase and calpain inhibitors on the inner ear hair cells after aminoglycoside treatment, and to explore the cell death pathway. Cochlea explant cultures were prepared from mice of postnatal 6 days, cultured with neomycin and/or protease inhibitors, and then stained with phalloidin-fluorescein isothiocyanate (phalloidin-FITC), which was used as a marker to identify surviving hair cells. We demonstrated that neomycin (0.1-1 mM) reduced the number of outer hair cells in a dose-dependent manner. Furthermore, we showed that leupeptin, a calpain inhibitor, significantly protects against the neomycin-induced loss of outer hair cells, whereas a caspase inhibitor was effective only against a lower concentration of neomycin (0.2 mM). Using the TdT-mediated dUTP-biotin nick and labeling method, we also found that a calpain inhibitor, but not a caspase inhibitor, prevents apoptotic DNA fragmentation after treatment with 1 mM neomycin. These results suggest that calpain, rather than caspase, may be responsible for apoptosis induced by aminoglycoside. Thus, leupeptin may prevent hearing loss from aminoglycoside ototoxity.

Inflammatory pseudotumour (plasma cell granuloma) arising in the maxillary sinus.

CONCLUSIONS: Inflammatory pseudotumours in the maxillary sinus may present as malignant tumours and manifest locally aggressive features characteristic of such tumours. Despite their locally destructive features, they pursue a benign course after local excision. OBJECTIVE: Inflammatory pseudotumour (plasma cell granuloma) is an uncommon non-neoplastic lesion comprising a proliferation of spindle myofibroblasts and chronic inflammatory cells. Despite its benign histopathological nature, it may exhibit aggressive behaviour that is yet to be characterized in the head and neck area. MATERIAL AND METHODS: We present the cases of two adult patients with inflammatory pseudotumour arising from the maxillary sinus. Immunohistochemistry and polymerase chain reaction for immunoglobulin from tissue sections were performed to confirm the polyclonality of the infiltrating plasma cells. RESULTS: CT and MRI disclosed expansive soft masses eroding surrounding soft and bony tissues. Histopathologically, the lesions were unencapsulated and composed of numerous plasma cells, histiocytes and spindle cells with minimal nuclear pleomorphism.