The expression of oxidative stress response genes is modulated by a combination of resveratrol and N-acetylcysteine to ameliorate ototoxicity in the rat cochlea.

Aminoglycoside antibiotics are used widely in medicine despite their ototoxic side-effects. Oxidative stress and inflammation are key mechanisms determining the extent and severity of the damage. Here we evaluate the protective effect of a treatment with resveratrol plus N-acetylcysteine on the ototoxic actions of kanamycin and furosemide in the rat. Resveratrol (10 mg/kg) and N-acetylcysteine (400 mg/kg) were administered together to Wistar rats on 5 consecutive days. The second day, a concentrated solution of kanamycin and furosemide was placed on the round window to induce ototoxicity. Hearing was assessed by recording auditory brainstem responses before and 5, 16 and 23 days after the beginning of the treatment. Cochlear samples were taken at day 5 (end of the treatment) and at day 23, and targeted PCR arrays or RT-qPCR were performed to analyze oxidative balance and inflammation related genes, respectively. In addition, the cytoarchitecture and the presence of apoptosis, oxidative stress and inflammation markers were evaluated in cochlear sections. Results indicate that administration of resveratrol plus N-acetylcysteine reduced the threshold shifts induced by ototoxic drugs at high frequencies (≈10 dB), although this protective effect fades after the cessation of the treatment. Gene expression analysis showed that the treatment modulated the expression of genes involved in the cellular oxidative (Gpx1, Sod1, Ccs and Noxa1) and inflammatory (Il1b, Il4, Mpo and Ncf) responses to injury. Thus, co-administration of resveratrol and NAC, routinely used individually in patients, could reduce the ototoxic secondary effects of aminoglycosides.

Current indications for the osteoplastic flap.

INTRODUCTION AND OBJECTIVES: Endoscopic sinus surgery is the technique of choice in most of the frontal sinus diseases, both inflammatory and tumour-related. This is why the external approach using osteoplastic flap (OF) would be limited to cases with a difficult endoscopic approach. Our aim was to review the current indications of the osteoplastic flap in the treatment of frontal sinus pathology, through a retrospective study of patients undergoing this technique. METHODS: We performed a retrospective study of 14 patients who were treated with the osteoplastic flap procedure. All the surgical indication criteria, type of sinus disease, presence or absence of prior endoscopic surgery, surgical findings, complications and recurrence were reviewed. RESULTS: The pathologies found were 1 osteoma (7.1%), 3 inverted papilloma (21.4%) and 10 mucoceles (71.4%). Nine patients had a prior endoscopic surgery and 10 patients had an orbital dehiscence (9 mucocele, 1 papilloma). Frontal osteoma was Grade IV and the papilloma cases were Krouse Stage III. Surgical revision was required for 21.4%. CONCLUSIONS: The main indications for an OF in patients with inflammatory disease are lateral extension and frontal recess neo-osteogenesis. In osteoma cases, it depends on the size of the tumour. In inverted papilloma cases, the indication is multifocal implantation with origin in the anterior and lateral wall. In all cases, performing the osteoplastic flap must be individualised.

Direct drug application to the round window: a comparative study of ototoxicity in rats.

OBJECTIVE: To assess the validity of inducing ototoxicity in rats by applying a sponge soaked in kanamycin and furosemide on the round window. STUDY DESIGN: Basic, randomized, nonblind experimental study. SETTING: Animal models of cochlear damage and reliable methods of local drug delivery are fundamental to study hearing loss and to design new therapies. SUBJECTS AND METHODS: Four experimental groups of six Wistar rats with different methods of drug administration were used: (1) injection of subcutaneous kanamycin (400 mg/kg) and intravenous furosemide (100 mg/kg); (2) local application of a sponge soaked in saline close to the round window; (3) animals for which the sponge was soaked in a solution containing kanamycin (200 mg/mL) and furosemide (50 mg/mL); and (4) sham-operated rats. The tympanic bulla was exposed using a ventral approach, and a bullostomy was performed to visualize the round window membrane. Cochlear function was assessed by measuring the auditory brainstem response, and hearing thresholds in response to click and tone burst stimuli were determined as peak and interpeak latencies. At the end of the study, cochlear histology was analyzed. RESULTS: Systemic administration of kanamycin and furosemide induced profound hearing loss and severe hair cell damage. Local delivery of these ototoxic drugs caused comparable damage but avoided the systemic side effects of the drug. Sham-operated and saline control animals did not experience functional alterations. CONCLUSION: Situating a sponge soaked in kanamycin and furosemide on the round window membrane through the ventral approach is a reliable method to provoke local ototoxicity in rats.