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Objectives Cisplatin is employed for chemotherapeutic purposes in several types of adult and pediatric cancer. However, side-effects including nephrotoxicity, ototoxicity, gastrointestinal effects and neuropathy restrict the use of the drug due to their adverse impacts on quality of life. This study aimed to determine whether levosimendan exhibits a protective effect against cisplatin-related ototoxicity in a rat model by means of functional, biochemical and histochemical analysis. Methods The study was employed with 24 female Sprague Dawley rats. After distortion product otoacoustic emissions (DPOAE) tests applied to all rats, rats were randomly assigned into four groups of six animals each. A single intraperitoneal 15 mg/kg dose of cisplatin was administered to Cisplatin group. Levosimendan group received intraperitoneal levosimendan at a dose of 100 mg/kg for five consecutive days. Cisplatin + Levosimendan group received intraperitoneal levosimendan at a dose of 100 mg/kg for five consecutive days and a single intraperitoneal dose of 15 mg/kg cisplatin at 3rd day of the study. Control group received 8 mL/kg/day intraperitoneal saline solution for five consecutive days. The DPOAE test was repeated on the 6th day of the study. All rats were then sacrificed, the cochleas were removed and set aside for biochemical and histopathological analyses. Results A significant increase in levels of Malondialdehyde (MDA) and significantly lower activities of superoxide dismutase (SOD) and Glutathione peroxidase (GPx) were observed at rats of cisplatin group. Administration of levosimendan showed significantly lower cochlear MDA levels, while SOD and GPx activities both increased significantly. The DPOAE test performed at 6th day of the study showed a significant impairment in the signal-noise ratio (SNR) levels of rats in Cisplatin group. The SNR levels of rats treated with levosimendan were significantly higher than those of cisplatin group and were similar to those of the control group. Cisplatin impaired the cochlear structure and a severe Caspase 3 and 8-hydroxy-2' -deoxyguanosine (8-OHdG) immunopositivity was observed at cochlea of the rats of cisplatin group. Administration of levosimendan protected the structure of cochlea and there was a mild Caspase 3 and 8OHdG immunopositivity. Conclusion Our data demonstrate that levosimendan protects hearing against cisplatin-induced ototoxicity and obviates cellular degeneration. It also significantly reduces oxidative stress and apoptosis, probable mechanisms involved in ototoxicity.

Septorhinoplasty is a surgical procedure widely employed by otolaryngologists and plastic surgeons. The purpose of this study was to investigate the effects of a single pre-emptive dose of iv ibuprofen on postoperative pain and opioid consumption in patients undergoing septorhinoplasty.50 patients scheduled for septorhinoplasty were included in this prospective, randomized, double-blinded study. Control group (n = 25) was administered 100 mL iv saline solution 30 min preoperatively, while Ibuprofen group (n = 26) received 800 mg ibuprofen iv. in 100 mL saline solution. Intravenous fentanyl was administered with a Patient Controlled Analgesia device after surgery for postoperative pain management. Postoperative pain was evaluated using a Visual Analogue Scale (VAS) with 0 representing no pain and 10 the worst pain possible.VAS scores at 10, 20, and 30 min and at 1, 2, 4, 8, 12 and 24 h were lower in the ibuprofen group than in the control group (p 0.05). Total fentanyl consumption was lower in the ibuprofen group compared to the placebo group (148.8 ± 86.4 mcq vs 338.00 ± 81.00 mcq), respectively.We suggest that the pre-emptive use of iv ibuprofen at a dosage of 800 mg 30 min before septorhinoplasty will be beneficial in reducing opioid consumption and pain scores.

Allergic rhinitis is an IgE-mediated inflammatory disease which effects 10%-50% of the normal population. The mechanism of its formation and the circadian rhythm of cortisol and melatonin in allergic rhinitis have not been investigated.Salivary levels of melatonin and cortisol were measured by radioimmunoassay in 35 newly diagnosed allergic rhinitis patients and in 23 control subjects matched for age and gender.In the study group; amplitude, baseline and peak levels of salivary melatonin were significantly decreased compared with healty controls (p0.001). No differences were found in the acrophase and the peak duration of salivary melatonin between the study and control groups (p0.05). In the study subjects, the circadian rhythm of cortisol was flattened when compared with the control group. The amplitude and the 24h mean levels of salivary cortisol in the study group were significantly lower than in the control group and the acrophase was delayed in patients compared with control subjects (p0.001).The circadian rhythms of salivary melatonin and cortisol were found to be disrupted in patients with allergic rhinitis. These results may also be contributive data to explain the pathogenesis of allergic rhinitis and also they can be applicable as adjunctive therapeutic tools in the future and melatonin drugs might be an alternative in the therapy of resistant allergic rhinitis patients or allergic rhinitis patients who cannot use cortisol drugs.

Letters regarding the paper “Epidemiological study of the structural alterations present in the nasal cavity associated to the obstructive sleep apnea syndrome (OSAS)”, published on the Brazilian Journal of Otorhinolaryngology 72 (4) July/August 2006. Paper available at: http://www.rborl.org.br/conteudo/acervo/acervo_english.asp?id=3258