Protective effect of N-acetylcysteine against cisplatin ototoxicity in rats: a study with hearing tests and scanning electron microscopy.

INTRODUCTION: Ototoxicity is a health problem appearing after powerful treatments in serious health conditions. It is sometimes inevitable when treatment of the serious disease is required. Cisplatin is an antineoplastic agent which was investigated previously to reveal increased nitrogen and reactive oxygen radicals that damages hair cells, resulting in ototoxicity. N-acetylcysteine, previously shown to decrease ototoxicity caused by different agents, is known to be a powerful in vitro antioxidant. Probably N-acetylcysteine, in addition to its antioxidant effect, blocks a cascade where reactive oxygen species result in apoptosis in the cochlea. OBJECTIVES: The possible preventive effect of N-acetylcysteine in cisplatin ototoxicity was studied with auditory brain stem responses, otoacoustic emissions, and histopathological investigation of the cochlea in a scanning electron microscopy. METHODS: This study was conducted on 21 Wistar Albino rats in four groups. 1mL/kg/day three times in total intraperitoneal (i.p.) Saline (n=5), 500mg/kg/day i.p. three times in total N-acetylcysteine (n=5), i.p. 15mg/kg cisplatin alone (single dose) (n=5) and i.p. 15mg/kg cisplatin plus 500mg/kg/day N-acetylcysteine (n=6) were administered. The rats were anesthetized to study the hearing tests before and after the experiment. The rats were sacrificed to investigate the cochleas by scanning electron microscopy. RESULTS: Auditory brain stem responses and otoacoustic emissions values were attenuated in the cisplatin group. The group that received N-acetylcysteine in addition to cisplatin had better auditory brain stem responses thresholds and otoacoustic emissions. The samples obtained from the cisplatin group showed surface irregularities, degeneration areas, and total or partial severe stereocilia losses. The changes were milder in the cisplatin+N-acetylcysteine group. CONCLUSION: Cisplatin ototoxicity can be detected by auditory brain stem responses and otoacoustic emissions testing in rats. N-acetylcysteine may protect the cochlear cells from histopathological changes. We concluded that N-acetylcysteine given 4h after cisplatin injection has a potential otoprotective effect against cisplatin ototoxicity. which suggests it could be used in clinical trials.

Research of genetic bases of hereditary non-syndromic hearing loss.

AIM: Hearing loss is the most common sensory disorder that affects approximately one per 1000 live births. With this project, we aimed to identify gene variants that were common causes of hearing loss in Turkey to contribute to the planning of genetic screening programs for hearing loss, as well as to improve genetic counseling to affected families. MATERIAL AND METHODS: Twenty-one families with at least two affected individuals and parental consanguinity who presented with non-syndromic severe-to-profound sensorineural hearing loss were included in this study. We first screened for mutations in GJB2 and mitochondrial DNA 12S RNA genes. Subsequently, we genotyped the TMIE c.250C>T and SNP markers flanking the SLC26A4, MYO7A, MYO15A, OTOF, CDH23, TMIE, TECTA, PCDH15, TMC1, TMPRSS3, TMHS genes in the remaining twelve families without mutations in GJB2. RESULTS: Screening for mutations in GJB2 gene showed c.[35delG];[35delG] mutation in four families, c.[35delG];[507C>A] mutation in two families, c.[35delG];[-23+1G>A] mutation in one family, and c.457G>A heterozygous mutation in one family. Genotyping SNP markers showed the c.[250C>T];[250C>T] mutation in TMIE in one family. A homozygous region with SNP genotypes was detected with the OTOF gene in one family, the TMPRSS3 gene in another family, and also a homozygous region was detected with TMHS, OTOF, and TMPRSS3 genes in another family. CONCLUSIONS: Further research will be required to determine the genetic bases of hearing loss in families with non-syndromic hearing loss.

N-acetylcysteine Prevents Gentamicin Ototoxicity in a Rat Model.

OBJECTIVE: The possible preventive effect of N-acetylcysteine (NAC) in gentamicin ototoxicity was studied with auditory brain stem responses (ABRs), otoacoustic emissions (OAEs), and histopathological investigation of the cochlea. MATERIALS AND METHODS: This study is conducted on 36 rats in three groups. Gentamicin, gentamicin plus NAC, and NAC alone were intraperitoneally administered for 15 days. The rats were sacrificed to study the cochleas after testing hearing levels. RESULTS: ABR thresholds and OAEs were attenuated in the gentamicin group, in which apoptosis was detected with histopathological investigation. The group that received NAC in addition to gentamicin had better ABR thresholds and better OAEs. The histopathological evidence of apoptosis in was considerably less in this group. CONCLUSION: Gentamicin ototoxicity can be detected by ABR and OAE testing in rats, and NAC may protect the cochlear cells from apoptosis.

Survivin expression correlates with nodal metastasis in T1-T2 squamous cell carcinoma of the tongue.

In this study, the correlation between neck metastasis and recurrence was investigated by studying specimens of tongue squamous cell carcinoma patients immunohistochemical with survivin antibodies in the primary biopsy. A retrospective review was conducted at the Academic University Hospital. 46 patients who had squamous cell carcinoma of the tongue, who underwent various types of glossectomy and neck dissections between 1991 and 2008, were evaluated. The patient's sex, TNM staging, differentiation and recurrence rates were analyzed. There were 20 T1 patients and 26 T2 patients; 27 of the patients were N0 and 19 had metastatic lymph nodes in the neck. Survivin antibodies were applied with streptavidin-biotin method to the sections that were prepared from the primary tumor biopsy specimens of the patients. The correlation between neck metastasis and recurrence and survivins' immunohistochemical staining was analyzed with statistical methods. There were no significant differences between the patient's age, sex, tumor's T stage, tumor differentiation and survivin staining density. Survivin staining was positive in 15 (79 %) of 19 patients with neck metastasis, while it was positive in 16 (59 %) of 27 patients without neck metastasis. Eleven (79 %) of the 14 patients who had recurrence and all 6 patients who had neck recurrence only were stained by survivin. Expression of nuclear and cytoplasmic survivin can be a useful marker for predicting cervical lymph node metastasis in T1-T2 tumors in tongue SCC.

Assessment of early atherosclerotic findings in patients with nasal polyposis.

OBJECTIVE: To investigate early markers of atherosclerosis in patients with nasal polyposis (NP) through measurements of carotid artery intima-media thickness (CIMT), flow-mediated vasodilatation (FMD) of the brachial artery and serum paraoxonase-1 (PON-1) activity. METHODS: Forty-five patients with NP were included in the study group and 45 healthy individuals in the control group. The diagnosis of patients with NP was predicated on anterior rhinoscopy, endoscopic nasal examination and coronal paranasal sinus computed tomography (CT). Measurements of CIMT and FMD of the brachial artery were performed by high-resolution ultrasonography. Serum PON-1 activity was evaluated by measuring the rate of paraoxon hydrolysis. RESULTS: Mean CIMT values were found to be increased in the NP group compared to the control group. However, mean FMD % values and serum PON-1 activity were significantly lower in the NP group compared to the control group. Moreover; the endoscopic polyps' scores and paranasal sinus CT scores were positively correlated with CIMT and negatively correlated with FMD % values and PON-1 activity. Disease duration also was positively correlated with CIMT and negatively correlated with FMD % values. CONCLUSION: Impaired FMD, increased CIMT and decreased serum PON-1 activity may be considered to be risk factors for accelerated atherosclerosis in patients with NP who may have subclinical atherosclerosis and be at risk for cardiovascular events in the future.

The ototoxic effect of intratympanic terbinafine applied in the middle ear of rats.

BACKGROUND: Otomycosis is defined as an infection of the external ear canal with fungal agents. The treatment of the disease is cleansing and drying of the external ear canal, identification and treatment of any predisposing factors and application of topical antifungal agents. Terbinafine is used as an antifungal agent to treat otomycosis. We proposed to investigate the probable ototoxic effect of terbinafine solution on auditory brain stem response (ABR) and distortion product otoacoustic emission (DPOAE) when applied intratympanically in the middle ear of rats. METHODS: The experiment was performed on 30 female Wistar albino rats. Thirty animals were divided into three groups of 10 animals each. 1% terbinafine solution was administered to the first group (group T). The second group (group G) was administered 40 mg/ml gentamicin solution (ototoxic control). The third group (group S) was administered saline solution (negative control). Baseline DPOAE measurements and ABR testing from the left ears were obtained from the animals in all groups under general anesthesia. Ear solutions were applied in the middle ear intratympanically with a dental needle. Treatment was initiated after baseline measurements and repeated once every two days for fifteen days. RESULTS: Pre and post-treatment DPOAE responses for all tested frequencies of group T and Group S showed no statistically significant difference. However, the group G demonstrated a significant change in ABR thresholds and DPOAE responses. CONCLUSIONS: Terbinafine solution is a broad spectrum antifungal agent effective in the treatment of otomycosis. The present study demonstrated that its direct administration in the middle ear of rats does not affect inner ear function as measured by ABR and DPOAE responses.

Evaluation of treatment efficacy in patients with minimal nasal septum deviation and concha bullosa using the nasal obstruction symptom evaluation scale.

OBJECTIVES: This study aims to compare the treatment efficacy of middle turbinate lateral lamella resection alone with septoplasty plus middle turbinate lateral lamella resection for nasal stuffiness in two patient groups using the nasal obstruction symptom evaluation (NOSE) scale in patients with concomitant minimal nasal septum deviation and concha bullosa. PATIENTS AND METHODS: A total of 80 patients who had minimal nasal septum deviation and concha bullosa at the middle turbinate were included in this study. Of these patients, 40 patients underwent middle turbinate lateral lamella resection, while 40 patients underwent middle turbinate lateral lamella resection plus septoplasty under general anesthesia. Complaints of nasal stuffiness in patients included were evaluated with the NOSE scale before the operation and three months after the operation. RESULTS: When preoperative and postoperative NOSE scale parameters were compared, all parameters statistically significantly improved postoperatively in both groups (p<0.05). The total NOSE scores were decreased significantly after surgery. CONCLUSION: Middle turbinate lateral lamella resection alone is as efficient as septoplasty plus middle turbinate lateral lamella resection for the treatment of symptomatic nasal stuffiness in selected patients.

Efficacy of a single preoperative dose of pregabalin for postoperative pain after septoplasty.

We aimed to investigate the role of preoperative single dose of pregabalin for attenuating postoperative pain and analgesic consumption in patients undergoing septoplasty. One hundred forty-three patients with ASA physical status I who underwent elective septoplasty were included in this prospective, randomized, and controlled study. Subjects were randomized to receive pregabalin 75 mg, pregabalin 150 mg, and control group. All the medications were administered orally 1 hour before surgery. A standard septoplasty technique was used for all patients. Postoperative pain intensity was evaluated by a 0- to 100-mm horizontal visual analog scale (VAS) (0, no pain; 100, worst imaginable pain). Total analgesic consumption 1 to 24 h after operation was also recorded.Visual analog scale scores in the 1st, 2nd, 4th, 6th, 12th, and 24th hour were significantly decreased in 75 and 150 mg pregabalin group compared with the control group, and VAS scores in the 12th and 24th hour were significantly decreased in pregabalin 150 mg compared with 75 mg. The 24th total analgesic consumption was significantly decreased in pregabalin 75 mg and 150 mg groups compared with the control group.In conclusion, a single preoperative oral dose pregabalin 75 or 150 mg is an effective method for reducing postoperative pain and total analgesic consumption in patients undergoing septoplasty.

Protective effect of thymoquinone against cisplatin-induced ototoxicity.

The aim of this study was to investigate the potential protective effect of thymoquinone against cisplatin-induced ototoxicity. This study is a prospective, controlled experimental animal study. Experiments were performed on 30 healthy female Sprague-Dawley rats. Thirty animals were divided into three groups of 10 animals each. Group 1 received an intraperitoneal (i.p.) injection of cisplatin 15 mg/kg. Group 2 received i.p. thymoquinone 40 mg/kg/day for 2 days prior to cisplatin injection and third day i.p. cisplatin 15 mg/kg was administered concomitantly. Group 2 continued to receive i.p. thymoquinone until fifth day. Group 3 received i.p. thymoquinone 40 mg/kg/day for 5 days. Pretreatment distortion product otoacoustic emissions (DPOAE) and auditory brain stem responses (ABR) testing from both ears were obtained from the animals in all groups. After the baseline measurements, drugs were injected intraperitonally. After an observation period of 3 days, DPOAE measurements and ABR testing were obtained again and compared with the pretreatment values. There was no statistically significant difference between pre and post-treatment DPOAE responses and ABR thresholds group 2 and 3. However, group 1 demonstrated significant deterioration of the ABR thresholds and DPOAE responses. Our results suggest that DPOAE responses and ABR thresholds were preserved in the cisplatin plus TQ-treated group when compared with the group receiving cisplatin alone. According to these results, cisplatin-induced ototoxicity may be prevented by thymoquinone use in rats.

Impact of septoplasty on mean platelet volume levels in patients with marked nasal septal deviation.

Nasal septal deviation (NSD) is a very common cause of recurrent and chronic nasal obstruction. Chronic nasal obstruction leads to increased upper respiratory tract resistance, and also upper respiratory tract resistance leads to chronic hypoxia and hypercarbic because of alveolar hypoventilation. Chronic hypoxia and hypercarbia show tendency for hypercoagulopathy.Mean platelet volume (MPV), the most commonly used measure of platelet size, is a potential marker of platelet reactivity. Large platelets that contain more dense granules are enzymatically and metabolically more active and have greater prothrombotic potential. In previous studies, increased MPV was demonstrated in hypertension, unstable angina pectoris, myocardial infarction, stroke, and obstructive sleep apnea.We aimed to determine whether MPV levels are elevated in patients with marked NSD (MNSD) compared with healthy controls. In addition, we tried to find out the effect of nasal septoplasty on MPV levels. We found that the MPV levels were significantly higher in the MNSD group than in the control healthy group, and also we found that MPV levels were significantly decreased in the MNSD group after septoplasty operation.In conclusion, in our knowledge, this is the first study investigating MPV levels in patients with MNSD. Increased platelet activation may be related to increase the cardiovascular risk in patients with MNSD. Our results suggest that MPV, a determinant of platelet activation, is elevated in patients with MNSD, and the increase in MPV levels of the cases with MNSD could be treated by septoplasty.

Correlation between hearing loss and peritonitis frequency and administration of ototoxic intraperitoneal antibiotics in patients with CAPD.

AIM: Aminoglycosides have been used in the treatment of CAPD peritonitis despite their potential risk for ototoxicity. The ototoxicity risk of intraperitoneally administered aminoglycosides has been investigated by a number of studies. However, their results are somewhat conflicting. The aim of the present study was to examine the frequency of hearing loss and the correlation between the repeated doses of aminoglycosides and hearing loss in CAPD peritonitis therapy. METHODS: Hearing functions of the CAPD patients who had developed peritonitis and had been treated with various antibiotics including aminoglycosides were compared with those CAPD patients who had never developed peritonitis. Threshold values for hearing were determined through "pure tone audiometry" measurements. RESULTS: Hearing threshold levels of the patients with history of peritonitis were found to be significantly higher in both lower [pure tone averages - 1 (PTA-1)] and higher [pure tone averages - 2 (PTA-2)] frequencies, when compared to the ones with no history of peritonitis (p values were 0.001 and 0.007, respectively). CONCLUSION: The present study showed that intraperitoneal aminoglycoside administration in CAPD patients is associated with the development of hearing loss. The severity of hearing loss may range from mild hearing loss to profound deafness. A remarkable correlation exists between the severity of the hearing loss and the repeated and total aminoglycoside dose received.

Castleman's disease as an unusual neck mass: case report.

Castleman's disease is a rare, benign disease of unknown cause that induces reactive lymph node hyperplasia, most commonly in the mediastinum. It has 2 histologic subtypes: hyaline vascular and plasma cellular. A definitive diagnosis necessitates tissue biopsy. A specimen may be even misdiagnosed as lymphoma in frozen section. Surgery is the treatment of choice for the solitary form, whereas chemotherapy, radiotherapy, and steroids are proposed for the multicentric type. A neck mass diagnosed as Castleman's disease in a 48-year-old woman is reported.