Topiramate and darbepoetin alpha ameliorate bilirubin-induced neuronal cell damage.

OBJECTIVE: The aim of this study was to determine whether prophylactic darbepoetin alpha and/or topiramate administration could prevent bilirubin neurotoxicity (BNTx) in experimental model of kernicterus. MATERIALS AND METHODS: A total of 60 Wistar albino rat puppies with experimental kernicterus model were included in the study. The Kernicterus was established administering a bilirubin injection via a cisterna magna puncture 30 minutes after ip drug injection. The puppies were divided into five groups with 12 in each group as shown below: a control group, bilirubin group, darbepoetin alpha group, topiramate group and darbepoetin alpha+ topiramate group. Darbepoetin alpha and/or topiramate were administered on day 5 intraperitoneally (ip). At the 6th and 24th hours, bilirubin induced neurological dysfunction (BIND) score was used to assess behavioral changes. Hearing functions were evaluated on days 10 and 28. On day 30, the Water Maze water tank test was implemented to evaluate spatial memory. The rats were sacrificed on days 6 and 34 and apoptosis in the globus pallidus and hippocampus was examined. RESULTS: The BIND score was improved following darbepoetin alpha treatment. Neither darbepoetin alpha nor topiramate therapy ameliorate spatial memory. There were no significant differences between groups in terms of the auditory brainstem response (ABR). The combined use of darbepoetin alpha and topiramate lead to slight decrease in apoptosis. CONCLUSIONS: Darbepoetin alpha or topiramate administration ameliorates bilirubin induced neurological dysfunction in experimental model of kernicterus.

Protective effect of acetyl-l-carnitine against cisplatin ototoxicity: role of apoptosis-related genes and pro-inflammatory cytokines.

OBJECTIVES: Cisplatin is an anti-neoplastic agent treatment with which causes many side effects including ototoxicity. The aim of this study was to investigate whether acetyl-L-carnitine would have protective effects on cisplatin-induced ototoxicity in vitro, and if present, to reveal roles of apoptotic gene expressions and pro-inflammatory cytokines. MATERIALS AND METHODS: House Ear Institute-Organ of Corti 1 cell line was used for this study. Apoptotic genes were evaluated with an apoptosis PCR array and pro-inflammatory cytokine levels were measured using ELISA. RESULTS: Apoptotic cell death reduced by around 22% with acetyl-L-carnitine-cisplatin treatment compared to cisplatin alone. Genes displaying increase in expression of apoptosis, related to cisplatin treatment, were Casp8, Bcl10, Bcl2, Bcl2l1, Bcl2l2, Bid, Naip1, Bnip3l, Card6, Pak7, Cd40, Trp 53inp1, Cideb and Cd70. The acetyl-L-carnitine-cisplatin combination caused reduced expression of genes Casp8, Fas, Casp1, Tnfrsf11b, Tnfrsf10b induced by cisplatin. Acetyl-L-carnitine-cisplatin also caused reduced levels of IL-6, IL-1ß and TNF-α, pro-inflammatory cytokines, induced by cisplatin. CONCLUSION: Protective mechanisms of aceytl-L-carnitine against cisplatin induced apoptosis, mainly due to activation of anti-apoptotic Bcl family members' genes, and in an Akt-related gene expression dependent manner. This is the first study to indicate that acetyl-L-carnitine can be an effective agent against cisplatin ototoxicity in auditory cells, with induction of anti-apoptotic gene expression and attenuating levels of pro-inflammatory cytokines.

Results of multiple-frequency tympanometry measures in normal and otosclerotic middle ears.

Tympanometry is a non-invasive, quick, and inexpensive method for examining the middle-ear function. Its limited value in differentiating otosclerotic from normal middle ears caused researchers to develop new methods for evaluation of middle ears. Resonant frequency had been found to be higher in otosclerotic middle ears than normals. We conducted multiple-frequency tympanometry measurements in 25 surgically confirmed otosclerotic ears and 100 normal ears. Mean middle-ear resonant frequency for the otosclerotic group was found to be 1190 Hz and mean middle-ear resonant frequency of the control group was 934.6 Hz (p<0.001). With a cut off value of 1025 Hz (based on 95% confidence interval), sensitivity was 80% and specificity was 82%. The present findings confirm the advantage of the resonant frequency estimation over conventional tympanometry in detecting middle-ear status and mechanics in patients with otosclerosis. As a conclusion, detecting resonant frequency when evaluating patients for otosclerosis must be an essential part of examination. Nevertheless, further investigation is necessary for better diagnosis of otosclerosis preoperatively.

Long-term outcome of neonatal hyperbilirubinaemia: subjective and objective audiological measures.

Neonatal hyperbilirubinaemia is a common cause of early onset sensorineural hearing loss. There is no exact method to detect the extent of the neurotoxicity of bilirubin. On the other hand, the auditory pathway is known to be one of the most sensitive parts of the central nervous system (CNS) to this toxic agent. This prospective follow-up study was performed to evaluate and compare the factors related to the hearing of neonates with severe hyperbilirubinaemia and an age-matched control group. Both of these groups were tested using auditory brainstem response (ABR) as well as evoked otoacoustic emissions. Additionally, both of these groups of children were evaluated subjectively using an early speech-language-communication evaluation questionnaire. There was no significant difference in either objective (ABR and evoked otoacoustic emission) or subjective assessment (questionnaire) between the study and control groups. Furthermore, no correlation between serum total bilirubin levels and ABR latencies or thresholds was found within the study group.