Antioxidant treatment with coenzyme Q-ter in prevention of gentamycin ototoxicity in an animal model

Aminoglycosides, such as gentamycin, are well known ototoxic agents. Toxicity occurs via an activation process involving the formation of an iron-gentamycin complex with free radical production. Antioxidants like Q-ter (a soluble formulation of coenzyme Q10, CoQ10), can limit or prevent cellular ototoxic damage. The present study was designed to investigate the possible protective effects of Q-ter on gentamycin ototoxicity in albino guinea pigs (250-300 g). Animals were divided into five experimental groups: I, a sham control group given an intra-peritoneal (I.P.) injection of 0.5 ml saline (SHAM); II, gentamycin group (GM), treated with an injection of gentamycin (100 mg/ kg); III, gentamycin + Q-ter group (GM+Q-ter), treated with gentamycin (same dose as group II) and an I.P. injection of coenzyme Q10 terclatrate (Q-ter) at 100 mg/kg body weight; IV, injected with gentamycin (100 mg/kg) plus saline; V, treated with Q-ter alone (100 mg/ kg). All animals were treated for 14 consecutive days. Auditory function was evaluated by recording auditory brainstem responses (ABR) at 15 and 30 days from the beginning of treatment. Morphological changes were analyzed by rhodamine-phalloidine staining. Gentamycininduced progressive high-frequency hearing loss of 45-55 dB SPL. Q-ter therapy slowed and attenuated the progression of hearing loss, yielding a threshold shift of 20 dB. The significant loss of outer hair cells (OHCs) in the cochlear medio-basal turn in gentamycin-treated animals was not observed in the cochleae of animals protected with Q-ter. This study supports the hypothesis that Q-ter interferes with gentamycin-induced free radical formation, and suggests that it may be useful in protecting OHC function from aminoglycoside ototoxicity, thus reducing hearing loss

La diagnosi audiologica precoce dell’ipoacusia dell’età pediatrica

Nell’ambito delle ipoacusie infantili permanenti, la diagnosi audiologica precoce rappresenta il presupposto per l’attivazione di un adeguato programma abilitativo, in modo da prevenire o limitare i noti effetti che la deprivazione uditiva determina sullo sviluppo del linguaggio e delle abilità cognitive nel bambino. Nella diagnosi audiologica possono riconoscersi schematicamente tre fasi: l’identificazione dei soggetti a rischio, la definizione dei caratteri dell’ipoacusia, la verifica dell’appropriatezza della diagnosi stessa e dell’abilitazione. La strategia ed i metodi della diagnosi audiologica sono ben definiti e prevedono l’integrazione dei dati provenienti dai metodi obiettivi, con quelli clinici e comportamentali. A fronte di una sostanziale efficacia delle procedure e di un diffuso consenso sul loro impiego e sulla loro interpretazione, esistono varie criticità rispetto al conseguimento di tale obiettivo, che saranno affrontate in questo lavoro

Ipoacusia e declino cognitivo: revisione della letteratura

La perdita dell’udito legata all’età o presbiacusia è un deficit correlato al processo irreversibile di invecchiamento che riconosce una patogenesi multifattoriale. Crescenti osservazioni hanno collegato la presbiacusia a una rapida progressione del declino cognitivo e incidentalmente con la demenza. Molti aspetti della vita quotidiana degli anziani sono stati collegati alle loro capacità uditive, mostrando che la perdita uditiva incide sulla qualità della vita, i rapporti sociali, le capacità motorie, gli aspetti psicologici, la funzione e la morfologia di specifiche aree cerebrali. Studi epidemiologici e clinici confermano l’ipotesi di un legame tra queste condizioni e questo lavoro ha lo scopo di fare il punto sui meccanismi patogenetici che sostengono tale associazione. Lo sforzo di un lavoro congiunto tra otorinolaringoiatri, audiologi, neurologi e cognitivisti è quello di chiarire gli aspetti comuni, le possibilità di diagnosi e di intervento precoce al fine di ridurre gli effetti dell’uno sull’altro di questi processi degenerativi. Le osservazioni sperimentali e cliniche si concentrano su differenti aspetti: in primo luogo la deprivazione uditiva per lungo tempo può avere un impatto negativo sulle prestazioni cognitive diminuendo la qualità della comunicazione che porta all’isolamento sociale e la depressione e quindi facilitare la demenza. Al contrario, le capacità cognitive limitate possono ridurre le risorse cognitive disponibili per la percezione uditiva, aumentando così gli effetti della perdita dell’udito. Inoltre, questa associazione può rappresentare la conseguenza di una ‘causa comune’ nella patogenesi del deficit uditivo e del sistema nervoso centrale. Infatti, molti dei fattori eziopatogenetici sono comuni, quali le cause microvascolari della malattia (es. diabete, aterosclerosi, ipertensione). La sfida di questi anni è quella di aumentare le conoscenze sui rapporti tra invecchiamento cerebrale e cognitivo ed ipoacusia, grazie anche ai progressi del neuroimaging. Sorprendentemente pochi dati sono stati pubblicati sull’utilità delle protesi acustiche nel cambiare la storia naturale di declino cognitivo. La protesizzazione e gli impianti cocleari possono migliorare le attività sociali e la sfera emotiva, la comunicazione e quindi più in generale la funzione cognitiva, con un globale impatto positivo sulla qualità della vita. Lo scopo di questo lavoro è quello di fornire le informazioni attualmente disponibili in letteratura su rapporto tra declino cognitivo e deficit uditivo nell’anziano, fornendo nuovi spunti di ricerca per il futuro

Transient evoked otoacoustic emissions (TEOAEs) in new-borns: normative data

Objective: Early diagnosis and rehabilitation of congenital hearing loss are mandatory in order to achieve a satisfactory linguistic and cognitive development. A universal hearing screening in order to identify congenital hearing losses before 3 months of age is required. Methods: TEOAEs are an easy to perform, short lasting, not invasive and low-cost test with a high sensitivity. 320 at term new-borns (640 ears) without any risk factor for hearing loss underwent TEOAEs. The new-borns were screened 3 days after birth. Those who failed the first test were retested when possible before the discharge from the hospital. ABR was performed 3 months later in cases who failed TEOAE. Results: The median TEOAE sampling time was 98 s, the median test duration was 14 min. The mean stimulus amplitude was 80 dB peSPL in the left ear and 81 dB peSPL in the right ear, noise levels within the external meatus during sampling were 44 dB SPL on the right ear and 43 dB SPL on the left one, noise contained within the response (A-B difference) was 8.65 dB SPL in the left ear and 8.74 dB SPL in the right ear, mean TEOAEs amplitudes were 21.49 dB SPL and 21.78 dB SPL in the right and left ear respectively, the mean lower and upper limit of the spectrum being 678 and 5720 Hz. According to these criteria 494/640 ears (77.2%) passed the test at the first recording, while TEOAEs resulted to be absent in 146/640 ears (22.8%). A retest was performed successfully before the discharge from the Hospital in 30/640 ears (4.7%). An ABR recording within the third month of life was scheduled as out-patient in the 58 new-borns (116 ears, 18.2%) who failed the test. 18 of them (36 ears, 5.6%) did not complete the program, 19 new-borns (38 ears, 11.8%) showed a normal ABR, while two new-borns (four ears, 0.6%) failed ABR after 3 months. A second ABR performed after 6 months was normal. Conclusions: TEOAEs recording seems at now the test of choice for a universal hearing screening. However, a greater standardization of criteria both in performing the test and in evaluating the results is needed

Clinical associations of serum antiendothelial cell antibodies in patients with sudden sensorineural hearing loss

Objectives/Hypothesis: The role of antiendothelial cell antibodies in systemic vasculitis has been reported. The aim of the study was to define the clinical associations of serum antiendothelial cell antibodies in patients with sudden sensorineural hearing loss. Study Design: A prospective study in patients with sudden sensorineural hearing loss. Methods: Serum samples were taken from 59 consecutive patients with sudden sensorineural hearing loss at time of presentation and from 28 normal control subjects. Indirect immunofluorescence assay was used to detect antiendothelial cell antibodies. Results: The prevalence of antiendothelial cell antibody detection was 54% (32 of 59 patients), with a statistically significant difference between patients and control subjects (P = .0004). Antiendothelial cell antibody positivity was significantly associated with absent recovery of hearing loss (P = .0020). Conclusions: The cytotoxicity to endothelial cells of the inner ear by antiendothelial cell antibody-positive sera might play a role in causing the stria vascularis damage in immune-mediated sudden sensorineural deafness. The appearance of antiendothelial cell antibody is related to the poor outcome of hearing loss, and its detection could be helpful in the selection of particular patients with sensorineural hearing loss for specific immunosuppressive treatments

Anti-endothelial autoantibodies in patients with sudden hearing loss

Objectives/Hypothesis: Sudden hearing loss (HL) can be caused by autoimmune disorders localized to the inner ear or secondary to systemic immune diseases. Studies in autoimmune animal strains showing HL have reported changes in the cochlear stria vascularis. The authors investigated the presence of antiendothelial cell antibodies (AECA) to see immune-mediated vasculitis may play a role in human sudden HL, Study Design: A prospective study in patients with sudden HL. Methods: Fifteen consecutive patients (mean age, 32 y) affected by sudden HL and 14 normal subjects were included. Patients with familial deafness and metabolic diseases were excluded. Extensive audiovestibular, imaging; microbiological, immunological, and routine examinations were performed. AECA were detected on rat kidney tissue sections on the sera collected at -20 degrees C, Results: AECA were positive in 8 of 15 patients (53%) (2 of 5 men and 6 of 10 women), thus differing significantly from the normal control population, in which only 2 of 14 tested AECA positive (P = .023). Conclusions: In patients with sudden HL, immune-mediated vascular damage can have a pathogenetic role and AECA might represent a serological marker of vasculitis