Prof. Massimo Ralli

Dott. Massimo Ralli

Systemic Lupus Erythematosus (SLE) and Hearing Disorders. Literature review and meta-analysis of clinical and temporal bone findings

Di Stadio A, Ralli M.
J Int Med Res. 2017 Feb

Objective: Aim of this literature review and meta-analysis is to review and correlate hearing and vestibular clinical symptoms, temporal bone findings and pathological mechanisms in Systemic Lupus Erythematosus. Study design:  Mini review and meta-analysis. Retrospective study of relevant papers available in the literature, analyzing clinical hearing aspects in patients with SLE and relevant temporal bone studies in the same field. Methods: PubMed and Google Scholar searches using the following keywords: “Auto-immunitary disease, Systemic Lupus Erythematosus (SLE), hearing loss, temporal bone study, vertigo, dizziness, tinnitus, ear symptoms, Treatment, diagnosis, symptoms, etiopathogenesis, Wegener granulomatosis, Sjogren, Polyarteritis nodosa, Cogan syndrome and granulomatosis”. The authors included in the review studies in which the following words were present: “SLE”, “Temporal Bone” and “Hearing Symptoms”. Review and conclusion: This literature review and meta-analysis focused on the pathological mechanisms through which Systemic Lupus Erythematosus can damage inner ear structures and determinate hearing and vestibular symptoms. Current research identified the main mechanisms involved in inner ear damage, that include the autoimmune response, the deposition of immune-complexes in the vessels and, at a lesser extent, cytotoxic damage.

Somatosensory Tinnitus: Correlation between Cranio-Cervico-Mandibular Disorder History and Somatic Modulation.

Ralli M, Altissimi G, Turchetta R, Mazzei F, Salviati M, Cianfrone F, Orlando MP, Testugini V, Cianfrone G. 
Audiol Neurootol. 2017 Jan 19;21(6):372-382. doi: 10.1159/000452472.

In a subpopulation of patients, tinnitus can be modulated by movements of the jaw or head and neck due to complex somatosensory-auditory interactions. In some of these subjects, tinnitus is related to an underlying temporomandibular (TMJ) or cranio-cervical (NECK) dysfunction that, if correctly identified, could streamline treatment and increase chances of tinnitus improvement. However, it is still unclear whether somatic modulation of tinnitus could be used as a screening tool to identify such patients. We included in this study 310 tinnitus patients with normal hearing, no psychiatric comorbidities and a positive history for TMJ and/or NECK dysfunction and/or a positive modulation of tinnitus to evaluate the characteristics of somatic modulation, investigate the relationship between positive history and positive modulation and identify factors most associated to somatic modulation. Tinnitus modulation was present in 79,67% of patients. We found a significant association within the same subjects between positive history and positive tinnitus modulation for the same district, mainly for TMJ in unilateral tinnitus patients and for TMJ NECK in bilateral tinnitus patients. A strong correlation between history and modulation in the same somatic district within the same subgroups of subjects was also identified. Most TMJ maneuvers resulted in an increased loudness, while NECK maneuvers showed an increase in tinnitus loudness in about 59% of cases. High-pitched tinnitus and male gender were associated with a higher prevalence of modulation; no differences were found for tinnitus onset, THI and age. In this paper, we report a clear association between history and modulation for the same districts within the same patients; such association should always be investigated for better chances of correctly selecting patients in which tinnitus can be treated by a selective approach to TMJ or NECK.

Renal cell carcinoma presenting as a paranasal sinus mass

Ralli M, Altissimi G, Turchetta R, Rigante M
Case Reports in Otolaryngology, Volume 2017, Article ID 9242374

Metastases in the paranasal sinuses are rare; renal cell carcinoma is the most common cancer that metastasizes to this region. We present the case of a patient with a 4-month history of a rapidly growing mass of the nasal pyramid following a nasal trauma, associated with spontaneous epistaxis and multiple episodes of hematuria. Cranial CT scan and MRI showed an ethmoid mass extending to the choanal region, the right orbit, and the right frontal sinus with an initial intracranial extension. Patient underwent surgery with a trans-sinusal frontal approach using a bicoronal incision combined with an anterior midfacial degloving; histological exam was compatible with a metastasis of clear cell renal cell carcinoma. Following histological findings, a total body CT scan showed a solitary 6 cm mass in the upper posterior pole of the left kidney identified as the primary tumor. Although rare, metastatic renal cell carcinoma should always be suspected in patients with nasal or paranasal masses, especially if associated with symptoms suggestive of a systemic involvement such as hematuria. A correct early-stage diagnosis of metastatic RCC can considerably improve survival rate in these patients; preoperative differential diagnosis with contrast-enhanced imaging is fundamental for the correct treatment and follow-up strategy.

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Relationship between hearing function and myasthenia gravis: a contemporary review.

Ralli M, Altissimi G, Di Stadio A, Mazzei F, Turchetta R, Cianfrone G.
J Int Med Res. 2016 Nov 10. pii: 0300060516672124.

A connection between the hearing function and myasthenia gravis (MG) has been investigated and increasing knowledge of the pathophysiological basis of such relation has been collected. Acetylcholine receptors (AChR) on outer hair cells play a central role; in patients with MG autoantibodies against AChR induce a progressive loss of AchRs on outer hair cells (OHC) decreasing their electromotility. The stapedial reflex decay test is altered in MG patients, and can be taken into account as an additional tool for diagnosis and monitoring of the disorder. Transient and Distorsion Product evoked otoacoustic emissions represent the main diagnostic tool to monitor OHC functionality in MG patients, and can be used to record subclinical hearing alterations before the onset of possible clinically evident hearing loss. The association of myasthenia gravis and hearing dysfunction embraces different specialties and therefore requires a multidisciplinary approach in which the otolaryngologist should always be taken into account to highlight a possible hearing dysfunction and monitor the progress of hearing alterations in patients with a diagnosis of MG. 

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Ocular Vestibular Evoked Myogenic Potentials and Intralabyrinthine Intravestibular Schwannomas

Ralli G, Nola G, Ralli M, Fusconi M, Sparvoli L
Ear, Nose and Throat Journal, Accepted September 2016, in press

Intralabyrinthine intravestibular schwannomas are uncommon benign tumors arising from the saccular, the utricular or the lateral and superior ampullary nerves. Diagnosis relies on audiovestibular examination and Magnetic Resonance Imaging; literature reports a delay of 8 years between the onset of symptoms and diagnosis. The aim of this paper is to present a case of intralabyrinthine intravestibular schwannoma in which we included in the diagnostic protocol the Ocular Vestibular Evoked Myogenic Potential (oVEMP) test, a new neurophysiological diagnostic exam that measures utricular function and contralateral superior vestibular nerve afferent fibers. We report the case of a patient presenting with progressive sensorineural hearing loss, dizziness, tinnitus and fullness in the right ear. Audiovestibular examination and MRI were performed to diagnose a right intralabyrinthine intravestibular schwannoma; oVEMPs were absent in the side contralateral to lesion and contributed to the diagnostic process in our patient. oVEMP can provide detailed information on the functionality of the superior and lateral ampullary nerves and the macula of utricle with a precise identification of the affected area. Based on this findings, we discuss the role of oVEMPs in the diagnosis of intravestibular intralabyrinthine schwannoma.

Hearing Disorders in Turner’s Syndrome

Ralli M, Turchetta R, Cianfrone G.
Otolaryngol Open J. 2016; 2(4): 115-119. doi: 10.17140/OTLOJ-2-126

Turner’s Syndrome is associated with hearing disorders in about 20 to 50% of affected individuals. The most common hearing disorders include congenital auricular malformations, recurrent otitis media and sensorineural hearing loss, although altered vestibular function and tinnitus have also been reported. Middle ear disorders, found in a range between 21 and 91% of subjects, are a consequence of morphological cranio-facial alterations resulting in middle ear ventilation dysfunction. Sensorineural hearing loss follows two main audiological profiles: a bilateral symmetrical mid-frequency dip and a high frequency down-sloping curve. Although the pathophysiologic basis of sensorineural hearing loss in Turner’s Syndrome patients are still unclear, several hypotheses have been made so far and are reviewed in this paper. In conclusion, literature confirms that hearing disorders, although not the most relevant clinical problem in these patients, have a high incidence in patients with Turner’s Syndrome and should therefore undergo early evaluation and monitoring over time.

Somatic Modulation of Tinnitus: A Review and Some Open Questions

Ralli M, Altissimi G, Turchetta R, Cianfrone G.
Otolaryngol Open J. 2016; 2(4): 111- 114. doi: 10.17140/OTLOJ-2-125

Tinnitus modulation by movements of the temporomandibular joint, head and neck musculoskeletal structures and the eye, also called somatosensory tinnitus, can be found in one to two thirds of tinnitus sufferers; unfortunately this condition is often overlooked by otolaryngologists. Although somatic modulation has been initially hypothesized as a fundamental characteristic of tinnitus, there is increasing evidence of a tight connection with disorders of non-auditory regions. The structure that mostly modulates tinnitus is the temporomandibular joint, which mainly causes an increase in tinnitus loudness, followed by head and neck movements that may result in an increase or decrease of loudness and eye movements (gaze-evoked tinnitus). Besides loudness, somatic movements can also modulate tinnitus pitch and localization. Somatosensory tinnitus is a relatively new  nding that leaves several open questions: are there individual predisposing factors to somatic modulation? How strong is the association between the capability to somatically modulate tinnitus and an underlying non-auditory disorder? Changes that occur after somatic maneuvers are only transitory? Why patients that have concomitant hyperacusis also have higher chances of tinnitus modulation? Further basic science and clinical research is required to address these and many other questions about somatosensory tinnitus.

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New Frontiers in Tinnitus, Hearing Loss and Hyperacusis

Ralli M.
Otolaryngol Open J. 2016; SE(5): Se1-Se2. doi: 10.17140/OTLOJ-SE-5-e001

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Quality of Life measure for patients with Chronic Suppurative Otitis Media: italian adaptation of “Chronic Ear Survey”

Ralli G., Milella C., Ralli M., Fusconi M., La Torre G
Acta Otorhinolaryngol Ital. 2016 - Jul 27

The Chronic Ear Survey (CES) is a sensitive and disease specific Quality of Life (QoL) measurement tool in patients with Chronic Suppurative Otitis Media (CSOM). It is a 13-item survey that evaluates the frequency, duration and severity of problems associated with this disease. It’s composed of three subscales that describe activity restrictions, symptoms, and medical resource utilization. Based on patient’s answers it’s possible to obtain a score resulting in a scale ranging from 0 to 100; the highest score indicates the best health, while the lowest score denotes poor health. The questionnaire was originally created in English. The aim of this study is to validate the CES questionnaire in the Italian language (CES-I). Translation was made following international guidelines. The application follows the stages of translation from English to Italian and linguistic adaptation, grammatical and idiomatic equivalence review. The CES-I and the Short Form Health Survey 36 (SF-36) questionnaires were administered to 54 patients with CSOM. A cross-sectional design was used to examine the internal consistency (Cronbach’s alpha) and concurrent validity (Pearson’s product moment correlation). To confirm the external validity of CES-I, the Pearson correlation coefficient, considering the total score and single subscales of CES and the 8 scales of the SF-36, was calculated. The Cronbach alpha coefficient for internal consistency was 0,737. The intraclass correlation coefficient , measured through mixed effects, was 0.737 (95% CI: 0.600–0.835, p<0.001) for average measures and 0.412 (95%CI: 0.273–0.559, p<0.001) for individual measures. According to our results, CES-I proved to be a reliable tool for the evaluation of QoL in patients with CSOM among the Italian-speaking population.

Test vestibolo-spinali bedside

Quaderno Monografico AOOI: Diagnosi bedside della vertigine acuta
G. Ralli, C. Milella, M. Ralli

I riflessi vestibolo-spinali (RVS) garantiscono il mantenimento dell’equilibrio statico e dinamico contribuendo, attraverso l’attivazione della muscolatura antigravitazionale dei muscoli estensori del tronco e degli arti inferiori e dei muscoli flessori degli arti superiori, alla stabilità del capo ed al mantenimento della stazione eretta e quindi del corretto assetto posturale del corpo. Le afferenze vestibolo-spinali si integrano a livello centrale con le afferenze visive e propriocettive. La valutazione della via vestibolo-spinale nella vertigine acuta dimostra ancora una certa valenza nel contesto della “bedside vestibular examination” e può essere svolta mediante l’esecuzione di esami che non richiedono strumentazione specifica. Sebbene la sensibilità e soprattutto la speci cità di questi test, quando presi singolarmente, sia abbastanza bassa, l’esecuzione di una batteria di esami e la loro integrazione con dati clinici e anamnestici può indirizzare il clinico, soprattutto nell’approccio non strumentale, sull’eziologia della vertigine. L’interpretazione dei test vestibolo-spinali deve tuttavia essere considerata solo di tipo orientativo e deve necessariamente essere integrata con altri esami, anche nel solo ambito “bedside”.

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Gli effetti del salicilato sulla funzione uditiva: neurotossicità ed acufene

Ralli M, Hayes SH, Chen GD, Salvi R, Sheppard A
Otoneurologia. 2015 Set 47:7-18

Il salicilato, precursore dell’aspirina, è un farmaco antipiretico, analgesico ed anti-infiammatorio molto diffuso nella pratica clinica. Gli effetti del salicilato sulla funzione uditiva sono noti ed includono, quando somministrato ad alti dosaggi, acufene ed ipoacusia. In periferia, la somministrazione acuta di salicilato induce una riduzione d’ampiezza dei prodotti di distorsione delle otoemissioni acustiche (DPOAE) e del potenziale d’azione composto (CAP), prevalentemente per le basse (<10 kHz) e per le alte (>20 kHz) frequenze; è interessante come questa alterazione corrisponda alla tonalità dell’acufene indotto sperimentalmente nell’animale, che varia tra i 12 e i 16 kHz. La somministrazione cronica induce invece un aumento transitorio dell’ampiezza dei DPOAE ed una up-regulation dell’mRNA e dell’espressione proteica della prestina. In vitro la tossicità del sodio salicilato si evidenzia prevalentemente a livello dei neuroni del ganglio spirale inducendo, a dispetto delle ben note proprietà antiossidanti, un rilascio paradosso di radicale superossido che avvia la catena apoptotica. A livello centrale, il salicilato ha la capacità di alterare la trasmissione GABA e serotonino-mediata inducendo iperattività in specifiche popolazioni neuronali. Molto interessanti sono gli effetti a livello della corteccia uditiva e dell’amigdala laterale dove è stata documentata, in seguito alla somministrazione sperimentale di salicilato, una variazione delle frequenze caratteristiche neuronali con una conseguente alterazione della tonotopia fisiologica, specialmente per le frequenze centrali (10-20 kHz). Nell’uomo gli effetti ototossici del salicilato, oltre ad ipoacusia transitoria ed acufene, includono una diminuita discriminazione verbale e difficoltà nell’integrazione temporale. In conclusione, l’utilizzo sperimentale del salicilato ha notevolmente accresciuto la nostra conoscenza sui meccanismi fisiopatologici alla base dell’insorgenza e della cronicizzazione di ipoacusia ed acufene, permettendo così alla ricerca audiologica di base, seppur alcune interazioni non siano ancora completamente chiare, di fare notevoli passi in avanti

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The effect of the NMDA channel blocker memantine on salicylate-induced tinnitus in rats.

Ralli M, Troiani D, Podda MV, Paciello F, Eramo SL, de Corso E, Salvi R, Paludetti G, Fetoni AR.
Acta Otorhinolaryngol Ital. 2014 Jun;34(3):198-204.

Short-term tinnitus develops shortly after the administration of a high dose of salicylate. Since salicylate selectively potentiates N-methyl- D-aspartate (NMDA) currents in spiral ganglion neurons, it may play a vital role in tinnitus by amplifying NMDA-mediated neurotransmission. The aim of this study was to determine whether systemic treatment with a NMDA channel blocker, memantine, could prevent salicylate-induced tinnitus in animals. Additional experiments were performed to evaluate the effect of memantine on the auditory brainstem response (ABR) and distortion product otoacoustic emissions (DPOAE) to test for changes in hearing function. Thirty-six rats were divided into 3 groups and treated daily for four consecutive days. One group (n = 12) was injected with salicylate (300 mg/kg/d, IP), the second (n = 12) was treated with memantine (5 mg/kg/d, IP) and the third group (n = 12) was injected with salicylate and memantine. All rats were tested for tinnitus and hearing loss at 2, 24, 48 and 72 h after the first drug administration and 24 h post treatment; tinnituslike behaviour was assessed with gap prepulse inhibition of acoustic startle (GPIAS), and hearing function was measured with DPOAE, ABR and noise burst prepulse inhibition of acoustic startle (NBPIAS). Rats in the salicylate group showed impaired GPIAS indicative of transient tinnitus-like behaviour near 16 kHz that recovered 24 h after the last salicylate treatment. Memantine did not cause a significant change in GPIAS. Combined injection of salicylate and memantine significantly attenuated GPIAS tinnitus-like behaviour at 48 hours after the first injection. None of the treatments induced permanent threshold shifts in the ABR and DPOAE, which recovered completely within one day post treatment. Animals treated with salicylate plus memantine showed results comparable to animals treated with salicylate alone, confirming that there is no effect of memantine on DPOAE which reflects OHC function. The present study confirms the role of cochlear NMDA receptors in the induction of salicylate-induced tinnitus.

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Review of salicylate-induced hearing loss, neurotoxicity, tinnitus and neuropathophysiology.

Sheppard A, Hayes SH, Chen GD, Ralli M, Salvi R.
Acta Otorhinolaryngol Ital. 2014 Apr;34(2):79-93.

Salicylate's ototoxic properties have been well established, inducing tinnitus and a sensory hearing loss when administered in high doses. Peripherally, acute dosing of salicylate causes frequency dependent reductions in DPOAEs and CAP amplitudes in low (<10 kHz) and high (>20 kHz) frequencies more than mid frequencies (10-20 kHz), which interestingly corresponds to the pitch of behaviourally-matched salicylate-induced tinnitus. Chronic salicylate dosing affects the peripheral system by causing a compensatory temporary enhancement in DPOAE amplitudes and up-regulation of prestin mRNA and protein expression. Despite salicylate's antioxidant properties, cultured cochlea studies indicate it also impairs spiral ganglion neurons (SGNs) by paradoxically causing an upsurge of superoxide radicals leading to apoptosis. Centrally, salicylate alters γ-aminobutyric acid (GABA) and serotonin mediated neurotransmission in the central nervous system (CNS), which results in classical and non-classical auditory regions showing hyperactivity after salicylate administration. In the auditory cortex (AC) and lateral amygdala (LA), neuron characteristic frequencies (CF) shift upward and downward to mid frequencies (10-20 kHz) altering tonotopy following salicylate administration. Additionally, current source density (CSD) analysis showed enhanced current flow into the supergranular layer of the auditory cortex after a high systemic dose of salicylate. In humans, auditory perception changes following salicylate or aspirin, including decreased word discrimination and temporal integration ability. The results of previous studies have partially identified the mechanisms that are involved in salicylate-induced tinnitus and hearing loss, however to date some interactions remain convoluted. This review discusses current knowledge of salicylate ototoxicity and interactions.

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In vivo protective effect of ferulic acid against noise-induced hearing loss in the guinea-pig.

Fetoni AR, Mancuso C, Eramo SL, Ralli M, Piacentini R, Barone E, Paludetti G, Troiani D.
Neuroscience. 2010 Sep 15;169(4):1575-88. 

Ferulic acid (FA) is a phenolic compound whose neuroprotective activity was extensively studied in vitro. In this study, we provided functional in vivo evidence that FA limits noise-induced hearing loss. Guinea-pigs exposed to acoustic trauma for 1 h exhibited a significant impairment in auditory function; this injury was evident as early as 1 day from noise exposure and persisted over 21 days. Ferulic acid (150 mg/kg i.p. for 4 days) counteracted noise-induced hearing loss at days 1, 3, 7 and 21 from noise exposure. The improvement of auditory function by FA was paralleled by a significant reduction in oxidative stress, apoptosis and increase in hair cell viability in the organ of Corti. Interestingly in the guinea-pig cochleae, the neuroprotective effect of FA was functionally related not only to its scavenging ability in the peri-traumatic period but also to the up-regulation of the cytoprotective enzyme heme oxygenase-1 (HO-1); in fact, FA-induced improvement of auditory function was counteracted by the HO inhibitor zinc-protoporphyrin-IX and paralleled the time-course of HO-1 induction over 3-7 days. These results confirm the antioxidant properties of FA as free-radical scavenger and suggest a role of HO-1 as an additional mediator against noise-induced ototoxicity.

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Comparison of salicylate- and quinine-induced tinnitus in rats: development, time course, and evaluation of audiologic correlates.

Ralli M, Lobarinas E, Fetoni AR, Stolzberg D, Paludetti G, Salvi R.
Otol Neurotol. 2010 Jul;31(5):823-31.

Salicylate and quinine have been shown to reliably induce short-term tinnitus when administered at high doses. The present study compared salicylate and quinine-induced tinnitus in rats using the gap prepulse inhibition of acoustic startle (GPIAS). Twenty-four rats were divided into 2 groups; the first group (n = 12) was injected with salicylate (300 mg kg d), whereas the second (n = 12) was treated with quinine orally at a dose of 200 mg kg d. Animals were treated daily for 4 consecutive days. All rats were tested for tinnitus and hearing loss before and 2, 24, 48, 72, and 96 hours after the first drug administration. Tinnitus was assessed using GPIAS; hearing function was measured with distortion product otoacoustic emissions (DPOAEs) and auditory brainstem response. Salicylate treatment induced transient tinnitus with a pitch near 16 kHz starting 2 hours posttreatment, persisting over the 4-day treatment period and disappearing 24 hours later. Animals in the quinine group showed GPIAS changes at a higher pitch (20 kHz); however, changes were more variable among animals, and the mean data were not statistically significant. Hearing function varied across treatments. In the salicylate group, high-level DPOAEs were slightly affected; most changes occurred 2 hours posttreatment. Low-level DPOAEs were affected at all frequencies with a progressive dose-dependent effect. In the quinine group, only high-level DPOAEs were affected, mainly at 16 kHz. The present study highlights the similarities and differences in the frequency and the time course of tinnitus and hypoacusis induced by salicylate and quinine. Transient tinnitus was reliably induced pharmacologically with salicylate, whereas hearing loss remained subclinical with only minor changes in DPOAEs.

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Too much of a good thing: long-term treatment with salicylate strengthens outer hair cell function but impairs auditory neural activity.

Chen GD, Kermany MH, D'Elia A, Ralli M, Tanaka C, Bielefeld EC, Ding D, Henderson D, Salvi R.
Hear Res. 2010 Jun 14;265(1-2):63-9.

Aspirin has been extensively used in clinical settings. Its side effects on auditory function, including hearing loss and tinnitus, are considered as temporary. A recent promising finding is that chronic treatment with high-dose salicylate (the active ingredient of aspirin) for several weeks enhances expression of the outer hair cell (OHC) motor protein (prestin), resulting in strengthened OHC electromotility and enhanced distortion product otoacoustic emissions (DPOAE). To follow up on these observations, we carried out two studies, one planned study of age-related hearing loss restoration and a second unrelated study of salicylate-induced tinnitus. Rats of different strains and ages were injected with salicylate at a dose of 200 mg/kg/day for 5 days per week for 3 weeks or at higher dose levels (250-350 mg/kg/day) for 4 days per week for 2 weeks. Unexpectedly, while an enhanced or sustained DPOAE was seen, permanent reductions in the amplitude of the cochlear compound action potential (CAP) and the auditory brainstem response (ABR) were often observed after the chronic salicylate treatment. The mechanisms underlying these unexpected, permanent salicylate-induced reductions in neural activity are discussed.

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The monitoring role of otoacoustic emissions and oxidative stress markers in the protective effects of antioxidant administration in noise-exposed subjects: a pilot study.

Fetoni AR, Garzaro M, Ralli M, Landolfo V, Sensini M, Pecorari G, Mordente A, Paludetti G, Giordano C.
Med Sci Monit. 2009 Nov;15(11):PR1-8.

Oxidative stress has been recently identified as the pivotal pathway of cochlear damage. The aims of this study were to evaluate whether distortion product otoacoustic emissions (DPOAEs) can discriminate normal subjects with a risk of damage induced by sound exposure, the effectiveness of OAEs in monitoring the protective effects of Coenzyme Q10 terclatrate (QTer), and the role of blood parameters in monitoring preventive therapies. Twenty volunteers were randomized to two groups: the first (n=10) was treated with Q-Ter (200 mg orally once daily) for 7 days before noise exposure and the second group was treated with placebo using the same schedule. All participants were exposed to white noise of 90 dB HL for 15 minutes. DPOAEs and pure-tone audiometry (PTA) were measured before and 1 h, 16 h, and 7 and 21 days after exposure. Inflammatory and oxidative stress parameters were measured before and 2 and 24 h after exposure. In the placebo group, DPOAE amplitudes were reduced 1 and 16 h after exposure compared with the baseline values (p<0.05). In the Q-Ter group, DPOAEs did not show any significant difference between baseline and post-exposure (p>0.1). PTA threshold values in the Q-Ter and placebo groups did not differ before and after exposure. No significantly different levels of the inflammatory markers were observed in the Q-Ter and placebo groups at the different time points. This pilot study confirms that DPOAEs represent a sensitive test for monitoring the effects of noise in preclinical conditions and pharmacological treatment.

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Protective effects of N-acetylcysteine on noise-induced hearing loss in guinea pigs.

Fetoni AR, Ralli M, Sergi B, Parrilla C, Troiani D, Paludetti G.
Acta Otorhinolaryngol Ital. 2009 Apr;29(2):70-5.

Increasing evidence suggests the involvement of oxidative stress in noise-induced hearing loss. The present study analysed, in an animal experimental model, the time course of the pathogenic mechanisms of noise-induced cochlear damage and the efficacy of the antioxidant drug N-acetylcysteine in reducing noise ototoxicity. Animals were divided into two groups, exposed to noise one treated with N-acetylcysteine for 3 days and one (the control group) with saline. Acoustic trauma was induced by a continuous pure tone of 6 kHz, at 120 dB SPL for 30 minutes. Electrocochleographic recordings were made from an implanted round window electrode and the compound action potentials were measured daily at 2-16 kHz for 7 days. Morphological changes were analysed by scanning electron microscopy. The acoustic threshold measured 1 hour after acoustic trauma was elevated in the control group to 70-90 dB in the higher frequencies of the compound action potential audiogram, with a maximum threshold elevation ranging between 12 and 16 kHz. During the first 24 h, following acoustic trauma, there was a partial recovery of compound action potential thresholds of about 20 dB to reach a final threshold elevation of about 50-70 dB; there was no further improvement over the remaining experimental week. Animals treated with N-acetylcysteine showed a similar temporary threshold shift but a clear improvement in the recovery of compound action potential thresholds, with significantly reduced permanent threshold shift and hair cell loss. These data suggest that N-acetylcysteine is able to attenuate the toxic effect of acoustic trauma and could represent an interesting molecule for preventing inner ear injuries.

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Protective properties of antioxidant drugs in noise-induced hearing loss in the guinea pig

Fetoni AR, Ralli M, Parrilla C, Paludetti G, Troiani D
Audiol. Med. 2008. 6:271-277

Oxidative stress plays a significant role in noise-induced hearing loss (NIHL) as it largely participates to the mechanisms that underlie cell death after noise exposure and lead to sensorineural hearing loss. Many antioxidant drugs have been tested to prevent NIHL. We present three molecules with antioxidant properties (Vitamin E, Idebenone, N-L-Acetylcisteine) that have been studied in our laboratory and compare their protective effects. We induced acoustic trauma in treated guinea pigs, evaluated their hearing function via electrophysiological measurements at 1, 7 and 21 days and performed morphological studies with scanning electron microscopy and TUNEL assay. All molecules had a certain effect in protecting hair cell from oxidative stress; vitamin E offered a nearly complete protection (80-95%), N-L-Acetylcisteine and Idebenone also significantly reduced the threshold shift and hair cell loss. Our results support the effectiveness of antioxidant drugs in protecting from NIHL and provide a rationale for exploring therapeutic strategies in humans.

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How relevant is the impairment of smell for the quality of life in allergic rhinitis?

Passali GC, Ralli M, Galli J, Calò L, Paludetti G.
Curr Opin Allergy Clin Immunol. 2008 Jun;8(3):238-42.

In the present review, the authors try to evaluate how relevant smell impairment is in patients suffering from allergic rhinitis and how it affects their quality of life. Smell dysfunction has a significant impact on the quality of life as it can lead to a wrong choice of food and intake, a reduction in appetite and eventually to weight loss, malnutrition, immunity reduction and worsening of medical illness. Patients with smell impairment are reported to use larger quantities of sugar and salt to highlight flavours, thus worsening their general health condition and increasing the risk of developing diabetes and hypertension. Recent studies estimate that a complete loss of the sense of smell can be found in at least 1% of the US population, and that an impairment in the olfactory function can be highlighted in about 24% of individuals aged 53-97 years and 19% of individuals aged 20-92 years. Despite the high prevalence, subjective complaints do not accurately reflect the real disturbance experienced by the patient, and usually go unnoticed. Current information in literature highlights the need for additional studies that concentrate on the impact of olfactory dysfunction on the quality of life of patients affected by allergic rhinitis.

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