Osmotic Drugs in the Treatment of Cochlear Disorders: A Clinical and Experimental Study

Filipo, Roberto; Barbara, Maurizio; Cordier, A. H.; Mafera, Barbara; Roméo, R; Attanasio, Giuseppe; Mancini, Patrizia; Marzetti, Andrea

doi:10.3109/00016489709117777

Cited by 9 publications

(5 citation statements)

References 5 publications

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“…Gene alterations at these loci restate reported cytogenetic [7, 12–22] and molecularly altered regions by LOH and array CGH studies in HNSCC [1, 5, 7, 23–28]. Additionally, copy number loss in tumor and corresponding gain in nontumor, and vice versa, advocate aneuploidy events.…”

Section: Resultsmentioning

confidence: 56%

Malignant and Nonmalignant Gene Signatures in Squamous Head and Neck Cancer

Worsham

Lü

Chen

et al. 2012

Journal of Oncology

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Genetic events specific to the pathogenesis of malignancy can offer clues to the tumorigenesis process. The objective of this study was to identify gene alterations that differentiate tumor and nontumor lesions in squamous head and neck cancer (HNSCC). DNA from 220 primary HNSCC with concurrently present tumor and nontumor lesions from the same patient was interrogated for genomic alterations of loss or gain of copy. Conditional logistic regression dealt with tumor and non-tumor records within a patient. Of 113 genes, 53 had univariate effects (P < 0.01), of which 16 genes remained in the multivariable model with P < 0.01. The model had a C-index (ROC) of 0.93. Loss of CDKN2B and gain of BCL6, FGF3, and PTP4A3 predicted tumor. Loss of BAK1 and CCND1 and gain of STCH predicted nontumor. This highly powered model assigned alterations in 16 genes specific for malignant versus nonmalignant lesions, supporting their contribution to the pathogenesis of HNSCC as well as their potential utility as relevant targets for further evaluation as markers of early detection and progression.

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Section: Resultsmentioning

confidence: 56%

Malignant and Nonmalignant Gene Signatures in Squamous Head and Neck Cancer

Worsham

Lü

Chen

et al. 2012

Journal of Oncology

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“…In clinical trials, dehydration agents (e.g., mannitol, isosorbide, and glycerol) are commonly used in the diagnosis and treatment of MD ( Kakigi et al, 2004 ), as their influences on hearing improvement have been confirmed by clinical trials and research ( Filipo et al, 1997 ; Degerman et al, 2019 ). The impacts of dehydration agents in animal models have usually been analyzed by tissue section or micro-CT.…”

Section: Discussionmentioning

confidence: 99%

The Effect of Endolymphatic Hydrops and Mannitol Dehydration Treatment on Guinea Pigs

Wang

et al. 2022

Front. Cell. Neurosci.

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BackgroundEndolymphatic hydrops (EH) is considered as the pathological correlate of Menière’s disease (MD) and cause of hearing loss. The mechanism of EH, remaining unrevealed, poses challenges for formalized clinical trials.ObjectiveThis study aims to investigate the development of hearing loss, as well as the effect of dehydration treatment on EH animal models.MethodsIn this study, different severity EH animal models were created. The laser Doppler vibrometer (LDV) and auditory brainstem responses (ABR) were used to study the effects of EH and the dehydration effects of mannitol. The LDV was used to measure the vibration of the round window membrane (RWM) reflecting the changes in inner ear impedance. ABR was used to evaluate the hearing changes. Furthermore, tissue section and scanning electron microscopy (SEM) observations were used to analyze the anatomical change to the cochlea and outer hair cells.ResultsThe RWM vibrations decreased with the severity of EH, indicating an increase in the cochlear impedance. The dehydration therapy lowered the impedance to restore acoustic transduction in EH 10- and 20-day animal models. Simultaneously, the ABR thresholds increased in EH models and were restored after dehydration. Moreover, a difference in the hearing was found between ABR and LDV results in severe EH animal models, and the dehydration therapy was less effective, indicating a sensorineural hearing loss (SNHL).ConclusionEndolymphatic hydrops causes hearing loss by increasing the cochlear impedance in all tested groups, and mannitol dehydration is an effective therapy to restore hearing. However, SNHL occurs for the EH 30-day animal models, limiting the effectiveness of dehydration. Our results suggest the use of dehydrating agents in the early stage of EH.

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“…However, in an open trial tinnitus was only relieved in 13.1% of patients treated with glycerol and 5.8% of those treated with mannitol (160). …”

Section: Existing Treatmentsmentioning

confidence: 99%

Emerging pharmacotherapy of tinnitus

Langguth

Salvi²,

Elgoyhen

2009

Expert Opinion on Emerging Drugs

116

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Tinnitus, the perception of sound in the absence of an auditory stimulus, is perceived by about one in 10 adults, and for at least 1 in 100, tinnitus severely affects their quality of life. Since tinnitus is frequently associated with irritability, agitation, stress, insomnia, anxiety and depression, the social and economic burdens of tinnitus can be enormous. No curative treatments are available. However, tinnitus symptoms can be alleviated to some extent. The most widespread management therapies consist of auditory stimulation and cognitive behavioural treatment, aiming at improving habituation and coping strategies. Available clinical trials vary in methodological rigor and have been performed for a considerable number of different drugs. None of the investigated drugs have demonstrated to provide replicable long-term reduction of tinnitus impact in the majority of patients, in excess of placebo effects. Accordingly, there are no FDA- or EMEA-approved drugs for the treatment of tinnitus. However, in spite of the lack of evidence, a large variety of different compounds are prescribed off-label. Therefore, more effective pharmacotherapies for this huge and still growing market are desperately needed and even a drug that produces only a small but significant effect would have an enormous therapeutic impact. This review describes current and emerging pharmacotherapies with its current difficulties and limitations. In addition, it provides an estimate of the tinnitus market. Finally, it describes recent advances in the tinnitus field which may help overcome obstacles faced in the pharmacological treatment of tinnitus. These include incomplete knowledge of tinnitus pathophysiology, lack of well established animal models, heterogeneity of different forms of tinnitus, difficulties in tinnitus assessment and outcome measurement and variablility in clinical trial methodology.

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Osmotic Drugs in the Treatment of Cochlear Disorders: A Clinical and Experimental Study

Cited by 9 publications

References 5 publications

Malignant and Nonmalignant Gene Signatures in Squamous Head and Neck Cancer

Malignant and Nonmalignant Gene Signatures in Squamous Head and Neck Cancer

The Effect of Endolymphatic Hydrops and Mannitol Dehydration Treatment on Guinea Pigs

Emerging pharmacotherapy of tinnitus

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